Longitudinal clinical and functional outcome in distinct cognitive subgroups of first-episode psychosis: a cluster analysis.

BACKGROUND: Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes. METHODS: 204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up. RESULTS: Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present. CONCLUSIONS: Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial.

BACKGROUND: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study. METHODS/DESIGN: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. DISCUSSION: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse. TRIAL STATUS: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 June 2017.

Continued cannabis use and outcome in first-episode psychosis: data from a randomized, open-label, controlled trial.

OBJECTIVE: Cannabis use has been found to increase the risk of psychosis. It is unclear whether, after a first psychotic episode has occurred, continued cannabis use is associated with poor functional outcome of psychosis. METHOD: As part of a randomized, open-label, controlled trial, the association of cannabis use and measures for psychopathology and social role functioning after 2 years of follow-up and for the recently proposed outcome measures of symptomatic remission, functional remission, and clinical recovery was explored in a group of 124 patients suffering from nonaffective first-episode psychosis (diagnosed according to DSM-IV and included from a catchment area in the Netherlands of 3.1 million inhabitants from October 2001 through December 2002). Other patient characteristics that were expected to be independently associated with outcome, among them alcohol and other drug use, were assessed at baseline. RESULTS: Continued cannabis use was not associated with symptomatic or functional remission or clinical recovery. After 2 years, cannabis use was related to certain aspects of social role functioning (economic and social activities; explained variance 5.6% and 8.4%, respectively) but not to psychopathology (Positive and Negative Syndrome Scale Positive, Negative, or General symptoms). CONCLUSIONS: Our findings support the notion that continued cannabis use after the onset of a first-episode psychosis is correlated with worse social outcome and should be discouraged whenever possible, but its role in outcome is modest in comparison to other factors. TRIAL REGISTRATION: Nederlands Trial Register: http://www.trialregister.nl (ID: NTR 374).

Neurocognition and recovery in first episode psychosis.

Cognitive functioning has been found to be a predictor of functional outcome of schizophrenia. It is unclear, however, whether clinical recovery can be predicted by scores on specific cognitive domains. The predictive value of specific neurocognitive domains and other clinical variables for symptomatic and functional outcome and clinical recovery after a 2-year follow-up is explored in a group of 51 patients with non-affective first-episode psychosis. A comprehensive neurocognitive battery was administered 18 and 41weeks after inclusion. Other patient characteristics, which were expected to independently predict clinical recovery, were assessed at baseline. Several neurocognitive tests, especially tests measuring speed of processing, and among others, Duration of Untreated Psychosis (DUP), were significant predictors of clinical recovery. Poor neuropsychological performance accurately predicted non-recovery, but improved neuropsychological performance did not accurately predict recovery. This study confirms previous findings of an association between neurocognition and outcome, but the results also suggest that in order to accurately predict recovery, the role of other factors needs to be investigated.