Before the advent of antipsychotic medication the treatments available to the psychiatrist were, with the exception of ECT, ineffective. Things changed in 1950 when chlorpromazine was first synthesised; now for the first time people working with the mentally ill had a way of improving the previously pretty dismal outcome for sufferers of schizophrenia. As discussed by Trevor Turner, this also improved the respectability of the psychiatric profession and provided the basis of an aetiological theory for psychotic illness.
Other medications followed in Chlorpromazine’s wake. These have become known as the ‘typical‘ antipsychotics and examples are Haloperidol and fluphenazine. Although good at reducing some of the symptoms of schizophrenia, they also produced some horrid side effects, most notably Parkinsonian symptoms and another movement disorder called tardive dyskinesia.
In 1958 Clozapine was developed. This was the first ‘atypical’ antipsychotic. Its difference was that it wasn’t nearly such a good blocker of D2 receptors, but had more activity at many other receptors including dopamine D4. It causes no tardive dyskinesia and leads to some improvement in schizophrenic negative symptoms. Other atypical drugs have followed, these include Olanzapine, Quetiapine and Risperidone. They too are less potent D2 receptor blockers, and are less likely to cause tardive dyskinesia. These newer drugs are currently the most widely used, although there is research that they are no better than the older and cheaper drugs at improving patient outcome.
Clozapine is the ‘psychiatric domestos’ of the title. It’s what psychiatrists use when all the other treatments of psychosis have failed and when it works it’s pretty impressive. As a medication it’s not without a chequered past and during the 1970s it was withdrawn because of its association with neutropaenia (3% of patients) and agranulocytosis (0.8%); however it was reintroduced following a study which proved it was more effective than other antipsychotics. Although it does not cause movement disorders, it does have a lot of other side effects, most notably hypersalavation, sedation and diabetes. Why it works more effectively than other drugs is unknown; although its action at D2 receptors is reduced, this still appears important. No one has ever synthesised an antipsychotic with no D2 activity.
So, these days, Clozapine is given to our most treatment resistant schizophrenic patients. It’s an expensive operation. Each patient requires strict monitoring including regular blood tests and there are dedicated ‘Clozapine clinics’. I hope that within my lifetime we’ll look upon it as a hopelessly antiquated way to treat our most difficult patients, but for now its the best we’ve got in an area where the search for new medication is frustratingly slow.