Do not attempt to use sleep deprivation as a therapy
for depression without medical supervision.
1: World J Biol Psychiatry 2000 Oct;1(4):180-6 Sleep in depression and sleep deprivation: a brief conceptual review. Holsboer-Trachsler E, Seifritz E. Department of Psychiatry, University of Basel, Switzerland. firstname.lastname@example.org Risk factors for somnipathies are psychological stress or psychiatric illness. More severe sleep difficulties have been found to be clearly related to psychiatric illness such as depression and phobias, as well as to addiction. Somnipathies can objectively be identified by means of polygraphy. Overall, polysomnographic measures in patients with affective disorders differ most frequently and significantly from those in normal control subjects. Persistent sleep disturbances are associated with significant risk of both relapse and recurrence in mood disorders and an increased risk of suicide. In addition to changes in sleep architecture, patients with major depression show profoundly altered patterns of nocturnal hormone secretion, possibly through mechanisms that link regulation of sleep with neuroendocrine activity. Basic and clinical approaches of sleep research established neurobiological models into the underlying pathophysiology associated with psychiatric disorders. PMID: 12607213 [PubMed - in process] 2: Sleep Med Rev 2002 Oct;6(5):361-77 Therapeutic use of sleep deprivation in depression. Giedke H, Schwarzler F. Department of Psychiatry, University of Tubingen, Osianderstr. 24, Germany. email@example.com Total sleep deprivation (TSD) for one whole night improves depressive symptoms in 40-60% of treatments. The degree of clinical change spans a continuum from complete remission to worsening (in 2-7%). Other side effects are sleepiness and (hypo-) mania. Sleep deprivation (SD) response shows up in the SD night or on the following day. Ten to 15% of patients respond after recovery sleep only. After recovery sleep 50-80% of day 1 responders suffer a complete or partial relapse; but improvement can last for weeks. Sleep seems to lead to relapse although this is not necessarily the case. Treatment effects may be stabilised by antidepressant drugs, lithium, shifting of sleep time or light therapy. The best predictor of a therapeutic effect is a large variability of mood. Current opinion is that partial sleep deprivation (PSD) in the second half of the night is equally effective as TSD. There are, however, indications that TSD is superior. Early PSD (i.e. sleeping between 3:00 and 6:00) has the same effect as late PSD given equal sleep duration. New data cast doubt on the time-honoured conviction that REM sleep deprivation is more effective than non-REM SD. Both may work by reducing total sleep time. SD is an unspecific therapy. The main indication is the depressive syndrome. Some studies show positive effects in Parkinson's disease. It is still unknown how sleep deprivation works. Publication Types: Review Review, Academic PMID: 12531127 [PubMed - indexed for MEDLINE] 3: Depress Anxiety 2002;16(1):1-3 Bright light augments antidepressant effects of medication and wake therapy. Loving RT, Kripke DF, Shuchter SR. Department of Psychiatry, University of California, San Diego, La Jolla, California 92093-0667, USA. Rloving@UCSD.edu Inpatient studies have suggested that bright light therapy can be used to sustain the antidepressant effects of wake therapy (sleep deprivation). In an outpatient trial, a half night of home wake treatment was followed by 1 week of light treatment. All subjects had Major Depressive Disorders according to DSM-IV criteria and were receiving concomitant antidepressant medication. Subjects were randomly assigned to receive either 10,000 lux bright white light for 30 min between 6 and 9 AM or dim red (placebo) light at a comparable time. Seven subjects completed treatment with bright white light and six completed treatment with placebo. On the Hamilton Depression Rating Scale (HDRS17, SIGH-SAD-SR version), the group receiving bright light improved 27% in 1 week (P=0.002). The group receiving placebo did not improve, except for one outlier. The benefit of bright light was significant compared to placebo with removal of the outlier (P<0.025). Copyright Wiley-Liss, Inc. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 12203667 [PubMed - indexed for MEDLINE] 4: J Clin Psychiatry 2002 Jul;63(7):628-40 Alternative treatments for depression: empirical support and relevance to women. Manber R, Allen JJ, Morris MM. Department of Psychiatry and Behavioral Sciences, Stanford University, Calif. 94305, USA. firstname.lastname@example.org BACKGROUND: This article is a critical review of the efficacy of selected alternative treatments for unipolar depression including exercise, stress management techniques, acupuncture, St. John's wort, bright light, and sleep deprivation. Issues related to women across the life span, including pregnancy and lactation, are highlighted. DATA SOURCES: Evidence of efficacy is based on randomized controlled trials. A distinction is made between studies that address depressive symptoms and studies that address depressive disorders. The review emphasizes issues related to effectiveness, such as treatment availability, acceptability, safety, and cost and issues relevant to women. DATA SYNTHESIS: Exercise, stress reduction methods, bright light exposure, and sleep deprivation hold greater promise as adjuncts to conventional treatment than as monotherapies for major depression. The evidence to date is not sufficiently compelling to suggest the use of St. John's wort in favor of or as an alternative to existing U.S. Food and Drug Administration-regulated compounds. Initial evidence suggests that acupuncture might be an effective alternative monotherapy for major depression, single episode. CONCLUSION: This review indicates that some unconventional treatments hold promise as alternative or complementary treatments for unipolar depression in women and have the potential to contribute to its long-term management. Additional research is needed before further recommendations can be made, and there is an urgent need to carefully document and report the frequency of minor and major side effects. Publication Types: Review Review, Tutorial PMID: 12143922 [PubMed - indexed for MEDLINE] 5: Life Sci 2002 Mar 1;70(15):1741-9 Sleep deprivation in depression stabilizing antidepressant effects by repetitive transcranial magnetic stimulation. Eichhammer P, Kharraz A, Wiegand R, Langguth B, Frick U, Aigner JM, Hajak G. Department of Psychiatry and Psychotherapy, University of Regensburg, Germany. email@example.com Partial sleep deprivation (PSD) has a profound and rapid effect on depressed mood. However, the transient antidepressant effect of PSD - most patients relapse after one night of recovery sleep - is limiting the clinical use of this method. Using a controlled, balanced parallel design we studied, whether repetitive transcranial magnetic stimulation (rTMS) applied in the morning after PSD is able to prevent this relapse. 20 PSD responders were randomly assigned to receive either active or sham stimulation during the following 4 days after PSD. Active stimulation prolonged significantly (p < 0.001) the antidepressant effect of PSD up to 4 days. This finding indicates that rTMS is an efficacious method to prevent relapse after PSD. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 12002519 [PubMed - indexed for MEDLINE] 6: Neuropsychobiology 2002;45 Suppl 1:7-12 Sleep and sleep-wake manipulations in bipolar depression. Riemann D, Voderholzer U, Berger M. Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Germany. firstname.lastname@example.org In the last 30 years, it has been convincingly demonstrated that sleep in major depression is characterized by disturbances of sleep continuity, a reduction of slow wave sleep, a disinhibition of REM sleep including a shortening of REM latency (i.e. the time between sleep onset and the occurrence of the first REM period) and an increase in REM density. Furthermore, manipulations of the sleep-wake cycle like total or partial sleep deprivation or phase advance of the sleep period have been proven to be effective therapeutic strategies for patients with unipolar depression. The database concerning sleep and sleep-wake manipulations in bipolar disorder in comparison is not yet as extensive. Studies investigating sleep in bipolar depression suggest that during the depressed phase sleep shows the same stigmata as in unipolar depression. During the hypomanic or manic phase, sleep is even more curtailed, though subjectively not experienced as disturbing by the patients. REM sleep disinhibition is present as well. An important issue is the question, whether sleep-wake manipulations can also be applied in patients with bipolar depression. Work by others and our own studies indicate that sleep deprivation and a phase advance of the sleep period can be used to treat bipolar patients during the depressed phase. The risk of a switch into hypomania or mania does not seem to be more pronounced than the risk with typical pharmacological antidepressant treatment. For patients with mania, sleep deprivation is not an adequate treatment--in contrast, treatment strategies aiming at stabilizing a regular sleep-wake schedule are indicated. Copyright 2002 S. Karger AG, Basel Publication Types: Review Review, Tutorial PMID: 11893871 [PubMed - indexed for MEDLINE] 7: J Psychiatr Res 2002 May-Jun;36(3):131-5 Relation between responses to repetitive transcranial magnetic stimulation and partial sleep deprivation in major depression. Padberg F, Schule C, Zwanzger P, Baghai T, Ella R, Mikhaiel P, Hampel H, Moller HJ, Rupprecht R. Department of Psychiatry, Ludwig-Maximilian University, Nussbaumstr. 7, 80336 Munich, Germany. email@example.com Repetitive transcranial magnetic stimulation (rTMS) has been found to ameliorate symptoms in major depression. However, its mechanism of action has to be further elucidated and the relationship between responses to rTMS and other antidepressant interventions except electroconvulsive therapy has not been investigated to date. Here we studied in an open trial whether the response to partial sleep deprivation may predict the clinical outcome of rTMS treatment. Thirty-three drug-free patients suffering from a major depressive episode underwent a partial sleep deprivation at least 5 days prior to rTMS and subsequently received 10 sessions of 10 Hz rTMS of the left prefrontal cortex. After rTMS a significant overall improvement of 32% on the Hamilton Rating Scale for Depression was observed. Forty-two percent of patients showed an antidepressant response after rTMS. Amelioration of depression after partial sleep deprivation was inversely correlated with improvement after rTMS. There was no clinically applicable predictive value of the response to partial sleep deprivation for the outcome after rTMS. Apparently, different subgroups of depressed patients respond to both interventions. Further studies are needed to characterize the response to rTMS by means of clinical and biological parameters. Publication Types: Clinical Trial PMID: 11886690 [PubMed - indexed for MEDLINE] 8: Psychiatry Res 2001 Nov 30;104(3):239-46 Dopaminergic augmentation of sleep deprivation effects in bipolar depression. Benedetti F, Campori E, Barbini B, Fulgosi MC, Colombo C. Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, Universita Vita-Salute San Raffaele, Via Stamira d'Ancona 20, 20127 Milan, Italy. firstname.lastname@example.org Total sleep deprivation (TSD) has been used in association with lithium salts and with serotonergic and noradrenergic antidepressants, leading to sustained improvements in patients affected by major depression. Current theories on the neurobiological mechanism of action of TSD propose a major role for enhanced dopamine activity. To test the clinical relevance of dopaminergic enhancement in TSD, we treated a homogeneous sample of 28 bipolar depressed patients with three cycles of TSD combined with placebo or with the dopaminergic antidepressant amineptine. Changes in mood over time were rated with self-administered visual analogue scales and with the Montgomery-Asberg Depression Rating Scale. Patients showed improved mean daily-mood scores after TSD, an effect that was highest at the first cycle and decreased with treatment repetition. Amineptine enhanced the effects of TSD on perceived mood during the first two TSD cycles, but patients in the placebo and amineptine groups showed comparable results at the end of the treatment. Despite its theoretical importance, the clinical usefulness of combining TSD with a dopaminergic agent must be questioned. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 11728613 [PubMed - indexed for MEDLINE] 9: J Psychiatr Res 2001 Nov-Dec;35(6):323-9 Sleep phase advance and lithium to sustain the antidepressant effect of total sleep deprivation in bipolar depression: new findings supporting the internal coincidence model? Benedetti F, Barbini B, Campori E, Fulgosi MC, Pontiggia A, Colombo C. Universita Vita-Salute San Raffaele, School of Medicine, Department of Neuropsychiatric Sciences, Via Stamira d'Ancona 20 20127, Milano, Italy. email@example.com Recent European studies suggested that sleep phase advance (SPA) could sustain the effects of total sleep deprivation (TSD) both with or without a combined antidepressant drug treatment. Previous studies by our group showed that an ongoing lithium treatment could enhance and sustain the effect of repeated TSD. In the present study we studied the effect of a single TSD followed by 3 days SPA (beginning with sleep allowed from 17:00 until 24:00, with daily shiftbacks of 2 h) in consecutively admitted bipolar depressed inpatients who were taking a chronic lithium salts treatment (n=16) or who were devoid of psychotropic medications (n=14). Changes in mood during treatment were recorded with self administered visual analogue scales and with Hamilton rating scale for depression. Results showed that SPA could sustain the acute antidepressant effect of TSD, and that lithium enhanced the effect of the chronobiological treatment. According to the internal coincidence model, the better clinical effects observed in lithium-treated patients could be due to the phase delaying effect of lithium on biological rhythms, leading to a better synchronization of biological rhythms with the sleep-wake cycle. Publication Types: Clinical Trial PMID: 11684139 [PubMed - indexed for MEDLINE] 10: Neuropsychopharmacology 2001 Nov;25(5 Suppl):S79-84 Sleep deprivation, EEG, and functional MRI in depression: preliminary results. Clark CP, Frank LR, Brown GG. University of California, San Diego and San Diego Veterans Affairs Medical Center, San Diego, CA, USA. firstname.lastname@example.org One night of total or partial sleep deprivation (SD) produces temporary remissions in 40-60% of patients with major depression. Two unmedicated patients with major depression and a matched control received quantitative perfusion MR images at baseline and after one night of partial SD (PSD). A reduction > or =30% in the 17-item Hamilton Depression Rating Scale (omitting sleep and weight loss items) defined antidepressant response. Theory, techniques, strengths and weaknesses of quantitative perfusion MRI are described in detail. At baseline, the responder exhibited elevated perfusion covering ventral anterior cingulate/medial frontal cortex; the control's maximal perfusion area was markedly smaller. The nonresponder's perfusion was lowest of all, particularly ventrally. PSD decreased perfusion over much of the responder's hyperperfused area but did not change the nonresponder's scan. These preliminary findings are consistent with previous SD studies using PET and SPECT. Publication Types: Clinical Trial PMID: 11682279 [PubMed - indexed for MEDLINE] 11: J Psychiatr Res 2001 May-Jun;35(3):155-63 Delta sleep ratio as a predictor of sleep deprivation response in major depression. Nissen C, Feige B, Konig A, Voderholzer U, Berger M, Riemann D. Department of Psychiatry and Psychotherapy of the University Hospital of Freiburg, Hauptstrasse 5, D-79104 Freiburg, Germany. The fast but short-lasting improvement of depressive symptoms by sleep deprivation (SD) in about 60% of patients with a major depressive disorder is well established, but the mechanisms of action are still not clear. Recent studies suggest that changes in non rapid eye movement (NREM) sleep, especially in slow wave activity (SWA), could be associated with the therapeutic outcome of SD. In the current study, spectral analysis of NREM sleep EEG directly prior to SD was performed to determine if automatically derived sleep parameters predict SD response. Sixteen pair matched and drug free patients with a major depressive disorder, 8 SD responders and 8 non-responders (response criterion: 50% reduction on the 6-item HAMD score), were included. Average EEG spectral power was calculated for the whole night before SD and for single NREM episodes. While whole-night averages of spectral power did not differ significantly between subgroups, SD responders showed a steady decrease of SWA across successive NREM episodes, whereas in non-responders an increase from the first to the second episode was observed. The different distribution of SWA was significantly expressed in the delta sleep ratio (quotient of SWA in the first to the second NREM episode). In conclusion, a high delta sleep ratio is a positive predictor for SD response. Referred to psycho- and pharmacotherapeutic results it is hypothesized that low and high values of the delta sleep ratio characterize subgroups of depressed patients with different neurobiological alterations, which could be relevant for further scientific and therapeutic approaches. PMID: 11461711 [PubMed - indexed for MEDLINE] 12: Fortschr Neurol Psychiatr 2001 Apr;69(4):156-63 [Sleep deprivation as a predictor of response to light therapy in major depression] [Article in German] Heller R, Fritzsche M, Hill H, Kick H. Psychiatrische Klinik, Universitat Heidelberg. Light therapy (LT) is regarded as the treatment of choice for seasonal affective disorder (SAD). In nonseasonal depression the results of light therapy are nonconclusive. Sleep deprivation (SD), however, is effective in 50-60% of the patients with major depression. The predictive value of Total Sleep Deprivation (TSD) for the treatment outcome of antidepressiva has been already examined. Purpose of the present study was to test whether light therapy is more beneficial in TSD responders than in TSD nonresponders. 