Subjective complaints during desipramine treatment. Relative importance of plasma drug concentrations and the severity of depression

Subjective complaints, including those traditionally considered tricyclic antidepressant side effects, were studied in 43 depressed inpatients during a three-week trial of desipramine hydrochloride. Multiple regression analysis was employed to examine the independent relationship of pretreatment symptoms, concurrent depression, and plasma drug concentrations to subjective complaints reported during treatment. As a group, subjective complaints were positively associated with pretreatment symptoms and the concurrent severity of depression, but not with plasma desipramine concentration. Of the 23 individual complaints studied, three increased during treatment and nine improved. Only two complaints, tremors and light-headedness, were significantly associated with plasma drug concentration. The data indicate that during initial treatment of severe depression with desipramine, subjective complaints are more likely to be symptoms of depression than side effects of the drug and that plasma desipramine determinations would not be useful for predicting or avoiding these complaints. The best management of most symptoms studied was adequate treatment of the depression.     

舍曲林与阿米替林治疗老年抑郁症对照研究

目的 探讨舍曲林与阿米替林治疗老年抑郁症的疗效及副反应。方法 将96例符合CCMD-3诊断标准的老年抑郁症患者采用随机分组的方法，分为舍曲林组和阿米替林组，治疗8周，采用4级临床疗效及HAMD（汉密尔顿抑郁量表）、HAMA（汉密尔顿焦虑量表）和TESS（副反应量表），评定疗效和不良反应。结果 舍曲林与阿米替林抗抑郁的疗效相似，抗焦虑效果优于阿米替林，而且副反应更轻。结论 舍曲林是一种既有效又安全的新型抗抑郁药，适合对老年抑郁症的治疗。     

西酞普兰治疗抑郁症临床观察

目的：评价西酞普兰治疗抑郁症的疗效和不良反应。方法：84例抑郁症患者，随机平分为两组，分别给予西酞普兰和阿米替林治疗，疗程8周。用汉密顿抑郁量表(HAMD)、临床疗效总评量表病情严重程度(CGI—SI)和副反应量表(TESS)评定疗效和不良反应结果：西酞普兰与阿米替林对抑郁症疗效相仿，但前者起效快，不良反应少于后者。结论：西酞普兰是一种安全有效的抗抑郁药。     

Desipramine-yohimbine combination treatment of refractory depression. Implications for the beta-adrenergic receptor hypothesis of antidepressant action

Preclinical investigations have shown that combined administration of the alpha 2-adrenergic receptor antagonist yohimbine hydrochloride and the tricyclic antidepressant desipramine hydrochloride produces a reduction in brain beta-adrenergic receptor function within four days. Since the ability of antidepressant treatments to reduce beta-adrenergic receptor function has been hypothesized to mediate antidepressant efficacy, it was predicted that combined desipramine-yohimbine treatment would be a more rapid-acting and potent antidepressant regimen than desipramine alone. In the present investigation, the effects of desipramine (N = 11) and desipramine-yohimbine (N = 10) treatment on depressive symptoms, norepinephrine turnover, and blood pressure were determined in patients with major depression who had a history of nonresponse to standard antidepressant treatments. Neither desipramine nor desipramine-yohimbine proved to be an effective treatment, although concomitant yohimbine administration did attenuate the ability of desipramine to decrease plasma free and 24-hour urinary 3-methoxy-4-hydroxyphenyl-ethyleneglycol levels and blood pressure. Fifteen of the 21 patients eventually had a good response to pharmacologic treatments, particularly a desipramine-lithium carbonate or lithium carbonate-tranylcypromine sulfate combination treatment (11 of 14 responded). This study provides evidence against the beta-adrenergic receptor hypothesis of antidepressant action.     

Depression,antidepressants, and plasma DBH

Plasma levels of dopamine-β-hydroxylase (DBH) were determined in 16 unmedicated patients with major depressive episodes (nonpsychotic) and in an equal number of normal subjects, before and after 4 weeks of treatment with tricyclic antidepressants. Some eight patients were treated with amitriptyline, and the remainder received desipramine. The controls remained medication free during the entire experimental period. Degrees of depression were quantified before and after treatment with the Hamilton Rating Scale of Depression (HRSD). There were no significant differences between the depressed patients and the controls on levels of DBH. Similarly, there were no within-group, pre-posttreatment differences on the enzyme levels in either group. Pre-and posttreatment HRSD scores did not correlate with corresponding plasma DBH levels. Plasma levels of amitriptyline, nortriptyline (product of amitriptyline in the body), and desipramine at the end of 4 weeks of treatment also failed to correlate with the enzyme levels.     

