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.     

Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial.

OBJECTIVE: To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. METHOD: Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. RESULTS: Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. CONCLUSIONS: The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.     

Comparison of short-term venlafaxine versus lithium monotherapy for bipolar II major depressive episode: a randomized open-label study

OBJECTIVE: Practice guidelines for the initial treatment of bipolar II (BP II) major depressive episode (MDE) recommend mood stabilizer (MS) monotherapy or combined MS plus antidepressant drug (AD) therapy. We hypothesized that initial AD monotherapy would be superior to MS monotherapy for BP II MDE with a low hypomanic switch rate. METHODS: Bipolar II MDE patients were randomized to a 12-week open-label treatment with either venlafaxine monotherapy (n = 43) or lithium carbonate monotherapy (n = 40). The primary outcome measure was the 28-item Hamilton Depression Rating Scale (HAM-D 28). The secondary outcome measures included the Young Mania Rating Scale (YMRS), clinical global impressions severity and change ratings, and the proportion of patients classified as responder (with > or = 50% reduction in baseline HAM-D score) or as remitter (final HAM-D score, < or = 8). RESULTS: Thirty-four venlafaxine-treated patients (79.1%) and 15 lithium-treated patients (37.5%) completed the trial (P < 0.0005). Venlafaxine monotherapy produced a greater reduction in HAM-D 28 scores, with a difference in change of -6.57 points (95% confidence interval, -11.97 to -1.18) (P = 0.017) between treatment conditions. There was a greater proportion of venlafaxine-treated (vs lithium-treated) patients classified either as treatment responder (58.1% vs 20.0%; P < 0.0005) or as treatment remitter (44.2% vs 7.5%; P < 0.0005) for the HAM-D 28 scores. There was no significant increase in mean YMRS scores over time in the venlafaxine (vs lithium) treatment condition, and no significant increase in mean YMRS scores at any study visit compared with baseline for either treatment. CONCLUSIONS: Results from this study suggest that AD monotherapy with venlafaxine may be an effective initial therapy for BP II MDE with a low hypomanic switch rate.     

Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder: a pooled analysis of two 6-week, double-blind, placebo-controlled studies

Prospectively planned pooled analysis evaluating the efficacy of quetiapine extended release (XR) monotherapy in major depressive disorder (MDD). Data were pooled from two 6-week, randomized, double-blind, placebo-controlled studies of quetiapine XR in outpatients with MDD. The primary endpoint was Montgomery-?sberg Depression Rating Scale (MADRS) total score change from randomization at week 6. Other evaluations were MADRS response/remission, Hamilton Rating Scale for Anxiety, and subgroup analyses. A total of 968 patients were randomized to quetiapine XR, 150 mg/day (n=315), 300 mg/day (n=323), or placebo (n=330). The mean MADRS total score reductions from randomization were significant at week 6 with quetiapine XR, 150 mg/day (-14.7; P<0.001) and 300 mg/day (-14.7; P<0.001) versus placebo (-11.1), with significant reductions versus placebo from week 1 onward. Response rates (week 6): 52.7% (P<0.001) quetiapine XR 150 mg/day and 49.5% (P<0.001) quetiapine XR 300 mg/day versus placebo (33.0%). MADRS remission (score≤8; week 6): 23.5% (P=0.208) quetiapine XR 150 mg/day and 28.8% (P<0.01) quetiapine XR 300 mg/day versus placebo (19.4%). Quetiapine XR (both doses) significantly improved eight of 10 MADRS items versus placebo at week 6. The therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as sex, age, or severity of depression. In patients with MDD, quetiapine XR (150 and 300 mg/day) monotherapy reduced depressive symptoms, with significant improvements compared with placebo from week 1 onward.     

Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study)

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P 相似文献   

Paroxetine and amitriptyline augmentation of lithium in the treatment of major depression: a double-blind study

To study the efficacy and safety of antidepressant augmentation of ongoing lithium therapy, lithium-maintained patients suffering from an breakthrough episode of major depression were randomly assigned under double-blind conditions to receive paroxetine 20 mg/day (N = 19) or amitriptyline 75 mg/day (N = 23). The initial dosages could be increased after 2 weeks to 40 mg/day and 150 mg/day, respectively, and the patients were treated for a total of 6 weeks. Efficacy was assessed weekly with the 21-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression Scale (CGI), and safety was assessed with the Dosage Record and Treatment Emergent Symptom Scale. After 4 weeks, a significantly greater proportion of patients in the paroxetine group had achieved a 50% reduction in baseline HAM-D scores, and the mean improvement in CGI severity of illness was significantly greater in the paroxetine group at weeks 3 and 5. The type and number of emergent events occurring during study treatment corresponded to the known side effect profiles of paroxetine and amitriptyline. Serum lithium levels were not affected by either antidepressant. The authors proposed that the more rapid improvement demonstrated by the group receiving the combination of lithium and paroxetine may be due to the synergistic serotonergic effects of these two medications.     

拉莫三嗪联合帕罗西汀治疗双相抑郁的临床疗效及安全性

目的:探讨拉莫三嗪联合帕罗西汀治疗双相抑郁的临床疗效及安全性。方法:将118例双相抑郁患者随机分入对照组(58例)与观察组(60例),给予对照组患者帕罗西汀口服治疗,观察组患者接受拉莫三嗪联合帕罗西汀口服,疗程8周。治疗前后采用汉密尔顿抑郁量表(HAMD)及临床总体印象量表(CGI)评估疗效。结果:治疗后8周,观察组治疗有效率显著高于对照组(88.3%(53/60)对70.7%(41/58),P<0.05);观察组HAMD认知障碍、焦虑/躯体化、阻滞以及睡眠障碍因子显著优于对照组(P<0.05);观察组CGI评分显著低于对照组(P<0.05);两组不良反应无显著性差别。结论:拉莫三嗪联合帕罗西汀治疗双相抑郁临床疗效确切,且不增加不良反应。     

Eight-week, placebo-controlled, double-blind comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR

The efficacy, safety and tolerability of bupropion XR and venlafaxine XR was assessed and compared with placebo in adult outpatients with major depressive disorder (MDD). Adults meeting DSM-IV criteria for MDD with a minimum Hamilton Depression Rating Scale (HAMD) 17-Item total score of > or =18 were randomized to eight weeks of double-blind treatment with either bupropion XR (150 mg/day), venlafaxine XR (75 mg/day) or placebo. At the end of the fourth week of treatment, a dosage increase to bupropion XR 300 mg/day or venlafaxine XR 150 mg/day was allowed if, in the opinion of the investigator, response was inadequate. The primary efficacy endpoint was mean change from baseline at week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score last observation carried forward (LOCF). Mean changes from baseline at week 8 (LOCF) in MADRS total score were statistically significant for bupropion XR and venlafaxine XR patients compared to the placebo group: -16.0 for bupropion XR (P = 0.006 vs placebo), -17.1 for venlafaxine XR (P < 0.001 vs placebo) and -13.5 for placebo. Secondary outcomes (including CGI-S, HAM-A, MEI, Q-LES-Q-SF, responder and remitter analyses) also improved significantly for both active treatment groups compared with placebo. The most frequently reported adverse events were dry mouth and insomnia for bupropion XR, and nausea, hyperhidrosis, fatigue, and insomnia for venlafaxine XR. In this double-blind, placebo-controlled trial, bupropion XR at doses up to 300 mg/day and venlafaxine XR at doses up to 150 mg/day demonstrated comparable antidepressant efficacy.     

