Open-label study of mirtazapine orally disintegrating tablets in depressed patients in the nursing home

OBJECTIVE: To evaluate the efficacy and tolerability of mirtazapine orally disintegrating tablets in depressed, elderly nursing home residents, under naturalistic study conditions. METHODS: In this open-label 12-week study, mirtazapine orally disintegrating tablets (15-45 mg/day) were administered to patients > or =70 years old with physician-diagnosed depression and a Mini-Mental State Examination (MMSE) score > or =10. Patients with medical comorbidities, cognitive impairment and/or concomitant medications were enrolled if they met study inclusion criteria and had illnesses and/or medication dosages that were considered stable. Assessments were performed at baseline by physicians and at days 14, 28, 56, and 84 (or early termination) by physicians or nurse coordinators using the Clinical Global Impression (CGI) scale, the 16-item Hamilton Rating Scale for depression (Ham-D-16 (the standard 17-item scale minus item 14)), and the Cornell Scale for Depression in Dementia (CSDD). Tolerability was evaluated based on treatment-emergent adverse events. RESULTS: A total of 119 patients in the intent-to-treat (ITT) group were treated with mirtazapine orally disintegrating tablets (mean daily dose: 19.4 mg) and evaluated for efficacy. At endpoint, 54% of patients in the ITT group showed CGI-I response (defined as a CGI-I score of 1 or 2 ('very much' or 'much' improved) and 47% were Ham-D-16 responders (defined as decrease from baseline of at least 50% in Ham-D-16 total score). CSDD mean scores and Ham-D-16 mean total scores demonstrated a progressive decrease from baseline to trial completion. The decrease in Ham-D scores from baseline to day 84 was statistically significant (p < 0.0001). Mean changes from baseline to day 84 were -6.6 +/- 6.9 (CSDD score) and -7.9 +/- 7.4 (Ham-D-16 total score). Ham-D Factor I, Factor VI and item 1 scores also decreased. Fourteen of 124 patients in the all-subjects-treated (AST) group (11.3%) discontinued prematurely due to adverse events. The most frequently occurring adverse events were urinary tract infection (19%), accidental injury (18%), fall (18%), somnolence (12%), and upper respiratory infection (12%). Mean body weight increased by 0.7 +/- 2.25 kg (1.54 +/- 5 lb) from baseline to day 28, and by 1.3 +/- 3.36 kg (2.86 +/- 7.4 lb) from baseline to day 84. CONCLUSIONS: The results suggest that mirtazapine orally disintegrating tablets provide antidepressant efficacy and are a relatively well-tolerated treatment for depression in this patient population of elderly nursing home residents with medical and cognitive comorbidities.     

Faster response on amisulpride 50 mg versus sertraline 50-100 mg in patients with dysthymia or double depression: a randomized, double-blind, parallel group study.

Amisulpride (50 mg o.d.) was compared with sertraline (50-100 mg o.d.) for 12 weeks in a double-blind, parallel-group study in 313 outpatients with dysthymia (DSM-IV +/- episode of major depression). Full response rate [> or = 50% decrease in Hamilton Depression Rating Scale (HAMD) total score] was higher with amisulpride after 4 weeks (63% versus 50%, P < 0.02) and 8 weeks (82% versus 69%, P < 0.009). Time to initial improvement (> or = 25% decrease in HAMD total score) and to > or = 50% HAMD decrease were significantly shorter with amisulpride (P < 0.0033 and P < 0.0080, respectively). A faster response was also present in the subgroup of patients with pure dysthymia. The improvement in HAMD, Montgomery and Asberg Depression Rating Scale and Social and Occupational Assessment Scale total scores, as well as Clinical Global Impression improvement, was significantly greater with amisulpride after 4 weeks. Both drugs were equally effective at week 12. The tolerability of both drugs was satisfactory. Amisulpride is significantly more effective than sertraline during the first weeks of treatment in dysthymia.     

