The British Journal of Psychiatry
1–7. doi: 10.1192/bjp.bp.116.187799
Review article
Strategies to prevent death by suicide:
meta-analysis of randomised controlled trials
Natalie B. V. Riblet, Brian Shiner, Yinong Young-Xu and Bradley V. Watts
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
Suicide is a worldwide health concern. According to the World
Health Organization (WHO), over 800 000 people die by suicide
every year.1 The most comprehensive review of available suicide
prevention strategies was published by Mann et al in 2005 and
updated by Zalsman et al in 2016.2,3 These reviews concluded that
restricting access to lethal means prevents suicide, and that
clozapine and lithium exert an anti-suicidal effect.2,3 However,
other reviews have drawn different conclusions about the role of
pharmacotherapy, psychotherapy and psychosocial interventions
in suicide prevention.4–12 Notably, many of these reviews rely
heavily on observational data to formulate their opinions, and
their conclusions are largely based on improvements in inter-
mediary outcomes including suicidal ideation and attempts
(rather than death by suicide).4-12 These intermediate outcomes
are susceptible to measurement bias and may not predict
suicide.13 The WHO has emphasised the critical need to identify
interventions with proven efficacy for preventing death by
suicide.1 To address these concerns, we conducted a meta-analysis
of randomised controlled trials (RCTs) comparing the efficacy of
various interventions versus control to prevent death by suicide
in adults. We believe our review will inform clinical practice and
illuminate promising areas in need of additional research, by
focusing on the hard outcome of death by suicide.14
Method
Review protocol
In preparation for our review, we drafted a study protocol
delineating our planned approach for identifying relevant studies.
We did not register our protocol with Prospero, but a copy is
available in online Appendix DS1. We used the standard
methodology outlined by Cochrane for our analysis and the
PRISMA guidelines for reporting our methods and findings.15,16
Eligibility criteria
We defined a priori inclusion criteria for this review. We limited
our review to RCTs and pooled results of RCTs published in the
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.
Declaration of interest
None.
Copyright and usage
B The Royal College of Psychiatrists 2017.
English language. We required that studies randomly assign
patients to an intervention aimed at suicide prevention or a
control condition including usual care, placebo or wait-list. We
included studies in which patients were aged 18 years or older.
To broaden our search, we included studies if they reported death
by suicide as a primary or secondary outcome. In the event that
death by suicide was a secondary outcome, we required that the
primary study aim included the prevention of suicidal ideation
and/or behaviour. We included studies even if there were no
suicide events because this is a more conservative approach and
improves the generalisability of our findings.17
We included pooled analysis of RCTs in our review. Pooled
analyses, which use a systematic method to identify suicides in
drug trials (e.g. US Food and Drug Administration summary
basis of approval reports), may offer unique insights into the
relationship between suicide and psychiatric medications. Because
it is currently unclear which interventions prevent suicide, we
excluded RCTs that compared two or more active treatments.
Instead, we provided a qualitative summary of these trials in
online Appendix DS2.
We acknowledge that there are inherent challenges in
using RCTs to study rare outcomes such as suicide and that
non-randomised, controlled studies may provide important
information about strategies to prevent suicide. We focused our
review on RCTs, however, because this study design is the gold
standard for establishing efficacy, and a sufficient number of RCTs
have explored suicide prevention.18
Study identification
We searched EMBASE, Medline, CINAHL, the Cochrane
Library, and PsycINFO from the inception of each database until
31 December 2015 to identify published articles addressing our
research question. We used exploded MeSH terms and key words
to generate the following themes: death by suicide, prevention/
control and treatment. We used ‘OR’ to combine prevention/
control and treatment. We then used the Boolean term ‘AND’ to
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Riblet et al
find the intersection between this collective theme and death by
suicide. We applied a highly sensitive search strategy to identify
RCTs in electronic databases. The details of the search strategy
are available in online Appendix DS1.
We attempted to locate additional published and unpublished
studies by searching ClinicalTrials.gov from inception to 31
December 2015 and reviewing the references of prior review
papers and included articles. When necessary, we contacted
investigators to determine whether an eligible study met our
inclusion criteria (online supplemental references35–43). In the
event that authors did not respond to our requests, we excluded
these studies (online supplemental references40–43).
Primary end-point and data abstraction
We defined death by suicide using the Centers for Disease Control
and Prevention (CDC) definition, ‘death caused by self-directed
injurious behavior with an intent to die as a result of the
behavior.’19
Based on a priori inclusion criteria, two reviewers (N.B.V.R.
and B.S.) screened the titles and abstracts of all potentially relevant
studies. The same reviewers then assessed the full text of the
remaining studies to make a final determination regarding
eligibility for review. In the event that it was unclear whether a
full text met all eligibility criteria, a separate reviewer (B.V.W.
independently evaluated these texts for study inclusion.
Discrepancies were resolved through consensus.
Using a piloted, standardised data collection form, two
reviewers (N.B.V.R. and B.S.) extracted data in duplicate from
included studies. We extracted data related to demographics,
methods, outcomes and risk of bias. We used the Cochrane
Risk of Bias Tool to assess study quality.20 In the case of
multiple reports of the same data-sets (online supplemental
references35,36,38,44–72), we selected the study that included the
most comprehensive and up-to-date information (online
supplemental references36,60–65,67–72). From pooled analysis, we
extracted total number of suicides and person-years of exposure
(number of patients at risk multiplied by the number of years
of exposure). To minimise bias, we preferentially selected pooled
analyses that limited their analysis to the double-blind period
and reported person-year exposure. We reviewed pooled analysis
to ensure that trials were not double counted. Discrepancies were
resolved through consensus.
Data analysis
We evaluated our primary outcome using the Peto method and
calculated summary odds ratios (ORs) with 95% confidence
intervals and P-values.21 More commonly used meta-analysis
methods (e.g. risk ratio) are generally not recommended for the
evaluation of rare outcomes such as suicide.21–23 The Peto method
is a powerful alternative for combining data when event rates are
below 1%.21–23 We did not apply a continuity correction for trials
with zero events because this is not recommended with the Peto
method.17
We formed groups and subgroups of strategies using Mann
et al’s conceptual framework of suicide prevention–intervention
domains and sub-domains.2 Several interventions included in our
review were not described by Mann et al (i.e. non-cognitive–
behavioural therapy (CBT), case management, letter/telephone
contact after a suicide attempt, higher-level care interventions,
mood stabilisers, somatic therapies and other classes of
antidepressants).2 Therefore, we used consensus among the
authors to develop additional domains and sub-domains to
categorise these interventions. Furthermore, we excluded two
2
domains reported in Mann et al’s review (screening for patients
at high risk, and media reporting guidelines for suicide), because
we found no related RCTs that met our inclusion criteria.2
To promote homogeneity, we stratified each of the inter-
vention domains based on the targeted population of interest
(e.g. patients with schizophrenia). For each domain, we evaluated
whether the intervention or control was favoured in each study
and we then determined whether these results were statistically
significant. We then evaluated the effect of combining these
studies on the magnitude, direction and statistical significance
of the overall summary estimate of the effect size.
We used the standard definition of an OR to interpret our
results (i.e. probability of an event occurring versus the probability
that the event will not occur in the intervention versus the
control). We deemed that an OR less than one meant that the
relative odds of death by suicide was smaller in the intervention
versus the control, and the opposite was true if the OR was greater
than one.24 We considered OR to be statistically significant if the
95% confidence interval did not cross one.
We used RevMan 5.3 to pool our results.25 We assessed
groupings for heterogeneity using Cochrane’s Q and the I 2
statistic.22 We used a conventional threshold of P50.10 and
I 2450% to indicate statistical significance and meaningful
heterogeneity, respectively.22
Confirmatory analysis
Many concerns have been raised about the validity of available
methods for conducting meta-analysis of rare events such as
suicide.26 To address these concerns, we felt that it was appropriate
to perform a confirmatory analysis. We used a Poisson regression
model with random effects and calculated an incidence rate ratio
(IRR) for suicides over person-year for each domain of
strategies. This approach accounts for differences in exposure time
across studies, addresses any potential heterogeneity between
trials and better accounts for trials with zero events.27,28 The
Poisson regression model with random intervention effects has
also been used in meta-analysis of rare event data, including
suicide.27,28 However, because the Poisson regression model is
not recommended if there is over-dispersion in the data, we first
performed a boundary likelihood-ratio test, evaluating whether
the alpha (the estimate of the dispersion parameter) for domains
(and sub-domains) of interest was significantly greater than
zero (defined as P50.05).29 If we encountered significant over-
dispersion, we calculated the IRR using the recommended
multilevel mixed-effects negative binomial regression rather than
the Poisson regression.30 Confirmatory analyses were conducted
using STATA statistical software version 14 (StataCorp).
Sensitivity analysis
We conducted a sensitivity analysis based on the quality of
included studies as judged by the Cochrane Risk of Bias Tool.20
We evaluated whether the magnitude and direction of the
summary estimate of each intervention domain changed if we
excluded studies that were judged to be at high risk of bias.
Assessment of reporting bias
Using STATA, we generated funnel plots for domains that
included at least ten studies, and we assessed for publication bias
using Harbord’s modified test for small-study effects.31 This
method uses a modified linear regression analysis to identify
significant funnel plot asymmetry which would indicate
publication bias.31 The Harbord method is more powerful in cases
 Strategies to prevent death by suicide

of few events per trial.31 We considered a P50.05 to suggest

publication bias. 11 866 records identified through 19 additional records
electronic database searching identified through
EMBASE – 3297 other sources
CINAHL – 2171 Reference review – 3
Results Medline – 4641 ClinicalTrials.gov –16
PsycINFO – 1525
As shown in Fig. 1, we identified 8634 records eligible for screening. Cochrane Library – 232

