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Research:
Corrado Barbui, MD, Eleonora Esposito, MD, and Andrea Cipriani, MD
Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies
CMAJ 2009; 180: 291-297 [Abstract] [Full text] [PDF]
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[Read eLetter] Adolescents dying by suicide are not taking SSRIs
Michael J Dudley   (17 March 2009)
[Read eLetter] Age-related risks of suicidal behavior during antidepressant treatment
Ross J Baldessarini, MD   (9 February 2009)

Adolescents dying by suicide are not taking SSRIs 17 March 2009
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Michael J Dudley,
Adolescent Service, Prince of Wales Hospital, Randwick, NSW, Australia 2031
Senior Lecturer in Psychiatry, University of New South Wales

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Re: Adolescents dying by suicide are not taking SSRIs

m.dudley{at}unsw.edu.au Michael J Dudley

The Editor Canadian Medical Association Journal

Dear Editor, We thank Barbui et al for their thought provoking paper (CMAJ, 3 February, 180:291-297) systematically reviewing observational studies on SSRIs and the risk of suicide. However, we are somewhat unsure of certain aspects of the paper, and their exclusion of some observational research referred to below is unexpected.

Although the risk of suicide for adolescents is highlighted by being reported in the abstract, this finding does not appear to be addressed specifically in the main text as might be anticipated for an emphasised finding based on two studies (Table 1). It is also evident that the authors have combined attempted suicide and suicide in a number of analyses of their selected papers.

As Gibbons and Mann note in their commentary (CMAJ 3 February 180:270 -271), the findings of Barbui et al need to be reconciled with other data. Gibbons and Mann refer to Sondergard et al’s (2006) post-mortem study of suicide victims, but they do not refer to a number of other studies which have also addressed this topic. Those studies are included in the appended table. They are studies of either toxicology data from consecutive suicides, or studies of whole-of-population pharmaco- epidemiological data, the latter specifically examining SSRI use in proximity to or overlapping the time of death. It could be argued that such data are more appropriate in elucidating this issue rather than data from, for example, the studies of Tiihonen et al and Olfson et al, which Barbui et al have included. Thus Tiihonen et al (2006) report only on those persons in a population who have been hospitalised for attempted suicide, thereby clearly having the potential to skew the results because of confounding by severity, as attempted suicide is the strongest risk factor for subsequent suicide. Olfson et al (2006), reporting on a population hospitalised at least once for depression, inherit the same methodological risk in selecting a more severely ill group for study.

Utilizing these whole of population data, we note that only 9 of 574 (1.6%) young people dying by suicide had recent exposure to SSRIs. Thus it is particularly rare for SSRIs to have been used prior to suicide in this younger population, which is said to be at risk in relation to SSRIs. Given the prevalence of depression in suicide in young persons (Shaffer et al, 1996, Beautrais, 2000), the weight of evidence from these pharmaco- epidemiological and toxicological data appears to be against the suggestion that SSRIs are associated with increased suicide in the young. Rather, the evidence can be interpreted as being consistent with the notion that most young people who die by suicide have not had the potential benefit of antidepressants at the time of their deaths (Goldney, 2008; Dudley et al, 2008).

Yours sincerely

Dr Michael Dudley Professor Robert Goldney, Professor of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia Mr Dusan Hadzi-Pavlovic, Senior Hospital Scientist, School of Psychiatry and Black Dog Institute, University of New South Wales, Sydney, Australia

References:

