Emotional Experience and Estimates of D2 Receptor Occupancy in Psychotic Patients Treated With Haloperidol, Risperidone, or Olanzapine: An Experience Sampling Study

Objective: Blockade of dopamine D-2 receptors is thought to mediate the therapeutic effects of antipsychotic medication but may also induce social indifference. As antipsychotic drugs differ in D-2 receptor binding, "tight" and loose" binding drugs may be hypothesized to differentially affect emotional experience. The present study investigates the differential effects of relatively tight versus looser binding drugs on the experience of emotions in the realm of daily life. Method: We assessed positive and negative affect in the daily life of 109 patients with a DSM-IV diagnosis of psychotic disorder who were currently taking antipsychotic medication by using the experience sampling method (a structured diary technique). Antipsychotic medication was classified as loose (olanzapine; n=35) or tight (haloperidol, risperidone; n=74) binding, based on the drug's dissociation constants at the D2 receptor. The study was conducted from 2007 to 2008. Results: Multilevel analyses showed a significant interaction between binding group (loose vs tight) and D-2 receptor occupancy estimates with regard to the experience of positive (P=.008) and negative (P=.019) affect. For tight-binding-agent users, a significant association was found between D-2 receptor binding estimates and both positive affect (P=.040) and negative affect (P=.0001) in the flow of daily life, with increasing levels of estimated D-2 receptor occupancy being associated with decreased feelings of positive affect and increased feelings of negative affect. For loose-binding-agent users, no such association was apparent. These associations were only partly mediated by clinical symptoms. Conclusions:These findings add ecological validity to previous laboratory findings showing an association between D-2 receptor occupancy and emotional experience.