Pharmacological Treatment of Schizophrenia
Pharmacological Treatment of Schizophrenia
Schizophrenia affects approximately 1% of the population worldwide and, in around 80% of those, it is a lifelong, disabling disorder. Both genetic and environmental factors contribute to the development of the disorder.
The symptoms of schizophrenia can be classified into three groups:
• positive symptoms (e.g. hallucinations and delusions);
• negative symptoms (e.g. anhedonia, social withdrawal and lack of initiative and energy); and
• disorganisation (e.g. incoherence, loose associations and poverty of thought content).
Cognitive impairment and deterioration are core features of schizophrenia and they are strongly related to disability.
Short History of Antipsychotic Drugs
Drug therapy has been the main treatment modality for schizophrenia. Chlorpromazine, the first modern antipsychotic drug, was introduced into psychiatry in 1952. It was followed by a number of other antipsychotics (e.g. haloperidol and thioridazine), also called neuroleptics because of their neurological side effects, such as Parkinsonian syndrome and tardive dyskinesia. The antipsychotic properties of these drugs were inseparable from extrapyramidal effects.
Clozapine was introduced into psychiatry in Europe in the 1970s and in the US in the 1990s. The frequency of the extrapyramidal neurological side effects of clozapine is comparable with placebo. Clozapine was followed by the introduction of other antipsychotics (e.g. risperidone and olanzapine) with low frequency of neurological adverse events. As the term ‘neuroleptic’ was no longer appropriate for these new drugs, the term ‘atypical neuroleptics’ and later ‘second-generation antipsychotics’ was introduced. Dopamine, especially dopamine-2, and later serotonin and other neurotransmitter receptors were identified as targets for antipsychotic drugs.
First-generation Antipsychotics
Many of the first-generation antipsychotics – e.g. flupentixol, haloperidol, perphenazine, trifluoperazine and thiothixene – are much more potent at blocking dopamine receptors than chlorpromazine. Increased potency of these drugs was not related to increased effectiveness, but to higher incidence and prevalence of extrapyramidal side effects caused mainly by dopamine blockade of the basal ganglia.
The first-generation antipsychotics had a dramatic effect on the life of patients suffering from schizophrenia. About 20% of the patients had full remission and, based on the results of two-year studies, only approximately 30% to 40% of the patients relapsed during treatment with first-generation antipsychotics, compared with approximately 80% without treatment.