After title and abstract screening, we found that 351 records

remained, and 97 reports (78 studies) met inclusion criteria based 6 6
on full text review (online supplemental references36,60–65,67–137). 8647 unique records from all sources
(duplicates removed)

Characteristics of included studies 7 Ongoing studies – 13

Tables 1–3 display the characteristics of included studies, which
spanned five decades. Over 50% were published in the past 10 6
years. Although most trials studied interventions targeted at 8634 records screened
for eligibility
individuals with known risk factors for suicide, some trials
evaluated interventions in a general or primary care population.
8283 records excluded
For example, one trial investigated a central storage facility for 7 by abstract & title review
pesticides in villages practising floriculture in Southern India
(online supplemental reference94). Except for one trial that 6
351 full-text records
used a wait-list control and one trial that used sham (online assessed for eligibility
supplemental references96,136), all trials of non-pharmacological
interventions used a usual care comparison. Pharmacological 254 records excluded by
studies used pill placebo as a control group. full-text review
7 Incorrect study design – 69
Incorrect population – 9
Assessment of quality Incorrect outcome – 156
No usable data – 3
We identified a number of methodological concerns (online Table 6
DS1). All studies were of randomised design, but many trials had 97 reports (78 studies)
small sample sizes, large losses to follow-up, and/or were of short included in quantitative
synthesis
duration. For non-pharmacological studies, it was difficult to
mask patients/personnel, and the usual care arm was not
standardised across studies. Some authors raised concerns about Fig. 1 PRISMA flow diagram.
the fidelity of the intervention. Several authors suggested that
patients in the usual care arm may have benefited from study
assessments, and these benefits may have obscured the true effect intervention included an educational session on suicide
of the intervention. Finally, although many trials used robust prevention followed by regular contact with a trained provider (by
methods to identify suicide, several trials relied on methods that telephone or in person) for up to 18 months (online supplemental
were either unclear or at high risk for bias, which may have references60,73,74). There was no evidence that other complex
resulted in over- or underestimation of the true effect of the psychosocial interventions reduce the risk of suicide (online
intervention. For example, Sun et al used informants (caregivers) Fig. DS1 and online Table DS2).
to report suicide and suicidal behaviour, but raised concerns that
information may have been withheld owing to the stigma of
suicide (online supplemental references65). Effects of psychotherapy
There were 24 unique RCTs (n = 3056) of psychotherapies to
Analysis of heterogeneity address suicidal behaviour (online supplemental references67,68,
95–116
As shown in online Fig. DS1, we encountered little heterogeneity ). In six trials of CBT for suicide prevention, 3 out of 514
in our analysis, except there was modest heterogeneity when we patients in the intervention group and 10 out of 526 patients in
evaluated intensive follow-up interventions (Q = 7.17 (P = 0.05), the control group died by suicide (Fig. 2). The results, however,
I 2 = 48%). This reflects the distinct differences between the types were not statistically significant (OR = 0.34, 95% CI 0.12–1.03,
of interventions tested. Reassuringly, the heterogeneity resolved P = 0.06; IRR = 0.30, 95% CI 0.08–1.11, P = 0.07) (online
when we categorised these interventions into three sub-domains. supplemental references67,95–99). Common features of the
intervention included reviewing a recent suicide attempt, applying
cognitive strategies and learning relapse prevention. There was no
Effects of complex psychosocial interventions evidence that other CBT or non-CBT therapies reduce the risk of
Twenty-nine RCTs (n = 22 135) reported on complex psychosocial suicide (online Fig. DS1 and online Table DS2).
interventions (online supplemental references36,60–65,73–94). In the
three trials of the WHO brief intervention and contact (BIC)
intervention, 3 out of 1041 patients in the intervention group Effects of pharmacotherapy
and 24 out of 987 patients in the control group died by suicide, There were 14 RCTs (n = 2443) reporting on pharmacotherapy
and the difference was significant (OR = 0.20, 95% CI 0.09–0.42, and death by suicide (online supplemental references117–130). After
P50.0001; IRR not calculable owing to insufficient number of accounting for random effects and length of follow-up, there was
studies) (Fig. 2) (online supplemental references60,73–74). The no evidence among the pooled trials that pharmacotherapy reduced
WHO BIC was tested in low- and middle-income countries as part the risk of suicide (OR = 0.21, 95% CI 0.05–0.86; IRR = 0.10, 95%
of the Multisite Intervention Study on Suicidal Behaviours. The CI 0.00–32.27) (online Fig. DS1 and online Table DS2). In 6 trials

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Table 1 Characteristics of included studies: complex psychosocial interventions a
Riblet et al

Years Study Intervention Control Age, years: Female, Setting, Follow-up, months: Attrition %, Rigour in data
covered N N N mean (s.d.) n (%) Europe: n (%) median (IQR) median (IQR) collectionb

Case management – psychosis 1996–2007 4 771 774 33.1 (11.4) 623 (61) 4 (100) 35 (25) 4 (11) B
Intensive follow-up 1992–2015 11 2447 2613 39.4 (15.2) 2868 (56) 5 (46) 12 (3) 16 (19) A
Aftercare strategy 1989 1 68 73 NR NR 1 (100) 12 (0) 4 (0) B
Letter/telephone contact 1976–2011 7 2863 2922 29.4 (12.6) 3436 (62) 4 (57) 13 (30) 13 (18) A
PCMH integration 2005–2010 3 1754 1633 71.0 (7.6) 1597 (67) 0 (0) 24 (27) 6 (4) B
RN education of caregivers 2013 1 51 54 41.0 (16.6) 33 (54) 0 (0) 12 (0) 42 (0) C
Follow-up with GP after SB 2015 1 101 101 37.8 (NR) 111 (55) 1 (100) 6 (0) 13 (0) A
Lethal means restriction 2013 1 4446 3307 NR 3877 (50) 0 (0) 18 19 A
Psychotherapiesc
CBTd 1987–2015 20 1711 1542 30.7 (11.0) 1818 (54) 9 (45) 12 (14) 19 (16) B
Non-CBTd 2001–2016 5 263 278 33.5 (10.0) 222 (41) 4 (80) 18 (12) 23 (10) B

CBT, cognitive–behavioural therapy; GP, general practitioner; IQR, interquartile range; NR, not reported; PCMH, primary care mental health; RN, nurse; SB, suicidal behaviour.
a. Reported results for age, gender and drop-out are limited to those studies for which data were available.
b. Grading of suicide assessment: A: 550% of trials used rigorous methods (e.g. coroner report); B: 550% of trials methods were unclear; C: 550% of trials methods were at risk for bias (e.g. informant).
c. Except for one trial (online CBT module to prevent suicide) which used a wait-list control (van Spijker et al; online supplemental reference96), all trials of non-pharmacological interventions used a usual care or standard care control condition.
d. A third arm of the CBT trial conducted by Tarrier et al (online supplemental reference107) evaluated supportive therapy for psychosis. This arm was included in the analysis of non-CBT therapies.

Table 2 Characteristics of included studies: pharmacological interventionsa

Years Study Intervention Control Age, years: mean Female, Setting, Follow-up, months: Attrition %, Rigour in data
covered N N N (s.d.) n (%) Europe: n (%) median (IQR) median (IQR) collectionb

Randomised placebo-controlled trials of medications

Antidepressants 1982–2013 7 894 891 54.0 (16.0) 966 (57) 3 (43) 3 (3) 27 (16) B
Lithium 1973–2014 6 257 308 42.0 (10.9) 199 (60) 3 (50) 12 (6) 27 (45) B
Omega-3 fatty acids 2007 1 22 27 30.6 (NR) 32 (65) 1 (100) 3 (0) 20 (0) B
Pooled analysis of randomised trials of medications
Antidepressants 2005–2007 3 41 099 14 944 43.6 (2.7) 29 378 (58) n/a PY median: 1367 (2086.7) NR B
Antipsychotics 2003–2013 2 42 203 7042 41 (NR) 15 771 (37) n/a PY median: 3201 (4275.8) NR B
Mood stabilisers 2005 1 2449 1423 NR NR n/a PY median: 730 (0) NR B

IQR, interquartile range; n/a, not available; NR, not reported; PY, person-year exposure.
a. Reported results for age, gender and drop-out are limited to those studies for which data were available.
b. Grading of suicide assessment: A: 550% of trials used rigorous methods (e.g. coroner report); B: 550% of trials methods were unclear; C: 550% of trials methods were at risk for bias (e.g. informant).

