A new study by European researchers, Michael Hengartner and Martin Plöderl, published on 24 June 2019, reviewed the information held by the US Food and Drug Administration (FDA) from randomly controlled trials that reported on the association between SSRI antidepressant use and suicide.[1]
The results are detailed below in Table 1 from their paper.
The objective of Hengartner and Plöderl’s research was to “examine whether the use of newer-generation antidepressants, relative to placebo” increased the risk of suicide “when the analysis is based on the number of patients instead of patient exposure years”.[1]
A 2018 study exploring the same data, by Arif Khan and colleagues, found no statistically significant differences in suicide risks between antidepressants and placebo.[2] Kahn et al.’s analysis was based on patient exposure years rather than the number of patients treated. The patient exposure years method places as much weighting on the experience of one patient who is on antidepressants for two years as 24 patients who are on antidepressants for a month. However, the risk of severe adverse events, including suicide, is much higher within the first 3–4 weeks of commencing antidepressant use, and reduces significantly after that.[3] The number of patients treated is therefore a much better measure of the true suicide risk, and the FDA requires that this method is used in its own evaluations.[4]
The choice of the patient exposure years method, in Kahn et al.’s study created an unrealistically favourable impression of the safety of antidepressants. It is notable that Arif Khan has been the principal investigator for at least 503 clinical trials sponsored by over 80 pharmaceutical companies and 30 Contracted Research Organisations.[2]
In contrast, Hengartner and Plöderl analysed the FDA data using the FDA-approved method, conducting the analysis by patient numbers. Their study was limited to adults, which raises the question: Should the FDA suicide warning be extended from just those under 25 years to people of all ages? Further research investigating the risks for different age groups (older versus younger adults) would very useful.
Recent Australian (all age) experience of antidepressant use and suicide
As demonstrated in Figure 1 below, the per-capita rate of antidepressant use by Australians of all ages rose steadily from 10.44% to 12.18% over the period 2012 to 2017. The per-capita suicide rate was more volatile, but trended upwards, increasing from 11.4 in 2012, to 12.7 per 100,000 Australians in 2017.
Australia's recent experience is consistent with the key finding of Hengartner and Plöderl's study, i.e. that antidepressant use increases the risk of suicide.
McGorry and Hickie continue to deny antidepressants increase youth suicide risk
On the same day, 24 June 2019, that Hengartner and Plöderl’s study was published, PsychWatch Australia published our blog on antidepressant use and youth suicide. Our blog revealed that Australian per-capita 0 to 27 year old antidepressant use rates increased approximately 60% from 2009 to 2017, and that the per-capita 0 to 24 year old suicide rate rose 40% over the same period. The increase in suicides was predictable, given the prior (2004) warning by the US Food and Drug Administration (FDA) that antidepressants roughly double the risk of suicidal behaviour in people aged under 25 years.
As detailed in the blog, in the late 2000s influential Australian psychiatrists Professor Patrick McGorry and Professor Ian Hickie, both of whom had received financial support from multiple pharmaceutical companies, diminished the importance of the FDA warning.[5] [6] Independently and together, they both asserted that antidepressant use was likely to reduce youth suicide.
In response to concerns raised in our blog that their advice, however well intended, may have contributed to avoidable deaths of young Australians, Patrick McGorry doubled down on his denial of the antidepressant youth suicide link. He told The West Australian “Antidepressants don’t increase suicide. Evidence shows there can be a temporary increase in suicidal ideation . . . (but) they reduce suicide risk in most”.[7]
In a similar vein, Ian Hickie told The West Australian, “They (critics) are acting like there’s something wrong with increasing treatment…As treatment goes up, we have to be careful, we do run the danger as we increase access . . . that the trade-off is low-quality care. But what’s the alternative? No care?''.[7]
The obvious response to Professor Hickie is that, when “increasing treatment” is clearly associated with increasing death by suicide of young Australians, “there's something wrong”.
