单用或联用瑞波西汀治疗抑郁障碍的疗效与安全性研究

目的:探讨瑞波西汀单独应用或联合其他抗抑郁药治疗重症抑郁症障碍的疗效与安全性。方法:对194例重症抑郁发作患者,分为单用组和联用组,分别单独给予瑞波西汀或者瑞波西汀联用其他抗抑郁药(主要是选择性5-羟色胺再摄取抑制剂)治疗,为期8周。应用汉密尔顿抑郁量表(HDRS)、汉密尔顿焦虑量表(HARS)评估抗抑郁疗效,并观察不良反应的发生情况。结果:194例患者的HDRS评分、HARS评分均明显下降。单用组的HDRS减分率[(73.39±17.73)%]显著高于联用组[(62.71±29.33)%](P<0.01),有效率(90.8%)也显著高于联用组(78.8%)(P<0.05)。常见不良反应为头晕、口干和出汗,多为轻微和轻度,总体不良反应发生率为39.2%;未发生严重不良事件。结论:瑞波西汀单独及联合应用治疗抑郁症均疗效明显,且瑞波西汀单独应用疗效优于联合应用。瑞波西汀具有良好的耐受性。     

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.     

Double-blind comparison of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia

The purpose of this study was to compare the efficacy and tolerability of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia. This was an 8-week, multicentre, randomized, double-blind, parallel-group comparison of venlafaxine and amitriptyline. Outpatients with DSM-IV major depression, a minimum score of 20 on the 21-item Hamilton Depression Rating Scale (HAM-D), and depressive symptoms for at least 1 month were eligible. Patients were randomly assigned to venlafaxine or amitriptyline, both drugs titrated to a maximum of 150 mg/day until study day 15. The primary efficacy variables were the final on-therapy scores on the HAM-D, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression severity scales. Data were evaluated on an intent-to-treat basis using the LOCF method. One hundred and 16 patients were randomized, and 115 were evaluated for efficacy. Both drugs showed efficacy in the treatment of depression with or without melancholia. No significant differences were noted between treatments for any efficacy parameter. However, significantly (p < 0.05) more patients in the amitriptyline group had at least one adverse event. These results should support the efficacy and tolerability of venlafaxine in comparison with amitriptyline for treating major depression with or without melancholia.     

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.     

Effect of metyrapone supplementation on imipramine therapy in patients with treatment-resistant unipolar depression

The paper describes the effect of metyrapone supplementation on imipramine therapy in patients (with treatment-resistant unipolar depression) who fulfilled DSM IV criteria for major depression. Nine patients were enrolled to the study on the basis of history of their illness and therapy. Following 2 weeks of washout period, the patients were treated with imipramine twice daily (100 mg/day) for 6 weeks, and then metyrapone was introduced (twice daily, 500 mg/day), and administered jointly with imipramine for further 6 weeks. Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) were used to assess efficacy of antidepressant therapy. Imipramine changed neither HDRS nor BDI score after 6 weeks of treatment when compared with baseline (before treatment). Metyrapone supplementation significantly reduced both HDRS and BDI scores after 6-week supplementation. Moreover, pharmacokinetic data indicate that metyrapone did not influence significantly the plasma concentration of imipramine and its metabolite, desipramine in the patients during joint treatment with metyrapone and imipramine, what suggests the lack of pharmacokinetic interaction. This preliminary study is the first demonstration of the benefit of metyrapone supplementation in imipramine therapy of treatment-resistant unipolar depression and suggests that a change in the level of neurotransmitters, hormones and immunological parameters, which are disturbed in depression, may contribute to the mechanism of the action of this drug.     

