Citalopram for Depression:
A MEDLINE Search by, Ivan Goldberg, MD
Acta Psychiatr Scand 1998 May;97(5):374-380
Serotonergic 'vulnerability' in affective disorder: a study of the tryptophan
depletion test and relationships between peripheral and central serotonin
indexes in citalopram-responders.
Aberg-Wistedt A, Hasselmark L, Stain-Malmgren R, Aperia B, Kjellman BF, Mathe
AA
Karolinska Institute, Institution of Clinical Neuroscience, Department of
Psychiatry, St Goran's Hospital, Stockholm, Sweden.
A double-blind study of the tryptophan depletion (TD) challenge was performed
on a sample consisting of 20 patients with a major depressive disorder in
clinical remission after citalopram treatment. TD was induced by the intake of
43 g of an amino acid mixture containing the five large neutral amino acids.
The control group received the same mixture, to which 2.3 g tryptophan had been
added. Five of the 12 challenged patients showed a worsening of depressive
symptoms during the day of the test. In contrast, there was no mood alteration
in the eight control patients. Baseline cortisol levels were significantly
higher in responders to TD compared to those in non-responders and controls.
Platelet serotonin-receptor function and plasma prolactin levels were
correlated. There was a significant positive correlation in the baseline data
between rated mood state and plasma cortisol and a significant inverse
correlation between related mood state and plasma tryptophan concentration.
Thus low mood appeared to be associated with low serotonin precursor
availability as well as with high cortisol levels.
J Affect Disord 1998 Apr;49(1):79-82
Use of the selective serotonin reuptake inhibitor citalopram in the treatment
of generalized social phobia.
Bouwer C, Stein DJ
Dept. of Psychiatry, University of Stellenbosch, Tygerberg, South Africa.
BACKGROUND: There is increasing evidence that social phobia responds to
treatment with selective serotonin reuptake inhibitors (SSRIs). However, the
efficacy of citalopram, the most selective of the SSRIs, in social phobia has
not been well documented. METHODS: Citalopram was used on an open-label
naturalistic basis in 22 social phobia patients presenting for treatment (40 mg
daily for 12 weeks). Patients were rated with the Liebowitz Social Anxiety
Scale and the Clinical Global Impressions (CGI) scale. RESULTS: Ratings on the
Liebowitz Social Anxiety Scale and the CGI were significantly improved after
treatment. A total of 86% of patients were responders at week 12. LIMITATION:
Open, uncontrolled study. CONCLUSIONS: Citalopram appears to be effective in
the treatment of social phobia. A controlled trial is warranted to confirm
these data. The role of serotonin in social phobia deserves further study.
Alcohol Alcohol 1998 Mar;33(2):151-156
Effects of fluvoxamine and citalopram in maintaining abstinence in a sample of
Italian detoxified alcoholics.
Angelone SM, Bellini L, Di Bella D, Catalano M
Istituto di Ricovero e Cura a Carattere Scientifico H. San Raffaele,
Dipartimento di Scienze Neuropsichiche, Centro di Alcologia, Milano, Italy.
A 16-week, randomized study was performed to test the efficacy of two selective
serotonin reuptake inhibitors (SSRIs) fluvoxamine and citalopram, in decreasing
relapse and craving in alcoholics, and to investigate possible differences in
their clinical profile. After detoxification, each of the 81 patients (55 males
and 26 females) was randomly assigned to one of three groups: 23 subjects did
not receive any pharmacological treatment, 25 were treated with fluvoxamine,
150mg/day, and 33 with citalopram, 20 mg/day. All patients received standard
cognitive-behavioral therapy. Craving was assessed twice a month using a
10-step scale. Every intake of alcohol was considered a relapse and the subject
was taken out of the study. At the end of the study, both the fluvoxamine and
citalopram groups showed a statistically higher rate of continuous abstinence
(63.6 and 60.7%, respectively) compared to the group without pharmacological
treatment (30.4%). Relapse severity did not differ among the three groups. Only
citalopram showed a significant effect on craving throughout the study period.
This study confirmed the efficacy of SSRIs as an adjunct to psychotherapy to
prevent relapse in alcoholics. The relationship between the effects of these
SSRIs on abstinence and craving, as well as the differences between their
profiles, are discussed.
Int Clin Psychopharmacol 1997 Nov;12(6):323-331
A double-blind multicenter trial comparing sertraline and citalopram in
patients with major depression treated in general practice.
Ekselius L, von Knorring L, Eberhard G
Department of Psychiatry, University Hospital, Uppsala, Sweden.
The purpose of this double-blind, multicenter trial was to compare the efficacy
and safety of sertraline (50-150 mg/day) with those of citalopram (20-60
mg/day) in patients with major depression in general practice during 24 weeks
of treatment. The patients were assessed using the Montgomery-Asberg Depression
Rating Scale and the Clinical Global Impressions of severity and improvement
scales. Observed and spontaneously reported adverse events were recorded and
side-effects were assessed by means of the UKU Side-Effect Scale. Altogether
400 patients were randomized into the study. A total of 308 patients completed
the 24-week study in accordance with the protocol. A significant reduction in
the total Montgomery-Asberg Depression Rating Scale scores was observed in both
treatment groups as early as 2 weeks, with no statistically significant
differences between the drugs. In the intention to treat-last observation
carried forward analysis 76% responded to treatment in the sertraline and 81%
in the citalopram group. The final mean doses were 82 mg/day (64% higher than
baseline) in the sertraline group and 34 mg/day (70% higher than baseline) in
the citalopram group. The response rate in completers in accordance with
protocol was 90% in the sertraline group and 93% in the citalopram group. The
side-effects were those usually seen, and both sertraline and citalopram were
considered to be well tolerated. It was concluded that patients with major
depression in general practice respond well to 24 weeks of treatment with
sertraline or citalopram. With regard to efficacy, no statistically significant
differences were found between the drugs.
Int Clin Psychopharmacol 1997 Nov;12(6):323-331
A double-blind multicenter trial comparing sertraline and citalopram in
patients with major depression treated in general practice.
Ekselius L, von Knorring L, Eberhard G
Department of Psychiatry, University Hospital, Uppsala, Sweden.
The purpose of this double-blind, multicenter trial was to compare the efficacy
and safety of sertraline (50-150 mg/day) with those of citalopram (20-60
mg/day) in patients with major depression in general practice during 24 weeks
of treatment. The patients were assessed using the Montgomery-Asberg Depression
Rating Scale and the Clinical Global Impressions of severity and improvement
scales. Observed and spontaneously reported adverse events were recorded and
side-effects were assessed by means of the UKU Side-Effect Scale. Altogether
400 patients were randomized into the study. A total of 308 patients completed
the 24-week study in accordance with the protocol. A significant reduction in
the total Montgomery-Asberg Depression Rating Scale scores was observed in both
treatment groups as early as 2 weeks, with no statistically significant
differences between the drugs. In the intention to treat-last observation
carried forward analysis 76% responded to treatment in the sertraline and 81%
in the citalopram group. The final mean doses were 82 mg/day (64% higher than
baseline) in the sertraline group and 34 mg/day (70% higher than baseline) in
the citalopram group. The response rate in completers in accordance with
protocol was 90% in the sertraline group and 93% in the citalopram group. The
side-effects were those usually seen, and both sertraline and citalopram were
considered to be well tolerated. It was concluded that patients with major
depression in general practice respond well to 24 weeks of treatment with
sertraline or citalopram. With regard to efficacy, no statistically significant
differences were found between the drugs.
BMJ 1998 Jan 24;316(7127):307-308
Drug treatment of depression. Citalopram in overdose may result in serious
morbidity and death.
Power A
J Child Adolesc Psychopharmacol 1997;7(3):157-166
Child and adolescent obsessive-compulsive disorder treated with citalopram:
findings from an open trial of 23 cases.
Thomsen PH
Research Center, Psychiatric Hospital for Children and Adolescents in Risskov,
Denmark.
The adverse effects and potential clinical value of citalopram, a highly
selective serotonin reuptake inhibitor, were examined in 23 children and
adolescent (9-18 years old, 11 boys) with obsessive-compulsive disorder (OCD)
in an open-label trial of citalopram 10-40 mg (modal 40 mg) daily. After 10
weeks of citalopram treatment, statistically significant improvements were
reflected in OCD symptom ratings (mean Total Y-BOCS/CY-BOCS scores, 30 +/- 4
vs. 21 +/- 4, p < 0.001) and global assessment scores (mean CGAS, 59 +/- 11 vs.
