1: JAMA 2000 Apr 12;283(14):1837-44

Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a
randomized controlled trial.

Brady K, Pearlstein T, Asnis GM, Baker D, Rothbaum B, Sikes CR, Farfel GM

Department of Psychiatry, Medical University of South Carolina, Charleston
29425, USA. brady@musc.edu

CONTEXT: Despite the high prevalence, chronicity, and associated comorbidity of
posttraumatic stress disorder (PTSD) in the community, few placebo-controlled
studies have evaluated the efficacy of pharmacotherapy for this disorder.
OBJECTIVE: To determine if treatment with sertraline hydrochloride effectively
diminishes symptoms of PTSD of moderate to marked severity. DESIGN: Twelve-week,
double-blind, placebo-controlled trial preceded by a 2-week, single-blind
placebo lead-in period, conducted between May 1996 and June 1997. SETTING:
Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical
research centers. PATIENTS: A total of 187 outpatients with a Diagnostic and
Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD
and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity
score of at least 50 at baseline (mean age, 40 years; mean duration of illness,
12 years; 73% were women; and 61.5% experienced physical or sexual assault).
INTERVENTION: Patients were randomized to acute treatment with sertraline
hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at
25 mg/d (n=94); or placebo (n=93). MAIN OUTCOME MEASURES: Baseline-to-end-point
changes in CAPS-2 total severity score, Impact of Event Scale total score (IES),
and Clinical Global Impression-Severity (CGI-S), and CGI-Improvement (CGI-I)
ratings, compared by treatment vs placebo groups. Results Sertraline treatment
yielded significantly greater improvement than placebo on 3 of the 4 primary
outcome measures (mean change from baseline to end point for CAPS-2 total score,
-33.0 vs -23.2 [P =.02], and for CGI-S, -1.2 vs -0.8 [P=.01]; mean CGI-I score
at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score,
showing a trend toward significance (mean change from baseline to end point,
-16.2 vs -12.1; P=.07). Using a conservative last-observation-carried-forward
analysis, treatment with sertraline resulted in a responder rate of 53% at study
end point compared with 32% for placebo (P=.008, with responder defined as >30%
reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1
[very much improved], or 2 [much improved]). Significant (P<.05) efficacy was
evident for sertraline from week 2 on the CAPS-2 total severity score.
Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom
clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on
reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia
the only adverse effect reported significantly more often than placebo (16.0% vs
4.3%; P=.01). CONCLUSIONS: Our data suggest that sertraline is a safe,
well-tolerated, and effective treatment for PTSD.
=========================================================
2: J Clin Psychiatry 2000 Feb;61(2):101-9

Psychosocial functioning in women with premenstrual dysphoric disorder before
and after treatment with sertraline or placebo.

Pearlstein TB, Halbreich U, Batzar ED, Brown CS, Endicott J, Frank E, Freeman
EW, Harrison WM, Haskett RF, Stout AL, Yonkers KA

Butler Hospital and Brown University, Providence, RI 02906, USA.

BACKGROUND: The objective of this study was to evaluate the pretreatment
psychosocial functioning of women with premenstrual dysphoric disorder (PMDD)
and the effect of sertraline treatment on psychosocial functioning in these
patients. METHOD: Two hundred forty-three women recruited from 12
university-affiliated sites and meeting DSM-IV criteria for PMDD completed 1
cycle of single-blind placebo and were randomly assigned to flexible dose
sertraline or placebo for 3 cycles. Psychosocial functioning was assessed by the
Daily Record of Severity of Problems (DRSP), the Social Adjustment Scale (SAS),
and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).
RESULTS: SAS scores during the follicular phase were similar to SAS scores of
community norms, whereas the pretreatment SAS and Q-LES-Q scores during the
luteal phase were similar to scores of women with depressive disorders.
Sertraline was significantly more effective than placebo in improving
psychosocial functioning as measured by the SAS, the Q-LES-Q, and the 3 DRSP
items of impaired productivity, interference with social activities, and
interference with relationships with others. Improvement in psychosocial
functioning assessed by SAS and Q-LES-Q correlated with improvement in
symptomatology assessed by the Clinical Global Impressions-Improvement (CGI-I)
scale and the Hamilton Rating Scale for Depression (HAM-D). Remitters (CGI-I
score of 1) were more likely to function better at baseline and showed larger
improvements in functioning and quality of life with treatment compared with
nonremitters. CONCLUSION: Sertraline was superior to placebo in improving
psychosocial functioning in women with PMDD as reflected by SAS, Q-LES-Q, and
DRSP measures. Functional improvement correlated with improvement in
premenstrual symptomatology and was apparent by the second cycle of treatment.
Comparison of pretreatment SAS scores in women with PMDD with the scores of
other populations of women documents the degree of luteal phase functional
impairment in women with PMDD and a relative absence of follicular phase
impairment.
=========================================================
3: Br J Psychiatry 1999 May;174:444-8

Changes in personality traits during treatment with sertraline or citalopram.