Influence of monoamine oxidase A and serotonin receptor 2A polymorphisms in SSRI antidepressant activity

The aim of the present study was to test a possible effect of the monoamine oxidase A (MAOA) and serotonin receptor 2A (5-HT-2A) gene variants on the antidepressant activity of fluvoxamine and paroxetine in a sample of major (n = 248) and bipolar (n = 195) depressives, with or without psychotic features. A total of 443 in-patients were treated with 300 mg fluvoxamine (n = 307) or 20-40 mg paroxetine (n = 136) for 6 wk. The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression (HAMD). Allele variants were determined in each subject using a PCR-based technique. We observed a marginal association between 5-HT-2A variants and antidepressant response while MAOA genotypes were not associated. Possible stratification factors, such as sex, diagnosis, presence of psychotic features, HAMD scores at baseline, pindolol augmentation and SSRIs plasma levels did not significantly influence the observed results. The investigated MAOA and 5-HT-2A gene variants, therefore, do not seem to play a major role in SSRI antidepressant activity.     

Asenapine: a review of its use in the management of mania in adults with bipolar I disorder

Asenapine is an atypical antipsychotic agent available in sublingual formulations (5 or 10 mg) and indicated in the US (Saphris) for the acute treatment, as monotherapy or adjunctive therapy, of manic and mixed episodes and in the EU (Sycrest) for the treatment of moderate to severe manic episodes, in adult patients with bipolar I disorder. In two large (both n = 480), well designed, 3-week trials in adult patients with bipolar I disorder, asenapine monotherapy was significantly more effective than placebo at improving mania symptoms, as assessed using the Young Mania Rating Scale total score (YMRS; primary endpoint), with significant differences between the asenapine and placebo groups occurring after 2 days of treatment. In both trials, Clinical Global Impression for Bipolar Disorder (CGI-BP) scale mania severity scores exceeded those of placebo. In one trial, response and remission rates exceeded those of placebo. In a 9-week extension study that recruited completers from the monotherapy trials, there were no significant differences between asenapine and olanzapine groups in terms in Montgomery-?sberg Depression Rating Scale (MADRS) scores, CGI-BP mania severity scores, YMRS response rates or YMRS remission rates during the extension phase. In the extension study, the efficacy of asenapine monotherapy appeared to be maintained over 40 weeks (total treatment duration of 52 weeks). In a 12-week trial of asenapine as adjunctive therapy to lithium or valproate, asenapine was more effective than placebo in improving manic symptoms, based on the difference between groups in the YMRS total score at week 3 (primary endpoint). Most adverse events associated with asenapine were of mild to moderate severity, with <7% of asenapine recipients experiencing serious adverse events (vs 7% with placebo). In a pooled analysis of the monotherapy trials, the most common adverse events (occurring in ≥ 5% of patients and at twice the incidence of placebo) reported during acute phase asenapine monotherapy for bipolar mania were somnolence, dizziness, extrapyramidal symptoms (EPS, other than akathisia) and increased bodyweight, which were similar in nature to those occurring during longer-term monotherapy with asenapine. EPS did not worsen in severity during longer-term asenapine monotherapy. Asenapine had minimal effects on plasma glucose, lipid and prolactin levels over both short- and longer-term treatment periods, and had little pro-arrhythmogenic potential. Further active comparator trials and longer-term tolerability and safety data are required. In the meantime, asenapine is a further option for the management of manic and/or mixed symptoms in patients with bipolar I disorder and may be of particular value for patients who are at high risk for metabolic abnormalities.     

Paroxetine for prevention of depressive symptoms induced by interferon-alpha and ribavirin for hepatitis C

