A placebo-controlled, randomized withdrawal study of sertraline for panic disorder in Japan

The objective of this double-blind, placebo-controlled randomized withdrawal study was to evaluate the efficacy and safety of sertraline for 8 weeks in treating Japanese patients with DSM-IV panic disorder. Patients (n=394) were initially treated with 8 weeks of open-label sertraline followed by 8 weeks of double-blind treatment with either sertraline (50-100 mg/day) or placebo. Responders during the open-label phase were eligible to be entered into the double-blind phase. Two hundred and forty patients were entered to the double-blind phase and randomly assigned to receive sertraline (n=119) or placebo (n=121). On the primary efficacy measure (relapse), there was no significant difference between the two treatment groups (sertraline 10.1%; placebo 13.2%). However, the frequency of panic attacks was significantly (P=0.012) lower for sertraline compared to placebo. The proportion of sertraline-treated patients who met response criteria (Clinical Global Impression-Improvement Scale score of 1 or 2) at the end of double-blind phase treatment was also significantly (P=0.003) higher for sertraline (89.9%) compared to placebo (74.4%). Panic Disorder Severity Scale total score was significantly (P=0.012) lower in the sertraline group compared to the placebo group. Adverse events during acute treatment were consistent with the known adverse event profile of sertraline, and the incidence of adverse events during the double-blind phase treatment was not different between sertraline and placebo.     

Double-blind clinical trial of sertraline treatment for alcohol dependence

Clinical studies that have evaluated serotonergic medications to reduce alcohol consumption have yielded conflicting results. These studies primarily treated patients with alcohol dependence, excluding those with a current depressive disorder, in an effort to differentiate any medication effects directly on drinking from those on mood. Yet despite the exclusion of current depression, a group of alcohol-dependent patients who are not depressed can be highly heterogeneous. For example, this subgroup can include those with a lifetime depressive disorder. If these patients were more sensitive to serotonergic medications than patients without a lifetime depressive disorder, medication effects in a subgroup of patients who were not depressed could be obscured. Thus, the purpose of this study was to examine the efficacy of sertraline for treating alcohol dependence in patient groups that were differentiated by the presence or absence of lifetime depression. This study examined the effectiveness of sertraline (200 mg/day) or placebo for 14 weeks in 100 alcohol-dependent subjects with (N = 53) or without (N = 47) a lifetime diagnosis of comorbid depression. Sertraline treatment seemed to provide an advantage in reducing drinking in alcohol-dependent patients without lifetime depression, illustrated best with a measure of drinking frequency during treatment. However, sertraline was no better than placebo in patients with a diagnosis of lifetime comorbid depression, and current depression did not change the results. Treatment with selective serotonin reuptake inhibitors may be useful in alcohol-dependent patients who are not depressed. Subtyping those with alcohol dependence on the basis of the absence versus the presence of a lifetime depressive disorder may help to resolve conflicting findings in the literature on the treatment of alcohol dependence with serotonergic medications.     

The antidepressant effect of sertraline is not enhanced by dose titration: results from an outpatient clinical trial

