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 design.

The aim of this study was to investigate if premorbid or early substance use predicts long-term clinical and social course in schizophrenia.

A systematic review to identify potentially relevant studies was conducted. Studies with a follow-up period of at least two years were included. Following outcomes were studied: negative, positive and total symptoms, clinical remission, hospitalizations, social functioning, employment, and global outcome. Spearman's correlations were used to summarize results, negative correlations indicating poorer outcome with substance use.

The search identified 10776 unique potentially relevant articles of which 25 studies met our inclusion criteria. The meta-analysis included 5 to 13 studies in each outcome category. Moderate to high heterogeneity was found between studies in each outcome group. In meta-analysis, substance use associated modestly with outcome. All the associations were non-significant and correlations between −0.06 and 0.09. Non-significant findings are explained by the fact that the original studies found often opposite results, indicating both worse and better long-term outcome for early substance users.

Although comorbid substance use associates with poorer outcome in schizophrenia, the early substance use has only a modest effect on long-term outcome. This difference to studies on current comorbidity may indicate that those who continue substance abuse have poor outcome, e.g. due to poor treatment adherence, whereas those who stop the abuse may have relatively good outcome.