Comparative cardiac effects of maprotiline and doxepin in elderly depressed patients

In a double-blind study, 49 elderly patients with primary major depression, with or without cardiovascular disease, were treated with maprotiline or doxepin. Holter monitors, 12-lead ECGs, and orthostatic blood pressure measurements were used. Maprotiline was associated with decreased PVCs in patients with a "high" baseline rate, while doxepin was associated with increased PVCs in this group. There were no significant differences in orthostatic blood pressure changes between treatment and nontreatment phases or between the two drugs. Small but significant increases in heart rate and prolonged PR interval were noted with both drugs. QRS interval was prolonged by maprotiline but decreased by doxepin. Neither drug produced untoward effects in patients with stable angina or an old myocardial infarction. Maprotiline may have an antiarrhythmic effect which could be beneficial in the treatment of depression with concomitant PVCs. Conversely, doxepin may be more appropriate for depressed patients with heart block or intracardiac conduction delays. Further research is necessary to confirm these suggestions.     

Maprotiline-a double-blind study of a new tetracyclic antidepressant in severe depression.

A double-blind study was carried out comparing the antidepressant properties of maptotiline (a new tetracyclic antidepressant) and amitriptyline. Twenty-one hospitalized severely depressed patients, selected on the basis of clinical and psychometric criteria, completed the trial period of 28 days. The new drug was found to have an order of effectiveness similar to that of amitriptyline and both drugs were effective in agitated as well as retarded forms of depression. For both, the "day of effect", intended as the timing of sharp clinical improvement, tended to occur during the second week of treatment. Both drugs were well tolerated by most patients but one of the maprotiline patients presented a generalized rash which resolved after discontinuation of the drug. In conclusion, maprotiline is seen as an interesting addition to the group of major antidepressant drugs.     

Response to total sleep deprivation before and during treatment with fluvoxamine or maprotiline in patients with major depression--results of a double-blind study

To test the hypothesis that the antidepressant effects of total sleep deprivation (TSD) are linked to the serotonergic and/or noradrenergic system the authors carried out a double-blind study (fluvoxamine versus maprotiline) in 42 inpatients with endogenous depression (ICD). Patients were randomized to a four-week treatment with either fluvoxamine (100-300 mg/day) or maprotiline (100-300 mg/day). In addition, patients underwent a TSD procedure before and after one week of antidepressant medication. There was a statistically significant reduction of depression ratings (HDRS) in both the fluvoxamine and maprotiline group. The day-1 response to TSD before antidepressive medication was not associated with a clear relationship to the outcome after four weeks of treatment with either fluvoxamine or maprotiline. On the other hand, the day-2 response to TSD was significantly correlated with a good outcome to subchronic treatment with maprotiline. Furthermore, the results of the authors' data suggest that a favorable short-term outcome of TSD may be connected to antidepressants enhancing the serotonergic neurotransmission. The global comparison between fluvoxamine and maprotiline revealed that the group of patients treated with fluvoxamine had a significantly higher efficiency index (CGI) than the maprotiline group; fluvoxamine was rated to be tolerated excellently in 70% of the patients whereas this percentage was only 43% in the maprotiline group. There was also significantly more vertigo and dry mouth in the maprotiline group whereas the fluvoxamine group was rated to have significantly more sleep disturbances during the trial.     

Citalopram versus maprotiline: a controlled, clinical multicentre trial in depressed patients

In a double-blind trial, comprising 96 depressed patients, citalopram was compared with maprotiline. The trial period was 6 weeks with ratings (MADRS, CGI) and side effects recordings taking place at Weeks 0, 1, 2, 4, and 6. Both drugs were administered as a single evening dose, 40 or 60 mg for citalopram, and 75 or 150 mg for maprotiline. MADRS total scores and CGI scores showed a highly significant reduction in both groups with no significant difference between them, whether the groups were considered as a whole or whether they were subdivided into endogenously/non-endogenously depressed or melancholic/non-melancholic patients. Side effects were not significantly different, but the maprotiline group showed more anticholinergic side effects, whereas the citalopram group showed more nausea, increased sweating and headache. Two patients on maprotiline were withdrawn because of side effects (hypotension and somnolence in the one case; tremor and insomnia in the other). One patient in each group was withdrawn because of increased transaminases, the citalopram-treated patient having increased values, however, already at baseline. Apart from this, no cardiovascular side effects and no pathological laboratory values related to treatment were observed. The authors conclude that citalopram is a safe antidepressant drug and as effective as maprotiline.     

