Continuous versus extended antipsychotic dosing in schizophrenia: Less is more

Antipsychotic drugs temper psychotic symptoms by interacting with dopamine D2 receptors to reduce dopamine neurotransmission. Currently, the standard of care involves antipsychotic treatment protocols that achieve steady-state levels of medication. Maintaining patients on continuous treatment is thought to be necessary to keep them stabilised. However, continuous antipsychotic exposure increases the risk of adverse effects over time. These effects include metabolic and cardiovascular disorders, extrapyramidal complications, and dopamine receptor supersensitivity, the latter of which could potentially promote both treatment tolerance and psychosis relapse. In the present review, we describe evidence showing that continuous exposure to antipsychotic drugs can not only worsen long-term outcome, but—past acute phase treatment—it is also unnecessary to effectively manage schizophrenia symptoms. We also describe evidence that regular but extended dosing, allowing predictable periods of lower antipsychotic levels/D2 occupancy, is both safe and effective in patients, and it greatly reduces drug exposure overall. Studies in laboratory animals show that compared to continuous antipsychotic exposure, regular but extended dosing actually has superior antipsychotic-like efficacy, and it also substantially reduces the likelihood of both motor side effects and dopamine receptor supersensitivity. We propose that regular, but extended dosing should be considered in the long-term treatment of people with schizophrenia, because the available evidence suggests it can be just as effective as continuous treatment, while decreasing overall drug exposure and potentially reducing harmful side effects.