71 +/- 11, p < 0.001). Over 75% of these youth showed a marked improvement (4
patients had more than 50% reduction in CY-BOCS scores) or moderate improvement
(14 patients had 20%-50% reduction) in OCD symptoms. No patient was found to
have worsened during citalopram treatment. Adverse effects appeared minor and
transient. None of the 23 patients dropped out of the study or had the
medication discontinued because of side effects. These open trials of
citalopram do not allow for any firm conclusions regarding its effectiveness in
the treatment of childhood and adolescent OCD, but these preliminary findings
suggest that citalopram might be particularly well-tolerated in children and
adolescents with OCD at doses up to 40 mg daily.
Orv Hetil 1997 Oct 12;138(41):2605-2607
[Clinical experiences with the analgesic effects of citalopram].
[Article in Hungarian]
Baraczka K, Janko Z, Vargha K, Markus H
Orszagos Reumatologiai es Fizioterapias Intezet, Budapest.
Antidepressive drugs influencing the serotonin metabolism have shown some
efficacy in treatment of generalized pain syndrome. The aim of the present
study was to observe the analgesic effect of citalopram <
1-[3-(dimetilamino)propil]-1-(p-florofenil)-5-ftal+ ++ankarbonitin > in 20 non
depressive patients with chronic pain syndrome (fibromyalgy and/or radicular
pain). On the base of a short time (6 weeks) observation a limited clinical
effect was observed, however, the Seropram seems to have some benefits in the
treatment of chronic pain.
Acta Psychiatr Scand 1997 Nov;96(5):343-346
Citalopram in the treatment of obsessive-compulsive disorder: an open pilot
study.
Koponen H, Lepola U, Leinonen E, Jokinen R, Penttinen J, Turtonen J
Moisio Hospital, Mikkeli, Finland.
Obsessive-compulsive disorder (OCD) is a common anxiety disorder, which often
causes significant impairment of the affected individual's social, occupational
or interpersonal functioning. Previous reports suggest that the disorder may be
treated with the tricyclic antidepressant clomipramine, and also with the more
recently introduced selective serotonin reuptake inhibitors (SSRIs), such as
fluoxetine, fluvoxamine, sertraline and paroxetine. The present 24-week open
pilot study was designed to examine the efficacy, appropriate dose range,
side-effects and clinical usefulness of citalopram in OCD. A total of 29 OCD
patients were included in the study, of whom 76% showed alleviation of symptoms
as evaluated by various self- and observer-rated scales, such as the Yale-Brown
Obsessive Compulsive Scale. In most cases the citalopram doses used were in
most cases 40 or 60 mg daily, and the treatment was well tolerated. The most
commonly experienced adverse events during the study were nausea, vomiting,
increased dreaming and decreased sleep. Diminished sexual desire and orgasmic
dysfunction were also reported. Despite having the limitations of an open
study, our results suggest that citalopram may be effective in the treatment of
obsessive-compulsive disorder.
J Affect Disord 1997 Oct;46(1):51-58
Citalopram and viloxazine in the treatment of depression by means of slow drop
infusion. A double-blind comparative trial.
Bouchard JM, Strub N, Nil R
C.H.S. Gerard Marchant, Toulouse, France.
Antidepressant efficacy and tolerability of citalopram and viloxazine were
compared under double-blind conditions during the first two weeks of treatment
with slow drop infusion, followed by oral administration for the rest of the
six week trial period. The 62 severely depressed and hospitalized patients
included in the intention-to-treat analysis had a mean age of 45 years (range
23 to 70 years). About two thirds of the patients were female. Thirty patients
were allocated to the citalopram and 32 patients to the viloxazine group. The
mean MADRS total score at baseline was 34 in both groups and decreased to 12.3
in the citalopram and to 16.9 in the viloxazine group after 14 days of
infusion. On day 42 (end point) the scores dropped to 6.7 in the citalopram and
to 13.1 in the viloxazine group respectively. The group differences reached the
level of significance at both time points (p < 0.05) in favor of citalopram.
The analysis of treatment emergent adverse events based on the UKU scale showed
a higher frequency of nausea on day 14 and constipation at study end in the
viloxazine group (p < 0.05) whereas reported weight gain (day 21) and
concentration difficulty (day 21) were more frequently seen in the citalopram
group (p < 0.05). Standard laboratory investigations and ECG analyses did not
show clinically relevant abnormalities. It is concluded that antidepressant
treatment with citalopram infusion followed by oral citalopram may be more
efficacious than a corresponding treatment schedule with viloxazine.
Chirality 1997;9(7):686-692
Steady-state pharmacokinetics of the enantiomers of citalopram and its
metabolites in humans.
Sidhu J, Priskorn M, Poulsen M, Segonzac A, Grollier G, Larsen F
Department of Pharmacokinetics/Dynamics, H. Lundbeck A/S, Copenhagen, Denmark.
The steady-state pharmacokinetics in serum and urine of the enantiomers of
citalopram and its metabolites, demethylcitalopram (DCT) and
didemethylcitalopram (DDCT), were investigated after multiple doses of
rac-citalopram for 21 consecutive days (40 mg per day) to healthy human
subjects who were extensive metabolizers of sparteine and mephenytoin.
Comparable pharmacokinetic variability was noted for (+)-(S)-, (-)-(R)- and
rac-citalopram. Enantiomeric (S/R) serum concentration ratios for citalopram
were always less than unity and were constant during the steady-state dosing
interval. A modest, but statistically significant, stereoselectivity in the
disposition of citalopram and its two main metabolites was observed. Serum
levels of the (+)-(S)-enantiomers of citalopram, DCT, and DDCT throughout the
steady-state dosing interval investigated were 37 +/- 6%, 42 +/- 3% and 32 +/-
3%, respectively, of their total racemic serum concentrations. The
(+)-(S)-enantiomers of citalopram, DCT, and DDCT were eliminated faster than
their antipodes. For (-)-(R)- and (+)-(S)-citalopram, respectively, the serum
t1/2 averaged 47 +/- 11 and 35 +/- 4 h and AUCss averaged 4,193 +/- 1,118
h.nmol/l and 2,562 +/- 1,190 h.nmol/l. The observed enantiospecificities were
apparently more related to clearance, rather than to distributional mechanisms.
Eur Arch Psychiatry Clin Neurosci 1997;247(4):234-236
Use of the selective serotonin reuptake inhibitor citalopram in treatment of
trichotillomania.
Stein DJ, Bouwer C, Maud CM
Department of Psychiatry, University of Stellenbosch, Tygerberg, South Africa.
Previous trials of selective serotonin reuptake inhibitors (SSRIs) in the
treatment of trichotillomania have provided conflicting data. Furthermore, the
efficacy of citalopram, the most selective of the SSRIs, in trichotillomania
has not previously been documented. Citalopram was used on an open-label
naturalistic basis in 14 (1 male and 13 females) patients who presented with
chronic hair-pulling and met DSM-IV criteria for trichotillomania. Ratings were
completed every 2 weeks for 12 weeks, during which time dosage was increased to
a maximum of 60 mg daily (mean dose 36.2 +/- 13.9 mg). One patient was unable
to tolerate citalopram. In completers, ratings on each of the scales employed
were significantly improved after treatment. Of completers 38.5% were
responders (Clinical Global Impressions score of 2 or less) at week 12.
Citalopram appears to be safe in trichotillomania, and it may be effective in a
subset of patients. Given the relatively low response rate, however, a
controlled trial is needed before this agent can be said to be more effective
than placebo. The pharmacotherapy of trichotillomania deserves further study.
Clin Neuropharmacol 1997 Oct;20(5):419-433
Lack of adverse interactions between concomitantly administered selegiline and
citalopram.
Laine K, Anttila M, Heinonen E, Helminen A, Huupponen R, Maki-Ikola O,
Reinikainen K, Scheinin M
Department of Pharmacology and Clinical Pharmacology, University of Turku,
Finland.