Table 3 Characteristics of included studies: higher-level care interventions a

Years Study Intervention Control Age, years: Female, Setting, Follow-up, months: Attrition %, Rigour in data
covered N N N mean (s.d.) n (%) Europe, n (%) median (IQR) median (IQR) collectionb

Partial hospital admission 1999–2008 2 163 87 35.9 (10.7) 122 (49) 2 (100) 15 (3) 28 (15) A/C
Special care unit 1997 1 140 134 36.3 (15.1) 180 (66) 1 (100) 12 (0) NR A
Somatic therapies
ECT 2013 1 28 28 57 (15.8) 28 (50) 1 (100) 12 (0) 0 (0) B
rTMSc 2014 1 20 21 42.5 (15.7) 6 (15) 0 (0) 6 (0) 27 (0) B

ECT, electroconvulsive therapy; IQR, interquartile range; NR = not reported; rTMS, repetitive transcranial magnetic stimulation.
a. Reported results for age, gender and drop-out are limited to those studies for which data were available.
b. Grading of suicide assessment: A: 550% of trials used rigorous methods (e.g. coroner report); B: 550% of trials methods were unclear; C: 550% of trials methods were at risk for bias (e.g. informant)
c. The comparison arm received sham rTMS.
 Strategies to prevent death by suicide

Author, year Population Intervention Control

Comprehensive follow-up programmea Events Total Events Total Weight % Odds ratio (95% CI)d
WHO BIC
Amadeo, 2015 Self-harm event(s) 0 100 2 90 6.5 0.12 (0.01–1.94
Fleischmann, 2008 Suicide attempt 2 872 18 827 64.7 0.19 (0.08–0.45)
Mousavi, 2014 Suicide attempt 1 69 4 70 15.9 0.29 (0.05–1.75)
Sub-total 3 1041 24 987 0.20 (0.09–0.42)
Heterogeneity: w2 = 0.33 d.f. = 2 (P = 0.85) I 2 = 0%
Test for overall effect: Z = 4.19 (P50.0001)
Other programmes
Hvid, 2011 (OPAC) Suicide attempt or self harm event(s) 2 69 1 64 9.7 1.82 (0.19–17.88)
Mouaffak, 2015 (OSTA) Suicide attempt 1 152 0 151 3.3 77.34 (0.15–369.95)
Sub-total 3 221 1 215 2.60 (0.36–18.65)
Heterogeneity: w2 = 0.36 d.f. = 1 (P = 0.55) I 2 = 0%
Test for overall effect: Z = 0.95 (P = 0.034)
Total 6 1262 25 1202 100 0.28 (0.14–0.56)
Heterogeneity: w2 = 6.41 d.f. = 4 (P = 0.17) I 2 = 38%
Test for overall effect: Z = 3.57 (P50.017)

Cognitive–behavioural therapy for suicide preventionb

Brown, 2005 Suicide attempt 0 60 1 60 7.8 0.14 (0.00–6.82)
Raj, 2001 Suicide attempt 0 20 1 20 7.8 0.14 (0.00–6.82)
Rudd, 2015 Suicide attempt or SI w/intent 1 76 1 76 15.8 1.00 (0.06–16.14)
Slee, 2008 Self-harm event(s) 0 40 2 42 15.4 0.14 (0.01–2.25)
Tyrer, 2003 Self-harm event(s) 2 202 5 208 53.6 0.43 (0.10–1.92)
Van Spijker, 2014 Mild–moderate SI 0 116 0 120 0.0 No events
Total 3 514 10 526 100 0.34 (0.12–1.03)
Heterogeneity: w2 = 1.50 d.f. = 4 (P = 0.83) I 2 = 0%
Test for overall effect: Z = 1.91 (P = 0.06)

Treatment with lithiumc

Bauer, 2000 MDD in remission 0 14 1 15 14.4 0.14 (0.00–7.31)
Girlanda, 2014 Refractory MDD & self-harm 1 29 0 25 14.3 76.44 (0.13–327.93)
Khan, 2011 Depressive disorder & SI 0 40 0 40 0.0 No events
Lauterbach, 2008 Depressive disorder & suicide attempt 0 84 3 83 42.6 0.13 (0.01–1.27)
Prien, 1973a Bipolar & unipolar depression 0 45 1 39 14.3 0.12 (0.00–5.91)
Prien, 1973b Bipolar depression 0 101 1 104 14.4 0.14 (0.00–7.02)

Total 1 313 6 306 100 0.23 (0.05–1.02)

Heterogeneity: w2 = 3.23 d.f. = 4 (P = 0.52) I 2 = 0%
Test for overall effect: Z = 1.94 (P = 0.05)
0.0 0.50 1.0 50.0 100.0

Fig. 2 Forest plots of the odds of suicide with three different targeted interventions to prevent suicide v. control condition.
MDD, major depressive disorder; OPAC, outreach, problem solving, adherence and continuity; SI, suicidal ideation; w2, Cochrane’s Q; WHO BIC, World Health Organization brief
intervention and contact programme.
a. Programmes included: WHO BIC (educational intervention plus telephone or face-to-face contact with providers trained in suicide prevention), OPAC (a nurse specialising in
suicide prevention was assigned to follow the patient throughout the course of the intervention), and OSTA (regular telephone and letter contact with patient plus interprofessional
collaboration). Study duration ranged from 12 to 18 months.
b. Patients received between 5 and 12 sessions of the therapy intervention.
c. The study duration ranged from 1 month to 24 months.
d. The odds ratio has a skewed distribution. Although the lower end of the odds ratio is bounded by zero (an odds ratio cannot be negative), the upper end can reach infinity
(online supplemental reference139).

of lithium, 1 out of 313 patients in the intervention group and references70–72,131–133), and there was insufficient granularity to
6 out of 306 patients in the control group died by suicide. The compare specific pharmacotherapy agents.
results, however, were not statistically significant (OR = 0.23, 95%
CI 0.05–1.02, P = 0.05; IRR = 0.14, 95% CI 0.00–9.41, P40.1) Other interventions
(online Fig. 2 and online Table DS2) (online supplemental
We found no evidence that higher-level care interventions such as
references117–122). Several trials tested lithium in patients with
partial hospital admission (2 trials, n = 432; OR = 0.36, 95% CI 0.07–
depressive symptoms and suicidal behaviour (Fig. 2). With the
1.86, P40.10) (online supplemental references69,134,135) or somatic
exception of one trial that evaluated low-dose lithium (300 mg/
therapies such as electroconvulsive therapy (2 trials, n = 92;
day) (online supplemental references120), trials were designed to
OR = 0.14, 95% CI 0.00–6.82, P40.10) (online supplemental refer-
reach a target therapeutic lithium level (online supplemental
ences136,137) reduce the risk of suicide (online Fig. DS1). There were
references117–119,121,122). We identified no placebo-controlled trials
too few studies available to calculate an IRR for these interventions.
of clozapine for suicide prevention.
A large amount of data were included in pooled analyses
(6 trials, 23 016 person-years) to evaluate pharmacotherapy. The Sensitivity analysis
overall summary estimate yielded non-significant results We performed a sensitivity analysis in which we excluded trials
(IRR = 1.15, 95% CI 0.56–2.39, P40.10) (online supplemental that had one or more high risk for bias based on the Cochrane

