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PubMed1987

The greater safety of trazodone over tricyclic antidepressant agents: 5-year experience in the United States.

Trazodone demonstrates comparable efficacy with the tricyclic antidepressant agents (TCAs) but produces fewer of the untoward side effects associated with these drugs. All of the TCAs are potentially lethal when taken in overdose; they cause serious cardiovascular side effects; produce anticholinergic effects, which often are severe enough to result in discontinuation of medication; and impair cognition, especially in elderly patients. In contrast, trazodone is relatively safe when taken in overdose; no deaths have been reported to the manufacturer when trazodone was the only agent taken. Trazodone produces fewer and milder cardiovascular disturbances and anticholinergic effects than TCAs. If anticholinergic side effects do occur then they are rarely bothersome enough to result in discontinuation of therapy. In addition, cognitive skills, even in elderly patients, are less impaired in patients receiving trazodone therapy than in patients receiving TCA drugs. Although trazodone therapy has been associated with lethargy, dizziness, drowsiness, and confusion in some patients, symptoms have been mild and can be further minimized by administering the drug either after meals or once daily at bedtime.

Antidepressive Agents, Tricyclic↗
PubMed1994

Pharmacogenetics and drug metabolism of newer antidepressant agents.

A wide variety of drugs are metabolized by the human cytochrome P450 system, including antidepressants such as tricyclic antidepressants and serotonin selective reuptake inhibitors (SSRIs). Each P450 isoenzyme is the product of a separate gene; a number of genes have multiple alleles that result in genetic polymorphism in the population. Both CYP2D6 and CYP2C gene families are polymorphic; both families are important in antidepressant metabolism. A number of polymorphisms result in dysfunctional or inactive enzymes. The clinical importance is highly dependent upon the patient's clinical state, coadministered drugs, therapeutic index, and the relative importance of the defective pathway in the total process of drug elimination. In addition, a number of drugs can also act as P450 enzyme inhibitors, which have the potential of causing drug interactions. In patient management, it is important to consider the fact that most antidepressants can also act as enzyme inhibitors. A number of adverse reactions resulting from coadministration of tricyclic antidepressants and SSRIs have been described. Such drug interactions can be minimized or avoided by following simple clinical logic.

Alleles↗
PubMed1993

Debrisoquin and mephenytoin hydroxylation phenotypes and CYP2D6 genotype in patients treated with neuroleptic and antidepressant agents.

Debrisoquin and S-mephenytoin hydroxylation phenotypes were determined in 72 Spanish psychiatric patients treated with neuroleptic or antidepressant agents. One patient (1.4%) was classified as a poor metabolizer of S-mephenytoin. Between both neuroleptic- and antidepressant-treated patients, the distribution of the debrisoquin metabolic ratio was shifted toward higher values compared with 54 drug-free healthy subjects. Forty percent of patients treated with neuroleptics and 5% of patients treated with antidepressants were classified as poor metabolizers of debrisoquin. CYP2D6 genotype analysis in 36 neuroleptic-treated patients confirmed that the high metabolic ratios were attributable to inhibition of CYP2D6 and not to overrepresentation of subjects with poor metabolizer genotypes. In 48 selected Spanish drug-free subjects, CYP2D6 genotype predicted the phenotype with 95% accuracy. Neuroleptics and antidepressants interfere at therapeutic doses with phenotyping for CYP2D6 but not for S-mephenytoin hydroxylation capacity. In psychotropic-treated patients, genotyping provides a valuable tool for prediction of the CYP2D6 phenotype.

Adult↗
PubMed1990

[Antidepressive agents in the elderly].

Depressive disorders are the most common psychiatric illness in the elderly. All tricyclic antidepressants show comparable therapeutic efficacy, thus the choice of drug is based on their side effects profiles rather than on degree of therapeutic efficacy. The secondary amines nortriptyline and desipramine are drugs of choice for the elderly depressive patient because of their relatively mild side effects profile. New-generation antidepressants remain second choice. Patients suffering from a psychotic depression often require a combination of an antidepressant drug with an antipsychotic drug. Addition of lithium to a cyclic antidepressant can produce a rapid and lasting remission in patients with a major depressive disorder who do not respond to a cyclic antidepressant alone. Treatment with MAO-inhibitors or electroconvulsive therapy can also be considered in refractory cases.

Aged↗
PubMed1991

[Effects of antidepressive agents on tolerance of hypoxia and physical exercise].

In experiments on mice and rats we studied the influence of antidepressants on hypoxic and physical tolerance. The antidepressants pyrazidol, azaphen, imipramine and moclobemide as well as the nootropic drug piracetam prolonged the life of animals in conditions of hypoxic and hemic hypoxia and increased the survival rate of rats in circulatory hypoxia. In experiments on mice antidepressants increased also the time of swimming.

Animals↗
PubMed1978

[Inhibition and antidepressive agents].

The author distinguishes inhibition as a symptom from inhibition as a processus in the three following situations: a) Antidepressants and melancholic inhibition: the action on inhibition is studied referring to Kielholz classification of antidepressants. The author points out the risk of suicide by suppressing inhibition. b) Antidepressants and chronical psychoses: the author compares effects of antidepressants and stimulating neuroleptics in these syndroms. He thinks that with the two types of psychotropic drugs, one can obtain a desinhibitory effect. But antidepressants can be better used in paranoid personnalities, loss of ego boundaries, and some schizophrenic-like syndroms, when neuroleptics seem to be more desinhibitory in hebephrenics. The author stresses the depressive core in these psychotic personnalities. c) The antidepressant effect has been studied in neurotic depressions. The author describes essentially cases with reinforcement of inhibition as a negative therapeutic reaction by antidepressants. It deals with neurotic depressions evoluting on narcissic personnality back ground.

Adjustment Disorders↗
PubMed1991

Continuation and maintenance therapy with antidepressive agents. Meta-analysis of research.

The purpose of this study was to ascertain the clinical benefits of long-term antidepressant drug treatment in patients with recurrent major depression. Bibliographic reviews of four textbooks and five review articles, literature searches using MEDLINE (1977-1987) and EXCERPTA MEDICA (1974-1987), hand-searching of the bibliographies of identified papers, and a private set were used for data identification. The most informative, definitive research report was selected using explicit criteria for evaluating study design and quality, of each described, randomized, controlled, double-blind trial of long-term antidepressant agent treatment. The trials were started at a specified period after recovery from an affective episode, in patients with major depression. Of the fifty-five originally identified articles, nine were selected that specifically addressed this purpose. The basic data were extracted in the form of 2 x 2 tables comparing the number of patients with an affective relapse to those remaining well and meta-analysed. Six of the selected trials addressed continuation and three addressed maintenance therapy. In two trials of continuation and in one trial of maintenance treatment, antidepressants were significantly more active than a placebo. In none of the trials were antidepressants inferior to a placebo. Continuation therapy with antidepressants (amitriptyline and imipramine) is effective. There are insufficient data to allow any conclusions about the efficacy of maintenance therapy with antidepressants, long-term treatment with antidepressants relative to that with lithium carbonate, or long-term antidepressant treatment in patients with chronic depression.

Antidepressive Agents↗