A double-blind,comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients

A randomized, double-blind, parallel-group, 6-week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of the selective serotonin reuptake inhibitors paroxetine and fluoxetine. After a 1-week placebo wash-out, patients suffering from DSM-III major depression and with a score of 18 or more on the 21-item Hamilton Rating Scale for Depression (HRSD) received either paroxetine or fluoxetine. The patients were assessed for efficacy using the HRSD, Montgomery-Åsberg Depression Rating Scale and Clinical Global Impression; for tolerability, adverse events were elicited by the use of a non-leading question and a side effects checklist. The groups of patients were comparable on entry to the study. One hundred patients were recruited into the study, of whom 78 were evaluable for the efficacy analysis. Paroxetine and fluoxetine showed comparable efficacy at the end of the 6-week treatment period, but a statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed. This could suggest an earlier onset of action with paroxetine. Also, associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at week 3. Patients on paroxetine reported fewer adverse events than those on fluoxetine. The most commonly reported adverse events were nausea and vomiting in both groups.     

Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice

The enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants (TCAs), and the frequency and type of adverse events, have made the treatment of depression in this group difficult. The selective serotonin reuptake inhibitors (SSRIs) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs. We compared the therapeutic actions and side effects produced by citalopram, the most selective SSRI available, with amitriptyline in a group of elderly patients (aged 65 and older) diagnosed with major depression. In a double-blind, double-dummy, parallel-group, multicenter comparison of citalopram (20 or 40 mg/day) and amitriptyline (50 or 100 mg/day), patients who did not respond to placebo during a 1-week single-blind phase were randomly assigned to receive citalopram or amitriptyline for 8 weeks. Efficacy measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAMD), and Clinical Global Impressions. Both drug treatments produced equivalent time-related declines in severity of depression, so that by 8 weeks slightly more than 50% of the patients in each group experienced marked recovery, defined as MADRS scores ≤ 12. Amitriptyline produced a greater overall incidence of adverse events, including a significantly higher (P < 0.001) percentage of patients reporting dry mouth (34% vs. 7%), as well as a significantly higher (P < 0.02) incidence of somnolence. Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group. For only one event (nausea) did the citalopram group report a significantly greater (P = 0.012) incidence (12.8% vs. 4.8%). On the basis of these results, it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly. Because of its low incidence and low magnitude of side effects, citalopram seems especially useful in private practice. Depression and Anxiety 8:147–153, 1998. © 1998 Wiley-Liss, Inc.     

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.     

Platelet counts in depressed patients treated with amitriptyline or paroxetine.

OBJECTIVE: To assess whether therapy with two widely used antidepressants influences platelet counts. SUBJECTS AND METHODS: In 90 patients hospitalized for treatment of a major depressive episode according to DSM-IV, platelet counts were performed after a 6 d antidepressant-free run-in period and again after 35 d of active standardized treatment with amitriptyline (n = 40) or paroxetine (n = 50). RESULTS: There was a trend for platelet counts to increase during treatment with amitriptyline (from 245.5 +/- 68.6 to 256.8 +/- 69 cells x 10(9) L(-1), P < 0.06); no change was observed during treatment with paroxetine (from 232.6 +/- 58.3 to 234.6 +/- 68.9 cells x 10(9) L(-1), n.s). CONCLUSION: Treatment with amitriptyline tends to be associated with elevated platelet counts. The cause for this increase is not known, but may be relevant in terms of patients' long-term thromboembolic risk.     