Effects of joint administration of imipramine and amantadine in patients with drug-resistant unipolar depression

The paper describes the effect of amantadine (AMA) supplementation on imipramine (IMI) therapy in patients (with treatment-resistant unipolar depression) who fulfilled DSM IV criteria for major depression. Twelve patients were enrolled to the study on the basis of history of their illness and therapy. Following 2 weeks of washout period, the patients were treated with IMI twice daily (100-150 mg/day) for 6 weeks, and then AMA was introduced (twice daily, 100-150 mg/day) and administered jointly with IMI for further 6 weeks. Thereafter, AMA was withdrawn, and the patients were treated with IMI alone for 2 weeks. Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) were used to assess efficacy of antidepressant therapy. IMI changed neither HDRS nor BDI score after 3 or 6 weeks of treatment when compared with washout (before treatment). AMA supplementation significantly reduced both HDRS and BDI scores after 3- or 6-week supplementation. AMA augmentation of IMI treatment was beneficial and lasted even after AMA withdrawal. Moreover, pharmacokinetic data indicate that AMA did not influence significantly the plasma concentration of the IMI and its metabolite, desipramine, in the patients during joint treatment with AMA and IMI, what suggests the lack of pharmacokinetic interaction. These results suggest that joint therapy with IMI and AMA may be successful in the treatment-resistant unipolar depression.     

A prospective trial of bupropion SR augmentation of partial and non-responders to serotonergic antidepressants

Many patients fail to achieve an adequate response to a given antidepressant trial. The best-studied augmentation agents, lithium and thyroid supplementation are less commonly used. Augmenting antidepressants with bupropion has become an increasingly common strategy in the treatment of resistant depression. Several case reports and 2 open label studies suggest efficacy of this strategy. The purpose of this study is to further examine the utility of bupropion sustained release (SR) augmentation in patients with inadequate response to selective serotonin reuptake inhibitors. Patients who met DSM-IV criteria for major depression and had failed to achieve adequate response to an SSRI were considered for this study. Eligible patients were required to have a score of 16 on the 24-item Hamilton Depression Rating Scale (HDRS). Patients were treated openly for 6 weeks with bupropion SR added to their existing antidepressant. The dose range of bupropion was 150 to 300 mg per day. At each visit, patients were assessed using the Beck Depression Inventory (BDI), the Hamilton Depression Ratings Scale (HDRS), and the Clinical Global Impression (CGI). Twenty-eight patients (12 men, 16 women) entered the study. Twenty-five patients completed the six-week trial. With respect to the clinical benefit of bupropion SR augmentation, 15 out of 28, or 54% of patients, were classified as responders, showing a decrease in their HDRS or BDI scores of 50% or more between baseline and Week 6. This prospective, open-label trial supports the use of bupropion SR in the augmentation of SSRIs and venlafaxine. Placebo controlled trials should be completed to further evaluate the efficacy of this strategy.     

Pindolol and mianserin augment the antidepressant activity of fluoxetine in hospitalized major depressed patients, including those with treatment resistance

The aims of this study were to examine whether pindolol, a serotonin (5-hydroxytryptamine [5-HT])-1A receptor antagonist, and mianserin, a 5-HT2A/C and alpha2-adrenoceptor (alpha2-AR) antagonist, may augment the clinical efficacy of fluoxetine, a selective serotonin reuptake inhibitor, and shorten the latency of onset of antidepressive activity in the treatment of major and treatment-resistant depression (TRD). Ten days after admission to the hospital, 31 major depressed patients were randomly assigned using a double-blind, controlled design to receive fluoxetine 20 mg daily, fluoxetine 20 mg daily plus pindolol 7.5 mg daily, or fluoxetine 20 mg plus mianserin 30 mg daily for 5 weeks. The 17-item Hamilton Rating Scale for Depression (HAM-D) score was the primary outcome measure. Analysis of efficacy was conducted according to the intent-to-treat analysis principle considering the change from baseline to endpoint. It was found that fluoxetine plus pindolol and fluoxetine plus mianserin were significantly more effective than fluoxetine alone. Using an outcome measure of 50% reduction in the HAM-D, a 60% response rate was found in patients treated with either fluoxetine plus pindolol or fluoxetine plus mianserin compared with a 9% response rate in patients treated with fluoxetine alone. The HAM-D score 1 week after starting fluoxetine plus mianserin decreased more than 4 points and was significantly greater than that obtained by fluoxetine alone. The results suggest that pindolol and mianserin augment the efficacy of fluoxetine in the treatment of TRD and that mianserin, but not pindolol, may significantly shorten the latency of onset of antidepressive action when combined with fluoxetine.     

