Novel approaches to the pharmacotherapy of schizophrenia

Abstract Numerous attempts to extend the pharmacotherapy of schizophrenia beyond conventional neuroleptics are reviewed. Clozapine and melperone are atypical neuroleptics that produce few extrapyramidal side effects during acute usage and possible less tradive dyskinesia with prolonged use. Decreasing dopamingeric activity with a tyrosine hydroxylase inhibitor or dopamine autoreceptor agonists may also be of value. Neuroleptics that block voltage‐sensitive calcium channels or calcium channel blockers per se have been advocated for treatment of negative symptoms or the deficit state. Among other possible clinical approaches reviewed are: beta adrenergic blockers, clonidine, tryptophan, 5‐hydroxytryptophan, fenfluramine, GABA drugs, including high dose benzodiazepines, lithium, carbamazepine, opioid agonists and antagonists, gamma‐endorphins, TRH analogs and vasopressin. Most studies indicate these agents produce inconsistent or slight‐to‐modest benefits, either in comparison with standard neuroleptic drugs or inaddition to neuroleptics, in groups of schizophrenic patients, including some double blind placebo‐controlled trials. Those individuals who do respond sometimes, but not always, fail to relapse when the experimental drug is discontinued or fail to respond to it in subsequent trials. Consistent with the presumed heterogeneity of schizophrenia, there is some evidence supporing non‐neuroleptic drug treatment for specific schizophrenic subtypes. The various stages of this usually life‐long disorder, together with the possible mutability of the underlying etiological factors over time, requires the utmost care in clinical trials.