40 inpatients with major depressive disorder completed one night of TSD. Twenty TSD responders and 20 TSD nonresponders were randomly assigned to 14 days of bright light therapy (2500 lux, 7-9 a.m.) or 14 days of dim light therapy (red light 50 lux, 7-9 a.m.). Manova with repeated measurements revealed a significant difference in the course of depression over the time between TSD responders and nonresponders, but no significant difference between bright and dim light. Questions of placebo effect, of SAD and of personality variables as predictors of response to SD and LT are being discussed. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 11386120 [PubMed - indexed for MEDLINE] 13: J Affect Disord 2001 May;64(2-3):257-60 Patterns of response to repeated total sleep deprivations in depression. Wiegand MH, Lauer CJ, Schreiber W. Department of Psychiatry and Psychotherapy, Technical University, Munich, Germany. email@example.com BACKGROUND: Patterns of response and nonresponse in repeated sleep deprivation (SD) are of both clinical and scientific interest; as yet, studies have yielded inconsistent results. METHODS: Eighteen inpatients suffering from a major depression were subjected to a series of six scheduled total sleep deprivations within 3 weeks; 12 of them completed the whole protocol. All were under a constant antidepressant medication with amitriptyline. SD effects were measured using observer and self rating scales. RESULTS: Each single SD led to a significant improvement. Of the 12 patients who completed the protocol, seven were classified as responders at endpoint (i.e., 1 week after the sixth TSD). The majority of patients exhibited a pattern of responses and nonresponses randomly distributed over time. There was no temporal trend. The initial effect did not predict the average response to the following SDs. LIMITATIONS: One third of patients dropped out before completing the protocol which limits the scope of the study. CONCLUSIONS: Response to a single SD is not generalizable on a series of following SDs in an individual. The mechanism of action of SD does probably not involve mechanisms subjected to habituation or sensitization. PMID: 11313092 [PubMed - indexed for MEDLINE] 14: J Affect Disord 2001 Feb;62(3):207-15 Sleep deprivation as a predictor of response to light therapy in major depression. Fritzsche M, Heller R, Hill H, Kick H. Voss-Str. 2, Department of Psychiatry, University of Heidelberg, D-69115 Heidelberg, Germany. BACKGROUND: While the majority of depressed patients benefit from total sleep deprivation (TSD), light therapy is regarded as a first-line treatment only for seasonal affective disorder (SAD). The results of light therapy in nonseasonal major depressive disorder have been non-conclusive. We examined the correlation of TSD response and light therapy response in major depressed patients. METHODS: 40 inpatients with major depressive disorder (seven with seasonal pattern, 33 without seasonal pattern) were deprived of a night's sleep. The TSD responders, as well as the TSD nonresponders, were randomly assigned to receive adjunct light therapy either with bright white light (2500 lux) or dim red light (50 lux) during 2 weeks beginning on the third day after TSD. RESULTS: The 20 TSD responders improved significantly better under the light therapy than the 20 TSD nonresponders (according to the Hamilton Depression Rating Scale and the self-rating depression scale Bf-S; v. Zerssen). LIMITATIONS: No significant difference could be found between the two light intensities. Since the patients were additionally treated with medication an interaction with the two adjunctive therapies cannot be excluded. CONCLUSION: Our results indicate that a positive TSD response in major depressed patients can be predicative of beneficial outcome of subsequent light therapy. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 11223108 [PubMed - indexed for MEDLINE] 15: Psychiatry Res 2000 Dec 4;97(1):41-9 The clinical response to total sleep deprivation and recovery sleep in geriatric depression: potential indicators of antidepressant treatment outcome. Hernandez CR, Smith GS, Houck PR, Pollock BG, Mulsant B, Dew MA, Reynolds CF 3rd. Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. The clinical response to antidepressant treatment in late-life depression is often delayed and highly variable. Better indicators of antidepressant efficacy are needed early in the course of treatment, so that augmentation strategies or alternative treatments may be initiated. The goal of this study was to evaluate whether the change in the Hamilton depression rating scale (HDRS) after 36 h of total sleep deprivation (TSD) and recovery sleep predicted clinical outcome after 12 weeks of antidepressant treatment, and whether greater predictive value was observed in certain aspects of depressive symptomology. Fifteen elderly patients diagnosed with major depression underwent combined treatment with an initial 36 hours of TSD and a 12-week trial with the antidepressant paroxetine. Six HDRS subscores were evaluated with respect to how the changes after TSD and after one night of recovery sleep correlated with HDRS scores after 12 weeks of treatment. A significant correlation was obtained between the change in the core depressive symptomology subscale from baseline to recovery sleep and the HDRS score at 12 weeks, but the correlation was not significant when evaluating the change from baseline to TSD. These results indicate that the decrease in symptoms after recovery sleep compared with baseline levels (indicating the persistence of the antidepressant response), rather than the symptom reduction after TSD, has greater predictive value with respect to treatment outcome. PMID: 11104856 [PubMed - indexed for MEDLINE] 16: J Affect Disord 2000 Nov;60(3):201-12 Can critically timed sleep deprivation be useful in pregnancy and postpartum depressions? Parry BL, Curran ML, Stuenkel CA, Yokimozo M, Tam L, Powell KA, Gillin JC. Department of Psychiatry, University of California - San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA. firstname.lastname@example.org BACKGROUND: The aim of this study was to test the efficacy of critically timed sleep deprivation in major mood disorders (MMD) occurring during pregnancy and postpartum. METHODS: Nine women who met DSM-IV criteria for a MMD with onset during pregnancy or within 1 year postpartum underwent a trial of either early-night sleep deprivation (ESD), in which they were sleep deprived in the early part of one night and slept from 03:00-07:00 h, or late-night sleep deprivation (LSD), in which they were deprived of sleep in the latter part of one night and slept from 21:00-01:00 h. Mood was assessed before the night of sleep deprivation, after the night of sleep deprivation, and after a night of recovery sleep (sleep 22:30-06:30 h) by trained clinicians, blind to treatment condition, using standardized scales. RESULTS: More patients responded to LSD (nine of 11 trials: 82%) compared with ESD (two of six trials: 33%) and they responded more after a night of recovery sleep (nine of 11 nights: 82%) than after a night of sleep deprivation (six of 11 nights: 55%). Pregnant women were the only responders to ESD and the only nonresponders to LSD. LIMITATIONS: The small and heterogeneous sample size prevents us from making more definitive conclusions based on statistical analyses. CONCLUSIONS: Although the findings are preliminary, the results suggest that with further study, critically timed sleep deprivation interventions may benefit women with pregnancy or postpartum major mood disorders and potentially provide a viable alternative treatment modality for those women who are not candidates for pharmacologic or psychotherapeutic interventions. Such interventions are needed to help prevent the devastating effects of depression during pregnancy and the postpartum period on the mother, infant, her family and society. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 11074109 [PubMed - indexed for MEDLINE] 17: Biol Psychiatry 2000 Aug 15;48(4):323-6 Thyroid function and response to 48-hour sleep deprivation in treatment-resistant depressed patients. David MM, Owen JA, Abraham G, Delva NJ, Southmayd SE, Wooltorton E, Lawson JS. Department of Psychiatry, Queen's University and Kingston Psychiatric Hospital, and School of Medicine, Queen's University (EW), Kingston, Canada. BACKGROUND: Clinical depression is associated with abnormalities of the hypothalamic-pituitary-thyroid axis. Changes in thyroid function during sleep deprivation may be related to its antidepressant effects. METHODS: Levels of thyroid-stimulating hormone, tri-iodothyronine, tri-iodothyronine uptake, thyroxine, and free thyroxine were measured before, during, and after a 48-hour sleep deprivation in nine treatment-resistant depressed patients. Clinical state was assessed every 4 hours. A retrospective study of 26 similar patients was added for cross-validation. RESULTS: Significant increases in thyroid-stimulating hormone and tri-iodothyronine during sleep deprivation were not correlated with clinical improvement. Sleep deprivation responders had lower tri-iodothyronine uptake levels than nonresponders in both the prospective (p <.02) and the retrospective (p <.03) samples. CONCLUSIONS: The lower tri-iodothyronine uptake values in responders may identify a subgroup of depressed patients who respond to sleep deprivation by virtue of some abnormality of the hypothalamic-pituitary-thyroid axis that is temporarily corrected by sleep deprivation. PMID: 10960165 [PubMed - indexed for MEDLINE] 18: Psychiatry Res 2000 Jul 24;95(1):43-53 Total sleep deprivation combined with lithium and light therapy in the treatment of bipolar depression: replication of main effects and interaction. Colombo C, Lucca A, Benedetti F, Barbini B, Campori E, Smeraldi E. Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, University of Milan, School of Medicine, Italy. The clinical usefulness of total sleep deprivation (TSD) in the treatment of bipolar depression is hampered by a high-rate short-term relapse. Previous literature has suggested that both long-term lithium treatment and light therapy could successfully prevent relapse. We randomized 115 bipolar depressed inpatients to receive three cycles of TSD, alone or in combination with morning light exposure, given at an intensity of 150 or 2500 lux. Forty-nine patients were undergoing long-term treatment with lithium salts (at least 6 months), while 66 patients were taking no psychotropic medication. Mood was self-rated by the Visual Analogue Scale three times a day during treatment. The results showed that both light therapy and ongoing lithium treatment significantly enhanced the effects of TSD on the perceived mood, with no additional benefit when the two treatments were combined. Subjective sleepiness during TSD, as rated by the self-administered Stanford Sleepiness Scale, was significantly reduced by light exposure, and was correlated with the outcome. This study confirms the possibility of obtaining a sustained antidepressant response to TSD in bipolar patients. Publication Types: Clinical Trial Controlled Clinical Trial PMID: 10904122 [PubMed - indexed for MEDLINE] 19: J Clin Psychiatry 2000;61 Suppl 9:57-67 The treatment of bipolar depression. Compton MT, Nemeroff CB. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Ga 30322, USA. BACKGROUND: The treatment of bipolar depression represents a relatively understudied area in clinical psychiatry. The depressive phases of bipolar disorder can be very disabling, with significant associated comorbidity and suicide risk, impairment in functioning, and infringement on quality of life. We review the current evidence for the management of bipolar depression. METHOD: References for this review were obtained through MEDLINE searches of the medical literature on subjects pertaining to the treatment of bipolar depression. Search terms included bipolar depression, antidepressants, and bipolar disorder. Only publications in English are reviewed here. RESULTS: Lithium is currently the gold standard and most appropriate initial treatment for the depressive phase of bipolar disorder. Other mood stabilizers have demonstrated preliminary efficacy. Of the antidepressants, bupropion and the selective serotonin reuptake inhibitors may be associated with less risk of inducing hypomania, mania, and rapid cycling compared with tricyclic antidepressants. Monoamine oxidase inhibitors should be considered for patients with anergic bipolar depression. Electroconvulsive therapy has been shown to be highly efficacious. Other treatment modalities, including psychotherapy, sleep deprivation, phototherapy, and newer medications, require further research. CONCLUSIONS: Although the treatment of bipolar depression can be a complicated clinical task, the treatment armamentarium is expanding. Further research, especially in the form of randomized controlled trials, is warranted. Clinicians should be familiar with general guidelines for the use of psychopharmacologic agents for treating bipolar depression. Publication Types: Review Review, Tutorial PMID: 10826663 [PubMed - indexed for MEDLINE] 20: J Affect Disord 2000 Jul;59(1):77-83 Preliminary evidence of an association between increased REM density and poor antidepressant response to partial sleep deprivation. Clark C, Dupont R, Golshan S, Gillin JC, Rapaport MH, Kelsoe JR. Department of Psychiatry 9116A University of California at San Diego 92093, USA. email@example.com BACKGROUND: One night of total sleep deprivation or of late-night partial sleep deprivation (PSD) produces a temporary remission in approximately 40-60% of patients with major depressive disorder; however, little is known about polysomnography (PSG) characteristics of responders to these types of sleep deprivation (SD). METHODS: Twenty-three unmedicated unipolar patients (17-item Hamilton Depression Rating Scale (HDRS17) >16) and 14 normal controls underwent 1 night of late-night PSD (awake after 3 a.m.) Subjects underwent baseline PSG and received the HDRS17 at standard times before and after PSD. Clinical response was defined as a reduction of >30% in the modified HDRS17 (omitting sleep and weight loss items) following PSD. RESULTS: The 12 responders and 11 nonresponders did not differ from each other significantly on baseline HDRS17 or PSG variables. The only PSG variable correlating with percent decrease in modified HDRS17 was baseline REM density (Pearson's r=-0.52, n=23, P=0.01.) In other words, the lower the baseline REM density, the more robust the antidepressant response was. Limitations: Subject numbers are relatively small. CONCLUSIONS: Increased REM density, which reflects the number of rapid eye movements per epoch of REM sleep, may be a physiological marker for severity or poor prognosis in a variety of psychiatric disorders, including relapse in recovering alcoholics, suicidality in schizophrenia, and poor response to PSD or interpersonal psychotherapy in depression. PMID: 10814775 [PubMed - indexed for MEDLINE] 21: Psychiatry Res 1994 Jun;55(2):101-9 Increased limbic blood flow and total sleep deprivation in major depression with melancholia. Ebert D, Feistel H, Barocka A, Kaschka W. Department of Psychiatry, University of Erlangen, Germany. Single photon emission computed tomography (SPECT) with technetium-99m-d,l-hexamethyl-propylene amine oxime (99Tcm-HMPAO) was carried