We have evaluated the risk for pharmacokinetic and/or pharmacodynamic
interactions of concomitantly administered selegiline, a selective monoamine
oxidase type B inhibitor, and citalopram, a widely used selective serotonin
uptake inhibitor antidepressant. Two parallel groups of healthy volunteers
received 20 mg of citalopram (n = 12) or placebo (n = 6) once daily for 10 days
in a randomized, double-blind fashion, followed by concomitant selegiline 10 mg
once daily for 4 days. The safety of this drug combination was assessed by
measurements of blood pressure, heart rate, body temperature, and inquiries for
adverse events. Blood samples were taken for the analysis of serum
concentrations of both study drugs and their metabolites and plasma prolactin,
adrenaline, noradrenaline, and 3,4-dihydroxyphenylglycol (DHPG); urinary
excretion of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were assessed.
After a 5-week washout, the 12 subjects who took citalopram in the first part
of the study received 10 mg of selegiline once daily for 4 days to compare the
pharmacokinetics of selegiline with and without concomitant citalopram. The
safety analysis showed no significant differences in vital signs or the
frequency of adverse events between the study groups. Plasma prolactin
concentrations were increased by 40% after 10 days' treatment with citalopram
(p = 0.03); this was not potentiated by concomitantly administered selegiline.
The comparison of plasma concentrations of noradrenaline, adrenaline, and DHPG
and the amount of serotonin and 5-HIAA excreted into urine between the study
groups indicated no signs of subclinical pharmacodynamic interaction between
selegiline and citalopram. The relative bioavailability of selegiline was
slightly reduced (by 29%; p = 0.008) when citalopram was coadministered
compared with selegiline alone. However, no indication of a pharmacokinetic
interaction was found in the analysis of serum concentrations of the three main
metabolites of selegiline. The pharmacokinetics of citalopram remained
unaffected by concomitant selegiline. The present results indicate lack of
clinically relevant pharmacodynamic or pharmacokinetic interactions between
selegiline and citalopram.
Br J Psychiatry 1997 Jun;170:549-553
The effect of citalopram in panic disorder.
Wade AG, Lepola U, Koponen HJ, Pedersen V, Pedersen T
Clydebank Health Centre, Dunbartonshire, Scotland.
BACKGROUND: Citalopram is a serotonin reuptake inhibitor which has been
demonstrated to be highly selective and with a superior tolerability profile to
the classical tricyclic antidepressants. This study was designed to test
whether there was any difference in efficacy in the management of panic
disorder (PD) between citalopram and placebo. METHOD: This was a double-blind,
placebo and clomipramine controlled, parallel group eight-week study. A total
of 475 patients with PD, with or without agoraphobia, were randomized to
treatment with either placebo, clomipramine 60 or 90 mg/day, or citalopram 10
or 15 mg/day, or 20 or 30 mg/day, or 40 or 60 mg/day. Doses were increased over
the first three weeks, stabilized during the fourth week and fixed between
weeks five and eight. RESULTS: Treatment with citalopram at 20 or 30 mg, 40 or
60 mg and clomipramine were significantly superior to placebo, judged by the
number of patients free of panic attacks in the week prior to the final
assessment. All rating scales examined suggested that citalopram 20 or 30 mg
was more effective than citalopram 40 or 60 mg. CONCLUSION: The most
advantageous benefit/risk ratio for the treatment of PD was associated with
citalopram 20 or 30 mg/day.
Lancet 1997 Sep 13;350(9080):818
Citalopram toxicity.
Glassman AH
Br J Clin Pharmacol 1997 Sep;44(3):295-298
Excretion of citalopram in breast milk.
Spigset O, Carieborg L, Ohman R, Norstrom A
Division of Clinical Pharmacology, Norrland University Hospital, Umea, Sweden.
AIMS: The objective of this study was to measure to secretion of the selective
serotonin uptake inhibitor citalopram in breast milk. METHODS: The excretion of
citalopram in breast milk was studied at steady-state conditions in two
patients with depression and in one healthy volunteer after ingestion of a
single dose citalopram. RESULTS: Milk/serum concentration ratios based on
single pairs of samples from the two patients ranged from 1.16 to 1.88. Based
on milk concentration data from the patients, the absolute dose ingested by a
suckling infant would be 4.3-17.6 micrograms kg-1 day-1, and the relative dose
0.7-5.9% of the weight-adjusted maternal dose. Based on
area-under-the-time-concentration curves from the healthy volunteer, the
milk/serum ratio was 1.00, the absolute dose to the infant during steady-state
conditions would be 11.2 micrograms kg-1 day-1 and the relative dose 1.8% of
the weight-adjusted maternal dose. CONCLUSION: The study shows that the
relative dose to a suckling infant is close to that reported for fluoxetine,
and higher than reported for fluvoxamine, paroxetine and sertraline.
Lancet 1997 Aug 16;350(9076):518-519
Citalopram toxicity.
Personne M, Persson H, Sjoberg E
Clin Pharmacol Ther 1997 Aug;62(2):209-224
Using fuzzy logic to predict response to citalopram in alcohol dependence.
Naranjo CA, Bremner KE, Bazoon M, Turksen IB
Psychopharmacology Research Program, Sunnybrook Health Science Centre, Toronto,
Ontario, Canada. naranjo@owl.sunnybrook.utoronto.ca
INTRODUCTION: The prediction of patient response to new pharmacotherapies for
alcohol dependence has usually not been successful with standard statistical
techniques. We hypothesized that fuzzy logic, a qualitative computational
approach, could predict response to 40 mg/day citalopram and 40 mg/day
citalopram with a brief psychosocial intervention in alcohol-dependent
patients. METHODS: Two data sets were formed with patients from our studies who
received 40 mg/day citalopram alone (n = 34) or 40 mg/day citalopram and a
brief psychosocial intervention (n = 28). The output variable, "response," was
the percentage decrease in alcohol intake from baseline. Input variables
included age, gender, baseline alcohol intake, and levels of anxiety,
depression, alcohol dependence, and alcohol-related problems. RESULTS: A fuzzy
rulebase was created from the data of 26 randomly chosen patients who received
40 mg/day citalopram and was used to predict the responses of the remaining
eight patients. Eight rules related response with depression, anxiety, alcohol
dependence, alcohol-related problems, age, and baseline alcohol intake. The
average magnitude of the error in the predictions (RMSE) was 2.6 with a bias
(ME) of 0.6. Predicted and actual response correlated (r = 0.99; p < 0.001). A
fuzzy rulebase was created from the data of 28 randomly chosen patients who
received 40 mg/day citalopram and a brief psychosocial intervention and was
used to predict the responses of the remaining five patients. Six rules related
response with age, anxiety, depression, alcohol dependence, and baseline
alcohol intake with good predictive performance (RMSE = 6.4; ME = -1.5; r =
0.96; p < 0.01). CONCLUSIONS: This study indicates that fuzzy logic modeling
can predict response to pharmacotherapies for alcohol dependence.
Br J Clin Pharmacol 1997 Aug;44(2):199-202
Investigation of multiple dose citalopram on the pharmacokinetics and
pharmacodynamics of racemic warfarin.
Priskorn M, Sidhu JS, Larsen F, Davis JD, Khan AZ, Rolan PE
H. Lundbeck A/S, Copenhagen, Denmark.
AIMS: An open, controlled, randomized, crossover study was conducted in healthy
males to assess the possible occurrence of a pharmacokinetic/pharmacodynamic
interaction between warfarin and the selective serotonin re-uptake inhibitor
citalopram. METHODS: Twelve subjects received a single 25 mg dose of racemic
warfarin either alone or on Day 15 of a 21-day oral dosing regimen of 40 mg
citalopram daily. Blood samples for pharmacokinetic analysis were obtained over
a 168 h period after warfarin dosing. The degree of anticoagulation was
assessed by the prothrombin time. RESULTS: Citalopram produced no change in the
pharmacokinetics of (R)- and (S)-warfarin, indicating that citalopram does not
alter the metabolism of warfarin mediated via CYP1A2, CYP3A4 and CYP2C9.