米氮平与西酞普兰治疗老年抑郁症的对照研究

目的探讨米氮平和西酞普兰对老年抑郁症的疗效和安全性。方法将72例老年抑郁症患者随机分为研究组和对照组,分别给予米氮平和西酞普兰治疗,疗程8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。结果治疗8周后,研究组和对照组有效率分别为88.89%,86.11%(P>0.05)。两组治疗后HAMD总分、焦虑/躯体化因子分及睡眠障碍因子分均有明显下降(P<0.05或0.01),但研究组下降更迅速、更明显(P<0.05或0.01)。两组不良反应发生率和TESS评分均无明显差异(P>0.05)。结论与西酞普兰相比,米氮平治疗老年性抑郁症同样安全有效,但起效更快,对于改善失眠、焦虑、躯体化症状尤其有优势。     

Open-label study of mirtazapine orally disintegrating tablets in depressed patients in the nursing home

SUMMARY

Objective: To evaluate the efficacy and tolerability of mirtazapine orally disintegrating tablets in depressed, elderly nursing home residents, under naturalistic study conditions.

Methods: In this open-label 12-week study, mirtazapine orally disintegrating tablets (15–45mg?day^?1) were administered to patients >70 years old with physician-diagnosed depression and a Mini-Mental State Examination (MMSE) score >10. Patients with medical comorbidities, cognitive impairment and/or concomitant medications were enrolled if they met study inclusion criteria and had illnesses and/or medication dosages that were considered stable. Assessments were performed at baseline by physicians and at days 14, 28, 56, and 84 (or early termination) by physicians or nurse coordinators using the Clinical Global Impression (CGI) scale, the 16-item Hamilton Rating Scale for depression (Ham-D-16 (the standard 17-item

scale minus item 14)), and the Cornell Scale for Depression in Dementia (CSDD). Tolerability was evaluated based on treatment-emergent adverse events.

Results: A total of 119 patients in the intent-to-treat (ITT) group were treated with mirtazapine orally disintegrating tablets (mean daily dose: 19.4mg) and evaluated for efficacy. At endpoint, 54% of patients in the ITT group showed CGI-I response (defined as a CGI-I score of 1 or 2 ('very much' or 'much' improved) and 47% were Ham-D-16 responders (defined as decrease from baseline of at least 50% in Ham-D-16 total score). CSDD mean scores and Ham-D-16 mean total scores demonstrated a progressive decrease from baseline to trial completion. The decrease in Ham-D scores from baseline to day 84 was statistically significant (p?<?0.0001). Mean changes from baseline to day 84 were ?6.6?±?6.9 (CSDD score) and ?7.9?±?7.4 (Ham-D-16 total score). Ham-D Factor I, Factor VI and item 1 scores also decreased. Fourteen of 124 patients in the all-subjects-treated (AST) group (11.3%) discontinued prematurely due to adverse events. The most frequently occurring adverse events were urinary tract infection (19%), accidental injury (18%), fall (18%), somnolence (12%), and upper respiratory infection (12%). Mean body weight increased by 0.7?±?2.25?kg (1.54?±?5lb)

from baseline to day 28, and by 1.3?±?3.36?kg (2.86?±?7.4lb) from baseline to day 84.

Conclusions: The results suggest that mirtazapine orally disintegrating tablets provide antidepressant efficacy and are a relatively well-tolerated treatment for depression in this patient population of elderly nursing home residents with medical and cognitive comorbidities.     

Efficacy and safety of amisulpride 50 mg versus paroxetine 20 mg in major depression: a randomized, double-blind, parallel group study.

The efficacy of amisulpride in depressive disorders has been demonstrated in dysthymia and in double depression. Limited data are available in major depression. A randomized, double-blind, parallel group, multicentre study was set up to compare the efficacy and tolerability of amisulpride (50 mg o.d.) and paroxetine (20 mg o.d.) for 8 weeks in 272 patients with major depression (DSM-IV and baseline Hamilton Depression Rating Scale (HAMD) score > or = 18). The study was designed as a non-inferiority trial based on the proportion of responders (> or = 50% decrease in HAMD total score) at end-point, with a maximal allowable difference of 15%; secondary end-points included HAMD total and cluster scores, Montgomery and Asberg Depression Rating Scale score and responders rates and Clinical Global Impression improvement. The tolerability evaluation was based on incidence of adverse events and routine laboratory tests. The results did not disclose statistically significant differences between treatments, although the hypothesis of an efficacy difference between the two treatments within the set limit at day 56 could not be accepted. The issue of non-inferiority trials is discussed.     

