Suicide rates and antidepressants

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Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care databaseBMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h517 (Published 18 February 2015)Cite this as: BMJ 2015;350:h517


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Carol Coupland, associate professor and reader in medical statistics1,
Trevor Hill, research statistician1,
Richard Morriss, professor of psychiatry and community mental health2,
Antony Arthur, professor of nursing science3,
Michael Moore, professor of primary care research4,
Julia Hippisley-Cox, professor of clinical epidemiology and general practice1Author affiliations
Correspondence to: C Coupland carol.coupland@nottingham.ac.uk
Accepted 30 December 2014

Abstract

Objective To assess the associations between different antidepressant treatments and the rates of suicide and attempted suicide or self harm in people with depression.

Design Cohort study.

Setting Patients registered with UK general practices contributing data to the QResearch database.

Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011, followed up until 1 August 2012.

Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use, and commonly prescribed individual antidepressant drugs. Cox proportional hazards models were used to calculate hazard ratios adjusting for potential confounding variables.

Main outcome measures Suicide and attempted suicide or self harm during follow-up.

Results During follow-up, 87.7% (n=209 476) of the cohort received one or more prescriptions for antidepressants. The median duration of treatment was 221 days (interquartile range 79-590 days). During the first five years of follow-up 198 cases of suicide and 5243 cases of attempted suicide or self harm occurred. The difference in suicide rates during periods of treatment with tricyclic and related antidepressants compared with selective serotonin reuptake inhibitors was not significant (adjusted hazard ratio 0.84, 95% confidence interval 0.47 to 1.50), but the suicide rate was significantly increased during periods of treatment with other antidepressants (2.64, 1.74 to 3.99). The hazard ratio for suicide was significantly increased for mirtazapine compared with citalopram (3.70, 2.00 to 6.84). Absolute risks of suicide over one year ranged from 0.02% for amitriptyline to 0.19% for mirtazapine. There was no significant difference in the rate of attempted suicide or self harm with tricyclic antidepressants (0.96, 0.87 to 1.08) compared with selective serotonin reuptake inhibitors, but the rate of attempted suicide or self harm was significantly higher for other antidepressants (1.80, 1.61 to 2.00). The adjusted hazard ratios for attempted suicide or self harm were significantly increased for three of the most commonly prescribed drugs compared with citalopram: venlafaxine (1.85, 1.61 to 2.13), trazodone (1.73, 1.26 to 2.37), and mirtazapine (1.70, 1.44 to 2.02), and significantly reduced for amitriptyline (0.71, 0.59 to 0.85). The absolute risks of attempted suicide or self harm over one year ranged from 1.02% for amitriptyline to 2.96% for venlafaxine. Rates were highest in the first 28 days after starting treatment and remained increased in the first 28 days after stopping treatment.

Conclusion Rates of suicide and attempted suicide or self harm were similar during periods of treatment with selective serotonin reuptake inhibitors and tricyclic and related antidepressants. Mirtazapine, venlafaxine, and trazodone were associated with the highest rates of suicide and attempted suicide or self harm, but the number of suicide events was small leading to imprecise estimates. As this is an observational study the findings may reflect indication biases and residual confounding from severity of depression and differing characteristics of patients prescribed these drugs. The increased rates in the first 28 days of starting and stopping antidepressants emphasise the need for careful monitoring of patients during these periods.

Introduction

Rates of suicide and self harm are greatly increased in people with depression1 2 and reduction of these risks is a major consideration when treating such patients. Paradoxically, although antidepressants have been shown to be effective in reducing the symptoms of depression3 4 there is concern that rates of suicide and self harm may actually be increased by treatment, particularly in younger people.5 6 A meta-analysis of 372 randomised placebo controlled trials of antidepressants found that among adults aged less than 25 the risk of suicidal behaviour was increased during treatment with antidepressants, whereas no association was found in adults aged 25 to 64, and in those aged 65 or more the risk was reduced.7 These findings were supported by a meta-analysis of eight observational studies involving more than 200 000 patients,8 which found an increased risk of suicide among adolescents treated with selective serotonin reuptake inhibitors compared with no antidepressant treatment, but a reduced risk among adults.

The meta-analysis by Stone7 indicated possible differences in risk of suicidal behaviour between different antidepressants, but these findings were based on a small number of events. In a cohort study, venlafaxine was associated with an increased risk of suicide and attempted suicide compared with three other antidepressants,9although the authors concluded that this may have been due to residual confounding. In another cohort study the reported rates of suicide and attempted suicide were similar for different antidepressants, except for a higher rate of suicidal acts in users of venlafaxine compared with selective serotonin reuptake inhibitors, but this association was reduced in secondary analyses.10 In a cohort study of adults aged 65 or more with depression the highest rates of attempted suicide or self harm were in those treated with venlafaxine, mirtazapine, or trazodone.11

Uncertainty remains about the risks of suicide and self harm for different antidepressants and whether these risks vary by dose and duration of use. This is particularly important to determine, now that suicide rates in the United Kingdom and many other countries have started to increase after a period when they were decreasing.1213 14 We carried out a cohort study in people aged 20 to 64 to investigate the associations between different antidepressants and the risk of suicide and attempted suicide or self harm.

http://www.bmj.com/content/350/bmj.h517