Co-occurring schizophrenia and substance use disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment and diagnosis
- E Cabrina Campbell, MD
E Cabrina Campbell, MD
- Associate Professor of Psychiatry
- Perelman School of Medicine, University of Pennsylvania; Cpl. Michael J. Crescenz VA Medical Center
- Stanley N Caroff, MD
Stanley N Caroff, MD
- Emeritus Professor of Psychiatry
- Perelman School of Medicine, University of Pennsylvania
- Stephan C Mann, MD, DLFAPA
Stephan C Mann, MD, DLFAPA
- Lenape Valley Foundation
- Section Editors
- Andrew J Saxon, MD
Andrew J Saxon, MD
- Section Editor — Substance Use Disorders
- Professor and Director, Addiction Psychiatry Residency Program, Department of Psychiatry & Behavioral Sciences
- University of Washington
- Stephen Marder, MD
Stephen Marder, MD
- Section Editor — Psychotic Disorders
- Professor of Psychiatry
- Semel Institute of Neuroscience at UCLA
Schizophrenia and addiction are both chronic disorders with serious complications, consequences, and costs for individuals and society. Both conditions are associated with poor adherence to treatment and poorer outcomes when the co-occurring disorder is present.
Some of the symptoms of schizophrenia overlap with symptoms of intoxication, chronic use, or withdrawal from alcohol or other drugs. Family history and the temporal relationship of symptoms can help to distinguish patients with a substance use disorder (SUD) alone from co-occurring schizophrenia and SUD.
The psychiatric diagnoses, substance abuse and substance dependence, in DSM-IV-TR were replaced by one diagnosis, substance use disorder, in DSM-5 . Although the crosswalk between DSM-IV and DSM-5 disorders is imprecise, substance dependence is approximately comparable to substance use disorder, moderate to severe subtype, while substance abuse is similar to the mild subtype.
The epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis of schizophrenia and substance use disorder are described here. Treatment of co-occurring schizophrenia and substance use disorder are described separately. The epidemiology, pathogenesis, clinical manifestations, course, assessment, diagnosis and treatment of schizophrenia occurring alone and substance use disorder occurring alone are also discussed separately. (See "Psychosocial interventions for co-occurring schizophrenia and substance use disorder" and "Schizophrenia: Epidemiology and pathogenesis" and "Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment" and "Schizophrenia: Clinical manifestations, course, assessment, and diagnosis" and "Pharmacotherapy for schizophrenia: Side effect management" and "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis" and "Cannabis use disorder: Epidemiology, comorbidity, and pathogenesis" and "Cannabis use disorder: Clinical features and diagnosis" and "Risky drinking and alcohol use disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Cocaine use disorder in adults: Epidemiology, pharmacology, clinical manifestations, medical consequences, and diagnosis".)
Prevalence — Epidemiologic studies have generally shown that the prevalence of substance use disorder (SUD) is elevated in persons with schizophrenia compared with the general population. As examples, in a study of substance use among 9142 individuals with severe psychotic disorders, including 5586 subjects with schizophrenia or schizoaffective disorder, the odds of nicotine (smoking), alcohol, marijuana, and other drug use were higher (odds ratios = 3.5 to 4.6) in patients with psychosis compared with 10,195 nonpsychiatric controls . Rates of substance use varied among subgroups based on age, gender, and race or ethnicity. Having a psychotic disorder further increased the odds of substance use in each subgroup. The lifetime prevalence of the DSM-IV-TR disorders substance abuse and substance dependence among patients with schizophrenia has been estimated to range from 47 to 59 percent in the United States (US), compared with 16 percent in the general population [3-5]. Differences between schizophrenia patients and normal controls in substance use may be diminished when the effects of low socioeconomic status (common among schizophrenia patients) is taken into account [6-14]. High rates of co-occurrence have also been observed internationally (eg, in Australia, Switzerland, Italy, Germany, England) . Many with these co-occurring disorders used two or more substances.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
- Hartz SM, Pato CN, Medeiros H, et al. Comorbidity of severe psychotic disorders with measures of substance use. JAMA Psychiatry 2014; 71:248.
- Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA 1990; 264:2511.
- Kendler KS, Gallagher TJ, Abelson JM, Kessler RC. Lifetime prevalence, demographic risk factors, and diagnostic validity of nonaffective psychosis as assessed in a US community sample. The National Comorbidity Survey. Arch Gen Psychiatry 1996; 53:1022.