Ekselius L, Von Knorring L

Department of Neuroscience, Psychiatry, University Hospital, Uppsala, Sweden.

BACKGROUND: Recent studies indicate that selective serotonin re-uptake
inhibitors (SSRIs) reduce the symptoms accompanying personality disorders and
modulate a normal personality. AIMS: To examine the effect of two SSRIs,
sertraline and citalopram, on personality traits in major depressed patients.
METHOD: Personality traits were evaluated at baseline and after six months using
the Karolinska Scales of Personality (KSP). RESULTS: After treatment,
significant changes in the direction of normalisation were seen in all scales.
To determine whether the observed changes could be explained by improved
depressive symptoms, multiple stepwise regressions with the separate KSP as
dependent variables were performed. Improvements in depressive symptoms only
accounted for 0-8.4% of the observed variance. CONCLUSIONS: In depressed
patients treated with SSRIs significant effects are seen on personality traits
measured by the KSP.
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4: Int Clin Psychopharmacol 1999 Sep;14(5):259-75

Predictors of an acute antidepressant response to fluoxetine and sertraline.

Flament MF, Lane RM, Zhu R, Ying Z

CNRS UMR 7593, Hopital La Salpetriere, Paris, France. flament@ext.jussieu.fr

Sertraline and fluoxetine have different pharmacologic and pharmacokinetic
profiles which may be of clinical relevance in the determination of response in
different subtypes of depression. A randomized, double-blind, 6-week study
comparing sertraline (50-100 mg/day) with fluoxetine (20-40 mg/day) in 286
outpatients with major depression, who had demonstrated comparable efficacy and
tolerability for the two drugs, was analysed by subgroups of patients at
baseline with melancholia, severe depression, single depressive episode,
multiple depressive episodes, high anxiety, low anxiety, psychomotor retardation
and psychomotor agitation. Multiple logistic regression with regressors
including treatment-by-subgroup variables revealed that, within certain
subgroups, the efficacy might differ substantially from that of the whole
treatment group. However, the only treatment-by-subgroup interaction term that
was significant was anxiety (P < 0.05). There was no evidence of interaction in
single or recurrent episode subgroups, and these were not included in subsequent
analyses. Subsequent two-sample statistical comparison tests of response (i.e.
Hamilton Depression Scale reduction > or = 50%) rates at study endpoint between
treatment groups demonstrated that patients with melancholic depression and
those with symptoms of psychomotor agitation yielded a significantly greater
proportion of responders with sertraline compared to fluoxetine (P < 0.05).
Response rates in sertraline- and fluoxetine-treated patients, respectively,
were: overall study 59%, 51%; melancholia 59%, 44%; severe depression 59%, 41%;
low anxiety 71%, 55%; high anxiety 47%, 48%; psychomotor retardation, 48%, 46%;
and psychomotor agitation 62%, 39%. Multiple logistic regression adjusting for
possible confounding factors, that included a treatment by anxiety interaction
term, also led to similar findings. In particular, the analysis showed that
significant differences existed in favour of sertraline in patients with low
anxiety in the melancholia and severe depression subgroups (P < 0.05),
indicating that these characteristics predicted a superior response to 6 weeks
of treatment with sertraline relative to fluoxetine. Sertraline also
demonstrated advantages over fluoxetine on parameters such as sleep and weight
disturbance in severely depressed patients, and sleep disturbance, weight,
cognitive disturbance and retardation in melancholic patients.
=========================================================
5: Can J Clin Pharmacol 1999 Spring;6(1):12-4

Hypoglycemia associated with high doses of sertraline and sulphonylurea compound
in a noninsulin-dependent diabetes mellitus patient.

Takhar J, Williamson P

London Psychiatric Hospital, Ontario. j.takhar@julian.u.w.o.ca

Unlike other selective serotonin reuptake inhibitors (SSRIs), sertraline has
linear pharmacokinetics so that increases in dose lead to proportional increases
in drug concentration. The half-life of sertraline is about 26 h so that it
reaches a steady state in one week, according to the product monograph.
Hypoglycemia associated with sertraline and coadministration of oral
hypoglycemics belonging to the sulphonylurea derivatives has rarely been
reported. A patient with schizoaffective disorder with non-insulin-dependent
diabetes mellitus (NIDDM) treated with sertraline, risperidone and glyburide who
developed hypoglycemia is presented. The article highlights that inhibition of
P450 enzymes can be affected by several different factors. Interactions are
possible whenever a patient concomitantly receives two drugs that bind to the
same P450 system Greater inhibition was likely induced at doses higher than
those recommended. This process was reversed within 10 days of discontinuing the
sertraline. Good glycemic control followed discontinuation of psychotropic drugs
and the oral hypoglycemic agent. Knowledge of the individual P450 enzymes is
important in the metabolism of individual drugs, together with an understanding
of the patient's drug metabolizing ability. These factors may lead to more
appropriate prescribing and further research into specific P450 enzymes
responsible for metabolism of particular drugs, which remains unclear.
=========================================================
6: J Clin Psychopharmacol 1999 Apr;19(2):172-6

Placebo-controlled, multicenter study of sertraline treatment for
obsessive-compulsive disorder.