BACKGROUND: Whether antidepressants prevent depression during interferon-alpha/ribavirin treatment for hepatitis C virus infection has yet to be established. AIM: To investigate the use of paroxetine in a prospective, double-blind, placebo-controlled study for this indication. METHODS: Sixty-one hepatitis C virus-infected patients were randomly assigned to the antidepressant, paroxetine (n = 28), or placebo (n = 33), begun 2 weeks before and continued for 24 weeks during interferon-alpha/ribavirin treatment. Primary endpoints included development of major depression and severity of depressive symptoms measured by the Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: Rates of major depression during the study were low (17%) and did not differ between groups. Nevertheless, using published MADRS cut-off scores, the percent of subjects who met criteria for mild, moderate or severe depression during interferon-alpha/ribavirin therapy was significantly lower in paroxetine- vs. placebo-treated subjects (P = 0.02, Fisher's exact test). Assignment to paroxetine was also associated with significantly reduced depressive symptom severity. This effect was largely accounted for by participants with depression scores above the median (MADRS > 3) at baseline in whom paroxetine was associated with a maximal reduction in MADRS scores of 10.3 (95% CI: 2.1-18.5) compared with placebo at 20 weeks (P < 0.01). Study limitations included a small sample size and high drop-out rate. CONCLUSION: This double-blind, placebo-controlled trial provides preliminary data in support of antidepressant pre-treatment in hepatitis C virus patients with elevated depressive symptoms at baseline.     

A comparative, randomised, double-blind study of trazodone prolonged-release and paroxetine in the treatment of patients with major depressive disorder

OBJECTIVES: To evaluate the efficacy and safety of trazodone prolonged release compared with paroxetine in the treatment of patients with major depression. RESEARCH DESIGN AND METHODS: A total of 108 patients aged 20-68 years were enrolled in this multicentre, double-blind, double-dummy, randomised, paroxetine-controlled study. Each patient received 3 days single-blind placebo treatment followed by 6 weeks double-blind treatment with either trazodone prolonged release 150-450 mg/day (n = 55) or paroxetine 20-40 mg/day (n = 53). OUTCOME MEASURES: Efficacy was evaluated by the rate of patients responding to each treatment and considered to be in remission, and by mean changes from baseline in the Hamilton Depression Rating scale scores (HAM-D), Montgomery Asberg Depression Rating Scale scores (MADRS), and Clinical Global Impression (CGI)--Severity and Global Improvement scores. Time to onset of efficacy and safety were assessed. RESULTS: Trazodone and paroxetine were equally effective at reducing symptoms of depression and promoting remission. Onset of efficacy was slightly faster for patients treated with paroxetine. Overall, there were no significant differences between the groups at endpoint in efficacy measures, and in percentage of responders (> 85%) or patients in remission (> 65%). Sleep disorders (HAM-D subset) were significantly less evident for patients in the trazodone group at the end of the study (p < 0.05). Adverse drug reactions were reported by 35% of trazodone-treated patients (mainly of the nervous system) and 26% of paroxetine-treated patients (mainly gastrointestinal), although none was considered to be serious. CONCLUSIONS: This study showed that after a 6-week period trazodone and paroxetine are not different in reducing the symptoms of depression and, in many patients, in producing the remission of the illness. The known divergence in tolerability profile of the two medications, related to their differing pharmacological properties, was also confirmed. Trazodone may be of advantage in depressed patients with sleep difficulties.     

Efficacy of adjunctive aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy

To evaluate the efficacy of adjunctive aripiprazole in patients with minimal response to prior antidepressant therapy (ADT). Pooled data from three randomized, double-blind, placebo-controlled studies assessing the efficacy of adjunctive aripiprazole to ADT in patients with major depressive disorder who had a minimal response [< 25% reduction on the Montgomery-?sberg Depression Rating Scale (MADRS)] to an 8-week prospective ADT. During the 6-week, double-blind adjunctive phase, response was defined as at least 50% reduction in the MADRS score and remission as at least 50% reduction in MADRS score and a MADRS score ≤ 10. Rates were examined using analysis of covariance and Cochran-Mantel-Haenszel tests. Kaplan-Meier curves were used to calculate time to response and remission. Of 1038 patients, 72% (n=746) exhibited a minimal response to ADT (ADT minimal responder). Time to response and remission were significantly shorter for ADT minimal responders receiving aripiprazole+ADT versus adjunctive placebo+ADT. ADT minimal responders on aripiprazole+ADT showed significantly greater improvements in MADRS score at endpoint compared with minimal responders on placebo+ADT (-10.3 vs. -6.5, P<0.0001). In addition, ADT minimal responders exhibited significantly higher response rates with aripiprazole+ADT than placebo+ADT (36 vs. 19%, respectively, P<0.0001) and higher remission rates (24 vs. 12%, respectively, P<0.0001). The numbers needed to treat with aripiprazole+ADT were six for response and eight for remission. Aripiprazole augmentation had a rapid and clinically meaningful effect in ADT minimal responders.     

