Allan Fohlmann

Treatment of cannabis use disorders in people with schizophrenia spectrum disorders — A systematic review

BACKGROUND Cannabis use disorders (CUD) are prevalent among people with schizophrenia spectrum disorders (SSD), with a range of detrimental effects, e.g. reduced compliance to medication and psychosocial interventions, and increased level of psychotic-dimension symptoms. The aim of this study was to review literature on treatments of CUD in SSD-patients. METHODS PubMed, PsycINFO, EMBASE, and The Cochrane Central Register of Controlled Trials were searched. RESULTS 41 articles were selected, 11 treating cannabis as a separate outcome. Contingency management was only effective while active. Pharmacological interventions appeared effective, but lacked randomized controlled trials (RCTs). Psychosocial interventions, e.g. motivational interviewing and cognitive behavior therapy (CBT), were ineffective in most studies with cannabis as a separate outcome, but effective in studies that grouped cannabis together with other substance use disorders. CONCLUSIONS Insufficient evidence exists on treating this form of dual-diagnosis patients. Studies grouping several types of substances as a single outcome may overlook differential effects. Future RCTs should investigate combinations of psychosocial, pharmacological, and contingency management.

Correlations and agreement between delta‐9‐tetrahydrocannabinol (THC) in blood plasma and timeline follow‐back (TLFB)‐assisted self‐reported use of cannabis of patients with cannabis use disorder and psychotic illness attending the CapOpus randomized clinical trial

AIMS To assess correlations and agreement between timeline follow-back (TLFB)-assisted self-report and blood samples for cannabis use. DESIGN Secondary analysis of a randomized trial. SETTING Copenhagen, Denmark. PARTICIPANTS One hundred and three patients from the CapOpus trial with cannabis use disorder and psychosis, providing 239 self-reports of cannabis use and 88 valid blood samples. MEASUREMENTS Delta-9-tetrahydrocannabinol (THC), 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) detected in plasma using high-performance liquid chromatography with tandem mass spectrometry detection. Self-report of cannabis-use last month by TLFB. Pearsons r, sensitivity and specificity calculated as measures of correlation or agreement. FINDINGS Correlations were strong; r = 0.75 for number of days and r = 0.83 for number of standard joints in the preceding month when excluding outliers. Including outliers, coefficients were moderate to strong (r = 0.49). There were differences in subgroups, mainly inconsistent, depending on inclusion or exclusion of outliers. Sensitivity and specificity for TLFB detecting the presence or absence of cannabis use were 95.7% [95% confidence interval (CI) 88.0-99.1%) and 72.2% (95% CI 46.5-90.3%), respectively. Using 19 days as cut-off on TLFB, they were 94.3% (95% CI 86.0-98.4%) and 94.4% (95% CI 72.2-99.9%), respectively. Area under the receiver operating characteristic (ROC) curve was 0.96. CONCLUSIONS Timeline follow-back (TLFB)-assisted self-report of cannabis use correlates highly with plasma-delta-9-tetrahydrocannabinol in patients with comorbid cannabis use disorder and psychosis. Sensitivity and specificity of timeline follow-back appear to be optimized with 19 days as the cut-off point. As such, timeline follow-back may be superior to analysis of blood when going beyond 19 days of recall.

Design paper: The CapOpus trial: A randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis

BackgroundA number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders. There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis.ObjectivesThe major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual.DesignThe trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are primarily recruited through early-psychosis detection teams, community mental health centers, and assertive community treatment teams. Patients are randomized to one of two treatment arms, both lasting six months: 1) specialized addiction treatment plus treatment as usual or 2) treatment as usual. The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy, and incorporates both the family and the case manager of the patient.The primary outcome measure will be changes in amount of cannabis consumption over time. Other outcome measures will be psychosis symptoms, cognitive functioning, quality of life, social functioning, and cost-benefit analyses.Trial registrationClinicalTrials.gov NCT00484302.

Treatment of adult patients with schizophrenia and complex mental health needs: A national clinical guideline

Abstract Background and aim: The Danish Health and Medicines Authority assembled a group of experts to develop a national clinical guideline for patients with schizophrenia and complex mental health needs. Within this context, ten explicit review questions were formulated, covering several identified key issues. Methods: Systematic literature searches were performed stepwise for each review question to identify relevant guidelines, systematic reviews/meta-analyses, and randomized controlled trials. The quality of the body of evidence for each review question was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Clinical recommendations were developed on the basis of the evidence, assessment of the risk-benefit ratio, and perceived patient preferences. Results: Based on the identified evidence, a guideline development group (GDG) recommended that the following interventions should be offered routinely: antipsychotic maintenance therapy, family intervention and assertive community treatment. The following interventions should be considered: long-acting injectable antipsychotics, neurocognitive training, social cognitive training, cognitive behavioural therapy for persistent positive and/or negative symptoms, and the combination of cognitive behavioural therapy and motivational interviewing for cannabis and/or central stimulant abuse. SSRI or SNRI add-on treatment for persistent negative symptoms should be used only cautiously. Where no evidence was available, the GDG agreed on a good practice recommendation. Conclusions: The implementation of this guideline in daily clinical practice can facilitate good treatment outcomes within the population of patients with schizophrenia and complex mental health needs. The guideline does not cover all available interventions and should be used in conjunction with other relevant guidelines.

