Efficacy and response time to sertraline versus fluoxetine in the treatment of unipolar major depressive disorder

BACKGROUND: Few studies have compared the treatment efficacy of the 2 selective serotonin reuptake inhibitors sertraline and fluoxetine. METHOD: A randomized, single-blind, parallel-group study of 10 weeks' duration comparing the efficacy of sertraline, 50 mg/day; sertraline, 100 mg/day; and fluoxetine, 20 mg/day, was conducted in 44 psychiatric outpatients with DSM-IV unipolar major depressive disorder. Antidepressant dosages were doubled at 6 weeks for subjects who had not achieved remission. Primary outcome measurements included the 21-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions-Improvement scale (CGI-I), with scores of < or = 7 on the HAM-D and < or = 2 on the CGI-I representing a positive treatment response, i.e., remission. RESULTS: At 4 weeks, significant differences in rate of positive treatment response were noted, with 0% for sertraline, 50 mg; 46% for sertraline, 100 mg; and 31% for fluoxetine, 20 mg (p = .023). At 6 weeks, positive treatment response rates were 21%, 43%, and 31% for subjects taking 50 mg of sertraline, those taking 100 mg of sertraline, and those taking 20 mg of fluoxetine, respectively, with treatment groups no longer differing significantly from each other. In subjects for whom antidepressant dose was doubled at week 6, response rates at week 10 (4 weeks on increased dose) were 40% for sertraline, 100 mg; 43% for sertraline, 200 mg; and 55% for fluoxetine, 40 mg. CONCLUSION: Subjects taking sertraline, 100 mg, and fluoxetine, 20 mg, demonstrated an earlier treatment response compared with subjects taking sertraline, 50 mg. For patients without a positive response at 6 weeks, an increased antidepressant dose resulted in remission for a substantial proportion of patients when assessed 4 weeks later.     

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.     

Effect of concurrent anxiety on response to sertraline and imipramine in patients with chronic depression

Anxiety commonly complicates the clinical presentation of depression and has been associated with poorer long-term outcome, but little information is available on the clinical correlates, and comparative effect on treatment response, of subsyndromic or secondary anxiety. Patients diagnosed with chronic major or double depression were randomized to 12 weeks of double-blind treatment with either sertraline or imipramine in a 2:1 ratio. A high anxiety subgroup was operationally defined by a HAM-D anxiety/somatization factor score > or = 7. The effect of study treatment was measured utilizing the HAM-D, CGI, HAM-D anxiety/somatization factor, as well as a quality of life measure (Q-LES-Q) and a measure of psychosocial functioning (the MOS-SF-36). Two hundred nine patients were treated with imipramine and 426 patients were treated with sertraline. Thirty-six percent of the total met criteria for the high anxiety subgroup. According to Kaplan-Meier probability estimates, patients with significant concurrent anxiety symptoms were more likely to respond by 12 weeks (66.4%) than those without significant anxiety symptoms (54.2%). There was no significant difference in response rates for sertraline vs. imipramine. Both drugs were effective at treating high baseline levels of anxiety, with 60% of sertraline patients and 58% of imipramine patients having 50% or greater reduction from baseline in HAM-D anxiety/somatization factor scores, and only 4.6% and 9.9%, respectively, reporting treatment-emergent worsening in anxiety at study endpoint. Despite the chronicity of depressive illness, acute treatment with both sertraline and imipramine significantly improved psychosocial and quality of life measures. High baseline levels of anxiety did not reduce overall antidepressant response but did somewhat delay the onset of response to sertraline or imipramine in patients with chronic depression.     