Citalopram coadministration resulted in a statistically significant increase in
the maximum prothrombin time (R(max); by 1.6 +/- 3.0 s) and the area under the
prothrombin time-time curve (AUC(PT); by 5.0 +/- 5.7%). The 90% confidence
intervals for R(max) and AUC(PT) ratios (citalopram + warfarin/warfarin alone)
were 1.01-1.10 and 1.03-1.07, respectively. CONCLUSIONS: The small increase in
prothrombin time observed in this study with coadministration of citalopram and
warfarin is not considered to be of importance in the clinical setting.
J Clin Psychopharmacol 1997 Aug;17(4):267-271
Efficacy of fluvoxamine, paroxetine, and citalopram in the treatment of
obsessive-compulsive disorder: a single-blind study.
Mundo E, Bianchi L, Bellodi L
Department of Neuropsychiatric Sciences, San Raffaele Hospital, University of
Milan School of Medicine, Italy.
Obsessive-compulsive disorder (OCD) has been successfully treated with
proserotonergic agents for some years. Clomipramine was the first drug used,
but several clinical trials have been conducted more recently to assess the
antiobsessional efficacy of selective serotonin reuptake inhibitors (SSRIs).
The aim of this study was to compare the antiobsessional efficacy of three
SSRIs, fluvoxamine, paroxetine, and citalopram. Thirty obsessive-compulsive
patients without comorbid axis I diagnoses except for tic disorder as assessed
by DSM-III-R criteria gave informed consent and were recruited consecutively;
they underwent a 10-week randomized treatment with fluvoxamine, paroxetine, or
citalopram. Ratings were performed under blind conditions every 2 weeks from
baseline to the end of the study and by the Yale-Brown Obsessive-Compulsive
Scale, the National Institute of Mental Health-Obsessive-Compulsive Scale, the
Clinical Global Impressions Scale, and the Hamilton Rating Scale for
Depression. Quantitative and qualitative analyses of the antiobsessional
efficacy of the three drugs were completed with analysis of variance with
repeated measures and survival analysis. The results showed no significant
differences between the three treatments. The preliminary conclusions drawn
from this study concern the interchangeable antiobsessional effects of
different SSRIs, although further studies of "cross-response" to these drugs
are needed.
Lancet 1997 May 31;349(9065):1602
Symptoms and signs of severe citalopram overdose.
Grundemar L, Wohlfart B, Lagerstedt C, Bengtsson F, Eklundh G
Lakartidningen 1997 Apr 23;94(17):1603-1604
[Picture of poisoning in citalopram overdose. Convulsions and ECG symptoms can
occur].
[Article in Swedish]
Personne M, Persson H, Sjoberg G
Giftinformationscentralen, Stockholm.
Ther Drug Monit 1997 Apr;19(2):236-239
Citalopram and desmethylcitalopram concentrations in breast milk and in serum
of mother and infant.
Jensen PN, Olesen OV, Bertelsen A, Linnet K
Department B, Psychiatric Hospital, Arhus, Risskov, Denmark.
A case is presented with measurements of the selective serotonin reuptake
inhibitor (SSRI)-antidepressant citalopram in serum of mother and breast-fed
infant and in breast milk. We found a milk-to-serum concentration ratio of
approximately 3 for both citalopram and the main metabolite
desmethylcitalopram. Peak milk concentrations of citalopram occurred 3-9 h
after drug intake by the mother. The infant received approximately 5% of the
mother's dose, adjusted for weight. Accordingly, the serum level in the infant
of approximately 7 nM corresponded to approximately 1/15 of the trough serum
concentration of the mother (104 nM). No signs of drug effects in the infant
were observed.
Int Clin Psychopharmacol 1997 Mar;12(2):121-122
Citalopram-associated clitoral priapism: a case series.
Berk M, Acton M
Department of Psychiatry, University of the Witwatersrand Medical School,
Parktown, Johannesburg, South Africa.
Priapism is documented to occur in association with treatment with a variety of
psychotropic agents. Three cases of clitoral priapism associated with treatment
with citalopram are presented.
Pharmacogenetics 1997 Feb;7(1):1-10
Identification of three cytochrome P450 isozymes involved in N-demethylation of
citalopram enantiomers in human liver microsomes.
Rochat B, Amey M, Gillet M, Meyer UA, Baumann P
Unite de Biochimie et Psychopharmacologie Clinique, Departement Universitaire
de Psychiatrie Adulte, Prilly-Lausanne, Switzerland.
Using in vitro techniques, the present study demonstrates that CYP2D6, and 3A4
are involved in N-demethylation of citalopram (CIT) enantiomers. Human liver
microsome incubations performed with specific inhibitors of these three CYP
isozymes have shown up to 60% inhibition of desmethylcitalopram production. cDNA
expressed human cytochrome P-450 3A4, 2C19 and 2D6 isozymes, but not CYP1A2,
were identified to be involved in N-demethylation of CIT enantiomers. Kinetics
using cDNA expressed CYP2C19 and CYP3A4 show K(m) values in the same range: 198
microM, 211 microM for CYP2C19 and 169 microM, 163 microM for CYP3A4 for S- and
R-CIT demethylation, respectively. In contrast, kinetics using cDNA expressed
CYP 2D6 show a K(m) of 18 microM and 22 microM for S- and R-CIT demethylation,
respectively. Nevertheless, kinetics using cDNA expressed CYP2C19 and 3A4 have
a range of Vmax values ten times higher than that of CYP2D6. For this reason,
intrinsic clearance values (Vmax/K(m)) for S- and R-CIT were within a small
range for these three isozymes: 0.25 to 0.39 microliter h-1 x pmol-1 of CYP.
CYP2D6 has an opposite stereoselectivity in the biotransformation of CIT
enantiomers than CYP2C19 and 3A4; the S/R ratios of the intrinsic clearance
were 0.71, 1.57 and 1.37, respectively. Taking into account that CYP isozymes
are expressed at various levels, CYP2D6, which is expressed at lower levels
than CYP2C19 and CYP3A4, plays a minor role in the biotransformation of CIT
enantiomers. These results confirm that the use of cDNA expressed CYP isozymes
is a potent tool for the measurement of kinetic constants and help to predict
clearance modifications of CIT enantiomers, especially in poor metabolizers of
mephenytoin (with a CYP2C19 deficiency) or patients comedicated with potent
CYP2C19 or 3A4 inhibitor(s). For instance, fluvoxamine (100 microM) inhibits
CIT N-demethylation by 64% in microsomes.
J Pharmacol Exp Ther 1997 Feb;280(2):927-933
Identification of cytochrome P450 isoforms involved in citalopram
N-demethylation by human liver microsomes.
Kobayashi K, Chiba K, Yagi T, Shimada N, Taniguchi T, Horie T, Tani M, Yamamoto
T, Ishizaki T, Kuroiwa Y
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa
University, Tokyo, Japan.
Studies to assess the enzyme kinetic behavior and to identify the cytochrome
P450 (CYP) isoform(s) involved in the major metabolic pathway (N-demethylation)
for citalopram (CIT), a selective serotonin reuptake inhibitor, were performed
using human liver microsomes and cDNA-expressed human cytochrome P450 isoforms.
The N-demethylation activities showed significant correlations with the alpha-
and 4-hydroxylation activities of triazolam (r(s) = 0.818 and 0.851,
respectively; P < .01) in 10 different human liver microsomes. Anti-CYP3A
antibodies and ketoconazole strongly inhibited CIT N-demethylation. In
addition, there was a significant correlation between CIT N-demethylation and
(S)-mephenytoin 4'-hydroxylation (r(s) = 0.773, P < .05), although little
inhibition was observed in the presence of anti-CYP2C antibodies or
(S)-mephenytoin. cDNA-expressed CYP3A4 and CYP2C19 catalyzed CIT
N-demethylation, whereas no appreciable activities were observed for CYP1A2,
CYP2A6, CYP2B6, CYP2C9, CYP2D6 and CYP2E1. The percentage contributions of
CYP3A4 and CYP2C19 to the overall N-demethylation of CIT in human liver
microsomes were estimated using a relative activity factor; respective values
of 70% and 7% were calculated for microsomes obtained from livers from putative
extensive metabolizers for (S)-mephenytoin 4'-hydroxylation. These results
suggest that CYP3A4 is the major isoenzyme and CYP2C19 is the minor form
involved in the major metabolic pathway for CIT in human liver microsomes.
