Antipsychotic dopamine D₂ affinity and negative symptoms in remitted first episode psychosis patients

Negative symptoms can be an integral part of schizophrenia spectrum pathology and can be secondary to other psychotic symptoms or caused by antipsychotic medication. As antipsychotic drugs differ in their affinity to dopamine receptors and some antipsychotics have partial agonistic effects, antipsychotic drugs are expected to vary in their ability to cause negative symptoms. The association between negative symptoms and antipsychotic medication divided into partial agonists, or antagonists with high or low D₂ affinity was assessed in 310 remitted first episode psychosis (FEP) patients. Severity of negative symptoms was assessed with the Comprehensive Assessment of Symptoms and History, and the Positive and Negative Syndrome Scale. Linear regression analyses were performed while controlling for differences in clinical and sociodemographic characteristics between the groups using inverse probability of treatment weighting. Patients using partial agonists (n = 78) showed fewer negative symptoms compared to those using high affinity antagonists (n = 84). Patients using partial agonists displayed less severe negative symptoms compared to those using low affinity antagonists (n = 148) at a trend level (p = 0.051). Negative symptom severity was higher in patients who had higher antipsychotic doses. In remitted FEP patients, we observed that the use of antipsychotic medication classified as partial agonists was associated with lower severity of negative symptoms, while the use of antagonists with high D₂ affinity was associated with more severe negative symptoms.