Kronig MH, Apter J, Asnis G, Bystritsky A, Curtis G, Ferguson J, Landbloom R,
Munjack D, Riesenberg R, Robinson D, Roy-Byrne P, Phillips K, Du Pont IJ

Department of Psychiatry, Hillside Hospital of LIJMC, Glen Oaks, New York, USA.

The safety and efficacy of sertraline versus placebo were examined in a group of
nondepressed outpatients with obsessive-compulsive disorder (OCD). Patients with
moderate-to-severe OCD were recruited at 10 sites. After a 1-week placebo
lead-in, patients were treated in a double-blind fashion for 12 weeks with
sertraline or placebo. Sertraline was administered at a starting dose of 50
mg/day, with flexible titration up to 200 mg/day. The efficacy measures were the
Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the National Institute of Mental
Health Global Obsessive Compulsive Scale (NIMH), and the Clinical Global
Impression Scale (CGI) Severity of Illness and Improvement subscales. One
hundred sixty-seven patients were randomly assigned and received at least one
dose of double-blind medication: 86 received sertraline and 81 received placebo.
All efficacy measures showed significantly greater improvement in the sertraline
group from the end of week 8 until the end of week 12. Significantly greater
improvement (p < 0.05) in the sertraline group first became apparent by the end
of week 3 on the Y-BOCS and the CGI Improvement scale, and by the end of weeks 6
and 8, respectively, on the NIMH and CGI Severity scale. Sertraline was well
tolerated, without serious adverse effects. In conclusion, sertraline was safe
and effective in the treatment of patients with OCD.
=========================================================
7: J Clin Psychiatry 1998 Dec;59(12):669-75

Predictors of response to acute treatment of chronic and double depression with
sertraline or imipramine.

Hirschfeld RM, Russell JM, Delgado PL, Fawcett J, Friedman RA, Harrison WM,
Koran LM, Miller IW, Thase ME, Howland RH, Connolly MA, Miceli RJ

Department of Psychiatry and Behavioral Sciences, University of Texas Medical
Branch at Galveston 77555-0429, USA.

BACKGROUND: The literature on predictors of response to treatment of nonchronic
major depression has identified shorter duration of illness, acute onset, and
less severity of illness as positive predictors. Unfortunately, there are almost
no data on predictors of response to treatment for chronic depression. This
study examined predictors of response to pharmacotherapy (sertraline or
imipramine) in the treatment of outpatients who had DSM-III-R-defined chronic
major or double depression. METHOD: The acute phase of the Chronic Major
Depression and Double Depression Study is a double-blind, randomized,
parallel-group 12-week comparison of sertraline and imipramine. Analyses are
based on 623 patients who comprised the intent-to-treat sample, of whom 299 were
nonresponders and 324 were responders, defined by a priori criteria as either
remission or satisfactory therapeutic response. A stepwise logistic multiple
regression analysis was performed on candidate clinical, psychosocial, and
demographic variables previously identified as statistically significant in an
attempt to develop a predictive model of positive antidepressant response.
RESULTS: The sociodemographic variables that were predictive of positive
response included living with spouse or partner or being at least a high school
graduate. With regard to symptomatology and clinical history, responders had
significantly lower baseline depression severity scores. In general, comorbid
anxiety, substance abuse, and personality disorders did not influence rates of
response. However, the presence of depressive personality traits was associated
with a higher nonresponse rate. Among psychosocial variables, longer duration of
personal relationships as well as higher baseline quality of life were
associated with positive response. A stepwise logistic multiple regression
identified 5 variables-living with spouse or partner, higher educational level,
passive-aggressive personality, lower introverted-tense personality traits, and
higher quality of life--that significantly and independently contributed to the
predictive model. This model correctly classified 67% of patients. CONCLUSION: A
higher baseline quality of life, living with spouse or partner, and having more
education were the strongest predictors of response to acute pharmacotherapy
among chronically depressed patients. Clinical variables and comorbidity were
not identified as independent predictors, although personality traits did appear
to influence treatment response. Overall, the predictive value of these baseline
measures was modest, and therefore of limited clinical utility.
=========================================================
8: Br J Psychiatry 1998 Jul;173:54-60

Sertraline in the treatment of panic disorder. A multi-site, double-blind,
placebo-controlled, fixed-dose investigation.

Londborg PD, Wolkow R, Smith WT, DuBoff E, England D, Ferguson J, Rosenthal M,
Weise C

Summit Research Network, Seattle, Washington 98104, USA.