out in 20 melancholic patients before and after total sleep deprivation. Findings in 11 responders to total sleep deprivation (defined by > or = 40% improvement on the Hamilton Rating Scale for Depression) were compared with findings in nine nonresponders. On the basis of a semiquantitative evaluation of SPECT findings, responders showed relative hyperperfusion before sleep deprivation in the right anterior cingulate cortex and in the right and left fronto-orbital cortex and basal cingulate gyrus. Responders who showed > or = 50% improvement also showed hippocampal overactivation before sleep deprivation. It is possible that limbic overactivation may characterize depressed responders to total sleep deprivation as a distinct subtype. Another possibility is that the pattern of limbic hyperactivation reflects the increased number of bipolar patients in the responder group, with response to total sleep deprivation being only a covariate of this bipolar-unipolar distinction. PMID: 10711798 [PubMed - indexed for MEDLINE] 22: Wien Med Wochenschr 1999;149(18):520-4 [Therapeutic sleep deprivation and phototherapy] [Article in German] Praschak-Rieder N, Willeit M, Neumeister A, Hilger E, Kasper S. Klinischen Abteilung fur Allgemeine Psychiatrie, Universitatsklinik fur Psychiatrie, Wien. firstname.lastname@example.org Since ancient times the influence of chronobiological factors on the pathogenesis, course, and treatment of depression has been well known. Amongst antidepressive treatment strategies two are based on chronobiological knowledge: therapeutic sleep deprivation, which exerts a rapid and dramatic, albeit usually short-lasting, improvement of mood in the majority of patients with major depressive disorder, and light therapy with full-spectrum bright light. About sixty percent of all depressed patients improve after a single night of total or partial sleep deprivation. It has been shown that a combination of pharmacotherapy with antidepressants and sleep deprivation is superior to pharmacotherapy alone. Moreover, sleep deprivation has proved to hasten the onset of action of antidepressant medication and repeated sleep deprivation can also be an efficient treatment strategy in drug refractory depression. Light therapy with bright artificial light is especially beneficial in patients with a fall/winter pattern of depressive symptomatology that has been termed seasonal affective disorder. Similar to sleep deprivation, bright light therapy is characterized by a fast onset of antidepressant action and by the exertion of additive properties to antidepressive medication. Bright light therapy, beginning in the morning after partial sleep deprivation, is able to prevent the depressive relapse after the next night of sleep in sleep deprivation responders. Publication Types: Review Review, Tutorial PMID: 10637957 [PubMed - indexed for MEDLINE] 23: Eur Arch Psychiatry Clin Neurosci 1999;249(5):231-7 How to preserve the antidepressive effect of sleep deprivation: A comparison of sleep phase advance and sleep phase delay. Riemann D, Konig A, Hohagen F, Kiemen A, Voderholzer U, Backhaus J, Bunz J, Wesiack B, Hermle L, Berger M. Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Hauptstr. 5, D-79104 Freiburg, Germany. Dieter_Riemann@Psyallg.UKL.Uni-Freiburg.de Total sleep deprivation (TSD) leads to an immediate amelioration of depressed mood in approximately 70 % of patients with the melancholic subtype of depression. The clinical utility of this procedure is limited, as the improvement usually subsides after the next night of sleep. In the present study, 40 depressed inpatients, being free of psychoactive medication for at least 7 days and who had responded to a TSD were then distributed (according to a matched-pair design) to a sleep phase advance (SPA = time in bed scheduled from 1700-2400 hrs) or a sleep phase delay (SPD = time in bed from 0200-0700 hrs) with a succeeding shift back (for one hour in the SPA group per day) respectively shift forward (for 30 minutes in the SPD group per day), until the initial sleep phase (2300-0600 hrs) was reached after seven days again. Based on previous observations it was hypothesized that a phase advance of the sleep period should prevent responders to TSD from relapsing. Whereas 75% of the TSD responders were stabilized by the phase advanced condition and did not relapse over a period of seven days, only 40% of the patients in the phase delayed condition did not relapse. Polysomnography during the course of the study gave no evidence that the unusual sleep schedules caused prolonged sleep deprivation. Abnormalities of REM sleep persisted both in the clinical responders and non-responders after the sleep wake manipulation. It is concluded that the clinical effectiveness of TSD can be significantly improved by combining TSD with a following phase advance of the sleep period. Publication Types: Clinical Trial Controlled Clinical Trial PMID: 10591988 [PubMed - indexed for MEDLINE] 24: Psychiatr Clin North Am 1999 Sep;22(3):585-607 Rapid-cycling bipolar disorder. An overview of research and clinical experience. Kilzieh N, Akiskal HS. VA Puget Sound Health Care Services, Tacoma, Washington, USA. Although many studies of RCBD have been reported over the last 2 decades, knowledge remains limited. Higher incidence in women is the sole clearly replicated finding in most studies. This finding might be mediated by cyclothymia, a temperament that is of higher prevalence in women and that might be considered as a normal variant of RC. Many questions remain unanswered. Review of putative risk factors, such as hypothyroidism and treatment with antidepressants, provides no conclusive answers. There is clinical evidence to implicate both factors. In principle, the thyroid connection can be approached rationally, yet there seems to be no relationship between thyroid status and response to thyroid augmentation. For this reason and given the potential risks of long-term thyroid use, this strategy should not be the first one to be tried in RC. Cumulatively, naturalistic studies over the past 30 years have strongly implicated antidepressants in switching and cycle acceleration, yet the double-blind, controlled, prospective studies that are needed to provide definitive answers are unlikely to be conducted for ethical reasons discussed in this article. Bipolar family history of RC probands appears indistinguishable from non-RC probands, indicating that most likely RCBD does not breed true. Although RC seems to be more lithium resistant with less likelihood of being symptom-free after 2 to 5 years of follow-up, many of these patients nonetheless have resolution of the RC course. There is no marked difference in suicide rates. An association of RC with bipolar type II, D-M-I pattern and those who switch into mania or hypomania on antidepressants is a provocative possibility: Antidepressants might introduce RC by first inducing a switch during a depressive episode, creating a D-M-I pattern, a pattern that is poorly responsive to lithium, which eventually degenerates into RC. Again, this sequence might be mediated by the high prevalence of cyclothymia in bipolar II patients. Thus, data from phenomenology, family history, and long-term outcome do not support RC as a separate entity. RC appears to be a temporary complicated phase in the illness, not a stable feature. This was noted by Kraepelin: I think I am convinced that that kind of classification must of necessity wreck on the irregularity of the disease. The kind and duration of the attacks and the intervals by no means remain the same in the individual case but may frequently change, so that the case must be reckoned always to new forms. Data by Gottschalk et al testify to the chaotic mood swings of contemporary bipolar disorder. Moreover RC is seen in other medical diseases, such as epilepsy, in which patients have phases of increase in frequency of episodes (seizures) that become refractory to treatment. Further longitudinal prospective studies are required to understand the complexity of this intriguing phenomenon and to provide better treatments. Algorithms deriving from tertiary research or university-based clinical experience may not generalize to RC or otherwise treatment-resistant bipolar patients seen in more routine practice. Illness severity in RCBD generally precludes double-blind controlled investigations. Meanwhile, clinicians may rely on discontinuing antidepressants, maintaining patients on combined mood stabilizers--of which valproate is probably the most useful--and making judicious use of atypical neuroleptics. Benzodiazepines and alcohol (which produce withdrawal), caffeine, stimulants, exposure to bright light, and sleep deprivation during excited phases should be avoided. Thyroid and nimodipine augmentation can be considered in those with the most malignant course. These are patients who need the maximal support that their psychiatrist can provide them. Office visits must be arranged as the last appointment of the day. Publication Types: Review Review, Tutorial PMID: 10550857 [PubMed - indexed for MEDLINE] 25: Psychiatry Res 1999 Jun 30;86(3):267-70 Rate of switch from depression into mania after therapeutic sleep deprivation in bipolar depression. Colombo C, Benedetti F, Barbini B, Campori E, Smeraldi E. IRCCS Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, University of Milan, School of Medicine, Italy. Sleep deprivation is a potentially useful non-pharmacological treatment for depression. A relationship between sleep loss and the onset of mania has been reported, so it is possible that a switch from depression into mania after sleep deprivation might be expected in bipolar depressed patients who are treated with sleep deprivation. In a sample of 206 bipolar depressed treated with three cycles of sleep deprivation, alone or in combination with heterogeneous medications, we observed a 4.85% switch rate into mania and a 5.83% switch rate into hypomania. These percentages are comparable to those observed with antidepressant drug treatments. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 10482346 [PubMed - indexed for MEDLINE] 26: J Clin Psychopharmacol 1999 Jun;19(3):240-5 Ongoing lithium treatment prevents relapse after total sleep deprivation. Benedetti F, Colombo C, Barbini B, Campori E, Smeraldi E. Department of Neuropsychiatric Sciences, Instituto Scientifico Ospedale San Raffaele, University of Milan, School of Medicine, Milano, Italy. email@example.com Forty bipolar depressed inpatients underwent three consecutive cycles of total sleep deprivation (TSD). At the beginning of the study, 20 patients were free of psychotropic drugs and 20 had been receiving lithium medication for at least 6 months. Mood was rated on the Hamilton Rating Scale for Depression before and after TSD; perceived mood changes during treatment were evaluated with self-administered visual analog scales. Patients undergoing long-term lithium treatment showed a significantly better response to TSD as rated on both scales: 13 of 20 patients (vs. 2 of 20 patients without lithium) showed a sustained response during a follow-up period of 3 months. This preliminary evidence of a positive interaction of TSD and long-term lithium treatment could be explained by a synergistic effect of both treatments on brain serotonergic function, possibly via a desensitization of 5-hydroxytryptamine-1A inhibitory autoreceptors. Publication Types: Clinical Trial PMID: 10350030 [PubMed - indexed for MEDLINE] 27: J Psychiatr Res 1999 Jan-Feb;33(1):69-72 Worsening of delusional depression after sleep deprivation: case reports. Benedetti F, Zanardi R, Colombo C, Smeraldi E. Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, University of Milan, School of Medicine, Italy. firstname.lastname@example.org Five patients (three bipolars and two unipolars) affected by a major depressive episode with psychotic features were treated with total sleep deprivation (TSD) without concurrent psychotropic medication. After TSD we observed a worsening in psychotic as well as in depressive symptoms as rated on the Dimension of Delusional Experience Rating Scale and on Hamilton Rating Scale for Depression, respectively. TSD is known to markedly enhance the activity of brain monoaminergic pathways. Given the interaction between brain serotonergic and dopaminergic systems in delusional depression, it is possible that an enhancement in dopaminergic activity may be responsible of the symptomatological worsening in delusional depressives observed after TSD. Publication Types: Clinical Trial PMID: 10094242 [PubMed - indexed for MEDLINE] 28: Neuropsychopharmacology 1999 Apr;20(4):380-5 Sustained antidepressant effect of sleep deprivation combined with pindolol in bipolar depression. A placebo-controlled trial. Smeraldi E, Benedetti F, Barbini B, Campori E, Colombo C. Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, University of Milan, School of Medicine, Italy. Total sleep deprivation (TSD) shows powerful but transient clinical effects in patients affected by bipolar depression. Pindolol blocks the serotonergic 5-HT1A autoreceptor, thus improving the antidepressant effect of selective serotonin reuptake inhibitors. We evaluated the interaction of TSD and pindolol in the treatment of acute episodes of bipolar depression. Forty bipolar depressed inpatients were randomized to receive pindolol 7.5 mg/day or placebo for nine days in combination with three consecutive TSD cycles. Pindolol significantly improved the antidepressant effect of TSD, and prevented the short-term relapse after treatment. The response rate (HDRS scores < 8) at the end of treatment was 15/20 for pindolol, and 3/20 for placebo. Coadministration of pindolol and TSD resulted in a complete response, which could be sustained for six months with lithium salts alone, in 65% of cases. This results suggest a major role for serotonergic transmission in the mechanism of action of TSD, and makes TSD treatment more effective in the treatment of bipolar depression. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 10088139 [PubMed - indexed for MEDLINE] 29: Psychiatry Res 1998 Jun 2;79(1):43-50 The unipolar-bipolar dichotomy and the response to sleep deprivation. Barbini B, Colombo C, Benedetti F, Campori E, Bellodi L, Smeraldi E. IRCCS Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, University of Milan, School of Medicine, Milano, Italy. Fifty-one inpatients affected by a major depressive episode were divided into four groups according to mood disorder diagnosis and previous clinical history (bipolar disorder type I; bipolar disorder type II; major depressive disorder with at least three previous depressive episodes; and single depressive episode patients) and administered three consecutive total sleep deprivation (TSD) cycles. Mood changes were rated with a reduced version of the Hamilton Depression Rating Scale and with self-administered visual analogue scales. TSD caused better clinical effects in bipolar and single-episode patients; in particular, unipolar patients lacked effects in perceived mood after the first TSD and showed worse Hamilton ratings in respect to the other groups after the three TSD treatments. Discriminant function analysis could correctly classify 80% of bipolar patients, post hoc, based on TSD response. Further researches on the clinical efficacy of TSD must take into account the heterogeneity of depression and of its biological substrate. Publication Types: Clinical Trial PMID: 9676825 [PubMed - indexed for MEDLINE] 30: Brain Res Mol Brain Res 1998 Jun 15;57(2):235-40 REM sleep deprivation increases the levels of tyrosine hydroxylase and norepinephrine transporter mRNA in the locus coeruleus. Basheer R, Magner M, McCarley RW, Shiromani PJ. VA Medical Center and Harvard Medical School, Brockton, MA 02401, USA. The present study was conducted to determine the effects of REM sleep deprivation on the levels of tyrosine hydroxylase (TH) and norepinephrine transporter (NET) mRNA in the locus coeruleus (LC) of rats. The animals were deprived of REM sleep for 1, 3 or 5 days, then killed and changes in the mRNA levels were determined using in situ hybridization. The levels of both TH and NET mRNA increased in animals deprived of REM sleep for 3 days or longer whereas no change in these messages were observed in the LC of control animals. REM sleep deprivation has been used as a mode of treatment for major depression. Others have shown that treatment with tricyclic antidepressants also results in increased levels of TH and NET mRNA in LC. Our results suggest that the antidepressant effect of REM sleep deprivation and tricyclic antidepressants may share similar molecular changes in the norepinephrine system. PMID: 9675421 [PubMed - indexed for MEDLINE] 31: Biol Psychiatry 1998 Jun 1;43(11):829-39 Microsleep during partial sleep deprivation in depression. Hemmeter U, Bischof R, Hatzinger M, Seifritz E, Holsboer-Trachsler E. Depression Research Unit, Psychiatric University Hospital, Basel, Switzerland. BACKGROUND: Sleep deprivation (SD) exerts a beneficial effect on mood and sleep in about 60% of depressed patients usually followed by a relapse into depression after the recovery night. Short phases of sleepiness, especially naps in the early morning, may be responsible for this phenomenon. METHODS: To evaluate the effect of short, even ultrashort phases of sleep-microsleep (MS) during partial sleep deprivation (PSD) on mood, cognitive psychomotor performance (CPP), and sleep, an electroencephalograph (EEG) was continuously recorded over 60 hours in 12 patients with major depression. Subjective mood was assessed by a visual analogue scale and CPP by a letter cancellation test. RESULTS: The results illustrate that in depressed patients during PSD the amount of MS is increased, predominantly in the early morning, which was subjectively unrecognized and not observed by nursing staff. Patients with a low cumulative amount of MS during PSD improved significantly in mood, CPP, and sleep pattern compared to the patients with a high amount of MS who showed only slight changes. CONCLUSION: Therefore, accumulated MS may influence the SD-induced positive effects in depressed patients. PMID: 9611673 [PubMed - indexed for MEDLINE] 32: Nervenarzt 1998 Jan;69(1):66-9 [Sleep deprivation and subsequent sleep phase advance stabilizes the positive effect of sleep deprivation in depressive episodes] [Article in German] Albert R, Merz A, Schubert J, Ebert D. Psychiatrische Universitatsklinik mit Poliklinik, Erlangen. Approximately 60% of patients with major depression disorder show a beneficial response to total sleep deprivation (TSD), but the positive effect of TSD is short, and naps or the following night's sleep destroy it. Various methods have been tried to stabilize the positive sleep-deprivation effect. A consecutive 1-week advance in the sleep phase stabilized mood in more than 50% of the sleep-deprivation responders. We examined 40 male patients with major depression who in addition to medical treatment took part in a phase advance study to prove possible synergistic effects. About 60% of the patients showed positive mood stabilization after 1-week of treatment when the patients were sleep-deprivation responders. These results support data from other groups. PMID: 9522335 [PubMed - indexed for MEDLINE] 33: J Affect Disord 1998 Feb;48(1):69-74 Sleep deprivation response in seasonal affective disorder during a 40-h constant routine. Graw P, Haug HJ, Leonhardt G, Wirz-Justice A. Chronobiology and Sleep Laboratory, Psychiatric University Clinic, Basel, Switzerland. BACKGROUND: There are no controlled studies investigating the response of patients with seasonal affective disorder (SAD) to a total sleep deprivation (SD). METHODS: The clinical response to SD of patients with SAD in winter was investigated under the stringently controlled conditions of a 40-h constant routine protocol. RESULTS: 52% of the SAD patients (N=11 women) improved, using a mean of a multiple ratings. This is in the range of response found for non-seasonal major depression. In contrast, controls (N=8 women) showed less improvement of mood (29%). CONCLUSION: SAD patients respond to SD as do non-seasonal major depressives. The best discrimination of response was obtained in an observer rating (Clinical Global Impression: global severity improvement), and the morning values of two different self ratings (v. Zerssen depression scale, 100 mm VAS with the criterion of > or =10 mm improvement). LIMITATION: A more reliable estimate of the SD response rate in SAD patients would require a larger group. CLINICAL RELEVANCE: SAD patients do not differ from other subgroups of major depression in their response to SD, and therefore this is an additional treatment option to light therapy. PMID: 9495604 [PubMed - indexed for MEDLINE] 34: Depress Anxiety 1997;6(3):113-8 Accelerating response in geriatric depression: a pilot study combining sleep deprivation and paroxetine. Bump GM, Reynolds CF 3rd, Smith G, Pollock BG, Dew MA, Mazumdar S, Geary M, Houck PR, Kupfer DJ. Mental Health Clinical Research Center for the Study of Late-Life Mood Disorders, University of Pittsburgh, PA 15213, USA. Elderly depressed patients often require an average of 12 weeks of pharmacotherapy before attaining remission. The delay between treatment initiation and remission may decrease compliance and prolongs suffering; hence, interventions that decrease the time to onset of antidepressant activity are needed. Our objective was to evaluate, in an open trial, the use of one night of total sleep deprivation combined with paroxetine to accelerate antidepressant response in elderly patients. Thirteen elderly patients with major depression were sleep-deprived for one night and started paroxetine on the night of recovery sleep. Patients were followed for twelve weeks, and clinical improvement was rated using the 17-item Hamilton Depression Rating Scale and a version of the Hamilton modified for sleep deprivation studies. 8/13 (62%) patients experienced significant improvement of depressive symptoms by 2 weeks. Within 12 weeks 11/13 (85%) patients responded to the combination of sleep deprivation and paroxetine. Median response time was 2 weeks. Clinical response at 12 weeks was correlated with changes in Sleep Deprivation Depression Rating Scale Scores between baseline and recovery sleep. In an open trial, the combined use of total sleep deprivation and paroxetine appears to be an effective method for speeding the onset of clinical antidepressant activity in geriatric depression and for improving early recognition of non-response. Publication Types: Clinical Trial PMID: 9442985 [PubMed - indexed for MEDLINE] 35: Psychiatry Res 1997 Sep 29;75(2):67-74 Can response to partial sleep deprivation in depressed patients be predicted by regional changes of cerebral blood flow? Volk SA, Kaendler SH, Hertel A, Maul FD, Manoocheri R, Weber R, Georgi K, Pflug B, Hor G. Department of Clinical Psychiatry and Psychotherapy II, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. The possible predictive value of regional cerebral perfusion patterns with respect to the response to partial sleep deprivation (PSD) was evaluated in 15 major depressive patients (mean age = 54.9 years, mean Hamilton depression score = 21.6). Patients were studied with single photon emission computed tomography with technetium-99 m-D,L-hexamethyl-propylene amine oxime. Scans were performed on the morning before and after (at 08.00 h) PSD. Responders to PSD had significantly higher perfusion in the right orbitofrontal cortex than did non-responders before PSD. Multiple regression analysis indicated that right orbitofrontal/basal cingulate perfusion (r = -0.77, P < 0.001) before PSD, and left inferior temporal perfusion (r = 0.59, P = 0.01) after PSD, were fairly accurate predictors of change in Hamilton depression scores. Thus, it appears that the orbitofrontal cortex and the cingulate are involved in PSD and may serve as predictors of therapeutic response. PMID: 9351489 [PubMed - indexed for MEDLINE] 36: Am J Psychiatry 1997 Jun;154(6):870-2 Comment in: Am J Psychiatry. 1998 Aug;155(8):1134-5. Sleep deprivation combined with consecutive sleep phase advance as a fast-acting therapy in depression: an open pilot trial in medicated and unmedicated patients. Berger M, Vollmann J, Hohagen F, Konig A, Lohner H, Voderholzer U, Riemann D. Klinikum der Albert-Ludwigs-Universitat Freiburg, Germany. email@example.com OBJECTIVE: The authors' goal was to test the hypothesis that the antidepressant effect of total sleep deprivation can be maintained by initially avoiding sleep during a supposedly "critical" time period in the early morning. METHOD: They studied 33 inpatients with major depression, melancholic type, all of whom responded positively to total sleep deprivation. Twelve of the patients were men and 21 were women; their mean age was 46.7 years (SD = 13.7). After total sleep deprivation, the patients started a sleep schedule from 5:00 p.m. to 12:00 midnight, which then was shifted back by 1 hour each day until a sleep time of 11:00 p.m. to 6:00 a.m. was reached. RESULTS: Twenty (61%) of the 33 patients who responded to total sleep deprivation with an improved state of mood maintained this improvement during sleep phase advance therapy. Drug-free and medicated patients did not differ from each other. CONCLUSIONS: The rapid amelioration of mood observed with total sleep deprivation can be preserved with a succeeding phase shift of the sleep period. Publication Types: Clinical Trial PMID: 9167521 [PubMed - indexed for MEDLINE] 37: J Affect Disord 1997 Feb;42(2-3):93-101 Can negative self-schemes in depressives be altered through sleep deprivation? Baving L, Maes H, Bohus M, Lis S, Krieger S, Olbrich H, Berger M. Psychiatric Hospital, Albert-Ludwig University, Freiburg, Germany. This paper addresses the question whether negative cognitive style represents a state or trait variable of depressive patients. For this reason, it studies the influence of sleep deprivation on negative self-schemes of those patients. 10 patients suffering from DSM-III-R major depression were compared with 10 age- and sex-matched controls on a task for rating the self-descriptiveness of positive and negative adjectives as well as a subsequent word recognition task. Three sessions were involved: an initial session (baseline), the second following a night of sleep deprivation, and the third after a successive full night's sleep. During the baseline examination, depressives showed a relatively negative cognitive bias; that is, the same number of positive and negative self-scheme elements. In comparison to controls, they showed significantly more negative and significantly less positive self-scheme elements. The same pattern emerged in a word recognition task for the number of recognized self-scheme elements. These variables indicated no change in the depressive group following sleep deprivation. Depressive subjects' reaction times on self-descriptiveness rating were significantly longer for positive than for negative self-scheme elements at the baseline session. The opposite was true for controls. Here, a sleep deprivation effect was evident. There was no longer a difference in the speed of information processing for positive as compared to negative self-scheme elements. This applied to both depressive and control groups. PMID: 9105950 [PubMed - indexed for MEDLINE] 38: Eur Arch Psychiatry Clin Neurosci 1997;247(2):100-3 Sleep deprivation hastens the antidepressant action of fluoxetine. Benedetti F, Barbini B, Lucca A, Campori E, Colombo C, Smeraldi E. Department of Neuropsychiatric Sciences, Istituto Scientifico Ospedale San Raffaele, School of Medicine, University of Milan, Italy. Among ten bipolar depressed patients admitted to our psychiatric ward, five patients were treated with fluoxetine alone and five subjects were treated with fluoxetine in association with total sleep deprivation (TSD) in order to evaluate the effect of the interaction between the administration of the serotonergic antidepressant compound fluoxetine and repeated cycles of TSD. Patients treated with fluoxetine plus repeated TSD showed a faster amelioration of depressive symptomatology compared with the other group. We discuss our findings hypothesizing an enhancement in dopaminergic and possibly in serotonergic transmission due to repeated TSD adding to the increase in serotonergic transmission due to fluoxetine medication. Publication Types: Clinical Trial Controlled Clinical Trial PMID: 9177956 [PubMed - indexed for MEDLINE] 39: Psychiatry Res 1996 Dec 20;65(3):179-84 Dopamine agonist amineptine prevents the antidepressant effect of sleep deprivation. Benedetti F, Barbini B, Campori E, Colombo C, Smeraldi E. Istituto Scientifico Ospedale San Raffaele, IRCCS Department of Neuropsychiatric Sciences, University of Milan School of Medicine, Italy. In a double-blind study, the effects of the interaction between the administration of amineptine versus placebo and repeated cycles of total sleep deprivation (TSD), which is thought to act through an enhancement in dopaminergic transmission, were analyzed. Twenty-two consecutively admitted patients with bipolar depression formed the study group. Repeated administrations of TSD significantly enhanced perceived mood levels in placebo-treated patients, while amineptine administration blocked the antidepressant action of TSD. Hypothesized changes in brain dopaminergic transmission attributable to amineptine pretreatment are discussed. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 9029666 [PubMed - indexed for MEDLINE] 40: Neuropsychopharmacology 1996 Oct;15(4):332-9 Eye-blink rates and depression. Is the antidepressant effect of sleep deprivation mediated by the dopamine system? Ebert D, Albert R, Hammon G, Strasser B, May A, Merz A. Department of Psychiatry, University of Erlangen, Germany. A series of studies demonstrated a possible correlation between eye-blink rate and central dopamine activity. The hypothesis has been put forward that the antidepressant effect of sleep deprivation (SD) is mediated by an enhanced dopamine release resulting in an amphetaminelike action of SD. Therefore, the blink rates of 12 drug-naive patients with major depression and 12 healthy controls were compared before and after SD and before and after 2.5 mg bromocriptine as a dopaminergic challenge. The main result of the study was that the depressed patients had a significantly higher increase of blinking after SD both with and without a dopaminergic challenge. Basal eye-blink rate was not different in nonretarded major depression patients compared to controls. Sleep deprivation increased blink rate in depression patients but not in controls, and the increase was proportional to improvements in depressive state after sleep deprivation. Bromocriptine did not increase blink rate 1 hour after application. This result is consistent with the hypothesis that antidepressant SD acts through dopamine release, although it is not conclusive, because other neurotransmitters like acetylcholine may be involved in the regulation of blinking. PMID: 8887987 [PubMed - indexed for MEDLINE] 41: J Affect Disord 1996 Apr 12;37(2-3):121-8 Advanced vs. normal sleep timing: effects on depressed mood after response to sleep deprivation in patients with a major depressive disorder. Riemann D, Hohagen F, Konig A, Schwarz B, Gomille J, Voderholzer U, Berger M. Psychiatric Department, University of Freiburg, Germany. Total sleep deprivation (TSD) exerts beneficial but only transient effects on mood in patients with a major depressive disorder (MDD). Though approximately 50 to 70% of depressed patients improve after sleep deprivation, the majority relapse after recovery sleep, some even after a short nap. One theoretical model postulates a critical period in the early morning hours where sleep is likely to induce a relapse, and nap studies indicate that sleep may be particularly 'depressogenic' at this time of day. A second model attributes the relapse to the release of non-REM sleep. We therefore compared the impact of an advanced sleep period (17:00-24:00 h) to a normal sleep period (23:00-06:00 h) on mood in patients who had responded to sleep deprivation. Less relapses into depression occurred after advanced sleep. Polysomnographic data showed that, as expected, normal sleep was characterized by a more pronounced improvement of sleep continuity and increased slow-wave sleep. The normal sleep group showed a stronger decrease in REM sleep density than the advanced sleep group compared with baseline. These data add to a growing body of evidence that the timing of sleep following successful sleep deprivation may be crucial for a stabilization of its antidepressant effect. Thus, avoidance of sleep during a "critical period' for more than a single night is necessary to provide a longer-lasting treatment modality. PMID: 8731074 [PubMed - indexed for MEDLINE] 42: J Affect Disord 1996 Feb 12;37(1):31-41 Amitriptyline in combination with repeated late sleep deprivation versus amitriptyline alone in major depression. A randomised study. Kuhs H, Farber D, Borgstadt S, Mrosek S, Tolle R. Department of Psychiatry, University of Munster, Germany. Only few systematic studies are available on the status of sleep deprivation therapy in the overall treatment regimen of depressive patients. 51 patients suffering from a major depressive episode (ICD-10) were randomly allocated to 4 weeks' treatment with amitriptyline (150 mg/day) or to a combination of amitriptyline with six partial-sleep-deprivation treatments late in the night (at 4-5 day intervals). According to observer rating (Hamilton Rating Scale for Depression, 21- and 10-item version), a highly significant amelioration was recorded in both groups until the 14th day of treatment. A further improvement occurred, however, only in those patients treated with both antidepressants and sleep deprivation. Hence the response rate ( > or = 50% HAMD reduction) after 4 weeks' treatment was distinctly more favourable in this group than in those patients under pharmacotherapy alone. The superiority of the combined therapy cannot be confirmed statistically by self-rating (Befindlichkeitsskala: von Zerssen; Visual Analogue Mood Scale). The immediate antidepressive effect of sleep deprivation diminished in the course of the sleep deprivation series. The response to the first sleep deprivation was a predictor neither for the response to further sleep deprivation treatments nor for the overall treatment outcome. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 8682976 [PubMed - indexed for MEDLINE] 43: Wien Med Wochenschr 1996;146(13-14):309-10 [Subjective diurnal fatigue and sleep deprivation response] [Article in German] Volk S, von Nessen S, Brandt J, Georgi K, Pflug B. Klinik fur Klinische Psychiatrie und Psychotherapie II, Johann-Wolfgang-Goethe-Universitat, Frankfurt am Main, Deutschland. 29 major depressive patients, the majority suffering from a melancholic subtype and typical diurnal variation of mood, rated subjective tiredness on a 100 mm analogous scale before and after total sleep deprivation (TSD). In study A every four hours during the day before and after TSD and every 2 hours during the TSD-night ratings were performed, in study B at 8.00 a.m. before and after TSD. The mean response rate was 55.2% in the 2 studies. In study A subsequent responders were less tired during the afternoon before TSD. Responding patients were more alert the morning after sleep deprivation than non-responders. A higher inter-individually variability of tiredness ratings in responders before and after sleep deprivation was found in study B, assuming an arousing property and a greater variability in subjective arousal at least during the morning hours. In summary the determination of the subjective arousal level may help to predict response. PMID: 9012163 [PubMed - indexed for MEDLINE] 44: Prog Neuropsychopharmacol Biol Psychiatry 1995 Jul;19(4):593-602 Serial partial sleep deprivation as adjuvant treatment of depressive insomnia. Hemmeter U, Seifritz E, Hatzinger M, Muller MJ, Holsboer-Trachsler E. Departement of Psychiatry, University of Basel, Switzerland. 1. Sleep disturbance is a prominent symptom of major depression. Despite specific treatment with antidepressants, there is a substantial number of patients who improve in depressed mood but remain sleep disturbed. 2. Polysomnographic sleep (PSG) data and self reported sleep measures were assessed at baseline and after one week in 18 patients (35-65 years) randomly assigned to treatment with either trimipramine alone 200 mg/d (group 1) or trimipramine (200 mg/d) and additional serial partial sleep deprivation in the second half of the night (3x/week) (group 2). 3. In group 1 no marked changes between baseline and after treatment were found. 4. In group 2 the PSG data showed a significant increase of slow wave sleep and a compensatory decrease in stage 1. Sleep continuity improved in terms of numbers of awakenings, sleep onset latency and total sleep time. These changes were in parallel with the subjective estimation of sleep in group 2. 5. There was no significant difference in the Hamilton rating scale scores neither at baseline nor after treatment. 6. These observed effects on sleep following additional serial PSD therapy seem to occur independent from the antidepressive effect. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 8588058 [PubMed - indexed for MEDLINE] 45: Biol Psychiatry 1995 Apr 1;37(7):457-61 The relationship between tiredness prior to sleep deprivation and the antidepressant response to sleep deprivation in depression. Bouhuys AL, van den Burg W, van den Hoofdakker RH. Department of Biological Psychiatry, University Hospital, Groningen, The Netherlands. Recently it was hypothesized that the antidepressant response to total sleep deprivation (SD) results from a disinhibition process induced by the increase of tiredness in the course of SD. In the present study, the role of tiredness in the antidepressant response to SD is further investigated. Seventy-two depressed patients scored subjective tiredness and depressed mood three times daily (in the morning, afternoon, and evening) on the days preceding and following SD. It was found that averaged tiredness on the day prior to SD was related to the SD response, when the severity of depression prior to SD had been held statistically constant. Also, when both severity of depression and diurnal variation of mood prior to SD were partialed out, tiredness showed a positive correlation with the SD response: patients who reported a relatively low degree of tiredness on the day preceding SD improved by SD. This result suggests that tiredness has an influence on SD effects, and that this influence is independent from that of the severity of depression. The findings are in accordance with current ideas on the role of tiredness as a mediating factor in the induction of the therapeutic effects of SD. PMID: 7786959 [PubMed - indexed for MEDLINE] 46: Biol Psychiatry 1994 May 15;35(10):794-7 Effects of sleep on the antidepressant response to sleep deprivation. Reist C, Chen CC, Chhoeu A, Berry RB, Bunney WE Jr. Psychiatry Service, Veterans Affairs Medical Center, Long Beach, CA 90822. The effect of a 90-min nap period on mood was studied in 22 sleep-deprived patients with a diagnosis of major depression. All patients remained awake from 7 AM until 12 noon the following day at which time they were permitted to nap while being monitored by sleep encephalography. Fifteen subjects showed a significant response to sleep deprivation as defined by a 35% improvement on the Hamilton Rating Scale for Depression. After the nap a relapse of depressive symptoms occurred which was significantly related to the amount of non-rapid eye movement sleep time. PMID: 8043709 [PubMed - indexed for MEDLINE] 47: Psychiatry Res 1994 Mar;51(3):283-95 Lithium sustains the acute antidepressant effects of sleep deprivation: preliminary findings from a controlled study. Szuba MP, Baxter LR Jr, Altshuler LL, Allen EM, Guze BH, Schwartz JM, Liston EH. Department of Psychiatry, University of Pennsylvania, School of Medicine, Philadelphia 19104-4283. Early morning sleep deprivation (patient awake from 0200 to 2200 hours) produces a same-day antidepressant effect in approximately one-half of patients with major depression. Unfortunately, these antidepressant effects are short-lived and patients usually relapse to baseline depression levels within 48 hours. Recent work suggests, however, that the use of lithium with early morning sleep deprivation sustains this rapid antidepressant effect and makes it clinically useful. In a 30-day study, we compared the abilities of four different treatments (lithium plus early morning sleep deprivation, lithium plus a control sleep deprivation procedure, and desipramine with either of the two sleep manipulations) to induce a rapid (next-day) and sustained antidepressant response in 16 depressed patients. Lithium plus early morning sleep deprivation produced a quicker response than lithium with the control sleep deprivation, and the response was sustained for at least 30 days. In this design, however, lithium/early morning sleep deprivation was no faster than either of the two desipramine/sleep deprivation conditions in inducing remission. These results support the results of previous studies and suggest further investigation of this novel sleep/pharmacologic intervention is warranted. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 8208874 [PubMed - indexed for MEDLINE] 48: Br J Psychiatry 1993 Nov;163:679-80 Mania following sleep deprivation. Wright JB. St James's University Hospital, Leeds. A first episode of mania is described in a previously healthy man who was partially sleep deprived for four nights. The sleep deprivation preceded the psychosis. During the psychotic episode he believed that he was the Messiah. This case is discussed in the light of reports exploring the relationship between psychosis and sleep deprivation. PMID: 8298841 [PubMed - indexed for MEDLINE] 49: Psychiatry Res 1993 Nov;49(2):109-20 Naps after total sleep deprivation in depressed patients: are they depressiogenic? Riemann D, Wiegand M, Lauer CJ, Berger M. Sleep-EEG Laboratory, Psychiatric Clinic, Central Institute of Mental Health, Mannheim, Germany. Total sleep deprivation (TSD) exerts beneficial but transient effects on mood in approximately 60% of patients with a major depressive disorder. The positive effects of a night of total sleep deprivation are generally reversed after the next night of sleep. Several anecdotal reports and a pilot study by our group indicated that even short naps during the period of sleep deprivation are capable of re-inducing depressive mood in responders to TSD. The present study explored whether the structure of naps at 9 a.m. was crucial for the "depressiogenic" impact of naps on mood. A negative effect on mood was replicated, but this effect was not related to any of the nap sleep variables. The effect of naps on mood was attenuated in the early afternoon. The results support the assumption of a "depressiogenic" effect of naps in patients with major depression after successful TSD. PMID: 8153186 [PubMed - indexed for MEDLINE] 50: Biol Psychiatry 1993 Mar 15;33(6):467-76 Effect of morning and afternoon naps on mood after total sleep deprivation in patients with major depression. Wiegand M, Riemann D, Schreiber W, Lauer CJ, Berger M. Max Planck Institute of Psychiatry, Munich, Germany. In 30 depressed patients who had responded to total sleep deprivation therapy, morning naps led more frequently to relapses into depression than did afternoon naps. Longer naps were less detrimental than shorter ones, and there was no significant relationship between the effect of a nap on mood and its content of slow-wave-sleep. The amount of the rapid eye-movement sleep, too, was unrelated to clinical nap effects. Thus, some of the current theories on the relationship between sleep and depressive symptomatology are not supported by the data. Our results demonstrate the importance of nap timing, suggesting a circadian variation of propensity to relapse into depression. PMID: 8490073 [PubMed - indexed for MEDLINE] 51: Psychiatry Res 1993 Mar;46(3):213-27 A clinical trial of sleep deprivation in combination with antidepressant medication. Leibenluft E, Moul DE, Schwartz PJ, Madden PA, Wehr TA. Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, MD 20892. The literature suggests that sleep deprivation can potentiate the effect of antidepressant medication in depressed patients. However, the clinical efficacy of sleep deprivation has not been demonstrated definitively, in part because it is difficult to design an adequate control condition. We conducted a trial of sleep deprivation in 26 depressed patients who remained symptomatic despite 3 months of treatment with antidepressant medication. Since the literature indicates that early sleep deprivation (ESD), carried out in the first half of the night, is a less effective antidepressant than late sleep deprivation (LSD), carried out in the second half of the night, we designed a study that attempted to use ESD as a control condition for LSD. Patients were randomly assigned to ESD or LSD, received a total of 4 nights of sleep deprivation over 2 weeks, and were followed in clinic for the 3 subsequent weeks. ESD proved to be as effective an antidepressant as LSD, with the overall sample showing a mild, but statistically significant, response. There was a significant correlation between patients' acute response at the time of the first course of sleep deprivation treatments and their improvement over the course of the study. There were significant changes in plasma levels of thyroid stimulating hormone, free triiodothyronine, prolactin, and cortisol measured at 8 a.m. before and after sleep deprivation, and in the followup period, but there were no significant correlations between changes in hormonal levels and either acute or chronic response to sleep deprivation. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 8493292 [PubMed - indexed for MEDLINE] 52: Acta Psychiatr Scand 1993 Feb;87(2):102-9 Antidepressant response to sleep deprivation as a function of time into depressive episode in rapidly cycling bipolar patients. Gill DS, Ketter TA, Post RM. Biological Psychiatry Branch, US National Institutes of Mental Health, Bethesda, Maryland 20892. Three patients with treatment-resistant rapidly cycling bipolar disorder were studied with multiple sleep deprivations (SD) during several depressive episodes to assess the effect of phase or duration of a depressive episode on SD response. There was little response to SD early in a depressive episode, but responses were often robust late in an episode, sometimes triggering its termination. In 2 subjects, the duration of antidepressant response to SD increased linearly as time into episode increased. Neither the number of SD given in an episode nor the medication status of the patients appeared to account for the observed increases in antidepressant response. These results suggest that the neurobiological substrates underlying depression may change over the course of an episode, resulting in an increased responsivity to sleep deprivation later compared with earlier in the course of an episode in rapidly cycling patients. The generalizability of these findings to unipolar patients remains to be explored. PMID: 8447235 [PubMed - indexed for MEDLINE] 53: J Affect Disord 1993 Feb;27(2):107-16 Therapy and prevention of affective illness by total sleep deprivation. Papadimitriou GN, Christodoulou GN, Katsouyanni K, Stefanis CN. Department of Psychiatry, Athens University Medical School, Greece. The therapeutic effect of total sleep deprivation (SD) given twice a week, for 4 weeks, was investigated in 16 drug-free patients with major affective disorders. The response was excellent in five patients, satisfactory in three and minimal in eight patients. Six of these patients were treated prophylactically once a week, and four had an excellent response. Additionally, out of five normothymic drug-free patients with affective illness treated prophylactically with SD, without prior therapeutic SD treatment, three had an excellent response. The majority of responders were rapid cycling patients. This method is worth applying to patients resistant to classical treatment. PMID: 8440806 [PubMed - indexed for MEDLINE] 54: Biol Psychiatry 1993 Jan 1;33(1):54-7 Sleep deprivation with consecutive sleep-phase advance therapy in patients with major depression: a pilot study. Vollmann J, Berger M. Department of Psychiatry, University of Freiburg, Germany. PMID: 8420597 [PubMed - indexed for MEDLINE] 55: Eur Neuropsychopharmacol 1992 Dec;2(4):463-5 Sleep deprivation in rapid-cycling bipolar affective disorder: case report. Benjamin J, Zohar J. Division of Psychiatry, Ben Gurion University of the Negev, Israel. We describe a 4-month long hypomanic response to sleep deprivation in a patient with consistent (20-day cycles) rapid cycling. He subsequently reverted to very rapid cycling; however, sleep deprivation remained effective for each attack of depression. Sleep deprivation treatment, its immediate but short-lived beneficial effect, may have a role in the treatment of the ultra-short depressions encountered in very rapid cycling. PMID: 1490098 [PubMed - indexed for MEDLINE] 56: Acta Psychiatr Scand 1992 Dec;86(6):478-83 Evaluation of the effects of total sleep deprivation on cerebral blood flow using single photon emission computerized tomography. Volk S, Kaendler SH, Weber R, Georgi K, Maul F, Hertel A, Pflug B, Hor G. Department of Psychiatry II, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. HMPAO-single photon emission computerized tomography (SPECT) is a useful technique in studying cerebral blood flow (CBF). This method is suitable to evaluate the differences of CBF with reference to total sleep deprivation (TSD) within 24 h because of the short half-life of the radiopharmaceutical compound. In the present study, CBF before and after TSD was analysed in patients suffering from major depression. The morning before and after TSD, Tc-HMPAO-SPECT was performed in 20 patients. Hamilton Rating Scale for Depression scores and subjective ratings were obtained daily. Eleven patients responded to TSD; 9 were nonresponders. The main finding was a significant left temporal and mainly right parietal increase of CBF, which was observed in the responders only. CBF values and the severity of depression correlated inversely. PMID: 1471542 [PubMed - indexed for MEDLINE] 57: Acta Psychiatr Scand 1992 Jul;86(1):84-5 Therapeutic sleep deprivation in a depressed patient: prolongation of response with concurrent thyroxine. Southmayd SE, Kasurak P, MacDonald B, Waldron J. Department of Psychiatry, Queen's University Ontario, Canada. A 53-year-old woman with major depression was studied throughout 7 trials of therapeutic sleep deprivation (SD). Under