Zoloft

University of Pennsylvania School of Medicine.Oct 19, 2006
Zofolt can help to Treat Kids' Compulsive Disorder
Crystal Phend, Reviewed by Zalman S. Agus, MD; Emeritus Professor

Behavioral or cognitive behavioral therapy, with or without medication, is the top choice against obsessive-compulsive disorder in children and adolescents, according to a systematic Cochrane review. While behavioral therapy alone was as good as Zoloft (sertraline), Anafranil (clomipramine) and Luvox (fluvoxamine) at reducing repetitive actions, the combination was significantly more effective than medication alone, said Richard O'Kearney, Ph.D., of the Australian National University here, and colleagues. However, "there is still insufficient evidence to be able to specify the preferred sequence of treatments for pediatric obsessive compulsive disorder," noted the authors in the review published in the Oct. 18 issue of The Cochrane Library. Behavioral therapy involves exposure to the anxiety-producing triggers and then preventing the compulsive behavior. It is recommended as the treatment of choice for pediatric obsessive-compulsive disorder by the American Academy of Child and Adolescent Psychiatry primarily on the basis of conclusions reached in adult studies. Behavioral therapy was effective compared with no treatment. In the four studies reviewed, 37% to 88% fewer children had obsessive-compulsive disorder after treatment. This corresponded to a drop of eight points on the gold standard outcome measure of symptoms for the condition, the Children's Yale-Brown Obsessive Compulsive Scale, CY-BOCS. Outcomes were not significantly different between behavioral therapy and medication (weighted mean difference -3.87, 95% confidence interval -8.15 to 0.41). Compared with medication alone, the combination of behavioral therapy and psychotropic drugs significantly improved compulsive behaviors in children and adolescents (weighted mean difference -4.55, 95% CI -7.40 to -1.70). However, the combination was not superior to behavioral therapy alone (weighted mean difference -2.80, 95% CI -7.55 to 1.95). The four randomized or quasi-randomized clinical trials included in the review involved 222 participants with ages ranging from seven years to 18 years two months. Boys and girls were equally represented in each study. Participants were diagnosed by clinical assessment or standardized diagnostic interview. Behavioral interventions in the studies ranged from 12 to 20 sessions, each for 60 to 90 minutes, for a total of 30 hours, 21 hours, 14 hours, or 12 hours. Three studies used a medication comparison group. One of these used both medication and pill placebo comparison arms. The fourth used individuals on a wait list as controls. Dosing was reported as: • Zoloft at 150 mg daily for the combined group and 200 mg in the medication alone group, • Anafranil at 2.5 mg/kg of body weight with a range of 1.4 mg/kg to 3.3 mg/kg, and • Luvox at least 200 mg per day. The researchers found that the number of participants who continued to have compulsive behaviors (defined as more than 10 points on the Children's Yale-Brown Obsessive Compulsive Scale) after behavioral treatment was: • Significantly less than those receiving placebo in the least biased study (relative risk 0.63, 95% CI 0.46 to 0.86), • Significantly reduced compared to children and adolescents on a wait list (RR 0.13, 95% CI 0.04 to 0.36) in one study, and • Similarly fewer in another study compared to participants on a wait list (RR 0.24, 95% CI 0.13 to 0.46). Compared with medication alone, Dr. O'Kearney and colleagues found that the efficacy of behavioral therapy was: • Equivalent to that of Anafranil (weighted mean difference -8.50, 95% CI -17.44 to 0.44), and • Not significantly different from Zoloft (weighted mean difference -2.50, 95% CI -7.37 to 2.37). The studies also consistently found no difference in the number of participants who remained disordered after treatment between behavioral therapy and medication alone. The findings were: • Behavioral therapy alone and medication alone had equivalent proportions continuing to have symptoms after treatment in the pooled analysis (RR 0.75, 95% CI 0.54 to 1.05), • There was no difference between Anafranil and behavioral therapy (RR 0.69; 95% CI 0.30 to 1.61), and • There was no difference between Zoloft and behavioral therapy (RR 0.77, 95% CI 0.54 to 1.10). The combination of behavioral therapy and medication was superior to Luvox alone in symptom improvement (weighted mean difference -4.55, 95% CI -7.40 to -1.70). The combination with Zoloft was: • Not significantly different compared with behavioral therapy alone for symptom improvement (weighted mean difference -2.80, 95% CI -7.55 to 1.95), • Not significantly different compared with behavioral therapy alone for the number who continued to have the disorder after treatment (RR 0.76, 95% CI 0.47 to 1.26), and • Significantly better compared with Zoloft alone for the number who still had the disorder after treatment (RR 0.59, 95% CI 0.38 to 0.92). The investigators noted that they did not find a high rate of treatment refusal or drop-out (8.1% to 14.8% and 8.3% to 10.7%, respectively) with behavioral therapy, which has been one of its suggested disadvantages. Health professionals need to consider this therapy, Dr. O'Kearney said, particularly in view of the controversy about prescribing psychotropic medications to children and adolescents. However, the decision to try behavioral therapy may be influenced by other factors, such as patient preference, the availability of skilled practitioners, cost, and the patient's treatment history, he added. The prevalence of obsessive-compulsive disorder in childhood is estimated as 0.5% to 4%. The review was supported by the Australian National University.

Acta Psychiatr Scand. 2005 Jun;111(6):429-35.
Sertraline in generalized anxiety disorder: efficacy in treating the psychic and somatic anxiety factors.
Dahl AA, Ravindran A, Allgulander C, Kutcher SP, Austin C, Burt T.
Department of Clinical Cancer Research, Rikshospitalet-Radiumhospitalet Trust, University of Oslo, Oslo, Norway.

Dahl AA, Ravindran A, Allgulander C, Kutcher SP, Austin C, Burt T. Sertraline in generalized anxiety disorder: efficacy in treating the psychic and somatic anxiety factors. Acta Psychiatr Scand 2005: 111: 429-435. (c) Blackwell Munksgaard 2005.Objective: The objective was to study the efficacy of sertraline on symptoms of psychic and somatic anxiety in patients suffering from moderate-to-severe generalized anxiety disorder (GAD). Method: Out-patients with DSM-IV GAD were randomized to 12 weeks of double-blind treatment with placebo. The psychic and somatic anxiety factors of the Hamilton Anxiety Rating Scale (HAM-A) and the Quality of Life, Enjoyment, and Satisfaction Questionnaire were analyzed. Results: Treatment with sertraline resulted in significantly greater last observation carried forward (LOCF)-endpoint improvement than placebo on both the HAM-A psychic and somatic anxiety factors. At LOCF-endpoint, all items on the HAM-A psychic factor were more improved on sertraline than placebo, as were three of seven items on the somatic factor. Reduction of secondary depressive symptoms was more correlated with endpoint improvement in quality of life than either psychic- or somatic anxiety. Conclusion: Sertraline treatment demonstrated efficacy for both the psychic and somatic anxiety symptoms of GAD.

Depress Anxiety. 2005 May 9;21(2):78-89
Effects of sertraline on depressive symptoms and attentional and executive functions in major depression.
Constant EL, Adam S, Gillain B, Seron X, Bruyer R, Seghers A.
Department of Psychiatry, Universite Catholique de Louvain, Louvain, Belgium.

Reports on the severity and reversibility of cognitive disturbances in major depression in the literature diverge due to methodological biases. The present study, using a precise methodology, examined attention and executive functions in 20 relatively young, depressed patients presenting a first or second episode of unipolar major depression without psychotic or melancholic characteristics and all being treated with the same psychopharmacological treatment (sertraline) to investigate the changes in potential attentional and executive loss during a subacute period of treatment of 7 weeks. We compared their performance with a group of 26 control subjects who were administered the same cognitive tests. This study confirmed psychomotor slowing associated with attentional and executive disturbance in adults with major depression. Conscious attentional interference for words with a negative emotional valence also was shown. After the first weeks of treatment, the effect of the antidepressant treatment with sertraline was accompanied by a beneficial effect on psychomotor slowing on attentional and executive functions. Depression and Anxiety 21:78-89, 2005. (c) 2005 Wiley-Liss, Inc.

Drug Saf. 2005;28(2):137-52.
The safety of newer antidepressants in pregnancy and breastfeeding.
Gentile S.
Department of Mental Health ASL Salerno 1, District n. 4, Cava de' Tirreni (Salerno), Italy.

The pregnancy and postpartum periods are considered to be relatively high risk times for depressive episodes in women, particularly for those with pre-existing psychiatric illnesses. Therefore, it may be necessary to start or continue the pharmacological treatment of depression during these two timeframes. Hence, the aim of this review is to examine the effects on the fetus and infant of exposure, through the placenta and maternal milk, to the following drugs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram, mirtazapine, venlafaxine, reboxetine and bupropion.The teratogenic risks, perinatal toxicity and effects on the neurobehavioural development of newborns associated with exposure through the placenta or maternal milk to these medications need to be carefully assessed before starting psychopharmacological treatment in pregnant or lactating women. In spite of the limitations of some of the studies reviewed, the older selective serotonin-reuptake inhibitors (SSRIs) [as we await further data regarding escitalopram] and venlafaxine seem to be devoid of teratogenic risks. By contrast, the data concerning possible consequences related to exposure to SSRIs via the placenta and breastmilk on neonatal adaptation and long-term neurocognitive infant's development are still controversial. Nevertheless, a number of reports have shown that an association between placental exposure to SSRIs and adverse but self-limiting effects on neonatal adaptation may exist. In addition, the information on both teratogenic and functional teratogenic risks associated with exposure to bupropion, mirtazapine and reboxetine is incomplete or absent; at present, these compounds should not be used as first-line agents in the pharmacological treatment of depression in pregnancy and breastfeeding.Untreated depression is not without its own risks since mothers affected by depression have a negative impact on the emotional development of their children and major depression, especially when complicated by a delusional component, may lead to the mother attempting suicide and infanticide. Consequently, clinicians need to help mothers weigh the risks of prenatal exposure to drugs for their babies against the potential risks of untreated depression and abrupt discontinuation of pharmacological treatment. Given these situations, we suggest that choosing to administer psychopharmacological treatment in pregnant or breastfeeding women with depression will result primarily from a careful evaluation of their psychopathological condition; currently, the degree of severity of maternal disease appears to represent the most relevant parameter to take this clinical decision.