BACKGROUND: This study compared the efficacy and safety of sertraline to placebo
in treating panic disorder. METHOD: 178 out-patients with panic disorder who
exhibited at least four panic attacks during the four weeks prior to screening
and three during the two weeks of lead-in were randomly assigned to 12 weeks of
double-blind treatment with sertraline (50, 100 or 200 mg) or placebo. RESULTS:
Sertraline was superior to placebo in reducing the number of panic attacks,
situational attacks, unexpected attacks, limited symptom attacks, and time spent
worrying (all P < 0.01) and the Hamilton Anxiety Scale (P < 0.05), although
Clinical Global Impression (Improvement) did not significantly differentiate
groups at 12 weeks and at end-point. No serious adverse events were associated
with sertraline. No dose relationship was found for adverse events; overall
drop-out rates were not different for sertraline or placebo, although more
sertraline-treated subjects discontinued for adverse events, typically early in
the study. Only dry mouth and ejaculation failure (primarily ejaculation delay)
were associated significantly with sertraline. CONCLUSIONS: Sertraline was
effective and safe in reducing panic attacks. Higher doses were no more
effective than the 50 mg dose.
=========================================================
9: Int Clin Psychopharmacol 1998 Sep;13(5):205-11

Personality disorder comorbidity with major depression and response to treatment
with sertraline or citalopram.

Ekselius L, von Knorring L

Department of Neuroscience, Psychiatry, University Hospital, Uppsala, Sweden.

The purpose of this study was to investigate the frequency of DSM-III-R
personality disorders in depressed patients treated in primary care, and to
examine the effect of sertraline or citalopram on the diagnosis of personality
disorders. A total of 308 patients with a major depressive disorder were
assessed with the Swedish version of the Structured Clinical Interview for
Personality Disorders (SCID) screen questionnaire, before and after 24 weeks
double-blind treatment with sertraline (50-150 mg/day) or citalopram (20-60
mg/day). Following treatment, significant reductions in the frequency of
paranoid, borderline, avoidant and dependent personality disorder diagnoses were
seen in both treatment groups. When the personality disorders were analysed as
continuous, dimensional personality traits significant reductions were seen for
most personality categories. To elucidate if the observed reductions in
personality disorder criteria could be explained by the improvement in
depressive symptomatology, a series of multiple regressions were made. Reduction
of depression scores was of some importance for the changes in most personality
disorders. However, the multiple R never exceeded 0.24 (cluster C). Type of drug
was of importance only as concerns obsessive-compulsive personality disorder.
Overall, the results suggest that sertraline and citalopram may be beneficial in
the treatment of certain personality disorder traits in patients with major
depressive disorders.
=========================================================
10: Am J Psychiatry 1998 Sep;155(9):1189-95

Sertraline in the treatment of panic disorder: a double-blind multicenter trial.

Pohl RB, Wolkow RM, Clary CM

Department of Psychiatry and Behavioral Neurosciences, Wayne State University,
Detroit, USA.

OBJECTIVE: This study determined the efficacy and safety of sertraline in the
treatment of patients with panic disorder. METHOD: The study was a randomized,
double-blind, parallel-group, flexible-dose comparison of sertraline and placebo
in outpatients with a DSM-III-R diagnosis of panic disorder with or without
agoraphobia. After a 2-week single-blind placebo lead-in, 168 patients entered a
10-week double-blind phase in which they were randomly assigned to treatment
with either sertraline or placebo. RESULTS: Sertraline was significantly more
effective than placebo in decreasing the number of full and limited-symptom
panic attacks. Among patients who completed the study, the mean number of panic
attacks per week dropped by 88% in the sertraline-treated patients and 53% in
the placebo-treated patients. Sertraline-treated patients also had significantly
more improvement than placebo-treated patients in scores on the Quality of Life
Enjoyment and Satisfaction Questionnaire, patient global evaluation, and
Clinical Global Impression severity of illness and global improvement scales.
Overall, patients tolerated sertraline well, and only 9% terminated treatment
because of side effects. CONCLUSIONS: Sertraline is an effective and
well-tolerated treatment for patients with panic disorder.
=========================================================
11: J Neural Transm 1998;105(2-3):247-51

Sertraline induced parkinsonism. A case report and an in-vivo study of the
effect of sertraline on dopamine metabolism.

Di Rocco A, Brannan T, Prikhojan A, Yahr MD

The Mount Sinai Medical Center, Department of Neurology, New York, NY, USA.

We report a patient with a parkinsonian syndrome induced by sertraline (Zoloft),
an SSRI antidepressant, whose symptoms resolved after the drug was discontinued.
This case prompted us to investigate the effect of sertraline on dopamine
metabolism in animals. Sertraline (30 mg/kg, i.p.) or placebo (vehicle) was
administered to two groups of six normal, anesthetized rats and using cerebral
microdyalisis extracellular striatal levels of dopamine, the dopamine
metabolites (HVA and DOPAC), as well as the serotonin metabolite 5-HIIA were
monitored. In animals pre-treated with sertraline, DOPAC, HVA, and 5-HIAA levels
were significantly decreased compared to control animals (p < 0.01). These data
indicate that sertraline has an effect on dopamine metabolism, which may alter
function in the striatum and induce a parkinsonian syndrome.
=========================================================
12: Br J Clin Pharmacol 1998 May;45(5):453-7

Distribution and excretion of sertraline and N-desmethylsertraline in human milk.