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Riblet et al
Risk of Bias Tool (online supplemental references63–65,67,69,71,72,75–82,
84,86,88–91,93,94,96,97,99,101,104–108,110–114,116,118,119,134,137)
(online Table
DS1). This did not change our results in a substantial way, except
for our analysis of lithium trials. The results of the summary
estimate for lithium became statistically significant after removing a
more recent study (online supplemental references118) with several
methodological limitations (5 trials; OR = 0.13, 95% CI 0.03–0.66,
P = 0.01, test of heterogeneity P = 1.00 (Q = 0.01, I 2 = 0%)).
Reporting bias
We did not find any evidence to suggest publication bias among
complex psychosocial interventions, psychotherapy, intensive
follow-up strategies or CBT (Harbord’s modified test for small-study
effects; P = 0.20, P = 0.47, P = 0.57 and P = 0.71, respectively). We
were unable to formally assess for publication bias among the
remaining domains and sub-domains (as domains included
fewer than ten studies or most of the studies in the domain
reported no events).
Discussion
Summary of main results
The amount of research on suicide prevention, and specifically the
number of RCTs targeting suicide, has increased substantially over
the past decade. We located 56 RCTs of suicide prevention
strategies in adults that have been published since Mann et al’s
review.2 This suggests that more research using RCT methodology
is being done in the area of suicide prevention. Although most
interventions did not lead to a significant reduction in suicide,
we did find that the WHO’s BIC intervention was associated with
significantly lower odds of death by suicide. Although trials of
lithium and CBT for suicide prevention showed fewer deaths by
suicide among the intervention groups than the controls, we were
unable to draw any definitive conclusions, as the confidence
interval for the summary estimates spanned no difference. Trials
had several limitations. Most lithium trials had small sample sizes
(585 patients) and trials of CBT for suicide prevention were
generally of short duration (median 10.5 months). It is also worth
noting that the WHO’s BIC intervention may not be generalisable
to high-income countries, and that lithium was only studied in
patients with unipolar and bipolar depression.
Comparison with other studies
As with a meta-analysis of findings from the most recent
Cochrane review of psychosocial interventions for self-harm, we
found that CBT-based therapies were associated with lower odds
of suicide, but the results were not significant.8 Because these
authors did not perform a subgroup analysis, we cannot compare
our results for CBT for suicide prevention.8 Other reviews, how-
ever, have suggested that CBT for suicide prevention may prevent
suicidal behaviour in high-risk populations.2,4 Unlike prior
reviews, we found no evidence that problem-solving therapy or
dialectical behaviour therapy reduce the risk of suicide.2,3 Our
differing conclusions may reflect our focus on suicide deaths,
rather than on intermediary outcomes.
Consistent with others, we found that most psychosocial
interventions were ineffective,2,3 but we differed from Milner
et al 6 in that we found no evidence to support letter/telephone-
driven interventions. We believe the divergence in our results may
reflect our decision to evaluate postcard/telephone interventions
and intensive follow-up strategies separately.6 Furthermore, unlike
Mann et al 2 and Zalsman et al,3 we felt that there was strong
evidence that the WHO BIC programme was associated with
significantly lower odds of suicide. Our divergent conclusions
6
may reflect our inclusion of two additional RCTs and our focus
on death by suicide rather than on intermediary outcomes.2,3
Recently, Inagaki et al also reported that intensive follow-up
significantly reduced suicides.7 These authors, however, did not
specifically evaluate the WHO BIC programme.7
Akin to our results, a Cochrane review concluded that there is
an insufficient number of high-quality trials available to draw any
firm conclusions about the role of medications in patients who
self-harm.5 Although Zalsman et al reported that antidepressants
reduced the risk of suicide in adults,3 we did not replicate this
finding. The majority of RCTs of antidepressants included in
our review reported no suicides. In addition, unlike previous
reviews,2,3 we did not find that lithium significantly reduced
suicide. This may be explained by our inclusion of a recent RCT
with negative findings (online supplemental reference118).
Furthermore, although Mann et al 2 and Zalsman et al 3 concluded
that clozapine has an anti-suicidal effect, we did not replicate this
finding. This difference may reflect our decision to limit our
review to placebo-controlled trials. We located no placebo-
controlled trials of clozapine for suicide prevention. We also
focused our review on suicide deaths, rather than on intermediary
outcomes. Furthermore, prior reviews have relied heavily on the
results of the InterSePT study to support clozapine’s anti-suicidal
effect (online supplemental reference138).2 We excluded the
InterSePT study because clozapine was compared with olanzapine
(online supplemental reference138) rather than placebo. It is
notable, however, that the InterSePT study reported a higher
number of suicide deaths in the clozapine arm versus olanzapine,
although the results were not significant (online supplemental
reference138). Others have also raised concerns about the lack of
strong evidence to support clozapine’s anti-suicidal effect.32,33
Although many reviews stress the role of restricting access to
lethal methods in suicide prevention,2,3 we were unable to
systematically study this type of intervention because only one
study met our inclusion criteria. Restricting access to lethal means
such as gun control is not easily tested under randomised
conditions, although a plethora of observational data have
demonstrated that restricting access to lethal means can prevent
suicide.2,3 Finally, Zalsman et al concluded that other strategies
such as screening programmes and media education required
more testing.3 We were unable to assess these strategies because
no studies met our inclusion criteria.
Meaning and implications of the review
The WHO BIC intervention was associated with significantly
lower odds of suicide, but it will be important to test this strategy
in other populations. Although the summary estimates for CBT
for suicide prevention and lithium showed fewer deaths by suicide
among the intervention group than the control group, the results
were not statistically significant. Therefore, we believe our results
should be interpreted with caution.34 Our findings do not suggest
that lithium or CBT for suicide prevention cause harm, but they
also do not provide clear evidence of effectiveness. Our findings
suggest the need for further study of these interventions.
Strengths and weaknesses of the review
We performed a rigorous search of the literature and did not
exclude studies based on quality or relevance. This has been a
criticism of the Zalsman review.35 Although our focus on death
by suicide can be viewed as a strength,14,35 it is also a potential
limitation.13 RCTs offer the best evidence, but there are inherent
limitations in developing and testing targeted interventions to
address rare events such as suicide in the context of an RCT.13,18
Many studies were at risk for bias in their assessment of suicide,

and this may have obscured the true effect. Furthermore, for many
interventions there were insufficient data (i.e. limited number of
trials and/or small sample sizes) to draw any definitive conclusions
about their efficacy. In addition, owing to the small sample sizes,
we had poor precision around the summary estimate of the effect
size, further limiting our evaluation of these interventions. Since
our analysis did not include patient-level data, we were unable
to explore potential moderators or mediators of the efficacy of
suicide prevention interventions. Peto ORs can also yield biased
results when there are substantial differences in study arm sizes.
Reassuringly, the comparator arms of included RCTs were well
balanced. We did not calculate Peto ORs for pooled analysis
because of large differences in study arms. Finally, although many
novel approaches to suicide prevention (e.g. ketamine) are
emerging, no studies of these met our full inclusion criteria.
Overall, our review suggests that the WHO BIC intervention is
associated with significantly lower odds of suicide. Although trials
of CBT for suicide prevention and lithium showed fewer deaths by
suicide among the intervention groups than the controls, the
differences were not statistically significant. Available studies also
have several limitations that may threaten their internal and
external validity. More research is needed to evaluate the efficacy
of these and other interventions in a range of settings.
Natalie B. V. Riblet, MD, MPH, Brian Shiner, MD, MPH, Veterans Affairs Medical
Center, Vermont, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire,
and The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New
Hampshire, USA; Yinong Young-Xu, DSc, MS, Bradley V. Watts, MD, MPH,
Veterans Affairs Medical Center, Vermont, and Geisel School of Medicine at
Dartmouth, Hanover, New Hampshire, USA
Correspondence: Natalie Riblet, MD, MPH, Veterans Affairs Medical Center,
215 North Main Street, White River Junction, VT 05009, USA. Email:
Natalie.Riblet@dartmouth.edu
First received 14 May 2016, final revision 30 Jan 2017, accepted 4 Mar 2017
Funding
This work was supported by the VA National Center for Patient Safety Center of Inquiry
Program (PSCI-WRJ-SHINER). B.S. is the recipient of a VA Health Services Research and
Development Career Development Award (CDA11-263).
Acknowledgements
We thank Dr Gregory McHugo, Research Professor of Community and Family Medicine, and
of Psychiatry, of The Dartmouth Institute at the Geisel School of Medicine at Dartmouth, for
providing us with editing suggestions.
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Strategies to prevent death by suicide: a meta-analysis of randomised

controlled trials
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British Journal of Psychiatry doi: 10.1192/bjp.bp.116.187799

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1982;4:299-311.

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129. Verkes RJ, Van der Mast RC, Hengeveld MW, Tuyl JP, Zwinderman AH, Van Kempen GM.

Reduction by paroxetine of suicidal behavior in patients with repeated suicide attempts but not major

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130. Hallahan B, Hibbeln JR, Davis JM, Garland MR. Omega-3 fatty acid supplementation in patients

with recurrent self-harm: single-centre double-blind randomised controlled trial. Br J Psychiatry

2007; 190: 118-122.

131. Storosum JG, Wohlfarth T, Gispen-de Wied CC, Linszen DH, Gersons BPR, van Zwieten BJ, et

al. Suicide risk in placebo-controlled trials of treatment for acute manic episode and prevention of

manic-depressive episode. Am J Psychiatry 2005;162:799-802.

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132. Storosum JG, Van Zwieten BJ, Wohlfarth T, de Haan L, Khan A, Van den Brink W. Suicide risk

in placebo vs active treatment in placebo-controlled trials for schizophrenia. Arch Gen Psychiatry

2003;60:365-8.

