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.     

Fluvoxamine-controlled release formulation for the treatment of generalized social anxiety disorder

BACKGROUND: Generalized social anxiety disorder is a highly prevalent anxiety disorder with deleterious effects on social and family relationships, as well as work performance. We report the results of a multicenter, randomized, placebo-controlled trial comparing the efficacy, safety, and tolerability of fluvoxamine controlled release (CR) to placebo in patients with generalized social anxiety disorder. METHODS: A total of 279 adult patients meeting all inclusion/exclusion criteria was recruited at 23 United States sites and randomly assigned to receive either fluvoxamine CR (100-300 mg/d) or placebo for 12 weeks. The dose could be increased, based on efficacy and tolerability, in increments of 50 mg/d at weekly intervals. The dosage remained constant during weeks 6 to 12. RESULTS: Treatment with fluvoxamine CR resulted in statistically and clinically significant improvements in symptoms associated with generalized social anxiety disorder as early as week 4 on the Liebowitz Social Anxiety Scale and the Clinical Global Impression Scale Global Improvement, and at week 6 on the Sheehan Disability Scale, Clinical Global Impression Scale Severity of Illness and the Patient Global Impression of Improvement Scale. The most frequent adverse events reported by patients on fluvoxamine CR were headache, nausea, somnolence, and insomnia. No weight gain was observed for either treatment group, and at end point, there were no differences between treatments on overall sexual function, as measured by the Arizona Sexual Experience Scale. CONCLUSIONS: Both physician and patient-rated scales indicate that fluvoxamine CR is effective and safe for the treatment of generalized social anxiety disorder.     

Clinical experience with paroxetine in social anxiety disorder

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with proven efficacy in the treatment of depression, panic disorder and obsessive-compulsive disorder. Evidence that paroxetine may be effective in social anxiety disorder (social phobia) first arose from open-label studies. More recently, three multicentre, randomized, placebo-controlled trials have been performed, each lasting 12 weeks, to assess the efficacy and tolerability of paroxetine in the treatment of social anxiety disorder, and these studies are reviewed here. The data from all three studies consistently demonstrated that paroxetine was effective in reducing both the symptoms of anxiety and the disability and impairment of social anxiety disorder. Paroxetine performed significantly better than placebo on all primary (Liebowitz Social Anxiety Scale, Clinical Global Impression) and secondary (Social Avoidance and Distress Scale, Sheehan Disability Scale) outcome measures. Adverse events were restricted to those already known to be associated with SSRIs, no serious adverse events associated with medication were experienced, and the numbers withdrawing from the studies were not significantly different in the paroxetine and control groups. Taken together, these studies confirm that paroxetine is an effective and well tolerated treatment for patients with social anxiety disorder.     

A double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder

Venlafaxine extended release (ER) is a dual serotonin-norepinephrine reuptake inhibitor previously shown to be effective in the treatment of major depressive disorder and generalized anxiety disorder. This placebo-controlled, multicenter, randomized, double-blind trial examined the efficacy and safety of venlafaxine ER in outpatients with generalized social anxiety disorder. Two hundred seventy-two outpatients were randomly assigned to receive either a flexible dose of venlafaxine ER (75 to 225 mg/d) or placebo for 12 weeks. Venlafaxine ER was statistically significantly more effective than placebo as demonstrated by the Liebowitz Social Anxiety Scale total scores at weeks 4 to 12. Scores of both the Clinical Global Impression-Severity and Clinical Global Impression-Improvement scales showed that venlafaxine ER was significantly more effective than placebo at weeks 4 to 12. In addition, more venlafaxine ER-treated patients achieved CGI-Improvement scores of 1 or 2 than placebo-treated patients at weeks 4 to 12, demonstrating a greater percentage of responders to venlafaxine ER treatment. Assessment using the fear/anxiety and avoidance subscales of the Liebowitz Social Anxiety Scale and the Social Phobia Inventory Scale also showed venlafaxine ER to be more effective than placebo at weeks 4 to 12 and 6 to 12, respectively. The Sheehan Disability Inventory showed that patients in the venlafaxine ER-treated group had significantly better outcomes in social life at weeks 4 and 12, and in work at week 12. Adverse events were similar to those reported in studies of venlafaxine ER in depression and generalized anxiety disorder. Venlafaxine ER was safe, well tolerated, and efficacious in the short-term treatment of generalized social anxiety disorder.     