conditions where the patients was either medication-free or receiving antidepressant therapy, improvement with SD was followed by full relapse on returning to sleep. Four SD sessions conducted while the patient was receiving thyroxine each resulted in remission, sustained for several days. These results suggest that the beneficial effects of SD may be mediated by thyroid hormones, or associated activity in the hypothalamic-pituitary-adrenal axis. PMID: 1414408 [PubMed - indexed for MEDLINE] 58: J Clin Psychiatry 1992 Jun;53(6):204-6 Response to sleep deprivation in three women with postpartum psychosis. Strouse TB, Szuba MP, Baxter LR Jr. Department of Psychiatry and Biobehavioral Sciences, University of California, School of Medicine, Los Angeles. BACKGROUND: Postpartum psychotic disorders are rare and poorly understood phenomena occurring after approximately 1 in 2000 births. Increasing attention has been given to the concept of postpartum psychosis as an affective spectrum disorder. We sought to characterize the responses to sleep deprivation of three women with postpartum psychotic and mood symptoms. METHOD: Three hospitalized postpartum women with no prior history of psychotic disorder were treated according to a partial sleep deprivation protocol. Each patient was awakened at 2:00 a.m. and kept awake until 9:00 p.m. the following night. A full and an abbreviated Hamilton Rating Scale for Depression (HAM-D) were completed for each patient before and after partial sleep deprivation. RESULTS: Two of the three patients became transiently manic and the third became hypomanic after sleep deprivation. HAM-D scores decreased drastically for each patient. After recovery sleep, each patient de-escalated but required further treatment with mood-stabilizing agents. CONCLUSION: These findings suggest that postpartum psychosis in our patients may represent a variant of bipolar affective disorder. PMID: 1607349 [PubMed - indexed for MEDLINE] 59: Am J Psychiatry 1992 Apr;149(4):538-43 Effect of sleep deprivation on brain metabolism of depressed patients. Wu JC, Gillin JC, Buchsbaum MS, Hershey T, Johnson JC, Bunney WE Jr. Department of Psychiatry and Human Behavior, College of Medicine, University of California, Irvine 92717. OBJECTIVE: Sleep deprivation is a rapid, nonpharmacologic antidepressant intervention that is effective for a subset of depressed patients. The objective of this study was to identify which brain structures' activity differentiates responders from nonresponders and to study how metabolism in these brain regions changes with mood. METHOD: Regional cerebral glucose metabolism was assessed by positron emission tomography (PET) with [18F]deoxyglucose (FDG) before and after total sleep deprivation in 15 unmedicated awake patients with unipolar major depression and 15 normal control subjects, who did the continuous performance test during FDG uptake. RESULTS: After sleep deprivation, four patients showed a 40% or more improvement on the Hamilton Rating Scale for Depression. Before sleep deprivation the depressed responders had a significantly higher cingulate cortex metabolic rate than the depressed nonresponders, and this normalized after sleep deprivation. The normal control subjects and nonresponding depressed patients showed no change in cingulate metabolic rate after sleep deprivation. CONCLUSIONS: Overactivation of the limbic system as assessed by PET scans may characterize a subset of depressed patients. Normalization of activity with sleep deprivation is associated with a decrease in depression. PMID: 1554042 [PubMed - indexed for MEDLINE] 60: J Affect Disord 1992 Feb;24(2):101-8 Can non-REM sleep be depressogenic? Beersma DG, van den Hoofdakker RH. Department of Biological Psychiatry, University Hospital, Groningen, Netherlands. Sleep and mood are clearly interrelated in major depression, as shown by the antidepressive effects of various experiments, such as total sleep deprivation, partial sleep deprivation, REM sleep deprivation, and temporal shifts of the sleep period. The prevailing hypotheses explaining these effects concern the antidepressant potency of the suppression of either REM sleep or non-REM sleep. This issue is discussed in the light of present knowledge of the kinetics of non-REM sleep intensity, REM sleep production, and their interaction. Recent findings have led us to suggest that the suppression of non-REM sleep intensity is the common pathway in the set of experimental data on the antidepressant effects of sleep manipulations. PMID: 1541764 [PubMed - indexed for MEDLINE] 61: Encephale 1992 Jan;18 Spec No 1:45-50 The role of sleep and wakefulness in the genesis of depression and mania. Kasper S, Wehr TA. Psychiatric Department, University of Bonn, FRG. Disturbances of the sleep-wake cycle are frequently seen in affective illness and are exhibited in other psychiatric illness as well. In addition to being a useful research probe, manipulations of the sleep-wake cycle such as sleep deprivation (SD) and phase advance can cause depression to remit and thus can be used as alternative or as adjunctive to pharmacologic treatment. The antidepressant response to SD occurs whether antidepressant drugs are administered or not. However, there is some evidence that the concomitant use of antidepressants may prevent the relapses that occur after recovery sleep. Data from clinical investigations also indicate that disrupted sleep can trigger and intensify mania. Rapid cycling bipolar patients may be especially vulnerable to mania/hypomania after disrupted sleep or SD. Characteristic changes in body temperature have been recorded in sleep deprivation as well as in other antidepressant treatment modalities. Thermoregulatory physiology may therefore provide a framework for understanding the effects of sleep-wake manipulations in affective illness. Publication Types: Review Review, Tutorial PMID: 1600904 [PubMed - indexed for MEDLINE] 62: Acta Med Austriaca 1992;19 Suppl 1:98-102 Thyroid hormones and depressive illness: implications for clinical and basic research. Baumgartner A, Campos-Barros A, Meinhold H. Psychiatrische Klinik und Poliklinik, Universitatsklinikum Rudolf-Virchow (Charlottenburg), Germany. It has been well-known for at least 100 years that both hypo- and hyperthyroidism may cause almost any psychiatric symptom, depending on the severity of the illness. No thyroid disorder, however, induces symptoms that are specific for a psychiatric disorder. Laboratory tests show depressed patients to be euthyroid. Any abnormalities that have been found, such as slightly elevated T4 levels or decreased T3 or TSH concentrations, have frequently failed to be replicated and do not fit any endocrinological diagnosis. They could reflect either "intervening factors" such as stress, methodological problems or a disturbance of central thyroid hormone metabolism. All antidepressant therapies (antidepressant drugs, carbamazepine, lithium, electroconvulsive therapy and sleep deprivation) have a marked influence on peripheral thyroid hormone levels. In particular, decreases in serum T4 and rT3 levels are often correlated to antidepressant response, suggesting that an effect on central thyroid hormone metabolism is involved in the as yet unknown mechanism of action of these therapies. Indeed, animal studies have shown that antidepressants do affect deiodinase activities and T3 and T4 concentrations in rat brain. However, the effects are highly area specific and dependent on the drug administered and the time of day at which the investigation was conducted. Although the mechanism of thyroid hormone action on CSF signal transduction is as yet unknown, effects on "general CNS functions" such as second messengers, G-proteins or calcium homeostasis seem more likely than specific effects on the different receptor systems. PMID: 1519467 [PubMed - indexed for MEDLINE] 63: Biol Psychiatry 1991 Oct 15;30(8):817-29 Effects of partial sleep deprivation on the diurnal variation of mood and motor activity in major depression. Szuba MP, Baxter LR Jr, Fairbanks LA, Guze BH, Schwartz JM. Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine. Partial sleep deprivation (PSD), keeping a subject awake from 2 AM to 9 PM produces an acute mood improvement in 60% of patients with major depression. We sought to characterize the timing, subcomponent mood, and motor activity changes of this response. Thirty-seven subjects with major depression were rated with the 6-item Hamilton Depression Scale (HAM-6) at 1 PM and completed the Profile of Mood States (POMS) every 2 hr on the day before and day of PSD. Locomotor activity was monitored continuously during the trial with an automated device. Bipolar I patients responded more frequently than other groups. Positive mood responders had greater improvement than nonresponders in POMS subscales of depression, tension, confusion, and anger. The mood improvement increased steadily during the day, peaked in late afternoon, and declined thereafter. Responders showed significantly higher levels of locomotor activity on the baseline pre-PSD day than did nonresponders. All subjects increased motor activity following sleep deprivation, however. PMID: 1751624 [PubMed - indexed for MEDLINE] 64: Eur Neuropsychopharmacol 1991 May;1(2):107-11 Therapeutic sleep deprivation and antidepressant medication in patients with major depression. Kasper S, Kick H, Voll G, Vieira A. Psychiatric Department, University of Bonn, Germany. Although there is a body of literature on the therapeutic efficacy of sleep deprivation (SD) there are only a few investigations in which the relevance of antidepressive medication for the clinical efficacy of SD has been studied. Based on the literature and on our own investigations with major depressed patients it seems that for the day-1 response it does not matter if and what type of antidepressive medication the patient receives. Furthermore, the results of our double blind study reveal that the day-1 response to total sleep deprivation (TSD) is not associated with a clear relationship to the outcome after 4 weeks treatment with either fluvoxamine or maprotiline. On the other hand, our data indicate that the day-2 response to TSD is significantly correlated with a beneficial outcome after subchronic treatment with maprotiline. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 1821699 [PubMed - indexed for MEDLINE] 65: Biol Psychiatry 1991 Apr 1;29(7):707-10 Are there predictors for sleep deprivation response in depressed patients? Riemann D, Wiegand M, Berger M. Sleep-EEG Laboratory, Central Institute of Mental Health, Mannheim, FRG. PMID: 2054442 [PubMed - indexed for MEDLINE] 66: Biol Psychiatry 1991 Mar 15;29(6):600-12 Towards a model of mood responses to sleep deprivation in depressed patients. Bouhuys AL. Department of Biological Psychiatry, University Psychiatric Clinic, Groningen, The Netherlands. It is hypothesized that in depressed patients diurnal variation in mood (DV) is a daily recurring phenomenon, which fails to achieve expression on all days (showing a random distribution of DVs). From this perspective a meta-analysis was performed on the raw data of earlier presented studies. The effect of total sleep deprivation (TSD) on mood was examined in 14 so-called prototypical patients, showing on three successive days either positive DVs (feeling better in the evening) or inverse DVs. It was hypothesized that under baseline conditions mood follows a monotonous course with switching points at 7 AM and 11 PM and that during the TSD night the 7-AM switch took place earlier. The position of this switch was calculated, assuming that (1) before the switch the curve ran parallel to the nightly baseline curves, and (2) after the switch the curve showed a monotonous change parallel to the daily baseline curves. The best fit between predicted and measured depression after TSD was found for a switch at 3 AM, varying the switching point during the TSD night with hourly intervals. The characteristics based on prototypical patients contributed significantly to the prediction of the morning and the afternoon depression levels after TSD in a group of 53 patients (prototypical and nonprototypical). Publication Types: Meta-Analysis PMID: 1829009 [PubMed - indexed for MEDLINE] 67: Biol Psychiatry 1990 Dec 1;28(11):979-88 Sleep deprivation in depression: pattern of relapse and characteristics of preceding sleep. Southmayd SE, David MM, Cairns J, Delva NJ, Letemendia FJ, Waldron JJ. Department of Psychiatry, Queen's University, Kingston, Ontario, Canada. The pattern of relapse following therapeutic response to 40-hr sleep deprivation (SD) was examined in nine depressed patients. On the night ending SD patients were awakened from polygraphically recorded sleep on one or more occasions, in order to assess the clinical state. All subjects were found to demonstrate a precipitous and full relapse over this night, the timing of the relapse varying considerably between individuals. No association was found between deterioration in the clinical state and characteristics of preceding sleep. These results are consistent with the notion that, in predisposed individuals, some process associated with sleep has a depressogenic effect. However, they necessitate revision of theories of SD and depression that emphasize the infrastructure of sleep. Publication Types: Clinical Trial PMID: 2275955 [PubMed - indexed for MEDLINE] 68: Psychiatry Res 1990 Nov;34(2):149-62 Effects of total sleep deprivation on urinary cortisol, self-rated arousal, and mood in depressed patients. Bouhuys AL, Flentge F, Van den Hoofdakker RH. Department of Biological Psychiatry, Academic Hospital, University of Groningen, The Netherlands. The possibility that the clinical response to total sleep deprivation (TSD) is mediated by dimensions of arousal was investigated in a group of 16 depressed patients. Self-reports of activation, stress, and mood were assessed 3 days before, during, and 2 days after TSD. Urinary cortisol excretion and responses to the dexamethasone suppression test (DST) were also measured. TSD increased cortisol excretion in depressed patients and advanced the time of the maximal excretion of cortisol. No such changes have been reported for normal subjects. Neither the increased excretion nor the time shift was related to the mood response to TSD. The DST results were also unrelated to this response. Indications that the mood response to TSD may be mediated by dimensions of arousal are the significant relationships between this response and the responses of subjective stress and activation to TSD. The TSD-induced cortisol increase was not related to the subjective arousal response to TSD. The increased cortisol excretion itself could be predicted by the averaged baseline levels of subjective stress: the lower the stress levels before TSD, the larger the cortisol response to TSD. PMID: 2287648 [PubMed - indexed for MEDLINE] 69: J Affect Disord 1990 Oct;20(2):93-9 The influence of physical activity and posture on the antidepressant effect of sleep deprivation in depressed patients. Baumgartner A, Sucher N. Psychiatrische Klinik und Poliklinik of the Klinikum Rudolf-Virchow (Charlottenburg), Freie Universitat Berlin, Germany. A possible role of the factors 'physical activity' and 'posture' in the antidepressant effect of a total night's sleep deprivation (TSD) was investigated in 30 patients with major depressive disorder. Fifteen patients underwent TSD under 'conventional' conditions, while the other 15 were kept in bed during TSD but were not permitted to sleep. There was no significant difference between the antidepressant effects of TSD in the two groups. This result suggests that it is wakefulness itself rather than changes in physical activity or posture that is involved in the mechanism of the antidepressant action of TSD. Publication Types: Clinical Trial Controlled Clinical Trial PMID: 2148333 [PubMed - indexed for MEDLINE] 70: J Affect Disord 1990 Aug;19(4):249-58 Relations between depressed mood and vocal parameters before, during and after sleep deprivation: a circadian rhythm study. Bouhuys AL, Schutte HK, Beersma DG, Nieboer GL. Department of Biological Psychiatry, University Hospital Groningen, The Netherlands. The mechanism underlying improvement after total sleep deprivation (TSD) was studied in 14 major depressed patients. The suggestions that (1) circadian processes and/or (2) dimensions of arousal may play a role in the response to TSD were investigated. Diurnal variation of depressed mood and of mood- and arousal-related vocal parameters was studied in relation to the effect of TSD on depressed mood and vocal parameters. During 3 baseline days, during TSD and 2 days after TSD vocal parameters and depressed mood were assessed 6 and 3 times daily respectively. The mean fundamental frequency (frequency of vocal fold vibration, F0) (presumably reflecting aspects of arousal) as well as the range of the F0 (proposed to reflect sadness) showed a clear circadian pattern with a peak at about 