西酞普兰与阿米替林治疗抑郁症的对照研究

目的　探讨选择性五羟色胺再摄取抑制剂西酞普兰治疗抑郁症的疗效及安全性。方法　将 6 0例符合CCMD 3诊断标准的抑郁症患者随机分为两组 ,分别给予西酞普兰和阿米替林治疗 ,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　西酞普兰组显效率 80 % ,阿米替林组显效率 76 .6 7% ,差异无显著性 ,各因子分中西酞普兰组认知障碍减分多于阿米替林组 ,差异有显著性。HAMA减分西酞普兰组少于阿米替林组 ,差异无显著性。西酞普兰常见副反应有恶心、口干、头痛等 ,但比较轻微。结论　西酞普兰见效快 ,疗效肯定 ,副反应发生率少而轻微。     

西酞普兰与阿米替林治疗抑郁症的对照研究

目的比较西酞普兰与阿米替林治疗抑郁症的疗效与副反应。方法80例抑郁症随机分成两组,一组服用西酞普兰,另一组服用阿米替林,治疗8周。结果西酞普兰组显效率为82.5%,总有效率95%;阿米替林组显效率为67.5%,总有效率92.5%。起效时间:西酞普兰为11天,平均(13.4±2.6)天。阿米替林为15天,平均(16.2±2.1)天。西酞普兰组和阿米替林组的副反应发生率分别为12.5%和47.5%,差异有显著性(p〈0.01)。结论西酞普兰治疗抑郁症疗效确切,起效快,副反应小,安全性大,可作为一线抗抑郁药物。     

A double blind comparison of viloxazine and amitryptyline in involutional and endogenous depression

Thirty-two hospitalized patients with either endogenous (n = 15) or involutional (n = 17) depression were entered into a double blind study to compare the effectiveness and acceptability of viloxazine with amitriptyline. The severity of the depression was assessed before starting treatment and at day 7, 14 and 28 using the Hamilton Rating Scale. Spontaneously reported side effects were recorded. Patients received viloxazine 50 mg three times a day during the first week followed by 100 mg three times a day during the next three weeks or amitriptyline 25 mg three times a day during the first week followed by 50 mg three times a day during the following three weeks. Viloxazine and amitriptyline were equally effective in endogenous depression, but viloxazine was significantly more effective than amitriptyline in patients with involutional depression. Nausea and vomiting were the main side effect of viloxazine during early treatment necessitating the withdrawal of two patients. Anticholinergic side effects were reported during amitryptyline treatment, but were absent in patients on viloxazine. It is concluded that viloxazine is an effective antidepressant and particularly useful in the treatment of involutional depression.     

万拉法新与阿米替林治疗抑制症对照研究

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,以阿米替林为对照组,应用HAMD、HAMA、TESS量表,在疗前、疗后1、2、6周进行疗效及副反应评定.结果万拉法新的痊愈率(70%)高于阿米替林(45%),但无显著差异(x2=2.56,P＞0.05);显效率(85%)与阿米替林(80%)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、副作用轻微.     

A double-blind comparison of citalopram (Lu 10-171) and amitriptyline in depressed patients

In a controlled, clinical, multicentre trial comprising a total of 43 patients (17 men and 26 women) citalopram was compared double-blindly with amitriptyline. Nineteen patients of each group were classified as endogeneously depressed, whereas four patients of the citalopram group and one of the amitriptyline group were classified as non-endogenously depressed. The patients were seriously ill with a high frequency of previous depressive episodes and of mental disorders among their closest relatives. Thirteen of the patients in either group had received antidepressants without satisfactory effect before entry into the trial. Each patient was treated for a period of at least 3 weeks with daily citalopram doses of 30-60 mg or daily amitriptyline doses of 75-225 mg. A statistically significant reduction of MADRS scores (total scores as well as each of the 10 individual items) was recorded in both groups. The only difference between the groups was a trend towards a better effect on sleep disturbances in the amitriptyline group. Side-effects were recorded more frequently in the amitriptyline group than in the citalopram group, global assessment of side effects being significantly different in favour of citalopram. It is concluded that citalopram is an effective and safe drug in the treatment of endogenous depression - probably as efficacious as amitriptyline, but with fewer side effects.     

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.     

西酞普兰治疗抑郁症的疗效对照研究

目的 探讨选择性五羟色胺再摄取抑制剂西酞普兰治疗抑郁症的疗效及安全性.方法 将60例符合CCMD-3诊断标准的抑郁症病人随机分为两组,分别给予西酞普兰和阿米替林治疗.疗程6周.采用汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）评定疗效,并以不良反应量表（TESS）评定不良反应.结果 西酞普兰组显效率为83.33%,阿米替林组为76.67%,差异无显著性.西酞普兰不良反应少而轻微,主要有恶心、口干、头痛.结论 西酞普兰是一见效快、疗效肯定及不良反应少而轻微的抗抑郁药.     