Perhaps Professor Hickie needs to ponder the meaning of 'first do no harm'.
Given the real world evidence of surging Australian antidepressant use and youth suicide, the responses of both Professor McGorry and Professor Hickie in The West Australian were disappointing. In view of their undoubted influence, how they respond to the new study will be significant.
Hengartner and Plöderl's study reinforces existing concerns about antidepressant use and youth suicide and potentially broadens them to include older patients. It adds further weight to the case for changing Australia’s approach to suicide prevention, that is detailed in PsychWatch Australia's recent open letter to Prime Minister Morrison and Health Minister Greg Hunt.
Without change, it is very likely that Australian antidepressant use and suicide rates (particularly for young Australians) will continue to increase.
References
[1] Hengartner M.P. Plöderl M. (24 June 2019) Newer-Generation Antidepressants and Suicide Risk in Randomized Controlled Trials: A Re-Analysis of the FDA Database. Psychotherapy Psychosomatics. Available at
https://www.karger.com/Article/Pdf/501215 (accessed 17 July 2019)
[2] Khan A, Fahl Mar K, Gokul S, Brown WA. Decreased suicide rates in recent antidepressant clinical trials. Psychopharmacology (Berl). 2018 May;235(5):1455–62. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920087/ (accessed 17 July 2017)
[3] Healy D, Whitaker C. Antidepressants and suicide: risk-benefit conundrums. J Psychiatry Neurosci. 2003 Sep;28(5):331–7. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193979/ (accessed 17 July 2017)
[4] Stone M, Laughren T, Jones ML, Levenson M, Holland PC, Hughes A, et al. Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ. 2009 Aug;339 aug11 2:b2880. Available at https://www.bmj.com/content/339/bmj.b2880 (accessed 17 July 2017)
[5] Professor McGorry has received unrestricted grants from Janssen-Cilag, Eli Lilly, Bristol Myer Squibb, Astra-Zeneca, Pfizer, and Novartis and has acted as a paid consultant or speaker for most of these companies. McGorry P.D. ‘Is early intervention in the major psychiatric disorders justified? Yes’, BMJ 2008;337:a695 https://www.bmj.com/content/337/bmj.a695.full (accessed 20 July 2019)
Organisations closely associated with Professor McGorry that have also received funding from multiple drug companies include the International Early Psychosis Association which has received funds from Astra[MR2] Zeneca, Lilly and Janssen-Cilag (http://www.iepa.org.au/2010/) and Orygen Youth Health which has received support from AstraZeneca, Bristol Myer Squibb, Eli Lilly, and Janssen-Cilag. Orygen Youth Health, Research Centre – Other Funding https://web.archive.org/web/20110803034537/http://rc.oyh.org.au/ResearchCentreStructure/otherfunding (accessed 20 July 2019)
[6] Professor Hickie has extensive and longstanding financial ties to the pharmaceutical industry. To the best of my knowledge, details of the quantum and conditions of funding have not been publicly disclosed. However, the quantum is certainly in the hundreds of thousands of dollars and may be in the millions. He has received honoraria for presentations of his own work at educational seminars from Servier, Pfizer, AstraZeneca, and Eli Lilly. He has also received funding for research from Servier, Pfizer, AstraZeneca, and Eli Lilly as well as funding from funds from Roche Pharmaceuticals and Bristol-Myers Squibb. Available at https://researchdata.ands.org.au/ian-hickie/406527 (accessed 21 July 2019).
[7] Ison S. It's time to rethink kids pills. The West Australian. 27 June 2019. Available at http://enewspaper2.smedia.com.au/wandaily/shared/ShowArticle.aspx?doc=WAN%2F2019%2F06%2F27&entity=Ar01104&sk=A415DC25&fbclid=IwAR3PYvVtboWfBL6SfewRk65LlSicNEnVzJgYN_veQ06s_Ilxv6TA8e8-qMU (accessed 20 July 2019)