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Strategies to prevent death by suicide: Meta-analysis of randomised controlled trials

  • Natalie B. V. Riblet (a1), Brian Shiner (a1), Yinong Young-Xu (a2) and Bradley V. Watts (a2)
Abstract
Background

Few randomised controlled trials (RCTs) have shown decreases in suicide.

Aims

To identify interventions for preventing suicide.

Method

We searched EMBASE and Medline from inception until 31 December 2015. We included RCTs comparing prevention strategies with control. We pooled odds ratios (ORs) for suicide using the Peto method.

Results

Among 8647 citations, 72 RCTs and 6 pooled analyses met inclusion criteria. Three RCTs (n = 2028) found that the World Health Organization (WHO) brief intervention and contact (BIC) was associated with significantly lower odds of suicide (OR = 0.20, 95% CI 0.09–0.42). Six RCTs (n = 1040) of cognitive–behavioural therapy (CBT) for suicide prevention and six RCTs of lithium (n = 619) yielded non-significant findings (OR = 0.34, 95% CI 0.12–1.03 and OR = 0.23, 95% CI 0.05–1.02, respectively).

Conclusions

The WHO BIC is a promising suicide prevention strategy. No other intervention showed a statistically significant effect in reducing suicide.

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Copyright
Corresponding author
Natalie Riblet, MD, MPH, Veterans Affairs Medical Center, 215 North Main Street, White River Junction, VT 05009, USA. Email: Natalie.Riblet@dartmouth.edu
Footnotes
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See editorial, pp. 381–383, this issue.

Declaration of interest

None.

Footnotes
References
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Strategies to prevent death by suicide: Meta-analysis of randomised controlled trials

  • Natalie B. V. Riblet (a1), Brian Shiner (a1), Yinong Young-Xu (a2) and Bradley V. Watts (a2)
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eLetters

Response to “Strategies to prevent death by suicide: meta-analysis of randomised controlled trials”

Emmert Roberts, MRC Clinical Research Fellow, National Addiction Centre and Department of Psychological Medicine, King's College London
Andrea Cipriani, Associate Professor, Department of Psychiatry, University of Oxford
John R Geddes, Professor of Epidemiological Psychiatry, University of Oxford and Oxford Health NHS Foundation Trust
Andrew A Nierenberg, Director, Dauten Family Center for Bipolar Treatment and Innovation, Massachusetts General Hospital
Allan H Young, Consultant Psychiatrist, Centre for Affective Disorders, King's College London
10 September 2017

We read with interest the recently published meta-analysis of suicide prevention strategies by Riblet et al. [1] However we have some concerns about the authors’ conclusion that “unlike previous reviews, [2,3] we did not find that lithium significantly reduced suicide.”

This statement is at odds with the finding from our own meta-analysis in 2013, which found that lithium was more effective than placebo in reducing the number of suicides [4]. The difference between the two meta-analyses relies solely on the addition of data from a single non-blind, pragmatic trial. [5] Whilst the authors do state that ‘the results of the summary estimate for lithium became statistically significant after removing a more recent study with several methodological limitations [5]’, they fail to point out two key issues with regards the addition of this trial, on which one of us, AC, was co-investigator.

Riblet et al fail to highlight that this study was not placebo controlled, unlike all other studies contributing data to their meta-analysis, and was reported as essentially a failed, underpowered study (5). Including this study is, at the very least, highly questionable. Just as the author’s reasonably included only randomised controlled trials in their analysis, so we would argue that it is inappropriate to include a non-placebo-controlled trial in a meta-analysis aiming to estimate the efficacy of lithium.

Futhermore, the fact that the addition of data from a single randomised controlled trial with 53 patients, and just one completed suicide appears to materially change the estimate of effect serves to highlight the major point that Riblet et al. fail to discuss. As we have previously noted (4), randomised data in this area are sparse and estimates of efficacy are therefore highly unstable. It simply is not yet possible to determine whether lithium does or does not reduce the risk of suicide on the basis of randomised evidence alone - and this may be an enduring uncertainty given the low event rate of suicide and the practical and feasibility challenges of conducting adequately powered trials.

While acknowledging the limitations of the randomised evidence, it is important to note that there are several large-scale observational studies that also find a reduced incidence of completed suicide in those on lithium treatment of a size consistent with the randomised evidence [6, 7, 8]. Taking the randomised and observational data together, and in view of the sensitivity of Riblet et als results to the inclusion or exclusion of a single, methodologically heterogeneous trial, we believe that the combined current evidence indicates that lithium probably has a substantial and clinically important antisuicidal effect.

References:

1.Riblet N, Shiner B, Young-Xu Y and Watts B. Strategies to prevent death by suicide: meta-analysis of randomised controlled trials. British Journal of Psychiatry 2017 210, 396–402

2.Mann JJ, Apter A, Bertolote J, Beautrais A, Currier D, Haas A, et al. Suicide prevention strategies: a systematic review. JAMA 2005; 294: 2064–74

3.Zalsman G, Hawton K, Wasserman C, Van Heeringen K, Arensman E, Sarchiapone M, et al. Suicide prevention strategies revisited: 10-year systematic review. Lancet Psychiatry 2016; 3: 646–59

4.Cipriani A, Pretty H, Hawton K, Geddes JR. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Am J Psychiatry 2005;162(10):1805-19

5.Girlanda F, Cipriani A, Agrimi E, Appino M, Barichello A, Beneduce R, et al. Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial. BMC Research Notes 2014;7:1-8.

6.Song J, Sjölander A, Joas E, Bergen SE, Runeson B, Larsson H, Landén M, Lichtenstein P. Suicidal Behavior During Lithium and Valproate Treatment: A Within-Individual 8-Year Prospective Study of 50,000 Patients With Bipolar Disorder. Am J Psychiatry. 2017;174(8):795-802

7.Hayes JF, Pitman A, Marston L, Walters K, Geddes JR, King M, Osborn DP. Self-harm, Unintentional Injury, and Suicide in Bipolar Disorder During Maintenance Mood Stabilizer Treatment: A UK Population-Based Electronic Health Records Study. JAMA Psychiatry. 2016;73(6):630-7

8.Silverman SL. From randomized controlled trials to observational studies. Am J Med. 2009;122(2):114-20

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