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.     

Epilepsy, depression and antidepressant drugs.

Apart from constituting an important management problem, depression coexisting with epilepsy is also an interesting psychiatric phenomenon, with multiple interacting biological, psychological and social factors involved in its causation. New research approaches to the study of epilepsy and depression, including neuroimaging, neurochemical and neuroendocrine techniques, and the arrival of new classes of antidepressants in recent years, suggest it is timely to reconsider this topic. We review current knowledge of the prevalence and causes of interictal depression in epilepsy, focussing mainly on neurobiological factors, and give an overview of recent concepts concerning the management of depression. We also discuss pharmacological treatment of depression in epilepsy, focussing on the association between antidepressants and seizures, and drug interactions.     

西酞普兰治疗抑郁症的疗效及安全性的多中心临床研究

目的系统了解西酞普兰治疗抑郁症的疗效及安全性。方法采用多中心、开放性研究,对5052例抑郁症患者(单纯抑郁症4683例,伴发躯体疾病161例,伴发强迫症112例,双相抑郁96例)进行可变剂量西酞普兰治疗,剂量为10～80mg/d,共观察8周。分别在治疗前及治疗第2,4,6,8周末以汉密尔顿抑郁量表(17项,HAMD)总分减分率评价疗效,描述性记录不良反应。结果治疗第8周末,HAMD总分平均减分率达(81.1±16.8)%。5052例中3697例(73.18%)的患者达到临床痊愈标准。伴发躯体疾病、伴发强迫症及双相抑郁患者的病情均获显著改善,后两者第8周的平均治疗剂量[(28.5±10.9)mg/d,(26.9±11.7)mg/d]均明显高于单纯抑郁症患者[(24.5±9.1)mg/d],而伴发躯体疾病患者[(22.4±7.8)mg/d]的平均治疗剂量则低于单纯抑郁症患者,差异均有统计学意义(P<0.05)。病程短、首次发作及年龄<45岁患者的疗效明显优于病程较长、反复发作及≥45岁患者。治疗过程中西酞普兰的主要不良反应为中枢神经系统和消化系统反应,症状轻微,多出现于治疗早期。结论西酞普兰安全有效,可用于治疗抑郁症或其他疾病伴发的抑郁症。     

Monoamines, depression and antidepressant drugs

The noradrenergic control of melatonin secretion in rat and man appears to have the property of a typical central noradrenergic system. Using the pineal as a model, increases and decreases in plasma melatonin levels are used to monitor the respective changes in noradrenergic transmission. Although in rats chronic imipramine treatment reduced pineal adrenoreceptor binding sites and melatonin levels, in depressed patients chronic treatment with desimipramine results in increases in plasma melatonin levels. These data support the classical view that in man antidepressants act by increasing monoamine transmission. The author postulates in depression a primary lesion distal to the monoaminergic projections but proximal to the hypothalamic nuclei, and further, that antidepressants may have a common effect on an as yet unidentified, hypothalamic neuropeptide.     

Long-term antidepressant efficacy and safety of olanzapine/fluoxetine combination: a 76-week open-label study

BACKGROUND: The olanzapine/fluoxetine combination has demonstrated effectiveness in treatment-resistant depression (TRD). Although this combination is being used by prescribers, this is the first study to examine long-term use. Long-term efficacy and safety were therefore investigated in a group of patients with major depressive disorder (MDD) with and without TRD. METHOD: 560 patients who met DSM-IV diagnostic criteria for MDD were enrolled in this 76-week, open-label study (Feb. 2000-July 2002). The Montgomery-Asberg Depression Rating Scale (MADRS) total score was the primary efficacy measure. Safety was assessed via adverse events, vital signs, laboratory analytes, electrocardiography, and extrapyramidal symptom measures. RESULTS: MADRS mean total scores decreased 7 points from baseline (31.6 [N = 552]) at 1/2 week of treatment, 11 points at 1 week of treatment, and 18 points at 8 weeks of treatment. This effect was maintained to endpoint with a mean decrease of 22 points at 76 weeks. Response and remission rates for the total sample were high (62% and 56%, respectively), and the relapse rate was low (15%). Response, remission, and relapse rates for TRD patients (N = 145) were 53%, 44%, and 25%, respectively. The most frequently reported adverse events were somnolence, weight gain, dry mouth, increased appetite, and headache. At endpoint, there were no clinically meaningful changes in vital signs, laboratory analytes, or electrocardiography. There were no significant increases on any measure of extrapyramidal symptoms. CONCLUSIONS: The olanzapine/fluoxetine combination showed rapid, robust, and sustained improvement in depressive symptoms in patients with MDD, including patients with TRD. The long-term safety profile of the combination was similar to that of its component monotherapies.     

