A 12-week double-blind multi-centre study of paroxetine and imipramine in hospitalized depressed patients

Fifty-seven inpatients with major depression (DSM-III-R) entered a 12-week study comparing paroxetine and imipramine. Trends (not reaching statistical significance) in favour of paroxetine were seen on the Hamilton Depression Rating Scale (HDRS) and the Montgomery-Åsberg Depression Rating Scale (MADRS). The UKU Side Effect Rating Scale showed a significant difference in favour of paroxetine on reduced salivation. Global evaluation of side effect symptoms showed that significantly more paroxetine patients had no side effects, both in the investigators’ and the patients’ opinion. These results are in line with previous findings of paroxetine being an effective and well tolerated antidepressant.     

Platelet paroxetine binding in depressed and nondepressed chronic pain patients

Analysis of ³H-paroxetine binding was used to determine the number of serotonin transporters in platelet membranes of chronic pain patients and controls. The pain patients who also suffered from depression in addition to the pain had significantly more serotonin transporters than the controls.     

A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients

Fluoxetine, a selective serotonin reuptake inhibitor, was compared with mianserin and placebo in a double-blind study. In total, 81 depressed patients were included. Patients were rated weekly on the Hamilton Depression Rating Scale (HDRS) and the Montgomery & Asberg Depression Rating Scale (MADRS). The duration was 6 weeks, and 52 patients completed the study. Significantly more patients on fluoxetine improved than patients on placebo. For mianserin no significant differences were found with either fluoxetine or placebo. Mean HDRS at the end of the study was also statistically significantly lower for fluoxetine, but not for mianserin, than placebo. Subscores of the MADRS showed improved sleep on mianserin at weeks 2 and 3. Suicidal feelings were reduced to a greater degree on fluoxetine than on mianserin and placebo at weeks 6 and 7. Fluoxetine induced weight loss, while patients on mianserin gained weight. Side effects were present in most patients on the two active drugs; those on fluoxetine experienced nausea and vomiting, and those on mianserin drowsiness.     

抗精神病药合并帕罗西汀治疗慢性精神分裂症

目的：探讨抗精神病药合并帕罗西汀治疗慢性精神分裂症阴性症状的疗效。方法：对68例以阴性症状为主的慢性精神分裂症患者，在原用抗精神病药基础上，随机分为合用组和对照组，分别给予帕罗西汀和安慰剂，疗程12周。疗效和药物不良反应评定采用阳性与阴性症状量表（PANSS）和治疗中出现的症状量表（TESS），于治疗前及治疗4、8、12周各评定一次。结果：治疗第8周起合用组PANSS总分及阴性因子分均比治疗前显著降低。结论：以阴性症状为主的慢性精神分裂症患者，在使用抗精神病药同时联用帕罗西汀可改善阴性症状，两组不良反应无明显差异。     

A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease

OBJECTIVE: To examine the efficacy of fluoxetine in the treatment of depression in patients with probable Alzheimer's disease (AD). METHODS: This double-blind, parallel-design study included a consecutive series of 41 AD subjects meeting DSM-IV criteria for major or minor depression who were randomized to receive fluoxetine (up to 40 mg/day) or identical-appearing placebo. All patients received biweekly evaluations consisting of the Hamilton Depression Scale (HAM-D) and the Clinical Global Impression as primary efficacy measures, and the Mini-Mental State Exam, Hamilton Rating Scale for Anxiety, and the Functional Independence Measure as secondary efficacy measures. RESULTS: Complete remission of depression was found in 47% of subjects treated with fluoxetine and in 33% of subjects treated with placebo. Both the fluoxetine and the placebo groups showed a significant decline in HAM-D scores over time, but the magnitude of mood improvement was similar for both groups. Fluoxetine was well tolerated, and most side effects were mild. CONCLUSION: Fluoxetine treatment for depression in AD did not differ significantly from treatment with placebo. Our study also confirms the presence of a placebo effect in the treatment of depression in AD.     

维生素B12辅助治疗抑郁症对照研究

目的:探讨维生素B12辅助治疗抑郁症的疗效和安全性.方法:采用双盲对照方法,对60例抑郁症患者随机分为两组,服用盐酸帕罗西汀和胶囊(内容物分别为维生素B12和中性淀粉),疗程6周.采用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)及治疗中出现的症状量表(TESS)评定疗效和不良反应.结果:治疗6周末时两组的有效率相仿,但研究组HAMD评分值显著低于对照组(P＜0.05);两组间TESS评分差异均无显著性(P均＞0.05).结论:维生素B12辅助治疗抑郁症起效快、疗效好、安全性高,值得临床应用.     