Effectiveness of fluoxetine and doxepin in treatment of melancholia in depressed patients

It has been suggested that serotonin reuptake inhibitors (SSRIs) may be less effective than tricyclic antidepressants (TCAs) in treatment of melancholic depression. We treated 36 depressed ambulatory patients with doxepin or fluoxetine in a double-blind, randomized 6-week trial with placebo run-in. Seven patients treated with doxepin and 13 patients treated with fluoxetine met diagnostic criteria for melancholic depression. Average daily dose was 169.4 ± 41.6 mg for doxepin and 36.8 ± 18 mg for fluoxetine. We observed a 50% response rate in both treatment groups, using as outcome criterion reduction of Hamilton Depression Scale Score to less than 10. Regardless of how strict the definition of response, we found fluoxetine to be as effective as doxepin in our group of melancholic outpatients. Depression and Anxiety 7:69–72, 1998. © 1998 Wiley-Liss, Inc.     

A controlled comparison of clonidine and doxepin in the treatment of the opiate withdrawal syndrome

Clonidine and doxepin alleviate the symptoms of the opiate withdrawal syndrome. Clonidine was slightly more effective in controlling sweating, hot flushes, palpitations and nausea, and doxepin was slightly more effective in relieving the craving for opiates, lassitude and depression. Adverse effects such as sedation, dry mouth and falls in blood pressure occurred in both groups. There were six cases of collapse during treatment with high doses of doxepin, whereas only one subjective circulatory effect occurred in the clonidine group. At these high doses, doxepin may cause orthostatic hypotension via a peripheral alpha-receptor blockade. Clonidine reduced pulse rate whereas doxepin, with its anticholinergic action and indirectly via its alpha-receptor blocking action, raised it. Several patients in the doxepin group hat fits, as opposed to only one in the clonidine group. It is possible that the use of barbiturates had reduced the convulsive threshold in some of our patients. Overall, clonidine and doxepin were equipotent at adequate individual dose levels, and both were well tolerated. In this trial, serious side-effects occurred less often in the clonidine group.     

Controlled trial on the possible advantages of a combined therapy with maprotiline and haloperidol in endogenous depression

There is some clinical evidence that neuroleptics are able to increase the therapeutic effect of antidepressant drugs. From a theoretical viewpoint this could be due to influences on pharmacokinetics or receptor sensitivity. In a controlled three-week trial in 28 patients with endogenous depression the potential advantages of a combined medication of 150 mg maprotiline and 9 mg haloperidol per day (given for the first six days) in comparison with monotherapy with maprotiline were tested. Neither during the time of combined medication nor following withdrawal of haloperidol did this treatment regimen show better clinical results in comparison with controls. In keeping with results described elsewhere, the serum levels of the antidepressant, but not of its desmethyl metabolite, were higher in the experimental group.     

Results of a clinical trial of levoprotiline]

The authors submit results of a double blind clinical trial of levoprotiline controlled by maprotiline. In the multicentre study (which is processed and interpreted in stages) participated after written informed consent 58 patients with the diagnosis of a major depressive disorder. During the first three weeks the results of levoprotiline and maprotiline (from 26 patients each) were processed. The trial lasted 42 days. The psychopathology of the patients was evaluated by independent blind raters by means of Montgomery and Asberg's scale (MADRS), Hamilton's scale for depression (HRDS) and general clinical impression (CGI). In all patients also the pharmacological and EEG response was assessed. In comparison to maprotiline, levoprotiline was clinically ineffective. Its plasma levels (40 ng/ml) were one third to one half of the values obtained with maprotiline in the same daily dosage (150 mg). Although levoprotiline has an EEG profile typical for classical thymoleptics, its clinical antidepressive action is negligible.     