- Thoma P, Daum I. Comorbid substance use disorder in schizophrenia: a selective overview of neurobiological and cognitive underpinnings. Psychiatry Clin Neurosci 2013; 67:367.
- Sara GE, Large MM, Matheson SL, et al. Stimulant use disorders in people with psychosis: a meta-analysis of rate and factors affecting variation. Aust N Z J Psychiatry 2015; 49:106.
- Fryers T, Melzer D, Jenkins R, Brugha T. The distribution of the common mental disorders: social inequalities in Europe. Clin Pract Epidemiol Ment Health 2005; 1:14.
- Scott KM, Al-Hamzawi AO, Andrade LH, et al. Associations between subjective social status and DSM-IV mental disorders: results from the World Mental Health surveys. JAMA Psychiatry 2014; 71:1400.
- Gara MA, Vega WA, Arndt S, et al. Influence of patient race and ethnicity on clinical assessment in patients with affective disorders. Arch Gen Psychiatry 2012; 69:593.
- Rost K, Hsieh YP, Xu S, et al. Potential disparities in the management of schizophrenia in the United States. Psychiatr Serv 2011; 62:613.
- Brown T, Platt S, Amos A. Equity impact of European individual-level smoking cessation interventions to reduce smoking in adults: a systematic review. Eur J Public Health 2014; 24:551.
- Bull ER, Dombrowski SU, McCleary N, Johnston M. Are interventions for low-income groups effective in changing healthy eating, physical activity and smoking behaviours? A systematic review and meta-analysis. BMJ Open 2014; 4:e006046.
- Lindenberg CS, Solorzano RM, Bear D, et al. Reducing substance use and risky sexual behavior among young, low-income Mexican-American women: comparsion of two interventions. Appl Nurs Res 2012; 15:137.
- Bradizza CM, Stasiewicz PR, Paas ND. Relapse to alcohol and drug use among individuals diagnosed with co-occurring mental health and substance use disorders: a review. Clin Psychol Rev 2006; 26:162.
- Buckley PF. Prevalence and consequences of the dual diagnosis of substance abuse and severe mental illness. J Clin Psychiatry 2006; 67 Suppl 7:5.
- Koskinen J, Löhönen J, Koponen H, et al. Prevalence of alcohol use disorders in schizophrenia--a systematic review and meta-analysis. Acta Psychiatr Scand 2009; 120:85.
- Koskinen J, Löhönen J, Koponen H, et al. Rate of cannabis use disorders in clinical samples of patients with schizophrenia: a meta-analysis. Schizophr Bull 2010; 36:1115.
- Chapman S, Ragg M, McGeechan K. Citation bias in reported smoking prevalence in people with schizophrenia. Aust N Z J Psychiatry 2009; 43:277.
- Ziedonis D, Williams JM, Smelson D. Serious mental illness and tobacco addiction: a model program to address this common but neglected issue. Am J Med Sci 2003; 326:223.
- Swartz MS, Wagner HR, Swanson JW, et al. Substance use and psychosocial functioning in schizophrenia among new enrollees in the NIMH CATIE study. Psychiatr Serv 2006; 57:1110.
- Kivimies K, Repo-Tiihonen E, Kautiainen H, et al. Opioid abuse and hospitalization rates in patients with schizophrenia. Nord J Psychiatry 2016; 70:128.
- Marieczurrena R. Recovery from addiction without treatment: an interview study. Scand J Behav Ther 1996; 25:57.
- Lybrand J, Caroff S. Management of schizophrenia with substance use disorders. Psychiatr Clin North Am 2009; 32:821.
- Mueser KT, Essock SM, Drake RE, et al. Rural and urban differences in patients with a dual diagnosis. Schizophr Res 2001; 48:93.
- Tsai J, Rosenheck RA. Psychiatric comorbidity among adults with schizophrenia: a latent class analysis. Psychiatry Res 2013; 210:16.
- Dubertret C, Bidard I, Adès J, Gorwood P. Lifetime positive symptoms in patients with schizophrenia and cannabis abuse are partially explained by co-morbid addiction. Schizophr Res 2006; 86:284.
