Effects of two antidepressants on memory performance in depressed outpatients: a double-blind study

Forty outpatients with primary depression were randomly assigned on a double-blind basis to treatment with amitriptyline (a tricyclic antidepressant) or clovoxamine (a nontricyclic, experimental antidepressant). Memory and depression were assessed during a pretreatment baseline period and at the end of days 4, 7, and 28 of drug treatment. A signal detection recognition memory task and conventional memory measures (including the Benton Visual Retention, Wechsler Logical Memory, and verbal learning tests) were used to assess memory.Although both drugs led to comparable clinical improvement in depression, they affected memory performance differently. The signal detection recognition memory task detected an impairment in memory after chronic amitriptyline administration, as contrasted with an improvement in memory after chronic administration of clovoxamine. The memory impairment in the amitriptyline group and improvement in the clovoxamine group were the result of changes in sensitivity [P(A)]. No changes in response bias (BO were detected. Conventional memory tests failed to detect drug-related differences in memory between the two groups. On the Benton, errors decreased over time within both drug treatment groups, whereas correct reproductions increased within the amitriptyline group only. However, between-group differences on the Benton did not reach significance.Results from the signal detection task suggest an amitriptyline-associated memory impairment. However, this interpretation is tempered by the finding that conventional memory measures failed to detect differences in memory performance between the two groups. We discuss the limitations of traditional memory measures and the utility of a signal detection approach in studies of psychopharmacologic influences on memory.     

Cianopramine and amitriptyline in the treatment of depressed patients — a placebo-controlled study

3-Cyano-imipramine (cianopramine) is a potent and selective inhibitor of serotonin uptake into synaptosomes. In a double-blind trial, 60 patients with various types of depression fulfilling the DSM-III criteria of depressive episodes were treated with either cianopramine (n=20, mean daily dose 3.3±0.6 mg) amitriptyline (n=20, mean daily dose 86.4±21 mg) or placebo (n=20) orally. According to the ratings of the Hamilton Scale of Dpression and clinical global evaluations, both active drugs showed statistical superiority over placebo (P<0.02). The frequencies of anticholinergic side effects in the cianopramine group were comparable to those of the placebo group and were less than in the amitriptyline group. The findings suggest that cianopramine is a promising new antidepressant.     

A double-blind comparison of clovoxamine and amitriptyline in the treatment of depressed outpatients

Forty-two outpatients with major depression were treated in a 4-week double-blind parallel-group comparison of the new antidepressant clovoxamine--a member of oximethers of aralkylketones--with amitriptyline. The two drugs were comparable in efficacy, although because of the small sample size a moderate clinical difference between treatments may not have been detected. The magnitude of unwanted effects also was comparable, but clovoxamine produced fewer "anticholinergic" effects; this was determined by patient complaints of typical anticholinergic symptoms, by decreased salivary flow, and by a new signal detection memory test.     

Clomipramine and amitriptyline in depressed outpatients

Clomipramine (75–125 mg/day), a relatively new tricyclic anti-depressant, was compared to amitriptyline (75–125 mg/day) in a double-blind 6 week trial carried out with 93 psychiatric and 75 non-psychiatric depressed out patients. Psychiatric patients were initially more depressed, more pretreated, but less chronically ill, took a higher daily dosage of medication, yet reported fewer side effects, dropped out less frequently, and reported more improvement than nonpsychiatric patients. Clomipramine tended to produce more side effects, particularly of sedative nature, was associated with greater dosage deviation and attrition, and appeared slightly faster in its onset of action than amitriptyline. While amitriptyline produced significantly more improvement than clomipramine according to several endpoint measures, a number of improvement criteria showed both agents to be of comparable efficacy.Clomipramine was particularly effective in the less depressed non-psychiatric low somatizing patients, while it produced a particularly poor response in high somatizing patients. Amitriptyline was especially effective in the more depressed psychiatric patients, and was not affected by level of somatic complaints. Both agents produced a high degree of clinical improvement in this non-psychotic depressed population.Drs. Weise, Feldman, Rosenfeld, and Whalen are members of our Private Practice Research Group; and Drs. Csanalosi and Chung are members of our Psychopharmacology Research Clinic.This research was supported in part by USPHS Grants MH-08957-8. Medications were provided by Ciba-Geigy Pharmaceutical Company. The authors wish to thank Drs. W. George Case, Richard J. Morris, Juliette E. Nathanson, Lawrence C. Parish, Jorge A. Pereira-Ogan, and Peter T. Hesbacher for their participation in the data collection phase of this study; and Miss Joanne Johnson and Mrs. Janice Vlahovich for statistical and editorial assistance.     