A double-blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients

Hnyberg OJ, Maragakis B, Mullin J, Norum D, Stordall E, Ekdahl P, Ose E, Moksnes KM, Sennef C. A double-blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients. Acta Psychiatr Scand 1996: 93: 184–190. © Munksgaard 1996. A total of 115 elderly patients (60–85 years of age) with DSM III diagnosis of major depressive episode were randomly assigned to 6 weeks of treatment with either mirtazapine, 15–45 mg/day, or amitriptyline, 30–90 mg/day. Efficacy was assessed biweekly, using tbe Hamilton Rating Scale for Depression (HRSD) and Montgomery and Åsberg Depression Rating Scale (MADRS) as primary outcome variables. The treatment with both drugs resulted in a similar reduction of total HRDS and MADRS scores, with no statistically significant differences between treatment groups at any assessment point or at endpoint. Statistically significant differences favouring amitriptyline were present according to CGI-Global Improvement Scale at endpoint, HRDS cognitive disturbance factor at weeks 2, 4 and 6 and endpoint and retardation factor at week 6. Adverse events were reported by a similar number of patients in both treatment groups. Additional research is needed to assess further the efficacy and tolerability of mirtazapine among elderly depressed patients.     

奥氮平对老年抑郁症的增效作用

目的：探讨帕罗西汀联合小剂量奥氮平治疗老年抑郁症的疗效和安全性。方法：将96例老年抑郁症患者随机分为研究组和对照组,研究组采用帕罗西汀合并奥氮平治疗,对照组用帕罗西汀治疗,治疗12周。两组分别在治疗2、4、8、12周,采用汉密尔顿抑郁量表（HAMD）、临床疗效总评量表（CGI）评定疗效,用治疗中出现的症状量表（TESS）评定不良反应。结果：研究组HAMD评分降分率显著较大,CGI评分显著较低,两组TESS评分相仿。结论：帕罗西汀联合小剂量奥氮平治疗老年抑郁症的疗效好,不良反应无明显增加。     

A comparison of paroxetine and placebo in depressed outpatients

To compare the safety and efficacy of paroxetine (n= 167) and placebo (n= 169), data from 4 centres using the same protocol were pooled. A double-blind parallel group design was used, with therapy lasting 6 weeks. Significant differences between paroxetine- and placebo-treated patients were found on the major efficacy outcome variables by week 2 and on all efficacy variables by week 4 of the study. Improvement on the sleep factor of the Hamilton Rating Scale for Depression was found after 7 d. Observer and patient global efficacy ratings were in agreement by week 4. No serious adverse events occurred, and paroxetine had no clinically significant effects on vital signs or laboratory safety data. Side effects were more common on paroxetine and were similar to other serotonin reuptake inhibitors. In general, these were well tolerated and did not lead to dropout. Symptoms of increased arousal were not seen during early therapy.     

米氮平与氟西汀治疗老年抑郁症对照研究

目的:比较米氮平和氟西汀对老年抑郁症的疗效和不良反应. 方法:将60例老年抑郁症患者随机分为米氮平组和氟西汀组,分别给予米氮平和氟西汀治疗,疗程6周.采用汉密尔顿抑郁量表(HAMD)及副反应量表(TESS)评定疗效和不良反应. 结果:米氮平组和氟西汀组显效率分别为83.3%和76.7%,二者疗效相仿.HAMD评分米氮平组治疗1周即显著下降,氟西汀组治疗4周时显著下降.米氮平组嗜睡较多,而氟西汀组口干、失眠、兴奋或激越等发生率较高. 结论:米氮平是一种安全、有效的抗抑郁药物,能用于老年抑郁症患者.     

不同剂量氟西汀治疗抑郁症对照研究

目的：比较不同剂量氟西汀治疗抑郁症的疗效及不良反应。方法：将50例抑郁症患者随机分为两组,分别给予氟西汀60mg／d(60mg组)及20mg/d(20mg组)治疗8周。以20mg／d治疗8周无显著疗效者,加量至60mg／d(加量组),继续治疗6周。采用汉密尔顿抑郁量表(HAMD)和副反应量表(TESS),每2周评定1次。结果：两组问显效率、不良反应差异均无显著性,但HAMD减分率在治疗第2、4周末差异有显著性。加量组8例,14周末HAMD评分及减分率与8周末比较差异均有显著性,4例显效。结论：氟西汀治疗抑郁症,较大剂量对部分患者更适宜。     

A feasibility study of antidepressant drug therapy in depressed elderly patients with chronic obstructive pulmonary disease