J Clin Psychiatry. 2005 Jan;66(1):28-33. Related Articles, Links
Sertraline treatment of pathological gambling: a pilot study.
Saiz-Ruiz J, Blanco C, Ibanez A, Masramon X, Gomez MM, Madrigal M, Diez T.
Department of Psychiatry, Hospital Ramon y Cajal, Universidad de Alcala, Madrid, Spain.

OBJECTIVE: Several open-label and double-blind studies have suggested that selective serotonin reuptake inhibitors may be useful in the treatment of pathological gambling. The purpose of this study was to evaluate the efficacy of sertraline in the treatment of pathological gambling. METHOD: Sixty patients meeting the DSM-IV criteria for pathological gambling were treated for 6 months in a double-blind, flexible-dose, placebo-controlled study of sertraline 50 to 150 mg/day. Data were collected from November 1998 to January 2001. The primary outcome measure assessing change in clinical status was the responder rate with respect to the Criteria for Control of Pathological Gambling Questionnaire (CCPGQ). Secondary measures included the Clinical Global Impressions scale (CGI) (Severity of Illness and Improvement subscales), and Visual Analogue Scales assessing gambling frequency, severity, amount, and improvement. Concomitant medication and psychotherapy were not allowed during the study. RESULTS: At the end of the study, 23 sertraline-treated subjects (74%) and 21 placebo-treated subjects (72%) were considered as responders on the CCPGQ (p = .9). Similar results were obtained when the CGI-Improvement scale limited to symptoms of pathological gambling was used as an outcome measure. Sertraline was well tolerated throughout the study. CONCLUSION: Sertraline was not statistically significantly superior to placebo in the overall sample. The power of the study was limited by the high placebo-response rate and the small sample size.

Hum Psychopharmacol. 2005 Mar;20(2):97-104.
Comparing effects of methylphenidate, sertraline and placebo on neuropsychiatric sequelae in patients with traumatic brain injury.
Lee H, Kim SW, Kim JM, Shin IS, Yang SJ, Yoon JS.
Department of Psychiatry and Research Institute of Medical Science, Chonnam National University Medical School, Kwangju, Republic of Korea.

BACKGROUND: This study aimed to investigate the effects of methylphenidate and sertraline compared with placebo on various neuropsychiatric sequelae associated with traumatic brain injury (TBI). METHODS: This was a 4 week, double-blind, parallel-group trial. Thirty patients with mild to moderate degrees of TBI were randomly allocated to one of three treatment groups (n = 10 in each group) with matching age, gender and education, i.e. methylphenidate (starting at 5 mg/day and increasing to 20 mg/day in a week), sertraline (starting at 25 mg/day and increasing to 100 mg/day in a week) or placebo. At the baseline and at the 4 week endpoint, the following assessments were administered: subjective (Beck Depression Inventory) and objective (Hamilton Depression Rating Scale) measures of depression; Rivermead Postconcussion Symptoms Questionnaire for postconcussional symptoms; SmithKline Beecham Quality of Life Scale for quality of life; seven performance tests (Critical Flicker Fusion, Choice Reaction Time, Continuous Tracking, Mental Arithmetic, Short-Term memory, Digit Symbol Substitution and Mini-Mental State Examination); subjective measures of sleep (Leeds Sleep Evaluation Questionnaire) and daytime sleepiness (Epworth Sleepiness Scale). All adverse events during the study period were recorded and their relationships to the drugs were assessed. RESULTS: Neuropsychiatric sequelae seemed to take a natural recovery course in patients with traumatic brain injury. Methylphenidate had significant effects on depressive symptoms compared with the placebo, without hindering the natural recovery process of cognitive function. Although sertraline also had significant effects on depressive symptoms compared with the placebo, it did not improve many tests on cognitive performances. Daytime sleepiness was reduced by methylphenidate, while it was not by sertraline. CONCLUSIONS: Methylphenidate and sertraline had similar effects on depressive symptoms. However, methylphenidate seemed to be more beneficial in improving cognitive function and maintaining daytime alertness. Methylphenidate also offered a better tolerability than sertraline. Copyright (c) 2005 John Wiley & Sons, Ltd.

Adv Ther. 2004 Jul-Aug;21(4):232-7.
Treatment of bulimia nervosa with sertraline: a randomized controlled trial
Milano W, Petrella C, Sabatino C, Capasso A.
Mental Health Operations Unit, District 44 ASLNAI Naples, Italy.

Bulimia nervosa (BN) is one of the most frequently encountered eating disorders in industrialized societies. It has been suggested that reduced serotonin activity may trigger some of the cognitive and mood disturbances associated with BN. Thus, pharmacologic treatment of BN is mainly based on the use of selective serotonin reuptake inhibitors, which have proved effective. At present, the biological basis of this disorder is not completely clear. The aim of this randomized, controlled trial was to verify the efficacy of sertraline, a selective serotonin reuptake inhibitor, in a group of patients with a diagnosis of BN. Twenty female outpatients, with an age range of 24 to 36 years and a diagnosis of purging type BN as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV), were assigned randomly to two treatment groups. The first group received sertraline 100 mg/day for 12 weeks; the second group received placebo. The study was conducted for 12 weeks, with weekly clinical assessments. At the end of the observation period, the group treated with sertraline had a statistically significant reduction in the number of binge eating crises and purging compared with the group who received placebo. In no case was treatment interrupted because of side effects. This study confirms that sertraline is well tolerated and effective in reducing binge-eating crises and purging in patients with BN.

Consum Rep. 2004 Oct;69(10):22-9.
Drugs vs. talk therapy: 3,079 readers rate their care for depression and anxiety.
With or without drugs, most people who sought care for depression or anxiety gained relief. A survey of thousands of CR subscribers who recently received treatment for those conditions found that: (1) a combination of talk therapy and drugs often worked best. But "mostly talk" therapy was almost as effective if it lasted for 13 or more visits. (2) "Mostly drug" therapy was also effective for many people. Drugs had a quicker impact on symptoms than talk therapy, but it often took trial and error to find a drug that worked without unacceptable side effects. (3) Forty percent of people who took antidepressants complained of adverse sexual side effects. (4) Care from primary-care doctors was effective for people with mild problems, but less so for people with severe ones.

Am J Psychiatry. 2004 Sep;161(9):1642-9.
Efficacy of sertraline in a 12-week trial for generalized anxiety disorder.
Allgulander C, Dahl AA, Austin C, Morris PL, Sogaard JA, Fayyad R, Kutcher SP, Clary CM.
Karolinska Institutet, Neurotec Department, Section of Psychiatry at Huddinge, University Hospital, 141 86 Huddinge, Sweden. Christer.Allgulander@neurotec.ki.se
OBJECTIVE: Sertraline's efficacy and tolerability in treating generalized anxiety disorder were evaluated. METHOD: Adult outpatients with DSM-IV generalized anxiety disorder and a total score of 18 or higher on the Hamilton Anxiety Rating Scale were eligible. After a 1-week single-blind placebo lead-in, patients were randomly assigned to 12 weeks of double-blind treatment with placebo (N=188, mean baseline anxiety score=25) or flexible doses (50-150 mg/day) of sertraline (N=182, mean anxiety score=25). The primary outcome measure was baseline-to-endpoint change in the Hamilton anxiety scale total score. A secondary efficacy measure was the Clinical Global Impression (CGI) improvement score; response was defined as a score of 2 or less. RESULTS: Sertraline patients had significantly greater improvement than placebo patients on all efficacy measures at week 4. Analysis of covariance of the intent-to-treat group at endpoint (with the last observation carried forward) showed a significant difference in the decrease from baseline of the least-square mean total score on the Hamilton anxiety scale between sertraline (mean=11.7) and placebo (mean=8.0). Significantly greater endpoint improvement with sertraline than placebo was obtained for mean scores on the Hamilton anxiety scale psychic factor (6.7 versus 4.1) and somatic factor (5.0 versus 3.9). The rate of responders, based on CGI improvement and last observation carried forward, was significantly higher for sertraline (63%) than placebo (37%). Sertraline was well tolerated; 8% of patients versus 10% for placebo dropped out because of adverse events. CONCLUSIONS: Sertraline appears to be efficacious and well tolerated in the treatment of generalized anxiety disorder.