Quetiapine monotherapy for mania associated with bipolar disorder: combined analysis of two international, double-blind, randomised, placebo-controlled studies

OBJECTIVE: To evaluate the efficacy and safety of quetiapine monotherapy for mania in bipolar disorder by an a priori defined combined analysis of data from two placebo-controlled studies. METHOD: The intent-to-treat (ITT) populations from two studies of patients with DSM-IV bipolar I disorder, manic episode, randomised to 12 weeks of double-blind treatment with quetiapine (up to 800 mg/day) or placebo were combined. The primary efficacy endpoint was change in Young Mania Rating Scale (YMRS) score from baseline to Day 21. Secondary endpoints included change from baseline in YMRS to Day 84, YMRS response and remission rates and change from baseline to Days 21 and 84 in the Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI), Clinical Global Impressions-Bipolar (CGI-BP) and the Positive and Negative Syndrome Scale (PANSS). These endpoints were analysed as continuous variables, using an analysis of covariance (ANCOVA), with the baseline as covariate. In order to account for any difference in response between studies, the analyses were stratified by study as a fixed effect, and centre as a random effect. The Cochran-Mantel-Haenszel test was used to analyse binary variables. A chi square test was used to compare the frequency of adverse events between the treatment groups. RESULTS: The combined analysis included a total of 403 patients from two quetiapine monotherapy studies in patients with bipolar I disorder. A significant improvement in YMRS score was observed from Day 4 (p = 0.021) onward in the quetiapine group compared with placebo. The treatment advantage of quetiapine over placebo continued to increase to Day 21 (p < 0.001) and Day 84 (p < 0.001). Significantly more quetiapine-treated than placebo-treated patients achieved a response (p < 0.001). The average quetiapine dose in responders was approximately 600 mg daily. Of adverse events occurring in > or = 5% of patients, quetiapine-treated patients had a significantly greater incidence versus placebo of somnolence (16.3% vs. 4.0%), dry mouth (15.8% vs. 3%), weight gain (9.1% vs. 1.5%) and dizziness (6.7% vs. 2.5%). CONCLUSIONS: The data from this combined analysis support the results from the individual studies and indicate that quetiapine monotherapy is effective across a broad range of mood symptoms, fast-acting and well tolerated in the treatment of mania.     

A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients

OBJECTIVE: This randomised, double-blind, fixed-dose study evaluated the efficacy of escitalopram and paroxetine in the long-term treatment of severely depressed patients with major depressive disorder (MDD). RESEARCH DESIGN AND METHODS: Patients with a primary diagnosis of MDD and baseline Montgomery-Asberg Depression Rating Scale (MADRS) >or= 30 were randomised to 24 weeks of double-blind treatment with fixed doses of either escitalopram (20 mg) (n = 232) or paroxetine (40 mg) (n = 227). The primary analysis of efficacy was an analysis of covariance (ANCOVA) of change from baseline to endpoint (Week 24) in MADRS total score (last observation carried forward, LOCF). MAIN OUTCOME MEASURES; RESULTS: At endpoint (24 weeks), the mean change from baseline in MADRS total score was -25.2 for patients treated with escitalopram (n = 228) and -23.1 for patients with paroxetine (n = 223), resulting in a difference of 2.1 points (p < 0.05). The difference in the change in the MADRS total score (LOCF) was significantly in favour of escitalopram from Week 8 onwards. The proportion of remitters (MADRS or= 35), there was a difference of 3.4 points at endpoint in the MADRS total score in favour of escitalopram (p < 0.05). The overall withdrawal rate for patients treated with escitalopram (19%) was significantly lower than with paroxetine (32%) (p < 0.01). The withdrawal rate due to adverse events was significantly lower for escitalopram (8%) compared to paroxetine (16%) (p < 0.05). There were no significant differences in the incidence of individual adverse events during treatment. CONCLUSION: Escitalopram is significantly more effective than paroxetine in the long-term treatment of severely depressed patients.     