OBJECTIVES: To examine the acceptability of fluoxetine in elderly depressed patients with chronic obstructive pulmonary disease (COPD). SETTING: A university teaching hospital. METHOD: Single-blinded (open) study. One hundred and thirty-seven outpatients (69 male) with symptomatic irreversible, moderate to severe COPD were recruited. Major depression was diagnosed using the Geriatric Mental State Schedule. Quality of life was assessed by the Breathing Problems Questionnaire, physical disability by the Manchester Respiratory Activities of Daily Living Questionnaire and severity of depression using the Montgomery Asberg Depression Rating Scale. Exclusion criteria were: use of oral steroids within 6 weeks, acute or chronic confusion, known cancer and known psychosis. RESULTS: Fifty-seven patients (42%) (25 males) with a mean age of 72 years (range 60-89 years) were depressed. Fourteen (six male) agreed to undergo therapy with fluoxetine 20 mg/day for 6 months, while 36 (72%) refused antidepressant drug therapy. Only seven subjects completed the trial; of these, four (57%) responded to fluoxetine therapy. Five subjects withdrew because of side-effects. Twenty-two of those who refused treatment (61%) agreed to be interviewed, and of these 19 (86%) were still depressed. CONCLUSION: Patient acceptance of fluoxetine was poor. The reasons for refusing treatment varied but were largely due to misapprehension by the patient. Untreated depression became chronic. Offering antidepressants to COPD patients with depression is not an effective strategy. Why this might be so is discussed.     

A Double-Blind Study of Paroxetine, Fluoxetine, and Placebo an Outpatients with Major Depression

We report results from a multicenter, placebo-controlled, randomized, double-blind comparison of the efficacy and tolerability of paroxetine and fluoxetine in outpatients with major depression. Across five U.S. sites, 128 outpatients (mean age: 41.3 ± 12.6; 63 men and 65 women) with moderate to moderately severe major depression without a history of mania or hypomania were recruited between 1993 and 1994. All 128 patients completed a 1-week placebo washout period, and were then randomized to 12 weeks of double-blind treatment with paroxetine up to 50 mg/day (n = 55), fluoxetine up to 80 mg/day (n = 54), or placebo (n = 19). Subjects were evaluated weekly for the first 4 weeks, then at weeks 6, 9, and 12 with the 21-item HAMD and the Covi Anxiety Scale. There were no significant differences among the three treatment groups in baseline and endpoint depression and anxiety severity, as well as in the degree of depression and anxiety improvement. There were no statistically significant differences in rates or mean numbers of adverse events between paroxetine-treated patients and fluoxetine-treated patients. In summary, our results, although limited by the lack of a significant difference from placebo in treatment outcome, suggest that the SSRIs paroxetine and fluoxetine have comparable antidepressant and antianxiety efficacies among depressed outpatients, as well as similar safety and tolerability profiles.     

Dose escalation vs. continued doses of paroxetine and maprotiline: a prospective study in depressed out-patients with inadequate treatment response

In view of the fact that controlled prospective studies on the benefits of dose escalation of the selective serotonin re-uptake inhibitor (SSRI) paroxetine are lacking, we conducted a double-blind, randomized, parallel-group multicentre study designed to compare the possible benefits of dose escalation of paroxetine and maprotiline in patients suffering from major or minor depression according to modified Research Diagnostic Criteria (RDC) with inadequate treatment response. The study sample consisted of 544 out-patients with different degrees of severity of depression. Patients received either 20 mg paroxetine (n=271) or 100 mg maprotiline (n=273) for the first 3 weeks in a double-blind manner. Response after 3 weeks was defined using explicit operationalized criteria. Patients with inadequate treatment response (paroxetine group, n=86; maprotiline group, n=88) were again randomized to either continuation of the previous dosage (paroxetine, n=36; maprotiline, n=48) or increased doses, i.e. 40 mg paroxetine (n=50) or 150 mg maprotiline (n=40), respectively. Intention-to-treat and completer analyses were performed. Defining response as a reduction in Hamilton Depression Rating Scale (17-item version) (HAMD-17) score of at least 50% from baseline, no significant benefits of dose escalation were found for either paroxetine or maprotiline. Stratification according to baseline severity of depression also revealed no significant benefits of dose escalation. After dose escalation, new adverse events that had not been present during treatment with lower doses rarely occurred. Our results support the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients.     