A previous report suggested that 5 weeks of continued treatment with 20 mg of fluoxetine was approximately as effective as double-blind titration to a dose of 60 mg in patients who had failed to respond to 3 weeks of initial treatment at 20 mg. The current study was undertaken to evaluate whether 150 mg of sertraline was any more effective than 50 mg in treating depressed patients who were non-responders at 3 weeks. Ninety-one outpatients with DSM-IV major depressive disorder who had a 17-item Hamilton Depression Rating Scale (HAM-D) score > or = 18 were treated with open label sertraline for 3 weeks. Patients who did not achieve remission (defined as 17-item HAM-D total score < or = 8 by week 3) were then randomized to 5 more weeks of double-blind treatment with either 50 mg of sertraline or immediate titration to 150 mg of sertraline. Efficacy was assessed at each visit with the HAM-D, Clinical Global Impressions (CGI)-severity and improvement scale, and the Hopkins Symptom Checklist. There were no significant between-group differences in clinical or demographic features at baseline for the three treatment groups. After 3 weeks of open-label treatment, 16 patients were not randomized, of whom 11 (69%) met responder criteria. The remaining patients were randomized, double-blind, to 50 mg of sertraline (n = 37; HAM-D = 19.2 +/- 5.0) or 150 mg of sertraline (n = 38; HAM-D = 18.4 +/- 5.0). PROC-Mixed analyses found no significant difference in slopes for any outcome measure when comparing 50 mg and 150 mg sertraline treatment groups. At week 8 (LOCF), the overall remission rate (HAM-D < or = 8) for 3-week non-responders was 40%, with no statistically significant between-group difference for the 50 mg versus 150 mg doses of sertraline (P > 0.10). A completer analysis yielded similar results. Adverse events were mostly mild on both doses of sertraline and led to few treatment discontinuations. The results suggest that for most patients continued treatment with 50 mg dose of sertraline yields a rate of antidepressant response that is comparable to what is achieved by dose escalation from 50 mg to 150 mg of sertraline after 3 weeks of treatment. While some patients clearly benefit from higher doses, the results of the current study are consistent with the lack of any evidence for a dose-response curve with sertraline in the treatment of depression.     

Paroxetine: an update of its use in psychiatric disorders in adults

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or =60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.     

Spotlight on paroxetine in psychiatric disorders in adults

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or = 60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.     

Do antidepressants selectively suppress spontaneous (unexpected) panic attacks? A replication

The purpose of this study was to test the following interrelated hypotheses in a larger sample by attempting to replicate supportive results from a small therapeutic study: (1) the pathogenesis of panic disorder includes at least two identifiable components: a biological component represented by spontaneous (unexpected) panic attacks, and a cognitive component represented by situational attacks and especially by phobias; (2) these components respond differently to treatment; (3) many biological processes respond to an effective intervention in proportion to their deviance from "normal" prior to treatment ("Law of Initial Value"); and (4) the response of spontaneous panic attacks to an effective treatment conforms to that model. Previously, the authors reanalyzed an 8-week therapeutic study of panic disorder that included groups treated with placebo and with imipramine (225 mg daily). The criteria of response were spontaneous panic attacks (biological component), situational panic attacks (both components), and agoraphobia ratings (cognitive component). The analyses compared the regression lines for posttreatment status on pretreatment status in the imipramine and placebo groups. The effect of imipramine on spontaneous panic attacks fitted the hypothesized model: the pre-post slope in the placebo group was approximately 1 (45 degrees), whereas the slope in the imipramine group was approximately 0. There was no significant difference in pre-post slopes between the imipramine and placebo groups for situational panic attacks or agoraphobia ratings. For this report, the authors applied the same approach to another larger data set from a study using a similar design, but a different antidepressant. In this multicenter, double-blind study, patients with panic disorder were randomly assigned to receive 10 weeks of treatment with placebo (N = 78) or fluoxetine 10 mg (N = 84) or 20 mg (N = 81) daily. Spontaneous and situational panic attacks were registered in a daily diary, and agoraphobia was rated at each visit. Using baseline and endpoint data, fluoxetine had a statistically significant, dose-dependent, suppressive effect on spontaneous panic attacks, as measured by the pre-post slopes in the three treatment groups. The placebo group showed some response (slope = 0.69). There were no significant drug effects on situational panic attacks. On ratings of agoraphobia, the slopes in the placebo and the fluoxetine 20 mg groups did not differ, but the slope in the fluoxetine 10 mg group was significantly less than that in the placebo group, suggesting a therapeutic drug effect on agoraphobia only at the lower dose. These results are consistent with the stated hypotheses. They suggest that the therapeutic effects of antidepressants on panic disorder may be due primarily to the specific suppression of spontaneous panic attacks among patients with high baseline pathologic findings. Implications of these results for concepts of pathogenesis, clinical practice, and therapeutic research regarding panic disorder are discussed.     