Biochem Pharmacol. 2004 Sep 1;68(5):833-42.
Blockade of calcium entry in smooth muscle cells by the antidepressant imipramine.
Becker B, Morel N, Vanbellinghen AM, Lebrun P.
Laboratory of Pharmacology and Experimental Hormonology, Faculty of Medicine (CP 617), Universite Libre de Bruxelles, Route de Lennik 808, B-1070 Brussels, Belgium.
The present study was designed to evaluate the effects of antidepressants on smooth muscle contractile activity. In rat aortic rings, the antidepressants imipramine, mianserin and sertraline provoked concentration-dependent inhibitions of the mechanical responses evoked by K+ (30 mM) depolarization. These myorelaxant effects were not modified by the presence of glibenclamide or 80 mM K+ in the bathing medium. Moreover, the vasodilator properties of imipramine were not affected by atropine, phentolamine and pyrilamine. Radioisotopic experiments indicated that imipramine failed to enhance 86Rb outflow from prelabelled and perifused aortic rings whilst counteracting the increase in 45Ca outflow provoked by a rise in the extracellular K+ concentration. Simultaneous measurements of contractile activity and fura-2 fluorescence revealed that, in aortic rings, imipramine reduced the mechanical and fluorimetric response to K+ challenge. In A7r5 smooth muscle cells, whole cell recordings further demonstrated that imipramine inhibited the inward Ca2+ current. Under different experimental conditions, the ionic and relaxation responses to the antidepressants were reminiscent of those mediated by the Ca2+ entry blocker verapamil. Lastly, it should be pointed out that imipramine exhibited a myorelaxant effect of similar amplitude on rat aorta and on rat distal colon. All together, these findings suggest that the myorelaxant properties of imipramine, and probably also setraline and mianserin, could result from their capacity to inhibit the voltage-sensitive Ca2+ channels.

Environ Toxicol Chem. 2004 Sep;23(9):2229-33.
Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubia.
Henry TB, Kwon JW, Armbrust KL, Black MC.
Department of Environmental Health Science, University of Georgia, Athens, Georgia 30602, USA. thenry@uga.edu
Contamination of surface waters by pharmaceutical chemicals has raised concern among environmental scientists because of the potential for negative effects on aquatic organisms. Of particular importance are pharmaceutical compounds that affect the nervous or endocrine systems because effects on aquatic organisms are possible at low environmental concentrations. Selective serotonin reuptake inhibitors (SSRIs) are drugs used to treat clinical depression in humans, and have been detected in low concentrations in surface waters. In this investigation, the acute and chronic toxicity of five SSRIs (fluoxetine, Prozac; fluvoxamine, Luvox; paroxetine, Paxil; citalopram, Celexa; and sertraline, Zoloft) were evaluated in the daphnid Ceriodaphnia dubia. For each SSRI, the 48-h median lethal concentration (LC50) was determined in three static tests with neonate C. dubia, and chronic (8-d) tests were conducted to determine no-observable-effect concentrations (NOEC) and lowest-observable-effect concentrations (LOEC) for reproduction endpoints. The 48-h LC50 for the SSRIs ranged from 0.12 to 3.90 mg/L and the order of toxicity of the compounds was (lowest to highest): Citalopram, fluvoxamine, paroxetine, fluoxetine, sertraline. Mortality data for the 8-d chronic tests were similar to the 48-h acute data. The SSRIs negatively affected C. dubia reproduction by reducing the number of neonates per female, and for some SSRIs, by reducing the number of broods per female. For sertraline, the most toxic SSRI, the LOEC for the number of neonates per female was 0.045 mg/L and the NOEC was 0.009 mg/L. Results indicate that SSRIs can impact survival and reproduction of C. dubia; however, only at concentrations that are considerably higher than those expected in the environment.

Biol Psychiatry. 2004 Jul 15;56(2):121-8.
Neuroimmune and cortisol changes in selective serotonin reuptake inhibitor and placebo treatment of chronic posttraumatic stress disorder.
Tucker P, Ruwe WD, Masters B, Parker DE, Hossain A, Trautman RP, Wyatt DB.
Department of Psychiatry, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA.
BACKGROUND: To explore relations between neuroimmune and neuroendocrine systems relative to posttraumatic stress disorder (PTSD) treatment, cortisol and cytokine changes in response to selective serotonin reuptake inhibitor (SSRI) and placebo treatment of chronic PTSD were assessed prospectively. METHODS: Baseline measures of PTSD, depression, salivary 8 am and 4 pm cortisol, and serum interleukin-1beta (IL-1beta; pro-inflammatory) and soluble interleukin-2 receptors (IL-2R; cell-mediated immunity) were obtained for 58 PTSD and 21 control subjects. The PTSD subjects participated in a 10-week, double-blind treatment with citalopram (n = 19), sertraline (n = 18), or placebo (n = 7). RESULTS: At baseline, PTSD subjects had significantly greater PTSD, depression, and IL-1beta and lower IL-2R levels than control subjects, with no group differences found for am or pm cortisol levels. Both SSRI groups' IL-1beta correlated negatively with IL-2R; neither cytokine correlated with cortisol levels. Treatment significantly lowered PTSD, depression, and IL-1beta levels and increased IL-2R for all groups to control subject levels. After treatment, both SSRI groups' IL-1beta correlated with an end cortisol measure (one negatively, one positively). CONCLUSIONS: Our results support a complex relationship between neuroimmune and neuroendocrine systems with PTSD treatment. Implications of normalization of cytokine levels with effective SSRI treatment and placebo are discussed.

Am J Psychiatry. 2004 Jul;161(7):1290-2.
Prevention of postpartum depression: a pilot randomized clinical trial.
Wisner KL, Perel JM, Peindl KS, Hanusa BH, Piontek CM, Findling RL.
Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA. WisnerKL@upmc.edu
OBJECTIVE: The authors attempted to reduce the rate of postpartum depression in high-risk women and to increase the time to recurrence. METHOD: Nondepressed pregnant women with at least one past episode of postpartum major depression were recruited into a randomized clinical trial. Mothers were assigned randomly to a 17-week trial of sertraline or placebo immediately after birth and assessed for 20 sequential weeks with the Hamilton Rating Scale for Depression. RESULTS: Of 14 subjects who took sertraline, one (7%) suffered a recurrence. Of eight subjects who were assigned to placebo, four (50%) suffered recurrences. This difference was significant. The time to recurrence was significantly longer in the sertraline-treated women than in the placebo-treated women. CONCLUSIONS: Sertraline conferred preventive efficacy for postpartum-onset major depression beyond that of placebo.

Int J Eat Disord. 2004 Jul;36(1):48-54
Efficacy of sertraline for bulimia nervosa.
Sloan DM, Mizes JS, Helbok C, Muck R.
Department of Psychology, Temple University, Philadelphia, Pennsylvania 19122, USA. dsloan@temple.edu
OBJECTIVE: The current study examined the efficacy of sertraline in the treatment of individuals diagnosed with bulimia nervosa. METHOD: Eighteen women enrolled in an 8-week open trial of sertraline. Eating disorder psychopathology and depressive symptoms were assessed at baseline and at the end of the trial using both semistructured interviews and self-report questionnaires. RESULTS: Findings indicated significant reductions in eating disorder psychopathology, including the number of binges and purges per week, as well as significant reductions in depressive symptoms. In addition, participants did not experience significant weight gain or any other sertraline side effect assessed at the end of the trial compared with baseline. DISCUSSION: Findings from the current study indicate that sertraline is efficacious in the treatment of bulimia nervosa. A double-blind controlled trial of sertraline is recommended for future research. Copyright 2004 by Wiley Periodicals, Inc.

J Perinatol. 2004 Jun;24(6):392-4.
Transient neonatal jitteriness due to maternal use of sertraline (Zoloft).
Santos RP, Pergolizzi JJ.
Department of Pediatrics, State University of New York, Upstate Medical University, 750 East Adam Street, Syracuse, NY 13210, USA.
We describe the occurrence of marked jitteriness and an enhanced startle response in a term infant after being exposed to sertraline in utero. An umbilical cord blood sample taken at the time of birth showed a sertraline concentration (<10 ng/mL) below the reference range. On the third day during the peak of the symptoms, sertraline plasma concentration was <10 ng/mL, while his serotonin level (6 ng/mL) was below the reference range. The neurologic symptoms resolved by the fifth day. To date, there are no reports of transient neonatal jitteriness with maternal use of sertraline documented with low cord and neonatal plasma samples consistent with withdrawal syndrome.

Prescrire Int. 2004 Jun;13(71):103-4.
Neonatal complications after intrauterine exposure to SSRI antidepressants.
(1) Newborns exposed to selective serotonin reuptake inhibitor (SSRI) antidepressants towards the end of pregnancy sometimes show signs of agitation, altered muscle tone, and breathing and suction problems. Similar symptoms can occur after exposure to tricyclic antidepressants. (2) These neonatal symptoms have been noted with all five SSRI antidepressants available in France, namely citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. (3) An estimated 20% to 30% of newborns exposed to an SSRI towards the end of pregnancy are affected. (4) The symptoms are variously attributed to withdrawal or to the drug itself. (5) In practice, doctors should be aware of this risk when considering antidepressant treatment for women in the third trimester of pregnancy. There is no consensus on the treatment of affected newborns, but close monitoring is mandatory.