Eur J Clin Pharmacol 1997;52(3):241-242
Pharmacokinetic interaction study of citalopram and cimetidine in healthy
subjects.
Priskorn M, Larsen F, Segonzac A, Moulin M
Therapie 1997 Jan;52(1):76-77
Galactorrhea induced by a pharmacodynamic interaction between citalopram,
alprazolam and tramadol: a case report.
Bondolfi G, Rubin C, Bryois C, Eap CB
Int Clin Psychopharmacol 1997 Jan;12(1):61-63
Combined serotonin syndrome and hyponatremia caused by a citalopram-buspirone
interaction.
Spigset O, Adielsson G
Division of Clinical Pharmacology, Norrland University Hospital, Umea, Sweden.
Int Clin Psychopharmacol 1997 Jan;12(1):31-35
Citalopram as an adjuvant in schizophrenia: further evidence for a serotonergic
dimension in schizophrenia.
Taiminen TJ, Syvalahti E, Saarijarvi S, Niemi H, Lehto H, Ahola V, Salokangas
RK
Department of Psychiatry, Turku University Central Hospital, Finland.
There is increasing evidence suggesting that symptoms of depression and anxiety
may also be associated with serotonergic dysfunction in schizophrenic patients.
The effect of the adjuvant selective serotonin reuptake inhibitor citalopram
was assessed regarding the symptom dimensions of schizophrenia measured with
the Positive and Negative Syndrome Scale (PANSS) and with the Hamilton Rating
Scale for Depression (HRSD). Citalopram alleviated symptoms of the
depression/anxiety dimension of the PANSS, but not the symptoms of the four
other PANSS domains or depressive symptoms measured with the HRSD. The results
support the hypothesis of a serotonergic dimension in schizophrenia.
Am J Geriatr Psychiatry 1997;5(1):70-78
An open pilot study of citalopram for behavioral disturbances of dementia.
Plasma levels and real-time observations.
Pollock BG, Mulsant BH, Sweet R, Burgio LD, Kirshner MA, Shuster K, Rosen J
Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA.
Citalopram, in European studies, has shown some early promise for treatment of
poststroke depression and behavioral complications of dementia. An open pilot
study of citalopram was conducted in 16 patients with dementia and behavioral
disturbances. Citalopram was well tolerated by 13 of the patients, and 9 had a
clinically impressive response. A significant overall mean reduction in
disruptive vocalizations was observed by means of a novel technique of
computer-assisted real-time observation. The mean citalopram plasma
level-to-dose ratio was found to be twice that previously reported in younger
patients. These pilot findings should encourage future placebo
concentration-controlled trials.
J Toxicol Clin Toxicol 1997;35(3):237-240
Citalopram overdose--review of cases treated in Swedish hospitals.
Personne M, Sjoberg G, Persson H
Swedish Poisons Informaation Centre, Karolinska Hospital, Stockholm, Sweden.
gic.@gic.ks.se
BACKGROUND: The toxic effects of acute citalopram overdose are reported by the
Swedish Poisons Information Centre. DESIGN: Case reports received from Swedish
hospitals during 1995 have been analyzed. Forty-four cases of pure citalopram
intoxication have been studied in detail. RESULTS: At doses below 600 mg, mild
symptoms were observed. Doses above 600 mg caused ECG abnormalities and
convulsions in some patients, while doses greater than 1900 mg caused such
symptoms in all patients. CONCLUSIONS: The findings are consistent with
previous reports claiming that selective serotonin reuptake inhibitors are less
toxic compared to tricyclic antidepressants. However, there is a risk of
developing serious symptoms when large doses have been ingested.
[published erratum appears in J Toxicol Clin Toxicol 1997;35(5):577]
Psychopharmacol Bull 1997;33(1):109-112
Plasma levels of citalopram enantiomers and metabolites in elderly patients.
Foglia JP, Pollock BG, Kirshner MA, Rosen J, Sweet R, Mulsant B
Department of Psychiatry, University of Pittsburgh, School of Medicine, PA
15213, USA.
Ten patients with dementia and significant behavioral disturbances (mean age of
77.2 +/- 8.2 years) received citalopram, 10 mg/day for 3 days, followed by 20
mg/day for 2 weeks. Six of the 10 patients completing 17 days of treatment had
a clinically impressive response, as assessed by significant improvement in six
target items on the Neurobehavioral Rating Scale. Eight patients were also
analyzed by measuring the racemic and enantiomeric plasma levels of citalopram
(CIT) and desmethylcitalopram (DCIT). A sensitive high-performance liquid
chromatography (HPLC) assay for citalopram enantiomers and metabolites was
developed using ultraviolet detection. The lower limit of detection was 10
ng/ml for each enantiomer. Steady-state plasma level ranges were 11.2 to 92.2
ng/ml for the biologically active S(+) citalopram and 12.8 to 95.7 ng/ml for
the inactive R(-) enantiomer. For the S and R enantiomers of
desmethylcitalopram, plasma levels ranged from 11.0 to 22.0 ng/ml and 9.2 to
22.0 ng/ml, respectively. The racemic citalopram plasma level to dose ratio of
3.50 was higher than the ratio (1.96) reported by Overo (1982) for 55 younger
patients. The stereoselective metabolism of the enantiomers for citalopram and
desmethylcitalopram (S(+) and R(-) enantiomers) in these older subjects
differed from that reported in younger patients, suggesting possible
age-associated changes in CYP2C19 activities. We hypothesize that
quantification of S(+) citalopram will permit a more accurate examination of
dose/response relationships. This measure seems to be especially important for
older subjects, given the wide ranges and higher concentrations evident from
our preliminary results.
Int Clin Psychopharmacol 1996 Dec;11(4):273-278
Phasic craving for carbohydrate observed with citalopram.
Bouwer CD, Harvey BH
Department of Psychiatry, University of Stellenbosch Medical School, Tygerberg,
Republic of South Africa.
The serotonin selective reuptake inhibitors (SSRIs) have clinically and
ancedotally been associated with nausea and weight loss as a side effect of
their action. The tricyclic antidepressants have been linked to carbohydrate
(CHO) craving and weight gain in patients with major depressive disorders. This
side effect has been attributed to the strong anti-histaminergic actions of
these agents and is recognized as a causal factor of non-compliance in a
substantial percentage of patients. CHO craving is an important feature and
complication of the treatment of depression and is often ignored. A total of 18
patients were treated with the SSRI citalopram in our mood disorder clinic. In
eight cases there was a significant increase in CHO craving together with
weight gain shortly after initiation of treatment. The craving for CHO took on
a phasic presentation. These cases are presented, together with data on the
change in mood and anxiety symptom rating scales. Our observations appear
paradoxical, given that serotonin (5-HT) typically mediates a reduction in CHO
intake and that citalopram displays potent and select 5-HT-enchancing actions.
However, the receptor binding profile of citalopram may predict a risk for
inducing this adverse event. These, together with serotonergic, dopaminergic,
histaminergic and other possible mechanisms are discussed. A profound influence
on patient acceptability was observed, suggesting that the impact on compliance
needs to be considered.
Psychopharmacology (Berl) 1996 Dec;128(4):421-425
Non-response to citalopram in depressive patients: pharmacokinetic and clinical
consequences of a fluvoxamine augmentation.
Bondolfi G, Chautems C, Rochat B, Bertschy G, Baumann P
Department of Universitaire de Psychiatrie Adulte, Hopital de Cery, CH-1008
Prilly-Lausanne, Switzerland.
The effect of comedication with fluvoxamine on the plasma concentrations of the
enantiomers of citalopram and its metabolites in dextromethorphan/mephenytoin
phenotyped patients pretreated with citalopram (CIT) was studied: seven female
patients (45.1 +/- 13.9 years) suffering from a major depressive episode
[ICD-10: F32.2 (n = 3 patients), F33.2 (n = 2), F32.10 (n = 1) or F32.11 (n =
1)], who were non-responders to a 3-week treatment with 40 mg/day CIT (From
day-21 to day 0) (day 0: MADRS score > or = 12), were co-medicated for another
3 weeks with fluvoxamine (50 mg/day from day 1-7, 100 mg/day from day 14-21).