Escitalopram (S‐Enantiomer of Citalopram): Clinical Efficacy and Onset of Action Predicted from a Rat Model

Abstract: Escitalopram is the active S‐enantiomer of citalopram. In a chronic mild stress model of depression in rats, treatments with both escitalopram and citalopram were effective; however, a faster time to onset of efficacy compared to vehicle treatment was observed for escitalopram‐treated (5 mg/kg/day) than for citalopram‐treated (10 mg/kg/day) rats at Week 1. To study the predictability of this observation in the clinic, we analysed 4‐week data from an 8‐week, double‐blind, randomised, placebo‐controlled, flexible‐dose study that compared escitalopram and citalopram to placebo in primary care patients with major depressive disorder (baseline Montgomery and Åsberg Depression Rating Scale (MADRS) scores ≥22 and ≤40). Since the flexible dosing started after Week 4, analysis of 4‐week data ensured that the patients received fixed doses of 10 mg/day escitalopram (155 patients), 20 mg/day citalopram (160 patients), or placebo (154 patients). The efficacy analysis showed a significantly superior therapeutic effect for escitalopram versus placebo from Week 1 onwards (observed cases) with an adjusted mean change in MADRS at Week 4 (last observation carried forward) of 2.7 points (P=0.002). By comparison, 20 mg/day citalopram did not demonstrate a statistically significant effect compared to placebo. Escitalopram was well tolerated with an adverse event profile similar to that of citalopram. The preclinical observation that escitalopram possesses a faster time to onset of efficacy than citalopram was also seen in primary care patients with major depressive disorder. Thus, escitalopram is efficacious in depression and the effect occurs earlier than for citalopram.     

Escitalopram (S-enantiomer of citalopram): clinical efficacy and onset of action predicted from a rat model

Escitalopram is the active S-enantiomer of citalopram. In a chronic mild stress model of depression in rats, treatments with both escitalopram and citalopram were effective; however, a faster time to onset of efficacy compared to vehicle treatment was observed for escitalopram-treated (5 mg/kg/day) than for citalopram-treated (10 mg/kg/day) rats at Week 1. To study the predictability of this observation in the clinic, we analysed 4-week data from an 8-week, double-blind, randomised, placebo-controlled, flexible-dose study that compared escitalopram and citalopram to placebo in primary care patients with major depressive disorder (baseline Montgomery and Asberg Depression Rating Scale (MADRS) scores > or =22 and < or =40). Since the flexible dosing started after Week 4, analysis of 4-week data ensured that the patients received fixed doses of 10 mg/day escitalopram (155 patients), 20 mg/day citalopram (160 patients), or placebo (154 patients). The efficacy analysis showed a significantly superior therapeutic effect for escitalopram versus placebo from Week 1 onwards (observed cases) with an adjusted mean change in MADRS at Week 4 (last observation carried forward) of 2.7 points (P=0.002). By comparison, 20 mg/day citalopram did not demonstrate a statistically significant effect compared to placebo. Escitalopram was well tolerated with an adverse event profile similar to that of citalopram. The preclinical observation that escitalopram possesses a faster time to onset of efficacy than citalopram was also seen in primary care patients with major depressive disorder. Thus, escitalopram is efficacious in depression and the effect occurs earlier than for citalopram.     

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

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

A placebo-controlled, randomized withdrawal study of sertraline for major depressive disorder in Japan

The objective of this double-blind, placebo-controlled, multicentre randomized withdrawal study was to evaluate the efficacy and tolerability of sertraline for 16 weeks in treating Japanese patients with major depressive disorder (MDD) who had achieved a response to 8 weeks of sertraline treatment. Patients (n=361) were initially treated with 8 weeks of open-label sertraline treatment followed by 16 weeks of double-blind treatment with either sertraline (50-100 mg/day) or placebo. Responders during the open-label phase were eligible to be entered into the double-blind phase. A total of 235 patients (65.1%) were entered to the double-blind phase and randomly assigned to receive sertraline (n=117) or placebo (n=118). A significantly (P=0.016) lower relapse rate was found for sertraline (8.5%) compared to placebo (19.5%) during the double-blind phase. Examination of time-to-relapse showed that the relapse free rate curve was significantly higher for sertraline (log-rank test, P=0.026) than placebo. Mean changes from beginning to end of the double-blind phase on measure of depressive symptoms, quality of life and global improvement also significantly favoured sertraline over placebo. Sertraline was well-tolerated, with similar adverse events as found in previous studies. These results confirm the efficacy of sertraline in preventing the relapse of MDD in Japanese patients.     

Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial*

ABSTRACT

Objective: This trial was conducted to compare the efficacy and tolerability of a fixed dose of escitalopram 10?mg/day with sertraline optimally dosed within its recommended dose range (50–200?mg/day) for the treatment of major depressive disorder.

Methods: In this multicenter trial, depressed patients (DSM?IV defined; baseline Montgomery–Asberg Depression Rating Scale [MADRS] ≥ 22) aged 18–80 years were randomly assigned to 8 weeks of double-blind treatment with escitalopram (10?mg/day) or sertraline (50–200?mg/day) following a 1?week single-blind placebo lead-in period. There was no placebo comparison arm. Sertraline was initiated at 50?mg/day, and could be increased by 50?mg/day at weekly intervals based on clinical need and tolerability at the lower dose level. The blind was maintained with matching double-blind placebo capsules for the escitalopram group. Change from baseline to endpoint in MADRS total score (last observation carried forward) was the primary efficacy measure.

Results: A total of 212 patients received double-blind medication. At week 8, the mean sertraline dosage was 144?mg/day (median = 150?mg/day). Mean changes from baseline to endpoint in MADRS scores were –19.1 and –18.4 for the escitalopram and sertraline groups, respectively. At endpoint, 75% and 70% of escitalopram- and sertraline-treated patients, respectively, were responders (≥ 50% improvement from baseline in mean MADRS scores). Both treatments were generally well tolerated; only 2% and 4% of patients prematurely discontinued escitalopram and sertraline treatment, respectively, due to adverse events.

Conclusion: No differences in efficacy were observed for fixed-dose escitalopram 10?mg/day and sertraline flexibly dosed from 50–200?mg/day. At these doses, both escitalopram and sertraline were generally well tolerated.     

Clomipramine, a better reference drug for panic/agoraphobia. I. Effectiveness comparison with imipramine

An 8-week, double-blind, flexible-dose trial comparing low doses of clomipramine (mean=50 mg) with moderate doses of imipramine (mean=113.8 mg and propanteline (active placebo), was carried out in 60 out-patients with panic disorder with or without agoraphobia. Efficacy evaluation included global, anxiety and depression rating scales, and the determination of rates of relapse over up to 10 weeks of single-blind placebo follow-up. Both tricyclics were significantly more effective than propanteline, but clomipramine tended to act faster and more consistently than imipramine on most measures. Given the degree of blindness achieved and the significantly lower doses of clomipramine, this seems a better reference drug than imipramine for clinical trials in panic/agoraphobia.     

Sertraline in panic disorder: initial treatment versus switch strategy

The study explored whether there is differential efficacy for patients with panic disorder treated with sertraline initially (primary group) versus those switched (transfer group) after intolerance or nonresponse to imipramine in the context of the open 24-week treatment phase of a long-term maintenance/discontinuation study. Similar assessment and treatment procedures were used in the 2 groups and there were no concurrent cognitive behavioral interventions. A consistent pattern suggesting decreased efficacy for the transfer treatment group (n = 11, 68 +/- 25 mg/d) compared with the primary treatment group (n = 11, 70 +/- 25 mg/d) was found on response rates, univariate repeated measures analysis of variance and within group effect sizes in intent to treat, and completer samples. These preliminary findings concord well with clinical intuition but are contrary to findings in the treatment of depression. Replication studies seem warranted.     

