Current Data on and Clinical Insights into the Treatment of First Episode Nonaffective Psychosis: A Comprehensive Review

Implementing the most suitable treatment strategies and making appropriate clinical decisions about individuals with a first episode of psychosis (FEP) is a complex and crucial task, with relevant impact in illness outcome. Treatment approaches in the early stages should go beyond choosing the right antipsychotic drug and should also address tractable factors influencing the risk of relapse. Effectiveness and likely metabolic and endocrine disturbances differ among second-generation antipsychotics (SGAs) and should guide the choice of the first-line treatment. Clinicians should be aware of the high risk of cardiovascular morbidity and mortality in schizophrenia patients, and therefore monitoring weight and metabolic changes across time is mandatory. Behavioral and counseling interventions might be partly effective in reducing weight gain and metabolic disturbances. Ziprasidone and aripiprazole have been described to be least commonly associated with weight gain or metabolic changes. In addition, some of the SGAs (risperidone, amisulpride, and paliperidone) have been associated with a significant increase of plasma prolactin levels. Overall, in cases of FEP, there should be a clear recommendation of using lower doses of the antipsychotic medication. If no or minimal clinical improvement is found after 2 weeks of treatment, such patients may benefit from a change or augmentation of treatment. Clinicians should provide accurate information to patients and relatives about the high risk of relapse if antipsychotics are discontinued, even if patients have been symptom free and functionally recovered on antipsychotic treatment for a lengthy period of time.This review was carried out at the Hospital Marque´s de Valdecilla, University of Cantabria, Santander, Spain, with the following Grant support: Instituto de Salud Carlos III PI020499, PI050427, PI060507, Plan Nacional de Drugs Research Grant 2005-Orden sco/3246/2004, SENY Fundacio´ Research Grant CI 2005-0308007, Fundacio´n Marque´s de Valdecilla API07/011 and CIBERSAM

No Effects of Cognitive Remediation on Cerebral White Matter in Individuals at Ultra-High Risk for Psychosis-A Randomized Clinical Trial

Background: Individuals at ultra-high risk for psychosis (UHR) present with subtle alterations in cerebral white matter (WM), which appear to be associated with clinical and functional outcome. The effect of cognitive remediation on WM organization in UHR individuals has not been investigated previously. Methods: In a randomized, clinical trial, UHR individuals aged 18 to 40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation for 20 weeks. Cognitive remediation comprised 20 x 2-h sessions of neurocognitive and social-cognitive training. Primary outcome was whole brain fractional anisotropy derived from diffusion weighted imaging, statistically tested as an interaction between timepoint and treatment group. Secondary outcomes were restricted to five predefined region of interest (ROI) analyses on fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity. For significant timepoint and treatment group interactions within these five ROIs, we explored associations between longitudinal changes in WM and cognitive functions/clinical symptoms. Finally, we explored dose-response effects of cognitive remediation on WM. Results: A total of 111 UHR individuals were included. Attrition-rate was 26%. The cognitive remediation group completed on average 12 h of neurocognitive training, which was considerably lower than per protocol. We found no effect of cognitive remediation on whole-brain FA when compared to treatment as usual. Secondary ROI analyses revealed a nominal significant interaction between timepoint*treatment of AD in left medial lemniscus (P=0.016) which did not survive control for multiple comparisons. The exploratory test showed that this change in AD correlated to improvements of mental flexibility in the cognitive remediation group (p=0.001). We found no dose-response effect of neurocognitive training on WM. Conclusions: Cognitive remediation comprising 12 h of neurocognitive training on average did not improve global or regional WM organization in UHR individuals. Further investigations of duration and intensity of cognitive training as necessary prerequisites of neuroplasticity-based changes are warranted. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02098408

Daily Use, Especially of High-Potency Cannabis, Drives the Earlier Onset of Psychosis in Cannabis Users

Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16-1.74; P <.001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11-1.68; P <.001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06-1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50-2.65; P <.0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users