A double-blind,randomized, group-comparative study of the tolerability and efficacy of 6 weeks' treatment with mirtazapine or fluoxetine in depressed Chinese patients

AIM: To compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Chinese patients suffering moderate-to-severe depression. METHOD: 133 patients with a diagnosis of major depressive episode (DSM-IV) and scoring 15 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomly assigned to receive 6 weeks of treatment with either mirtazapine (15-45 mg/day) or fluoxetine (20-40 mg/day). Efficacy was assessed using the HAM-D and Clinical Global Impressions scale, with analyses performed on the intent-to-treat sample using the last-observation-carried-forward method. Safety analysis was based on the all-subjects-treated group. RESULTS: Mean daily doses were 34.1 mg for mirtazapine (N = 66) and 30.7 mg for fluoxetine (N = 66). Thirty patients in the mirtazapine group and 22 in the fluoxetine group dropped out. Both drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period. At day 42, the mean reductions in HAM-D total score (compared with baseline) were 11.8 and 10.6 for the mirtazapine and fluoxetine groups, respectively; however, the changes were not statistically significant. Both treatments were well tolerated, with more nausea and influenza-like symptoms observed for the fluoxetine group, and greater weight increase and somnolence for the mirtazapine analog. CONCLUSION: Both mirtazapine and fluoxetine were indistinguishable in effectiveness for treatment of depressive symptoms, and both were well tolerated by our population of depressed Chinese patients. In line with analogous Western reports, the safety of mirtazapine and fluoxetine was comparable for our depressed Chinese patients; however, slightly different side effect profiles were noted for the 2 drugs in our study.     

A double-blind comparison of moclobemide and doxepin in depressed general practice patients

A total of 56 patients attending a general practitioner for treatment of depression, most of whom met the criteria for major depression, were included in this double-blind, parallel group, 6-week study, in which the selective MAO-A inhibitor moclobemide (MOC; maximum dose 600 mg) was compared with the tricyclic antidepressant doxepin (DOX; maximum dose 250 mg). Thirty patients on MOC and 23 on DOX were assessed after treatment for at least 1 week and are included in the response evaluation. Improvement was assessed primarily with the Montgomery-Asberg Depression Rating Scale (MADRS). There were only 4 drop-outs in the MOC group and three in the DOX group after 1 week. Overall improvement measures showed a nonsignificant difference in favor of DOX. Two factors were found to have prognostic significance: (1) previous or present panic attacks (10 patients in the MOC group and – by chance – only one in the DOX group) were associated with significantly lower improvement within the MOC group. Since we had no a priori hypothesis about this effect, it could be a chance finding. (2) Improvement was negatively correlated with age; this was statistically significant in the total group as well as in the MOC group, with a nonsignificant trend in the same direction in the DOX group. Side effects differed little between the two groups; only dryness of mouth appeared with markedly higher frequency in the DOX group.     

An Australian multicentre study of moclobemide versus amitriptyline in the treatment of depression.

This paper reports the results of a multicentre study of the new monoamine oxidase inhibitor, moclobemide, in the treatment of major depression. Moclobemide is a specific monoamine oxidase-A inhibitor which does not bind irreversibly to the enzyme, unlike the currently available MAOIs. Recent studies would suggest that in subjects taking moclobemide blood pressure elevation caused by tyramine is significantly less than that induced by the irreversible MAOIs, particularly when tyramine is administered in an oral form. Forty-eight patients with major depression were randomly allocated to treatment with either moclobemide or amitriptyline for 4 weeks in a double-blind comparison. There were no statistically significant differences between the two groups on measures of efficacy. Patients taking amitriptyline reported a greater number of side-effects and more patients in the amitriptyline group dropped out because of these. There were no reports of interactions with tyramine-containing foods.     

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.     

A randomized,double-blind,placebo-controlled phase 2 study to assess safety,tolerability, and efficacy of RT001 in patients with amyotrophic lateral sclerosis

Background and purpose

RT001 is a deuterated synthetic homologue of linoleic acid, which makes membrane polyunsaturated fatty acids resistant to lipid peroxidation, a process involved in motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

Methods

We conducted a randomized, multicenter, placebo-controlled clinical trial. Patients with ALS were randomly allocated to receive either RT001 or placebo for 24 weeks. After the double-blind period, all patients received RT001 during an open-label phase for 24 weeks. The primary outcome measures were safety and tolerability. Key efficacy outcomes included the ALS Functional Rating Scale (ALSFRS-R), percent predicted slow vital capacity, and plasma neurofilament light chain concentration.