BDNF plasma levels after antidepressant treatment with sertraline and transcranial direct current stimulation: Results from a factorial,randomized, sham-controlled trial

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that modifies cortical excitability according to the stimulation parameters. Preclinical and clinical studies in healthy volunteers suggest that tDCS induces neuroplastic alterations of cortical excitability, which might explain its clinical effects in major depressive disorder (MDD). We therefore examined whether tDCS, as compared to the antidepressant sertraline, increases plasma brain-derived neurotrophic factor (BDNF) levels, a neurotrophin associated with neuroplasticity. Patients (n=73) with major depressive disorder were randomized to active/sham tDCS and sertraline/placebo (four groups) in this 6-week, double-blind, placebo-controlled trial. We measured BDNF plasma levels at baseline and endpoint, observing no significant changes of BDNF levels after treatment. In addition, no significant changes were observed in responders and non-responders as well as no relationships between BDNF levels and clinical and psychopathological variables related to depression. Thus, in one of the few placebo-controlled trials evaluating BDNF changes over an antidepressant treatment course, we did not observe BDNF increase regardless of clinical improvement in depressed patients. Regarding tDCS, BDNF plasma levels might not be a good candidate biomarker to evaluate depression improvement or be a predictor of response in patients treated with tDCS, as our results showed that BDNF increase was not necessary to induce clinical response. Finally, our findings do not support a relationship between BDNF and improvement of depression.     

Paroxetine with pindolol augmentation: a double-blind, randomized, placebo-controlled study in depressed in-patients.

Pindolol, a 5-HT1A autoreceptor antagonist, given in combination with selective serotonin reuptake inhibitors (SSRIs), may enhance and/or accelerate the therapeutic efficacy of SSRIs. Fifty patients, meeting ICD-10 criteria for major depressive disorder or bipolar depression, were enrolled in our randomized, placebo-controlled, double-blind trial. One group received paroxetine plus pindolol (2.5 mg t.i.d.), and the other group received paroxetine plus placebo. The proportion of patients with sustained response (>or=50% reduction of baseline HAM-D 17 score maintained until the endpoint; p=0.252) and the proportion of patients with remission (HAM-D 17 相似文献   

Treatment of depression with comorbid anxiety disorders: differential efficacy of paroxetine versus moclobemide

To compare the efficacy and tolerability of moclobemide versus paroxetine for the treatment of depression with comorbid anxiety disorders. Outpatients fulfilling DSM-III-R criteria for major depression or dysthymia and for a co-occurring comorbid anxiety disorder (panic disorder, generalized anxiety disorder or obsessive-compulsive disorder) after a 1-week run-in phase were randomly assigned to open-label moclobemide (300-600 mg/day) or paroxetine (20-40 mg/day) for 4 months. Primary criterion for response was a 50% score reduction from baseline on Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores. Mean changes in Clinical Global Impressions Severity of Illness and Improvement Scales (CGI-I) were also used to evaluate treatment response. Of the 123 patients included in the study, 65 were randomly assigned to moclobemide and 58 to paroxetine. At study end, the two treatment groups did not differ significantly in terms of proportion of responders. Treatment group differences emerged when comorbid anxiety diagnoses were considered. In patients with comorbid panic disorder, paroxetine was superior to moclobemide in improving both anxiety and depression (five patients out of 18 in the moclobemide group and nine out of 14 in the paroxetine group were rated as responders according to CGI-I, P = 0.04). Neither medication was superior in treating comorbid generalized anxiety disorder. These findings indicate that both moclobemide and paroxetine are effective for treatment of depression with comorbid anxiety disorders. However, in the subgroup with comorbid panic disorder, paroxetine is more effective than moclobemide in reducing both depressive and anxiety symptoms.     

A fixed-dose study of alprazolam 2 mg, alprazolam 6 mg, and placebo in panic disorder.

