Association between substance

abuse and long-term outcome

of schizophrenia –

a meta-analysis

Jouko MiettunenProfessor of Clinical Epidemiology

University of Oulu, Finland

Conflicts of interest:None

Alcohol and other substance use problems are common

among individuals with schizophrenia.

Many of the previous studies have focused on clinical

comorbidity, not on longitudinal studies aiming to look

for possible causal associations.

Cannabis is a potential risk factor for schizophrenia

We aimed to investigate if premorbid or early substance

use predicts long-term clinical and social course in

schizophrenia.

Koskinen J, Löhönen J, Koponen H, Isohanni M, Miettunen J. Rate of cannabis use disorders in clinical samples of patients with schizophrenia: a meta-analysis. Schizophr Bull 2010; 36: 1115-30.

• Approximately every fourth schizophrenia patient had a

diagnosis of cannabis use disorders (35 studies).

• median current rate of cannabis use disorders was 16.0%

and median lifetime rate was 27.1%

• higher in first-episode vs. long-term patients (current

28.6% vs. 22.0%)

• Approximately every fifth schizophrenia patient had a

diagnosis of cannabis use disorders (60 studies).

Koskinen J, Löhönen J, Koponen H, Isohanni M, Miettunen J. Prevalence of alcohol use disorders in schizophrenia - a systematic review and meta-analysis. Acta Psychiatr Scand 2009; 120: 85-96.

Prevalence of cannabis use disorder

A meta-analysis including nine mainly cross-sectional studies found that substance using patients have more positive, but less negative symptoms (Talamo et al. 2006).

In depressive symptoms, Potvin et al. (2007) found that substance using schizophrenia patients have more depressive symptoms, although the difference was smaller than commonly assumed.

Other outcomes, such as employment or social functioning, have not been studied in systematic reviews.

Substance Abuse and Outcome

Potvin S, et al. Austr NZ J Psychiatry 2007; 41: 792-9; Talamo A, et al. Schizophr Res. 2006;86:251–255.

A systematic review to identify potentially relevant studies was conducted. Only studies with a follow-up period of at least two years were included.

We studied following outcomes: negative, positive and total symptomsclinical remissionhospitalizationssocial functioningemploymentglobal outcome

Current data search until January 2014

Substance Abuse and Outcome

The search identified 9582 unique

potentially relevant articles of which 25

studies presenting results from 30 samples

met our inclusion criteria.

The meta-analysis included 5 to 13 studies in

each outcome category.

Identification of Studies

Reference Sample (M/F)

Outcome(s)

Addington and Addington 1998 (Canada)

80 (54/26) positive, negative and total symptoms (PANSS)

Arndt et al. 1992 (USA) 131 (93/38) symptoms (SANS/SAPS), hospitalization, global outcome (GAS), social and overall functioning

Blow et al. 1998 (USA) 682 (660/22) hospitalization, symptoms (BPRS), functioning (GAF)

Bodén et al. 2009 (Sweden) 71 functioning (living independently, work/ studying 50%, and meeting friends)

Bühler et al. 2002 (Germany)

46 employment

Caspari 1999 (Germany) 53 (41/12) global outcome (GAS), hospitalization, employment, positive and negative symptoms (BPRS, AMDP)

Cleghorn et al. 1991 (Canada)

27 (19/8) positive and negative symptoms

Dubertret et al. 2006 (France)

181 (~118/63) positive and negative symptoms

Foti et al. 2010 (USA) 162 symptoms (SAPS, SANS), global (GAF)

Haro et al. 2011 (worldwide: six areas)

11078 clinical and functional (social) remission

Reference Sample(M/F)

Outcome(s)

Hodgins et al. 2008 (UK) 225 men real life functioning

Huguelet et al. 1996 (Switzerland)

37 (18/19) hospitalization, relapse, functioning (GAF)

Jockers-Scherübl et al. 2007 (Germany)

39 (23/16) positive and negative symptoms, hospitalization, global clinical outcome (CGI)

Jordan et al. 2014 (Canada) 159 (108/51) social functioning

Juola et al. 2013, Miettunen et al. 2007 (Finland)

105 (63/43) employment

Kozaric-Kovacic et al. 1995 (Croatia)

312 (150/162)

social functioning, hospitalization, course

Manrique-Garcia et al. 2014 357 (357/0) hospitalization

Marwaha et al. 2009 (United Kingdom, France, Germany)

213 to 773 employment (losing or getting job)

Orlandi and Bersani 2001 (Italy)

125 negative, positive, total symptoms, hospitalization

Pencer et al. 2005 (Canada) 49 employment/ productivity

Verdoux et al. 2010 (France) 108 (72/36) employment

Whitty et al. 2008 (United Kingdom)

97 (63/34) Strauss–Carpenter Scale outcome scale (total score)

Yen et al. 2009 (Taiwan) 118 (99/19) symptoms (PANSS)

Summary of results

positive symptoms (n=7)

negative symptoms (n=6)

total psychotic symptoms (n=6)

clinical remission (n=8)

hospitalizations (n=7)

social functioning (n=13)

employment (n=7)

global outcome (n=5)

Study

-0.00 (-0.08, 0.07)

0.09 (-0.02, 0.21)

0.03 (-0.09, 0.15)

-0.01 (-0.05, 0.02)

-0.05 (-0.18, 0.07)

-0.00 (-0.06, 0.05)

-0.06 (-0.16, 0.04)

-0.05 (-0.13, 0.04)

correlation (95% CI)

-0.00 (-0.08, 0.07)

0.09 (-0.02, 0.21)

0.03 (-0.09, 0.15)

-0.01 (-0.05, 0.02)

-0.05 (-0.18, 0.07)

-0.00 (-0.06, 0.05)

-0.06 (-0.16, 0.04)

-0.05 (-0.13, 0.04)

0-0.2 -0.1 0 0.1 0.2 0.3

correlation

outcomes

Odds Ratio < 1 indicates lower likelihood of achieving remission

Haro JM, et al. Cross-national clinical and functional remission rates: Worldwide Schizophrenia Outpatient Health Outcomes (W-SOHO) study. Br J Psychiatry 2011; 199:194-201.

Mullin K, Gupta P, Compton MT, Nielssen O, Harris A, Large M. Does giving upsubstance use work for patients with psychosis? A systematic meta-analysis. Aust N Z J Psychiatry 2012; 46:826-39.

See also: Large M et al. Aust N Z J Psychiatry 2014; 48:418-32; Gupta P et al. Aust N Z J Psychiatry 2013; 47:524-37

although comorbid substance use associates with poorer outcome in schizophrenia, the early substance use has only a modest effect as a predictor of long-term outcome

changes in substance use?effect of medication? alcohol vs. cannabis ?covariates?milder disease?

Tiina-Mari Paaso, BMed, Katja Kasurinen, BMed, Antti Mustonen, BMed, Eetu Oinas, BMed, Juha Käkelä, BMed, Erika Jääskeläinen, Adjunct Professor, Jouko Miettunen, Professor Center for Life Course Epidemiology and Systems Medicine and

Research Unit for Clinical Neuroscience, University of Oulu, Oulu, Finland

Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland

Noora Hirvonen, MAInformation studies, Faculty of Humanities, University of

OuluEmail: jouko.miettunen@oulu.fi

Homepage: www.joukomiettunen.net