Proc Natl Acad Sci U S A. 2004 May 25;101(21):8186-91. Epub 2004 May 17.
Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.
Cryan JF, O'Leary OF, Jin SH, Friedland JC, Ouyang M, Hirsch BR, Page ME, Dalvi A, Thomas SA, Lucki I.
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mice unable to synthesize norepinephrine (NE) and epinephrine due to targeted disruption of the dopamine beta-hydroxylase gene, Dbh, were used to critically test roles for NE in mediating acute behavioral changes elicited by different classes of antidepressants. To this end, we used the tail suspension test, one of the most widely used paradigms for assessing antidepressant activity and depression-related behaviors in normal and genetically modified mice. Dbh(-/-) mice failed to respond to the behavioral effects of various antidepressants, including the NE reuptake inhibitors desipramine and reboxetine, the monoamine oxidase inhibitor pargyline, and the atypical antidepressant bupropion, even though they did not differ in baseline immobility from Dbh(+/-) mice, which have normal levels of NE. Surprisingly, the effects of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine were also absent or severely attenuated in the Dbh(-/-) mice. In contrast, citalopram (the most selective SSRI) was equally effective at reducing immobility in mice with and without NE. Restoration of NE by using L-threo-3,4-dihydroxyphenylserine reinstated the behavioral effects of both desipramine and paroxetine in Dbh(-/-) mice, thus demonstrating that the reduced sensitivity to antidepressants is related to NE function, as opposed to developmental abnormalities resulting from chronic NE deficiency. Microdialysis studies demonstrated that the ability of fluoxetine to increase hippocampal serotonin was blocked in Dbh(-/-) mice, whereas citalopram's effect was only partially attenuated. These data show that NE plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including most SSRIs.

J Clin Psychopharmacol. 2004 Feb;24(1):42-8.
Predictors of response in generalized social phobia: effect of age of onset.
Van Ameringen M, Oakman J, Mancini C, Pipe B, Chung H.
Anxiety Disorders Clinic, McMaster University Medical Centre, McMaster University, Hamilton, Ontario, Canada; dagger Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
SUMMARY: Selective serotonin reuptake inhibitors (SSRIs) are the gold standard for the pharmacological treatment of generalized social phobia (GSP). However, little is known about the predictors of response to treatment. Two hundred and four outpatients with GSP were randomized to sertraline (Zoloft) or placebo, for a 20-week double-blind study, with a flexible dose range of sertraline 50 to 200 mg/d. Response was defined as the percentage of patients with a Clinical Global Impression-Improvement scale (CGI-I) of 1 (very much improved) or 2 (much improved). Outcome analyses were conducted using regression models including treatment group as a categorical predictor and study visit as a repeated measure. Dependent measures included Marks Fear Questionnaire (MFQ), Brief Social Phobia Scale (BSPS), CGI-I, and Sheehan Disability Scale (SDS). We investigated several possible predictors of response to treatment including DSM-IV comorbidity, age, sex, age of onset of GSP, and duration of illness. Patients with later-onset (especially adult-onset) GSP tend to have a better response to treatment than those with earlier-onset GSP. This result generally appears in our analyses as a 2-way interaction, where the association with response is greatest for patients with adult-onset GSP (in contrast to those with child or adolescent onset). This finding is most robust for symptom measures, but is still apparent for the Sheehan measure of disability at work. This advantage for later-onset GSP can be accounted for neither by severity of illness nor by duration of illness. Superior treatment outcome for later-onset GSP may be mediated by the degree of social and family disability.

Expert Opin Pharmacother. 2003 Nov;4(11):2065-78
Treatment of premenstrual dysphoric disorder with luteal phase dosing of sertraline.
Halbreich U, Kahn LS.
Biobehavioural Program, School of Medicine & Biomedical Sciences, Hayes C, Suite 1, 3435 Main St, Building 5, Buffalo, NY 14214-3016, USA.
Sertraline (Zoloft( trade mark ), Pfizer Inc.) is a selective serotonin re-uptake inhibitor (SSRI) which has been approved by the US FDA for the treatment of premenstrual dysphoric disorder (PMDD). PMDD is a severe form of premenstrual syndrome (PMS) which affects at least 5 - 8% of women of reproductive age. It is characterised by cyclic appearance at the late luteal phase of the menstrual cycle, and disappearance following the beginning of menses, with no symptoms during at least 1 week of the cycle - usually during the mid-follicular phase. Due to the cyclic luteal occurrence of PMDD, luteal phase dosing of SSRIs has been suggested and proven effective for sertraline as well as several other SSRIs. The clinical response of sertraline is reported to be within several days following initiation of treatment. Despite repeated cyclic discontinuation, no significant discontinuation adverse effects have been reported. In addition to its proven clinical efficacy, luteal-phase dosing may offer the advantages of minimising adverse effects of SSRIs while reducing the personal and economic burden of taking a prescription medication continuously for long periods and thus increasing compliance.

JAMA. 2003 Aug 27;290(8):1033-41.
Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials.
Wagner KD, Ambrosini P, Rynn M, Wohlberg C, Yang R, Greenbaum MS, Childress A, Donnelly C, Deas D; Sertraline Pediatric Depression Study Group.
University of Texas Medical Branch, Department of Psychiatry and Behavioral Sciences, Galveston 77555-0188, USA.
CONTEXT: The efficacy, safety, and tolerability of selective serotonin reuptake inhibitors (SSRIs) in the treatment of adults with major depressive disorder (MDD) are well established. Comparatively few data are available on the effects of SSRIs in depressed children and adolescents. OBJECTIVE: To evaluate the efficacy and safety of sertraline compared with placebo in treatment of pediatric patients with MDD. DESIGN AND SETTING: Two multicenter randomized, double-blind, placebo-controlled trials were conducted at 53 hospital, general practice, and academic centers in the United States, India, Canada, Costa Rica, and Mexico between December 1999 and May 2001 and were pooled a priori. PARTICIPANTS: Three hundred seventy-six children and adolescents aged 6 to 17 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined MDD of at least moderate severity. INTERVENTION: Patients were randomly assigned to receive a flexible dosage (50-200 mg/d) of sertraline (n = 189) zoloft or matching placebo tablets (n = 187) for 10 weeks. MAIN OUTCOME MEASURES: Change from baseline in the Children's Depression Rating Scale-Revised (CDRS-R) Best Description of Child total score and reported adverse events. RESULTS: Sertraline-treated patients experienced statistically significantly greater improvement than placebo patients on the CDRS-R total score (mean change at week 10, -30.24 vs -25.83, respectively; P =.001; overall mean change, -22.84 vs -20.19, respectively; P =.007). Based on a 40% decrease in the adjusted CDRS-R total score at study end point, 69% of sertraline-treated patients compared with 59% of placebo patients were considered responders (P =.05). Sertraline treatment was generally well tolerated. Seventeen sertraline-treated patients (9%) and 5 placebo patients (3%) prematurely discontinued the study because of adverse events. Adverse events that occurred in at least 5% of sertraline-treated patients and with an incidence of at least twice that in placebo patients included diarrhea, vomiting, anorexia, and agitation. CONCLUSION: The results of this pooled analysis demonstrate that sertraline is an effective and well-tolerated short-term treatment for children and adolescents with MDD.

J Clin Psychiatry. 2003 Jul;64(7):785-92.
Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind, placebo-controlled study.
Liebowitz MR, DeMartinis NA, Weihs K, Londborg PD, Smith WT, Chung H, Fayyad R, Clary CM.
New York State Psychiatric Institute, New York, NY, USA.
BACKGROUND: Generalized social anxiety disorder is an early onset, highly chronic, frequently disabling disorder with a lifetime prevalence of approximately 13%. The goal of the current study was to evaluate the efficacy and tolerability of sertraline for the treatment of severe generalized social anxiety disorder in adults. METHOD: After a 1-week single-blind placebo lead-in period, patients with DSM-IV generalized social phobia were randomly assigned to 12 weeks of double-blind treatment with flexible doses of sertraline (50-200 mg/day) or placebo. Primary efficacy outcomes were the mean change in the Liebowitz Social Anxiety Scale (LSAS) total score and the responder rate for the Clinical Global Impressions-Improvement scale (CGI-I), defined as a CGI-I score </= 2. Data were collected in 2000 and 2001. RESULTS: 211 patients were randomly assigned to sertraline (intent-to-treat [ITT] sample, 205), and 204 patients, to placebo (ITT sample, 196). At week 12, sertraline produced a significantly greater reduction in LSAS total score compared with placebo (mean last-observation-carried-forward [LOCF] change from baseline: -31.0 vs. -21.7; p =.001) and a greater proportion of responders (CGI-I score </= 2: 55.6% vs. 29% among week 12 completers and 46.8% vs. 25.5% in the ITT-LOCF sample; p <.001 for both comparisons). Sertraline was well tolerated, with 7.6% of patients discontinuing due to adverse events versus 2.9% of placebo-treated patients. CONCLUSION: The results of the current study confirm the efficacy of sertraline, zoloft in the treatment of severe social anxiety disorder.