133. Aursnes I, Tvete IF, Gaasemyr J, Natvig B. Suicide attempts in clinical trials with paroxetine

randomised against placebo. BMC Medicine 2005;3:1-5.

134. Jones G, Gavrilovic J, McCabe R, Becktas C, Priebe S. Treating suicidal patients in an acute

psychiatric day hospital: a challenge to assumptions about risk and overnight care. J Ment Health

2008;17(4):375-87.

135. van der Sande R, van Rooijen L, Buskens E, Allart E, Hawton K, van der Graaf Y, et al. Intensive

in-patient and community intervention versus routine care after attempted suicide: a randomised

controlled intervention study. Br J Psychiatry 1997;171:35-41.

136. George MS, Raman R, Benedek DM, Pelic CG, Grammer GG, Stokes KT, et al. A two-site pilot

randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS)

for suicidal inpatients. Brain Stimul 2014; 7: 421-31.

137. Nordenskjold A, Von Knorring L, Lyung T, Carlborg A, Brus O, Engstrom I. Continuation

electroconvulsive therapy with pharmacotherapy versus pharmacotherapy alone for prevention of

relapse of depression: a randomized controlled trial. J ECT 2013; 29: 86-92.

138. Meltzer HY, Alphs L, Green AI, Altamura AC, Anand R, Bertoldi A, et al. Clozapine treatment

for suicidality in schizophrenia: international suicide prevention trial (InterSePT). Arch Gen

Psychiatry 2003;60:82-91.

139. Bland JM, Altman DG. Statistics notes: the odds ratio. BMJ 2000; 320: 1468.

11
Table DS1 Methodological quality and results of trials evaluating suicide prevention strategiesa
Random Blinding of Blinding of Incomplete
sequence Allocation participants outcome outcome Selective Other
Author, Year OR (95%CI) generation Concealment & personnel assessment data Reporting Biases
Cognitive Behavioral Therapies
Blum, 2008 No events Low Unclear High Unclear Unclear Low Unclear

Brown, 2005 0.14 (0.00 – 6.82) Low Unclear Unclear Unclear Low Low Low

Davidson, 2010 0.77 (0.05 – 12.80) Low Low Unclear Low Low Low Unclear

Davidson, 2014 3.91 (0.05 – 328.91) Low Low Unclear Unclear Low Low Unclear

Grawe, 2006 No events Low Low High Unclear Low Unclear Unclear

Hawton, 1987 8.41 (0.17 – 426. 74) Unclear Unclear Unclear High Unclear Unclear Unclear

Husain, 2014 1.10 (0.15 – 7.93) Low Low Unclear Unclear Low Low Unclear

Linehan, 1991 6.80 (0.13 – 343.88) Unclear Unclear Unclear Unclear Unclear Unclear Unclear

Linehan, 2006 No events Low Unclear High Unclear Unclear Unclear Unclear

McAuliffe, 2014 0.49 (0.05 – 4.70) Low Low High Unclear Unclear Unclear High

McMain, 2012 No events Low Low Unclear Low Low Unclear Unclear

Morley, 2014 No events Unclear Low Unclear Unclear Unclear Unclear High

Power, 2003 1.00 (0.06 – 16.55) Unclear Unclear Unclear Low Low Unclear High

Raj, 2001 0.14 (0.00 – 6.82) High Unclear Unclear Unclear Unclear Unclear Unclear

Rudd, 1996 No events Unclear Unclear Unclear Unclear High Unclear Unclear

Rudd, 2015 1.00 (0.06 – 16.14) Low Unclear Unclear Low Low Unclear Unclear

Slee, 2008 0.14 ( 0.01 – 2.25) Low Low Unclear Unclear Unclear Low High
CBT: 6.84 (0.14 – 345.58)
Tarrier, 2006 Low Low Unclear High Unclear Unclear Low
Sup: 6.61 (0.41 – 107.35)
Tyrer, 2003 0.43 ( 0.10 – 1.92) Low Unclear High Unclear Low Low Unclear

Van Spijker, 2014 No events Low Low High High Low Low High

OR = Odds Ratio; 95%CI = 95 percent confidence interval; CBT = Cognitive Behavioral Therapy; Sup = Supportive Therapy
a. Based on the Cochrane Risk of Bias Tool; Low = low risk of bias; High = high risk of bias; Unclear= Insufficient evidence to judge risk of bias

Table DS1 Methodological quality and results of trials evaluating suicide prevention strategiesa (continued)
Random Blinding of Blinding of
sequence Allocation participants & outcome Incomplete Selective Other
Author, Year OR (95% CI) generation Concealment personnel assessment outcome data Reporting Biases
Non-Cognitive Behavioral Therapies
Gregory, 2008 0.14 (0.00 – 6.82) Low Unclear High Unclear Low Unclear High

Guthrie, 2001 No events Low Unclear Unclear Unclear Low Unclear Unclear
Gysin-Maillart,
1.00 (0.06 – 16.18) Low Low High Unclear Low Low Unclear
2016
Winter, 2007 0.83 (0.08 – 8.95) High High Unclear Unclear Unclear Unclear Unclear
Complex Psychosocial Interventions
Allard, 1992 2.79 (0.38 – 20.26) Unclear Low High Low Low Unclear High

Amadeo, 2015 0.12 (0.01 – 1.94) Low Unclear Unclear Low Low Low Unclear

Bertelsen, 2007 0.59 (0.13 – 2.67) Unclear Unclear Unclear Low Low Unclear Unclear

Carter, 2005 0.87 (0.26 – 2.85) Low Low High Low Low Unclear High

Cedereke, 2002 1.07 (0.07 – 17.32) Unclear Low High Low Low Unclear High

Clarke, 2002 1.12 (0.07 – 18.10) Low Unclear Unclear Unclear Low Unclear High

Connolly, 1996 1.42 (0.31 – 6.40) Unclear Unclear Unclear Unclear Unclear Unclear Unclear
Dekker, 2002 7.71 (0.48 – 125.04) Unclear Unclear Unclear Unclear Low Unclear Unclear

De Leo, 2007 No events Low Low High Unclear High Unclear High

Evans, 1999 1.92 (0.20 – 18.49) Unclear Low Unclear Low Low Unclear Unclear

OR = Odds Ratio; 95%CI = 95 percent confidence interval

a. Based on the Cochrane Risk of Bias Tool; Low = low risk of bias; High = high risk of bias; Unclear= Insufficient evidence to judge risk of bias

Table DS1 Methodological quality and results of trials evaluating suicide prevention strategiesa (continued)
Random Blinding of Blinding of
sequence Allocation participants & outcome Incomplete Selective Other
OR (95%CI) generation Concealment personnel assessment outcome data Reporting Biases
Complex Psychosocial Interventions (continued)
Fleischmann,
0.19 (0.08 – 0.45) Low Low Unclear Unclear Unclear Low Unclear
2008
Grimholt, 2015 1.41 (0.08 – 23.64) Low Low High Low Low Low High
Hassanian-
Moghaddam, 1.95 (0.63 – 6.07) Low Low Unclear Low Low Unclear Low
2015
Hvid, 2011 1.82 (0.19 – 17.88) Low Low Unclear Low Low Low High

Kawanishi, 2014 0.88 (0.52 – 1.51) Low Low High Low Low Low Unclear

Moller, 1992 1.61 (0.27 – 9.52) High Unclear Unclear Unclear Low Unclear Unclear

Morgan, 1993 No events Unclear Low Unclear High Low Unclear Unclear

Morthorst, 2012 7.21 (0.14 – 363.52) Low Low Unclear High Low Low High

Motto, 2001 1.13 (0.64 – 1.99) Unclear Unclear Unclear Low Low Unclear Unclear

Mouaffak, 2015 7.34 (0.15 – 369.95) Unclear Low High Low Low Unclear Unclear
Mousavi, 2014 0.29 (0.05 – 1.75) Unclear Unclear Unclear Unclear Unclear Low Unclear

Raue, 2010 6.50 (0.13 – 330.64) Low Unclear High Low Low Low Unclear

Schulberg, 2005 No events Low Low Unclear Unclear Low Unclear Unclear

Sun, 2012 1.06 (0.15 – 7.76) Unclear Low Unclear High High Unclear High

Unutzer, 2006 No events Low Low High Low Unclear Low Unclear

Vaiva, 2006 0.70 (0.07 – 6.99) Low Low High Low Low Unclear High
Van Heeringen,
0.85 (0.28 – 2.56) Low Unclear Unclear Low Low Unclear High
1995
Vijayakumar,
0.61 (0.08 – 4.58) Unclear Unclear Unclear Low High Unclear Unclear
2013
Walsh, 2001 1.23 (0.33 – 4.59) Unclear Low Unclear High Low Unclear High