Olanzapine orally disintegrating tablets in the treatment of acutely ill non-compliant patients with schizophrenia

The objective of this study was to determine if the orally disintegrating tablet formulation of olanzapine, Zyprexa Zydis, would facilitate antipsychotic medication compliance in acutely ill, non-compliant patients. Eighty-five acutely ill patients with schizophrenia or schizoaffective disorder who met medication non-compliance criteria received open-label olanzapine orally disintegrating tablets (1020 mgd) for up to 6 wk. Improvement in medication compliance was assessed using various rating scales to measure changes in psychopathology, medication-taking and compliance attitudes, and nursing care burden. Safety variables were also measured. Significant improvement from baseline was demonstrated in the Positive and Negative Syndrome Scale total score at Week 1 and subsequently (p0.001). Significant improvement from baseline was also seen in various scales measuring medication compliance, attitude, and nursing care burden (p0.05). Olanzapine orally disintegrating tablets were well-tolerated. Olanzapine orally disintegrating tablets may benefit acutely ill, non-compliant schizophrenic patients by facilitating acceptance of active antipsychotic drug therapy.     

文拉法辛治疗首次抑郁发作临床研究

目的探讨文拉法辛治疗首次抑郁发作的疗效与不良反应。方法 102例首次抑郁发作患者随机平分为文拉法辛组和帕罗西汀组,每组51例。两组分别给予文拉法辛与帕罗西汀治疗,疗程8周。采用汉密尔顿抑郁量表（HAMD）、治疗中出现的症状量表（TESS）评定疗效及不良反应。结果治疗后两组HAMD评分均较治疗前有显著降低（P〈0.01）;治疗2周末文拉法辛组显著低于帕罗西汀组（χ2=7.121,P〈0.01）;两组中重度抑郁患者（HAMD〉24分）治疗后HAMD评分仍以文拉法辛组显著为低（t=2.25,P〈0.05）;两组间比较差异无统计学意义（P〉0.05）。结论文拉法辛起效快,对重度抑郁症的疗效明显。     

Intravenous mirtazapine in the treatment of depressed inpatients.

Mirtazapine is a novel antidepressant with a noradrenergic and specific serotonergic mode of action. So far, mirtazapine has been administered orally. This naturalistic study evaluates the antidepressant efficacy, safety, and tolerability of mirtazapine 15 mg/day administered intravenously to 27 inpatients with moderate to severe major depression. Compared with baseline, we found a significant decrease of the Hamilton Depressive Rating Scale (HDRS) total score (P<0.001). Side effects were mild and transient. Altogether, the results of this preliminary study show that intravenous mirtazapine is an effective, safe and well tolerated treatment for depressed inpatients.     

利培酮对首发精神分裂症S100B蛋白含量影响与疗效关系

目的:探讨首发精神分裂症S100B蛋白是否异常;利培酮对S100B影响与疗效之间关系。方法:收集符合美国精神障碍诊断与统计手册第4版诊断标准首发精神分裂症住院患者53例,正常对照58例。患者组单一利培酮治疗12周,阳性和阴性综合症量表(positive and negative syn-drome scale,PANSS)、临床总体印象量表(clini-cal general impression,CGI)、汉密尔顿抑郁量表(hamiton depression rating scale,HAMD)评定病情,酶联免疫吸附法(enzyme linked immu-nosorbent assay,ELISA)检测研究对象的S100B含量。结果:基线患者组的S100B蛋白含量显著高于正常对照组(P<0.01)。12周利培酮治疗后S100B含量显著低于治疗前,但仍高于正常对照(P<0.05)。基线S100B蛋白含量与发病年龄、HAMD评分呈显著负相关(r=-0.22,-0.23,P均<0.05);治疗后S100B蛋白含量有效组低于无效组,与治疗前后PANSS减分值、阴性症状减分值呈显著负相关(r=-0.28、-0.31,P均<0.05)。结论:首发精神分裂症S100B含量显著高于正常对照;利培酮治疗降低S100B含量且与临床疗效有一定的相关性;精神分裂症患者中枢神经系统可能存在着结构性损伤。     

A 12-week study comparing moclobemide and sertraline in the treatment of outpatients with atypical depression

