Antipsychotics are drugs used for the treatment of psychoses, mainly for schizophrenia and bipolar disorder, but also for psychoses associated with other disorders, including neurodegenerative diseases. This article describes first-generation, or typical, and second-generation, or atypical, antipsychotics with D2 antagonism as a common feature and serotonin blocking effect as an additional feature. Some antipsychotics do not fit into these categories. This article describes mechanism of action, indications for use, and adverse effects of various antipsychotic agents.
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• Antipsychotic agents are dopamine antagonists that were originally designed as an alternative to surgical lobotomy for intractable psychiatric disorders such as schizophrenia.
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• Several antipsychotics are approved for schizophrenia as well as bipolar syndrome, whereas others are in use for psychoses associated with other conditions, including neurodegenerative disorders such as Parkinson disease.
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• The neurologic adverse effects of antipsychotics include drug-induced movement disorders such as tardive dyskinesia and neuroleptic malignant syndrome.
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• The effective and safe use of antipsychotics requires a personalized approach based on pharmacogenetics, therapeutic drug monitoring, and drug-drug interactions.
Historical note and terminology
The term "antipsychotic" is applied to a drug used for the treatment of psychoses, mainly schizophrenia and bipolar disorder. Antipsychotics are sometimes referred to as neuroleptics, which is a broader term that literally refers to drugs "taking hold of the nerve,” implying psychotropic as well as adverse effects on the nervous system. Antipsychotics are usually described as typical or first generation and were introduced in the 1950s. The first antipsychotic, chlorpromazine, was originally developed as an anesthetic and was later used on psychiatric patients because of its powerful calming effect, referred to as “pharmacological lobotomy,” which was an alternative to the surgical lobotomy that was still performed at that time (17). The first of the atypical or second-generation antipsychotics, clozapine, was introduced in the 1970s. Both types of antipsychotics block dopamine receptors, but atypical antipsychotics block serotonin receptors as well. The division between the 2 types, however, is not accurate. Third-generation antipsychotics are partial D2 agonists. Several new antipsychotic drugs are in development.
The focus of this article is on atypical antipsychotics, which are now used in clinical practice, but the adverse effects of typical antipsychotics will also be considered.