A randomized trial of sertraline as a cessation aid for smokers with a history of major depression

OBJECTIVE: Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression. Specifically, sertraline's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated. METHOD: The study design included a 1-week placebo washout, a 9-week double-blind, placebo-controlled treatment phase followed by a 9-day taper period, and a 6-month drug-free follow-up. One hundred thirty-four smokers with a history of major depression were randomly assigned to receive sertraline (N=68) or matching placebo (N=66); all received intensive individual cessation counseling during nine clinic visits. RESULTS: Sertraline treatment produced a lower total withdrawal symptom score and less irritability, anxiety, craving, and restlessness than placebo. However, the abstinence rates did not significantly differ between treatment groups: 28.8% (19 of 66) for placebo and 33.8% (23 of 68) for sertraline at the end of treatment and 16.7% (11 of 66) for placebo and 11.8% (eight of 68) for sertraline at the 6-month follow-up. No moderating effects of single or recurrent major depression, depressed mood at baseline, nicotine dependence level, or gender were observed. CONCLUSIONS: Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline.     

Treatment of dysthymia with sertraline: a double-blind, placebo-controlled trial in dysthymic patients without major depression

BACKGROUND: The selective serotonin reuptake inhibitor sertraline has been shown to be efficacious and well tolerated for the treatment of major depressive disorder. Relatively few trials, however, have examined the role of pharmacotherapy in dysthymia without concurrent major depression. The current investigation focuses on the use of sertraline for the treatment of dysthymia. METHOD: In this 12-week, multicenter, double-blind study, 310 patients with a DSM-III-R diagnosis of dysthymic disorder without concurrent major depression were randomly assigned to receive either sertraline (N = 158) or placebo (N = 152). Sertraline was initiated at a dose of 50 mg daily, with titration permitted to a maximum of 200 mg daily. The primary evaluation criteria were the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version (SIGH-SAD), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales. RESULTS: Mean percentage reductions for the intent-to-treat population in SIGH-SAD scores were 44.6% for the sertraline-treated group and 33.2% for the placebo-treated group (p = .03); MADRS scores, 43.6% and 33.0% (p = .02); and CGI-S scores, 32.8% and 22.8% (p = .02). A significantly greater proportion of the sertraline-treated group was classified as responders (defined for HAM-D and MADRS scores as a 50% score reduction and for CGI-I as a score of 1 or 2 by the final visit) and remitters (SIGH-SAD score < or = 8) relative to the placebo-treated group by the final visit. In addition, sertraline-treated patients experienced greater improvements in all 9 domains of the Battelle Quality of Life Questionnaire than placebo-treated patients did, with a significant difference observed in favor of sertraline in 8 of the 9 domains. The life satisfaction and social interaction quality of life domains showed significantly greater response in sertraline responders compared with placebo SIGH-SAD responders. Sertraline was well tolerated. Thirteen percent of the sertraline-treated group versus 8% of the placebo-treated group withdrew from therapy owing to adverse events (p = .14). CONCLUSION: Sertraline is efficacious and well tolerated in the short-term treatment of dysthymia without concurrent major depression.     

Prevention of postpartum depression: a pilot randomized clinical trial

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.     

Efficacy of sertraline in preventing relapse of posttraumatic stress disorder: results of a 28-week double-blind, placebo-controlled study.

OBJECTIVE: The study examined the efficacy of sertraline, compared with placebo, in sustaining improvement and preventing relapse over 28 weeks in patients with posttraumatic stress disorder (PTSD) who had completed a 12-week double-blind, placebo-controlled acute treatment study and a subsequent 24-week open-label study of continuation treatment with sertraline. METHOD: Ninety-six patients were randomly assigned, in a double-blind design, to 28 weeks of maintenance treatment with sertraline (50-200 mg, N=46; 78% were women) or placebo (N=50; 62% were women). Measures used in biweekly assessments included the Clinician-Administered PTSD Scale, the Impact of Event Scale, and the Clinical Global Impression severity and improvement ratings. Kaplan-Meier analyses were used to estimate time to discontinuation from the study due to relapse, relapse or study discontinuation due to clinical deterioration, and acute exacerbation. RESULTS: Continued treatment with sertraline yielded lower PTSD relapse rates than placebo (5% versus 26%). Patients who received placebo were 6.4 times as likely to experience relapse as were patients who received sertraline. Kaplan-Meier analyses confirmed the protective effect of sertraline in significantly extending time in remission. The ability of sertraline to sustain improvement was comparable across the three core PTSD symptom clusters (reexperiencing/intrusion, avoidance/numbing, and hyperarousal). A regression analysis found early response during acute treatment to be associated with a more than 16-fold reduced risk of relapse after placebo substitution. Sertraline, at a mean endpoint dose of 137 mg, was well tolerated, with no sertraline-related adverse events observed at a rate of 10% or higher. CONCLUSIONS: The results provide evidence for the ability of sertraline both to sustain improvement in PTSD symptoms and to provide prophylactic protection against relapse.     

Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer's disease: initial results from the Depression in Alzheimer's Disease study

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.     

An 8-week multicenter,parallel-group,double-blind,placebo-controlled study of sertraline in elderly outpatients with major depression

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.     

Pharmacoeconomic analysis of sertraline treatment of depression in patients with unstable angina or a recent myocardial infarction

BACKGROUND: The prevalence of major depressive disorder in patients with acute coronary syndromes (ACSs) is high and associated with worse cardiovascular outcomes and higher health care costs. Sertraline is the only treatment for major depressive disorder studied in a placebo-controlled trial of patients with ACS and found to be safe and effective. The cost implications of providing antidepressant treatment in this population have not yet been examined. The objective was to evaluate from a payer perspective the potential reduction in costs and psychiatric and cardiovascular events and procedures following sertraline versus placebo treatment of major depressive disorder in patients hospitalized for ACS. METHOD: Data were analyzed from a randomized, double-blind, placebo-controlled 24-week trial (Sertraline Antidepressant Heart Attack Randomized Trial) of sertraline treatment for major depressive disorder in patients hospitalized for ACS. Main outcome measures included frequency and costs (derived from Medicare diagnosis-related group fee schedules) of psychiatric and cardiovascular events occurring during the treatment period. RESULTS: There was a trend toward significantly fewer psychiatric or cardiovascular hospitalizations in the sertraline compared with the placebo group (55/186 vs. 76/183; p = .054). The mean per patient cost associated with psychiatric and medical events over the course of treatment was 2733 US dollars for sertraline and 3326 US dollars for placebo, but the difference was not statistically significant (p = .32). After including the costs of the sertra-line (360 US dollars over 24 weeks), there was no increase in treatment costs for sertraline compared with placebo. CONCLUSION: Sertraline treatment of major depressive disorder following hospitalization for a recent myocardial infarction or unstable angina appears to be a cost-effective strategy.     

A randomized, placebo-controlled trial of sertraline for prophylactic treatment of highly recurrent major depressive disorder

OBJECTIVE: Previous antidepressant maintenance trials have used the same medication from acute through maintenance phases, confounding the interpretation of prophylactic effects. The purpose of this study was to determine whether sertraline prevents the recurrence of major depressive disorder among patients with recurrent depression who had been treated to remission with medications other than sertraline. METHOD: Patients who had experienced at least three documented episodes of major depressive disorder within the last 4 years and who were currently in full remission were eligible. The last episode must have been treated for at least 4 months with any antidepressant except sertraline. For the initial single-blind placebo lead-in phase, 371 patients were included; 288 were included in the analyses for the 18-month double-blind phase in which patients were randomly assigned to sertraline (50 or 100 mg) or placebo (two capsules per day). Recurrence was defined as a depressive episode that fulfilled DSM-IV criteria or the appearance of symptoms that required the administration of another antidepressant treatment. RESULTS: Sixty-one patients discontinued before the double-blind phase, including 33 who experienced a relapse. Out of the 288 who entered the double-blind prophylactic phase, 123 discontinued, including 65 for recurrences. Recurrences were significantly lower in the sertraline groups compared with placebo (sertraline, 50 mg: 16 [16.8%] of 95; sertraline, 100 mg: 16 [17.0%] of 94; placebo: 33 [33.3%] of 99). Patients treated with sertraline also had a significantly longer time until recurrence compared with placebo-treated patients. CONCLUSIONS: Among remitted patients with a history of multiple depressive episodes, sertraline at a dose of either 50 or 100 mg/day prevented recurrences significantly more than did placebo.     

Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study

OBJECTIVE: The authors evaluated the efficacy, safety, and tolerability of sertraline, a selective serotonin reuptake inhibitor, in the treatment of generalized social phobia. METHOD: Adult outpatients with generalized social phobia (N=204) from 10 Canadian centers were randomly assigned to receive sertraline or placebo in a 2:1 ratio for a 20-week double-blind study following a 1-week, single-blind, placebo run-in. The initial dose of sertraline was 50 mg/day with increases of 50 mg/day every 3 weeks permitted after the fourth week of treatment (dosing was flexible up to a maximum of 200 mg/day). Primary efficacy assessments were the percentage of patients rated much or very much improved on the Clinical Global Impression (CGI) improvement item and the mean changes from baseline to study endpoint in total score on the social phobia subscale of the Marks Fear Questionnaire and total score on the Brief Social Phobia Scale. RESULTS: In intent-to-treat endpoint analyses of 203 of the patients, significantly more of the 134 patients given sertraline (N=71 [53%]) than of the 69 patients receiving placebo (N=20 [29%]) were considered responders according to their CGI improvement scores at the end of treatment. The mean reductions in the social phobia subscale of the Marks Fear Questionnaire and in the total score on the Brief Social Phobia Scale were 32.6% and 34.3% in the sertraline group and 10.8% and 18.6% in the placebo group, respectively. Analysis of covariance showed superiority of sertraline over placebo on all primary and secondary efficacy measures. Sertraline was well tolerated: 103 (76%) of the 135 sertraline-treated patients and 54 (78%) of the 69 placebo-treated patients completed the study. CONCLUSIONS: Sertraline is an effective treatment for patients with generalized social phobia.     

Psychosocial outcomes following long-term,double-blind treatment of chronic depression with sertraline vs placebo

BACKGROUND: Chronic forms of depression are associated with significant functional and psychosocial impairments. To date, no study has measured psychosocial functioning in this population during long-term maintenance antidepressant treatment or following the double-blind discontinuation of treatment. METHODS: Patients with chronic major or double depression completed 12 weeks of short-term treatment followed by 16 weeks of continuation treatment with sertraline hydrochloride. Responders at the end of the continuation phase were randomized, double-blind, to 18 months of maintenance therapy with either sertraline (n = 77) or placebo (n = 84). Multiple domains of psychosocial functioning were assessed during double-blind therapy. RESULTS: Substantial worsening in psychosocial function measures occurred in patients taking placebo compared with sertraline during maintenance. Patients with reemergence of depression lost psychosocial gains regardless of treatment. In the subsample of patients who remained in remission throughout maintenance, most of the observed improvement in psychosocial functioning occurred during short-term treatment. By maintenance end point, normalization of functioning was achieved by 58% to 84% of remitters, depending on the outcome measure used. CONCLUSIONS: These results indicate that long-term treatment of chronic forms of depression can result in sustained psychosocial benefits. Discontinuation of treatment results in frequent reemergence of symptoms and loss of psychosocial gains. Long-term treatment resulted in only modest further improvement of psychosocial measures over that achieved in the short-term phase.     

Sertraline treatment of panic disorder: results of a long-term study.

OBJECTIVE: To investigate the long-term efficacy, prevention of relapse and safety of sertraline in the treatment of panic disorder. METHOD: This study consisted of 52 weeks of open-label sertraline treatment (n=398) followed by a 28 weeks of a double-blind, placebo-controlled discontinuation trial (n=183). RESULTS: Ninety-three patients were randomized to sertraline and 90 were randomized to placebo. Discontinuation due to insufficient clinical response occurred in 23.6% of placebo-treated patients and 12.0% of sertraline-treated patients (log-rank test, P=0.040). Thirty-three per cent of placebo-treated patients had an exacerbation of panic symptomatology, versus 13% of sertraline-treated patients (log-rank test, P=0.005). Abrupt cessation of sertraline resulted in dizziness (4.3% sertraline vs. 16.9% placebo; P=0.007) and insomnia (4.3% sertraline vs. 15.7% placebo; P=0.013) occurring at significantly higher rates. CONCLUSION: Long-term sertraline treatment was effective in preventing relapse of panic disorder, well tolerated and associated with minimal discontinuation symptoms.     

Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy,and the benefits of depression reduction: the DIADS

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.     

Venlafaxine versus placebo in the preventive treatment of recurrent major depression