OR = Odds Ratio; 95%CI = 95 percent confidence interval

a. Based on the Cochrane Risk of Bias Tool: Low = low risk of bias; High = high risk of bias; Unclear= Insufficient evidence to judge risk of bias

Table DS1 Methodological quality and results of studies evaluating strategies to prevent suicidea (continued)
Random Blinding of Blinding of
sequence Allocation participants & outcome Incomplete Selective Other
OR (95%CI) generation Concealment personnel assessment outcome data Reporting Biases
Higher Level Care Interventions
Bateman, 2008 0.12 (0.00 – 5.89) Unclear Unclear High High Unclear Unclear Unclear

Jones, 2008 0.40 (0.02 – 8.21) High Low High Low Low Unclear High
Van Der Sande,
0.49 (0.05 – 4.74) Low Low Unclear Low Low Unclear Unclear
1997
Somatic Therapies

George, 2014 No events Unclear Unclear Low Low Unclear Unclear Unclear
Nordenskjold,
0.14 (0.00 – 6.82) Low Low Unclear Unclear Low Unclear High
2013
Randomized Controlled Trials of Medications

Antidepressants

Hirsch, 1982 No events Unclear Unclear Unclear Unclear Unclear Unclear Unclear
Montgomery,
No events Unclear Unclear Low Unclear Unclear Unclear Unclear
1983
Nelson, 2007 No events Unclear Unclear Low Low Low Unclear Unclear

Phillips, 2009 No events Low Low Low Unclear Unclear Unclear Unclear

Rosenthal, 2013 No events Low Low Low Unclear Low Low Unclear

Verkes, 1998 0.13 (0.00 – 6.67) Unclear Unclear Low Unclear Low Low Low

Zisook, 2011 No events Unclear Unclear Low Low Low Unclear Unclear

Mood Stabilizers

Bauer, 2000 0.14 (0.00 – 7.31) Unclear Unclear Low Unclear Low Unclear Unclear

Girlanda, 2014 6.44 (0.13 – 327.93) Low Low Unclear Unclear High Low High

Khan, 2011 No events Low Low Low Unclear Low Low Low
Lauterbach,
0.13 (0.01 – 1.27) Low Unclear Low Unclear Unclear Low High
2008

OR = Odds Ratio; 95%CI = 95 percent confidence interval

a. Based on the Cochrane Risk of Bias Tool: Low = low risk of bias; High = high risk of bias; Unclear= Insufficient evidence to judge risk of bias
Table DS1 Methodological quality and results of studies evaluating strategies to prevent suicidea (continued)
Random Blinding of Blinding of
sequence Allocation participants & outcome Incomplete Selective Other
OR (95% CI) generation Concealment personnel assessment outcome data Reporting Biases
Mood Stabilizers (continued)
Prien, 1973a 0.12 (0.00 – 5.91) Unclear Unclear Unclear Low Unclear Unclear Unclear

Prien, 1973b 0.14 (0.00 – 7.02) Unclear Unclear Unclear Low Unclear Unclear Unclear

Nutritional Supplement
Hallahan,
No events Low Low Low Unclear Low Unclear Unclear
2007
Pooled Analysis of Randomized Controlled Trials of Medicationsb

Antidepressants

Aursnes, 2005 n/a Low Low Low Low Low Unclear Low

Hammad, 2006 n/a Low Low Low Low Low Unclear Low

Khan, 2007 n/a Low Low Low Low Low Unclear High

Antipsychotics

Khan, 2013 n/a Low Low Low Low Low Unclear High

Storosum, 2003 n/a Low Low Low Low Low Unclear Low

Mood Stabilizers

Storosum, 2005 n/a Low Low Low Low Low Unclear Low

OR = Odds Ratio; 95%CI = 95 percent confidence interval; N/A = not applicable

a. Based on the Cochrane Risk of Bias Tool; Low = low risk of bias; High = high risk of bias; Unclear= Insufficient evidence to judge risk of bias
b. Peto odds ratios could not be calculated for the results of individual pooled analysis of randomized controlled trials due to large imbalances in treatment arms.
Table DS2 Incidence rate ratios of death by suicide for various suicide prevention strategiesa

Intervention domain N IRR 95% Confidence Interval

Complex Psychosocial Interventions 29 0.93 0.65 – 1.33

Intensive follow-up programs 11 0.71 0.34 – 1.48

Comprehensive follow-up programs 5 0.30 0.07 – 1.22

Case management after suicidal behavior 4 0.93 0.56 – 1.54

Case management for psychosis 4 1.16 0.50 – 2.55

Letter/Phone Contact 7 1.16 0.75 – 1.79

Psychotherapyb 24 0.79 0.41 – 1.53

Cognitive Behavioral Therapies 20 0.72 0.34 – 1.53

Cognitive Behavioral Therapy-Suicide Prevention 6 0.30 0.08 – 1.11

 Problem Solving Therapy 4 1.00 0.25 – 4.04

Non-Cognitive Behavioral Therapies 5 1.10 0.27 – 4.38

Medications (Randomized Trials) 14 0.10 0.00 – 32.27

Lithium 6 0.14 0.00 – 9.41

Medications (Pooled Analysis) 6 1.15 0.56 – 2.39

IRR = incidence rate ratio; N = number of studies

a. There were too few studies to calculate IRR for the following domains: means restriction; cognitive behavioral therapies (except for cognitive behavioral therapy designed to address
suicidal behavior and problem solving therapy); non-cognitive behavioral therapies; aftercare; other types of intensive follow-up programs, primary mental health integrated care; nursing-
led caregiver education; higher-level care; somatic therapies, and medications by type (except for lithium).
b. A third arm of the CBT trial conducted by Tarrier et al (online supplemental references107) evaluated supportive therapy for psychosis. This arm was included in the analysis of non-CBT
therapies.
Fig. DS1
Systematic Review and Meta-Analysis Protocol

Appendix DS1

Title: Strategies to prevent death by suicide: a meta-analysis of randomized controlled trials

Authors: Riblet NB, Shiner B, Young-Xu Y, Watts BV

Introduction:

Suicide is a significant public health concern in the United States. The Centers for Disease

Control estimates that over 30,000 people die by suicide each year in the U.S.1 Suicide is also the

tenth leading cause of death among people of all ages1 and the third leading cause of death among

adolescents ages 15 to 24 years old.1 Suicidal behavior is associated with significant costs to

society with an estimated annual loss of 34.6 billion dollars due to healthcare costs and lost

earnings.2 Caring for a loved one who is suicidal can also cause considerable emotional toll on

family members and loved ones.3

Although many strategies have been proposed to prevent suicide, the efficacy of these various

interventions remains unclear.4-5 For example, antidepressants may have a protective effect in

mood disorders but these findings are largely based on studies which are underpowered and of

short duration.5 Similarly, it is unclear whether antipsychotics or mood stabilizers have an anti-

suicidal effect.5 The role of behavioral interventions and more comprehensive suicide prevention

programs in reducing suicide also remains unclear. Safer packaging of medications has shown

some promise but these studies may be limited by confounding and inadequate duration.6

In 2005, Mann et al published a comprehensive systematic review of all available suicide

prevention strategies.7 These authors concluded that there was evidence to support the following

interventions including physician education in depression recognition, gatekeeper education and

lethal means restriction.7 The authors, however, determined that the efficacy of individual

components of multifaceted strategies for suicide prevention remains unclear.7

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Systematic Review and Meta-Analysis Protocol

Since Mann et al’s review, there have been several additional studies of suicide prevention

interventions. These studies continue to produce mixed results. For example, a randomized

controlled trial of a worldwide disseminated gatekeeper training called ASIST found that there

was no significant improvement in gatekeeper knowledge about suicide prevention with this

training.8 On the other hand, a randomized controlled trial of a brief psychological intervention

after self harm found that the therapeutic intervention was associated with a significant (and

sustained) reduction in symptoms of suicidal ideation.9

Our current review provides an update to the previous comprehensive systematic review

completed by Mann et al in 2005.7 We have used the conceptual framework previously developed

by Mann et al to understand and to evaluate existing strategies for suicide prevention.7 Our aim is

to provide a complete and all-inclusive summary of all of the available evidence for interventions

to prevent suicide. We believe that this information will help inform clinical decisions about

suicide prevention and illuminate areas in need of additional research.

Research Question: Among adults 18 years and older (P), which interventions that are designed

to prevent death by suicide (or suicidal behavior or ideation) (I) have greater efficacy than usual

care condition, placebo or waitlist (C) at preventing death by suicide (O)?