Discontinuation symptoms in depression and anxiety disorders

The present overview investigates whether different antidepressants have differing discontinuation symptoms upon treatment cessation, if these symptoms vary between depression and anxiety disorders, and with length of treatment. Data came from two comparative studies of escitalopram in major depressive disorder (MDD) (one vs. venlafaxine XR and one vs. paroxetine), two studies in social anxiety disorder (SAD) (one of which used paroxetine as the active reference), and one study in generalized anxiety disorder (GAD), using paroxetine as an active reference [total number of patients: escitalopram (n=1051); paroxetine (n=336); venlafaxine XR (n=124); placebo (n=239)]. All studies included a defined discontinuation period and used the Discontinuation Emergent Signs and Symptoms (DESS) checklist to record the number of discontinuation symptoms. All three antidepressants showed more discontinuation symptoms compared with placebo (p<0.001). Patients reported significantly fewer discontinuation symptoms with escitalopram than with paroxetine and venlafaxine XR in MDD (p<0.05). Escitalopram showed significantly fewer discontinuation symptoms than paroxetine in SAD (p<0.05) and GAD (p<0.001). For each antidepressant, no differences in discontinuation symptoms were observed between the three indications and there was no evidence for increased symptom incidence with increased length of treatment. Thus, discontinuation profiles differ between antidepressants of the same class and are broadly similar in different disorders. No evidence was seen for a higher discontinuation burden with longer treatment.     

帕罗西汀治疗广泛性焦虑症

目的 :探讨帕罗西汀对广泛性焦虑症的疗效和副作用。方法 :帕罗西汀组 30例 ,男性 12例 ,女性 18例 ,予帕罗西汀 2 0～ 4 0mg·d- 1,po ;苯二氮类组 30例 ,男性 13例 ,女性 17例 ,其中 16例予阿普唑仑 0 .4～ 0 .8mg ,po ,2～ 3次·d- 1,14例予氯硝安定 1～ 2mg ,po ,2～ 3次·d- 1;安慰剂组 30例 ,男性 11例 ,女性 19例 ,给予安慰剂 1片 ,po ,tid。疗程均为 12wk ,治疗前及治疗wk 2 ,4 ,8,12末采用HAMA ,SAS ,CGI ,TESS评定疗效及副作用。结果 :帕罗西汀组显效率 90 % ,苯二氮类组显效率 50 % ,经Ridit分析 ,P <0 .0 1。帕罗西汀组常见副作用有口干、便秘、恶心等 ,不影响治疗。结论 :帕罗西汀长期治疗广泛性焦虑症疗效确切 ,副作用轻微。     

Paroxetine controlled release

A controlled-release (CR) formulation of the SSRI paroxetine has been developed. This CR formulation delays the release of paroxetine until the tablet has passed through the stomach; the drug is then released over 4-5 hours. In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD]). The duration of treatment was 12 weeks or, in PMDD, over three menstrual cycles (intermittent or continuous administration). Paroxetine CR also demonstrated efficacy in three well designed studies in patients with panic disorder with or without agoraphobia. Paroxetine CR was generally well tolerated in clinical trials, with an adverse-event profile typical of SSRIs, although recipients of paroxetine CR experienced significantly less nausea than recipients of immediate-release paroxetine in the first week of treatment.     

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.     

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.     

