Objectives: Tardive dyskinesia, psychotic relapse and treatment-refractory psychosis have long been associated. A common underlying mechanism involving antipsychotic-induced ‘supersensitivity’, albeit in different brain pathways, was proposed as early as 1978. This piece seeks to reappraise the concept and potential implications of antipsychotic-induced supersensitivity. Conclusions: Evidence increasingly suggests that chronic antipsychotic exposure induces neuroadaptive physiological changes in dopaminergic, and other, neurotransmitter systems that may render some individuals more vulnerable to psychotic relapse - including those receiving continuous antipsychotic treatment. It is possible that in treating every episode of psychosis with prolonged or indefinite antipsychotic therapy, we paradoxically increase the risk of psychotic relapse in a significant proportion of people. A greater appreciation of supersensitivity may allow us to optimise any potential benefits of antipsychotics while minimising the risk of inadvertent iatrogenic harms. More research is needed to improve our understanding of the underlying neurophysiology of supersensitivity and to better identify which individuals are most vulnerable to its development. It is time we paid more attention to the concept, emerging evidence and potential implications of antipsychotic-induced supersensitivity and, where appropriate, adjusted our practice accordingly.
Inhibitory and excitatory neurotransmitter systems in depressed and healthy: a positron emission tomography and magnetic resonance spectroscopy study