All patients were extensive metabolizers of mephenytoin (CYP2C19) and
dextromethorphan (CYP2D6), except one patient, who had a genetic deficiency of
CYP2D6. There was a significant increase of the plasma concentrations of S- and
R-citalopram from day 0 (27 +/- 14 micrograms/l and 55 +/- 23 micrograms/l,
respectively) to day 21 (83 +/- 38 micrograms/l and 98 +/- 44 micrograms/l,
respectively), after addition of fluvoxamine (P < 0.02, for each comparison),
and the mean ratio S/R-citalopram increased from 0.48 to 0.84. S-Citalopram
inhibits more potently 5-HT uptake than R-citalopram: therefore, fluvoxamine
increases the pharmacologically more active S-citalopram with some
stereoselectivity. According to a previous in vitro study, this pharmacokinetic
interaction occurs on the level of CYP2C19, but also of CYP2D6 and CYP3A4
which, in contrast to CYP1A2, contribute to the N-demethylation of citalopram
and which are stereoselectively inhibited by fluvoxamine. All but one patient
showed clinical improvement by a decrease of the MADRS score by at least 50%
and a final score < or = 13 (mean +/- SD: day 0:30.6 +/- 9.2; day 21:11.0 +/-
6.5). Some patients showed minor symptoms, such as nausea and tremor, but the
combined treatment was generally well tolerated.
Lancet 1996 Nov 16;348(9038):1380
Fatal overdose with citalopram?
Brion F, Brion N, Durigon M
Lancet 1996 Oct 12;348(9033):1033
Risks with citalopram in perspective.
Isacsson G, Bergman U
Int Clin Psychopharmacol 1996 Sep;11(3):157-164
Efficacy and tolerability of citalopram in comparison with fluvoxamine in
depressed outpatients: a double-blind, multicentre study. The LUCIFER Group.
Haffmans PM, Timmerman L, Hoogduin CA
Psychiatric centre Bloemendaal, The Hague, The Netherlands.
In 16 depression clinics in hospitals and outpatient facilities in the
Netherlands, a study was performed to evaluate and compare the efficacy and
tolerability of citalopram and fluvoxamine and to determine the difference in
the incidence of gastrointestinal side-effects. A total of 217 patients with a
depressive disorder (DSM-III-R criteria) and a score of at least 16 on the
Hamilton rating scale for depression were randomized to treatment. The results
of this study indicate that the two drugs are equally effective. The adverse
events occurring during treatment show a similar pattern between the two drugs,
but citalopram is better tolerated than fluvoxamine. Citalopram induces fewer
gastrointestinal adverse events compared with fluvoxamine. However, this did
not affect the drop-out rates.
Acta Psychiatr Scand 1996 Sep;94(3):175-180
Citalopram as an adjuvant in chronic schizophrenia: a double-blind
placebo-controlled study.
Salokangas RK, Saarijarvi S, Taiminen T, Kallioniemi H, Lehto H, Niemi H,
Tuominen J, Ahola V, Syvalahti E
Department of Psychiatry, University of Turku, Finland.
The effects of citalopram--the most selective serotonin reuptake inhibitor on
the market--on psychopathological symptoms were studied in chronic
schizophrenic patients on a stable regimen of neuroleptic medication.
Outpatients suffering from schizophrenic disorder (DSM-III-R) with Positive and
Negative Symptom Scale (PANSS) scores higher than 50 were included in a
double-blind placebo-controlled add-on study. The daily dose of citalopram was
20 mg in the first week and 40 mg for the remaining period. A total of 90
patients (45 patients receiving citalopram and 45 receiving placebo) completed
the 12-week trial. There were no changes in neuroleptic plasma levels during
the trial. There was a significant decrease in total PANNS scores during the
trial, although no statistically significant differences between the citalopram
group and the placebo group were revealed. The number of responders in terms of
severity of illness (CGI) was higher and the increase in subjective well-being
(VAS) was greater in patients on citalopram than in those receiving placebo.
There were no significant differences in the occurrence of side-effects. It is
concluded that, in chronic schizophrenic out-patients, citalopram has no clearon the psychopathological symptoms; it may improve the general clinical
condition, and it appears to increase the subjective well-being of these
patients. Citalopram appears to be safe when used to treat schizophrenic
patients who are receiving concomitant neuroleptic treatment.
Behav Brain Res 1996 Sep;79(1-2):183-192
Citalopram: differential sleep/wake and EEG power spectrum effects after single
dose and chronic administration.
Neckelmann D, Bjorvatn B, Bjorkum AA, Ursin R
Department of Physiology, University of Bergen, Norway.
dag.neckelmann@phs.ulaval.ca
The sleep/wake effects of the selective serotonin re-uptake inhibitor
citalopram were studied in both a single-dose study with three dose levels
(0.5, 2.0 and 5.0 mg/kg), and a 5-week chronic administration study (15
mg/kg/24 h). Single doses of citalopram resulted in a dose-dependent inhibition
of rapid eye movement (REM) sleep. After chronic citalopram treatment there was
a sustained REM sleep inhibition. Single doses of citalopram resulted in only
minor changes in non-REM (NREM) sleep as well as in NREM EEG power spectral
density. Chronic administration resulted in a major shift from SWS-2 to SWS-1.
The observed corresponding changes in EEG power density were regional. A 30 to
40 percent reduction of power density in the 0.5-15 Hz range in the
fronto-parietal EEG derivation was seen for the whole 8-h registration period.
In the fronto-frontal EEG derivation only minor changes were seen. A decreasing
trend in NREM sleep power density between 0.5 and 7 Hz, usually seen during the
course of the light period, was not observed in the chronic condition, but was
seen in control and single-dose condition, suggesting altered diurnal
distribution of slow wave activity in the chronic condition. The data indicate
that acute and chronic administration of citalopram shows clear differences in
sleep effect, which may be caused by alteration of serotonergic transmission,
and may be related to the antidepressant effect.
J Neurol Neurosurg Psychiatry 1996 Sep;61(3):285-290
A non-selective (amitriptyline), but not a selective (citalopram), serotonin
reuptake inhibitor is effective in the prophylactic treatment of chronic
tension-type headache.
Bendtsen L, Jensen R, Olesen J
Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
OBJECTIVES: Although the tricyclic antidepressant amitriptyline is extensively
used in the prophylactic treatment of chronic tension-type headache, only few
studies have investigated the efficacy of this treatment and the results are
contradictory. In addition, the new selective serotonin reuptake inhibiting
antidepressants, which are widely used in depression and of potential value in
pain management, have never been investigated in a placebo controlled study of
tension-type headache. The aim was to evaluate the efficacy of amitriptyline
and of the selective serotonin reuptake inhibitor citalopram in chronic
tension-type headache. METHODS: Forty non-depressed patients with chronic
tension type headache were included in a 32 week, double blind, placebo
controlled, three-way crossover study. RESULTS: Thirty four patients completed
the trial. Amitriptyline reduced area under the headache curve by 30% compared
with placebo (P = 0.002), whereas citalopram had no significant effect (P =
0.68). Explanatory analyses showed that amitriptyline significantly reduced the
duration of headache (P = 0.01), headache frequency (P = 0.01), and intake of
analgesics (P = 0.02) but not headache intensity (P = 0.12). CONCLUSION:
Although amitriptyline did not eliminate the headache, it provided a clinically
important reduction of headache in the majority of otherwise treatment
resistant patients. The differential effect of amitriptyline and citalopram
indicates that mechanisms other than inhibition of serotonin reuptake are
involved in the analgesic effect of the tricyclic antidepressants.
Amitriptyline, but not citalopram, is valuable in the prophylactic treatment of
chronic tension type headache.
Ugeskr Laeger 1996 Aug 26;158(35):4920-4923
[Citalopram and desmethylcitalopram for psychiatric patients].
[Article in Danish]
Linnet K, Olesen OV
Afdeling for biologisk psykiatri, Psykiatrisk Hospital i Arhus.