Kristensen JH, Ilett KF, Dusci LJ, Hackett LP, Yapp P, Wojnar-Horton RE, Roberts
MJ, Paech M

Department of Pharmacy, King Edward Memorial Hospital, Subiaco, Western
Australia.

AIMS: To characterise milk/plasma (M/P) ratio and infant exposure, for
sertraline and N-desmethylsertraline, in breast-feeding women taking sertraline
for the treatment of depression. METHODS: Eight women (mean age 28 years) taking
sertraline (1.05 mg kg(-1) day(-1)) and their infants (mean age 5.7 months) were
studied. Sertraline and N-desmethylsertraline in plasma and milk were measured
by high-performance liquid chromatography over a 24 h dose interval at
steady-state. M/P values were estimated from area under the plasma and milk
concentration-time curves. All milk produced was collected over the dose
interval. Infant exposure was estimated as the product of actual or estimated
milk production, and average drug concentration in milk, normalized to body
weight and expressed as a percentage of the weight-adjusted maternal dose.
RESULTS: Mean milk production was 321 ml day(-1) (range 34-974 ml). Mean M/P
values of 1.93 and 1.64 were calculated for sertraline and N-desmethylsertraline
respectively. Infant exposure estimated from actual milk produced was 0.2% and
0.3% of the weight-adjusted maternal dose for sertraline and
N-desmethylsertraline (as sertraline equivalents) respectively. When calculated
from estimated milk production (0.15 l kg(-1) day(-1)), infant exposure was
significantly greater (P<0.0001) at 0.90% and 1.32% for sertraline and
N-desmethylsertraline respectively. Neither sertraline nor its N-desmethyl
metabolite could be detected in plasma samples from the four infants tested. No
adverse effects were observed in any of the eight infants and all had achieved
normal developmental milestones. CONCLUSIONS: Irrespective of the method of
calculation of infant exposure, the mean total dose of sertraline and its
N-desmethyl metabolite transmitted to infants via breast-feeding is low and
unlikely to cause any significant adverse effects.
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13: Seizure 1998 Apr;7(2):163-5

Lamotrigine toxicity secondary to sertraline.

Kaufman KR, Gerner R

Department of Psychiatry, UMDNJ-RWJMS, New Brunswick, NJ 08901, USA.

Blood level monitoring helps to determine the therapeutic and toxic ranges for
anticonvulsants and antidepressants. We investigated initial drug-drug
interactions between lamotrigine and sertraline. We report on case histories of
two epileptic patients who were initially on lamotrigine and to whom sertraline
was added to control psychiatric features. In case 1, a total daily dose of 25
mg sertraline, with nondetectable sertraline and desmethylsertraline blood
levels, resulted in a doubling of the lamotrigine blood level with symptoms of
toxicity. In case 2, a 25 mg reduction in the total daily dose of sertraline
resulted in halving of the lamotrigine blood level even though the lamotrigine
dosage was increased by 33%. This shows that sertraline has potent interactions
with lamotrigine metabolism. The authors hypothesize that inhibition of
glucuronidation is responsible. Clinicians are advised to observe for symptoms
of toxicity and to do serial blood levels to monitor this interaction.
=========================================================
14: Am J Psychiatry 1998 May;155(5):690-2

Serum sertraline and N-desmethylsertraline levels in breast-feeding mother-infant pairs.

Wisner KL, Perel JM, Blumer J

Division of Pediatric Pharmacology and Critical Care, Case Western Reserve
University, Cleveland, OH 44106, USA. klw6@po.cwru.edu

OBJECTIVE: The authors' goal was to study the serum sertraline levels of
breast-feeding mothers and their infants. METHOD: They obtained serum levels of
sertraline and N-desmethylsertraline in nine mother-infant pairs. RESULTS:
Sertraline levels were very low (less than 2 ng/ml) in seven of the nine infants
and low (3 ng/ml) in one. N-Desmethylsertraline levels were also low (6 ng/ml or
less) in seven of the nine infants. One infant had a high level of
N-desmethylsertraline, and one infant had unusual serum sertraline and
N-desmethylsertraline values (half of its mother's levels). All infants were
thriving. CONCLUSIONS: Most breast-feeding infants whose mothers were taking
sertraline had very low serum levels of both sertraline and
N-desmethylsertraline, consistent with published reports. The authors discuss in
detail the one infant with unusually high levels.
=========================================================
15: J Psychopharmacol (Oxf) 1998;12(1):105-7

Pindolol augmentation of sertraline in resistant depression and its effect on sleep.

