A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors
de Leon J and Diaz FJ;
Commented by , 22 Aug 2005
Aim of the study
Although psychiatrists have observed for a long-time that smoking is very prevalent among people with schizophrenia, the degree of increased risk has not been assessed by a meta-analysis. It is also not clear whether only patients with schizophrenia are more prone to smoking or whether this phenomenon rather is equally frequent in other severe mental illnesses.
Furthermore, the reasons for the association of schizophrenia and smoking are not clear. One hypothesis is that there is a biological factor that makes people with schizophrenia vulnerable to tobacco smoking.
The aim of this article was to explore these hypotheses by a meta-analysis of all epidemiological studies available irrespective of their country of origine. One idea was that if the increased risk were found across across countries and cultures, the increase of risk can not only be explained by sociocultural factors.
Methods
The authors undertook a meta-analysis of world-wide epidemiological studies that were combined using odds ratios. These studies were identified by a MEDLINE search using "schizophrenia" and "smoking" or "nicotine" as search terms; by cross-referencing of the reference lists of the identified articles, and by further articles found by the authors during their long experience of research in this area.
Among others outcomes were current smoking, heavy smoking, nicotine dependence, smoking cessation and ever smoking.
Results
The authors found forty-two studies across 20 nations with 7593 patients that demonstrated a consistent association between schizophrenia and current smoking. Overall, 62% of the patients with schizophrenia were current smokers leading to an odds ratio (OR) compared to normal controls of 5.9 (95% confidence interval, CI 4.9–5.7).
The risk was more pronounced in male patients (32 studies, 71%, OR 7.2, CI, 6.1–8.3) than in female patients (25 studies, 44%, OR 3.3, CI, 3.0–3.6). Patients with schizophrenia also had higher rates of current smoking when compared to people with other severe mental disorders (18 studies, average OR 1.9, CI 1.7–2.1).
Heavy smoking and high nicotine dependence were also more frequent in smokers with schizophrenia compared to the general population. Although there was no consistent evidence that heavy smoking or high nicotine dependence is more frequent in schizophrenia than in other severe mental illnesses, this analysis was inconclusive due to a relatively low number of studies available.
Smoking people with schizophrenia had significantly lower cessation rates than the general population. They also had a higher prevalence of ever smoking compared to the general population (9 studies, OR = 3.1, CI 2.4–3.8) and compared to other severely mentally ill patients (5 studies, OR = 2.0, CI 1.6–2.4).
Dr Leucht's comments
The authors of the report must be lauded for summarising the enormous literature about the association between smoking and schizophrenia in a landmark meta-analysis. Compared to conventional reviews meta-analyses provide quantitative estimates of effects. By summarising all available data the results also become very robust.
The report made it very clear that a high rate of patients with schizophrenia (62%) across international settings are smokers and that people with schizophrenia are less likely to quit smoking. Weaknesses of the study are – as clearly mentioned by the authors – the restriction of the search to MEDLINE which is a database with a strong focus on English journals.
From a methodological point of view no statistical test of heterogeneity of single study results has been undertaken. Such heterogeneity statistics could have helped to identify outliers and reasons for discrepancies between trials.
Last but not least, in the discussion a strong emphasis is put on interpreting the findings in terms of a biological (e.g. genetic) risk factor for smoking that may be associated with schizophrenia. Although such a risk factor is possible other likely explanations have not been sufficiently pointed out to.
For example, other hypotheses are that people with schizophrenia try to alleviate positive, negative or depressive symptoms; or the side-effects of antipsychotic drugs by smoking. The latter factors may be in part supported by the fact that compared to other severe mental illnesses the increase of risk was less pronounced.
Thus, in spite of this meta-analysis a biological risk factor making people with schizophrenia prone to smoking remains a hypothesis.