Long-acting injectable risperidone compared with zuclopenthixol in the treatment of schizophrenia with substance abuse comorbidity.

OBJECTIVE: This study aimed to compare the efficacy of long-acting risperidone and zuclopenthixol in subjects with schizophrenia and substance abuse. METHOD: A total of 115 subjects with schizophrenia and substance use disorders were enrolled for an open, randomized, controlled, 6-month follow-up study. Fifty-seven subjects were selected for treatment with long-acting injectable risperidone, while another 58 were treated with zuclopenthixol-depot. RESULTS: Long-acting risperidone patients presented fewer positive urine tests (8.67 compared with 10.36, P = 0.005), showed improved scores on the Positive and Negative Syndrome Scale, and showed better compliance with the Substance Abuse Management program. The use of long-acting risperidone and less severe dependence explained the outcome at the end of the follow-up. CONCLUSIONS: Long-acting injectable risperidone was more effective than zuclopenthixol-depot in improving substance abuse and schizophrenia symptoms in subjects with dual diagnosis.     

Substance abuse comorbidity in schizophrenia: editors' introduction

Substance abuse is a pervasive problem in American society that extends to persons with mental illness. Despite the fact that substance abuse in the mentally ill is a major clinical problem, there have been very few systematic investigations of the dimensions, nature, and treatment of this problem. This issue of the Schizophrenia Bulletin attempts to examine the problem of substance abuse in schizophrenia from various perspectives by reviewing the published literature, presenting original data, and identifying areas and approaches for future scientific investigation.     

Comorbid schizophrenia and substance abuse

At some point during their lives, many patients with schizophrenia abuse substances. The co-occurrence of substance use leads to poorer long- and short-term outcomes in schizophrenia and complicates the treatment of both conditions. The primary substances of abuse among schizophrenia patients are alcohol, cannabis, cocaine, and nicotine. This presentation describes the prevalence, outcomes, and basis for this comorbidity. A brief discussion about the neurobiology of schizophrenia explains how schizophrenia may create a biologic predisposition to substance abuse by altering the brain reward system. The efficacy of possible treatments for comorbid schizophrenia and substance abuse are weighed, including typical and atypical antipsychotics and psychosocial interventions, and a list of possible adjunctive agents is provided.     

Dopamine and alcoholism: neurobiological basis of ethanol abuse

The role of the dopamine (DA) system in brain reward mechanisms and the development of substance abuse has been well established. We review earlier animal and human studies on DA and alcoholism with some relevant issues relating to those studies. The present animal and human data suggest several alterations in the DA system in the context of alcoholism. Receptor studies imply that DA D₂ receptor density and function are lower at least among type 1 alcoholics, which suggests that they could benefit from drugs that enhance DAergic activity, such as partial DA agonists. These drugs could help to restore suboptimal levels of DAergic activity by reducing both the craving for alcohol in abstinence and the euphoria subsequent to alcohol's release of DA in the nucleus accumbens (NAC), thus providing negative reinforcement for relapse.     

Managing comorbid schizophrenia and substance abuse

Effective treatments for co-occurring schizophrenia and substance abuse have emerged over the past 15 years. They involve integration and melding of mental health and substance abuse treatments, helping people to acquire the skills and supports they need to manage both illnesses and to pursue functional goals, and a comprehensive, long-term approach to recovery. Further research is needed to refine specific interventions and to improve knowledge regarding implementing integrated treatment settings in routine mental health programs.     

Personality characterizations of outpatients with schizophrenia, schizophrenia with substance abuse, and primary substance abuse

The study extended previous research on the relationship between personality traits and Axis I disorders. It examined personality differences between individuals diagnosed with schizophrenia and substance abuse and also included individuals dually diagnosed with both schizophrenia and substance abuse. Comparisons were made with respect to characteristics of both normal personality, as measured by the NEO Five-Factor Inventory (NEO-FFI), and disordered personality, as measured by the Millon Multiaxial Personality Inventory. On the NEO-FFI, all groups differed significantly from the NEO-FFI normative sample on at least three personality domains. As predicted, the dual diagnosis group showed the most personality deviance and pathology. The schizophrenia group was primarily distinguished by higher levels of agreeableness, whereas the substance abuse group was more extroverted and showed a prominence of Cluster B personality patterns. An unexpected finding was an interaction between diagnostic group and age, such that older relative to younger individuals in the single diagnosis groups showed greater personality adaptivity and moderation, whereas older individuals in the dual diagnosis group showed less.     

