POSSIBLE ANTIDEPRESSIVE EFFECTS OF OPIOIDS: ACTION OF BUPRENORPHINE

The euphorogenic and anxiolytic properties of opiates and of endorphins * prompt questions as to the possibility that a defectively operating endorphinergic system may represent a causative factor in the pathogenesis of endogenous depression. Though from biochemical and pharmacological data the evidence in support of this hypothesis is weak (cf. ref. 3) it, nevertheless, requires additional evaluation. However, irrespective of the presence of a hypothetical constitutional deficit of endogenous morphinomimetic substances compensated for by an exogenous supply in the therapy of depressed patients, the question arises if, independently from such a possible type of metabolic dysfunction in depression, there may exist direct pharmacodynamic therapeutic effects of opioids in depressive syndromes. Since anxiety and sleep disturbances, in addition to melancholia, make up an integral part of the psychopathology of depression, from their profile of action, it may be anticipated that opioids could be highly effective, therapeutically, in depressive illness. the “opium cure” has been recommended for the treatment of depressed patients, employing slowly increasing and later decreasing dosages of tinctura opii and of other opiates.B Interestingly, according to reports of that time, although a standardized evaluation of the therapeutic efficacy was, and is, lacking, this treatment was effective and did not result in opiate addiction, possibly, since the doses applied were comparatively low. Later, Fink et al.7 applied the mixed agonist/antagonist cyclazocine (1.0-3.0 mg) in 10 severely depressed patients and observed a strong antidepressive effect, in particular concerning the items “depressed mood” and “apathy.” A further clinical evaluation of possible beneficial effects of opiates has been deferred, possibly owing to the psychotomimetic effects of cyclazocine and, furthermore, in view of the fact that the discovery of tricyclic antidepressants and of MAO-inhibitors opened a new era in the pharmacotherapy of depressive syndromes. Interestingly, immediately after the discovery of the endorphins, which shed new light onto the possible psychotropic effects of an activation of opiate receptors, new attempts were initiated in the evaluation of the possible antidepressive effects of opioids. Kline et a1.* were the first to perform clinical trials in different types of psychiatric disorders (schizophrenia, depression, neuroses) by use of /3-endorphin infusions (1.5-6.0 mg) and observed in two depressed patients, in an open design, positive effects of this treatment. Angst et a1.,8 also in an open trial, investigated the possible antidepressive action of infusions of 10 mg of B-endorphin and detected a switch to hypomania/ mania in three of six depressed patients. Subsequently, doubleblind trials as to the possible antidepressant efficacy of &endorphin have been Indeed, since the time of Emil Kraepelin