西酞普兰与帕罗西汀治疗抑郁症对照研究

目的:比较西酞普兰与帕罗西汀治疗抑郁症的临床疗效和安全性. 方法:将68例符合中国精神障碍分类与诊断标准第3版抑郁发作诊断标准的患者,随机分为西酞普兰组与帕罗西汀组,疗程6周.用汉密尔顿抑郁量表(HAMD)评定疗效,用副反应量表(TESS)评定不良反应. 结果:西酞普兰组和帕罗西汀组的有效率分别为85.3%和82.4%,两组相仿.但治疗1周及2周后,西酞普兰组的有效率高于帕罗西汀组.两组间不良反应比较差异无显著性. 结论:西酞普兰是一种起效较快,且安全、有效的新型抗抑郁药.     

噻萘普汀与帕罗西汀治疗抑郁症对照研究

目的:比较噻萘普汀与帕罗西汀的抗抑郁效果及不良反应。方法:随机将60例心境障碍(抑郁发作)的患者分为噻萘普汀组和帕罗西汀组各30例。疗程6周。在治疗前及治疗1、2、4、6周评定汉密尔顿抑郁量表(HAMD,17项),并记录不良反应。结果:噻萘普汀组从治疗2周HAMD评分开始显著下降,而帕罗西汀组从治疗1周就开始显著下降;治疗6周噻萘普汀有效率90.0%,显效率73.3%,帕罗西汀组分别为90.0%和80.0%。两组患者的不良反应相仿。结论:噻萘普汀和帕罗西汀治疗抑郁症疗效相当,不良反应少。     

文拉法辛与氟西汀治疗抑郁症伴躯体症状对照研究

目的：比较文拉法辛与氟西汀治疗抑郁症伴躯体症状的临床疗效。方法：将77例患者随机分为两组,分别给予文拉法辛与氟西汀治疗6周,用汉密尔顿抑郁量表（HAMD）和治疗中出现的症状量表（TESS）作为评定指标分别于治疗前后评定疗效和不良反应。结果：文拉法辛组总有效率和临床治愈率分别为89.74%和66.67%,明显高于氟西汀组（分别为71.05%和39.47%）;两组HAMD评分治疗后均显著下降（P〈0.01）,文拉法辛组总分和焦虑/躯体化因子分,明显低于氟西汀组（P〈0.05）。结论：在治疗躯体症状方面,文拉法辛优于氟西汀。     

米氮平与帕罗西汀治疗抑郁症对照研究

目的:评价米氮平对抑郁症的疗效和不良反应。方法:将门诊和住院患者56例随机分为两组,分别给予米氮平和帕罗西汀治疗,疗程6周。采用Hamilton抑郁量表(HAMD)和临床疗效总评量表病情严重程度(CGISI)及副反应量表(TESS)评价疗效和不良反应。结果:米氮平组在治疗1、2周末HAMD、CGISI评分显著低于帕罗西汀组(P<0.05)。治疗6周时两组临床疗效相似。两组不良反应均轻微。结论:米氮平是一种安全有效的抗抑郁药,起效较快。     

A randomized,placebo-controlled trial of paroxetine in nursing home residents with non-major depression

Depression is common across a broad spectrum of severity among nursing home residents. Previous research has demonstrated the effectiveness of antidepressants in nursing home residents with major depression, but it is not known whether antidepressants are helpful in residents with less severe forms of depression. We conducted a randomized double-blind placebo-controlled 8-week trial comparing paroxetine and placebo in very old nursing home residents with non-major depression. The main outcome measure was the primary nurse's Clinical Impression of Change (CGI-C). Additional outcome measures were improvement on the interview-derived Hamilton Depression Rating Scale (HDRS) and Cornell Scale for Depression (CS) scores. Twenty-four subjects with a mean age of 87.9 were enrolled and twenty subjects completed the trial. Placebo response was high, and when all subjects were considered, there were no differences in improvement between the paroxetine and placebo groups. Two subjects that received paroxetine developed delirium, and subjects that received paroxetine were more likely to experience a decrease in Mini Mental State Exam scores (P =.03). There were no differences in serum anticholinergic activity between groups. In a subgroup analysis of 15 subjects with higher baseline HDRS and CS scores, there was a trend toward greater improvement in the paroxetine group in an outcome measure that combined the CGI-C and interview-based measures (P =.06). Paroxetine is not clearly superior to placebo in this small study of very old nursing home residents with non-major depression, and there is a risk of adverse cognitive effects. Because of the high placebo response and the trend towards improvement in the more severely ill patients, it is possible that a larger study would have demonstrated a significant therapeutic effect for paroxetine as compared with placebo. The study also illustrates the discordance between patient and caregiver ratings, and the difficulties in studying very elderly patients with mood disorders.