One hundred and ninety-seven outpatients with atypical depression [Atypical Depression Diagnostic Scale (ADDS) score=4] were randomized to 12 weeks of double-blind treatment with sertraline or moclobemide in a multicentre, parallel-group clinical trial. Patients were started on either 50 mg/day sertraline or 300 mg/day moclobemide. If the therapeutic response was not satisfactory after 4 weeks, the dose could be increased to either 100 mg/day sertraline or 450 mg/day moclobemide. Primary efficacy evaluations were the 29-item Hamilton Psychiatric Rating Scale for Depression (HAM-D) and the Clinical Global Impression of Improvement (CGI-I) response rate (much or very much improved) at study endpoint. Secondary efficacy evaluations included the ADDS, the Hamilton Anxiety Scale (HAMA), the Leeds Sleep Scale, and the Battelle Quality of Life Battery (BQOLB). In the analysis of the 172 patient efficacy-evaluable population, there was significant baseline to endpoint improvement in all primary and secondary efficacy assessments after treatment with either sertraline or moclobemide. At the endpoint, the proportion of responders on CGI-I, was 77.5% in the sertraline group and 67.5% in the moclobemide group (p=0.052). The baseline to endpoint mean 29-item HAM-D score decreased from 35.9 to 14.5 in the sertraline group and from 36.3 to 16.1 in the moclobemide group. Sertraline also resulted in a significantly (p < 0.05) greater degree of improvement at the endpoint, compared with moclobemide, in the proportion of remitters on the HAMA (total score < or = 7), ADDS Category IID (Rejection Sensitivity), Leeds Sleep Factor 4 (Integrity of Behaviour Following Awakening), and on three dimensions of the BQOLB (Energy/Vitality, Social Interaction and Life Satisfaction). There were no other significant differences between treatment groups. Overall, both medications were well tolerated. In this study, both sertraline and moclobemide improved the symptoms of atypical depression.     

Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder

This randomized, multicenter, double-blind study was designed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets (ODT) with venlafaxine extended-release (XR) formulation in outpatients with major depression. Both treatments were administered in a rapidly escalating dosing regimen. Target doses (mirtazapine ODT, 45 mg OD; venlafaxine XR, 225 mg OD) were reached by day 6 of treatment. On the primary efficacy parameter [the average of the change in HAM-D (17-item) total score on days 5, 8, 11, and 15], mirtazapine ODT was significantly superior to venlafaxine XR (P = 0.008). In addition, calculating the HAM-D score without the sleep items resulted in significant reductions in favor of mirtazapine ODT on days 8 (P = 0.006) and 11 (P = 0.037). The proportion of responders (HAM-D decrease of > or =50% from baseline) was higher in the mirtazapine ODT group on all assessment days, being significant on days 8 (P = 0.002), 11 (P = 0.004), and 22 (P = 0.027). More patients in the mirtazapine ODT group achieved remission (HAM-D total score of < or =7) up to day 29, and the difference was statistically significant on day 15 (P = 0.016). Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 (P = 0.019), 11 (P = 0.004), and 15 (P = 0.031), and the CGI of severity on days 8 (P = 0.014) and 11 (P = 0.033). Both treatments were well tolerated. These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR in patients with major depressive disorder, and that this effect is independent of its sleep-improving properties.     

奥氮平辅助治疗难治性抑郁症患者的疗效及对生活质量的影响

目的探讨奥氮平辅助治疗难治性抑郁症患者的疗效及对生活质量的影响。方法68例难治性抑郁症患者随机分为研究组（奥氮平＋舍曲林n=34）和对照组（单用舍曲林n=34）,疗程8周。以汉密尔顿抑郁量表（HAMD）及不良反应量表（TESS）分别在治疗前及治疗第1、2、4、6和8周末各评定1次,以生活质量综合问卷（GQOH-74）在治疗前和治疗后8周末各评定一次生活质量。结果研究组于第1周末起效,对照组于第2周末起效,治疗后1、2、4、6周末HAMD评分差异有统计学意义（P〈0．01）。两组间TESS评分差异无统计学意义（P〉0．05）。8周末,研究组除物质生活维度外,其他维度得分明显高于对照组,有显著性差异（P〈0．01）。结论奥氮平辅助治疗难治性抑郁症起效快,可增加疗效,优于单用舍曲林治疗,且明显改善患者的生活质量。     

Mirtazapine treatment of generalized anxiety disorder: a fixed dose, open label study

We investigated the efficacy of mirtazapine in the treatment of generalized anxiety disorder (GAD). Forty-four adult outpatients with GAD were treated openly with a fixed dose of mirtazapine (30 mg) for 12 weeks. The primary outcome measure was the change from baseline in total score on the Hamilton Rating Scale for Anxiety (HAM-A). The Clinical Global Impression of Improvement (CGI-I) was rated at the endpoint. Patients with a reduction of 50% or more on the HAM-A total score and a CGI-I score of 1 or 2 at endpoint were considered responders to treatment; remission was defined as a HAM-A score 相似文献   