BACKGROUND: Major depression is often chronic and recurrent, yet most long-term therapeutic trials are not adequately designed to assess antidepressant efficacy in recurrence prevention. Long-term efficacy and safety of prophylactic venlafaxine treatment were evaluated in outpatients with recurrent major depression. METHOD: Patients with a history of recurrent DSM-III-R major depression received open-label treatment with venlafaxine, 100 to 200 mg/day, for 6 months. Those who responded to treatment (Hamilton Rating Scale for Depression [HAM-D(21)] score < or = 12, day 56) and remained relapse-free (no more than 2 HAM-D(21) scores > 10 and no Clinical Global Impressions-Severity of Illness [CGI-S] score > or = 4, months 2-6) either continued taking venlafaxine, 100 to 200 mg/day, or were switched in a double-blind fashion to placebo for 12 months. The primary efficacy outcome was the number of patients experiencing a recurrence of major depression (CGI-S score > or = 4). The cumulative probability of recurrence was calculated using the Kaplan-Meier method of survival analysis. Data were collected from November 1992 through December 1995. RESULTS: Of the 235 patients who enrolled in the recurrence-prevention period, 225 (N = 109, venlafaxine; N = 116, placebo) provided efficacy data. Survival analysis determined a 22% cumulative probability of recurrence in venlafaxine-treated patients after 12 months compared with 55% for the placebo group (p <.001). More than twice as many placebo-treated patients (48%) as venlafaxine-treated patients (21%) discontinued treatment because of lack of efficacy (p <.001). CONCLUSION: Twelve-month maintenance venlafaxine treatment was significantly more efficacious than placebo in preventing major depression recurrence in patients who had been successfully treated with venlafaxine for 6 months.     

Sertraline in children and adolescents with major depressive disorder

OBJECTIVE: To explore time to first response and time to first persistent response of sertraline versus placebo and compare these parameters between children (6-11 years old, n = 177) and adolescents (12-17 years old, n = 199) with major depressive disorder. METHOD: A 10-week placebo-controlled treatment was followed by a 24-week open-label sertraline treatment. The double-blind studies were not powered to detect efficacy differences between age groups. A post hoc analysis explored time to first response and first persistent response using the Children's Depression Rating Scale-Revised and Clinical Global Impressions-Improvement predefined criteria. RESULTS: There were no statistically significant differences in time to first response or first persistent response between sertraline and placebo in children, except for time to first response on Clinical Global Impressions-Improvement. Sertraline had a significantly faster time to first persistent response in adolescents compared to placebo. Within treatment groups, children had a significantly faster time to first response than adolescents, whether treated with placebo or sertraline, but not on time to first persistent response. Both age groups showed similar improvement over 34 weeks of treatment. CONCLUSION: In the double-blind studies, children and adolescents had different patterns of response with sertraline vs. placebo.     

Suicidal thinking and behavior during treatment with sertraline in late-life depression.

OBJECTIVE: To determine effects of sertraline on suicidal thinking and behavior in patients with late-life major depression. METHODS: This was a secondary analysis of an eight-week, placebo-controlled, double-blind randomized trial of a multicenter trial at 66 clinical sites. Outpatients >/=60 years of age with major depression and a Hamilton Depression Rating (HAMD) score >/=18 were included. Intervention was sertraline 50-100 mg/day or placebo for eight weeks. Measurements were 17-item HAMD administered at baseline and two-week intervals. HAMD Item 3 used to assess suicidal ideation (SI) and behavior. Reports of serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, and spontaneously reported adverse events reviewed. RESULTS: A total of 747 patients received at least one dose of medication, and 728 had at least one posttreatment assessment. Mean age (+/-SD) was 69.8 +/- 6.7 years (range: 59-97 years) and 56% were female. There were no completed suicides or suicide attempts during the double-blind trial. One SAE, hospitalization, was associated with SI in a patient on sertraline. No other AEs were associated with SI or behavior. HAMD Item 3 ratings progressively declined during the trial with significantly lower values for sertraline than placebo (Z = 2.41, p <0.02). In 248 patients with HAMD Item 3 of zero at baseline, the percentage of patients whose Item 3 ratings increased during treatment did not differ in the two groups (22.4% versus 25.8% for sertraline and placebo, respectively.) CONCLUSION: Sertraline was associated with significantly lower HAMD Item 3 scores than placebo during treatment. There was no evidence of greater emergent suicidal thinking or behavior with sertraline than placebo.     

Efficacy of sertraline in a 12-week trial for generalized anxiety disorder

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.     

From the Bench to the Trench: A Comparison of Sertraline Treatment of Major Depression in Clinical and Research Patient Samples