Amantadine as an additive treatment in patients suffering from drug-resistant unipolar depression

The paper describes the effect of amantadine addition to imipramine therapy in patients suffering from treatment-resistant unipolar depression who fulfilled DSM IV criteria for major (unipolar) depression. Fifty patients were enrolled in the study on the basis of their histories of illness and therapy. After a 2-week drug-free period, 25 subjects belonging to the first group were treated only with imipramine twice daily (100 mg/day) for 12 weeks, and 25 subjects belonging to the second group were treated with imipramine twice daily (100 mg/day) for 6 weeks and then amantadine was introduced (150 mg/day, twice daily) and administered jointly with imipramine for the successive 6 weeks. Hamilton Depression Rating Scale (HDRS) was used to assess the efficacy of antidepressant therapy. Imipramine did not change the HDRS score after 3, 6 or 12 weeks of treatment when compared with the washout (before treatment). The addition of amantadine to the classic antidepressant reduced HDRS scores after 6-week joint treatment. Moreover, the obtained pharmacokinetic data indicated that amantadine did not significantly influence the plasma concentration of imipramine and its metabolite desipramine in patients treated jointly with imipramine and amantadine, which suggests lack of a pharmacokinetic interaction. The obtained results indicate that joint therapy with an antidepressant and amantadine may be effective in treatment-resistant unipolar depression.     

Citalopram versus amitriptyline in elderly depressed patients with or without mild cognitive dysfunction: a danish multicentre trial in general practice

This double-blind, multicenter trial, carried out in general practice in Denmark, comprised 221 women and 70 men, aged 58 to 97 years, with major depression (with or without mild cognitive dysfunction) or dysthymia (DSM-III-R). Patients had a total score > or =13 on the 17-item Hamilton Depression Rating Scale (HDRS) and a score > or =20 on the Mini Mental State Examination scale. The efficacy and tolerability of citalopram (20-40 mg daily) and amitriptyline (50-100 mg daily) were compared over 12 weeks. The participating general practitioners were trained at corating sessions in the use of the HDRS and Melancholia Scale (MES) prior to and during the study. The inter-observer reliability was assessed to investigate if general practitioners were able to use scales that measure the severity of depression. The two treatments were considered equally effective; the 90% confidence interval for the difference between the treatment groups in change from baseline to end-point in HDRS total score (-0.84 to +1.23) was within the predefined interval (-4 to +4). Significantly more patients on citalopram (50%) than on amitriptyline (31%) reported no adverse events at all (P = .001). Moreover, patients on amitriptyline reported adverse events significantly earlier and more frequently than patients on citalopram. The inter-observer reliability was highly satisfactory, with intra-class correlation coefficients (ICC-U) of .83 for the HDRS and .82 for the MES; however, the ICC-U for the Clinical Global Impressions was .54, indicating a poorer consensus in the investigators clinical judgment. Training in the use of the HDRS and MES scales improved the inter-observer reliability.     

Venlafaxine in treatment-resistant major depression: a Canadian multicenter, open-label trial.

This was an 8-week, multicenter, open-label study of the efficacy and tolerability of venlafaxine in patients with treatment-resistant depression conducted in Canada. Inpatients or outpatients aged 18 to 70 years with major depression were eligible if they had a 21-item Hamilton Rating Scale for Depression (HAM-D-21) score of 2 > or = 18 and a documented history of unsatisfactory improvement after a minimum of 8 weeks of treatment with an adequate dose of an antidepressant. Treatment with venlafaxine was started at 37.5 mg twice daily, and the dose could be titrated upward to a maximum of 375 mg/day during the first 4 weeks on the basis of the investigator's assessment of clinical response and tolerability. Of the 159 patients enrolled, 152 were evaluable for efficacy. The mean daily venlafaxine dose was 260 mg/day. The mean HAM-D-21 score decreased by 52%, and the mean Montgomery-Asberg Depression Rating Scale score decreased by 50% from baseline to day 56. A response (50% improvement from baseline) was achieved by 58% of patients on the HAM-D-21, and a remission (> or = 75% improvement in the HAM-D-21) was observed in 28% at day 56. By day 56, 88% of patients had improved from baseline on the Clinical Global Impression Improvement scale. Only 8% of the patients discontinued for adverse events. The most common adverse events were headache, insomnia, nausea, constipation, diaphoresis, and xerostomia. In conclusion, these results suggest that venlafaxine is effective and well tolerated for the management of patients with treatment-resistant major depression.     

Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial

BACKGROUND: Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients. METHODS: Under double-blind conditions, 93 hospitalized patients older than 59 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode, were randomly assigned to receive sertraline (150 mg daily) or fluvoxamine (200 mg daily) for 7 weeks. The clinical response was defined as a reduction on the Hamilton Rating Scale for Depression score to 8 or below. RESULTS: At study completion, the response rates were 55.6% (25/45) and 71.8% (28/39) for sertraline and fluvoxamine, respectively. No significant difference in final response rates was found between the 2 treatment groups (P = 0.12). A repeated-measures analysis of variance on Hamilton Rating Scale for Depression scores revealed a significantly different decrease of depressive symptoms between the 2 treatment groups, favoring fluvoxamine (P = 0.007). The overall safety profile of sertraline and fluvoxamine was favorable with no differences between the 2 drugs. CONCLUSION: The results of this double-blind trial show that sertraline and fluvoxamine may be effective compounds in the treatment of elderly depression with the latter showing some advantage in terms of speed of response. These findings warrant further replication in placebo-controlled studies.     

A randomized, single-blind, comparison of venlafaxine with paroxetine in elderly patients suffering from resistant depression

It is estimated that up to 45% of patients with depression do not have an adequate response to a first trial of antidepressant therapy with even higher reported rates for the elderly patients. To compare the efficacy and the tolerability of venlafaxine vs. paroxetine in elderly patients suffering from resistant major depression, who did not respond to at least two previous adequate trials of antidepressants. Patients entered an 8-week single-blind study. Patients were rated using the Clinical Global Impression Scale, Hamilton Rating Scale for Depression, and the Geriatric Depression Scale. Assessments were performed at baseline and on days 7, 14, 21, 28, 42 and 56. Side effects were recorded in a systemic manner. Thirty patients were included in the study, (17 women, 13 men; mean age=75.9 years, range: 68-83) and all had completed the 6-week trial. Mean dose of venlafaxine used was 165 mg/day (SD=73.8; range 75-300 mg). Mean dose of paroxetine used was 26 mg/day (SD=15.04; range 10-60 mg). Nine patients treated with venlafaxine (60%) and five patients treated with paroxetine (33%) remitted after 8 weeks of treatment. Four patients treated with venlafaxine and eight patients treated with paroxetine failed to respond. Significant improvement in Hamilton Rating Scale for Depression scores between baseline and endpoint were observed in both groups of patients. The mean Hamilton Rating Scale for Depression change for paroxetine was -12.5 and for venlafaxine -19.1 (P<0.05). The mean Geriatric Depression Scale change for paroxetine was -3.2 and for venlafaxine -6.0 (P<0.3). The mean Clinical Global Impression Scale change was -2.3 for paroxetine and -3.5 for venlafaxine (P<0.05). Venlafaxine was significantly superior to paroxetine on Clinical Global Impression Scale and Hamilton Rating Scale for Depression measures. Side effects were transient and did not differ between treatment groups. Elderly depressed patients resistant to previous treatments had responded to a trial of paroxetine or venlafaxine. Remission rates were higher for venlafaxine and tolerability was acceptable for both compounds.     