Acute antidepressant response to fluoxetine and sertraline in psychiatric outpatients with psychomotor agitation

INTRODUCTION: Sertraline and fluoxetine have different pharmacologic and pharmacokinetic profiles, which may be of clinical relevance in the determination of treatment response in different subtypes of depression. OBJECTIVE: To analyse the efficacy of sertraline and fluoxetine in a subgroup of 78 patients with evidence of significant psychomotor agitation (HAM-D item 8 &#104 1 and HAM-D item 9 &#83 2 at study entry) in a 6-week study comparing sertraline (50 - 100 mg/day) and fluoxetine (20 - 40 mg/day) for the treatment of major depression in 286 psychiatric outpatients. RESULTS: The proportion of patients with psychomotor agitation responding ( &#83 50% reduction HAM-D score) at last visit was significantly ( P < 0.05) higher in the sertraline group than in the fluoxetine group (62% vs 39%, respectively). Most of the secondary efficacy parameters showed significantly ( P &#104 0.05) greater improvement in the sertraline treatment group at last visit: HAM-D &#104 8, HAM-D total score, HAM-D anxiety/somatization factor, HAM-D weight factor, HAM-A total score, CGI-S, Raskin Depression score, and Covi Anxiety score. CONCLUSION: The findings of this retrospective data analysis suggest that fluoxetine may be a less efficacious antidepressant than sertraline in patients with psychomotor agitation.     

Sertraline is more effective than imipramine in the treatment of non-melancholic depression: results from a multicentre,randomized study

The acute treatment efficacy, tolerability, and effects on health-related quality of life of sertraline (50-200 mg/day) versus imipramine (75-225 mg/day) were compared in outpatients with non-melancholic depression. The study employed an open-label, parallel-group design. One hundred and sixteen patients were randomized to receive sertraline and 123 to receive imipramine for 8 weeks. In the intent-to-treat (ITT), last-observation-carried-forward (LOCF) analysis, sertraline produced statistically significantly greater improvements in depressive (21-item Hamilton Depression Rating Scale [HAM-D(21)] scores of 24.9 and 24.4 were reduced to 10.3 and 13.1 at endpoint, P<.005) and anxiety symptoms (Hamilton Anxiety Rating Scale [HAM-A] scores of 21.8 and 21.9 were reduced to 9.5 and 13.9, P<.01), as well as in response (69.0% versus 53.7% at endpoint, P=.016) and remission rates (51.3% versus 38.0% at endpoint, P=.041) from week 4 onwards compared with imipramine. The proportion of patients who were 'very much improved' or 'much improved' (Clinical Global Impressions Scale of Improvement [CGI-I] score of 1 or 2) was significantly higher at endpoint in the sertraline group (76.1%) than in the imipramine group (62.8%) (P=.028). At week 8, patients in both treatment groups showed clear improvements in quality of life, although nonstatistically significant differences were evident in the quality of life of sertraline- versus imipramine-treated patients. Sertraline was significantly superior in tolerability with less discontinuations due to adverse events (10.3%) compared with the imipramine group (24.4%) (P=.004). It was concluded that sertraline is more effective than imipramine in the acute treatment of depressive and anxiety symptoms in patients with non-melancholic depression.     

A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients.

Depression is associated with considerable morbidity and mortality. As depressive disorders carry a high risk of relapse, treatment strategies include the use of a 6-month continuation period after resolution of the acute episode. Tolerability is of major importance when determining compliance and outcome during long-term therapy. Due to the superior tolerability profile of the selective serotonin reuptake inhibitors (SSRIs) over the older tricyclic antidepressants (TCAs), the former may be more suitable for extended therapy. Comparative studies have not shown differences between the SSRIs in terms of efficacy, but side-effect profiles may vary. A multicenter, double-blind, comparative study of sertraline and fluoxetine was carried out in outpatients fulfilling DSM-III-R criteria for major depressive disorder. Patients were randomised to receive sertraline (50-150 mg, n = 118) or fluoxetine (20-60 mg, n = 120) for 24 weeks. Assessments for depression (HAM-D, HAD, CGI-I, CGI-S), anxiety (Covi), sleep (Leeds Sleep Evaluation scale) and quality of life (SIP) were made at study entry and at weeks 2, 4, 8, 12, 18 and 24. All adverse events were recorded to allow evaluation of tolerability. In total, 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group. Side effects were responsible for the premature treatment withdrawal of seven (6%) sertraline patients and 12 (10%) fluoxetine patients. Two-hundred and thirty-four patients were included in an ITT analysis up to last visit (116 sertraline, 118 fluoxetine). At study endpoint, both treatments produced a significant improvement over baseline on all efficacy variables (P < 0.001). Although the magnitude of global changes in depression, anxiety, and quality of life was larger with sertraline than fluoxetine, none of the between-group differences reached statistical significance. However, significant differences in favour of sertraline were observed for individual HAM-D items including item 4 (insomnia onset) (P = 0.04), item 9 (agitation) (P = 0.02), and item 13 (general somatic symptoms) (P = 0.008). In addition, sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest, emotional behaviour and ambulation. Both sertraline and fluoxetine were well tolerated with no significant differences between treatments.     