BACKGROUND: New medications that enter the marketplace have been tested almost exclusively in controlled clinical trials conducted in specialty research settings. There is some concern that these carefully selected patient samples may not provide information generalizable to the "real world" clinical population. The purpose of this investigation was to compare results from a large, open-label study of sertraline in the treatment of major depression in the clinical practice setting with pooled results from 2 multicenter, double-blind, placebo-controlled studies conducted in specialty research settings. METHOD: Clinical practice patients (N = 1482), aged 21 to 65 years, from 228 psychiatric clinical practice sites across the United States participated in the open-label treatment study (Clinical Practice sample). Patients who met DSM-III-R criteria for moderate-to-severe unipolar major depression (i.e., had pretreatment Hamilton Rating Scale for Depression [HAM-D] scores >/= 18) were treated for 8 weeks with sertraline in a flexible dosing fashion (50-200 mg daily). Outcomes on the HAM-D and Clinical Global Impressions-Improvement scale (CGI-I) were compared with the pooled results from 2 previously published placebo-controlled, multicenter treatment studies of sertraline in outpatients with major depression (N = 280). The overall response to sertraline in the Clinical Practice sample was compared with the outcome from the research study patient sample (Clinical Research sample). Additionally, comparison of outcomes of patients with common depressive subtypes (double depression, anxious depression, and melancholic ["endogenous"] depression) were examined. RESULTS: The percentage of sertraline-treated patients rated as responders on the CGI-I was significantly higher in the Clinical Practice sample compared with the Clinical Research sample (87% vs. 73%; p <.001). Sertraline was also much better tolerated in the Clinical Practice sample than in the Clinical Research sample as evidenced by significantly lower overall reports of adverse events (9.4% vs. 13.2%; p <.05) and lower patient dropout rates (17.5% vs. 34.3%; p <.01). Among clinical practice patients, sertraline was found to be equally effective in treating endogenous/melancholic and anxious subtypes and only mildly less effective in achieving a response in patients with double depression (chronic low-grade depression with a superimposed major depression). A regression analysis identified older age and double depression as being predictors of a slower time to response. More than 70% of patients who reported nonresponse to previous treatment with fluoxetine or a tricyclic antidepressant responded to sertraline. CONCLUSION: The effectiveness and tolerability of sertraline treatment was found to be significantly better in the Clinical Practice sample, suggesting that the results from controlled studies in research settings may represent an underestimate of the benefits of a drug. More effectiveness research is needed to confirm and extend these findings.     

Seasonal affective disorder and its prevention by anticipatory treatment with bupropion XL.

BACKGROUND: Seasonal affective disorder (SAD) can cause significant distress and impairment. No antidepressant studies have previously attempted to prevent the onset of autumn-winter depression. METHODS: Three prospective, randomized, placebo-controlled prevention trials were conducted on 1042 SAD patients, enrolled in autumn and treated while still well, across the northern US and Canada. Patients received either bupropion XL 150-300 mg or placebo daily by mouth from enrollment until spring and were then followed off medications for 8 additional weeks. Primary efficacy variables were end-of-treatment depression-free rates and survival distributions of depressive recurrence. RESULTS: Despite a reported average of 13 previous seasonal depressive episodes, almost 60% of patients had never previously been treated for depression. Major depression recurrence rates during the three studies for bupropion XL and placebo groups were 19% versus 30% (p = 0.026), 13% versus 21% (p = 0.049), and 16% versus 31%; yielding a relative risk reduction across the three studies of 44% for patients taking bupropion XL. Survival analyses for depression onset also favored bupropion XL over placebo (p = .081, .057, and <.001). CONCLUSIONS: It is possible to prevent recurrence of seasonal major depressive episodes by beginning bupropion treatment early in the season while patients are still well.     

Efficacy of sertraline in the long-term treatment of obsessive-compulsive disorder.

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.     

Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder

BACKGROUND: Posttraumatic stress disorder (PTSD) is a common illness associated with significant disability. Few large, placebo-controlled trials have been reported. METHODS: Outpatients with a DSM-III-R diagnosis of moderate-to-severe PTSD were randomized to 12 weeks of double-blind treatment with either sertraline (N = 100) in flexible daily doses in the range of 50 to 200 mg or placebo (N = 108). Primary outcome measures consisted of the Clinician-Administered PTSD Scale (CAPS-2) total severity score, the patient-rated Impact of Event Scale (IES), and the Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) ratings. RESULTS: Mixed-effects analyses found significantly steeper improvement slopes for sertraline compared with placebo on the CAPS-2 (t = 2.96, P =.003), the IES (t = 2.26, P =.02), the CGI-I score (t = 3.62, P<.001), and the CGI-S score (t = 4.40, P<.001). An intent-to-treat end-point analysis found a 60% responder rate for sertraline and a 38% responder rate for placebo (chi(2)(1) = 8.48, P =.004). Sertraline treatment was well tolerated, with a 9% discontinuation rate because of adverse events, compared with 5% for placebo. Adverse events that were significantly more common in subjects given sertraline compared with placebo consisted of insomnia (35% vs 22%), diarrhea (28% vs 11%), nausea (23% vs 11%), fatigue (13% vs 5%), and decreased appetite (12% vs 1%). CONCLUSION: The results of the current study suggest that sertraline is a safe, well-tolerated, and significantly effective treatment for PTSD.