Reboxetine: a double-blind comparison with fluoxetine in major depressive disorder

The aim of this study was to compare the efficacy and tolerability of reboxetine, a uniquely selective noradrenaline reuptake inhibitor, with the selective serotonin reuptake inhibitor, fluoxetine. A double-blind, randomized, parallel-group, multicentre design was employed. One hundred and sixty-eight patients with acute major depressive episodes were randomized to receive oral reboxetine (8-10 mg/day) or oral fluoxetine (20-40 mg/day). The treatment period was 8 weeks. Reboxetine and fluoxetine were similarly effective as assessed by the mean reduction in total Hamilton Depression Rating Scale score, the percentage of responders and patients in remission, Clinical Global Impression severity of illness and global improvement scores and Montgomery-Asberg Depression Rating Scale. A sub-analysis of patients with severe depression indicated that reboxetine had superior efficacy compared with fluoxetine. Both treatments resulted in some improvement in Social Adaptation Self-evaluation Scale total scores and this was more evident for those patients treated with reboxetine who achieved remission. Both treatments were well tolerated. The results indicate that reboxetine is an effective and well tolerated antidepressant, being more effective than fluoxetine in patients with severe depression, and more effective in terms of social functioning in those patients who achieved remission.     

Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients

INTRODUCTION: Depression is a major global problem associated with large medical, sociological and economic burdens. Mirtazapine (Remeron, Organon NV, The Netherlands) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression. However, this agent has not yet been tested in patients with severe depression alone. OBJECTIVE: To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression (> or = 25 points on the first 17 items of the Hamilton Depression Rating Scale [HDRS-17]). METHODS: In this double-blind study, 297 severely depressed patients were randomised to receive mirtazapine 15-60 mg/day (n = 147) or fluoxetine 20-40 mg/day (n = 152) for 8 weeks. 294 subjects were actually treated and 292 included in the intent-to-treat population. Symptom severity was measured by the HDRS-17, Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) rating scale. Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Questionnaire and the Quality of Life, Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study. RESULTS: No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point; both treatments were associated with large (approximately 15 points) decreases by study end. However, more mirtazapine-treated patients tended to exhibit a > or = 50% decrease in HDRS score (significant at day 7; 9.0% vs 0.7%, p = 0.002). Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores (-10.9 vs -8.5, p = 0.006) and the proportion of patients with > or = 50% decrease in MADRS score (21.4% vs 10.9%, p = 0.031). On the CGI, the proportion of 'much/very much improved' patients tended to be greater with mirtazapine (significant at day 7; 9.7% vs 3.4%, p = 0.032). No significant between-group differences were observed for the majority of quality-of-life measures. However, mirtazapine produced significantly better improvements on 'sleeping assessment 1' (14.9 +/- 5.2 vs 13.7 +/- 5.4, p = 0.028) and 'sleeping assessment 2' (p = 0.013) than fluoxetine. Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 +/- 2.7 kg compared with a mean decrease in weight of 0.4 +/- 2.1 kg for fluoxetine-treated patients (p < 0.001). CONCLUSIONS: Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression.     

Clinical efficacy of agomelatine in depression: the evidence

Despite the advances of recent decades, there is still an urgent need for antidepressants with improved efficacy, safety and tolerability. Agomelatine is a new antidepressant with an innovative pharmacological profile. It is the first melatonergic antidepressant, and is a potent agonist of melatonin receptors (MT1 and MT2) with 5-HT2C antagonist properties. The efficacy of 25 mg/day agomelatine in treating major depressive disorder (MDD) has been demonstrated in a number of placebo-controlled studies. Evidence of improvement in depressive symptoms was observed in a dose-ranging study in which 25 mg/day agomelatine was significantly better than placebo, whatever the rating scale used (Hamilton Rating Scale for Depression, Clinical Global Impression, and Montgomery-Asberg Depression Rating Scale). These results have been confirmed in two similarly designed placebo-controlled studies. Agomelatine also produces a significant improvement in anxiety compared to placebo, according to Hamilton Rating Scale for Anxiety scores. The efficacy of agomelatine has been studied in subpopulations with more severe depression, demonstrating its efficacy in these difficult-to-treat patients. In view of the available data on agomelatine, this antidepressant can be regarded as an innovative treatment for MDD patients, offering a new approach in the management of depressed patients.     

