Psychological side effects of antipsychotic medication after remission from first-episode psychosis: a HAMLETT ecological momentary assessment study

Background. Evidence on psychological side effects (PSEs) of antipsychotic medication after remission from first-episode psychosis (FEP), and their momentary impact on daily life, is limited. This study examined how Dopamine-2 (D-2) affinity and antipsychotic dosage relate to momentary PSEs. Methods. This ecological momentary assessment (EMA) study included baseline data from 56 participants in the ongoing Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment (HAMLETT) trial. Momentary mental states indicative of reduced affect intensity, stability, and variability, as well as avolition and mental fatigue, were assessed 10x/day for eight days (N = 3,005 data points). Since these PSEs may result from D-2-receptor actions, antipsychotics were classified by receptor affinity and mechanism of action. Multilevel mixed-effects regression models examined serial cross-sectional associations between D-2 affinity or dosage and concurrent PSEs, both overall and separately for mornings, daytimes, and evenings. Results. Higher antipsychotic dosages were associated with reduced affect variability (Beta [B] = -1.40 [95% confidence interval [CI]: -2.52; -0.29]) and decreased positive affect stability (B = 0.23 [95% CI: 0.04; 0.42]) and intensity (B = -1.11 [95% CI: -1.97; -0.24]). The latter was also associated with the use of high-affinity D-2 antagonists versus partial D-2 agonists (B = 12.98 [95% CI: 2.43; 23.53]) and versus low-affinity D-2 antagonists (B = 10.04 [95% CI: 0.59; 19.49]). Other PSEs were not associated with D-2 affinity/dosage. Results were relatively consistent across daytimes. Conclusions. Higher antipsychotic dosage and high-affinity D-2 antagonists were associated with decreased positive affect after remission from FEP, which may partly drive the frequently reported blunting of emotional experience.