氟哌噻吨美利曲辛联合多虑平治疗脑卒中后中重度抑郁

目的探讨氟哌噻吨美利曲辛联合多虑平治疗脑卒中后中重度抑郁的疗效。方法选择69例脑卒中后中重度抑郁症患者,随机分为观察组35例和对照组34例,两组在针对脑卒中给予常规治疗基础上,观察组接受氟哌噻吨美利曲辛联合多虑平抗抑郁治疗,对照组单纯服用多虑平,疗程为6周。治疗前及治疗6周对所有患者进行汉密尔顿抑郁量表（HAMD,24项标准）、神经功能缺损程度（NDS）及日常生活活动能力（BI）评分。结果观察组抗抑郁治疗有效率为91．43％,对照组有效率为70．59％,两组差异有统计学意义（P〈0．05）。观察组神经功能缺损疗效为88．57％,对照组为67．65％,两组差异有统计学意义（P〈0．05）。治疗后两组BI评分均较治疗前均增加,且两组治疗后差异有显著统计学意义（P〈0．001）。结论氟哌噻吨美利曲辛联合多虑平治疗卒中后中重度抑郁疗效优于单独应用多虑平抗治疗,同时可有效改善患者神经功能缺损,减轻残疾程度,提高生活质量。     

氟西汀与麦普替林治疗Alzheimer''s病抑郁症状的比较研究

目的 比较氟西汀与麦普替林在AD抑郁症状治疗中的疗效和副反应。方法 氟西汀组45例,麦普替林组41例。均诊断为AD,HAMD-17>18分。比较两组病人治疗后的HAMD-17减分率及副反应发生率。结果 氟西汀组与麦普替林组总体疗效相当,但氟西汀组起效较快,副反应发生率低。结论 氟西汀在AD抑郁症状治疗中具有一定优势,值得临床推广。     

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.     

A comparison of clomipramine and doxepin in neurotic depression

Results of a double-blind 4-week trial in depressed outpatients given clomipramine (N = 30) or doxepin (N = 36) are reported. Both groups showed significant improvement in physician-rated measures after 1 week of treatment; comparison of the groups favored clomipramine over doxepin for four of six measures. The response to treatment was less clear-cut with the patient-rated measures. The overall incidence and severity of adverse experiences were similar for both treatment groups. Clomipramine was effective, safe, and well tolerated as compared to doxepin in the treatment of outpatients with neurotic depression.     

万拉法新与马普替林治疗抑郁症对照研究

目的 研究万拉法新的抗抑郁疗效及副作用。方法 采用随机对照方法,以马普替林为对照组,应用HAMD、HAMA、TESS量表,在疗前、疗后1、2、4、6周进行疗效及副反应评定。结果 万拉法新的痊愈率(63.6％)高于马普替林(45.5％),但无显著性差异(X~2=0.825,P>0.05);其显效率(81.8％)与马普替林(77.3％)相近。万拉法新见效快,副作用发生率低而轻微。结论 万拉法新抗抑郁疗效肯定、副作用少。     

丁螺环酮联合马普替林与马普替林单独治疗抑郁症的疗效对照观察

目的　探讨丁螺环酮联合马普替林治疗抑郁症的效果。方法　随机将 6 4例抑郁症患者分成两组 ,分别给予丁螺环酮合并马普替林与单纯应用马普替林治疗 8周 ;以汉密顿抑郁量表 (HAMD)评定疗效 ,以不良反应症状量表 (TESS)评定副反应。结果　两组间HAMD于第 2、4、6、8周末减分率比较差异均有显著性(P <0 .0 1/P <0 .0 5 )。两组TESS评分各周差异均不明显。结论　丁螺环酮联用马普替林治疗抑郁症疗效优于单纯使用马普替林 ,且耐受性好     

A double-blind comparison of mianserin and maprotiline in depressed medically ill elderly people