A double-blind, randomized, placebo-controlled prophylaxis trial of oxcarbazepine as adjunctive treatment to lithium in the long-term treatment of bipolar I and II disorder

We evaluated the prophylactic efficacy and the long-term tolerability of oxcarbazepine administration in the treatment of bipolar I and II disorder as an adjunctive therapy to lithium. We conducted a 52-wk, double-blind, randomized, placebo-controlled, parallel-group, multicentre, clinical trial. Bipolar I and II DSM-IV outpatients, having had two or more episodes in the last year, but currently being in remission, were randomly assigned on a 1:1 ratio to oxcarbazepine (n=26) or placebo (n=29) as adjuncts to ongoing treatment with lithium. The primary efficacy variable was the length of the remission period assessed by means of the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS). Other assessments were the Clinical Global Impression (CGI-BP-M), functional activity (GAF), anxiety (HAMA) and impulsiveness (BIS-11). The average time until first recurrence of any type was 19.2+/-13.9 wk and 18.6+/-17.0 wk for oxcarbazepine and placebo respectively (p=0.315). Ten (38.46%) patients had a recurrence of any kind in the oxcarbazepine group vs. 17 (58.62%) in the placebo group (p=0.1354). There was a trend for depressive episodes being less likely in the oxcarbazepine group compared to the placebo group (11.54% and 31.03% respectively, p=0.085), and for better functionality with the GAF (p=0.074). Impulsivity was significantly better prevented by oxcarbazepine (p=0.0443). Overall, oxcarbazepine was well tolerated. This pilot, randomized clinical trial, suggests that oxcarbazepine might have some prophylactic efficacy with regards to impulsivity and perhaps mood episodes in patients taking lithium, although further, adequately powered controlled trials are needed to confirm these findings.     

米安色林与丙咪嗪治疗抑郁症的临床对照研究

目的 评价米安色林与丙咪嗪治疗抑郁症的临床疗效和安全性。方法 将51例符合CCMD-3抑郁症诊断标准的抑郁症患者随机分为两组，分别给予米安色林和丙咪嗪治疗，于治疗前和治疗后1，2，4，6周末分别采用汉密尔顿抑郁量表（HAMD量表）、临床疗效总体评定量表及不良反应量表评定。结果 米安色林与丙咪嗪总体疗效相似（P〉0．05）；米安色林组治疗第1周就起效；治疗前与治疗后比较，HAMD评分两组均有显著性差异（P〈0．01），两组之间则无显著性差异（P〉0．05），米安色林组的不良反应少于丙咪嗪组。结论米安色林是一种安全有效的新一代抗抑郁药物，适用于伴有失眠症状的老年抑郁症患者。     

Olanzapine monotherapy for acute depression in patients with bipolar I or II disorder: results of an 8‐week open label trial

