Sex differences in clinical presentation and response in panic disorder: pooled data from sertraline treatment studies.

OBJECTIVE: Gender differences in clinical presentation and response to sertraline treatment were examined for patients diagnosed with DSM-III-R panic disorder with or without agoraphobia. METHOD: Data was pooled from 4 double-blind, placebo-controlled outpatient studies (males, N = 335; females, N = 338). Two were 12-week fixed-dose studies (sertraline 50 mg vs. 100 mg vs. 200 mg) and 2 were 10-week flexible-dose studies (sertraline 50-200 mg). Primary outcome measures consisted of the Clinical Global Impression-Improvement scale (CGI-I) and change in panic attack frequency. RESULTS: The clinical presentation of panic disorder was similar except that men reported an earlier age of onset, shorter duration of illness, and significantly more frequent history of alcohol and/or substance dependence/abuse. Sertraline was significantly more effective than placebo in both women and men on the 2 primary outcome measures. When between-sex efficacy was compared, women achieved significantly greater improvement than men on panic frequency and CGI-I, but had equivalent improvement on all other measures. There was no significant between-sex difference in study completion rates, or in adverse event profiles. CONCLUSIONS: There was a modest but consistent trend for women to show superior efficacy at the end of acute sertraline treatment. This gender effect only occasionally achieved significance, and must be confirmed by future treatment research.

Characterizing the effects of sertraline in post-traumatic stress disorder.

BACKGROUND: Sertraline has a proved efficacy in post-traumatic stress disorder (PTSD), but it is unknown which symptoms respond or in what sequence this occurs. Such information might be useful clinically and heuristically. METHOD: The study examined the effects of sertraline on the individual symptoms of PTSD. It also examined whether early changes in anger explained drug-induced change in other symptoms over time. Mixed models analysis was applied to datasets from two 12-week placebo-controlled trials of sertraline. A validated self-rating scale (DTS) was used to assess treatment efficacy. RESULTS: Sertraline was superior to placebo on 15 of 17 symptoms, especially in the numbing and hyperarousal clusters. A strong effect was found on anger from week 1, which partly explained the subsequent effects of sertraline on other symptoms, some of which began to show significantly greater response to drug than to placebo at week 6 (emotional upset at reminders, anhedonia, detachment, numbness, hypervigilance) and week 10 (avoidance of activities, foreshortened future). CONCLUSIONS: Sertraline exercises a broad spectrum effect in PTSD. Effects are more apparent on the psychological rather than somatic symptoms of PTSD, with an early modulation of anger and, perhaps, other affects, preceding improvement in other symptoms.

Estrogen replacement therapy and antidepressant response to sertraline in older depressed women.

The influence of the use of estrogen replacement therapy (ERT) on the antidepressant response to sertraline of 127 women over 60 years old was evaluated with data from two multicenter trials. At endpoint, sertraline-treated women taking ERT had significantly greater global improvement and quality of life than those not receiving ERT. Modest improvements were also observed in anxiety symptoms and cognitive functioning. The results provide preliminary evidence that ERT use (without progesterone) in older depressed women may augment the antidepressant response to sertraline in terms of quality of life and general improvement.

The effect of selective serotonin reuptake inhibitor treatment of panic disorder on emergency room and laboratory resource utilization.

BACKGROUND: While it has been well documented that patients with untreated panic disorder frequently utilize emergency room (ER) and laboratory services, no published data evaluate whether selective serotonin reuptake inhibitor (SSRI) treatment of patients with panic disorder is associated with decreased use of these services in the managed care organization setting. METHOD: A medical and pharmacy claims database representing individuals from several managed care organizations was used to analyze ER and laboratory resource utilization and cost for 120 patients with panic disorder (ICD-9-CM criteria) who received SSRI treatment. RESULTS: SSRI treatment was associated with a reduction in the mean number of ER and laboratory visits and costs in the 6-month period following therapy initiation compared with the 6-month period prior to therapy initiation (sertraline: visits, -79.5%; costs, -85.2%; p < .05; fluoxetine: visits, -25.0%; costs, -69.5%; p = NS; and paroxetine: visits, -8.6%; costs, -30.8%; p = NS). CONCLUSION: The results of the current study suggest that appropriate treatment of panic disorder may decrease unnecessary resource utilization for the medical symptoms associated with panic disorder.

Clinical and treatment response characteristics of late-life depression associated with vascular disease: a pooled analysis of two multicenter trials with sertraline.