Managing comorbid schizophrenia and substance abuse

Effective treatments for co-occurring schizophrenia and substance abuse have emerged over the past 15 years. They involve integration and melding of mental health and substance abuse treatments, helping people to acquire the skills and supports they need to manage both illnesses and to pursue functional goals, and a comprehensive, long-term approach to recovery. Further research is needed to refine specific interventions and to improve knowledge regarding implementing integrated treatment settings in routine mental health programs.     

Enhancing readiness-to-change substance abuse in persons with schizophrenia. A four-session motivation-based intervention.

This article describes a four-session intervention designed for persons with co-occurring substance abuse and schizophrenia-spectrum disorders, to be administered as an add-on module to supplement ongoing mental health treatment in an outpatient setting. The intervention targets those dually diagnosed individuals with low readiness-to-change as indicated by current use, and/or low level of engagement in treatment for substance abuse. The intervention is designed to increase problem recognition, to enhance motivation to change maladaptive patterns of substance use, and to facilitate engagement in substance abuse treatment. To achieve these goals, the authors have adopted constructs from the Transtheoretical Model of Change, the authors used principles of motivational and harm reduction interventions, and tailored them to the target population.     

Clinical aspects of substance abuse in persons with schizophrenia.

OBJECTIVE: To review the current knowledge on the problem of psychoactive substance abuse by persons with schizophrenia, with particular attention to issues of direct relevance to clinical practice. METHOD: The author examined the literature from the last 2 decades and data from studies in which he was involved. RESULTS: Schizophrenia sufferers show an elevated liability for substance abuse. Such comorbidity may derive from self-medication attempts, a common neuropathology for addiction and schizophrenia, the psychotogenic properties of certain drugs, or the influence of environmental factors. Among schizophrenia patients receiving treatment, substance misuse is associated with more severe symptoms and poorer therapeutic response. The presence of a chronic psychosis impedes treatment of the substance problem in traditional, nonpsychiatric addiction programs. Better outcomes are observed in integrated therapy services, where patients receive appropriate care for both conditions. CONCLUSION: Dual-pathology patients need comprehensive care with appropriate pharmacotherapy and psychosocial interventions. This treatment can be best provided within the context of a continuing care psychiatric service.     

Past substance abuse and clinical course of schizophrenia.

To evaluate the effects of previous alcohol and drug use on the course and symptoms of schizophrenia, the authors compared 34 patients with schizophrenia who had histories of substance abuse with 17 patients with schizophrenia who were lifelong abstainers. Surprisingly, they did not find that individuals with past histories of abuse were more impaired or had more symptoms.     

DSM-V research agenda: substance abuse/psychosis comorbidity

For diagnosis of patients with comorbid psychotic symptoms and substance use disorders (SUDs), Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, makes clear distinctions between independent psychotic disorders (eg, bipolar disorder, schizophrenia) and substance-induced syndromes (eg, delirium, dementias). Most substance-induced psychotic symptoms are considered to be short lived and to resolve with sustained abstinence along with other symptoms of substance intoxication and withdrawal. These guidelines are challenged by practical difficulties in distinguishing between substance-induced and independent psychoses and by mounting evidence that marijuana use may be a contributing cause of schizophrenia. To inform the diagnostic distinction between substance-induced vs independent psychotic symptoms, 2 kinds of information could be sought from longitudinal research: (a) identification of early markers that clearly differentiate the 2 conditions and (b) more precise information about duration of psychotic symptoms induced by different substances. Evidence of this type could emerge from reanalysis of existing data from large-scale longitudinal studies of community samples. To inform possible nosological changes related to the possible schizophrenia-inducing role of marijuana (eg, designating a "cannabis-induced" subtype), a wide range of research evidence will be needed to clarify the relationship between effects of cannabis and schizophrenia symptoms. Ultimately, the ideal psychiatric nomenclature will define syndromes on the basis of established etiology and/or pathophysiology. Given the strong association between SUDs and psychotic disorders, research on the neurobiology of psychotic disorders could fruitfully include subjects with comorbid SUDs to shed light on shared etiology and pathophysiology.     