STUDY INCLUSION CRITERIA

Inclusion Criteria Table & Outcomes of Interest:

Category Inclusion Criteria Justification/Explanation Order

Study Design: Randomized While RCTs are not ideal for studying a rare 1

Controlled Trials outcome such as death by suicide, we will

(RCTs), pooled limit our review to this study design because

analysis of RCTs RCTs are the highest quality study design

and the gold standard for evaluating the

efficacy of an intervention.10-11 We will also

Page 2 of 23
Systematic Review and Meta-Analysis Protocol

include the results of pooled analysis of

RCTs of pharmacological interventions to

better understand the role of medications in

preventing death by suicide. We have chosen

this approach because death by suicide is a

rare outcome and individual drug trials are

unlikely to be powered to evaluate for this

particular outcome but pooled analysis using

a systematic approach to identify death by

suicide in drug trials may offer unique

insights.

Population Any adult age 18 Since the risk for death by suicide spans all 2

and older types of adult populations and covers a wide

range of risk factors (e.g. known mental

health problems, access to lethal means,

Veteran status), we plan to broaden our

population to include interventions targeted

at reducing risk for suicide in all adults over

the age of 18. 11 In order to be comprehensive

and include as many studies as possible, we

will include studies if the total population (or

the large majority) was 18 years and older.

We have decided to exclude children and

adolescents from our review since this

population may have uniquely different

Page 3 of 23
Systematic Review and Meta-Analysis Protocol

responses to potential therapeutic

interventions to prevent death by suicide.

Therefore, a comprehensive review of

interventions to prevent death by suicide in

the child/adolescent population would be

warranted but is beyond the scope of the

current review.

Intervention: Interventions We will use a framework based on the work 3

targeted at presented by Mann et al’s in their systematic

preventing death by review of the literature.7 These interventions

suicide (or suicidal fall into the following major categories:7

behavior or 1) Education and Awareness Programs

ideation) in a 2) Screening for individuals at high risk

population 3) Pharmacotherapy

4) Psychotherapy

5) Follow-up Care for Suicide Attempts

6) Restriction of Access to Lethal Means

7) Media Reporting Guidelines for suicide

If necessary, we will create additional

domains and sub-domains (or remove

domains) based on consensus if we identify

new interventions which were not covered

in Mann et al’s review and do not readily fit

into the domains developed in their review

or we identify that there are certain domains

Page 4 of 23
Systematic Review and Meta-Analysis Protocol

which were not studied using a randomized

design methodology.7

Comparison Usual care or Since the primary concern in the literature is 4

placebo condition whether any suicide prevention strategies are

(placebo or sham) effective, we will include as our comparator

or waitlist arm usual care condition or placebo or

waitlist. Usual care may include any

intervention that would be considered

standard of care based on current clinical

practice and would be unethical to withhold

from a patient. This may include typical

supportive care interventions such as routine

visits with a physician and provider

education as well as allowing patients to seek

out psychotherapy or continue taking

pharmacological agents. Similarly, we will

allow waitlist comparison. We will also

allow the comparison arm to include placebo

or sham as this would be relevant (and

expected) in the case of pharmacotherapy

trials or somatic therapies such as

electroconvulsive therapy and transcranial

magnetic stimulation. Since there is limited

knowledge about the efficacy of any

available interventions to prevent death by

Page 5 of 23
Systematic Review and Meta-Analysis Protocol

suicide, we have not included active

treatment as a comparison. The aim of this

review is to identify which interventions are

superior to standard treatment. Our review

will not address issues of equivalency or

non-inferiority. We will, however, briefly

summarize in a qualitative fashion the results

of trials that evaluate active treatment as

comparison.

Outcomes: Death by suicide We will require that included studies report 5

on death by suicide. While studies are more

likely to report on intermediary outcomes

such as suicidal behavior or suicidal ideation,

these outcomes are known to be more

susceptible to measurement bias.12

Furthermore, it is clear that from a societal

perspective the prevention of death by

suicide is the most relevant clinical

outcome.1-2 To broaden our search and be as

inclusive as possible, we will include studies

that report death by suicide as a primary

outcome or a secondary outcome. In the

event that death suicide was a secondary

outcome, we will require that the primary

aim of the report included the prevention of

Page 6 of 23
Systematic Review and Meta-Analysis Protocol

suicidal ideation and/or suicidal behavior.

We have selected this method to help

minimize biases due to the fact that these

studies will be far less likely to be powered

to evaluate for death by suicide. In addition,

we will exclude a study if they do not clearly

state whether or not death by suicide

occurred in one or both arms (i.e. we will not

assume that no mention of death by suicide

means no death by suicide occurred).

However, to be as inclusive as possible, we

will include studies even if the methods that

they used to assess for death by suicide were

at higher risk for bias (e.g. informants, chart

review). Finally, given that death by suicide

is a rare outcome, we will include studies

even if they report that no events (death by

suicide) occurred in either arm.

Outcomes of Interest:

Primary Outcome:

Odds of death by suicide

Justification: This is the most relevant question with regards to whether suicide

prevention strategies are effective.1-2

Search Strategy:

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Systematic Review and Meta-Analysis Protocol

Databases:

We used the following databases for our review including Medline (via Ovid), the

Cochrane Library, PsycINFO, Excerpta Medica Database (EMBASE) and The

Cumulative Index to Nursing and Allied Health Literature (CINAHL).

Search terms:

We used exploded MeSH terms and key words to generate the following themes: suicide,

prevention and control and treatment. We then used “OR” to combine the theme

prevention and control and treatment and the Boolean term “AND” to find their

intersection with the theme suicide (see search strategy below). We applied this approach

during our search of the Medline database and modified our approach as necessary to

search the Cochrane Library, PsycINFO, EMBASE, CINAHL and clinicaltrials.gov.

Limits:

We applied a randomized controlled trial limit in our search of the Cochrane Library.

Special Strategies:

We applied Cochrane’s recommended highly sensitive search strategy for identifying

randomized controlled trials in our Medline, EMBASE and PsycINFO search because our

original search yielded an unfeasible number of studies to search manually.13-16 Similarly,

we applied a sensitive search strategy for identifying randomized controlled trials in

CINAHL recommended by the Scottish Intercollegiate Guidelines Network.17

Results of Search Strategy:

Using the above search terms, we identified 11,866 potentially eligible studies through

our electronic database searching. Details of the structure and findings of our various

search strategies are provided below (see search strategy).

Additional Search methods:

In order to identify relevant published and unpublished studies which may have been

missed in our preliminary search, we searched clinicaltrials.org and manually reviewed

Page 8 of 23
Systematic Review and Meta-Analysis Protocol

references of relevant articles. The results of our clinicaltrials.gov search and reference

review are provided below (see search strategy).

Prior Reviews:

There have been several prior reviews of this topic both in the general population as well as in

specific subpopulations such as Veterans.4-7 The most recent comprehensive systematic review

that has been published, however, was the review undertaken by Mann et al in 2005.7 We feel

that updating the work of Mann et al is important since there have been several additional

randomized controlled trials which have been published since 2005 which may help shed

additional light on this topic.8-9

Results of Preliminary Search

We have provided an example of an abstract that we located during our initial search which meets

all of our inclusion criteria (see preliminary abstracts).

Protocol Amendments:

Since our protocol was written, we have made one amendment. Please see the protocol

amendments section below for further details.

Page 9 of 23
Systematic Review and Meta-Analysis Protocol

Search Terms Table

Theme MeSH Terms Key Words

Suicide Suicidal Ideation, Suicide, Attempted, Suicide Suicide

Prevention and Health education, Health promotion, mass
control screening, risk assessment, school health
services, student health services, firearms, gas
poisoning, pesticides, drug overdose, mass
media, harm reduction, emergency services,
hospital,
Health education, Health
promotion, Mass screening,
risk assessment, school
health services, student
health services, firearms, gas
poisoning, pesticide, drug
overdose, mass media, harm
reduction, emergency service
hospital, means restriction,
restricted access, media,
suicide prevention

pc.fs (free floating

subheading of prevention &
control)

Treatment antidepressive agents/pd [pharmacology], serotonin uptake inhibitors,

serotonin uptake inhibitors, antipsychotic ECT, TCA, SSRI, MAOI,
agents/pd [pharmacology], psychotropic CBT, rTMS, ketamine, VNS,
drugs/pd [pharmacology], antimanic vagus nerve stimulator,
agents/pd [pharmacology], electroconvulsive TENS
therapy, monoamine oxidase inhibitors/pd
[pharmacology], psychotherapy, cognitive
therapy, transcranial magnetic stimulation,
ketamine, vagus nerve stimulation,
transcutaneous electric nerve stimulation

Search Strategy

Page 10 of 23
Systematic Review and Meta-Analysis Protocol

Database: Ovid MEDLINE(R) inception (1945) to Present (December 31, 2015)

The search strategy was created with assistance from a Librarian at the Dartmouth Hitchcock
Medical Library

