Relevance of new psychotropic drugs for the neurologist
- Raymond Way Neuropsychiatric Research Group, University Department of Clinical Neurology, Institute of Neurology, Queen Square, London WC1N 3BG, UK
- Correspondence to: Professor M R Trimble
Clinicians can now select psychotropic agents from a wide choice
The discovery of neuroleptic and antidepressant drugs about 50 years ago marked a breakthrough in pharmacotherapeutics, which has revolutionised the therapy of many neuropsychiatric conditions. The efficacy of the early and then standard agents in alleviating depressive and psychotic symptoms and preventing their reoccurrence has been established in numerous trials, but other factors limit their utility. These include the facts that not all patients respond to treatment, and that they tend to often have an unacceptable incidence of side effects, many of which are neurological in nature—such as parkinsonism, dystonia, tardive dyskinesia, and seizures.
In an effort to match improved therapeutic efficiency with a better side effect profile, various new antidepressant and antipsychotic drugs have recently been developed. These are becoming widely used and their introduction may have important consequences for neurological practice.
ANTIPSYCHOTIC DRUGS
According to the dopamine hypothesis for schizophrenia, limbic D2 receptor blockade is essential for a drug to have antipsychotic activity.1 Classic neuroleptic drugs, such as haloperidol, antagonise dopamine D2 receptors and their clinical efficacy correlates with inhibitory activity at these receptor subtypes. Haloperidol leads to parkinsonism in 15%-45% of treated schizophrenic patients.2
The development of clozapine with properties differing from traditional neuroleptic agents has heralded the era of “atypical” antipsychotic drugs which are claimed to have improved tolerability and effectiveness compared with conventional neuroleptic drugs. The effectiveness of clozapine in treating patients with schizophrenia refractory to other medications,3 coupled with a low incidence of extrapyramidal side effects, has been attributed to a unique receptor profile and marked a major advance in psychopharmacotherapy. However, therapy with clozapine is limited by its potential for serious adverse effects, in particular the induction of agranulocytosis in 1%–2% of patients and it is therefore considered a second line therapy. …
