2006 issue 2

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Volume 22, issue 2

Only for Pharmacotherapy in Psychiatry and Neurology

Antidepressants – facts and controversy

Stanisław Pużyński1
1. II Klinika Psychiatryczna Instytutu Psychiatrii i Neurologii w Warszawie
Farmakoterapia w Psychiatrii i Neurologii, 2006, 2, 69–78
Keywords: anidepressants I and II generation, position in pharmacothertapy of depression, mechanisms of action, risk of switch depression to mania, risk of suicide, evaluation of antidepressant effect, problems of pharmacoeconomy of antidepressants

Abstract

In the 50th aniversary of implementation to the clinical practice imipramine – first TCA antidepressant – author analyzed positive and controversial problems related to first and second generation of antidepressants.
Classical tricyclic antidepressants (TCA), still regarded as essential in the treatment of depression, are called by pharmacologists “dirty” due to the complex (not “clean”) mechanism underlying action of these drugs, involving several types of neurotransmission. Numerous side effects are connected with such a complex action. It should be noted that basic TCAs are characterized by a considerable effectiveness, so that imipramine is still used as a reference drug (a “golden standard”) in the evaluation of new drugs efficacy. One of major directions in the development of contemporary psychopharmacology of depression is to synthesize drugs showing a selective effect on neurotransmis-sion, affecting a single, specific system (NA or 5HT). Implementation of such drugs in the clinical practice involves a number of questions, concerning: mechanisms underlying their antidepressant action, pathogenesis of depression (i.e. which of the two neurotransmission systems is changed: NA or 5HT), and effectiveness of drugs selectively enhancing a specific type of neurotransmission. These problems have not been elucidated so far, and research findings reported in the literature are inconsistent. Undoubtedly, antidepressants with selective action are safer than TCAs – however, it is not clear yet whether they are equally effective. It can be hoped that these controversial problems may be settled due to the implementation in clinical practice of antidepressants affecting both the NA and 5HT systems, but having no influence on other types of neurotransmission (DA, ACh, H1 and H2 receptors).
Among controversial problems need further inwestigation author indicates: short and long term influence of antidepressants on the course of bipolar disorder (f.ex. induce switching depression of mania, rapid cycling course), increase the risk of suicide during the first days of treatment.
This paper discusses actual, often controversial, problems related to clinical investigations of antidepressants. Such problems include criteria of results evaluations (50% reduction of pretreatment number of point in the Hamilton Depression Rating Scale is not satisfactory from clinical point of view, this criterion could be replaced by remission), duration of treatment (4-6 weeks observation period is to short for adequate evaluation of treatment effects). Author critically evaluate some aspects pharmacoeconomy and abuse of pharmacoeconomy by pharmaceutical industry.

Address for correspondence:
Stanisław Pużyński
II Klinika Psychiatryczna IPiN
Al. Sobieskiego 9; 02-957 Warszawa
tel. (022) 4582-764
e-mail: puzynsk@ipin.edu.pl