Douglas L. Noordsy

Substance abuse in schizophrenia: service utilization and costs

Utilization and cost of institutional and outpatient services were prospectively measured over 1 year for three groups of schizophrenic patients: current substance abusers, past substance abusers, and those without a history of substance abuse. Current abusers had significantly greater utilization and cost of institutional (hospital and jail) services. Current abusers also had greater utilization of emergency services. There were no significant differences between the groups in utilization and cost of other services, including psychosocial rehabilitation, outpatient treatment (case management, psychotherapy, and psychiatric visits), and housing supports. The implications for developing cost-effective treatments for dually diagnosed individuals are discussed.

Treatment of substance abuse in severely mentally ill patients

Substance abuse is the most common comorbid complication of severe mental illness. Current clinical research converges on several emerging principles of treatment that address the scope, pace, intensity, and structure of dual-diagnosis programs. They include a) assertive outreach to facilitate engagement and participation in substance abuse treatment, b) close monitoring to provide structure and social reinforcement, c) integrating substance abuse and mental health interventions in the same program, d) comprehensive, broad-based services to address other problems of adjustment, e) safe and protective living environments, f) flexibility of clinicians and programs, g) stage-wise treatment to ensure the appropriate timing of interventions, h) a longitudinal perspective that is congruent with the chronicity of dual disorders, and i) optimism.

The role of self-help programs in the rehabilitation of persons with severe mental illness and substance use disorders

Substance abuse treatment programs in the United States frequently incorporate self-help approaches, but little is known about the use of self-help groups by individuals with dual disorders. This paper brings together several current studies on the role of self-help programs in treating substance use disorders among individuals with severe mental illness. These studies indicate that only a minority of individuals with dual disorders become closely linked to self-help. Psychiatric diagnosis and possibly social skills are correlates of participation. Dually disordered consumers often experience the use of 12-step philosophy and jargon by mental health professionals as alienating and unempathic. The authors propose suggestions for incorporating self-help approaches into the comprehensive community care of individuals with dual disorders.

Antisocial personality disorder, conduct disorder, and substance abuse in schizophrenia.

The validity of subtypes based on antisocial personality disorder (APD) or childhood conduct disorder without adult APD (CD only) in patients with schizophrenia (or schizoaffective disorder) and a substance use disorder (abuse or dependence) was examined. APD patients scored lower on personality measures related to socialization and higher on antisocial behavior, psychopathy, and aggression. APD patients also reported higher rates of aggression and legal problems. APD, and to a lesser extent CD only, was associated with more severe psychiatric symptoms, an earlier age of onset of substance abuse, more severe symptoms of substance abuse, and a stronger family history of substance abuse and psychiatric hospitalization. The findings suggest that schizophrenia patients with APD represent a high-risk subgroup vulnerable to more severe substance abuse, psychiatric impairment, aggression, and legal problems.

Randomized, double-blind 6-month comparison of olanzapine and quetiapine in patients with schizophrenia or schizoaffective disorder with prominent negative symptoms and poor functioning.

Abstract: This study compared the effects of olanzapine (OLZ) with those of quetiapine (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning. In this 6-month, multicenter, double-blind clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20 mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans. The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms. Secondary measures assessed changes in functioning, psychopathology, and treatment tolerability. Treatment with OLZ or QUE led to a significant reduction in negative symptoms, with no between-group difference (P = 0.09). Both treatment groups also showed significant improvement on most efficacy measures. Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale, Quality of Life Instrumental Role domain, and level of effort in psychosocial or occupational rehabilitation programs. Significantly more OLZ-treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment differences in safety were relatively small and not thought to be clinically relevant. Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE. Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy.

Family history of alcoholism in schizophrenia

Previous research has shown that family history of alcoholism (FHA) is associated with several aspects of the development and expression of alcohol use disorder in people who are not mentally ill. This study examined FHA in a group of 66 schizophrenic outpatients who were well characterized in terms of their alcohol use and were followed prospectively in treatment for 4 years. The FHA-positive probands (42.4% of the group) were more likely to have alcohol use disorder. Contrary to our prediction, the relationship between FHA and alcoholism in the probands was significant for women but not for men. Among schizophrenic probands with alcoholism, positive FHA was associated with more severe alcoholism and with the use of other drugs. Probands with positive FHA also responded less well to alcoholism treatment than did probands with negative FHA. These exploratory findings have significant implications for understanding risk, for conducting assessment, and for studying treatment, but should be confirmed in larger and more representative samples of people with schizophrenia.

A Randomized Trial of Clozapine Versus Other Antipsychotics for Cannabis Use Disorder in Patients With Schizophrenia

Objective: Cannabis use disorder is the most common co-occurring drug use disorder in people with schizophrenia and is associated with poor outcomes. The authors launched a randomized controlled trial to assess the impact of clozapine compared with treatment as usual on cannabis use in patients with schizophrenia and co-occurring cannabis use disorder. Methods: Thirty-one patients with schizophrenia and co-occurring cannabis use disorder were randomly assigned to switch to clozapine or to stay on their current antipsychotic and were then followed weekly for 12 weeks. Blinded raters assessed participants weekly with the Timeline Followback for substance use and the expanded Brief Psychiatric Rating Scale for symptoms. Longitudinal random effects models were used to investigate the time-varying differences in cannabis use and other outcomes between the treatment as usual and clozapine groups. Results: The two groups differed in average intensity of cannabis use by approximately 4.5 joints/week, with lesser use in the clozapine group (t = −1.77; df = 28.5; p = .086; effect size ∼ 0.6). Symptoms and functioning were not different between the two groups. Conclusions: Clozapine may reduce cannabis use among patients with schizophrenia and co-occurring cannabis use disorder. Further controlled trials are warranted.