Results

In total, 43 patients (RT001 = 21; placebo = 22) were randomized. RT001 was well tolerated; one patient required dose reduction due to adverse events (AEs). Numerically, there were more AEs in the RT001 group compared to the placebo group (71% versus 55%, p = 0.35), with gastrointestinal symptoms being the most common (43% in RT001, 27% in placebo, p = 0.35). Two patients in the RT001 group experienced a serious AE, though unrelated to treatment. The least-squares mean difference in ALSFRS-R total score at week 24 of treatment was 1.90 (95% confidence interval = −1.39 to 5.19) in favor of RT001 (p = 0.25). The directions of other efficacy outcomes favored RT001 compared to placebo, although no inferential statistics were performed.

Conclusions

Initial data indicate that RT001 is safe and well tolerated. Given the exploratory nature of the study, a larger clinical trial is required to evaluate its efficacy.     

Tianeptine and amitriptyline. Controlled double-blind trial in depressed alcoholic patients

129 chronic alcoholic patients, withdrawn from alcohol and presenting major depression or dysthymic disorder, were treated for 4-8 weeks under double-blind conditions either with a new antidepressant, tianeptine (37.5 mg per day), or with amitriptyline (75 mg per day). Both groups presented steady improvement of the symptoms of depression during treatment, as scored on the Montgomery and Asberg Depression Rating Scale and the Hopkins Symptom Checklist self-evaluation; for the latter scale, the improvement was significantly greater in the tianeptine group. In addition to the improvement of mood, tianeptine also produced significant reduction of the somatic complaints of the depressed patients. Furthermore, tianeptine possesses anxiolytic activity, as shown by the change of the Hamilton Anxiety Rating Scale global score, similar to that produced by amitriptyline. The anxiolytic activity of tianeptine was not accompanied by any impairment of vigilance, unlike that of amitriptyline. Tianeptine produced rare, mild anticholinergic effects. The results obtained show that tianeptine is an effective anxiolytic antidepressant, with better safety than amitriptyline, suitable for use in the treatment of mood disorders following alcohol withdrawal.     

帕罗西汀与阿米替林治疗抑郁症的对照研究

目的 探讨帕罗西汀治疗抑郁症的疗效和安全性。方法 61例抑郁症病人随机分为阿米替林组31例。帕罗西汀组30例。共治疗6周，采用汉密尔顿抑郁量表（HAMD）和临床总体评定量表（CGI）评定临床疗效，采用副反应量表（TESS）评定副反应。结果 帕罗西汀组与阿米替林组治疗前后HAMD和CGI-SI分值比较均有显著性差异。而两组减分相比治疗前后无显著性差异。帕罗西汀组副作用明显比阿米替林组轻，在植物神经，心血管以及神经系统方面二者有显著性差异。结论 帕罗西汀治疗抑郁症疗效好，副反应小，服用方便，依从性好，是治疗抑郁症的理想药物。     

帕罗西汀与阿米替林治疗抑郁症的对照研究

目的验证帕罗西汀治疗抑郁症的疗效及安全性.方法对60例抑郁症患者分别以帕罗西汀与阿米替林治疗,共治疗6周.采用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、临床总体评定量表(CGI)评定临床疗效,采用副反应量表(TESS)评定副反应.结果帕罗西汀组与阿米替林组治疗前后HLAMD、HAMA、CGI-SI评分及减分比较均无显著性差异(P＞0.05).帕罗西汀组的副反应较阿米替林组少而轻,帕罗西汀常见的副反应有恶心、头晕、口干等.结论帕罗西汀治疗抑郁症的疗效同阿米替林相当,副反应少而轻.     