Bell C, Wilson S, Nutt DJ

Psychopharmacology Unit, School of Medical Sciences, Bristol, UK.

A case is reported of a 34-year-old lady with a 2-year history of resistant
depression who responded to pindolol augmentation of sertraline. It also
illustrates the use of sleep electroencephalogram measures as a way of assessing
changes in brain 5-hydroxytryptamine function.
=========================================================
16: J Clin Psychiatry 1997 Sep;58(9):399-402

Intermittent luteal phase sertraline treatment of dysphoric premenstrual syndrome.

Halbreich U, Smoller JW

Biobehavioral Program, State University of New York (SUNY) Clinical Center,
Buffalo 14215, USA.

BACKGROUND: Dysphoric premenstrual syndrome (PMS) has been associated with
serotonergic dysregulation, and serotonergic medications have been reported to
alleviate the symptoms of PMS. We investigated the effects of the serotonin
reuptake inhibitor sertraline given during only the luteal phase in women with
dysphoric PMS. METHOD: After baseline ratings were obtained during two menstrual
cycles, 15 women with dysphoric PMS who also met DSM-IV criteria for
premenstrual dysphoric disorder (PMDD) entered single-blind treatment with
sertraline 100 mg/day for one full menstrual cycle. Women who responded to this
treatment were randomly assigned to a four-cycle double-blind placebo-controlled
crossover study in which sertraline 100 mg/day or placebo was each given only
during luteal phases of two consecutive menstrual cycles. RESULTS: Eleven (79%)
of fourteen women responded to single-blind full-cycle treatment with sertraline
and were randomly assigned to the double-blind crossover study. Three patients
dropped out of the study while taking placebo owing to nonresponse. For the
remaining patients, sertraline given during the luteal phase produced
significant improvements in depression, impairment, and global ratings compared
with placebo and was equivalent in efficacy to sertraline given during the
entire menstrual cycle. CONCLUSION: Women with dysphoric PMS who responded to
continuous sertraline treatment responded equally well to sertraline treatment
that was restricted to the luteal phase. Luteal phase treatment may have
advantages in side effect burden and costs. Larger controlled trials are
warranted to confirm this finding.
=========================================================
17: Am J Psychiatry 1997 Sep;154(9):1255-60

Sertraline and desmethylsertraline in human breast milk and nursing infants.

Stowe ZN, Owens MJ, Landry JC, Kilts CD, Ely T, Llewellyn A, Nemeroff CB

Department of Psychiatry and Behavioral Sciences, Emory University School of
Medicine, Atlanta, GA 30322, USA.

OBJECTIVE: The purpose of this study was to determine the concentrations of
sertraline and desmethylsertraline in both human breast milk and infant serum.
METHOD: Breast milk samples from 12 women were collected at specific time
intervals after oral doses of sertraline (25-200 mg once daily). For 11
mother-infant pairs, maternal serum levels 24 hours after a dose and their
infants' serum levels 2-4 hours after nursing were ascertained by
high-performance liquid chromatography. RESULTS: Sertraline and
desmethylsertraline were present in all breast milk samples, with a gradient
from "fore" milk to "hind" milk. The highest concentrations of sertraline were
observed in hind milk 7-10 hours after maternal dose. Increasing the maternal
dose of sertraline resulted in increased breast milk concentrations of both
sertraline and desmethylsertraline. Detectable concentrations of sertraline were
found in three nursing infants and desmethylsertraline in six. No adverse
effects of exposure were observed in any infant. CONCLUSIONS: Sertraline and
desmethylsertraline were present in the breast milk of nursing women treated
with sertraline. Concentrations were affected by aliquot of milk sampled, time
after maternal dose, and maternal daily dose. The infants' serum concentrations
detected were below the detection limit of most commercial laboratories. The
presence of desmethylsertraline in six infants' samples underscores the
importance of metabolite monitoring in determining infant exposure. Estimates of
daily infant exposure can be determined after analysis of sertraline and
desmethylsertraline concentrations from one full breast at maternal serum steady
state. Future studies of breast milk and infant serum samples should address
these issues.
=========================================================
18: Clin Pharmacol Ther 1997 Apr;61(4):476-87

Comparative sexual side effects of bupropion, fluoxetine, paroxetine, and sertraline.

Modell JG, Katholi CR, Modell JD, DePalma RL

Department of Psychiatry, University of Alabama at Birmingham School of Medicine
35294-0018, USA.