Long-acting injectable vs oral risperidone for schizophrenia and co-occurring alcohol use disorder: a randomized trial.

OBJECTIVE Alcohol use disorders worsen the course of schizophrenia. Although the atypical antipsychotic clozapine appears to decrease alcohol use in schizophrenia, risperidone does not. We have proposed that risperidones relatively potent dopamine D2 receptor blockade may partly underlie its lack of effect on alcohol use. Since long-acting injectable (LAI) risperidone both results in lower average steady-state plasma concentrations than oral risperidone (with lower D2 receptor occupancy) and encourages adherence, it may be more likely to decrease heavy alcohol use (days per week of drinking 5 or more drinks per day) than oral risperidone. METHOD Ninety-five patients with DSM-IV-TR diagnoses of schizophrenia and alcohol use disorder were randomized to 6 months of oral or LAI risperidone between 2005 and 2008. Explanatory (efficacy) analyses were carried out to evaluate the potential benefits of LAI under suitably controlled conditions (in contrast to real-world settings), with intent-to-treat analyses being secondary. RESULTS Explanatory analyses showed that heavy drinking in the oral group worsened over time (P = .024) and that there was a statistical trend toward significance in the difference between the changes in heavy drinking days in the oral and LAI groups (P = .054). Furthermore, the 2 groups differed in the mean number of drinking days per week (P = .035). The intent-to-treat analyses showed no difference in heavy drinking but did show a difference in average drinking days per week similar to that obtained from the explanatory analyses (P = .018). Neither explanatory nor intent-to-treat analyses showed any between-group differences in alcohol use as measured by intensity or the Alcohol Use Scale. The plasma concentrations of the active metabolite 9-hydroxyrisperidone were significantly lower in patients taking LAI (P < .05), despite their significantly (overall) better treatment adherence (P < .005). CONCLUSION For the population considered here, schizophrenia patients with alcohol use disorder appear to continue drinking some alcohol while taking either form of risperidone. Nonetheless, our data suggest that injectable risperidone may be a better choice than the oral form for these dual diagnosis patients. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00130923.

Antipsychotic adherence, switching, and health care service utilization among Medicaid recipients with schizophrenia

Objective: To evaluate health care resource utilization in patients with schizophrenia who continued newly prescribed antipsychotic medications, compared with those switching to different treatments. Methods: Adults with schizophrenia in the California Medicaid (MediCal) database who initiated treatment with index medications in 1998–2001, were classified as having: 1) abandoned antipsychotic medications; 2) switched to another medication; or 3) continued with the index antipsychotic, for up to 6 months after the index date. Results: Of 2300 patients meeting eligibility criteria, 1382 (60.1%) continued index medications, 480 (20.9%) switched, and 438 (19.0%) abandoned antipsychotic treatment. Utilization in several resource categories occurred significantly more frequently among patients whose regimens were switched (vs those continuing index medications). These included using psychiatric (24.2% vs 14.5%; P < 0.001) or nonpsychiatric (31.5% vs 24.3%; P < 0.05) emergency services; being admitted to a hospital (10.6% vs 7.4%; P < 0.05); making nonpsychiatric outpatient hospital visits (43.3% vs 36.4%; P < 0.05) or nonpsychiatric physician visits (62.7% vs 56.4%; P < 0.05); and using other outpatient psychiatric (53.3% vs 40.7%; P < 0.001) or nonpsychiatric (82.7% vs 74.6%; P < 0.001) services. Conclusions: Switching antipsychotic medications is associated with significantly increased health care resource utilization (vs continuing treatment).

Pharmacologic Treatments for Co-Occurring Substance Use Disorders in Patients with Schizophrenia: A Research Review

Abstract Substance use disorders are a common comorbidity in patients with schizophrenia, and are associated with a variety of negative outcomes. Research assessing pharmacotherapy of substance use disorders in patients with schizophrenia is in its infancy, but preliminary data indicate that, in particular, atypical antipsychotic medications may help patients with co-occurring disorders reduce substance use. Clozapine, despite its potential side effects, shows the most promise. Data related to other medications, which may also be helpful in patients with schizophrenia, are reviewed. Further controlled trials are needed to assess the impact of atypical antipsychotics, mood stabilizers, and other agents on substance abuse in patients with schizophrenia. Until such data are avail-Mary F. Brunette, Douglas L. Noordsy, and Alan I. Green are affiliated with the Department of Psychiatry, Dartmouth Medical School. able, clinicians should follow established principles of pharmacotherapy for patients with dual disorders, which include using medications to treat both disorders simultaneously over time in the context of psychosocial treatment for dual disorders.