4.00 p.m. TSD affected the circadian organization of the mean F0 and advanced the peak of the curve. After one night of subsequent sleep this effect disappeared. In addition, improvement after TSD coincided with an increase of the mean F0. The diurnal variation of mood before TSD predicted the mood response to TSD, whereas diurnal variation of vocal parameters did not. Moreover, circadian changes in vocal parameters were not related to changes in depressed mood. These findings suggest that the diurnal variations in mood and vocal parameters are regulated by different mechanisms. Data support the presumption that circadian as well as arousal processes are involved in the mood response to TSD. Circadian changes in vocal parameters due to TSD are not likely to reflect changes in the biological clock. PMID: 2146301 [PubMed - indexed for MEDLINE] 71: Pharmacopsychiatry 1990 May;23(3):135-42 Response to total sleep deprivation before and during treatment with fluvoxamine or maprotiline in patients with major depression--results of a double-blind study. Kasper S, Voll G, Vieira A, Kick H. Psychiatric Department of the University of Bonn, FRG. To test the hypothesis that the antidepressant effects of total sleep deprivation (TSD) are linked to the serotonergic and/or noradrenergic system the authors carried out a double-blind study (fluvoxamine versus maprotiline) in 42 inpatients with endogenous depression (ICD). Patients were randomized to a four-week treatment with either fluvoxamine (100-300 mg/day) or maprotiline (100-300 mg/day). In addition, patients underwent a TSD procedure before and after one week of antidepressant medication. There was a statistically significant reduction of depression ratings (HDRS) in both the fluvoxamine and maprotiline group. The day-1 response to TSD before antidepressive medication was not associated with a clear relationship to the outcome after four weeks of treatment with either fluvoxamine or maprotiline. On the other hand, the day-2 response to TSD was significantly correlated with a good outcome to subchronic treatment with maprotiline. Furthermore, the results of the authors' data suggest that a favorable short-term outcome of TSD may be connected to antidepressants enhancing the serotonergic neurotransmission. The global comparison between fluvoxamine and maprotiline revealed that the group of patients treated with fluvoxamine had a significantly higher efficiency index (CGI) than the maprotiline group; fluvoxamine was rated to be tolerated excellently in 70% of the patients whereas this percentage was only 43% in the maprotiline group. There was also significantly more vertigo and dry mouth in the maprotiline group whereas the fluvoxamine group was rated to have significantly more sleep disturbances during the trial. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 2115680 [PubMed - indexed for MEDLINE] 72: Clin Neuropharmacol 1990;13 Suppl 1:S54-65 Manipulations of sleep and phototherapy: nonpharmacological alternatives in the treatment of depression. Wehr TA. Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, MD 20892. Manipulations of sleep and light (for winter depression) rapidly improve mood in 60% of depressed patients. These two unconventional treatments for depression may prove useful in patients who do not respond to drug treatments, in patients who prefer nonpharmacological treatments, or as adjuncts to drug treatments. This article reviews research on the parameters of effective sleep and light treatments and their biological mechanisms. The results of recent experiments suggest that the depressant effect of sleep may depend on thermoregulatory adjustments that occur after sleep begins. Publication Types: Review Review, Tutorial PMID: 2199036 [PubMed - indexed for MEDLINE] 73: Eur Arch Psychiatry Clin Neurosci 1990;240(1):60-1 Maintenance of antidepressant effect of sleep deprivation with the help of lithium. Grube M, Hartwich P. Department of Psychiatry, Stadtisches Krankenhaus Frankfurt am Main, Federal Republic of Germany. The antidepressant effect of sleep deprivation is often not longer than 1 or 2 days. Therefore we investigated systematically the combination of lithium and sleep deprivation on 26 depressive patients (ICD/DSM 296). We measured the depression scores with the Hamilton Depression Scale and the Brief Depression Rating Scale on 4 days. A comparison between sleep deprivation with and without lithium showed a highly significant difference on the 2nd and 3rd days after sleep deprivation. The positive antidepressant effect remained with those who received lithium. PMID: 2147906 [PubMed - indexed for MEDLINE] 74: J Psychiatr Res 1990;24(4):281-92 Thyrotropin (TSH) and thyroid hormone concentrations during partial sleep deprivation in patients with major depressive disorder. Baumgartner A, Graf KJ, Kurten I, Meinhold H. Psychiatrische Klinik und Poliklinik, Klinikum Rudolf-Virchow Charlottenburg, Berlin, Federal Republic of Germany. Thyrotropin (TSH), thyroxine (T4), free T4, triiodothyronine (T3), and free T3 (fT3) concentrations were measured in 25 patients with major depressive disorder at 8 a.m. both before and after partial sleep deprivation (PSD) during the second half of the night. Significant increases in TSH and T3 levels and a corresponding trend in fT3 levels were seen. No convincing correlations occurred between changes in the secretion of any of the hormones and the antidepressant effect of PSD. However, this does not rule out the possibility that the two phenomena, which occur in depression at different anatomical levels with presumably different degrees of disturbance in the respective receptor systems, have common underlying neurochemical mechanisms. Comparison of the effect of the PSD on changes in hormone secretion and mood with the corresponding effects in a sample of depressed patients who underwent total sleep deprivation showed no significant differences between the effects of these two forms of sleep deprivation on either variable. PMID: 2090827 [PubMed - indexed for MEDLINE] 75: Int Clin Psychopharmacol 1989 Jul;4(3):217-28 Treatment of resistant depression. Review on the efficacy of various biological treatments, specifically in major depression resistant to cyclic antidepressants. Nolen WA, Haffmans J. Department of Biological Psychiatry, Psychiatric Centre Bloemendaal, Hague, The Netherlands. The biological treatment of depression includes administration of psychoactive drugs (cyclic antidepressants, MAO-inhibitors, neuroleptics and lithium), use of certain substances which in small amounts are normally present in food such as, L-tryptophan (L-TP) and L-5-hydroxytryptophan (L-5HTP), electroconvulsive therapy (ECT) and various manipulations of the sleep-wake rhythms. This paper reviews the literature on the efficacy of these treatments in patients resistant to earlier adequate treatment(s) with cyclic antidepressants. Subsequently the following strategy for the biological treatment of (non-psychotic) major depression is suggested: (1) administration of a cyclic antidepressant; (2) if after a period of 4 to 6 weeks a patient has not responded to an adequate dose, another cyclic antidepressant should be tried, adding lithium if the patient still does not respond; (3) MAO-inhibitors and (4) ECT. In psychotic depression the suggestions for the first, third and fourth steps are the same. In the second step, the cyclic antidepressant should be combined with a neuroleptic. Publication Types: Review Review, Tutorial PMID: 2571635 [PubMed - indexed for MEDLINE] 76: Psychiatry Res 1989 Mar;27(3):253-65 Effects of brief naps on mood and sleep in sleep-deprived depressed patients. Gillin JC, Kripke DF, Janowsky DS, Risch SC. Department of Psychiatry, San Diego Veterans Administration Medical Center, CA. To determine the effects of brief naps on mood and electroencephalographic (EEG) sleep in sleep-deprived depressed patients, data from 19 hospitalized patients with depression were analyzed; all were kept awake from 0700h until the following day, when they were allowed 10-min naps at either 0830h or 1500h. Six of the patients showed a clinically significant improvement (greater than 40% change) on the Hamilton Rating Scale for Depression (HRSD) before the nap after all-night sleep deprivation, and the group as a whole showed a significant improvement on the HRSD, the Profile of Mood States, and the Brief Psychiatric Rating Scale subscale for depression. Naps did not alter mood in the responders, but did improve measured depression on the HRSD in the non-responders. Morning and afternoon naps did not differ significantly in their effects on mood or nap sleep. On the recovery sleep, patients who were classified as responders after the nap showed a significantly greater increase in delta (Stage 3 + 4) sleep compared with baseline than nonresponders. PMID: 2710868 [PubMed - indexed for MEDLINE] 77: Biol Psychiatry 1988 Oct;24(6):631-41 Nocturnal TSH and prolactin secretion during sleep deprivation and prediction of antidepressant response in patients with major depression. Kasper S, Sack DA, Wehr TA, Kick H, Voll G, Vieira A. Clinical Psychobiology Branch, NIMH, Bethesda, MD 20892. In order to test the hypothesis that changes in the hypothalamic-pituitary axis during sleep deprivation are related to the antidepressant effects of this procedure, we measured thyroid-stimulating hormone (TSH) and prolactin levels in 32 depressed patients at 2:00 AM during a night before, during, and after total sleep deprivation (TSD). TSH levels increased significantly (p less than 0.05) during TSD, and prolactin levels decreased significantly (p less than 0.0001). When we divided the patients into responder and nonresponder groups based on a 30% reduction in the Hamilton Rating Scale, there was no difference between the two groups in their hormone levels on the baseline, TSD, or recovery nights. Changes in prolactin or TSH were not correlated with clinical improvement when the two groups were considered together or in the responder/nonresponder groups separately. Baseline values of both hormones were significantly (p less than 0.01) correlated with their respective levels during TSD and recovery sleep. These findings indicate that the relative levels of nocturnal TSH and prolactin are stable even within acutely depressed individuals and that changes in their levels are not related to the clinical response to sleep deprivation. PMID: 3167147 [PubMed - indexed for MEDLINE] 78: Acta Psychiatr Scand 1988 Feb;77(2):219-24 The timing and duration of sleep in partial sleep deprivation therapy of depression. Sack DA, Duncan W, Rosenthal NE, Mendelson WE, Wehr TA. Clinical Psychobiology Branch, National Institute of Mental Health, Maryland. The antidepressant response to partial sleep deprivation early in the night (PSD-E) was compared with the response to partial sleep deprivation late in the night (PSD-L) in 16 drug-free depressed inpatients using a balanced order crossover design. PSD-L had a significantly greater antidepressant effect that PSD-E. The response to PSD-L was sustained and enhanced by a second night of treatment. Patients had significantly shorter sleep durations and reduced REM sleep on PSD-L that did not occur in the PSD-E situation. There was a significant negative correlation between response to PSD and sleep duration, and in particular, REM sleep duration, in the late sleep deprivation situation. Thus, the amount and timing of sleep appear to be factors in the response to PSD, but additional studies are needed to evaluate the relative importance of these parameters. PMID: 3364206 [PubMed - indexed for MEDLINE] 79: J Clin Psychopharmacol 1987 Dec;7(6 Suppl):24S-35S Modifications of the serotonin system by antidepressant treatments: implications for the therapeutic response in major depression. Blier P, de Montigny C, Chaput Y. Neuroscience Research Center, Montreal, Quebec, Canada. Results of electrophysiological single-cell recording studies suggest that most, if not all, types of antidepressant treatments increase 5-hydroxytryptamine (5-HT) neurotransmission. Tricyclic antidepressants, electroconvulsive shock treatment, mianserin, adinazolam, and possibly sleep deprivation may exert their therapeutic effect through sensitization of postsynaptic neurons to 5-HT. Serotonin reuptake blockers may relieve depression through an increased efficacy of the presynaptic element resulting from a desensitization of somatodendritic and terminal 5-HT autoreceptors. Similarly, monoamine oxidase inhibitors may act by increasing the efficacy of 5-HT neurons. Intensification of 5-HT function appears to be a common denominator to antidepressant treatments; however, evidence suggests that this modification may only be a link in a chain of events leading to an antidepressant response. Publication Types: Review Review, Tutorial PMID: 3323264 [PubMed - indexed for MEDLINE] 80: Acta Psychiatr Scand 1987 Jun;75(6):614-8 Effect of interrupted sleep patterns and partial sleep deprivation on DST and mood in psychiatric house officers. Altshuler LL, Kagan BL, Baxter LR Jr, Smith G, Wilkins JN. To gain further insight into clinical associations seen in depression, the authors investigated the effect of interrupted night-time sleep on the HPA axis and mood in 20 psychiatric house officers taking overnight call. Specific interest was in whether multiple awakenings could induce a positive DST. No statistically significant association emerged between number of nocturnal awakenings, number of hours of sleep deprivation or temporal occurrence of sleep deprivation and cortisol, DST or mood. The results suggest that cortisol and DST changes are not likely to be causally linked to, or epiphenomenon of disrupted sleep. The implications of these findings for major depression are discussed. PMID: 3618284 [PubMed - indexed for MEDLINE] 81: Am J Psychiatry 1987 Feb;144(2):201-4 Erratum in: Am J Psychiatry 1987 Apr;144(4):542 Sleep reduction as a final common pathway in the genesis of mania. Wehr TA, Sack DA, Rosenthal NE. Diverse psychological, interpersonal, environmental, and pharmacological factors that appear to trigger the onset of mania could act via their capacity to cause sleep deprivation, a mechanism that has been shown in experiments with bipolar patients to induce transient or sustained switches into mania. Since mania in turn causes insomnia, the development of mania is potentially self-reinforcing and could become autonomous after being initiated by precipitating factors. The sleep reduction model is based on experimental evidence and is a parsimonious explanation for the precipitation of manic episodes by a wide variety of factors. Furthermore, this model has clear implications for the prevention and treatment of mania and provides a conceptual focus and an experimental paradigm for psychological investigations of the causes of mania. PMID: 3812788 [PubMed - indexed for MEDLINE] 82: J Psychiatr Res 1987;21(2):151-61 Response to total sleep deprivation and clomipramine in endogenous depression. Elsenga S, Van den Hoofdakker RH. In 44 endogenously depressed patients, response to total sleep deprivation (TSD) was investigated as a function of several biographical and clinical variables. All patients were subjected to a schedule of sleep-TSD-sleep-TSD. Antidepressant drug treatment (clomipramine) was started on the day before the first TSD. Sex, age, educational status, number of previous hospitalizations and duration of the current depressive episode were not related to the response to either the first or the second TSD. Likewise, no significant differences were found in the responses of unipolar and bipolar patients. In contrast, diurnal variation appeared to be positively correlated with response to TSD. Depressives with psychotic features reacted more favourably than non-psychotic depressives. PMID: 3585805 [PubMed - indexed for MEDLINE] 83: Fortschr Neurol Psychiatr 1986 Nov;54(11):341-55 [Sleep deprivation (wakefulness therapy) as an antidepressant] [Article in German] Kuhs H, Tolle R. In this complete survey of publications concerning therapeutic sleep deprivation (including reports of a conference held in 1985) first the practical management and especially the advantages of sleep deprivation of the second half of the night are explained. After discussing the psychological conditions and methods of therapeutic evaluation the treatment results in endogenous depression (melancholia), the effectiveness of repetition and of combination with antidepressive pharmacotherapy, the comparison with electroconvulsive therapy and the predictors are described. Sleep deprivation is indicated in nearly every therapeutic situation, including drug-resistant melancholia, furthermore in severe neurotic depression and in depressive states of schizophrenic patients. Side effects are unimportant, and complications are almost absent. In addition psychophysiological, neuroendocrinological and biochemical investigations are reported, as far as they concern either the mechanism of action of