Efficacy and safety of 30 mg/d and 45 mg/d nemifitide compared to placebo in major depressive disorder

Nemifitide is a novel pentapeptide antidepressant, which appears to be effective in the treatment of major depressive disorder (MDD). In the present study 81 patients with MDD, DSM-IV criteria were randomized following a 1-wk screening period to receive 30 mg/d nemifitide, 45 mg/d nemifitide or placebo in a 6-wk double-blind, multicentre, outpatient efficacy study. Nemifitide or placebo was delivered by subcutaneous injection for 2 wk daily for 5 days (Monday to Friday) in the first 2 wk and patients were followed up for a further 4 wk. The primary efficacy measure was the change from baseline on the Montgomery-Asberg Depression Rating Scale. Secondary measures included the 17-item Hamilton Psychiatric Rating Scale for Depression (HAMD), the CGI severity and improvement scale and the Carroll Self-Rating Scale for Depression. This proof-of-principle study demonstrated a statistically significant superiority of the 45-mg/d dose vs. placebo at the time-point of peak effect (1 wk after the end of treatment). There appeared to be a greater effect with the 45 mg/d nemifitide dose than with 30 mg/d. An additional exploratory analysis by stratification of all patients by severity above and below or equal to the median baseline HAMD score of 22 showed a higher percentage of responders for both doses of nemifitide with statistical separation from placebo for patients with baseline HAMD score of >22 (above the median). There was no significant difference among treatment groups for patients with baseline HAMD score of 相似文献   

米氮平联合艾司西酞普兰治疗卒中后抑郁的临床疗效评价

目的：观察米氮平联合艾司西酞普兰治疗卒中后抑郁的临床效果。方法将符合卒中后抑郁症诊断的脑卒中患者98例随机分为两组,治疗组50例在常规药物治疗及康复训练的基础上加用米氮平联合艾司西酞普兰抗抑郁治疗,对照组48例单采用神经科常规药物治疗及康复训练,两组患者分别在入选时及病程1、3、6个月进行日常生活能力（BI）和汉密尔顿抑郁量表（HAMD）评分。结果治疗前两组BI、HAMD评分差异无统计学意义（P〉0.05）,治疗1、3、6个月后治疗组与对照组比较差异有统计学意义（P〈0.05）。治疗组HAMD、BI评分于治疗3、6个月后显著改善（P〈0.05）。结论米氮平联合艾司西酞普兰治疗卒中后抑郁具有显著临床疗效。患者抑郁症状改善的同时显著改善患者日常生活能力。     

瑞波西汀与氟西汀治疗抑郁症随机双盲多中心临床研究

目的:评价瑞波西汀治疗抑郁症的疗效和安全性。方法:采用随机、双盲双模拟、氟西汀平行对照、剂量固定的多中心研究。受试者分别口服瑞波西汀胶囊8mg·d-1或氟西汀片20mg·d-1。采用汉密尔顿抑郁量表(HAMD)总分减分值作为主要疗效指标,以临床总体印象量表(CGI)和汉密尔顿焦虑量表(HAMA)评分作为次要疗效指标;采用药物不良反应量表(TESS)、实验室检查、生命体征等观察药物安全性。结果:共收集符合意向治疗抑郁症病人(ITT)222例,瑞波西汀组(试验组)109例,氟西汀组(对照组)113例。符合研究方案病人(PP)213例,瑞波西汀组104例,氟西汀组109例。治疗6wk后,瑞波西汀组HAMD总分减分值为(16±s7)分,氟西汀组为(16±7)分,与治疗基线相比差异均有非常显著意义(P<0.01),但2组相比差异无显著意义(P>0.05);瑞波西汀组有效率(HAMD减分率≥50%)为81.7%,氟西汀组为77.9%,2组相比差异无显著意义(P>0.05);瑞波西汀组临床治愈率(HAMD总分≤8)为62.4%,氟西汀组为58.4%,2组差异无显著意义(P>0.05);在CGI,HAMA评分上,2组差异亦无显著意义。安全性分析显示,2组不良反应的症状和发生率相比差异均无显著意义。结论:瑞波西汀治疗抑郁症安全有效。     

米氮平和盐酸舍曲林治疗女性更年期抑郁障碍的随机对照研究

目的 探讨米氮平和盐酸舍曲林治疗更年期抑郁障碍的疗效.方法 将64例符合更年期首发抑郁障碍的患者随机分成米氮平组和盐酸舍曲林组.米氮平剂量1日15～45mg.舍曲林1日50～200mg,疗效采用汉密尔顿抑郁量表(HAMD),不良反应和安全性用TESS和实验室检查评定.观察时间为期6周.结果 米氮平组显效率84.38%,...     

