Does tobacco use cause psychosis? Systematic review and meta-analysis

Background: Although the association between psychotic illness and cigarette smoking is well known, the reasons are unclear why people with psychosis are more likely to smoke than are the general population. We aimed to test several hypotheses. First, that daily tobacco use is associated with an increased risk of psychotic illness in both case-control and prospective studies. Second, that smoking is associated with an earlier age at onset of psychotic illness. Finally, that an earlier age at initiation of smoking is associated with an increased risk of psychosis. We also aimed to derive an estimate of the prevalence of smoking in patients presenting with their first episode of psychosis.

Methods: We searched Embase, Medline, and PsycINFO and selected observational studies in which rates of smoking were reported in people with psychotic disorders, compared with controls. We calculated the weighted mean difference for age at onset of psychosis and age at initiation of smoking. For categorical outcomes, we calculated odds ratios from cross-sectional studies and risk ratios from prospective studies.

Findings: Of 3717 citations retrieved, 61 studies comprising 72 samples met inclusion criteria. The overall sample included 14 555 tobacco users and 273 162 non-users. The prevalence of smoking in patients presenting with their first episode of psychosis was 0·57 (95% CI 0·52-0·62; p<0·0001). In case-control studies, the overall odds ratio for the first episode of psychosis in smokers versus non-smokers was 3·22 (95% CI 1·63-6·33), with some evidence of publication bias (Egger's test p=0·018, Begg's test p=0·007). For prospective studies, we calculated an overall relative risk of new psychotic disorders in daily smokers versus non-smokers of 2·18 (95% CI 1·23-3·85). Daily smokers developed psychotic illness at an earlier age than did non-smokers (weighted mean difference -1·04 years, 95% CI -1·82 to -0·26). Those with psychosis started smoking at a non-significantly earlier age than did healthy controls (-0·44 years, 95% CI -1·21 to 0·34).

Interpretation: Daily tobacco use is associated with increased risk of psychosis and an earlier age at onset of psychotic illness. The possibility of a causal link between tobacco use and psychosis merits further examination.

Funding: NIHR Maudsley Biomedical Research Centre.