A recently reported multinational, 8-week double-blind, placebo-controlled study assessing the efficacy of alprazolam versus placebo in the treatment of panic disorder indicated significant differences favoring alprazolam. We now report the results of a three-site, 6-week, double-blind, fixed-dose study comparing alprazolam 2 mg, alprazolam 6 mg, and placebo in 94 patients with panic disorder with or without agoraphobia. Both alprazolam treatment groups (6 mg and 2 mg) improved significantly more than did the placebo treatment group on most outcome measures. Only a few statistically significant differences between the 6 mg and 2 mg alprazolam groups were discerned, although the pattern of treatment response across measures suggested a dose effect. Dropouts in the placebo group were primarily due to lack of efficacy and in the alprazolam 6 mg group were due to side effects, which may have contributed to the limited differences between groups at study end. The findings suggest that many patients may require less than 6 mg of alprazolam per day for effective treatment of panic disorder.     

The effects of sertraline on psychopathic traits

We examined whether antidepressants alter expression of psychopathic personality traits in patients with major depressive disorder (MDD). Data were collected from a double-blind, placebo-controlled 8-week trial evaluating the efficacy of sertraline (50-200 mg/day) combined with either tri-iodothyronine (T3) or matching placebo in adult outpatients with major depressive disorder. Administration of sertraline was open-label; T3/placebo was double-blind. At the baseline and week 8 visits, patients completed the short form of the Psychopathic Personality Inventory (PPI), a well-validated self-report measure assessing two major factors of psychopathy: Fearless Dominance (PPI-1) and Self-Centered Impulsivity (PPI-2). Change in PPI scores were assessed using paired t-tests for all participants who completed a baseline and postrandomization PPI. Ninety patients (84 completers and six who terminated the trial early) were eligible for the analysis. Both PPI factors changed significantly from baseline to endpoint, but in opposing directions. The mean score on PPI-1 increased significantly during treatment; this change was weakly correlated with change in depression scores. In contrast, the mean score on PPI-2 decreased significantly, but these changes were not correlated with changes in depression scores. Independent of their effects on depression, antidepressants increase adaptive traits traditionally observed in psychopathic individuals, such as social charm and interpersonal and physical boldness. Antidepressants reduce other, more maladaptive, traits associated with psychopathy, including dysregulated impulsivity and externalization.     

Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study

This 12-week, double-blind, multicenter trial evaluated the efficacy of venlafaxine extended release (ER), sertraline, and placebo in adult outpatients (N = 538) with a primary diagnosis of posttraumatic stress disorder (PTSD), as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, symptoms for 6 months or more and 17-item Clinician-administered PTSD Scale (CAPS-SX17) score of 60 or more. Patients were randomly assigned to receive placebo or flexible doses of venlafaxine ER (37.5-300 mg/d) or sertraline (25-200 mg/d) for 12 weeks or less. The primary outcome was the baseline-to-end point change in total CAPS-SX17 score (last observation carried forward). Secondary measures included CAPS-SX17 symptom cluster scores for reexperiencing/intrusion, avoidance/numbing, and hyperarousal; frequency of remission (CAPS-SX17 < or =20); and changes in Davidson Trauma Scale total score and symptom cluster scores for avoidance/numbing, hyperarousal, and reexperiencing/intrusion. Mean changes in CAPS-SX17 scores were -41.8, -39.4, and -33.9 for venlafaxine ER (P < 0.05 vs. placebo), sertraline, and placebo, respectively. Mean changes for venlafaxine ER, sertraline, and placebo in CAPS-SX17 cluster scores were -13.0, -11.7, and -11.0 for reexperiencing; -17.1, -16.8, and -13.7 (P < 0.05 both active treatments vs. placebo) for avoidance/numbing; and -11.8, -10.9, and -9.2 (P < 0.05 venlafaxine vs. placebo) for hyperarousal. Week 12 remission rates were venlafaxine ER 30.2% (P < 0.05 vs. placebo), sertraline 24.3%, and placebo 19.6%. The venlafaxine ER group had significantly better Davidson Trauma Scale total and cluster scores than placebo. Mean maximum daily doses were 225-mg venlafaxine ER and 151-mg sertraline. Both treatments were generally well tolerated. Study results suggest that venlafaxine ER is effective and well tolerated in the short-term treatment of PTSD.