Dementia with coexistent major depression

Eleven percent (N = 25) of 232 dementia patients seen in an active geropsychiatry service also met criteria for major depression. Ten patients with dementia/depression were prospectively compared with 10 non-depressed demented and 33 nondemented depressed patients on pretreatment and posttreatment ratings of depression and cognition/memory. Seventy percent (N = 7) of the dementia/depression group and 73% (N = 24) of the depression-only group responded to antidepressant therapy. Signs and symptoms of depression complicating dementia were similar to depressive phenomena in the depression-only group. Depression with dementia appeared to lower performance on cognitive tests. Following treatment, although cognitive impairment remained in the demented range, test performance improved.     

Dexamethasone suppression test as an aid for selection of specific antidepressant drugs in patients with endogenous depression

The dexamethasone suppression test (DST) and response to two different antidepressant drugs (maprotiline as a specific noradrenergic, and amitriptyline as a predominantly serotoninergic drug) were investigated in 44 endogenously depressed female inpatients. The more anxious and/or agitated patients were mostly treated with amtiriptyline, the non-anxious and retarded patients with maprotiline. It was found that among maprotiline responders (N = 15) there were significantly more abnormal DSTs and postdexamethasone serum cortisol levels were significantly higher than among amitriptyline responders (N = 16). On the other hand, DST abnormalities among amitriptyline non-responders (N = 10) were similar to those among maprotiline responders. The results confirm earlier reports by Brown et al. (1980), Ettigi et al. (1983) and Fraser (1983) and indicate that abnormal DST may identify the "noradrenergic" subtype of endogenous depression and that the DST represents a good way of selecting a specific antidepressant drug for the treatment of endogenously depressed patients.     

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.     

Effect of chronic antidepressant treatment with adinazolam and desipramine on melatonin output.

Output of melatonin or its main metabolite, 6-sulphatoxy melatonin, provides an index of noradrenergic activity in the pineal gland, which is of interest in major depression and during its treatment with antidepressants. Fifteen female depressed outpatients did not differ in levels of 24-hour urinary 6-sulphatoxy melatonin compared with 13 female control subjects. However, a subgroup of the depressed patients (n = 9) who were treated with desipramine showed a significant elevation of 6-sulphatoxy melatonin levels after 1 week of treatment and a return to baseline levels after 6 weeks. There was also a significant negative correlation between 6-sulphatoxy melatonin levels and symptom severity as measured by the Hamilton Rating Scale for Depression after 3 weeks of treatment with desipramine. The other subgroup of depressed patients (n = 6) were treated with adinazolam, a benzodiazepine with antidepressant properties. Despite comparable antidepressant effects to those achieved with desipramine, adinazolam was not associated with any apparent change in 6-sulphatoxy melatonin output during 6 weeks of treatment. There was also no correlation between 6-sulphatoxy melatonin levels and symptom severity.     

Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment: a positron emission tomography study with fluorine-18-labeled setoperone.

BACKGROUND: The neuroreceptor changes involved in therapeutic efficacy of various antidepressants remain unclear. Preclinical studies have shown that long-term administration of various antidepressants causes down-regulation of brain serotonin 2 (5-HT2) receptors in rodents, but it is unknown if similar changes occur following antidepressant treatment in depressed patients. Our purpose, therefore, was to assess the effects of treatment with desipramine hydrochloride on brain 5-HT2 receptors in depressed patients using positron emission tomography (PET) and fluorine-18 (18F)-labeled setoperone. METHODS: Eleven patients who met DSM-IV criteria for major depression as determined by a structured clinical interview for DSM-III-R diagnosis and suitable for treatment with desipramine were recruited. Ten patients underwent a PET scan before and another after 3 to 4 weeks of treatment with desipramine. RESULTS: Eight of the 10 patients responded to desipramine treatment as indicated by more than 50% decrease in Hamilton Depression Rating Scale scores. Depressed patients showed a significant decrease in 5-HT2 receptor binding as measured by setoperone binding in frontal, temporal, parietal, and occipital cortical regions following desipramine treatment. The decrease in 5-HT2 receptor binding was observed bilaterally and was particularly prominent in frontal cortex. CONCLUSIONS: Depressed patients showed a significant reduction in available 5-HT2 receptors in the brain following desipramine treatment, but it is unknown if this change in 5-HT2 receptors is due to clinical improvement or an effect of desipramine that is unrelated to clinical status.     

A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder

In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.     

Carbohydrate craving and increased appetite associated with antidepressant therapy

The symptom of carbohydrate craving and increased appetite (CHH) was studied in 180 outpatients receiving antidepressant treatment. One hundred and fifty-eight of these patients had a DSM-III diagnosis of panic disorder and 17, major depression. The incidence of CHH was similar in both diagnostic groups. Thus, antidepressant treatment is associated with CHH in patients with diagnoses, other than depression. Desipramine was least likely to induce CHH compared to imipramine, amitriptyline and doxepin. Most patients who developed CHH on imipramine no longer experienced this side effect when switched to desipramine. CHH was not more frequent among women and not associated with antidepressant dosage or treatment response. Histamine H-1 receptor blockade may be an important factor in the etiology of CHH.