J Am Pharm Assoc (Wash DC). 2003 Jul-Aug;43(4):497-502.
Evaluation of cost savings to a state Medicaid program following a sertraline tablet-splitting program.
Vuchetich PJ, Garis RI, Jorgensen AM.
Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, Omaha, Neb. 68178, USA.
OBJECTIVES: To evaluate the economic impact of implementing a sertraline (Zoloft--Pfizer) tablet-splitting program on the Nebraska Medicaid program based on the change in total and per-member-per-month (PMPM) prescription drug costs and to identify any real or perceived problems with tablet splitting using switches among selective serotonin reuptake inhibitors (SSRIs) as a proxy indicator. DESIGN: Retrospective study of prescription claims before and after the tablet-splitting program was implemented. SETTING: Nebraska Medicaid. PATIENTS: All 14,520 patients who received an SSRI during the study period, including 5,466 patients who received at least one prescription for sertraline. INTERVENTIONS: The Nebraska Medicaid program implemented a mandatory tablet-splitting program for sertraline. Pharmacists were paid a supplemental fee to split tablets. MAIN OUTCOME MEASURES: Total costs, PMPM costs, and switches among SSRIs. RESULTS: Using regression analysis, sertraline was the only SSRI that showed a downward slope in total cost per month, although the decrease was not statistically significant (P = .1156). Fluoxetine (Prozac--Eli Lilly) and paroxetine (Paxil--GlaxoSmithKline) both showed an upward slope, but the increases were not statistically significant (P = .1164 and .0671, respectively). Citalopram (Celexa--Forest) and fluvoxamine showed significantly positive upward slopes (P = .0001 and .0391, respectively). Sertraline was also the only SSRI that showed a downward slope in PMPM costs (P = .0093). Citalopram, fluvoxamine, fluoxetine, and paroxetine all showed an upward slope in PMPM costs (P = .4494, .0008, .0448, and .0482, respectively). The tablet-splitting program was not associated with a net change in patients being switched to or from sertraline. CONCLUSION: Implementing the sertraline tablet-splitting program significantly decreased the PMPM cost of sertraline prescriptions, but it did not significantly decrease total costs of sertraline, nor did it result in disproportionate numbers of patients switching from sertraline to other SSRIs. Total costs and PMPM costs of the other four SSRI drugs did not decrease.

J Clin Psychiatry. 2003 Aug;64(8):959-65.
Sertraline as monotherapy in the treatment of psychotic and nonpsychotic depression.
Simpson GM, El Sheshai A, Rady A, Kingsbury SJ, Fayek M.
Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
BACKGROUND: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) are effective when used alone in the treatment of unipolar depression with psychotic features. The purpose of the present study was to examine the response to sertraline for patients with and without psychotic features using standard criteria such as recovery and remission. METHOD: An 8-week open-label trial of sertraline in depressed inpatients was conducted. Twenty-five subjects had DSM-IV major depressive disorder with psychotic features, and 25 had DSM-IV major depressive disorder without psychotic features. After a 1-week open washout, all subjects were rated using the Hamilton Rating Scale for Depression (HAM-D) and Brief Psychiatric Rating Scale (BPRS) at baseline. The HAM-D was administered weekly, and the BPRS was administered again only at the end of the 8-week trial. Medication dosage was started at 50 mg/day, increased to 100 mg/day after 1 week, and then increased up to 200 mg/day if subjects had not remitted. RESULTS: Depressed patients without psychosis responded significantly better than did depressed patients with psychosis using the criteria of remission (HAM-D score - 7; p =.001), response (HAM-D score - 50% of baseline score; p =.011), referral for electroconvulsive therapy (HAM-D score >/= 15; p =.011), or change in HAM-D scores (p =.016). Baseline HAM-D score and psychosis independently predicted response, whereas baseline BPRS scores did not, regardless of whether psychotic status was entered into the analyses. CONCLUSION: Psychotic depression responds more poorly than depression without psychosis to sertraline alone. Psychosis was a predictor of response independent of degree of depression and general psychopathology. Limitations due to an open-label design are discussed, as are differences between this study and others using SSRIs for psychotic depression.

J Clin Psychiatry. 2003 Aug;64(8):875-82.
Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents.
Oslin DW, Ten Have TR, Streim JE, Datto CJ, Weintraub D, DiFilippo S, Katz IR.
Section of Geriatric Psychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pa., USA.
BACKGROUND: In nursing home residents and other frail elderly patients, old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications. The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents. METHOD: The study was a 10-week randomized, double-blind, controlled trial of venlafaxine (doses up to 150 mg/day) versus sertraline (doses up to 100 mg/day) among 52 elderly nursing home residents with a DSM-IV depressive disorder and, at most, moderate dementia. The primary measure of outcome was the Hamilton Rating Scale for Depression (HAM-D). Adverse events were monitored and recorded systematically during the trial. RESULTS: Twelve subjects were discontinued due to serious adverse events (SAE), 5 were discontinued due to other significant side effects, and 2 withdrew consent. Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events (log rank statistic = 5.28, p =.022), for serious adverse events or side effects (log rank statistic = 8.08, p =.005), or for serious adverse events, side effects, or withdrawal of consent (log rank statistic = 10.04, p =.002). Mean (SD) HAM-D scores at baseline were 20.2 (3.4) for sertraline and 20.3 (3.7) for venlafaxine; intent-to-treat endpoint HAM-D scores were 12.2 (5.1) and 15.7 (6.2) (F = 3.45; p =.069). There were no differences in categorical responses for the intent-to-treat sample or completers. CONCLUSION: In this frail elderly population, venlafaxine was less well tolerated and, possibly, less safe than sertraline without evidence for an increase in efficacy. This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly.

J Clin Psychiatry. 2003 Aug;64(8):959-65.
Sertraline as monotherapy in the treatment of psychotic and nonpsychotic depression.
Simpson GM, El Sheshai A, Rady A, Kingsbury SJ, Fayek M.
Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
BACKGROUND: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) are effective when used alone in the treatment of unipolar depression with psychotic features. The purpose of the present study was to examine the response to sertraline for patients with and without psychotic features using standard criteria such as recovery and remission. METHOD: An 8-week open-label trial of sertraline in depressed inpatients was conducted. Twenty-five subjects had DSM-IV major depressive disorder with psychotic features, and 25 had DSM-IV major depressive disorder without psychotic features. After a 1-week open washout, all subjects were rated using the Hamilton Rating Scale for Depression (HAM-D) and Brief Psychiatric Rating Scale (BPRS) at baseline. The HAM-D was administered weekly, and the BPRS was administered again only at the end of the 8-week trial. Medication dosage was started at 50 mg/day, increased to 100 mg/day after 1 week, and then increased up to 200 mg/day if subjects had not remitted. RESULTS: Depressed patients without psychosis responded significantly better than did depressed patients with psychosis using the criteria of remission (HAM-D score - 7; p =.001), response (HAM-D score - 50% of baseline score; p =.011), referral for electroconvulsive therapy (HAM-D score >/= 15; p =.011), or change in HAM-D scores (p =.016). Baseline HAM-D score and psychosis independently predicted response, whereas baseline BPRS scores did not, regardless of whether psychotic status was entered into the analyses. CONCLUSION: Psychotic depression responds more poorly than depression without psychosis to sertraline alone. Psychosis was a predictor of response independent of degree of depression and general psychopathology. Limitations due to an open-label design are discussed, as are differences between this study and others using SSRIs for psychotic depression.

Arch Gen Psychiatry. 2003 Jul;60(7):737-46.
Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS.
Lyketsos CG, DelCampo L, Steinberg M, Miles Q, Steele CD, Munro C, Baker AS, Sheppard JM, Frangakis C, Brandt J, Rabins PV.
Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.
CONTEXT: Major depression affects about 25% of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers. Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction. OBJECTIVES: To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease, and to evaluate the effect of depression reduction on activities of daily living, cognition, and nonmood behavioral disturbance. DESIGN: Randomized, placebo-controlled, parallel, 12-week, flexible-dose clinical trial with a 1-week, single-blind placebo phase. The study was conducted between January 1, 1998, and July 19, 2001. SETTING: University outpatient clinic. PARTICIPANTS: Forty-four outpatients who have probable Alzheimer disease and major depressive episodes. INTERVENTION: Sertraline hydrochloride, mean dosage of 95 mg/d, or identical placebo, randomly assigned. MAIN OUTCOME MEASURES: Response rate, Cornell Scale for Depression in Dementia, Hamilton Depression Rating Scale, Mini-Mental State Examination, Psychogeriatric Depression Rating Scale-activities of daily living subscale, and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress. RESULTS: In the sertraline-treated group 9 patients (38%) were full responders and 11 (46%) were partial responders compared with 3 (20%) and 4 (15%), respectively, in the placebo-treated group (P =.007). The sertraline-treated group had greater improvements in the scores for the Cornell Scale for Depression in Dementia (P =.002) and Hamilton Depression Rating Scale (P =.01), and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale (P =.07). There was no difference between the treatment groups in Mini-Mental State Examination (P =.22) or Neuropsychiatric Inventory (P =.32) ratings over time. When full responders, partial responders, and nonresponders were compared, full responders only, or full and partial responders had significantly better ratings on activities of daily living (P =.04), behavioral disturbance (P =.01), and caregiver distress (P =.006), but not on the Mini-Mental State Examination (P =.76). Safety monitoring indicated few differences in adverse effects between the 2 treatment groups. CONCLUSIONS: Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.