1. The safety and efficacy of sertraline in the treatment of moderate-to-severe major depression in elderly outpatients, aged 60 years and older, with comorbid vascular disease was evaluated. 2. An analysis of the pooled results for the sertraline treatment group drawn from two prospective, randomized, double-blind studies (sertraline vs. fluoxetine, and sertraline vs. nortriptyline) was done. Patients were retrospectively categorized into one of 3 clinical groups: 1) patients with a current diagnosis of hypertension but no other past or present cardiovascular illness (HTN), 2) patients reporting a current or past history of cardiovascular illness, but excluding hypertension (VASC), and 3) patients with no hypertension, and no other comorbid vascular illness (NoVASC). Patients received 12-3. weeks of double-blind treatment with sertraline in flexible daily doses in the range of 50 - 150 mg (in the nortriptyline comparator trial) or 50 - 100 mg (in the fluoxetine comparator trial). 4. Sertraline treatment yielded comparable levels of response in all 3 groups (response criterion: CGI-much or very much improved) at treatment endpoint on both a completer analysis (HTN, 86%; VASC, 89%; NoVASC, 77%) and significantly higher response rates on a 12-week endpoint analysis (HTN, 74%; VASC, 69%; NoVASC, 58%; p < 0.05). Sertraline treatment was well-tolerated, with no between-group differences in rates of adverse events, or in discontinuation due to adverse events. Patients taking 5 or more concomitant medications showed no difference, when compared with patients taking none-or-one concomitant medication, either in rates of adverse events, or in discontinuation due to adverse events. 5. Sertraline was found to be a safe, well-tolerated, and effective as an antidepressant in elderly patients suffering from hypertension and other forms of vascular comorbidity.

Panic disorder and response to sertraline: the effect of previous treatment with benzodiazepines.

More than 50% of patients who seek psychiatric care for panic disorder have previously received prescriptions for a benzodiazepine (BZ). Research on the treatment of generalized anxiety suggests that a history of BZ exposure might decrease the efficacy and tolerability of treatment with a serotonergic anxiolytic. This study examines the effect of prior BZ treatment on the efficacy and tolerability of sertraline treatment for panic disorder. Data were pooled (N = 705) from four double-blind, placebo-controlled studies of the efficacy of sertraline for the treatment of panic. Two of the studies were 12-week fixed-dose studies with starting doses of 50 mg, whereas 2 were flexible-dose studies of 10-week duration with starting doses of 25 mg. The effect of study treatment on the frequency of panic attacks, Clinical Global Impressions (CGI) Improvement Scale, and tolerability was examined for patients with or without prior BZ treatment. The efficacy of sertraline was not affected by prior treatment with BZs. The mean endpoint reduction in panic attack frequency was identical in patients with or without prior BZ use: 79% vs. 80% (not significant). A history of good versus poor response to prior BZ treatment did not significantly influence CGI responder rates for sertraline-treated patients (67% vs. 61%, respectively). Sertraline CGI responder rates were significantly greater than placebo response, which was 47% for the good-response prior-BZ subgroup (p = 0.007), and 36% for the poor-response BZ subgroup (p = 0.013). Placebo response was lower in patients with any prior BZ use by 10% on an intent-to-treat last-observation-carried-forward analysis (p = 0.106) and by 15% on a completer analysis (p = 0.045). Prior BZ use did not influence either rates of adverse events or discontinuation rates within the first 3 weeks in patients treated with either sertraline or placebo. Sertraline is both well-tolerated and has significant efficacy in patients with panic disorder, including the subset of patients with panic disorder who have previously been treated with BZs.

The efficacy of sertraline in panic disorder: combined results from two fixed-dose studies.

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.

A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients.

BACKGROUND: There has been a paucity of well-designed studies comparing selective serotonin reuptake inhibitor (SSRI) medications in the treatment of depression in the elderly. This multicenter study was designed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly outpatients. A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function. METHOD: Two hundred thirty-six outpatients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being randomly assigned to 12 weeks of double-blind, parallel-group treatment with flexible daily doses of either sertraline (range, 50-100 mg) or fluoxetine (range, 20-40 mg). Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings. Secondary outcome assessments included clinician- and patient-rated measures of depression symptoms and factors, cognitive functioning, and quality of life, as well as plasma drug concentrations, which were correlated with clinical response. RESULTS: Both drugs produced a similarly positive response on the primary efficacy measures, with 12-week responder rates of 73% for sertraline and 71% for fluoxetine. Sertraline-treated patients showed statistically greater cognitive improvement on several measures. Both drugs were safe and well tolerated. CONCLUSION: Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly outpatients. Differences in cognitive performance effects deserve further investigation.

Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life.