A double-blind, randomized 4-week mianserin vs maprotiline trial was conducted in 48 depressed geriatric medical inpatients. The drug dosages were up to 90 mg of mianserin and up to 150 mg of maprotiline per day. Efficacy was measured by the Geriatric Depression Scale, the Hopkins Symptom Check List depression subscale and the Clinical Global Impression Scale. The overall dropout figure was 27% of the sample. Side effects were relatively similar in the two treatment groups and suggested a safety profile somewhat better than that of the first-generation antidepressants. Mianserin showed some advantages in efficacy over maprotiline, particularly by the 4th week of the trial, but the overall figures of treatment responders were rather small (Geriatric Depression Scale: mianserin 48%, maprotiline 30%). Clinical trials vs placebo are needed to clarify the role of antidepressant pharmacotherapy in depressed geriatric medical inpatients.     

百忧解与马普替林联合治疗反复发作抑郁症的疗效观察

目的　评估百忧解与马普替林联合治疗反复发作抑郁症的作用。方法　将３３ 例百忧解和马普替林联合治疗的与３４ 例单用百忧解、３０ 例单用马普替林治疗的反复发作抑郁症病人进行对照研究。结果　百忧解合并马普替林组痊愈率为８８％ 、百忧解组为６８ ％ 、马普替林组为６７ ％ ,合并组显著优于两个单用组（ Ｐ＜ ０－０５） 。治疗结束时汉密顿抑郁量表评分结果显示：合并组３－８２ ±２－４４ ,百忧解组６－４４ ±５－０３ ,马普替林组５－６３ ±４－２４ ,合并组也显著优于单用组（ Ｐ＜ ０－０１） ,而百忧解组与马普替林组差异无显著性（ Ｐ＞ ０－０５） ,同时也显示副反应并未因合并用药而增多。结论　提示合并用药治疗反复发作抑郁症疗效优于单一用药。     

西酞普兰与马普替林治疗老年抑郁症的对照研究

目的比较西酞普兰与马普替林治疗老年抑郁症的疗效及安全性。方法将96例老年抑郁症住院患者随机分为两组,48例应用西酞普兰治疗,48例应用马普替林治疗,疗程均为8周。采用汉密尔顿抑郁量表（HAMD）、临床疗效总评定量表（CGI-SI）评定临床疗效,治疗中出现的不良反应量表（TESS）评定药物不良反应。结果西酞普兰与马普替林治疗老年抑郁症的疗效相当（P〉0.05）,但前者不良反应少（P〈0.05）。结论西酞普兰治疗老年抑郁症疗效显著,不良反应少,安全性高。     

抑郁症患者吸烟对马普替林治疗作用的影响

目的探讨抑郁症患者吸烟对马普替林治疗剂量、疗效和不良反应的影响。方法对120例符合CCMD-3诊断标准的抑郁症患者,采用HAMD量表减分率评价其临床疗效,用TESS评定其安全性。对吸烟和不吸烟的抑郁症患者进行马普林治疗剂量、疗效和不良反应的比较。结果吸烟的抑郁症患者所服马普替林日平均剂量显著高于不吸烟的患者、疗效显著差于不吸烟患者,不良反应显著轻于不吸烟患者。结论抑郁症患者在马普替林治疗期间少吸烟或不吸烟,可以减少马普替林的用量和提高疗效。     

Amitriptyline-perphenazine and doxepin in depressed outpatients: a controlled double-blind study

Amitriptyline-perphenazine (100/8-150/12 mg/day) and doxepin (100-150 mg/day) were compared for clinical efficacy and safety in a sample of 130 nonpsychotic depressed outpatients. Maximum study duration was 4 weeks; 19 amitriptyline-perphenazine and 29 doxepin patients completed less than or equal to 3 weeks of treatment and 45 amitriptyline-perphenazine and 37 doxepin patients completed 4 weeks of treatment. Patients in both groups showed significant improvement in depression, but amitriptyline-perphenazine produced greater improvement than doxepin on several measures of depressive symptomatology. The incidence of anticholinergic and sedative side effects was higher in the amitriptyline-perphenazine treated group.