Am J Psychiatry. 2003 Jul;160(7):1277-85.
An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression.
Schneider LS, Nelson JC, Clary CM, Newhouse P, Krishnan KR, Shiovitz T, Weihs K; Sertraline Elderly Depression Study Group.
Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, and the Leonard Davis School of Gerontology, University of SouthernCalifornia, Los Angeles, CA 90033, USA.
OBJECTIVE: There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients. This placebo-controlled study of sertraline was designed to confirm the results of non-placebo-controlled trials. METHOD: The subjects were outpatients age 60 years or older who had a DSM-IV diagnosis of major depressive disorder and a total score on the 17-item Hamilton Depression Rating Scale of 18 or higher. The patients were randomly assigned to 8 weeks of double-blind treatment with placebo or a flexible daily dose of 50 or 100 mg of sertraline. The primary outcome variables were the Hamilton scale and Clinical Global Impression (CGI) scales for severity and improvement. RESULTS: A total of 371 patients assigned to sertraline and 376 assigned to placebo took at least one dose. At endpoint, the patients receiving sertraline evidenced significantly greater improvements than those receiving placebo on the Hamilton depression scale and CGI severity and improvement scales. The mean changes from baseline to endpoint in Hamilton score were -7.4 points (SD=6.3) for sertraline and -6.6 points (SD=6.4) for placebo. The rate of CGI-defined response at endpoint was significantly higher for sertraline (45%) than for placebo (35%), and the time to sustained response was significantly shorter for sertraline (median, 57 versus 61 days). There were few discontinuations due to treatment-related adverse events, 8% for sertraline and 2% for placebo. CONCLUSIONS: Sertraline was effective and well tolerated by older adults with major depression, although the drug-placebo difference was not large in this 8-week trial.

J Clin Psychiatry. 2003 Jul;64(7):785-92.
Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind, placebo-controlled study.
Liebowitz MR, DeMartinis NA, Weihs K, Londborg PD, Smith WT, Chung H, Fayyad R, Clary CM.
New York State Psychiatric Institute, New York, NY, USA.
BACKGROUND: Generalized social anxiety disorder is an early onset, highly chronic, frequently disabling disorder with a lifetime prevalence of approximately 13%. The goal of the current study was to evaluate the efficacy and tolerability of sertraline for the treatment of severe generalized social anxiety disorder in adults. METHOD: After a 1-week single-blind placebo lead-in period, patients with DSM-IV generalized social phobia were randomly assigned to 12 weeks of double-blind treatment with flexible doses of sertraline (50-200 mg/day) or placebo. Primary efficacy outcomes were the mean change in the Liebowitz Social Anxiety Scale (LSAS) total score and the responder rate for the Clinical Global Impressions-Improvement scale (CGI-I), defined as a CGI-I score

Psychiatr Pol. 2002 Nov-Dec;36(6 Suppl):289-95.
The effect of sertraline on cognitive functions in patients with obsessive-compulsive disorder.
Borkowska A, Pilaczynska E, Araszkiewicz A, Rybakowski J.
Katedra i Klinika Psychiatrii AM w Bydgoszczy.
The aim of this study was to assess the effect of sertraline on psychopathological symptoms and cognitive functions and in patients with obsessive compulsive disorder (OCD). The investigated group consisted of 25 patients with OCD (12 male, 13 female) aged 17-47 (mean 29 +/- 9) years, duration of illness was 1-15 (mean 4 +/- 2) years. After treatment with sertraline, a significant improvement in OCD symptoms measured by YBOCS and in neuropsychological "frontal" tests were observed. Little correlation was found between the effect of sertraline on OCD symptoms and on cognitive dysfunctions. This may suggest that these two effects may be connected with different pharmacological properties of the drug. The effect of sertraline on OCD symptoms, similarly like other drugs inhibiting serotonin transporter (clomipramine, other SSRI) is associated with its influence on serotonergic system. On the other hand, the effect of sertraline on dopaminergic neurotransmission may be related to its favorable action on cognitive functions connected with the activity of frontal lobe.

Eur Neuropsychopharmacol. 2002 Jun;12(3):181-6.
Sertraline treatment of obsessive-compulsive disorder: efficacy and tolerability of a rapid titration regimen.
Bogetto F, Albert U, Maina G.
Anxiety and Mood Disorders Unit, Department of Neurosciences, Psychiatric Section, University of Turin, Via Cherasco 11, 10126 Turin, Italy.
The objective of this study was to compare in a single blind manner, over a period of 12 weeks, the efficacy and tolerability of two different titration regimens of sertraline in the treatment of OCD: 150 mg/day reached at day five from the beginning of therapy (rapid titration regimen) versus 150 mg/day reached at day 15 from the beginning (slow titration regimen). Patients with a DSM-IV diagnosis of OCD and a Y-BOCS greater or equal to 16 were randomly assigned to receive one of the two dosing regimens; an upper target dose of 150 mg/day was selected on the basis of a review of mean dosages used in flexible-dose sertraline studies. The primary efficacy measure was the Y-BOCS, which was completed at baseline and every 2 weeks. Thirty-two patients referred to the Anxiety and Mood Disorders Unit of the University of Turin were included in the study. Seventeen were assigned to the rapidly escalating dose regimen and 15 to the other titration regimen. Twenty-seven (84.4%) patients completed the 12 weeks of the study: 14 (82.4%) patients in the rapid and 13 (86.7%) in the slow titration regimen. The ANOVA analysis showed a significant difference between treatment groups at week 4 and 6 in favor of the rapid titration regimen group; this difference faded afterwards. Both titration regimens were effective in reducing OC symptoms and were well tolerated: no differences in drop-out or in adverse event rates emerged between the two groups. Limitations of the present study are the single-blind design and the lack of power to detect differences in tolerability.

Am J Psychiatry. 2002 Jan;159(1):88-95.
Efficacy of sertraline in the long-term treatment of obsessive-compulsive disorder.
Koran LM, Hackett E, Rubin A, Wolkow R, Robinson D.
Department of Psychiatry, Stanford University, CA 94305, USA.
OBJECTIVE: Obsessive-compulsive disorder (OCD) typically begins early in life and has a chronic course. Despite the need for long-term treatment, the authors found no placebo-controlled studies that have examined the relapse-prevention efficacy of maintenance therapy. METHOD: Patients who met criteria for response after 16 and 52 weeks of a single-blind trial of sertraline were randomly assigned to a 28-week double-blind trial of 50-200 mg/day of sertraline or placebo. Primary outcomes after the double-blind trial were full relapse, dropout due to relapse or insufficient response, or acute exacerbation of OCD symptoms. RESULTS: Of 649 patients at baseline, 232 completed 52 weeks of the single-blind trial and met response criteria. Among the 223 patients in the double-blind phase of the study, sertraline had significantly greater efficacy than placebo on two of three primary outcomes: dropout due to relapse or insufficient clinical response (9% versus 24%, respectively) and acute exacerbation of symptoms (12% versus 35%). Sertraline resulted in improvement in quality of life during the initial 52-week trial and continued improvement, significantly superior to placebo, during the subsequent 28-week double-blind trial. Long-term treatment with sertraline was well tolerated. Over the entire study period, less than 20% of the patients stopped treatment because of adverse events. CONCLUSIONS: Sertraline demonstrated sustained efficacy among patients responding to treatment and was generally well tolerated during the 80-week study. During the study's last 28 weeks, sertraline demonstrated greater efficacy than placebo in preventing dropout due to relapse or insufficient clinical response and acute exacerbation of OCD symptoms.

J Clin Psychopharmacol. 2002 Apr;22(2):190-5.
Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder.
Zohar J, Amital D, Miodownik C, Kotler M, Bleich A, Lane RM, Austin C.
Division of Psychiatry, Chaim-Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel.
The efficacy of sertraline in the treatment of civilian posttraumatic stress disorder (PTSD) has been established by two large placebo-controlled trials. The purpose of the current pilot study was to obtain preliminary evidence of the efficacy of sertraline in military veterans suffering from PTSD. Outpatient Israeli military veterans with a DSM-III-R diagnosis of PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50-200 mg/day; N = 23, 83% male, mean age = 41 years) or placebo (N = 19, 95% male, mean age = 38 years). Efficacy was evaluated by the Clinician-Administered PTSD Scale (CAPS-2) and by Clinical Global Impression Scale-Severity (CGI-S) and -Improvement (CGI-I) ratings. Consensus responder criteria consisted of a 30% or greater reduction in the CAPS-2 total severity score and a CGI-I rating of "much" or "very much" improved. The baseline CAPS-2 total severity score was 94.3 +/- 12.9 for sertraline patients, which is notably higher than that reported for most studies of civilian PTSD. On an intent-to-treat endpoint analysis, sertraline showed a numeric but not statistically significant advantage compared with placebo on the CAPS-2 total severity and symptom cluster scores. In the study completer analysis, the mean CGI-I score was 2.4 +/- 0.3 for sertraline and 3.4 +/- 0.3 for placebo (t = 2.55, df = 30, p = 0.016), CGI-I responder rates were 53% for sertraline and 20% for placebo (chi2 = 3.62, df = 1, p = 0.057), and combined CGI-I and CAPS-2 responder rates (>or=30% reduction in baseline CAPS-2 score) were 41% for sertraline and 20% for placebo (chi2 = 1.39, df = 1, p = 0.238). Sertraline treatment was well tolerated, with a 13% discontinuation rate as a result of adverse events. This pilot study suggests that sertraline may be an effective treatment in patients with predominantly combat-induced PTSD, although the effect size seems to be somewhat smaller than what has been reported in civilian PTSD studies. Adequately powered studies are needed to confirm these results and to assess whether continued treatment maintains or further improves response.