A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group

BACKGROUND: More treatment options for bipolar depression are needed. Currently available antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers appear to be less effective in treating depression than mania. Preliminary data suggest that lamotrigine, an established antiepileptic drug, may be effective for both the depression and mania associated with bipolar disorder. This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression. METHODS: Outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200 mg/day) or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly visit. RESULTS: Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared with placebo. Improvements were seen as early as week 3. Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures. The proportions of patients exhibiting a response on CGI-I were 51%, 41%, and 26% for lamotrigine 200 mg/day, lamotrigine 50 mg/day, and placebo groups, respectively. Adverse events and other safety results were similar across treatment groups, except for a higher rate of headache in the lamotrigine groups. CONCLUSION: Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression.     

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.     

Gender differences in treatment response to sertraline versus imipramine in patients with nonmelancholic depressive disorders

There is evidence of gender differences in depressive disorders in terms of epidemiology and clinical manifestations. However, few studies have addressed the gender differences in terms of antidepressant treatment response in clinical practice. The aim of this study was to examine gender differences in the acute antidepressant response to sertraline and imipramine in nonmelancholic depressive disorders. A total of 239 patients with nonmelancholic major depression or dysthymia (DSM-III-R) and a score of >/=18 at baseline on the Hamilton Depression Rating Scale (HAM-D) were randomised in a 1:1 ratio treatment with flexible doses of sertraline (50-200 mg/day) or imipramine (75-225 mg/day) for 8 weeks in a multicenter, randomised, open-labeled, parallel group comparative trial. Depressive and anxiety symptoms were assessed using the HAM-D and the Hamilton Anxiety Rating Scale (HAM-A). Using HAM-D criteria, women were significantly more likely to respond to sertraline than to imipramine (72.2% vs. 52.1%, P=.008), whilst men respond similarly to sertraline and to imipramine (56.5% vs. 59.3%, P>.05). Response analysis based on HAM-A shows similar results (women: 68.9% vs. 43.6%, P=.001; men: 56.5% vs. 51.9%, P>.05). Women taking sertraline show statistically significant higher reductions in HAM-D, HAM-A, and in CGI-S than women taking imipramine. The proportion of women who dropped out due to adverse events was much lower in sertraline than in imipramine (10.9% vs. 27.8%, P=.006), with no differences between treatments in men (8.3% vs. 11.5%, P>.05). It was concluded that sertraline is more effective and better tolerated than imipramine in the acute treatment of nonmelancholic depressive disorders in women, whereas men responded similarly to sertraline and to imipramine.     

Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder

BACKGROUND: Escitalopram is a highly selective serotonin reuptake inhibitor (SSRI). It is the therapeutically active S-enantiomer of citalopram. It has been shown, compared with placebo, to be an effective and well-tolerated treatment for major depressive disorders (MDD) in both primary and specialist care settings. A recent meta-analysis has found that escitalopram-treated patients showed significant higher response rates and increased mean change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores at weeks 1 and 8 compared with citalopram-treated patients. Each of these active drugs shares similar safety profiles. Although the efficacy of newer antidepressants has been well established for the treatment of mild-to-moderate depression, there are very few studies concerning severe depression. OBJECTIVE: To determine if escitalopram is more effective than citalopram in patients with severe depression. METHODS: Data were pooled from three different clinical trials, each similar in design and inclusion/exclusion criteria, primary endpoints and assessment schedules. This analysis was exhaustive because it included all trials in which the maximum dose for escitalopram (20 mg) could be administered. According to the cut-off point taken to define severe depression based on the MADRS total score ( 30), 506 patients were considered as severely depressed patients and so included in this analysis. Among them, 169 received escitalopram, 171 received citalopram and 166 received the placebo. The primary efficacy parameter was the mean change from baseline to end of treatment in MADRS total score between escitalopram and citalopram groups, based on last-observation-carried-forward method. The change from baseline to endpoint of the Hamilton rating scale for Depression (HAM-D) and the Clinical Global Impression of Improvement and Severity (CGI-I and CGI-S) were also analysed as secondary criteria. Clinical response was defined by at least a 50% reduction in baseline MADRS total score or by at least a 60% reduction in baseline HAM-D score or by a score of 1 (very much improved) on the CGI scale, and remission by a MADRS total score pound 12. RESULTS: Results showed that the mean change from baseline in the MADRS total score was significantly higher in the escitalopram group compared with the citalopram group (- 17.3 vs - 13.8 respectively, p=0.003). This significant difference was observed as early as week 1 (p=0.01). Response rates were significantly higher for escitalopram than for citalopram (56% vs 41% respectively, p=0.007). A borderline significant difference was found for remission rate in the observed-cases analysis (43% vs 33% respectively, p=0.07). Analyses of the HAM-D, CGI-I and CGI-S scores revealed consistent results. DISCUSSION: This study shows that the new SSRI escitalopram has better efficacy in the treatment of severe depression than citalopram, its racemic parent. Mean differences between treatments groups were in favour of escitalopram for all scales. The benefits of escitalopram compared with citalopram, as demonstrated by both magnitude of effect and time of onset, are superior to the benefits of citalopram, an antidepressant drug with proven efficacy. This evidence clearly supports the use of escitalopram as a legitimate first-line treatment for MDD.     

Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind,placebo-controlled study

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 相似文献   

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.     

Sertraline as monotherapy in the treatment of psychotic and nonpsychotic depression

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.     

A preliminary open-label study of zonisamide treatment for bipolar depression in 10 patients

OBJECTIVE: The purpose of this study was to investigate the effectiveness of zonisamide in the treatment of bipolar depression. METHOD: Ten patients with DSM-IV bipolar disorder, depressed phase, who had either not tolerated or not responded to previous treatments were given zonisamide in this add-on open-label study. Zonisamide treatment was started at 100 mg/day and increased by 100 mg every 2 weeks to a maximum of 300 mg/day in divided doses (b.i.d. or t.i.d.). Subjects underwent weekly visits at which they were administered the 17-item Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), and Clinical Global Impressions scale (CGI). Every 2 weeks, subjects also underwent laboratory tests, a urine examination, and a verbal memory test. Outcome measures were analyzed with repeated-measures analysis of variance. RESULTS: Eight subjects completed all 8 weeks of the study. Two subjects completed more than 4 weeks of the study, and their data were analyzed using the last observation carried forward. Bipolar depression subjects had a significant reduction in HAM-D scores (p < .001) and in CGI-Improvement (CGI-I) scores (p < .001). Five of 8 subjects who completed all 8 weeks of the study had more than a 50% decrease in HAM-D scores and were rated much improved on the CGI-I at the end of 8 weeks of treatment. There was no significant drug effect on YMRS scores, weight, or verbal memory. CONCLUSION: Zonisamide may be a useful drug in the treatment of bipolar depression. Further controlled clinical trials are needed.     

