Rationale and neurobiological effects of treatment with antipsychotics in patients with chronic schizophrenia considering dopamine supersensitivity

Behav Brain Res. 2021 Apr 9:403:113126. doi: 10.1016/j.bbr.2021.113126. Epub 2021 Jan 15.

Abstract

The long-term treatment of patients with schizophrenia often involves the management of relapses for most patients and the development of treatment resistance in some patients. To stabilize the clinical course and allow as many patients as possible to recover, clinicians need to recognize dopamine supersensitivity, which can be provoked by administration of high dosages of antipsychotics, and deal with it properly. However, no treatment guidelines have addressed this issue. The present review summarized the characteristics of long-acting injectable antipsychotics, dopamine partial agonists, and clozapine in relation to dopamine supersensitivity from the viewpoints of receptor profiles and pharmacokinetics. The potential merits and limitations of these medicines are discussed, as well as the risks of treating patients with established dopamine supersensitivity with these classes of drugs. Finally, the review discussed the biological influence of antipsychotic treatment on the human brain based on findings regarding the relationship between the hippocampus and antipsychotics.

Keywords: Antipsychotic; Clozapine; Dopamine; Dopamine partial agonist; Long-acting injectable antipsychotics (LAI); Relapse.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology*
  • Clozapine / administration & dosage
  • Clozapine / adverse effects
  • Clozapine / pharmacology*
  • Delayed-Action Preparations
  • Dopamine Agonists / administration & dosage
  • Dopamine Agonists / adverse effects
  • Dopamine Agonists / pharmacology*
  • Humans
  • Psychoses, Substance-Induced / etiology*
  • Schizophrenia / drug therapy*

Substances

  • Antipsychotic Agents
  • Delayed-Action Preparations
  • Dopamine Agonists
  • Clozapine