OBJECTIVE: To investigate patient reported prosexual side effects of the
aminoketone antidepressant bupropion (INN, amfebutamone) and to compare directly
the sexual side effects of bupropion and the selective serotonin reuptake
inhibitor (SSRI) antidepressants fluoxetine, paroxetine, and sertraline.
METHODS: One hundred seven psychiatric outpatient respondents receiving current
treatment with one of the above antidepressants anonymously completed
questionnaires that allowed reporting of both decreases and increases in sexual
function. The main outcome measures were antidepressant-associated changes in
libido, arousal, duration of time from arousal to orgasm, intensity of orgasm,
and duration of orgasm relative to that experienced before the onset of the
patients' psychiatric illnesses. RESULTS: Bupropion-treated patients reported
significant increases in libido, level of arousal, intensity of orgasm, and
duration of orgasm beyond levels experienced premorbidly. The three SSRIs to an
equal degree significantly decreased libido, arousal, duration of orgasm, and
intensity of orgasm below levels experienced premorbidly. Overall, 27% of the
SSRI-treated patients had no adverse sexual side effects; in contrast, 86% of
patients treated with bupropion had no adverse sexual effects, and 77% of
bupropion-treated patients reported at least one aspect of heightened sexual
functioning. CONCLUSIONS: SSRI-induced adverse sexual effects appear to be the
rule rather than the exception and may be substantially underreported unless
patients are specifically asked about the effects of these medications on
various aspects of sexual function. In contrast, prosexual effects were reported
by the majority of patients treated with bupropion. The findings are reviewed in
light of the neurochemistry of these agents and the sexual response.
=========================================================
19: J Trauma Stress 1996 Oct;9(4):865-71

Sertraline in the treatment of rape victims with posttraumatic stress disorder.

Rothbaum BO, Ninan PT, Thomas L

Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Posttraumatic stress disorder (PTSD) is a significant problem following rape,
yet reports on the efficacy of pharmacological agents in this population are
lacking. The results of an open 12-week clinical trial utilizing sertraline
(mean dose 105 mg) in the treatment of adult female rape victims with chronic
PTSD are presented. The five completers were, on average, 41.6 years old and
15.6 years postassault. Sertraline reduced PTSD and related symptoms in these
rape victims. The mean Clinician Administered PTSD Scale (CAPS) scores decreased
by 53%, with four out of five participants responding positively to treatment.
These preliminary results support the need for systematic assessment of
sertraline in this population.
=========================================================
20: Acta Psychiatr Scand 1996 Sep;94(3):194-7

An open trial of adjunctive sertraline in the treatment of chronic schizophrenia.

Thakore JH, Berti C, Dinan TG

Department of Psychological Medicine, St Bartholomew's Hospital, London, UK.

While the positive symptoms of schizophrenia are amenable to treatment with
standard neuroleptics, negative symptoms are often difficult to treat.
Co-prescribing antidepressants, such as sertraline, for patients on stable
neuroleptic depot preparations is one pharmacological method of overcoming this
problem. A total of 20 patients with chronic schizophrenia were enrolled in an
open trial over a 12-week period during which sertraline was added to their
usual antipsychotic medication. Prior to this, baseline scores for positive and
negative symptoms, and extrapyramidal side-effects, were measured. The addition
of sertraline resulted in global improvement, with a significant reduction in
positive and negative symptom scores and no increase in undesirable neuroleptic
side-effects. Sertraline may act by indirectly reducing dopaminergic activity.
=========================================================
21: Am J Emerg Med 1996 Sep;14(5):456-8

Analysis of sertraline-only overdoses.

Klein-Schwartz W, Anderson B

Maryland Poison Center, Department of Pharmacy Practice and Science, University
of Maryland School of Pharmacy, Baltimore 21201, USA.

Sertraline is an antidepressant for which preliminary data suggest a low
inherent toxicity. Previously reported case series have included coingestants or
had small numbers of patients. This study was undertaken to determine the
toxicity of overdoses of sertraline alone. A 2-year retrospective and 6-month
prospective study was conducted at a regional poison center. There were 52
patients with a mean age of 19.3 +/- 13.8 years and a mean dose of 727 +/- 686
mg. There were no symptoms in 34 cases. Symptomatic patients experienced mild
central nervous system, cardiovascular, and gastrointestinal effects. Two
patients developed bradycardia which resolved without therapy. While all but 3
of 38 adolescents and adults were treated in a health care facility, 10 of 14
children were managed at home. Gastrointestinal decontamination was performed in
37 cases. No other specific therapy was required. Serious toxicity would not be
expected following sertraline-only overdoses.
=========================================================
22: Int Clin Psychopharmacol 1996 Mar;11(1):58-9

Sertraline withdrawal in two brothers: a case report.

Rosenstock HA

Two case histories are reported describing sertraline withdrawal in two
brothers. The case histories document withdrawal symptoms of (1) dysequilibrium
(2) dysesthesias (3) dizziness and (4) a flushing sensation. The literature of
selected serotonin reuptake inhibitors (SSRI) withdrawal is reviewed. Advocated
is the monitoring of patients' withdrawal symptoms from SSRI's even when
prescribed at modest doses.
=========================================================
23: J Clin Psychiatry 1996 Feb;57(2):67-71

Does intolerance or lack of response with fluoxetine predict the same will
happen with sertraline?

Zarate CA, Kando JC, Tohen M, Weiss MK, Cole JO

Pharmaco-Epidemiology Center, McLean Hospital, Belmont, MA, USA.