J Clin Psychiatry. 2002 Jan;63(1):59-65.
Posttraumatic stress disorder and quality of life: results across 64 weeks of sertraline treatment.
Rapaport MH, Endicott J, Clary CM.
Department of Psychiatry, University of California, San Diego, La Jolla, CA 92037, USA.
OBJECTIVE: The goal of the current study was to characterize the quality of life (QOL) and functional impairment associated with posttraumatic stress disorder (PTSD) and to report the QOL/functional response over the course of long-term treatment. METHOD: QOL and psychosocial functioning were analyzed in 359 randomly assigned patients across a 3-phase study of sertraline in the treatment of chronic DSM-III-R-defined PTSD: (1) 12 weeks of double-blind, placebo-controlled acute treatment with sertraline in flexible doses of 50 to 200 mg/day, (2) 24 weeks of open-label continuation treatment with sertraline among all study completers (regardless of initial study drug assignment or endpoint responder status), and (3) 28 weeks of double-blind, placebo-controlled maintenance treatment with sertraline in continuation phase responders. Assessments included the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), emotional role functioning and mental health subscales of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), as well as the occupational and social functioning items on the Clinician-Administered PTSD Scale, Part 2 (CAPS-2). RESULTS: At acute phase baseline, QOL was significantly impaired as reflected by a mean Q-LES-Q score of 56% of the total possible score and a CAPS-2 social/occupational impairment composite score of 4.4. Sertraline treatment was associated with marked improvement on all QOL/functional measurements: at the end of the acute treatment phase, 58% of responders on treatment with sertraline had achieved Q-LES-Q total scores within 10% of community norms. Twenty-four weeks of continuation treatment led to an additional 20% improvement in QOL and measures of functioning. Double-blind discontinuation of sertraline resulted in recurrence of PTSD symptoms and a worsening of QOL and functional measures, although the degree of exacerbation in symptomatology and psychosocial impairment was notably less than at study entry. CONCLUSION: Sertraline treatment of chronic PTSD is associated with rapid improvement in quality of life that is progressive and sustained over the course of more than 1 year of treatment.

Obstet Gynecol. 2002 Dec;100(6):1219-29.
Efficacy of intermittent, luteal phase sertraline treatment of premenstrual dysphoric disorder.
Halbreich U, Bergeron R, Yonkers KA, Freeman E, Stout AL, Cohen L.
State University of New York at Buffalo School of Medicine, 14215, USA.
OBJECTIVE: Premenstrual dysphoric disorder is a menstrually related disorder that intermittently causes disabling emotional, behavioral, and physical symptoms. The goal of the current study was to evaluate the efficacy and tolerability of sertraline for premenstrual dysphoric disorder when treatment was limited to the luteal phase. METHODS: Two hundred eighty-one women who met Diagnostic and Statistical Manual of Mental Disorders (4th edition) criteria for premenstrual dysphoric disorder and who completed two prospective screening cycles and one single-blind placebo cycle were randomized to three cycles of double-blind, luteal phase treatment with either a placebo or sertraline in a flexible daily dose of 50-100 mg. Outcome measures included the Daily Record of Severity of Problems and the Clinical Global Impression Severity and Improvement scales. RESULTS: Luteal phase treatment with sertraline was significantly superior to the placebo, as demonstrated by end- point analysis of Clinical Global Impression Improvement scale scores (sertraline, 2.3 +/- 1.1, versus placebo, 2.7 +/- 1.1; P <.001), and cycle 3 Daily Record of Severity of Problems change scores (sertraline, 27.6 +/- 26.8, versus placebo, 17.6 +/- 23.3; P <.002). A significant difference was also noted in responder rates in favor of sertraline (50%) versus placebo (26%, P <.001) by cycle 1 (with responder defined as a Clinical Global Impression Improvement scale score of 1 or 2). Quality of life and functioning outcomes were also significantly improved. Intermittent luteal administration of sertraline was well tolerated, with only approximately 8% of patients on sertraline and less than 1% on placebo discontinuing because of adverse events. CONCLUSION: Sertraline was significantly more effective than a placebo and was well tolerated as a treatment for premenstrual dysphoric disorder when administered intermittently during the luteal phase of the menstrual cycle.

J Child Adolesc Psychopharmacol. 2001 Summer;11(2):131-42.
Sertraline effects in adolescent major depression and dysthymia: a six-month open trial.
Nixon MK, Milin R, Simeon JG, Cloutier P, Spenst W.
Mental Health Patient Service Unit, Childrens Hospital of Eastern Ontario, Ottawa, Canada.
This 6-month open-label study evaluated the efficacy, tolerability, and safety of sertraline in 21 adolescent psychiatric outpatients, ages 12 to 18 years, diagnosed with major depressive disorder (MDD, n = 13) or dysthymic disorder (DD, n = 8). Both groups showed clinically significant improvements on the Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale, and the Clinical Global Impression Scale-Severity (CGI-S). The MDD group showed maximal clinical response (based on the method of last observation carried forward) on the HAM-D and CGI at weeks 12 (76.9%) and 20 (76.9%), respectively. Response rates were maintained at week 24 with all six MDD study completers (100%) responding to treatment. The DD group achieved maximal response on the HAM-D (100%) and the CGI (75%) at week 6. Response rates in this group did not remain as elevated over time with two out of three (66.7%) DD study completers responding to treatment at week 24. Generally, sertraline was safe and well tolerated. Most adverse events were mild to moderate in severity and resolved with no action taken. Results suggest that sertraline may be efficacious in acute and continuation treatment of MDD in adolescents. DD patients showed evidence of clinical response and improvement, particularly in the acute treatment phase. Incorporating a longer evaluation period in the study of antidepressant therapy for adolescents with MDD and/or DD is emphasized.

J Med Assoc Thai. 2001 Jan;84(1):54-62.
An open, baseline controlled evaluation of sertraline safety and efficacy in the treatment of depression in Thai patients.
An open, baseline controlled study of sertraline in depressed patients was conducted in 6 treatment sites. Eighty-two patients between 20-82 years of age with DSM III-R diagnosis of a depressive illness received sertraline 50-200 mg/day. Among evaluable patients, there was a significant reduction in depressive symptoms at the final visit. A statistically significant change from baseline in Montgomery Asberg Depression Rating Scale (MADRS), Hospital Anxiety Depression Rating Scale (HAD), and Clinical Global Impression Severity of Illness Scale (CGI-S) scores was demonstrated. On the basis of MADRS criterion, 96.0 per cent of patients responded and on the basis of CGI-S criterion, 86.6 per cent of patients responded. In 73.2 per cent of patients the final sertraline dosage was 50 mg. All-cause adverse events were recorded in 35 patients (42.7%), whereas 22 (26.8%) had adverse events that were judged treatment-related. The most frequently reported events were nausea and headache. Overall, the patients tolerated sertraline very well. The results of the study suggest that sertraline is an effective, well-tolerated and safe treatment for depression in Thai patients.

J Clin Pharm Ther. 2000 Oct;25(5):363-71.
Sequential improvement of anxiety, depression and anhedonia with sertraline treatment in patients with major depression.
Boyer P, Tassin JP, Falissart B, Troy S.
Hopital de la Salpetriere, Bd de lhopital, 75013 Paris, France.
OBJECTIVE: To establish the therapeutic effect profile of sertraline in major depression. It was hypothesized that the antidepressant effect of sertraline showed three phases: Phase 1 where improvements in anxiety are most pronounced; Phase 2 where the greatest improvements are in depressive symptoms; and Phase 3 where the symptoms of anhedonia show the most improvement. To test this hypothesis, an 8-week, open-label study was conducted. METHODS: Patients with a major depressive episode (DSM-IV) and a score > or = 24 on the 17-item HAM-D were enrolled and treated with sertraline 50-150 mg/day. The three symptomatic clusters, anxiety, depression and hedonia, were defined a priori using the Inventory of Depressive Symptomatology-Clinician rated (IDS-C). Periods of interest were: Days 0-7 for anxiety, Days 7-21 for depression and Days 21-56 for anhedonia. Raters were blinded as to the constitution of the clusters and periods. RESULTS: 140 patients were recruited. Improvement in the anxiety cluster of the IDS-C was greatest during Days 0-7, whereas over Days 7-21 most improvement was observed in the depression cluster and the greatest improvement in the hedonic cluster occurred during Days 21-56. CONCLUSION: These preliminary results are consistent with the hypothesis that the therapeutic effects of sertraline occur in a sequential manner. The symptoms of anxiety improved first, followed by depression and then anhedonia.

Am J Psychiatry. 2000 Oct;157(10):1686-9.
Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimers disease: initial results from the Depression in Alzheimers Disease study.
Lyketsos CG, Sheppard JM, Steele CD, Kopunek S, Steinberg M, Baker AS, Brandt J, Rabins PV.
Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, USA.
OBJECTIVE: This study evaluated the efficacy and safety of sertraline in the treatment of major depression in 22 outpatients with Alzheimer's disease. METHOD: Twelve of the 22 patients were given sertraline and 10 were given placebo by random group assignment for 12 weeks. Response to treatment was measured by using the Cornell Scale for Depression in Dementia. The patients were also assessed with the Hamilton Depression Rating Scale, the activities of daily living subscale of the Psychogeriatric Dependency Rating Scales, and the Mini-Mental State. RESULTS: After 12 weeks of double-blind, placebo-controlled treatment, nine of the patients given sertraline and two of those given placebo were at least partial responders. Patients given sertraline had significantly greater mean declines from baseline in Cornell Scale for Depression in Dementia scores; the bulk of antidepressant response occurred by the third week of treatment. CONCLUSIONS: Sertraline is superior to placebo in reducing depression in patients with Alzheimer's disease who also suffer from major depression.