A multicentre, randomized, double-blind, placebo-controlled study to evaluate the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate Alzheimer's disease: the MALT study

BACKGROUND: Metrifonate is a long-lasting acetylcholinesterase inhibitor being developed for the symptomatic treatment of Alzheimer's disease (AD).OBJECTIVES: This study compared the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate AD, over a 26-week treatment period. METHODS: Six hundred and five patients were randomized to placebo (n=208), a 40/50 mg dose (40 or 50 mg by weight; n=200) or a 60/80 mg dose (60 or 80 mg by weight; n=197) metrifonate. Patients randomized to receive metrifonate were administered a once-daily loading dose of 80 or 120 mg based on weight for 2 weeks, followed by the relevant maintenance dose for 24 weeks. Four main clinical domains of AD were assessed: cognition (ADAS-cog and MMSE), psychiatric and behavioural symptoms (ADAS-noncog and NPI), instrumental and basic activities of daily living (DAD) and global functioning (CIBIC-plus, CIBIS-plus and GDS).RESULTS: ADAS-cog performance was significantly improved in the 60/80 mg and 40/50 mg dose groups, compared with placebo, in the intention-to-treat (ITT) population. In addition, statistically significant treatment differences were demonstrated between the 60/80 mg dose group and placebo on MMSE, ADAS-noncog, the NPI subitems of hallucinations and apathy, DAD, CIBIC-plus, CIBIS-plus and the GDS. The performance of the 40/50 mg dose group was also significantly superior to placebo on the CIBIS-plus and the NPI subitem aberrant motor behaviour. CONCLUSIONS: Metrifonate significantly improved a wide range of symptoms across all four clinical domains of AD in a dose-dependent manner, and was safe and well tolerated at both doses studied.     

Perspectives in clinical psychopharmacology of amitriptyline and fluvoxamine. A double-blind study in depressed inpatients.

The efficacy of fluvoxamine was compared to that of amitriptyline in a double-blind 6-week fixed-dose trial of 56 inpatients with major depressive episode. The two drugs were comparable in their antidepressant efficacy. We tested the percentage of improvement in Hamilton-D scores during the first and the second weeks of treatment as predictors of efficacy for the last week. Improvement rates during the second week significantly predicted the outcome. We also investigated whether or not some symptomatological characteristics would permit prior prediction of the outcome with amitriptyline or fluvoxamine, dividing our sample into responders and nonresponders to the two drugs. The four groups showed differences in their symptomatological profiles.     

A randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of adjunctive carisbamate treatment in patients with partial-onset seizures

Purpose: To assess the efficacy, safety, and tolerability of adjunctive carisbamate treatment at 800 mg/day and 1,200 mg/day in patients with partial‐onset seizures (POS). Methods: Patients ≥16 years of age with an established diagnosis of POS for ≥1 year and uncontrolled on one to three antiepileptic drugs were enrolled. Eligible patients remained on stable doses of prescribed antiepileptic drugs for an 8‐week pretreatment baseline phase and were then randomized (1:1:1) to receive carisbamate (800 mg/day or 1,200 mg/day), or placebo, for a 14‐week double‐blind phase. Primary efficacy endpoints were percentage reduction in POS frequency and responder rate (patients with ≥50% reduction in POS frequency) during the double‐blind versus baseline phase. Key Findings: Five hundred forty‐seven patients were randomized; 540 composed the intent‐to‐treat (ITT) analysis. Four hundred thirty‐four patients (79%) completed the study. The median percent reduction from baseline to treatment phase in POS frequency was: 21% (placebo); 30% (carisbamate 800 mg); 36% (carisbamate 1,200 mg), and 32% (combined carisbamate doses). The combined carisbamate dose group was not significantly different from placebo for the median percent reduction of POS frequency (p = 0.20) or responder rate (p = 0.18). Therefore, the difference from placebo for the individual carisbamate dose groups was also considered nonsignificant, based on a prespecified step‐down analysis. Dizziness was the most common treatment‐emergent adverse event, with a higher incidence (≥5% difference) in the combined carisbamate group (31%) than placebo (9%); the incidence was higher with carisbamate 1,200 mg (32%, n = 58) than with carisbamate 800 mg (30%, n = 53). Significance: Adjunctive carisbamate therapy in patients with POS did not demonstrate efficacy across the dose range assessed versus placebo. No new safety findings were observed.     