Serum samples were selected randomly from blood samples drawn in the morning
for other reasons in patients treated with citalopram, and the serum
concentrations of citalopram (S-citalopram) and its major metabolite
desmethylcitalopram were determined. A total of 44 patients, 13 males and 31
females, with a median age of 38.5 years (range 18-89) entered the study. In 17
patients given 20 mg/day of citalopram the S-citalopram was (median and range)
153 nmol/l (83-237). In 24 patients treated with citalopram 40 mg/day the
S-citalopram was 240 nmol/l (range 0-360). In one serum sample no S-citalopram
could be detected (non-compliance) and in another sample S-citalopram was just
above the detection limit (about 3 nmol/l). The latter may at least partly be
due to treatment with 600 mg/day of carbamazepine, which is known to accelerate
the metabolism of other drugs. The serum concentration of the major metabolite
desmethylcitalopram averaged 28% of S-citalopram and is most likely without
clinical importance. It is concluded that determination of S-citalopram may be
considered if there is doubt about the compliance of the patient, in drug
interaction cases or if the clinical effect is poor.
Lancet 1996 Aug 3;348(9023):339-340
Fatal overdose with citalopram.
Ostrom M, Eriksson A, Thorson J, Spigset O
J Clin Psychopharmacol 1996 Aug;16(4):307-314
A double-blind, placebo-controlled study of citalopram with and without lithium
in the treatment of therapy-resistant depressive patients: a clinical,
pharmacokinetic, and pharmacogenetic investigation.
Baumann P, Nil R, Souche A, Montaldi S, Baettig D, Lambert S, Uehlinger C,
Kasas A, Amey M, Jonzier-Perey M
Departement Universitaire de Psychiatrie Adulte, Prilly-Lausanne, Switzerland.
Sixty-nine depressive patients (DSM III criteria: 296.2, 296.3, 296.5, 300.4)
were treated with 40 to 60 mg citalopram (CIT) daily for 4 weeks. Among them,
45 responded to treatment (improvement > 50% on the 21-item Hamilton Rating
Scale for Depression [HAM-D]) and continued their treatment for another week
before being released from the study. The 24 nonresponders were randomized and
comedicated under double-blind conditions with lithium carbonate (Li) (2 x 400
mg/day) (CIT-Li group) or with placebo (CIT-Pl group) from days 29 to 35. For
days 36 to 42, the patients of both subgroups were treated openly with Li (800
mg/day) in addition to the ongoing CIT treatment. On day 35, 6 of 10 patients
responded to the CIT-Li combination, whereas 2 of 14 patients only responded to
the CIT-Pl combination. This group difference reached significance (p < 0.05)
on day 35 with lower HAM-D total scores in the CIT-Li group. No evidence was
seen of a pharmacokinetic interaction between CIT and Li, and this combination
was well tolerated. Patients were phenotyped with dextromethorphan and
mephenytoin at baseline and at day 28. As evaluated at baseline, three patients
(responders) were poor metabolizers of dextromethorphan and six patients (three
responders and three nonresponders) of mephenytoin. On day 28, the ratio
CIT/N-desmethylCIT (DCIT) in plasma was significantly higher in poor than in
extensive metabolizers of mephenytoin (p = 0.0001), and there was a significant
positive correlation between the metabolic ratio of dextromethorphan and the
ratio DCIT/N-didesmethylCIT in plasma (p < 0.001). These findings illustrate
the role of CYP2D6 and CYP2C19 in the metabolism of CIT. It can be concluded
that Li addition to CIT is effective in patients not responding to CIT alone
without any evidence of an accentuation or provocation of adverse events.
Int Clin Psychopharmacol 1996 Mar;11 Suppl 1:41-44
Scandinavian experience with citalopram in the elderly.
Gottfries CG
University of Goteborg, Department of Psychiatry and Neurochemistry, Molndal
Hospital, Sweden.
Depression is a common disorder among the elderly. Its prevalence is estimated
at 12-15%. A multifactorial genesis must be considered. Depression in the
elderly often manifests itself in an atypical way, with a somatized clinical
picture. As tricyclics are generally too toxic for elderly people, the use of
selective serotonin reuptake inhibitors (SSRIs) must be considered in this
patient group. Citalopram is an SSRI drug with an attractive pharmacokinetic
profile, i.e. few side effects and a low potential for interaction with other
drugs. In two inter-Nordic studies, this drug significantly improved emotional
disturbances in patients with dementia disorders. Significant improvement, with
a response rate of 53%, was also seen in elderly people with depression as
assessed using the Hamilton Depression Rating Scale. Sixty-six per cent of
these patients also suffered from physical illness and had other drug
treatment. The drug was well tolerated.
Int Clin Psychopharmacol 1996 Mar;11 Suppl 1:35-40
The safety and tolerability of citalopram.
Muldoon C
Lundbeck Ltd, Caldecotte, Milton Keynes, UK.
Since citalopram was first approved in 1989, it has been prescribed to an
estimated > 600 000 patients. An integrated safety database has been prepared,
including data from 3107 patients from 24 clinical trials. In
placebo-controlled trials, nausea, dry mouth, somnolence, increased sweating,
tremor, diarrhea, and ejaculation failure, mostly of mild to moderate
severity, occurred significantly (p < 0.05) more frequently with citalopram.
The excess incidence of these events over placebo was always less than 10%. In
pooled comparative studies, citalopram's tolerability profile was similar to
that of other selective serotonin reuptake inhibitors (SSRIs) and superior to
that of tricyclic antidepressants (TCAs). Spontaneous adverse event reports
arising from clinical use have confirmed the safety profile defined during the
trials program. Specific monitoring of all serious adverse events from around
10 000 patients receiving citalopram in clinical trials (including small open
studies) has indicated a low potential for convulsions and extrapyramidal
effects. There is no evidence of withdrawal phenomena on abrupt
discontinuation, no clinically relevant effects on cardiac or laboratory
parameters, and little or no effect on psychomotor function. When taken in
overdose alone, citalopram appears to have a relatively wide margin of safety.
Citalopram has been well tolerated in both short- and long-term use, and the
profile seen in trials has been confirmed in the clinic.
Int Clin Psychopharmacol 1996 Mar;11 Suppl 1:29-33
The antidepressant efficacy of citalopram.
Montgomery SA, Djarv L
St Mary's Hospital Medical School, London, UK.
Depression is a long-term illness requiring psychopharmacological treatment
over long periods of time. Treatments need to be effective and safe, but in an
illness requiring long-term medication, acceptability to patients must also be
addressed. Data from eight placebo-controlled studies addressing short-term
efficacy and two placebo-controlled studies of long-term (6 months) treatment
have demonstrated the antidepressant efficacy of citalopram. Fourteen studies
comparing citalopram with a reference antidepressant have provided supporting
evidence of efficacy. In all, 3905 patients have been included in clinical
efficacy studies, in which 2579 patients have been treated with citalopram, 486
with placebo and 840 with a reference antidepressant. The recommended dose of
20 mg appears appropriate for most patients, with the option of raising the
dose in non-responders, particularly if they have more severe depression.
Int Clin Psychopharmacol 1996 Mar;11 Suppl 1:5-11
Pharmacology and pharmacokinetics of citalopram and other SSRIs.
Baumann P
Unite de Biochimie et Psychopharmacologie Clinique, Departement Universitaire
de Psychiatrie Adulte, Prilly-Lausanne, Switzerland.
Citalopram together with fluoxetine, fluvoxamine, paroxetine and sertraline
belong to the group of SSRIs, so named because of their pharmacological action
as selective serotonin reuptake inhibitors in rat brain synaptosomes-their
potency of inhibiting noradrenaline uptake is low and, from a clinical point of
view, irrelevant. In contrast to classical tricyclic antidepressants and some
antipsychotics, the SSRIs have little affinity for the dopamine D2 receptors,
5-HT1A and 5-HT2A receptors, alpha 1-receptors, beta-receptors, muscarinic
receptors and histamine H1 receptors. Several authors have examined whether
SSRIs are ligands of other receptors, including the 5-HT3-5-HT7 receptors and
their subtypes, and the NMDA receptor, and whether chronic treatment with SSRIs
modifies the affinity and binding capacity of these receptors. The SSRIs differ
by their pharmacokinetics and pharmacogenetics of metabolism and by their
cytochrome P450 isozyme inhibition properties. Some situations are presented in
which plasma level monitoring of SSRIs is recommended, despite the lack of
clearly defined "therapeutic windows'.
Depress Anxiety 1996;4(5):253
Citalopram and panic disorder.