A controlled trial of adinazolam versus desipramine in geriatric depression

Thirty outpatients between the ages of 60 and 85 with DSM-III Major Depression entered an 8 week randomized, double-blind comparison of desipramine and adinazolam mesylate, a triazolobenzodiazepine derivative. Outcome was assessed on several measures including the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Rating Scale, Clinical Global Impressions (CGI), the 35-item Self-Rating Symptom Scale, and Carroll Depression Scale. Patients in both groups demonstrated a highly significant decrease in average HDRS scores (p less than 0.001) over the course of the study. Adinazolam was associated with significantly greater reduction in average HDRS scores by the third day. Repeated measures analysis of variance showed a significantly greater reduction in HDRS scores for adinazolam over the course of the study. The study medications were associated with distinct patterns of adverse reactions. Desipramine more often produced dry mouth, constipation and nervousness, while adinazolam was more likely to cause drowsiness and lightheadedness. Three of these elderly patients, all of whom were taking desipramine reported at least one fall during the study. Adinazolam may be a promising agent in the treatment of depression in the elderly.     

Prediction of the response to citalopram and reboxetine in post-stroke depressed patients

Rationale and objective Depression is a significant complication of stroke. The effectiveness of antidepressant drugs in the management of post-stroke depression (PSD) has been widely investigated. However, the choice of antidepressant drug is critically influenced by its safety and tolerability and by its effect on concurrent pathologies. Here we investigate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI), citalopram, and a noradrenaline reuptake inhibitor (NARI), reboxetine, in post-stroke patients affected by anxious depression or retarded depression.Methods This was a randomized double-blind study. Seventy-four post-stroke depressed patients were diagnosed as affected by anxious or retarded depression by using a synoptic table. Randomisation was planned so that 50% of the patients in each subgroup were assigned for 16 weeks to treatment with citalopram and the remaining 50% were assigned to treatment with reboxetine. The Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HDRS) and a synoptic table were used to score depressive symptoms.Results Both citalopram and reboxetine showed good safety and tolerability. Citalopram exhibited greater efficacy in anxious depressed patients, while reboxetine was more effective in retarded depressed patients.Conclusions Citalopram or other SSRIs and reboxetine may be of first choice treatment in PSD because of their good efficacy and lack of severe side effects. In addition, PSD patients should be classified according to their clinical profile (similarly to patients affected by primary depression) for the selection of SSRIs or reboxetine as drugs of choice in particular subgroups of patients.     

Citalopram in the treatment of dysthymic disorder

This study aimed to provide preliminary data on the tolerability and effectiveness of citalopram for patients with dysthymic disorder. Twenty-one adult subjects meeting DSM-IV criteria for dysthymic disorder were enrolled in this 12-week open-label study, of whom 15 had pure dysthymia (e.g. no major depression in the past 2 years). Citalopram was initiated at 20 mg/day, and increased to a maximum of 60 mg/day. Response was defined as 50% or greater drop in score on the Hamilton Depression Rating Scale (HDRS) and a Clinical Global Impressions-I score of 1 ('very much improved') or 2 ('much improved'). Of these 15 pure dysthymic disorder subjects, all completed the trial, and 11 (73.3%) were treatment responders. All paired sample t-tests were highly significant, demonstrating significant average improvement on all measures of symptomatology and functioning. Scores on the 24-item HDRS decreased from 22.3+/-4.3 at baseline to 9.1+/-7.8 at week 12 [t(14)=6.1, P<0.001]. In addition, improvement was noted in self-reported measures of temperament and social functioning. The average final dose of citalopram was 39 mg/day. Side-effects were reported by nine of 15 subjects (60%), most frequently gastrointestinal symptoms (n=5), dry mouth (n=5) and sexual side-effects (n=3). These findings suggest the effectiveness and tolerability of citalopram in treating dysthymic disorder. Double-blind prospective studies are needed comparing citalopram both to placebo and to other medications, assessing both initial and sustained response to treatment.     

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.