A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder

To date, no large-scale, controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75 mg/day or 150 mg/day), or paroxetine 40 mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions--Severity (CGI-S) and--Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder.     

A randomised, double-blind comparison of the efficacy and safety of citalopram compared to mianserin in elderly, depressed patients with or without mild to moderate dementia

Depression is the most common psychiatric disorder among the elderly and in old age may interact with emotional and cognitive functioning. Depression in old age has been shown to be associated with degenerative changes in the brain. It is, therefore, important that in this patient population antidepressants with a favourable tolerability profile, such as the selective serotonin reuptake inhibitors (SSRIs), are examined for both antidepressant efficacy and effect on cognitive function and emotional impairment. This randomised, double-blind study compared the efficacy and tolerability of citalopram and mianserin in 336 elderly, depressed patients with or without dementia. Patients received either citalopram 20-40 mg/day or mianserin 30-60 mg/day for 12 weeks. The treatments were equivalent with respect to change in Montgomery-Asberg Depression Rating Scale (MADRS) total score; patients in both treatment groups responded well. Patients with dementia showed a smaller decrease in total MADRS score than patients without dementia. Both treatments were well tolerated with a relatively low incidence of adverse events. Fatigue and somnolence were more frequent with mianserin, while insomnia was more frequent with citalopram. Overall, this study showed that the two treatments were equivalent in efficacy, and that citalopram is an effective, well-tolerated and non-sedative treatment for elderly depressed patients with or without dementia.     

帕罗西汀与阿米替林治疗抑郁症临床对照研究

目的为探讨帕罗西汀对抑郁症的临床疗效及其副反应。方法应用帕罗西汀与阿米替林进行对照治疗研究，采用ＨＡＭＤ、ＴＥＳＳ量表及临床疗效评定标准分别评定疗效及副反应。结果提示帕罗西汀与阿米替林对抑郁症的疗效及显效时间近似；帕罗西汀副反应较阿米替林少且轻微。结论帕罗西汀和阿米替林对抑郁症均有较好的疗效，但帕罗西汀副反应轻微，服药方式简便，患者有较好的依从性，值得临床推广     

A double-blind placebo-controlled study of the efficacy and safety of paroxetine in the treatment of pathological gambling

BACKGROUND: This randomized, double-blind, placebo-controlled study investigated the efficacy and tolerability of paroxetine in the treatment of pathological gambling. METHOD: Patients fulfilling DSM-IV criteria for pathological gambling and scoring > or = 5 on the South Oaks Gambling Screen were enrolled if no other Axis I disorder was present. A 1-week placebo run-in phase was followed by 8 weeks' treatment with paroxetine or placebo. The initial paroxetine dose of 20 mg/day could be increased after week 2 by 10 mg/week to a maximum of 60 mg/day. Changes in clinical status were assessed using the Gambling Symptom Assessment Scale (G-SAS) and the Clinical Global Impressions scale (CGI). Treatment-emergent symptoms were assessed weekly. RESULTS: Forty-five patients were included in an intent-to-treat analysis (N = 23 paroxetine, N = 22 placebo). Statistically significantly greater reductions in the total score of the G-SAS were observed in the paroxetine group compared with the placebo group at weeks 6 through 8 (p = .003, .003, and .042, respectively). Improvement on the CGI was also significantly greater in the paroxetine than in the placebo group at the same timepoints (p = .033, .014, and .025, respectively). A significantly greater proportion of patients in the paroxetine group were responders at weeks 7 and 8 (p = .011 and .010, respectively). CONCLUSION: The results of this trial indicate that paroxetine may be effective in the treatment of pathological gambling. There were no unexpected side effects from this treatment. However, additional studies with larger patient samples and a longer treatment phase are required to establish conclusively the efficacy and safety of paroxetine for this indication.