title: Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database.
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.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Patients registered with UK general practices contributing data to the QResearch database.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Primary Care, School of Medicine, University of Nottingham, University Park, Nottingham NG7 2RD, UK carol.coupland@nottingham.ac.uk.
authors.forename: Carol
authors.initials: C
authors.lastname: Coupland
authors.affiliation: Division of Primary Care, School of Medicine, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Trevor
authors.initials: T
authors.lastname: Hill
authors.affiliation: Institute of Mental Health, Jubilee Campus, Nottingham, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Morriss
authors.affiliation: School of Health Sciences, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.
authors.forename: Antony
authors.initials: A
authors.lastname: Arthur
authors.affiliation: University of Southampton Medical School, Primary Care and Population Sciences, Aldermoor Health Centre, Southampton, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Moore
authors.affiliation: Division of Primary Care, School of Medicine, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Hippisley-Cox
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016728:Self-Injurious Behavior; D013405:Suicide / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000706:statistics & numerical data*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000928:Antidepressive Agents