Comorbid substance use disorder in schizophrenia: A selective overview of neurobiological and cognitive underpinnings

Although individuals with schizophrenia show a lifetime prevalence of 50% for suffering from a comorbid substance use disorder, substance abuse usually represents an exclusion criterion for studies on schizophrenia. This implies that surprisingly little is known about a large group of patients who are particularly difficult to treat. The aim of the present work is to provide a brief and non‐exhaustive overview of the current knowledgebase about neurobiological and cognitive underpinnings for dual diagnosis schizophrenia patients. Studies published within the last 20 years were considered using computerized search engines. The focus was on nicotine, caffeine, alcohol, cannabis and cocaine being among the most common substances of abuse. All drugs of abuse target dopaminergic, glutamatergic and GABAergic transmission which are also involved in the pathophysiology of schizophrenia. Current literature suggests that neurocognitive function might beless disrupted in substance‐abusing compared to non‐abusing schizophrenia patients, but in particular the neuroimaging database on this topic is sparse. Detrimental effects on brain structure and function were shown for patients for whom alcohol is the main substance of abuse. It is as yet unclear whether this finding might be an artifact of age differences of patient subgroups with different substance abuse patterns. More research is warranted on the specific neurocognitive underpinnings of schizophrenia patients abusing distinct psychoactive substances. Treatment programs might either benefit from preserved cognitive function as a resource or specifically target cognitive impairment in different subgroups of addicted schizophrenia patients.     

Anxiety and substance use comorbidity among inpatients with schizophrenia

OBJECTIVE: To determine the association between lifetime anxiety symptoms and anxiety disorders and substance use disorders among patients with schizophrenia. METHOD: Participants were 184 inpatients with schizophrenia at the Schizophrenia Research Unit (SRU) at the New York State Psychiatric Institute (NYSPI). Multivariate logistic regression analyses were used to determine the relationship between specific anxiety symptoms and anxiety disorders and substance use disorders among inpatients with schizophrenia. RESULTS: Anxiety symptoms and anxiety disorders were prevalent among 31.5% of the sample. Panic attacks were associated with a significantly increased odds (OR=7.4 (1.2, 47.1)) of comorbid alcohol or substance use disorders (lifetime). This association was specific to panic attacks and persisted after adjusting for differences in sociodemographic characteristics and comorbid anxiety symptoms and anxiety disorders. CONCLUSIONS: These findings are consistent with and extend previous data by providing evidence of an association between panic attacks and increased likelihood of substance use disorders among inpatients with schizophrenia. Future studies that determine the nature of this relationship, the sequence of symptom onsets, and examine whether treatment of anxiety can influence the onset or outcome associated with substance use are needed.     

Prevalence estimates of substance abuse in schizophrenia and their correlates.

Published estimates of the prevalence of substance abuse in schizophrenia were correlated with several aspects of the studies in which they were obtained. Higher estimates of alcohol and stimulant abuse were found in studies published more recently. Rates of alcohol abuse were particularly high in one rural investigation. Rates of stimulant abuse were highest when patients were asked directly about use of stimulants. Increased prevalence estimates in more recent years could not be attributed to method of assessing substance abuse, method of defining substance abuse, or characteristics of the study sample.     

Differences in substance abuse patterns: multiple drug abuse alone versus schizophrenia with multiple drug abuse.

OBJECTIVE: To compare the lifetime consumption patterns of patients with schizophrenia and multiple substance abuse and multiple substance abusers without schizophrenia. METHOD: Two hundred and thirty in-patients of a specialized rehabilitation facility for young drug abusers were assessed with regard to their lifetime consumption patterns of 16 different classes of psychoactive drugs. While 110 patients had no diagnosis of a schizophrenic disorder, 120 patients had a comorbidity of multiple substance abuse and schizophrenia. RESULTS: Comorbid patients reported a higher lifetime consumption of hallucinogens, whereas multiple substance abusers without schizophrenia showed a higher lifetime consumption rate of cocaine. CONCLUSION: The differences found in lifetime consumption patterns between comorbid patients and substance abusers without psychotic disorder do not support the so-called self-medication hypothesis. Instead, the differences in lifetime consumption of certain drugs might be a result of lower social competence and standing in schizophrenic patients and lower ability to procure certain illicit drugs.     

