Antipsychotics in the treatment of autism

Abstract

Atypical antipsychotics have become indispensable in the treatment of a variety of symptoms in autism. They are frequently used to treat irritability and associated behaviors including aggression and self injury. They may also be efficacious for hyperactivity and stereotyped behavior. This review presents the rationale for the use of this drug class in autism and reviews the most important studies published on this topic to date. Significant adverse effects, including weight gain and the possibility of tardive dyskinesia, are reviewed. Future research directions are discussed.

Figure 1. Simplified schematic of a DA synapse showing synthesis of DA, a postsynaptic D₂ receptor, and intracellular mechanisms.

Most conventional and atypical antipsychotics block DA D₂ receptors. The D₂ receptor is coupled by an inhibitory G protein (G_i) to adenylyl cyclase (AC), which converts ATP to cAMP, a secondary messenger.

Figure 2. Simplified schematic of a serotonin (5-HT) synapse showing synthesis of 5-HT, a postsynaptic 5-HT₂ receptor, and intracellular mechanisms.

In contrast to conventional antipsychotics, most atypical antipsychotics block 5-HT₂ receptors. The 5-HT₂ receptor is coupled by a G protein (G_q) to phospholipase C (PLC). Phospholipase C hydrolyzes membrane-bound phosphatidyl inositol (PIP₂), generating 2 secondary messengers, inositol triphosphate (IP₃) and diacylglycerol (DAG).