Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy Long-term Follow-up of a 2-Year Randomized Clinical Trial

<p>IMPORTANCE Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before.</p><p>OBJECTIVE To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT) trial.</p><p>DESIGN Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR.</p><p>SETTING One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission.</p><p>PARTICIPANTS After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up assessment.</p><p>INTERVENTION After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician.</p><p>MAIN OUTCOMES AND MEASURES Primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR) was controlled for baseline parameters.</p><p>RESULTS The DR patients experienced twice the recovery rate of the MT patients (40.4% vs 17.6%). Logistic regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates.</p><p>CONCLUSIONS AND RELEVANCE Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice.</p>

Lower prefrontal activation during emotion regulation in subjects at ultrahigh risk for psychosis: An fMRI-study

Background: Previous research has shown that patients with schizophrenia experience difficulties with emotion regulation and activate prefrontal regions to a lesser extent during reappraisal of emotional information. It has been suggested that problems in emotion regulation might precede the onset of psychosis. Therefore, it could be hypothesized that also individuals at ultrahigh risk (UHR) for developing psychosis experience difficulties with emotion regulation. Aims: The aim of the current study was to investigate whether individuals at UHR for developing psychosis show abnormal brain activation during reappraisal of negative pictures. Methods: Using functional magnetic resonance imaging (fMRI), we scanned 15 UHR participants and 16 matched healthy controls while performing an emotion regulation task. During this task, participants had to reappraise their negative emotion elicited by International Affective Picture System pictures. Furthermore, the reported use of reappraisal was examined with the emotion regulation questionnaire (ERQ). Results: individuals at UHR for psychosis showed less activation in the left ventrolateral prefrontal cortex during reappraisal compared with healthy controls. Furthermore, they reported less use of reappraisal in daily life (P=0.01; 95% CI (0.24–1.63)). Conclusions: These findings indicate that dysfunctional emotion regulation may already occur in individuals at risk for psychosis. These regulation difficulties are underpinned by less ventrolateral prefrontal cortex activation, and may result in high negative affect, lower social functioning, and high rates of psychotic symptoms