Bertani A, Perna G, Politi E, Bellodi L
Int Psychogeriatr 1996;8(4):659-668
Long-term treatment of elderly individuals with emotional disturbances: an open
study with citalopram.
Ragneskog H, Eriksson S, Karlsson I, Gottfries CG
Department of Clinical Neuroscience, Goteborg University, Molndal, Sweden.
In the present open study, the long-term safety, tolerability, and efficacy of
citalopram in the treatment of elderly people with emotional disturbances were
studied. One hundred twenty-three elderly patients with symptoms of
depression-anxiety were included. Most of the patients (76%) were demented.
Fifty-two patients completed a 12-month treatment. Irritability, depressed
mood, anxiety, restlessness, and fear-panic were significantly reduced. The
severity of illness from baseline to Month 9 was rated as significantly
improved. The side effects were infrequent and mostly mild.
Acta Psychiatr Scand 1996 Jan;93(1):69-70
Successful treatment of citalopram-induced anorgasmia by cyproheptadine.
Lauerma H
Psychiatric Clinic, University Central Hospital of Turku, Finland.
This is the first report of the use of cyproheptadine to treat anorgasmia
induced by citalopram, a highly selective serotonin reuptake inhibitor (SSRI).
Total anorgasmia of a 47 year-old man who suffered from severe unipolar major
depression was successfully treated without adverse effects. This case
strengthens the impression that anorgasmia associated with SSRIs is related
primarily to the serotonin reuptake inhibition and not to various receptor
bindings of different compounds.
Eur J Clin Pharmacol 1996;51(1):73-78
Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram,
fluoxetine, fluvoxamine and paroxetine.
Jeppesen U, Gram LF, Vistisen K, Loft S, Poulsen HE, Brosen K
Department of Clinical Pharmacology, Odense University, Denmark.
OBJECTIVE: The purpose of this pharmacokinetic study was to investigate the
dose-dependent inhibition of model substrates for CYP2D6, CYP2C19 and CYP1A2 by
four marketed selective serotonin reuptake inhibitors (SSRIs): citalopram,
fluoxetine, fluvoxamine and paroxetine. METHODS: The study was carried out as
an in vivo single-dose study including 24 young, healthy men. All volunteers
had been identified as sparteine- and mephenytoin-extensive metabolizers. The
volunteers received in randomized order, at weekly intervals, increasing single
oral doses of one of the four SSRIs, followed 3 h later by sparteine (CYP2D6),
mephenytoin (CYP2C19) and caffeine (CYP1A2) tests. Fluoxetine was given at
3-week intervals because of the long half-life of fluoxetine and its metabolite
norfluoxetine. Citalopram, fluoxetine and paroxetine were given in doses of 10,
20, 40 and 80 mg and fluvoxamine was given in doses of 25, 50, 100 and 200 mg.
RESULTS: With increasing doses, there was a statistically significant increase
in the sparteine metabolic ratio (MR) (P < 0.01, Page's test for trend) for all
four SSRIs. The increase was modest after intake of citalopram and fluvoxamine,
while the increase was more pronounced after fluoxetine intake, although no
volunteers changed phenotype from extensive metabolizers to poor metabolizers.
Three of the six volunteers changed phenotype from extensive metabolizers to
poor metabolizers after intake of 40 or 80 mg paroxetine. There was a
statistically significant increase in the mephenytoin S/R ratio (P < 0.01,
Page's test for trend) with increasing doses of fluoxetine and fluvoxamine, but
not after citalopram and paroxetine. However, no volunteers changed phenotype
from extensive to poor metabolizers of S-mephenytoin. After intake of
fluvoxamine, the urinary excretion of the metabolites related to N3
demethylation of caffeine were below the limit of quantification, whereas there
were no significant changes in the urinary caffeine metabolic ratios after
intake of the other three SSRIs. CONCLUSION: This investigation confirms that
paroxetine and fluoxetine are potent inhibitors of CYP2D6, that fluvoxamine and
fluoxetine are moderate inhibitors of CYP2C19 and that fluvoxamine is a potent
inhibitor of CYP1A2 in humans in vivo. The clinical prediction of interaction
from single-dose experiments may have to take the degree of accumulation during
steady-state after multiple doses into account.
Pharmacopsychiatry 1996 Jan;29(1):42
A "therapeutic window" with citalopram in a case of depression.
Benazzi F
Pharmacopsychiatry 1996 Jan;29(1):30-32
Citalopram in the treatment of early-onset panic disorder and school phobia.
Lepola U, Leinonen E, Koponen H
Psychiatric Research Clinic of Kuopio, Finland.
Panic Disorder (PD) is a common anxiety disorder, which has its onset
relatively often during adolescence. Twenty-five percent of adult patients with
PD have previously suffered from school phobia. In young patients it often
represents a form of agoraphobia, although it may be present also in other
psychiatric disorders which have their onset in young age. In this report we
describe the results of 8 to 15-month citalopram treatment on three young
patients with school phobia associated with PD. In our patients, low doses with
citalopram were effective as in all patients the severity of school phobia
decreased and the panic attacks disappeared. There were few drug-related
side-effects as only one patient had mild headache at the beginning of the
treatment. Our very preliminary results suggest that citalopram may be
effective in school phobia related to PD. However, controlled studies are
needed to demonstrate the safety, efficacy and appropriate length of citalopram
treatment in childhood PD before it can be widely used in this disorder.
Pharmacopsychiatry 1996 Jan;29(1):27-29
Citalopram in the treatment of alcoholism: a double-blind placebo-controlled
study.
Tiihonen J, Ryynanen OP, Kauhanen J, Hakola HP, Salaspuro M
Department of Forensic Psychiatry, University of Kuopio, Finland.
The effect of citalopram and placebo in the treatment of alcoholism was studied
in a sample of 62 patients with a follow-up period of four months. The results
imply that the new 5-HT re-uptake inhibitor citalopram is significantly more
effective than placebo in the treatment of alcoholism. The present study
indicates that even severe alcoholism may be treated effectively with a
generally available psychopharmacological agent.
Arq Neuropsiquiatr 1995 Dec;53(4):841-848
Citalopram, depression and pseudo dementia: a neuropsychological case study.
Mattos P
Federal University of Rio de Janeiro.
The author presents a case of (depressive) pseudo dementia, commenting on the
clinical and neuropsychological findings before and after the use of
citalopram, a serotoninergic anti depressive drug. The case portrays the
current criticism about the old dichotomy between non-reversible ("functional")
and reversible ("organic") dementia. The 73 year old woman initially diagnosed
as pseudo demented showed some mild cognitive deterioration in
neuropsychological evaluation after the improvement of her depressive symptoms.
Some reasons for the divergent findings on pseudo dementia prognosis in the
literature are proposed.
Can J Psychiatry 1995 Aug;40(6):362
Hair loss associated with fluoxetine but not with citalopram.
Seifritz E, Hatzinger M, Muller MJ, Hemmeter U, Holsboer-Trachsler E
Pain 1995 Jun;61(3):445-449
A randomized controlled trial of citalopram in the treatment of fibromyalgia.
Norregaard J, Volkmann H, Danneskiold-Samsoe B
Department of Rheumatology, Frederiksberg hospital, Copenhagen, Denmark.
Amitriptyline and cyclobenzaprine have shown some efficacy in treatment of the
generalized pain syndrome, fibromyalgia. The aim of this study was to examine
the efficacy of antidepressant dosages of the serotonin re-uptake inhibitor
citalopram in fibromyalgia. In a double-blind, placebo-controlled study 22
patients with fibromyalgia were randomized to treatment with citalopram for 4
weeks at a dosage of 20 mg a day while 21 received placebo. After 4 weeks the
dosage was increased to 40 mg for a further 4 weeks if the subjects did not
report a marked improvement. After the end of treatment (8 weeks) no changes
were observed in self-assessment of symptoms, physician's global assessment,
tender points, Beck depression score or voluntary muscle strength and no
differences were observed between the groups. Citalopram showed no demonstrable
effect on this group of pain patients. The strength of the study was sufficient
to exclude an effect of citalopram of more than 1 steps of 10 on the categoric
scales for pain, fatigue and general condition (95% confidence limit), which
indicates that the sample size was sufficiently large.
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