Guy Chouinard proposed the concept of dopamine supersensitivity psychosis (DSP) in 1978, a consequence of chronic antagonism of dopamine D-2 receptors which also is posited to cause tardive dyskinesia (1). The proposed mechanism is upregulation of D2 receptors in the basal ganglia, and tardive dyskinesia is itself considered one of the markers of the condition, also characterized by tolerance to increasing doses of antipsychotic. Supersensitivity psychosis patients may therefore represent a subtype of treatment resistance. In this study from Japan, the investigators examined this hypothesis in a group of patients with chronic psychosis (2).
The 147 patients enrolled had treatment-resistant schizophrenia or schizoaffective disorder as defined by failure of at least 2 antipsychotics at a dose equivalent to 600 mg chlorpromazine for 4 weeks. Although specifics of antipsychotic therapy were not provided, none of the patients was on clozapine. Their mean duration of illness was about 23 years. Supersensitivity was diagnosed if a patient met one of 3 criteria, which were adopted from Chouinard:
- Antipsychotic tolerance indicated by relapse while on medication and failure to improve despite 20% or more increase in dosage
- Rebound psychosis manifested by swift relapse with reduction or discontinuation of medication; the psychosis may involve new symptoms for a patient
- Presence of tardive dyskinesia
The investigators found that 106 or 72.1% of the patients met at least one criterion for DSP; 56% had tolerance, 44% had tardive dyskinesia, and 42% had rebound psychosis. The patients were also classified by the presence or absence of deficit syndrome, defined by prominent negative symptoms assessed by standardized rating instruments. Of 55 patients judged to have deficit syndrome, the majority did not meet criteria for DSP; hence, DSP was significantly negatively associated with prominent deficit symptoms.
Although the researchers evaluated the present state of each subject, the main limitation of the study was reliance on chart reviews for the longitudinal course of patients’ illness. Furthermore, relapse of symptoms due to nonadherence could not be reliably distinguished from antipsychotic tolerance. The findings however suggest that supersensitivity psychosis may be an important contributor to treatment resistance, and that investigations using functional imaging and other techniques are warranted to validate the concept of DSP.