Amitriptyline and hydroxylated metabolite plasma levels in depressed outpatients

As part of a double-blind clinical trial comparing phenelzine and amitriptyline in outpatients with predominantly major depressive disorder, plasma tricyclic antidepressant drug concentrations were measured in 83 amitriptyline-treated patients. In 29 of these patients, hydroxymetabolites were also assayed. Patients were treated for 6 weeks at a fixed dose of 150 mg/day of amitriptyline after the first 5 days. Therapeutic outcome was assessed with a structured depression interview schedule, the Symptom Checklist-90, a side effects checklist, and a global improvement scale. Steady state plasma levels of 10-hydroxynortriptyline were in the same range as amitriptyline or nortriptyline concentrations. Clinical response did not relate significantly to plasma levels of either the parent drug, its metabolites, or the sum of all four pharmacologically active substances. Minimum threshold tricyclic antidepressant levels for therapeutic effect were not found. Assay of its active hydroxymetabolites does not appear to improve the clinical utility of routine amitriptyline level monitoring in patients with major depression in an outpatient setting.     

Amitriptyline and weight gain: a biochemical and endocrinological study

Summary

A study was carried out in 6 healthy volunteers to test the hypothesis that weight gain associated with amitriptyline treatment may be due to hypoglycaemia caused by increased circulating blood insulin. Subjects were treated with 50 mg amitriptyline b.d. for 28 days. Estimations made of serum levels of amitriptyline and its metabolite nortriptyline showed a steady state by the 10th day. No significant weight-gain was observed in any of the volunteers, although 2 reported an increase in appetite. There were no significant differences in any of the glucose tolerance curves, fasting or peak insulin levels or in the glucose I insulin curves for Days 0, 14 and 28.     

Chlorimipramine: A double-blind comparison of intravenous versus oral administration in depressed patients

A double-blind study was carried out in 30 patients to compare the results of chlorimipramine given orally and intravenously.The speed of onset of action and the overall improvement were excellent for both treatment modalities. No significant differences were found favoring either way of administration. As a consequence, our results do not support previous reports that suggest advantages and rationale for the intravenous usage of chlorimipramine.Also called Anafranil^® abroad and Clomipramine in the U.S.A.This investigation was supported in part by research grant MYP-5106 from the National Institute of Mental Health, U.S. Public Health Service.We thank Ms. Carol Umland, R. N. and Ms. Connie Ball, R. N. for their cooperation and dedication which made possible the successful completion of this study.     

Tricyclic plasma levels in depressed outpatients treated with amitriptyline

Seventy-four patients were treated with 150 mg/day amitriptyline (AT) to determine possible correlations between clinical improvement, demographic variables, and AT and nortriptyline (NT) plasma levels. Plasma level determinations after 2 and 6 weeks of treatment revealed that moderately significant correlations existed between AT plasma levels and clinical improvement, dosage intake, age, weight, sex, and coffee intake. Some of these findings were more pronounced after 2, and some after 6 weeks of treatment.     

Treatment of depressive outpatients with lorazepam,alprazolam, amytriptyline and placebo

This randomized double-blind study in 342 mildly to moderately depressive outpatients investigated the antidepressant effectiveness and speed of action of lorazepam, alprazolam and amitriptyline versus placebo. Six weeks of drug treatment were followed by a drug taper period, a control period with placebo and a control period without placebo, of 2 weeks duration each. Clinical improvement was assessed by rating scales (Clinical Global Impressions, Hamilton Rating Scales for Depression and Anxiety) and patient's self-ratings (Patient's Global Impressions, Self-rating Depression Scale and Visual Analogue Scale). At the end of week 6 all active drugs showed similar efficacy which was significantly superior to placebo. Compared to placebo, onset of efficacy was earlier on benzodiazepines than on amitriptyline. While tapering by decreasing the dosage, replacing drug with placebo and finally discontinuing placebo, clear withdrawal phenomena were not seen, but 20% of patients, equally distributed to all treatment groups, did not want to stop taking tablets after replacing drug with placebo. Drop-out rate during the treatment period was very low (9%). Significantly interfering adverse effects were seen in 27 patients, without predominance in one of the active drug groups.     