帕罗西汀联合阿普唑仑治疗广泛性焦虑症的疗效观察

目的探讨帕罗西汀联合阿普唑仑治疗广泛性焦虑症患者的疗效,关注其对焦虑和抑郁评分的影响,以期为临床工作提供帮助。方法收集本院诊治的广泛性焦虑症的患者80例,随机分为观察组（40例）与对照组（40例）,对照组单纯应用帕罗西汀治疗,观察组应用帕罗西汀联合阿普唑仑治疗,观察治疗对患者焦虑和抑郁评分的影响。结果观察组在治疗2、4、8周后对焦虑和抑郁的改善情况明显优于对照组,两组差异有统计学意义（P〈0.05）。结论帕罗西汀联合阿普唑仑治疗广泛性焦虑症患者的疗效明显,对焦虑和抑郁改善的效果理想,临床中可以积极应用。     

Advances in recognition and treatment of social anxiety disorder: a 10-year retrospective

Social anxiety disorder frequently begins in early life and is associated with the subsequent development of comorbid conditions such as depressive and substance use disorders. Social anxiety disorder, particularly the generalized subtype, is characterized by marked impairment in numerous functional domains, including education and social relations. Paroxetine, the first medication to receive an indication in the United States for the treatment of social anxiety disorder, has been shown to be effective in 50% to 60% of patients. The mechanism of action of paroxetine in the treatment of social anxiety disorder is at present unclear. A possible role for early treatment to prevent complications of social anxiety disorder should be explored.     

Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study

Estazolam, a triazolobenzodiazepine with an intermediate elimination half-life, has been shown previously to be an effective and safe hypnotic in insomniacs without concomitant psychiatric illness. Our study of the efficacy of estazolam in patients with insomnia associated with generalized anxiety disorder began when 108 patients meeting criteria for generalized anxiety disorder (mean total score of Hamilton Rating Scale for Anxiety [HAM-A] = 22.0 +/- 3.1 [SD]) and insomnia were given single-blind placebo for 7 nights. Nine patients whose anxiety and/or insomnia improved were dropped as placebo responders. The remaining 99 patients were randomly allocated (1:1) to double-blind treatment with either estazolam 2.0 mg or matching placebo for 7 nights. Hypnotic efficacy, as determined by patient-completed sleep questionnaires, was statistically significant for estazolam 2.0 mg versus placebo for all sleep indices (p less than 0.01). Patients treated with estazolam 2.0 mg showed significantly greater improvement in anxiety than those receiving placebo on the mean total score of HAM-A ([placebo, -3.4; estazolam, -7.1; p less than 0.001] and without the insomnia item [placebo, -2.7; estazolam, -5.5; p less than 0.001]). Anxiety scores on the State-Trait Anxiety Inventory showed greater improvement in the estazolam group, but without statistical significance (p = 0.237). Estazolam 2.0 mg is an effective hypnotic in patients with generalized anxiety disorder and appears to have a favorable anxiolytic action.     

A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder

This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to receive either fluvoxamine CR (N = 149) or placebo (N = 151) for 12 weeks. Mean changes from baseline to end point in Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression Severity of Illness Scale (CGI-S), Sheehan Disability Scale (SDS), as well as the mean end point scores in Clinical Global Impression Improvement Scale (CGI-I) and Patient Global Impression of Improvement Scale (PGI) were compared between the fluvoxamine CR and placebo treatment groups. Arizona Sexual Experience Scale (ASEX), adverse event, and other safety parameters were also assessed. The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score (primary measure) starting at week 4. At end point, there was a mean change from baseline of -36.1 +/- 2.7 (37% reduction) in the LSAS total score in the fluvoxamine CR group compared with -27.3 +/- 2.4 (28% reduction) in the placebo group (P = 0.020 for mean change). Fluvoxamine CR was also significantly superior to placebo in SDS, CGI-S, CGI-I at end point (secondary measures). When compared with placebo, fluvoxamine CR did not cause any significant weight gain or clinically significant sexual dysfunction as measured by ASEX. In summary, fluvoxamine CR is an efficacious, safe, and well-tolerated treatment of generalized social anxiety disorder.     