sleep deprivation or chronobiological hypotheses of depression. PMID: 3804162 [PubMed - indexed for MEDLINE] 84: Psychiatry Res 1986 Sep;19(1):17-23 Prolongation of the antidepressant response to partial sleep deprivation by lithium. Baxter LR Jr, Liston EH, Schwartz JM, Altshuler LL, Wilkins JN, Richeimer S, Guze BH. Depressed patients given a loading dose of lithium on the first of 2 successive days of partial sleep deprivation (PSD), and kept at maintenance levels thereafter, showed significantly greater prolongation of the antidepressant effects of PSD than patients treated with PSD and placebo, even though the acute elevation in mood derived from PSD was as great on placebo as on lithium. Depression was assessed 3 days after PSD with an augmented version of the Hamilton Rating Scale for Depression. Patients on lithium alone, without PSD, did not have the acute elevation in mood seen in the two PSD groups and had significantly less improvement in depression than those who received PSD with lithium. Publication Types: Clinical Trial Controlled Clinical Trial PMID: 3097691 [PubMed - indexed for MEDLINE] 85: Acta Psychiatr Scand 1986 Aug;74(2):190-2 Is there a relationship between response to total sleep deprivation and efficacy of clomipramine treatment in depressed patients? Hochli D, Riemann D, Zulley J, Berger M. Total sleep deprivation (TSD) and tricyclic medication are successful treatment modalities for patients with a major depressive disorder. Recent studies have suggested a positive relationship between TSD response and succeeding tricyclic treatment, even on a very specific level, thus supporting the assumption of two distinct biochemical subtypes of depression. The present study tested this hypothesis by treating 10 inpatients with a major depressive disorder first with TSD and succeedingly with clomipramine. Contrary to expectation, a negative relationship between clinical response to the two treatment modalities was found. PMID: 3776665 [PubMed - indexed for MEDLINE] 86: Acta Psychiatr Scand 1985 Aug;72(2):161-5 Antidepressant effects of sleep deprivation in bright and dim light. Wehr TA, Rosenthal NE, Sack DA, Gillin JC. In order to test whether exposure to bright artificial light at night is a necessary condition for the antidepressant response to sleep deprivation therapy, five patients were totally sleep-deprived on two separate nights, once in very bright light and once in nearly total darkness. During the day after the sleep-deprivation night patients were found to have responded equally well to sleep deprivation in both conditions. During the sleep-deprivation night, however, antidepressant responses may have been greater in the bright light condition. Thus, light at night is not necessary for the antidepressant response to sleep deprivation, but we cannot rule out the possibility that the effects of light exposure and sleep deprivation are additive or that exposure to light at some time after sleep deprivation begins (including during the following day) is necessary for the response. PMID: 4050508 [PubMed - indexed for MEDLINE] 87: Am J Psychiatry 1985 May;142(5):606-8 Potentiation of antidepressant medications by phase advance of the sleep-wake cycle. Sack DA, Nurnberger J, Rosenthal NE, Ashburn E, Wehr TA. Four patients with major depression who were unresponsive to antidepressant medications rapidly improved and remained euthymic after an advance of the sleep-wake cycle. Phase advance of the sleep-wake cycle and antidepressant treatment may have complementary effects on the circadian system. The authors suggest that the combination may be useful in treating drug nonresponders and in hastening response to antidepressant drugs. PMID: 3985199 [PubMed - indexed for MEDLINE] 88: Zh Nevropatol Psikhiatr Im S S Korsakova 1985;85(4):565-70 [Treatment of endogenous depressions by sleep deprivation] [Article in Russian] Nosachev GN. Eighty-six patients with endogenous depression (cyclothymia, manic-depressive psychosis and schizophrenia) were treated by sleep deprivation. The efficacy of this treatment with regard to the structure of the depressive syndrome, the course of the attack and nosological nature is discussed. The author also considers the frequency, sequence and effectiveness of sessions of sleep deprivation in both hospital and outpatient settings. Series of total sleep deprivation were shown to be highly effective in cyclothymia and manic-depressive psychosis with melancholic and anesthetic depression, including cases with a protracted course. PMID: 4002948 [PubMed - indexed for MEDLINE] 89: South Med J 1984 Nov;77(11):1435-42 The internship year: a study of sleep, mood states, and psychophysiologic parameters. Ford CV, Wentz DK. Previous reports have suggested that first-year graduate physicians have a high incidence of psychologic distress and may show cognitive impairment as a result of sleep deprivation. We periodically evaluated 27 interns during their training year to determine amount of sleep, mood states, reaction time, critical flicker fusion, and symptoms of depression. We found the incidence of major depression in our subjects (four of 27) to be lower than previously reported but higher than expected for that age group in the general population. Risk factors for depression during the internship year were history of major depression, female sex, and unmarried status. The only significant change in average mood state was that anger progressively increased during the year. Subjects slept an average of 5.95 hours per 24-hour day during the year. Correlational analysis indicated that, contrary to predictions, performance on reaction time and critical flicker fusion improved with less sleep. At the end of the year, subjects regarded the year as stressful but not more so than had been anticipated. PMID: 6494967 [PubMed - indexed for MEDLINE] 90: Can J Psychiatry 1984 Oct;29(6):530-6 Clinical and biological correlates of sleep deprivation in depression. Joffe RT, Brown P. Sleep deprivation is reported to have therapeutic effectiveness in depressive illness. Furthermore, the response to sleep deprivation has important research implications. Recent conceptual advances, resulting in increased understanding of the role of abnormal biological rhythms and neurotransmitter function of the pathophysiology of affective disorder, highlight the future role of sleep deprivation in the research and treatment of these disorders. Publication Types: Review PMID: 6149013 [PubMed - indexed for MEDLINE] 91: Biol Psychiatry 1984 Mar;19(3):347-52 Neuroendocrine predictors of the antidepressant effect of partial sleep deprivation. Joffe R, Brown P, Bienenstock A, Mitton J. Twenty-one patients with major depressive disorder were studied to establish the relationship between selective neuroendocrine responses and the antidepressant response to partial sleep deprivation. Dexamethasone suppression and normal thyrotropin response to TRH were associated with a positive mood response. PMID: 6426532 [PubMed - indexed for MEDLINE] 92: Psychiatr Clin (Basel) 1983;16(1):17-25 Dexamethasone suppression test combined with total sleep deprivation in depressed patients. Kasper S, Moises HW, Beckmann H. The effect of one night's total sleep deprivation (SD) on the dexamethasone suppression test (DST) was studied in groups of endogenously and nonendogenously depressed patients who were diagnosed according to different research classification systems. The DST was normal (less than 5 micrograms/dl) before and after SD in the group of nonendogenously depressed patients. Deterioration, no change or only slight clinical response in single items occurred. In the group of endogenous depressives 8 out of 11 were baseline nonsuppressors (greater than 5 micrograms/dl). After SD a large variability of cortisol nonsuppression was found in this group. Clinical response occurred in the majority of these patients but was more favorable in those who had a trend for normalization of DST. Clinical diagnosis as well as DST seem to have a therapy-predictive value for one night's total SD in patients with affective disorders. PMID: 6844658 [PubMed - indexed for MEDLINE] 93: Psychiatry Res 1982 Aug;7(1):93-9 The dexamethasone suppression test as a predictor of sleep deprivation antidepressant effect. King D, Dowdy S, Jack R, Gardner R, Edwards P. An abnormal dexamethasone suppression test (DST) result, a sensitive and specific marker for endogenous depression, was found to be associated with an antidepressant response to sleep deprivation in patients who met DSM-III criteria for Major Depressive Episode regardless of whether they met criteria for melancholia or psychotic subtypes of this disorder. These findings support previous reports of an association between an abnormal DST result and antidepressant effects of sleep deprivation in depressed patients. Our results extend the positive association between an abnormal DST result and the antidepressant response to sleep deprivation to include depressed patients who are clinically nonmelancholic during their current episode but who have an abnormal DST result. PMID: 6957903 [PubMed - indexed for MEDLINE] 94: Bibl Psychiatr 1981;(160):56-61 Sleep deprivation psychoprophylaxis in recurrent affective disorders. Papadimitriou GN, Christodoulou GN, Trikkas GM, Malliaras DE, Lykouras EP, Stefanis CN. Administration of prophylactic 36 h total sleep deprivation to 9 manic-depressive patients (5 bipolar and 4 unipolar depressives) reduced the frequency of relapses and increased the duration of normothymia in 5 patients, left the course of illness unchanged in 3 patients whilst in 1 patient the effect could not be evaluated. Sleep deprivation appeared to be more effective in women, 'rapid cyclers', patients with a positive family history of mental illness and patients with recurrent depression. These observations confirm previous impressions and suggest a possible prophylactic effect of sleep deprivation. PMID: 7458886 [PubMed - indexed for MEDLINE] 95: Chronobiologia 1980 Oct-Dec;7(4):505-11 Repeated sleep deprivation as a therapeutic Zeitgeber for circular type manic depressive disturbance. Lovett Doust JW, Christie H. A post-menopausal woman suffering from a circular type manic depressive psychosis who had been treated by drugs was followed for 8 months on a self-reporting mood rating scale. The drug regimen was continued over a further 8 months but with the addition of 5 nights of sleep deprivation at the depth of her recurrent depressed moods. Time series analyses of the subject's longitudinal mood scores revealed a persistent cycle of 32 days. After 5 sleep deprivation treatments this cycle shortened to 28 days which endured at least for the ensuing 8 months. After sleep deprivation and decrease of the amplitude, an improvement of mood was obtained. It is suggested that the increased LD ratio obtained in sleep deprivation may be as therapeutic as the actual loss of sleep itself. PMID: 7449580 [PubMed - indexed for MEDLINE] 96: Dis Nerv Syst 1977 Nov;38(11):873-9 Pathological and therapeutic consequences of sleep loss: a review. King D. Until recently sleep deprivation has been studied from the point of view of determining whether or not it produces deleterious effects. Evidence, however, has begun to accumulate indicating that both REM deprivation and single night sleep deprivation may have antidepressant effects. Although beneficial effects are found primarily in endogenously depressed patients, variable results have been obtained in both "endogenous" and "reactive" depressions, suggesting that these diagnostic categories include biologically heterogeneous populations. Publication Types: Review PMID: 199403 [PubMed - indexed for MEDLINE] 97: Acta Psychiatr Scand 1976 Sep;54(3):184-92 Sleep deprivation therapy in depression. Svendsen K. A study of sleep deprivation therapy was made in 62 females and 15 males, aged 20-72, with monopolar (60 patients) and bipolar (17 patients) types of manic-depressive psychosis. Of these patients, 30 had suffered only the current depression, 29 a maximum of five depressions, and 18 more than five depressions before the sleep deprivation therapy. Twenty-five patients had been treated with antidepressant drugs for less than 10 days, 12 patients for 10-24 days, and 36 patients for more than 24 days. Twenty-four patients were treated with one sleep deprivation, 29 patients with one sleep deprivations per week (average 1.59), and 24 patients with two sleep deprivations per week (average 2.5). The effect of the sleep deprivation therapy was evaluated clinically and by means of Cronholm-Ottosson's rating scale. The effect was found good and lasting in 29%, good but temporary in 38%, and poor in 32% of the cases. The best results were achieved with twice-weekly treatments, the poorest results with once-weekly treatment. The results were equal in monopolar and bipolar cases and were independent of the number of previous depressions as well as antidepressant drug treatment. No side effects have been observed, in particular no conversion to mania. The results of the present investigation indicate that depression and sleep disturbances are symptoms produced by a common factor which, however, it as yet unknown. Sleep deprivation therapy is seen to have at least some effect on all cases of endogenous depression. Sleep deprivation therapy has no side effects and is more quick-acting than any other treatment procedure hitherto known. It should therefore be considered the first treatment offer to all endogenously depressed patients in whom immediate ECT is not necessitated. PMID: 970195 [PubMed - indexed for MEDLINE] 98: Acta Psychiatr Scand 1976 Sep;54(3):167-73 Sleep deprivation as treatment for endogenous depression. Larsen JK, Lindberg ML, Skovgaard B. Twenty-six depressed patients, 19 of whom suffered from an endogenous depression, were sleep-deprived for one night, and eight of these were additionally sleep-deprived for three to nine nights with two sleep deprivations per week. While the sleep deprivation was being carried through, none of the patients were treated with tricyclic antidepressants. The patients were rated before and after the sleep deprivation(s). Sleep deprivation appeared to be effective for both unipolar and bipolar depressions. According to the rating scale an improvement was registered especially when the clinical picture was characterized by depressed mood, psycho-motor retardation and anxiety. As sleep deprivation cured 25% of the patients and further incidentally improved another 20% of the patients, it can be concluded that sleep deprivation seems to be a valuable treatment, especially in retarded endogenous depressions. PMID: 970193 [PubMed - indexed for MEDLINE] 99: Acta Psychiatr Scand 1976 Feb;53(2):148-58 The effect of sleep deprivation on depressed patients. Pflug B. In this paper an account is given of the effect of single-night sleep deprivation (SD) therapy in 124 depressive patients of different diagnostic groups. Phasic depressives showed a marked improvement after treatment by sleep deprivation. Because these improvements were often of short duration, we repeated the treatments and combined them with thymoleptic drugs. In the group of neurotic depressives the therapeutic effect of sleep deprivation varied; on the whole, however, the improvement was less marked. It is pointed out that the vital symptoms and "critical time" are of importance. Sleep deprivation can be explained as a resynchronization of disturbed circadian rhythms brought about by interrupting these rhythms. PMID: 1251760 [PubMed - indexed for MEDLINE] 100: Br J Psychiatry 1975 Sep;127:222-6 The treatment of psychotic depression by sleep deprivation: a replication study. Bhanji S, Roy GA. A replication study of the effects of single-night sleep deprivation therapy was carried out as a preliminary to a controlled comparison with orthodox antidepressent measures. The results show that sleep deprivation therapy was acceptable to a majority of the patients studied, and was followed by an improvement in over half those who completed treatment. Adverse effects were minimal. The authors feel that further clinical and physiological study is warranted. PMID: 1182378 [PubMed - indexed for MEDLINE] 101: Arch Gen Psychiatry 1975 Sep;32(9):1121-5 Total sleep deprivation on endogenous depression. van den Burg W, van den Hoofdakker RH. Ten endogenous depressive patients were deprived of sleep for two whole nights according to the following schedule: sleep/sleep deprivation/sleep/sleep deprivation/sleep. No drugs were administered. Experimental conditions were as neutral as possible. Blind and nonblind ratings were taken. The patients were generally rated as improved after sleep deprivation, but a substantial effect, though temporary with rapid relapse, occurred in only two cases. After subsequent sleep, relapse followed as a rule. The net antidepressive effect of the total procedure was slightly more than nil. Publication Types: Clinical Trial PMID: 1101846 [PubMed - indexed for MEDLINE]