Human platelet imipramine recognition sites: Biochemical and pharmacological characterization

The influence of the membrane environment on the integrity of the human platelet [³H]-imipramine recognition site was examined. When platelet membranes were isolated in a buffer containing enzyme inhibitors (EDTA, EGTA and antiproteases) a significantly greater number of high affinity [³H]-imipramine binding sites was observed. A calcium-stimulated degradation of imipramine sites was also demonstrated. This degradation occurred in vitro over physiologically relevant time periods. Furthermore, inactivation of imipramine binding was achieved by very low concentrations (1C₅₀=5 μg/ml) of phospholipase A₂. Specific serotonin reuptake inhibitors were potent displacers of [³H]-imipraminebinding; histamine (H₁), alpha-adrenergic (α₁),, and muscarinic agents were much less active. The receptor was shown to be proteinaceous in nature due to its sensitivity to proteases, heat denaturation and chemical modification with N-ethylmaleimide. From these results it is proposed that membrane lipid perturbations, catalyzed by calcium, may control expression of platelet [³H]-imipramine sites. The relation of this recognition site to aminergic systems and the possible relevancy to the action of antidepressants are addressed.     

Amitriptyline pharmacokinetics a crossover study with single doses of amitriptyline and nortriptyline

Six healthy volunteers were given single doses of amitriptyline (AT) and of nortriptyline (NT) separated by at least 10 days. Plasma concentrations of both compounds were measured at intervals for 48 or 72 h. the total areas under the concentration-time curves for the ingested drug were greater for NT, but AT concentrations showed much higher peak values and took more than 12 h to reach the terminal phase of elimination. Doses of 50 mg AT produced areas averaging slightly less than half those for 100 mg AT in the same subject, suggesting some saturation of the elimination process. The consumption of a large, fatty meal just before taking the AT tablets had little effect on the plasma drug concentration curves. NT half-lives, measured after ingestion of NT tablets, were used in analysing the production of NT from doses of AT in the same subject. There was a rapid early production, amounting to 30–67% of the total and presumably resulting from the first pass of AT through the liver. NT was then formed continuously at a rate always, proportional to the simultaneous rate of AT elimination. The total amount of NT entering the systemic circulation was about one-quarter of the AT dose.     

Sertraline and cognitive behavioral therapy for depressed alcoholics: results of a placebo-controlled trial

Alcoholism and depression are common disorders that frequently co-occur in the same individual. Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of depression and also had decreased drinking in some studies of heavy drinkers and alcoholics. The reported effect of serotonergic medications on alcohol intake in depressed alcoholics has not been consistent. Most previous studies have not investigated the use of an SSRI in the context of cognitive behavioral therapy (CBT), a known efficacious treatment of both alcoholism and depression. The study presented here was a randomized placebo-controlled 12-week trial of sertraline combined with individual CBT focused on both alcoholism relapse prevention and depressive symptoms. Subjects were 82 currently depressed, actively drinking alcohol-dependent individuals. Subjects had either primary (independent) major depression (70 subjects) or substance-induced mood disorder and at least 1 first-degree relative (parent, sibling, or child) with an affective disorder (12 subjects). Depression and alcohol consumption outcomes were measured weekly over 12 weeks. Sertraline was well tolerated and all subjects had decreases in both depression and alcohol use during the study compared with baseline. Subjects who received sertraline had fewer drinks per drinking day than subjects who received placebo, but other drinking outcomes were not different between the 2 treatment groups. Treatment with sertraline was associated with less depression at the end of treatment in female subjects compared with female subjects who received placebo. Less drinking during the study was associated with improved depression outcome. The findings in this study suggest that sertraline, compared with placebo, may provide some modest benefit in terms of drinking outcome and also may lead to improved depression in female alcohol-dependent subjects. Additionally, alcohol relapse prevention CBT, delivered according to manual guidelines with modifications that provide specific attention to depression, appeared to be of benefit to subjects, although this interpretation is limited by the design of the study.     

Antidepressants and human memory: an investigation of four drugs with different sedative and anticholinergic profiles

The effects on memory and psychomotor functions of four antidepressants which differ in sedative and anticholinergic properties were assessed. Amitriptyline (37.5, 70 mg), trazodone (100, 200 mg) viloxazine (100, 200 mg), protriptyline (10, 20 mg) or placebo were administered in a double blind, independent groups design in which 90 subjects participated. Subjects completed a battery of tests before and 2 and 4 h after drug administration. The different antidepressants produced different patterns of effects across tasks. The relatively non-sedating compounds viloxazine and protriptyline produced very similar profiles and did not impair psychomotor or memory functions. In contrast, the two more sedative antidepressants produced global impairments on test of attention, manual motor speed, recoding skills and primary memory. Although both amitriptyline and trazodone impaired performance on episodic memory tasks, the effect of amitriptyline was significantly greater and this may reflect specific anticholinergic action over and above global sedative effects.     