- Malchow B, Hasan A, Fusar-Poli P, et al. Cannabis abuse and brain morphology in schizophrenia: a review of the available evidence. Eur Arch Psychiatry Clin Neurosci 2013; 263:3.
- Mueser KT, Drake RE, Wallach MA. Dual diagnosis: a review of etiological theories. Addict Behav 1998; 23:717.
- Ng E, McGirr A, Wong AH, Roder JC. Using rodents to model schizophrenia and substance use comorbidity. Neurosci Biobehav Rev 2013; 37:896.
- Chambers RA, Bickel WK, Potenza MN. A scale-free systems theory of motivation and addiction. Neurosci Biobehav Rev 2007; 31:1017.
- Krystal JH, D'Souza DC, Gallinat J, et al. The vulnerability to alcohol and substance abuse in individuals diagnosed with schizophrenia. Neurotox Res 2006; 10:235.
- Power RA, Verweij KJ, Zuhair M, et al. Genetic predisposition to schizophrenia associated with increased use of cannabis. Mol Psychiatry 2014; 19:1201.
- Feng Y. Convergence and divergence in the etiology of myelin impairment in psychiatric disorders and drug addiction. Neurochem Res 2008; 33:1940.
- Westermeyer J. Comorbid schizophrenia and substance abuse: a review of epidemiology and course. Am J Addict 2006; 15:345.
- Wilkinson ST, Radhakrishnan R, D'Souza DC. Impact of Cannabis Use on the Development of Psychotic Disorders. Curr Addict Rep 2014; 1:115.
- Samaha AN. Can antipsychotic treatment contribute to drug addiction in schizophrenia? Prog Neuropsychopharmacol Biol Psychiatry 2014; 52:9.
- Mackowick KM, Barr MS, Wing VC, et al. Neurocognitive endophenotypes in schizophrenia: modulation by nicotinic receptor systems. Prog Neuropsychopharmacol Biol Psychiatry 2014; 52:79.
- Lohr JB, Flynn K. Smoking and schizophrenia. Schizophr Res 1992; 8:93.
- Chambers RA, Krystal JH, Self DW. A neurobiological basis for substance abuse comorbidity in schizophrenia. Biol Psychiatry 2001; 50:71.
- Mobascher A, Winterer G. The molecular and cellular neurobiology of nicotine abuse in schizophrenia. Pharmacopsychiatry 2008; 41 Suppl 1:S51.
- Sacco KA, Termine A, Seyal A, et al. Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms. Arch Gen Psychiatry 2005; 62:649.
- Radhakrishnan R, Wilkinson ST, D'Souza DC. Gone to Pot - A Review of the Association between Cannabis and Psychosis. Front Psychiatry 2014; 5:54.
- Chen J, Paredes W, Lowinson JH, Gardner EL. Delta 9-tetrahydrocannabinol enhances presynaptic dopamine efflux in medial prefrontal cortex. Eur J Pharmacol 1990; 190:259.
- Laviolette SR, Grace AA. The roles of cannabinoid and dopamine receptor systems in neural emotional learning circuits: implications for schizophrenia and addiction. Cell Mol Life Sci 2006; 63:1597.
- Ho BC, Wassink TH, Ziebell S, Andreasen NC. Cannabinoid receptor 1 gene polymorphisms and marijuana misuse interactions on white matter and cognitive deficits in schizophrenia. Schizophr Res 2011; 128:66.
- Onwuameze OE, Nam KW, Epping EA, et al. MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse. Psychol Med 2013; 43:619.
- Xie P, Kranzler HR, Krystal JH, et al. Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence. Addict Biol 2014; 19:955.
- Large M, Mullin K, Gupta P, et al. Systematic meta-analysis of outcomes associated with psychosis and co-morbid substance use. Aust N Z J Psychiatry 2014; 48:418.
- Pulver AE, Wolyniec PS, Wagner MG, et al. An epidemiologic investigation of alcohol-dependent schizophrenics. Acta Psychiatr Scand 1989; 79:603.
- Manning V, Betteridge S, Wanigaratne S, et al. Cognitive impairment in dual diagnosis inpatients with schizophrenia and alcohol use disorder. Schizophr Res 2009; 114:98.
- Sevy S, Kay SR, Opler LA, van Praag HM. Significance of cocaine history in schizophrenia. J Nerv Ment Dis 1990; 178:642.