BACKGROUND: The purpose of this study was to determine whether sertraline would
be well tolerated and effective in patients who had failed fluoxetine therapy or
were unable to tolerate the medication. METHOD: Hospital records were reviewed
for 88 consecutive patients started on sertraline treatment at McLean Hospital
from February 11, 1992 to August 28, 1992. Forty-two patients were identified
who had received sertraline treatment and who had had previous trials of
fluoxetine. Patients were contacted after discharge to determine sertraline
efficacy and side effects. A variety of patient characteristics and outcome
measures were compared. RESULTS: Thirty-nine subjects (93%) were available for
follow-up interviews. The DSM-III-R diagnoses at discharge were as follows:
major depression (N=25), bipolar depression (N=6), schizoaffective disorder
(N=4), and obsessive-compulsive disorder (N=4). The sertraline discontinuation
rate was 64% (25/39) by a mean +/- SD of 2.3 +/- 2.1 months. In patients with
major depression (N=25) and bipolar depression (N=6) discharged on sertraline,
only 13 (42%) were considered responders to sertraline therapy, and at
follow-up, only 8 (26%) of 31 were considered responders to sertraline therapy.
Patients who had previously discontinued fluoxetine because of side effects were
significantly more likely to have side effects during sertraline treatment (p =
.027), and to have discontinued sertraline at follow-up (p = .018). CONCLUSION:
Sertraline was found to be modestly efficacious and associated with numerous
side effects and discontinuation rates in patients who had previously
discontinued fluoxetine.
=========================================================
24: J Clin Psychiatry 1995 Jun;56(6):243-5

Breastfeeding and sertraline: a 24-hour analysis.

Altshuler LL, Burt VK, McMullen M, Hendrick V

UCLA Neuropsychiatric, USA.

BACKGROUND: Few reports exist on the levels of antidepressants in breast milk or
on observed behavioral effects, if any, of neonates who are breast-fed. Thus, a
dilemma exists for women who would like to breast-feed but require psychotropic
medications. METHOD: Analysis of sertraline levels was performed on eight
samples of breast milk obtained over a 24-hour period, after 3 weeks of
breastfeeding, from a lactating patient taking sertraline and nortriptyline.
During this same 24-hour period, two serum samples each were taken from mother
and child for analysis of sertraline and nortriptyline levels. After 7 weeks of
exclusive breastfeeding, an additional serum sample was obtained from mother and
child for analysis of sertraline levels. Drug metabolites were not measured.
RESULTS: Breast milk levels of sertraline were lowest 1 hour before the
ingestion of sertraline and highest 5 to 9 hours after ingestion of the drug.
The infant's serum sertraline and nortriptyline levels were nondetectable.
CONCLUSION: These data indicate that sertraline levels in breast milk vary
substantially over 24 hours and appear to be lowest within the 2 hours before
and 1 hour after ingestion of the medication, with the peak probably occurring
between Hours 1 and 9 postingestion. However, the absence of detectable serum
sertraline and nortriptyline levels in the infant suggests that if either
medication is present in infant serum, its concentration would be extremely low.
No abnormal occurrences have been noted in the development of the infant. It
would be important in future studies to measure metabolites in addition to
medication levels since the former have been associated with untoward events in
an infant.
=========================================================
25: Ann Pharmacother 1994 Jun;28(6):732-5

Sertraline-phenelzine drug interaction: a serotonin syndrome reaction.

Graber MA, Hoehns TB, Perry PJ

Department of Family Practice, College of Medicine, University of Iowa, Iowa
City 52242.

OBJECTIVE: To report a serious drug interaction possibly occurring with the
monoamine oxidase inhibitor phenelzine and the selective serotonin reuptake
inhibitor sertraline. CASE SUMMARY: A 61-year-old woman with
treatment-refractory major depressive disorder was being treated unsuccessfully
with lithium, phenelzine, thioridazine, and doxepin. Sertaline 100 mg/d was
added to the patient's therapy. Within three hours of ingesting the first dose,
the patient experienced a dramatic increase in her temperature, pulse, and
respirations along with labile blood pressure, and symptoms of rigidity,
diaphoresis, shivering, and decreased sensorium. The patient was transported to
the emergency room and treated with diazepam 10 mg iv, followed by midazolam 10
mg iv for control of rigidity. She was also intubated. The patient then
experienced precipitous falls in her blood pressure and respiratory rate. Ice
packs combined with a cooling blanket and dantrolene 80 mg iv were administered
to control fever and rigidity, respectively. She had an initial working
diagnosis of neuroleptic malignant syndrome, which was later changed to
serotonin syndrome. Dantrolene was continued for 72 hours at which time the
patient was extubated and transferred to a psychiatric unit. CONCLUSIONS:
Selective serotonin reuptake inhibitor antidepressants should not be combined
with monoamine oxidase inhibitor antidepressants because of the risk of
serotonin syndrome.

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