Sertraline versus imipramine treatment of comorbid panic disorder and major depressive disorder

OBJECTIVE: To evaluate the efficacy and tolerability of sertraline and imipramine in patients with comorbid panic disorder and major depressive disorder. METHOD: Outpatients meeting a DSM-IV diagnosis of panic disorder and concurrent major depressive disorder were randomized in a 2:1 ratio to 26 weeks of double-blind treatment with either sertraline, in daily doses of 50 to 100 mg, or imipramine, in daily doses of 100 to 200 mg. Primary outcome measures were panic attack frequency (derived from patient diaries) and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: 138 patients were treated with sertraline (76% female; mean age = 40 years) and 69 with imipramine (70% female; mean age = 40 years). The symptoms of both major depressive disorder and panic disorder responded significantly and equivalently to both drugs. Endpoint improvement with sertraline versus imipramine, respectively, on the MADRS was 11.1 +/- 10.8 versus 11.2 +/- 10.4, and on the Clinical Global Impressions-Improvement scale (CGI-I) was 2.1 +/- 1.3 versus 2.4 +/- 1.6. Among study completers, CGI-I responder rates were 88% with sertraline and 91% with imipramine. Treatment outcome was concordant for both diagnoses in approximately 70% of patients and discordant in approximately 30%. Overall, sertraline was significantly better tolerated with significantly fewer discontinuations due to adverse events (11% vs. 22%; chi(2) = 4.39, df = 1, p =.04). CONCLUSION: Both sertraline and imipramine were found to be highly effective treatments for both major depressive disorder and panic disorder, with sertraline showing significantly greater tolerability and compliance during long-term treatment than imipramine.     

A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression.

BACKGROUND: Despite the high prevalence of depression in elderly patients, few well-designed, placebo-controlled studies of antidepressants have been conducted in this population. This masked, placebo-controlled trial assessed the efficacy and safety of venlafaxine and fluoxetine in depressed patients older than 65 years. METHOD: Three hundred patients were randomly assigned to treatment with venlafaxine immediate release ([IR]; N = 104), fluoxetine (N = 100), or placebo (N = 96) in an eight-week trial. Venlafaxine doses were titrated from 37.5 to 225 mg per day and fluoxetine doses were titrated from 20 to 60 mg per day, as necessary, over 29 days. Efficacy variables included the 21-item Hamilton Depression Rating Scale (HAM-D21) total score, HAM-D21 depressed mood item score, scores on the Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity of Illness (CGI-S) and Improvement (CGI-I) scales, and rates of response (based on change from baseline HAM-D or MADRS score or CGI-I score) and remission (HAM-D17 < or =7). For the purposes of this report, efficacy analyses are focused on the HAM-D21 total score. Safety assessments included monitoring of adverse events (AEs), physical examinations, vital signs assessments, laboratory determinations, and electrocardiograms. RESULTS: In all three of the treatment groups, there was a significant reduction at week 8 compared with the baseline HAM-D21 total score. However, there were no significant differences among the three treatment groups on the change in HAM-D21, MADRS, or CGI scores from baseline to week 8. There was no statistically significant difference in the proportion of remitters at the last on-therapy visit. The incidence of individual AEs was higher in the venlafaxine group (27%) compared with patients taking fluoxetine (19%) or placebo (9%). CONCLUSION: In this study, there was no significant difference in efficacy among placebo, venlafaxine, and fluoxetine for the treatment of depression.     

Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison

OBJECTIVE: Several classes of medications have demonstrated efficacy in panic disorder, but direct comparison of 2 proven treatments is still uncommon. The purpose of this study was to compare sertraline and paroxetine in the acute treatment of panic disorder. METHOD: Adult outpatients with panic disorder with or without agoraphobia (DSM-IV and ICD-10 criteria) were randomly assigned in double-blind fashion to 12 weeks of treatment with flexible doses of sertraline (titrated up to 50-150 mg/day; N = 112) or paroxetine (titrated up to 40-60 mg/day; N = 113). Patients were then tapered off medication over 3 weeks. The primary analysis was a noninferiority analysis of Panic and Agoraphobia Scale (PAS) scores. Secondary measures included panic attack frequency and the Clinical Global Impressions-Improvement scale (CGI-I) (with responders defined as those with a CGI-I score < or = 2). Data were collected from January 2000 to June 2001. RESULTS: Sertraline and paroxetine were associated with equivalent levels of improvement on the PAS total score, as well as on all secondary outcome measures. Eighty-two percent of patients taking sertraline versus 78% of those taking paroxetine were CGI-I responders at endpoint. Numerically more patients on paroxetine treatment compared with sertraline treatment discontinued due to adverse events (18% vs. 12%; NS), and a significantly higher proportion of paroxetine patients showed > or = 7% weight gain (7% vs. < 1%; p <.05). During the taper period, the proportion of panic-free patients increased by 4% with sertraline but decreased by 11% with paroxetine (p <.05). CONCLUSION: Sertraline and paroxetine had equivalent efficacy in panic disorder, but sertraline was significantly better tolerated and was associated with significantly less clinical worsening during taper than paroxetine.     

Assessing full remission

The 17-item Hamilton Rating Scale for Depression (HAM-D17) has been used for 4 decades as the "gold standard" instrument to assess the severity of depression and response to therapy in clinical research. The clinical utility of the HAM-D17 is hampered, in part, by the length of time required to administer the interview and by concern about a lack of inter-rater reliability. Several groups have developed shorter versions of the HAM-D17 for use in clinical practice. However, despite extensive research highlighting the importance of achieving full remission in minimizing the risk of relapse and recurrence, these shortened questionnaires have not been validated for the task of distinguishing between remission and response. A shortened form of the HAM-D17 with cut-off scores for full remission would offer a useful tool that physicians could readily employ in clinical practice. On the basis of the responses of a sample of 292 patients with major depression who received standard clinical treatment at a tertiary university affiliated hospital (Depression Clinic, Centre for Addiction and Mental Health, Toronto Ont.) we derived a shortened version of the HAM-D. Seven items with the greatest frequency of occurrence and sensitivity to change with treatment were identified and designated as the Toronto HAM-D7. A score of 3 or less on the Toronto HAM-D7 was found to correlate with the 17-item HAM-D definition of full remission (i.e., score of 7 or less).     

Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression, but the rates, timing, and baseline predictors of remission in "real world" patients are not established. The authors' primary objectives in this study were to evaluate the effectiveness of citalopram, an SSRI, using measurement-based care in actual practice, and to identify predictors of symptom remission in outpatients with major depressive disorder. METHOD: This clinical study included outpatients with major depressive disorder who were treated in 23 psychiatric and 18 primary care "real world" settings. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks. The clinicians were assisted by a clinical research coordinator in the application of measurement-based care, which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures. Remission was defined as an exit score of or=50% in baseline QIDS-SR score. RESULTS: Nearly 80% of the 2,876 outpatients in the analyzed sample had chronic or recurrent major depression; most also had a number of comorbid general medical and psychiatric conditions. The mean exit citalopram dose was 41.8 mg/day. Remission rates were 28% (HAM-D) and 33% (QIDS-SR). The response rate was 47% (QIDS-SR). Patients in primary and psychiatric care settings did not differ in remission or response rates. A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment. Participants who were Caucasian, female, employed, or had higher levels of education or income had higher HAM-D remission rates; longer index episodes, more concurrent psychiatric disorders (especially anxiety disorders or drug abuse), more general medical disorders, and lower baseline function and quality of life were associated with lower HAM-D remission rates. CONCLUSIONS: The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials. The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results.     

Sertraline effects in adolescent major depression and dysthymia: a six-month open trial.

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.