- Green AI, Tohen MF, Hamer RM, et al. First episode schizophrenia-related psychosis and substance use disorders: acute response to olanzapine and haloperidol. Schizophr Res 2004; 66:125.
- Brunette MF, Mueser KT. Psychosocial interventions for the long-term management of patients with severe mental illness and co-occurring substance use disorder. J Clin Psychiatry 2006; 67 Suppl 7:10.
- Jones RM, Lichtenstein P, Grann M, et al. Alcohol use disorders in schizophrenia: a national cohort study of 12,653 patients. J Clin Psychiatry 2011; 72:775.
- Maat A, Fouwels A, de Haan L. Cocaine is a major risk factor for antipsychotic induced akathisia, parkinsonism and dyskinesia. Psychopharmacol Bull 2008; 41:5.
- Zhornitsky S, Stip E, Pampoulova T, et al. Extrapyramidal symptoms in substance abusers with and without schizophrenia and in nonabusing patients with schizophrenia. Mov Disord 2010; 25:2188.
- Swartz MS, Wagner HR, Swanson JW, et al. The effectiveness of antipsychotic medications in patients who use or avoid illicit substances: results from the CATIE study. Schizophr Res 2008; 100:39.
- Wobrock T, Falkai P, Schneider-Axmann T, et al. Comorbid substance abuse in first-episode schizophrenia: effects on cognition and psychopathology in the EUFEST study. Schizophr Res 2013; 147:132.
- Rosenberg SD, Goodman LA, Osher FC, et al. Prevalence of HIV, hepatitis B, and hepatitis C in people with severe mental illness. Am J Public Health 2001; 91:31.
- Ziedonis DM, Smelson D, Rosenthal RN, et al. Improving the care of individuals with schizophrenia and substance use disorders: consensus recommendations. J Psychiatr Pract 2005; 11:315.
- Himelhoch S, Lehman A, Kreyenbuhl J, et al. Prevalence of chronic obstructive pulmonary disease among those with serious mental illness. Am J Psychiatry 2004; 161:2317.
- Dixon L, Postrado L, Delahanty J, et al. The association of medical comorbidity in schizophrenia with poor physical and mental health. J Nerv Ment Dis 1999; 187:496.
- Schmidt LM, Hesse M, Lykke J. The impact of substance use disorders on the course of schizophrenia--a 15-year follow-up study: dual diagnosis over 15 years. Schizophr Res 2011; 130:228.
- Stubbs B, Vancampfort D, Bobes J, et al. How can we promote smoking cessation in people with schizophrenia in practice? A clinical overview. Acta Psychiatr Scand 2015; 132:122.
- Institute of Medicine. Improving the Quality of Health Care for Mental and Substance-Use Conditions: Quality Chasm Series, National Academies Press, Washington DC 2006. p.210.
- Tiet QQ, Finney JW, Moos RH. Screening psychiatric patients for illicit drug use disorders and problems. Clin Psychol Rev 2008; 28:578.
- Rogers E, Sherman S. Tobacco use screening and treatment by outpatient psychiatrists before and after release of the American Psychiatric Association treatment guidelines for nicotine dependence. Am J Public Health 2014; 104:90.
- Fals-Stewart W, O'Farrell TJ, Freitas TT, et al. The timeline followback reports of psychoactive substance use by drug-abusing patients: psychometric properties. J Consult Clin Psychol 2000; 68:134.
- McLellan AT, Kushner H, Metzger D, et al. The Fifth Edition of the Addiction Severity Index. J Subst Abuse Treat 1992; 9:199.
- Bellack AS, Bennett ME, Gearon JS, et al. A randomized clinical trial of a new behavioral treatment for drug abuse in people with severe and persistent mental illness. Arch Gen Psychiatry 2006; 63:426.
- Center for Substance Abuse Treatment. Substance Abuse Treatment for Persons With Co-Occurring Disorders, Substance Abuse and Mental Health Services Administration, Rockville, MD 2005.
- Risk factors
- Etiologic theories
- CLINICAL MANIFESTATIONS
- Clinical and psychosocial outcomes
- Antipsychotic side effects
- Medical comorbidities
- Substance use disorder in DSM-5
- Schizophrenia in DSM-5
- Differential diagnosis
- SUMMARY AND RECOMMENDATIONS