Olanzapine vs. risperidone in patients with first-episode schizophrenia and a lifetime history of cannabis use disorders: 16-week clinical and substance use outcomes.

The purpose of this study is to compare the efficacy of olanzapine and risperidone for the acute treatment of first-episode schizophrenia patients with cannabis use disorders. This secondary analysis of a previously published study included 49 first-episode patients with a diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder and a co-occurring lifetime diagnosis of cannabis use disorders randomly assigned to treatment with either olanzapine (n=28) or risperidone (n=21) for 16weeks. The olanzapine group did not differ significantly from the risperidone group for initial response rates of positive symptoms, and rates of cannabis use or alcohol use during the study. Positive symptoms and the Scale for Assessment of Negative Symptoms (SANS) global asociality-anhedonia scores improved over time but did not differ between study medications. In both groups, cannabis use during the study was higher in patients who used cannabis within three months of the admission. Thus, our results suggest that olanzapine and risperidone had a similar initial efficacy on psychotic symptoms and substance use in first-episode patients with co-occurring cannabis use disorders. If clinicians are choosing between olanzapine versus risperidone treatment for this population, their decision should be based upon factors other than symptom response and short-term substance misuse.

A prospective study of cannabis use as a risk factor for non-adherence and treatment dropout in first-episode schizophrenia.

INTRODUCTION: Although several studies have reported on cannabis use and adherence for first episode of psychosis patients, the findings remain unclear as to whether cannabis use is a risk factor for poor adherence in young people with first-episode schizophrenia. This study was designed to follow patients' use of cannabis and adherence in a naturalistic setting during the first 12 months of treatment. It examines whether cannabis use is a risk factor for two distinct types of non-adherence: non-adherence to medication and treatment dropout. METHODS: Participants were 112 first-episode schizophrenia patients of diverse backgrounds at two community hospitals, enrolled in a study of differential effectiveness of two second-generation antipsychotic medications. Multiple indicators were used to assess cannabis use and adherence to medication. Patients were encouraged to continue in the study even after periods of treatment refusal or change from study to standardized medication. Study hypotheses were tested using Cox proportional hazards models with cannabis use as a time-varying covariate. RESULTS: After 12 months, 23 had dropped out and 37 had at some point been non-adherent to medication. Of 34 participants who used cannabis during treatment, 32 had a prior diagnosis of cannabis abuse/dependence and 30 were male. Independently of age, race, socioeconomic status, gender, site, and medication assignment, cannabis use significantly increased hazard of non-adherence by a factor of 2.4 (p<.001) and hazard of dropout by a factor of 6.4 (p=.034). CONCLUSION: Results indicate that cannabis use is a risk factor for non-adherence to medication and dropout from treatment. Treatment for first-episode schizophrenia may be more effective if providers address the issue of cannabis use with patients throughout the early years of treatment, especially for those with existing cannabis abuse/dependence.

Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects.

Cerebral dopamine homeostasis has been implicated in a wide range of cognitive processes and is of great pathophysiological importance in schizophrenia. A novel approach to study cognitive effects of dopamine is to deplete its cerebral levels with branched chain amino acids (BCAAs) that acutely lower dopamine precursor amino acid availability. Here, we studied the effects of acute dopamine depletion on early and late attentive cortical processing. Auditory event-related potential (ERP) components N2 and P3 were investigated using high-density electroencephalography in 22 healthy male subjects after receiving BCAAs or placebo in a randomized, double-blind, placebo-controlled crossover design. Total free serum prolactin was also determined as a surrogate marker of cerebral dopamine depletion. Acute dopamine depletion increased free plasma prolactin and significantly reduced prefrontal ERP components N2 and P3. Subcomponent analysis of N2 revealed a significant attenuation of early attentive N2b over prefrontal scalp sites. As a proof of concept, these results strongly suggest that BCAAs are acting on basic information processing. Dopaminergic neurotransmission seems to be involved in auditory top-down processing as indexed by prefrontal N2 and P3 reductions during dopamine depletion. In healthy subjects, intact early cortical top-down processing can be acutely dysregulated by ingestion of BCAAs. We discuss the potential impact of these findings on schizophrenia research.

Volumetric and shape analysis of the thalamus in first-episode schizophrenia.

Thalamic abnormalities have been implicated in the pathogenesis of schizophrenia, although the majority of studies used chronic samples treated extensively with antipsychotics. Moreover, the clinical and neuropsychological correlates of these abnormalities remain largely unknown. Using high-resolution MR imaging and novel methods for shape analysis, we investigated thalamic subregions in 35 (25 M/10 F) first-episode schizophrenia patients compared with 33 (23 M/10 F) healthy volunteers. The right and left thalami were traced bilaterally on coronal brain slices and volumes were compared between groups. In addition, regional abnormalities were identified by comparing distances, measured from homologous thalamic surface points to the central core of each individual's surface model, between groups in 3D space. Patients had significantly less total thalamic volume compared with healthy volunteers. Statistical mapping demonstrated most pronounced shape abnormalities in the pulvinar; however, estimated false discovery rates in these regions were sizable. Smaller thalamus volume was significantly correlated with worse overall neuropsychological functioning and specific deficits were observed in the language, motor, and executive domains. There were no significant associations between thalamus volume and positive or negative symptoms. Our findings suggest that thalamic abnormalities are evident at the onset of a first episode of schizophrenia prior to extensive pharmacologic intervention and that these abnormalities have neuropsychological correlates.

The Insight-Adherence-Abstinence triad: an integrated treatment focus for cannabis-using first-episode schizophrenia patients.

Insight-Adherence-Abstinence focused treatment for first episode of schizophrenia and schizoaffective patients is described using examples from clinical practice with 68 patients, 30 of whom have recent or active cannabis misuse. The treatment model is based on the unique characteristics of first-episode patients, who have little insight or experience with the relapses of chronic patients, demonstrate a great deal of denial, and frequently attribute their illness to cannabis. Treatment focuses on building adherence, abstinence, and insight during the first year of treatment in order to prevent repeated relapse and to optimize recovery. Interventions recognize the many needs of cannabis-using first-episode patients and therefore include supportive, cognitive-behavioral, behavioral, and motivational therapies, as well as skill building and psychoeducation.