新型抗抑郁药治疗抑郁症的对照研究

目的：比较研究新型抗抑郁药治疗抑郁症的疗效。方法将187例抑郁症患者分为3组,分别给予三类新型抗抑郁药单药治疗（ A组：舍曲林、艾司西酞普兰和帕罗西汀,B组：文拉法辛、度洛西汀,C组：米氮平）,疗程共4周。采用17项汉密尔顿抑郁量表（ HDRS-17）作疗效评定,量表减分率≥50％为治疗有效,量表总分≤7分为痊愈。结果3组间基线资料差异无显著统计学意义（ P＞0.05）。终点时治疗有效127例（67.9％）,痊愈75例（40.1％）。3组药物间治疗有效率（χ^2＝1.336,P＝0.513）、痊愈率（χ^2＝1.988,P＝0.370）的差异均无显著性统计学意义。治疗4周后,各组患者的HDRS-17评分及减分率的差异均有显著统计学意义（F＝665.33和496.89,P＜0.05）,3组间各周HDRS-17评分及减分率的差异均无显著统计学意义（F＝2.01和1.36,P＞0.05）。结论新型抗抑郁药物治疗抑郁症均有较好、相当的疗效。     

A double-blind study of the efficacy and safety of sertraline and clomipramine in outpatients with severe major depression

This study compared the efficacy and safety of the selective serotonin reuptake inhibitor sertraline with that of the tricyclic antidepressant clomipramine in patients with severe depression, as defined by a baseline 17-item Hamilton Depression Rating Scale (HAM-D) of at least 25. The study included 166 outpatients, randomized to double-blind treatment with sertraline (50-200 mg) or clomipramine (50-150 mg) for 8 weeks. The efficacy of both treatments was similar, 74% of patients in the sertraline group and 71% of clomipramine patients being classified as responders at the end-point, as defined by a Clinical Global Impression-Improvement (CGI-I) score of 1 or 2. Mean HAM-D scores fell from 29.8 at baseline to 12.3 at endpoint in the sertraline group, and from 29.6-12.7 in the clomipramine group. There were more withdrawals due to adverse events in the clomipramine group than in the sertraline group (17% versus 12%). Dry mouth, tremor, dizziness and constipation were all substantially more common in the clomipramine group, whereas diarrhoea/loose stools was more common in the sertraline group. Overall, sertraline was as effective as clomipramine in this group of severely depressed outpatients, and showed better tolerability.     

A double-blind,randomized parallel-group,efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder

S-adenosyl-L-methionine (SAMe) is a natural substance which constitutes the most important methyl donor in transmethylation reactions in the central nervous system. Several clinical trials have shown that SAMe possesses an antidepressant activity. This multicentre study was carried out to confirm both efficacy and safety of SAMe in the treatment of major depression. SAMe was given intramuscularly (i.m.) at a dose of 400 mg/d, double-blind, vs. 150 mg/d oral Imipramine (IMI) in patients with a diagnosis of major depressive episode, with a baseline score on the 21-item Hamilton Depression Rating Scale (HAMD) of >or=18. A total of 146 patients received SAMe whereas 147 received IMI for a period of 4 wk. The two main efficacy measures were endpoint HAMD score and percentage of responders to Clinical Global Impression (CGI) at week 4. Secondary efficacy measures were the final Montgomery-Asberg Depression Rating Scale (MADRS) scores and the response rate intended as a fall in HAMD scores of at least 50% with respect to baseline. The analysis of safety and tolerability was conducted in all treated patients. SAMe and IMI did not differ significantly on any efficacy measure, either main or secondary. Adverse events were significantly less in patients treated with SAMe compared to those treated with IMI. These data show 400 mg/d i.m. SAMe to be comparable to 150 mg/d oral IMI in terms of antidepressive efficacy, but significantly better tolerated. These findings suggest interesting perspectives for the use of SAMe in depression.