曲唑酮治疗抑郁症患者睡眠障碍的交叉试验研究

目的：验证曲唑酮对抑郁症患者的睡眠改善作用。方法：以艾司唑仑为对照药，采用交叉试验。结果；随着治疗的进行，曲唑酮与艾司唑一样，明显改善了抑郁症患者的睡眠指标，且两药对大多数观察指标的影响无明显差异。结论：曲唑酮能较好地改善抑郁症患者的睡眠障碍，具有较好的应用前景。     

Trazodone in endogenous depressed patients: a negative report and a critical evaluation of the pertaining literature

The antidepressant efficacy of trazodone has been studied during three weeks in 13 endogenously depressed patients, using a fixed dosage of 5/10 mg/kg bodyweight per day. Psychopathological assessments were documented by means of observer rating (HDRS, AMP) and selfratings (Bf-S, EWL-K). Most variables assessed during course of treatment did not reveal amelioration of statistical significance or clinical relevance. If the most frequently applied response criteria of a 50% reduction of the initial HDRS-score was taken, only three patient improved. Those results were surprising in view of the previous and subsequent response to antidepressant therapy of the patient group studied. Plasmalevels of trazodone were monitored once weekly; they showed a nine-fold interindividual variation and did not correlate to the fixed dosage steps. A critical review of the pertaining literature led the authors assume, that the main indication of this drug is within non-endogenous-depression.     

三环类抗抑郁药对抑郁症患者淋巴细胞β受体的作用

本文以内源性抑郁症患者为实验对象，研究三环类药物对淋巴细胞肾上腺能β受体的作用．结果提示治疗前抑郁症患者淋巴细胞β受体最大结合（Ｂｍａｘ）明显低于正常，治疗后与正常对照无显著差异，且这一改变与临床疗效一致。受体亲和力无改变。本研究对三环类抗抑郁药的机理探讨，及抑郁症病因研究提供依据。     

Procedure- and age-dependent hyperactivity in a new animal model of endogenous depression

We have replicated the findings of Mirmiran and colleagues that neonatal administration of the antidepressant clomipramine (CLI) to male rats results in hyperactivity in open-field tests in adulthood. We report that this effect does not reliably occur in a "Digiscan" activity device. The difference in effect between the two activity measuring devices may be due to more stress being present in the open-field test, and we propose that the CLI-treated rats may be more reactive to stress. This hypothesized enhanced reactivity to stress may be similar to the proposed vulnerability of depressed humans to stress. In addition, we have found that the open-field effect does not occur until the rats are at least 4 months old; this delayed effect may be analogous to the progressive onset of endogenous depression in humans.     

The safety and efficacy of combined amitriptyline and tranylcypromine antidepressant treatment. A controlled trial

Sixty patients meeting DSM-III criteria for major depression were assigned randomly to double-blind treatment for four weeks according to fixed-dosage steps with (1) amitriptyline hydrochloride alone, up to a maximum dosage of 300 mg/day; (2) tranylcypromine alone, up to 40 mg/day; or (3) the combination of amitriptyline hydrochloride, up to 150 mg/day, and tranylcypromine, up to 20 mg/day. The conditions of patients in all three treatment groups improved equally. The combined treatment did not produce a higher frequency of side effects, and no side effects, such as hypertensive or hyperthermic crises, occurred in any patient. Both amitriptyline alone and combined treatment produced substantially more anticholinergic side effects than did tranylcypromine. These results support the safety and efficacy of the combined treatment, although claims for superior efficacy over single-antidepressant treatments in this heterogenous population were not supported.     

Decreased intracranial self-stimulation in a new animal model of endogenous depression

Neonatal treatment of rats with clomipramine may produce adult animals which model endogenous depression. We report here that a major factor of depression in humans, the diminished capacity for pleasure, appears present in these rats. At age 7 months, bar-press responding for rewarding hypothalamic stimulation is reduced across a range of intensities. At age 4 or 5 months this effect is not seen, although other behavioral abnormalities are present at the younger age. The delayed onset of diminished intracranial self-stimulation may relate to the gradual insidious onset of endogenous depression in humans.     

REM sleep abnormalities in a new animal model of endogenous depression

Endogenous depression has reliable REM sleep abnormalities. These include a short REM latency, frequent sleep onset REM periods, and after REM sleep deprivation (RSD), an abnormal temporal course of REM rebound in the presence of a normal total REM rebound. The reliability of these abnormalities suggests that they ought to be present in an animal model of endogenous depression. In 1982, we proposed a new animal model of endogenous depression. Our hypothesis is that in rats neonatal clomipramine (CLI) will produce adult animals that model endogenous depression. In this study we tested the prediction that after neonatal treatment with CLI, adult rats will show the above three REM sleep abnormalities of human endogenous depression. We found that neonatal treatment with CLI produced rats that at age 6 months had shorter REM latency, more sleep onset REM periods than control rats, and after RSD, had an abnormal temporal course of REM rebound in the presence of a normal total REM rebound. The finding of these REM sleep abnormalities supported the validity of the animal model of endogenous depression.