Comorbid substance abuse and neurocognitive function in recent-onset schizophrenia

Despite the high prevalence of comorbid substance use disorder (SUD) up to 65% in schizophrenia there is still few knowledge about the influence of substance abuse on neurocognitive function. In a prospective design we recruited 68 patients (aged 18–40 years) diagnosed as recent-onset schizophrenia or schizoaffective disorder consecutively admitted to hospital. The patients received standardized psychopathological evaluation of schizophrenic symptoms [Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS)], depressive symptoms [Montgomery Asberg Depression Rating Scale, (MADRS)] and global ratings [Clinical Global Impressions Scale (CGI), Global Assessment of Functioning Scale (GAF)]. Out of this sample 44 subjects underwent after stabilization (4–6 weeks after admission) neuropsychological investigation focusing on early information processing (Trail-Making-Test A, Digit Span), visuo-spatial ability (Corsi Block Tapping), verbal fluency (Verbal Fluency Test, semantic and letter category), and executive functioning and cognitive flexibility [Trail-Making-Test B, Wisconsin Card Sorting Test (WCST)]. About 36% of patients reported drug abuse [European Addiction Severity Index (EuropASI)] with a high prevalence for cannabis. Compared with nonabusers the sample of substance abusers was younger, predominantly male and had lower socioeconomic status. Attentional impairment according to the SANS subscale was less in abusers than in nonabusers on admission, no other psychopathological differences could be detected. Schizophrenic patients without substance abuse demonstrated significantly better performance only in a few neurocognitive tasks (Verbal Fluency, letter category and at trend level Digit Span, backwards), while there tended to be an advantage for substance abusers in executive functioning (WCST, not significant). These results are consistent with other studies of first-episode patients. The lack of higher cognitive disturbance in young schizophrenic patients with comorbid substance abuse may encourage clinicians to develop integrated treatment programmes using cognitive strategies of drug therapy.     

Hospital-based adolescent substance abuse treatment: comorbidity, outcomes, and gender

Positive change was demonstrated on a number of self-report scales administered to 129 adolescents at a hospital-based substance abuse program, of whom 72 were posttested after 8 weeks. Female subjects showed change on more measures than male subjects, and a greater number of female subjects went from the clinical to subclinical range. Based on number of sessions attended, subjects were grouped by "dose" into either "hi-attenders" or "lo-attenders." A Trials (pretest/posttest) x Dose interaction revealed significant reduction in drug use at posttest for hi-attenders who were initially heavier users. Multiple regression analyses determined how well "comorbidity" predicted attendance and change in drug use. Although comorbidity failed to predict attendance consistently, male subjects who reported more internalizing symptomatology reduced their drug use to a greater extent than those low on this dimension, and female subjects who initially reported experiencing more family problems became more self-efficacious about future drug avoidance.     

Diagnostic and demographic correlates of substance abuse in schizophrenia and major affective disorder.

The relationship between history of specific types of substance abuse (alcohol, stimulants, cannabis, hallucinogens, narcotics) and demographic and diagnostic variables was evaluated in a large (n = 263) sample of schizophrenic, schizoaffective, major depression and bipolar disorder patients. Prevalence rates were also compared with rates observed in a previous study (1983-1986) conducted using the same methods. Demographic characteristics (gender, age, race, educational level) were strong predictors of type of substance abuse. Patients with a history of cocaine abuse had fewer prior hospitalizations, suggesting that less impaired psychiatric patients may be more prone to illicit substance abuse. Diagnoses were not related to most types of substance abuse, although there was a trend for bipolar patients to have a history of alcohol abuse. The results demonstrate the importance of matching groups on demographic characteristics when exploring diagnostic differences in preference to abuse specific types of substances.