We evaluated the efficacy, tolerability, and safety of olanzapine monotherapy in 20 adult patients with bipolar I or II disorder, depressed phase. Patients received open‐label olanzapine monotherapy (mean modal dose, 15 mg/day) for 8 weeks. Assessments of psychopathology (Montgomery–Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology [QIDS‐SR‐16], Young Mania Rating Scale [YMRS]), clinical global state (Clinical Global Impressions [CGI] scale), and safety/tolerability were performed at baseline, and at 1, 2, 4, 6, and 8 weeks. Seventeen patients (85.0%) completed the study. Improvement in MADRS total scores was observed after the first week of treatment, and at all remaining follow‐up time points (p ≤ 0.005). Parallel improvement in QIDS‐SR‐16 (p < 0.001) and CGI‐Severity (p < 0.001) was observed between baseline and study endpoint. Nine (45%) subjects achieved positive treatment response, eight of whom (40%) also achieved symptom remission. There were significant increases in weight (+3.2 kg, p = 0.001) and body mass index (+1.1 kg/m², p = 0.001), but not fasting glucose or lipids, with the exception of reduced triglyceride levels in the overall sample, and reduced HDL cholesterol in females. Olanzapine may be an effective, well‐tolerated option for treating acute non‐psychotic depression across a variety of bipolar disorder subtypes. Copyright © 2009 John Wiley & Sons, Ltd.     

Efficacy of olanzapine monotherapy for treatment of bipolar I depression: a randomized,double-blind,placebo controlled study

Rationale and objective

Depression symptoms are now recognized to be the predominant cause of disability for bipolar disorder (BD) patients. The treatment strategies for the depressed phase of BD remain more anecdotal than data-based. Olanzapine has been investigated as an alternative to antidepressants and a mood stabilizer for acute bipolar depression. The purpose of this study was to assess the efficacy of olanzapine monotherapy for bipolar I depression.

Method

Sixty-eight patients with bipolar I depression were randomly assigned to treatment with olanzapine (mean final dose 14.4 mg/day) (n?=?34) or placebo (n?=?34) in a double-blind parallel-group study design. Planned assessments included Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Clinical Global Impressions-Severity of Illness scale (CGI-S), Clinical Global Impressions-Improvement scale (CGI-I), Hamilton Depression scale (HAMD), Hamilton Anxiety scale (HAMA), and Treatment Emergent Symptom Scale (TESS).

Results

Of the 68 patients who were randomly assigned, 57 (83.8 %) completed treatments. Improvements in MADRS total score, CGI-S, CGI-I, and HAMD in the olanzapine group were significantly greater relative to those in the placebo group during the 8-week follow-up period (p?<?0.001, p?=?0.0017, p?=?0.007, and p?<?0.001, respectively). Rates of categorical treatment response and remission in the olanzapine group (50.0 % and 35.3 %, respectively) were significantly higher than those in the placebo group (20.6 %, p?=?0.011 and 11.8 %, p?=?0.022, respectively). At the 8-week treatment, the mean weight and the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels increased significantly in the olanzapine group (p?=?0.037, p?=?0.029, p?=?0.030, and p?=?0.028, respectively).

Conclusions

Olanzapine is effective in the treatment of bipolar I depression but is associated with significant metabolic side effects.     

卡马西平单用及其与逍遥散合用治疗双相情感障碍随机双盲安慰剂对照临床研究

目的 评估卡马西平单用及其与逍遥散合用治疗双相情感障碍的疗效和安全性。方法 用随机双盲安慰剂对照方法，双相躁狂82例，双相抑郁76例，各随机分为3组。双相躁狂疗程8周，双相抑郁疗程12周。用Young与Bech—Rafaelsen躁狂量表、Hamilton与Montgomery—Asberg抑郁量表和临床总体印象量表评定疗效，用副反应量表观察药物不良反应。结果 双相躁狂患者3组药物临床有效率分别为：逍遥散合用卡马西平为79％，卡马西平单用为64％，安慰剂为45％，3组比较有显著性差异（P〈0．05）。双相抑郁患者3组药物临床有效率分别为：逍遥散合用卡马西平为75％，卡马西平单用为59％，安慰剂为33％，3组比较有显著性差异（P〈0．05）。逍遥散合用卡马西平较卡马西平单用，在头昏、视力模糊、皮疹、恶心发生率增加。结论 逍遥散作为辅助药物治疗双相障碍有效，但能增加卡马西平药物不良反应发生率。