OBJECTIVE: This study was designed to evaluate the comparative efficacy and safety of sertraline and nortriptyline for the treatment of major depressive disorder in older adults. METHOD: A double-blind, parallel group design was used to compare 210 outpatients, 60 years of age and older, who met DSM-III-R criteria for major depressive episode and had a minimum Hamilton Depression Rating Scale score of 18. The patients were randomly assigned to 12 weeks of treatment with either sertraline (50-150 mg/day) or nortriptyline (25-100 mg/day). RESULTS: The safety profiles of the two treatments were similar except that nortriptyline treatment was associated with a significant increase in pulse rate, whereas sertraline was associated with a nonsignificant decrease. Efficacy of both drugs was similar for both treatments at all time points, with 71.6% (N=53 of 74) of the sertraline-treated patients and 61.4% (N=43 of 70) of the nortriptyline-treated patients achieving responder status by week 12. Time to response was also similar, with more than 75% of the improvement in scores on the Hamilton depression scale having occurred by week 6. Secondary efficacy measures (posttreatment measures of cognitive function, memory, and quality of life) revealed a significant advantage for sertraline treatment. CONCLUSIONS: Primary efficacy measures showed sertraline and nortriptyline to be similarly effective. With secondary outcome measures there was consistent evidence of an advantage for the sertraline-treated group. The clinical impact of these measures on the long-term well-being of elderly depressed patients should be examined in a study of maintenance treatment.

Sertraline treatment of panic disorder: response in patients at risk for poor outcome.

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.

Comparative efficacy of sertraline vs. fluoxetine in patients age 70 or over with major depression.

Using data from a larger 12-week clinical trial, the authors evaluated the comparative efficacy and safety of sertraline (n=42) and fluoxetine (n=33) in patients over age 70 with a diagnosis of major depressive disorder. Similar improvement on measures of depression, including remission of depressive symptoms, was evident, although significantly more sertraline-treated patients achieved a criterion clinical response. Significantly greater improvement for the sertraline group was apparent on the Digit Symbol Substitution Test, but not on two other measures of cognitive functioning. Although there was no difference in the rate of adverse events experienced, fluoxetine-treated patients lost significantly more body weight over the 12-week trial than did sertraline-treated patients, whereas the latter group exhibited significantly more "shaking. "

Comparative efficacy and safety of sertraline versus nortriptyline in major depression in patients 70 and older.

BACKGROUND: Few randomized, double-blind studies that examine antidepressant treatment in patients 70 years and older are available. To provide additional data on the safety and efficacy of antidepressants in this rapidly growing population segment, a subgroup analysis of a larger sertraline vs. nortriptyline elderly depression treatment study was performed. METHODS: Outpatients (N = 76) who met DSM-III-R criteria for major depression with a minimum Hamilton Depression Rating Scale (HAM-D) severity score of 18 were randomized to 12 weeks of flexible dose treatment with sertraline (50-150 mg) or nortriptyline (25-100 mg). RESULTS: Both treatments significantly improved depression as measured by the HAM-D and Clinical Global Impression scales. At Weeks 10, 12, and endpoint, sertraline demonstrated a significantly greater reduction in depression severity compared to nortriptyline as measured by improvement on the 24-item HAM-D (mean adjusted change score of 14.8 vs. 7.6, respectively, at Week 12; p = .001). Sixty-five percent of sertraline-treated patients were responders by Week 12 (50% or greater reduction from baseline in 24-item HAM-D score) compared to 26% of nortriptyline-treated patients (p < .05). Sertraline treatment had a significantly more positive effect, when compared to nortriptyline, across almost all associated measures of cognitive function, energy, anxiety, and quality of life and was better tolerated than nortriptyline, with a lower attrition rate/side effect burden. CONCLUSION: The efficacy advantage of sertraline appeared to be even greater in this subgroup of older patients drawn from a larger treatment study of depression that included elderly individuals over the age of 60.

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

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

Methodologies and outcomes from the sertraline multicenter flexible-dose trials.

This article summarizes the results of a combined analysis from two identical multicenter clinical trials that investigated the efficacy and safety of sertraline versus placebo for treating panic disorder. Patients with panic disorder who were treated with sertraline had a statistically significant reduction in the mean number of panic attacks per week (the primary efficacy measure) as compared with placebo (4.8 vs. 2.5, p < .001). Sertraline-treated patients also showed greater improvement that was statistically significant on several ratings of panic disorder symptomatology and functioning. The design characteristics, clinical rating measures, and outcome measures in these trials included most of the features deemed essential by Shear and Maser (1994) in their summary of the NIMH Consensus Conference for the development of standardized assessments for panic disorder. This suggests that the NIMH Consensus Conference played a key role in developing successful multicenter pharmacological treatment studies, such as this one that ultimately demonstrated that sertraline was an effective treatment for panic disorder.