Enhancing effect of HT008-1 on cognitive function and quality of life in cognitively declined healthy adults: a randomized, double-blind, placebo-controlled, trial

HT008-1 is one of the most effective multiherb mixtures that have neuroprotective effects in traditional Korean medicine. The purpose of this study was to conduct a clinical trial of the efficacy of HT008-1 on the neuropsychological functioning and quality of life (QoL) in cognitively intact adults. One hundred and eighteen male (n = 42) and female (n = 76) volunteers who reported no history of dementia or significant neurocognitive impairments and obtained Korean Version of Mini Mental State Examination total scores of at least 24 were examined via an 8-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel group, clinical trial. Participants were randomly assigned to receive either HT008-1 (n = 59) or placebo (n = 59) for 8 weeks. Efficacy measures consisted of participants' performance scores from pretreatment baseline to those obtained just before termination of treatment on standardized neuropsychological measures from the subsets of Wechsler Memory Scale—III (WMS-III). QoL was assessed by subjective questionnaires WHOQoL-Bref about five categories. Participants who scored in the lower third of the Auditory recognition delayed at baseline and received HT008-1 exhibited improvement on the WMS-III Auditory recognition delayed subtest compared with placebo controls. The HT008-1 group also improved on general health scores in the QoL test.     

Buspirone in depressed outpatients: a controlled study

One hundred fifty-five outpatients suffering from major depression with significant anxiety entered a double-blind study comparing 8 weeks of treatment with buspirone or placebo. Twenty-nine percent of buspirone and 40 percent of placebo patients discontinued treatment before 8 weeks. Major efficacy measures were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D retardation and anxiety factors, the HAM-D Rickels and Bech core depression clusters, the Clinical Global Impressions (CGI), and the Hopkins Symptom Checklist (HSCL). Results were consistent across all outcome measures, including the two core depression clusters, with treatment response to buspirone significantly better than to placebo at treatment endpoint. Seventy percent of buspirone and 35 percent of placebo patients (p less than .01) were rated moderately or markedly improved after 8 weeks of therapy. Buspirone was found to be safe and well-tolerated by patients with major depression and concomitant anxiety at doses of up to 90 mg/day.     

盐酸氟西汀治疗抑郁症临床对照研究

目的：比较盐酸氟西汀和阿米替林治疗抑郁症的疗效和不良反应。方法：采用HAMD、HAMA和TESS量表及临床疗效评定标准分别评定疗效及副反应。结果：盐酸氟西汀与阿米替林治疗抑郁症均有良好效果。结论：盐酸氟西汀治疗抑郁症,疗效与阿米替林相当,副反应轻微,患者依从性较好。     

帕罗西汀与阿米替林治疗脑卒中后抑郁的比较

目的：比较帕罗西汀与阿米替林治疗脑卒中后抑郁的疗效与不良反应。方法：将符合CCMD—Ⅲ标准的68例脑卒中后抑郁患者，随机分为2组，分别用帕罗西汀和阿米替林治疗6周。采用HAMD、HAMA、CGI量表评定疗效，TESS量表评定不良反应。结果：治疗2周后帕罗西汀组优于阿米替林组，6周后两组抗抑郁疗效无差异，抗焦虑效果帕罗西汀组优于阿米替林组。帕罗西汀组不良反应较阿米替林组少而轻。结论：帕罗西汀治疗脑卒中后抑郁效果与阿米替林相当，抗焦虑效果优于阿米替林，且起效较快，耐受性好，安全性高。     

Amitriptyline in the treatment of anorexia nervosa: a double-blind, placebo-controlled study

The tricyclic antidepressant drug amitriptyline was evaluated as a short-term treatment of anorexia nervosa patients. In a 5-week double-blind, placebo-controlled study 11 patients were given amitriptyline and 14 received placebo. In addition, 18 patients who refused to participate in the drug trial and received only psychosocial treatment were used as an additional comparison group. Overall, patients in the three groups showed little improvement. No statistically significant differences favoring amitriptyline were found in any of the outcome variables. Plasma levels varied widely among patients receiving similar doses. No association was found between plasma levels and improvement in either psychiatric symptomatology or weight. Amitriptyline patients did not manifest any tendency for a reduction of depressive symptomatology. In addition, amitriptyline treatment was associated with substantial discomfort and adverse affects.