万拉法辛缓释剂与帕罗西汀治疗广泛性焦虑障碍的对照研究

目的研究万拉法辛缓释剂与帕罗西汀治疗广泛性焦虑障碍的疗效与安全性。方法根据DSM-IV诊断标准将广泛性焦虑障碍患者随机分成2组,万拉法辛缓释剂治疗组（25例）和帕罗西汀治疗组（23例）,均治疗8周;采用HAMA、CGI-SI评定疗效;采用TESS、实验室检查及体查评价安全性。结果HAMA、CGI-SI量表分在治疗过程中显著下降,2组疗效相当,均未有严重不良事件发生。结论万拉法辛缓释剂与帕罗西汀是安全有效的治疗广泛性焦虑障碍的药物,患者对药物的耐受性及依从性好。     

Efficacy of Venlafaxine ER in patients with social anxiety disorder: a double-blind, placebo-controlled, parallel-group comparison with paroxetine

This study evaluated the anxiolytic efficacy, safety and tolerability of a flexible dose of venlafaxine extended release (ER) compared with placebo and paroxetine in the short-term treatment of generalized social anxiety disorder (SAD). Adult outpatients with generalized SAD (n = 434) were randomized to receive capsules of venlafaxine ER 75 mg to 225 mg/day, paroxetine 20 mg to 50 mg/day, or placebo for 12 weeks. The primary efficacy variable was the Liebowitz social anxiety scale total score. Secondary efficacy variables included the patient-rated social phobia inventory and the proportion of responders in each group (a responder was defined as having a clinical global impression-improvement score of 1 or 2). Treatment with venlafaxine ER was associated with significantly greater improvement than treatment with placebo for all primary and secondary efficacy variables (p < 0.05). No significant differences in primary or secondary efficacy variables were observed between the venlafaxine ER and paroxetine groups. The week 12 response rates were 69%, 66% and 36% for the venlafaxine ER, paroxetine and placebo groups, respectively. Both active treatments were generally well tolerated and were associated with a similar incidence of adverse events. This study shows that venlafaxine ER is an effective, safe and well-tolerated drug treatment for SAD.     

广泛性焦虑症患者住院药物治疗的探讨

目的:探讨帕罗西汀联合氯硝西泮静脉用药治疗广泛性焦虑症临床效果及起效特点。方法:将70例广泛性焦虑障碍患者随机分为两组。研究组36例用帕罗西汀的同时,给予氯硝西泮静脉用药治疗;对照组34例只给予帕罗西汀治疗。两组于治疗前和治疗后第一天、2周、3周、4周末采用汉密尔顿焦虑量表和不良反应量表评定临床疗效与不良反应,并进行比较。结果:帕罗西汀对广泛性焦虑障碍有明显疗效,帕罗西汀联合氯硝西泮静脉用药效果显著,显效更快。在治疗1天及1周末,两组HAMA总分有极显著性差异,两组TESS分有显著性差异。结论:广泛性焦虑症患者住院治疗,用帕罗西汀联合氯硝西泮静脉用药见效快,效果显著。     

Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized controlled trial

Rationale There is a need for new pharmacological treatments for generalized social anxiety disorder (GSAD), which is a common, often disabling condition.Objective To compare the efficacy and safety over 6 months duration of two dose ranges of venlafaxine extended-release (ER) with placebo in patients with GSAD.Method Twenty-eight-week, double-blind, multi-center study in 386 adult outpatients with DSM-IV GSAD. Patients were randomized to placebo, venlafaxine ER fixed low dose (75 mg/day), or venlafaxine ER flexible higher dose (150–225 mg/day). Primary efficacy variable was change on the Liebowitz Social Anxiety Scale (LSAS). Secondary efficacy variables included, among others, the proportion of responders on the CGI Global Improvement Item (score 1 or 2), and the proportion of remitters (defined as an LSAS score of 30).Results Improvement on the LSAS was greater with venlafaxine ER (at 75 mg/day or 150–225 mg/day) than placebo, and was sustained throughout the 6-month trial. Of patients receiving venlafaxine ER (at any dose), 58% responded to treatment compared to 33% of those receiving placebo (P<0.001); corresponding remission rates were 31% and 16% (P<0.01). There were no differences in outcome according to venlafaxine ER dosage.Conclusions Venlafaxine ER was effective in the treatment of GSAD. The comparable efficacy at low and higher doses may indicate that norepinephrine reuptake blockade does not contribute to therapeutic effect in GSAD. This hypothesis should be tested using agents with specific actions on norepinephrine reuptake blockade.     

