title: Reporting of drug induced depression and fatal and non-fatal suicidal behaviour in the UK from 1998 to 2011.
abstract: BACKGROUND
  Psychiatric adverse drug reactions (ADRs) are distressing for patients and have important public health implications. We identified the drugs with the most frequent spontaneous reports of depression, and fatal and non-fatal suicidal behaviour to the UK's Yellow Card Scheme from 1998 to 2011.
  
  
  METHODS
  We obtained Yellow Card data from the Medicines and Healthcare products Regulatory Agency for the drugs with the most frequent spontaneous reports of depression and suicidal behaviour from 1964 onwards. Prescribing data were obtained from the NHS Information Centre and the Department of Health. We examined the frequency of reports for drugs and estimated rates of reporting of psychiatric ADRs using prescribing data as proxy denominators from 1998 to 2011, as prescribing data were not available prior to 1998.
  
  
  RESULTS
  There were 110 different drugs with ≥ 20 reports of depression, 58 with ≥ 10 reports of non-fatal suicidal behaviour and 33 with ≥ 5 reports of fatal suicidal behaviour in the time period. The top five drugs with the most frequent reports of depression were the smoking cessation medicines varenicline and bupropion, followed by paroxetine (a selective serotonin reuptake inhibitor), isotretinoin (used in acne treatment) and rimonabant (a weight loss drug). Selective serotonin reuptake inhibitors, varenicline and the antipsychotic medicine clozapine were included in the top five medicines with the most frequent reports of fatal and non-fatal suicidal behaviour. Medicines with the highest reliably measured reporting rates of psychiatric ADRs per million prescriptions dispensed in the community included rimonabant, isotretinoin, mefloquine (an antimalarial), varenicline and bupropion. Robust denominators for community prescribing were not available for two drugs with five or more suicide reports, efavirenz (an antiretroviral medicine) and clozapine.
  
  
  CONCLUSIONS
  Depression and suicide-related ADRs are reported for many nervous system and non-nervous system drugs. As spontaneous reports cannot be used to determine causality between the drug and the ADR, psychiatric ADRs which can cause significant public alarm should be specifically assessed and reported in all randomised controlled trials.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall 39 Whatley Road, Bristol BS8 2PS, UK. kyla.thomas@bristol.ac.uk.
authors.forename: Kyla H
authors.initials: KH
authors.lastname: Thomas
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.forename: John
authors.initials: J
authors.lastname: Potokar
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: David
authors.initials: D
authors.lastname: Gunnell
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D013222:State Medicine; D013405:Suicide; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000928:Antidepressive Agents