Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: prospective cohort study.

To compare the risk of suicide, self harm, and depression in patients prescribed varenicline or bupropion with those prescribed nicotine replacement therapy. Prospective cohort study within the Clinical Practice Research Datalink. 349 general practices in England. 119,546 men and women aged 18 years and over who used a smoking cessation product between 1 September 2006 and 31 October 2011. There were 81,545 users of nicotine replacement products (68.2% of all users of smoking cessation medicines), 6741 bupropion (5.6%), and 31,260 varenicline (26.2%) users. Outcomes were treated depression and fatal and non-fatal self harm within three months of the first smoking cessation prescription, determined from linkage with mortality data from the Office for National Statistics (for suicide) and Hospital Episode Statistics data (for hospital admissions relating to non-fatal self harm). Hazard ratios or risk differences were estimated using Cox multivariable regression models, propensity score matching, and instrumental variable analysis using physicians' prescribing preferences as an instrument. Sensitivity analyses were performed for outcomes at six and nine months. We detected 92 cases of fatal and non-fatal self harm (326.5 events per 100,000 person years) and 1094 primary care records of treated depression (6963.3 per 100,000 person years). Cox regression analyses showed no evidence that patients prescribed varenicline had higher risks of fatal or non-fatal self harm (hazard ratio 0.88, 95% confidence interval 0.52 to 1.49) or treated depression (0.75, 0.65 to 0.87) compared with those prescribed nicotine replacement therapy. There was no evidence that patients prescribed bupropion had a higher risk of fatal or non-fatal self harm (0.83, 0.30 to 2.31) or of treated depression (0.63, 0.46 to 0.87) compared with patients prescribed nicotine replacement therapy. Similar findings were obtained using propensity score methods and instrumental variable analyses. There is no evidence of an increased risk of suicidal behaviour in patients prescribed varenicline or bupropion compared with those prescribed nicotine replacement therapy. These findings should be reassuring for users and prescribers of smoking cessation medicines.