Symptom-onset treatment for women with premenstrual dysphoric disorder

Symptoms of premenstrual dysphoric disorder (PMDD) respond to serotonin reuptake inhibitors when treatment is limited to 14 days of the menstrual cycle. Many women have less than a week of symptoms, and shorter treatment intervals would further reduce medication exposure and costs. METHODS: Twenty women with PMDD were randomly assigned to either paroxetine CR or placebo for 1 cycle and crossed over to the other condition for a second cycle. Subjects initiated treatment when premenstrual symptoms began and stopped within 3 days of beginning menses. RESULTS: Women took capsules for an average of 9 days (range, 3-15 days), including the first few days of menses. Moderate "PMDD level" symptoms occurred in 1 subject (6%) for 2 days and 4 subjects (24%) for 1 day before starting paroxetine or placebo. Daily Record of Severity of Problems scores were lower in the paroxetine group compared with the placebo group, although the differences were not statistically significant. However, the mean on-treatment Inventory of Depressive Symptomatology (clinician-rated) score for the paroxetine group was 17.9 +/- 8.3 compared with 31.5 +/- 11.2 in the placebo group (adjusted mean difference = 13.6, P = 0.009). Response (Clinical Global Impressions Scale score of 1 or 2) occurred in 70% of subjects randomized to paroxetine CR and 10% of those assigned to placebo (chi2(1) = 7.5, P = 0.006). Discontinuation symptoms did not differ in the groups. CONCLUSION: These data suggest the need to further evaluate symptom-onset treatment in a larger randomized clinical trial.     

A placebo- and imipramine-controlled study of paroxetine

The objective of this study was to compare the safety and efficacy of paroxetine with imipramine and placebo in depressed outpatients. Following a 4- to 14-day placebo washout, patients were randomized into treatment groups and received study compound for up to 42 days. At Day 42, paroxetine was significantly more effective than placebo (p less than .05) in several observer- and patient-rated scales: the Retardation and Anxiety/Somatization factors of the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), the Raskin Depression Scale, the Covi Anxiety Scale, the Clinical Global Impressions (CGI) Improvement Scale, the Symptom Checklist-56 (SCL-56) Total, and the Patient's Global Evaluation (PGE). There were no significant differences between paroxetine and imipramine. Significantly more imipramine (75%) than paroxetine (35%) or placebo (23%) patients reported anticholinergic side effects, including blurred vision (5%, 0%, and 0%, respectively), constipation (35%, 8%, and 15%, respectively), and dry mouth (63%, 25%, and 15%, respectively). The data from this study indicated that paroxetine is a safe, well-tolerated, effective treatment for major depressive disorder.     

Zopiclone and triazolam in insomnia associated with generalized anxiety disorder: a placebo-controlled evaluation of efficacy and daytime anxiety

In a double-blind placebo-controlled study, following a 1 week washout, 75 outpatients suffering from generalized anxiety disorder with severe insomnia as the target symptom were randomly assigned to 4 weeks of treatment with zopiclone 7.5 mg, triazolam 0.5 mg or placebo at bedtime. Zopiclone was significantly better than placebo on most sleep parameters. Triazolam tended to be superior to placebo, but its superiority was significant only on the sleep induction factor. Triazolam-treated patients presented significantly more day-time-interdose anxiety than zopiclone as assessed by the weekly HARS and Clinical Global Assessment of Anxiety. Although daytime-interdose anxiety was observed with both drugs, this treatment emergent symptom was more frequent and severe with triazolam. Side-effects were of a mild to moderate intensity for both zopiclone and triazolam; however, taste perversion frequently appeared with zopiclone. Although both drugs share similar pharmacological properties and bind to benzodiazepine receptors, they differ significantly with respect to side-effects and daytime anxiety.