Psychiatric treatment following participation in the CapOpus randomized trial for patients with comorbid cannabis use disorder and psychosis

BACKGROUND Randomized trials targeting cannabis use disorders in patients with psychosis have generally been unsuccessful. One of the largest such trials was the CapOpus trial, which had an impact on the number of monthly joints used, but not on the number of days with cannabis use or positive or negative symptoms. OBJECTIVE To investigate the effects of CapOpus on psychiatric treatment. METHODS Six-month randomized trial on participants meeting ICD-10 criteria for cannabis use disorder and schizophrenia-spectrum psychosis. Participants were randomized to treatment as usual (TAU, n=51) alone versus TAU plus CapOpus (n=52) consisting of motivational interviewing and cognitive behavior therapy. Data regarding psychiatric treatment was obtained from complete nationwide registers. Analyses were intention-to-treat. Cox and poisson regression were used as appropriate. RESULTS Compared with treatment as usual, participants in the CapOpus group had an overall higher risk of having a psychiatric emergency room contact (hazard ratio 2.02, 95% confidence interval 1.22-3.34). Participants in CapOpus also had more contacts with psychiatric emergency rooms (incidence rate ratio 3.47 (2.64-4.57)) and more admissions to psychiatric hospitals (incidence rate ratio 2.24 (1.65-3.03)); conversely, CapOpus-participants spent fewer days admitted to psychiatric hospitals than treatment-as-usual participants (incidence rate ratio 0.72 (0.68-0.75)). CONCLUSIONS CapOpus led to earlier and more psychiatric emergency room contacts and admissions that, however, were of fewer days. This pattern could indicate that participants receiving treatment as usual were inadequately treated. However, it cannot be excluded that the differences might be an adverse reaction to the psychosocial intervention.

Intervention efficacy in trials targeting cannabis use disorders in patients with comorbid psychosis systematic review and meta-analysis.

INTRODUCTION Cannabis use disorders are highly prevalent in patients with schizophrenia and other psychoses, and are probably associated with a range of poor outcomes. Several trials have been conducted on this population, the results of which have been summarized in several systematic reviews but never in meta-analyses specifically regarding cannabis use. METHODS PubMed, PsycINFO, EMBASE, and The Cochrane Central Register of Controlled Trials were searched using predefined search terms. We included randomized trials of all types of interventions targeting cannabis use disorders in patients with schizophrenia spectrum disorders. We extracted information on intervention types, efficacy, trial characteristics, and risk of bias. RESULTS There was no evidence of an effect on frequency of cannabis use, but intervention effects of motivational intervention with or without cognitive behavior therapy were observed on quantity of use and on positive symptoms of schizophrenia. Psychosocial intervention did not have an appreciable effect on negative symptoms. Longer interventions appear to be more efficacious, and efficacy may be better in trials with comparatively few women. Larger trials may be better at establishing effects on positive symptoms. CONCLUSION Psychosocial interventions appear moderately efficacious in reducing quantity of cannabis-use and positive symptoms.

INTERIM ANALYSIS OF THE CAPOPUS TRIAL: A RANDOMIZED, PARALLEL-GROUP, OBSERVER-BLINDED CLINICAL TRIAL OF SPECIALIZED ADDICTION TREATMENT VERSUS TREATMENT AS USUAL FOR YOUNG PATIENTS WITH CANNABIS ABUSE AND PSYCHOSIS

Background: A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders. There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis. Objectives: The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. Design: The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are primarily recruited through early-psychosis detection teams, community mental health centers, and assertive community treatment teams. Patients are randomized to one of two treatment arms, both lasting six months: 1) specialized addiction treatment plus treatment as usual or 2) treatment as usual. The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy, and incorporates both the family and the case manager of the patient. The primary outcome measure will be changes in amount of cannabis consumption over time. Other outcome measures will be psychosis symptoms, cognitive functioning, quality of life, social functioning, and cost-benefit analyses. Trial registration: ClinicalTrials.gov NCT00484302.

P03-179 CapOpus trial: An observer-blinded RCT of specialized addiction treatment versus standard treatment for young patients with cannabis abuse and psychosis

Background A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders. There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis. Objectives The major objective for the CapOpus trial is to evaluate the effects of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual compared with just treatment as usual. Design The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are recruited through teams for early detection of people with psychosis, community mental health centers, and assertive community treatment teams. Patients are randomized to one of two treatment arms, both lasting six months: 1. specialized addiction treatment plus treatment as usual or 2. treatment as usual. The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy, and incorporates both the family and the case-manager of the patient. The primary outcome measurement will be amount of reduction in cannabis consumption. Other outcome measures will be improvements in psychosis symptoms, cognitive functioning, quality of life and social functioning, and cost-benefit of the treatments.

Treating cannabis use disorders in patients with psychosis

Cannabis use has been associated with the onset, course and relapse of psychosis. Population studies and data from samples of young people at high risk for psychosis have indicated that cannabis use may be related to the onset of psychosis. Cannabis use has also been found to have a deleterious impact on psychotic symptom severity and has emerged as the strong predictor of psychotic relapse. To date, there has been little collaboration between neuroscience and clinical research groups examining the link between cannabis use and psychosis, despite the potential for these fi elds to inform the other. This symposium seeks to begin to redress this gap.