Barbui C, Esposito E, Cipriani A. Selective serotonin reuptake inhibitors and risk fo suicide: a systematic review of observational studies. CMAJ 2009; 180 (3): 291-297. Beautrais A. Risk factors for suicide and attempted suicide among young people. Aust N Z J Psychiatry 2000; 34:420-436. Dudley M, Hadzi-Pavlovic D, Andrews D, Perich T. New generation antidepressants, suicide and depressed adolescents: how should clinicians respond to changing evidence? Aust N Z J Psychiatry 2008; 42: 456-466. Gibbons R, Mann JJ. Proper studies of selective serotonin reuptake inhibitorsare needed for youth with depression. CMAJ 2009; 180 (3): 270- 271. Goldney R. Suicide prevention. Oxford: Oxford University Press (Oxford Psychiatry Library), 2008. Isacsson G, Holmgren P, Ahlner J. Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14857 suicides. Acta Psychiatr Scand 2005; 111:286-290 Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal behaviors. JAMA 2004; 292:338-343 Leon A, Marzuk P, Tardiff K, Teres J. Paroxetine, other drugs and youth suicide in New York City, 1993 through 1998. J Clin Psychiatry 2004; 65:915-918. Leon A, Marzuk P, Tardiff K, Bucciarelli A, Piper T, Galea S. Antidepressants and youth suicide in New York City, 1999-2002. J Amer Acad Child Adolescent Psychiatry 2006; 45 (9): 1054-1058. Moskos M, Olson L, Halbern S, Keller T, Gray D. Utah youth suicide study: psychological autopsy. Suicide Life Threat Behav 2005; 35:536-546 Olfson M, Marcus SC, Shaffer D. Antidepressant drug therapy and suicide in severely depressed children and adolescents: a case-control study. Arch Gen Psychiatry 2006: 63: 865-872. Shaffer, D., Gould, M. S., Fisher, P., Trautman, P., Moeau, D., Kleinman, M., & Flory, M. Psychiatric diagnosis in child and adolescent suicide. Arch Gen Psychiatry 1996; 53: 339-348. Søndergård L, Kvist K, Andersen P, Kessing, LL. Do antidepressants precipitate youth suicide: a national pharmacoepidemiological study. Eur J Child Adolesc Psychiatr 2006; 15:232-240 Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Tanskanen A, Haukka J. Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort. Arch Gen Psychiatry 2006; 63:1358_1367.

Conflict of Interest:

Dr Dudley has not received drug company funding at any time. Professor Goldney has received honoraria, travel grants and research support from a number of pharmaceutical companies. Mr Hadzi-Pavlovic received payment some years ago for a lecture on statistics to registrars, and also was paid for travel and attendance at an international conference a few years ago that was heavily sponsored by European drug companies, though the invitation was via the conference organisers. Dr. Dudley is being sued for prescribing SSRI antidepressants to a severely depressed girl. She hanged herself while under guard in hospital and gave herself a brain injury (myoclonic movements). Dr. Dudley's peer reviewed articles on antidepressants antedate this lawsuit.
Age-related risks of suicidal behavior during antidepressant treatment 9 February 2009
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Ross J Baldessarini, MD
Professor of Psychiatry, Harvard Medical School, Boston, MA

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Re: Age-related risks of suicidal behavior during antidepressant treatment

rjb{at}mclean.org Ross J Baldessarini, MD

Dear CMAJ Editor:

Meta-analyses arising from 8 recent large, clinical observational studies in elderly, adult, and juvenile depressed patients by Barbui and his colleagues (CMAJ 2009;180:291-297) provides strong support for a decrease in risk of suicidal behaviors with increasing age, among patients treated with modern antidepressants versus not. This observation was found earlier by the US FDA (Laughren 2004, as cited by Barbui et al. 2009) in a massive post-hoc meta-analysis of findings from 372 randomized, controlled, pharmaceutical trials (RCTs) of such drugs, based on a range of incidentally and passively reported suicidal behaviors (mostly ideation).

Two possibilities may contribute to these findings: [1] depressed juveniles respond substantially less to all types of antidepressants than adults, and children may respond even less than adolescents (Tsapakis et al. 2008); [2] juvenile depressives have a relatively high risk of becoming over-stimulated or manic during exposure to antidepressants, and especially SSRIs, owing largely to the presence of previously undiagnosed bipolarity, with a possible increase in suicidal risk (Martin et al. 2004; Baldessarini et al. 2005). It would be of interest to analyze antidepressant responses further among young versus elderly depressed adults to see if the age-related decrease in suicide risk reported by Barbui et al. is perhaps paralleled inversely by antidepressant efficacy versus age.

References

Baldessarini RJ, Faedda GL, Hennen J. Risk of mania with serotonin reuptake inhibitors vs. tricyclic antidepressants in children, adolescents and young adults. Arch Pediatr Adolesc Med 2005;159:298–299.

Martin A, Young C, Leckman JF, Mukonoweshuro C Rosenheck R, Leslie D. Age Effects on antidepressant-induced manic conversion. Arch Pediatr Adolesc Med 2004;158:773-780.

Tsapakis EM, Soldani F, Tondo L, Baldessarini RJ. Efficay of antidepressants in juvenile depression: meta-analysis. Br J Psychiatry 2008;193:10-17.

Conflict of Interest:

Professor Baldessarini has recently been a consultant or investigator-initiated research collaborator with: AstraZeneca, Auritec, Biotrofix, Janssen, JDS-Noven, Lilly, Luitpold, NeuroHealing, Novartis, Pfizer, and SK-BioPharmaceutical Corporations; he is not a member of pharmaceutical speakers’ bureaus, nor does he or any family member hold equity positions in biomedical or pharmaceutical corporations.