J Clin Psychiatry. 2000 Dec;61(12):922-7.
Sertraline treatment of panic disorder: response in patients at risk for poor outcome.
Pollack MH, Rapaport MH, Clary CM, Mardekian J, Wolkow R.
Department of Psychiatry, Massachusetts General Hospital, Boston 02114-7541, USA.
BACKGROUND: More than one third of panic disorder patients have a chronic and/or recurrent form of the disorder, accounting for much of the individual and societal cost associated with the illness. Six clinical variables have been most consistently identified as high-risk predictors of poor outcome: (1) panic severity, (2) presence of agoraphobia, (3) comorbid depression, (4) comorbid personality disorder, (5) duration of illness, and (6) female sex. No published research has systematically examined the differential antipanic efficacy of selective serotonin reuptake inhibitors in patients at high risk for poor outcome. METHOD: Data were pooled (N = 664) from 4 double-blind, placebo-controlled studies of the efficacy of sertraline for the treatment of DSM-III-R panic disorder. Two of the studies were 12-week fixed-dose studies with starting daily doses of sertraline, 50 mg, and 2 were 10-week flexible-dose studies with starting daily doses of sertraline, 25 mg. All other study design features were the same, except for the exclusion of women of childbearing potential in the 2 fixed-dose studies. Exclusion of patients with marked personality disorders and depression meant that only 4 of the poor-outcome variables could be evaluated. RESULTS: Clinical improvement was similar for patients treated with sertraline whether or not they carried an agoraphobia diagnosis, had a duration of illness > 2 years, or were female. Patients with high baseline panic severity had significantly (p = .01) less improvement on the endpoint Clinical Global Impressions-Improvement (CGI-I) scale than patients with moderate severity, although the Clinical Global Impressions-Severity of Illness scale change score was higher in the patients with high severity (-2.00 vs. -1.31). For patients with 3 or more high-risk variables, there was a modest, but statistically significant, tendency for reduced global improvement (endpoint CGI-I score of 2.7 for the high-risk vs. 2.4 for the non-high-risk group; p = .017), although the high-risk group actually had a similar endpoint reduction in frequency of panic attacks (82%) compared with the non-high-risk group (78%). CONCLUSION: Treatment of panic disorder with sertraline was generally effective, even in the presence of baseline clinical variables that have been associated with poor treatment response. The main limitations of the analysis were the reliance on pooled data from 4 studies (even if the designs were similar) and our inability to examine the impact of depression and personality disorders on response to treatment because of the exclusion criteria of the clinical trials.

Int Clin Psychopharmacol. 2000 Nov;15(6):335-42.
The efficacy of sertraline in panic disorder: combined results from two fixed-dose studies.
Sheikh JI, Londborg P, Clary CM, Fayyad R.
Department of Psychiatry, Stanford University School of Medicine, CA 94305-5723, USA.
Data from two fixed-dose studies of sertraline in panic disorder were pooled in order to provide sufficient power for the analysis of treatment response in clinically relevant subgroups. Male and non-fertile female patients meeting DSM-III-R criteria for moderate-to-severe panic disorder with or without agoraphobia completed a 1-2 week placebo run-in period, and then were randomized to 12 weeks of double-blind treatment with either placebo, or one of three fixed daily doses of sertraline (50 mg, 100 mg, or 200 mg). Eighty-two patients were treated with placebo and 240 patients were treated with one of three doses of sertraline. All three sertraline doses produced significant efficacy compared to placebo, with no consistent evidence of a dose-response effect. For the subset of patients with subsyndromic depression at baseline [baseline Hamilton Depression Rating scale (HAM-D > 12 and < or = 21], sertraline yielded a significantly higher panic-free rate than did placebo (P = 0.021), again, by a conservative endpoint (Last Observation Carried Forward method, LOCF) analysis. Sertraline was well-tolerated at all dose levels, with no significant between-dose differences in patients discontinuing due to adverse events. The presence of mild-to-moderate subsyndromic levels of depression did not reduce the anti-panic efficacy of sertraline.

Int Clin Psychopharmacol. 2000 Nov;15(6):335-42.
The efficacy of sertraline in panic disorder: combined results from two fixed-dose studies.
Sheikh JI, Londborg P, Clary CM, Fayyad R.
Department of Psychiatry, Stanford University School of Medicine, CA 94305-5723, USA.
Data from two fixed-dose studies of sertraline in panic disorder were pooled in order to provide sufficient power for the analysis of treatment response in clinically relevant subgroups. Male and non-fertile female patients meeting DSM-III-R criteria for moderate-to-severe panic disorder with or without agoraphobia completed a 1-2 week placebo run-in period, and then were randomized to 12 weeks of double-blind treatment with either placebo, or one of three fixed daily doses of sertraline (50 mg, 100 mg, or 200 mg). Eighty-two patients were treated with placebo and 240 patients were treated with one of three doses of sertraline. All three sertraline doses produced significant efficacy compared to placebo, with no consistent evidence of a dose-response effect. For the subset of patients with subsyndromic depression at baseline [baseline Hamilton Depression Rating scale (HAM-D > 12 and < or = 21], sertraline yielded a significantly higher panic-free rate than did placebo (P = 0.021), again, by a conservative endpoint (Last Observation Carried Forward method, LOCF) analysis. Sertraline was well-tolerated at all dose levels, with no significant between-dose differences in patients discontinuing due to adverse events. The presence of mild-to-moderate subsyndromic levels of depression did not reduce the anti-panic efficacy of sertraline.

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.
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.

JAMA. 1997 Sep 24;278(12):983-8.
Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual
Dysphoric Collaborative Study Group.
Yonkers KA, Halbreich U, Freeman E, Brown C, Endicott J, Frank E, Parry B, Pearlstein T, Severino S, Stout A, Stone A, Harrison W.
Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, 75235, USA.
CONTEXT: Premenstrual dysphoric disorder is an important cause of symptoms and functional impairment in menstruating women. OBJECTIVE: To evaluate the efficacy of sertraline hydrochloride for treatment of premenstrual dysphoria by measuring changes in symptom expression and functional impairment. DESIGN: Two screening cycles followed by 1 single-blind placebo cycle and 3 cycles of randomized, double-blind, placebo treatment. SETTING: Twelve university-affiliated outpatient psychiatry and gynecology clinics. PATIENTS: Of the 447 women who requested participation, 243 met criteria for premenstrual dysphoric disorder and were randomized; 200 women completed the study. INTERVENTION: A flexible (50-150 mg) daily dose of sertraline hydrochloride. MAIN OUTCOME MEASURES: The Daily Record of Severity of Problems, Hamilton Rating Scale for Depression, Clinical Global Impression Scale, and Social Adjustment Scale. RESULTS: Mean (+/-SD) total daily symptom scores decreased significantly (P<.001) in the sertraline-treated (64+/-22 to 44+/-19) compared with the placebo-treated (62+/-22 to 54+/-24) groups. Significant improvement (P<.05) was found for all clinically derived symptom clusters (depressive, physical, and anger/irritability symptoms). Hamilton Rating Scale for Depression scores decreased by 44% and 29% in the sertraline and placebo groups, respectively (P<.002). End-point global ratings showed much or very much improvement in 62% of the active treatment group and 34% of the placebo treatment group (P<.001). Reported functional impairment was substantial at baseline. Improvement in psychosocial functioning with treatment was similar to what is found in studies of major depression. CONCLUSIONS: Sertraline was significantly better than placebo for treatment of premenstrual dysphoria as reflected by symptomatic improvement and change in reported functional impairment. Serotonin reuptake inhibitors such as sertraline are useful therapeutic options for women with premenstrual dysphoria.

Psychopharmacol Bull. 1996;32(1):41-6.
Sertraline in the treatment of premenstrual dysphoric disorder.
Yonkers KA, Halbreich U, Freeman E, Brown C, Pearlstein T.
University of Texas Southwestern Medical Center, Dallas, USA.
It is estimated that 2 to 9 percent of women suffer from premenstrual dysphoric disorder (PMDD). Despite decades of research, effective treatments for the condition have eluded investigators. Research criteria for (PMDD) were established to promote investigation into the treatment and psychobiology of severe, dysphoric premenstrual symptomatology. Application of these new criteria to clinical trials adds needed rigor to research in this area and justifies the identification of effective treatments. In this study, rigorous criteria were utilized in a 12-center trial investigating the efficacy of the serotonin reuptake inhibitor sertraline in the treatment of PMDD. The study was completed and data was available for 162 women. A preliminary analysis demonstrated a positive response (very much improved or much improved) in 68 percent of patients treated with sertraline, compared with only 40 percent of patients treated with placebo (p < .01). This preliminary analysis provides strong support for the efficacy of sertraline as a treatment of severe premenstrual dysphoria.

Adolesc Health. 1995 Mar;16(3):232-4.
Effects of long term treatment with sertraline (Zoloft) simulating hypothyroidism in an adolescent.
Harel Z, Biro FM, Tedford WL.
Department of Pediatrics, Childrens Hospital, Cincinnati, Ohio, USA.
A 16-year-old depressed adolescent, who had received sertraline treatment for the previous 18 months, developed insomnia, daytime somnolence and lack of energy. His thyroid function tests revealed low levels of total T4 with normal levels of free T4 and TSH, and a normal thyrotropin-releasing hormone (TRH) stimulation test. Discontinuing sertraline resulted in improved sleep and disappearance of daytime somnolence. Although daytime somnolence and low levels of total T4 can mimic hypothyroidism, in this case sertraline only displaced the bound-fraction of total T4 and was not associated with true hypothyroidism.