More choices for treating voices

Abstract

In psychiatry, 1997 may be remembered as the year in which the new generation of antipsychotics, the so-called atypicals, gained wide acceptance. The older antipsychotics, those of which chlorpromazine is the prototype and haloperidol a newer exemplar, have been the mainstay for treating schizophrenia and other psychotic disorders for more than forty years. There are now at least four of the newer antipsychotics available in most parts of the world. These new medications appear to be equally effective in reducing psychotic symptoms, they produce fewer extrapyramidal side-effects (EPS), and they are pharmacological ly broad spectrum. When the older antipsychotics were introduced, clinicians believed that efficacy and side-effects were linked, and that the optimal dose was achieved when the patient developed parkinsonian side-effects. This teaching was based on the assumption that blockade of D2 receptors in mesolimbic and nigrostriatal projections was the primary mechanism of action. We now know the story is not that simple. The newer medications affect other neurotransmitter systems (eg, serotonin), and the effects on limbic and striatal dopamine can be dissociated. Pilowsky and colleagues (Pilowsky) demonstrated that patients taking clozapine (an atypical agent) achieve the same degree of D2 and D3 blockade in the temporal cortex vs those taking typical antipsychotics (both -90%) , but significantly less blockade in the striatum (58% vs 90%). This study provides in vivo confirmation of the hypothesis that clozapine selectively blocks limbic dopamine without affecting striatal dopamine. Since noncompliance is the leading cause of relapse in schizophrenia, and since EPS is one of the leading causes of noncompliance, the newer drugs have the potential to improve quality of life. During 1997, imaging studies were used extensively to study new frontiers in mental function, such as the brain reward systems that mediate drug highs or the mechanisms of mood and emotion. For example, Volkow and colleagues demonstrated that the magnitude of cocaine-induced high among chronic users is directly correlated with the degree of striatal dopamine transporter blockade, and therefore the availability of free dopamine (Volkow). Studies in detoxified cocaine users showed craving to be associated with enhanced thalamic response to dopamine agonist stimulation (Nature 1997; 386: 830).