Number Search terms

1 Suicide.mp or exp Suicide/ or exp Suicide, Attempted/

2 Suicidal ideation.mp or exp Suicidal Ideation/

3 1 or 2

4 Health education.mp or exp Health Education/

5 Health promotion.mp or exp Health Promotion/

6 Mass screening.mp or exp Mass Screening/
7 Risk assessment.mp or exp Risk Assessment/

8 Student health services.mp or exp Student Health Services/

9 Firearms.mp or exp Firearms/

10 Gas poisoning.mp or exp Gas Poisoning/
11 Pesticides.mp or exp Pesticides/

12 Drug overdose.mp or exp Drug Overdose/

13 Mass media.mp or exp Mass Media/
14 Harm reduction.mp or exp Harm Reduction/

15 Emergency service hospital.mp or exp Emergency Service, Hospital/

16 Means restriction.mp

17 Restricted access.mp
18 Media.mp

19 Suicide prevention.mp

20 Exp Antidepressive Agents/pd [Pharmacology/]

21 Exp Serotonin Uptake Inhibitors/pd [Pharmacology/]

22 Serotonin uptake inhibitors.mp

23 Exp Antipsychotic Agents/pd [Pharmacology/]

24 Exp Psychotropic Drugs/pd [Pharmacology/]

25 Exp Antimanic Agents/pd [Pharmacology/]

26 Exp Electroconvulsive Therapy/ or ECT.mp

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Systematic Review and Meta-Analysis Protocol

27 Exp Monoamine Oxidase Inhibitors/pd [Pharmacology/]

28 Exp Psychotherapy/

29 Exp Cognitive Therapy/

30 TCA.mp
31 SSRI.mp

32 MAOI.mp

33 CBT.mp

35 Exp Transcranial Magnestic Stimulation/ or rTMS.mp

36 Ketamine.mp or exp.Ketamine/
37 VNS.mp or exp Vagus Nerve Stimulation/

38 Exp Transcutaneous Electric Nerve Stimulation/

39 Vagus nerve stimulator.mp

40 TENS.mp

41 Pc.fs

4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14 OR 15
OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 OR 23 OR 24 OR 25
42
OR 26 OR 27 OR 28 OR 29 OR 30 OR 31 OR 32 OR 33 OR 34 OR 35
OR 36 OR 37 OR 38 OR 39 OR 40 OR 41

43 3 and 42 (Citations located = 21,469)

(randomized controlled trial.pt OR controlled clinical trial.pt OR
44 randomized.ab OR placebo.ab OR drug therapy.fs. OR randomly.ab OR
trial.ab OR groups.ab)
45 Exp animals/not humans.sh

46 #44 NOT #45

47 46 and 43 (Citations located = 4,641)

*Of note we applied Cochrane’s recommended highly sensitive search strategy for identifying
randomized controlled trials (Line 44, 45, 46) because our original search yielded unfeasible
number of studies to search manually.13

EMBASE Search:

Dates Searched: Inception thru December 31, 2015

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Systematic Review and Meta-Analysis Protocol

Search terms were adapted from our Medline search to conform with Emtree and applied as

follows: (Suicide OR Suicidal Ideation OR Suicide Attempt) AND (health education OR health

promotion OR mass screening OR risk assessment OR health service OR firearms OR gas

poisoning OR pesticide OR drug overdose OR mass media OR harm reduction OR emergency

health service OR means restriction OR restricted access OR media OR suicide prevention OR

suicide prevention and control OR antidepressive agents OR serotonin uptake inhibitor OR

neuroleptic agent OR psychotropic drugs OR tranquilizer OR electroconvulsive therapy OR

monoamine oxidase inhibitor OR psychotherapy OR cognitive therapy OR TCA OR SSRI OR

MAOI OR CBT OR transcranial magnetic stimulation OR ketamine OR rTMS OR VNS OR

vagus nerve stimulation OR vagus nerve stimulator OR transcutaneous nerve stimulation OR

TENS) AND (random$ OR factorial$ OR crossover$ OR cross over$ OR cross-over$ OR

placebo$ OR doubl$ adj blind$ OR singl$ adj blind$ OR assign$ OR allocat$ OR volunteer$ OR

crossover-procedure OR double-blind procedure OR randomized controlled trial OR single-blind

procedure)

Search Strategy: We used the same search approach as described in our search of Medline but as

described above modified the search to conform with Emtree. Furthermore, because our original

search yielded an unfeasible number of citations to search by hand, we applied a sensitive search

strategy recommended by Cochrane for identifying randomized controlled trials.14

Total Citations Located (no limits): 33,832

Total Citations Located (sensitive strategy recommended by Cochrane): 3,297

PsycINFO Search

Dates Searched: Inception thru December 31, 2015

Search Terms: (Suicide OR Suicidal Ideation OR Suicide Attempt) AND (health education OR

health promotion OR mass screening OR risk assessment OR student health services OR firearms

OR gas poisoning OR pesticides OR drug overdose OR mass media OR harm reduction OR

emergency service hospital OR means restriction OR restricted access OR media OR suicide

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Systematic Review and Meta-Analysis Protocol

prevention OR antidepressive agents OR serotonin uptake inhibitors OR antipsychotic agents OR

psychotropic drugs OR antimanic agents OR electroconvulsive therapy OR monoamine oxidase

inhibitors OR psychotherapy OR cognitive therapy OR SSRI OR MAOI OR CBT OR TCA OR

transcranial magnetic stimulation OR ketamine OR rTMS OR VNS OR vagus nerve stimulation

OR vagus nerve stimulator OR transcutaneous electric nerve stimulation OR TENS) AND

(SU.EXACT (“Treatment Effectiveness Evaluation”) OR SU.EXACT.EXPLODE (“Treatment

Outcomes”) OR SU.EXACT(“Placebo”) OR SU.EXACT(“Followup Studies”) OR placebo* OR

random* OR “comparative stud*” OR clinical NEAR/3 trial* OR research NEAR/3 design OR

evaluat* NEAR/3 stud* OR prospectiv* NEAR/3 stud* OR (singl* OR doubl* OR trebl* OR

tripl*) NEAR/3 (blind* OR mask*))

Search Strategy: We used the same search approach as described in our search of Medline. We

applied a sensitive search strategy recommended by Cochrane for identifying randomized

controlled trials in PsycINFO.15-16

Total Citations Located (no limits)—19,592

Total Citations Located (with sensitive search strategy recommended by Cochrane)---1,525

CINAHL Search:

Dates Searched: Inception thru December 31, 2015

Search Terms: (Suicide OR Suicidal Ideation OR Suicide Attempt) AND (health education OR

health promotion OR mass screening OR risk assessment OR student health services OR firearms

OR gas poisoning OR pesticides OR drug overdose OR mass media OR harm reduction OR

emergency service hospital OR means restriction OR restricted access OR media OR suicide

prevention OR antidepressive agents OR serotonin uptake inhibitors OR antipsychotic agents OR

psychotropic drugs OR antimanic agents OR electroconvulsive therapy OR monoamine oxidase

inhibitors OR psychotherapy OR cognitive therapy OR SSRI OR MAOI OR CBT OR TCA OR

transcranial magnetic stimulation OR ketamine OR rTMS OR VNS OR vagus nerve stimulation

OR transcutaneous electric nerve stimulation OR vagus nerve stimulator OR TENS) and ((MH

Page 14 of 23
Systematic Review and Meta-Analysis Protocol

“Clinical Trials+”) OR PT Clinical Trial OR TX clinic* n1 trial* OR (TX ((singl* n1 blind*) or

(singl* n1 mask*)) or TX ((doubl* n1 blind*) or (doubl* n1 mask*)) OR TX ((tripl* n1 blind*)

or (tripl* n1 mask*)) or TX ((trebl* n1 blind*) or (trebl* n1 mask*)) OR TX randomi* control*

trial* OR (MH “Random Assignment”) OR TX random* allocate* OR TX placebo* OR (MH

“Placebos”) OR (MH “Quantitative Studies”) or TX allocate* random*)

Search strategy: We used the same search approach as described in our search of Medline. We

then applied a search filter limit to identify randomized trials recommended by the Scottish

Intercollegiate Guidelines Network.17

Total Citations Located (no limits)—8,212

Total Citations Located (with sensitive search strategy from SIGN)--- 2,171

Cochrane Library Search:

Dates Searched: Inception thru December 31, 2015

Search Strategy: Search Terms: (Suicide OR Suicidal Ideation OR Suicide Attempt) AND

(health education OR health promotion OR mass screening OR risk assessment OR student health

services OR firearms OR gas poisoning OR pesticides OR drug overdose OR mass media OR

harm reduction OR emergency service hospital OR means restriction OR restricted access OR

media OR suicide prevention OR antidepressive agents OR serotonin uptake inhibitors OR

antipsychotic agents OR psychotropic drugs OR antimanic agents OR electroconvulsive therapy

OR monoamine oxidase inhibitors OR psychotherapy OR cognitive therapy OR SSRI OR MAOI

OR CBT OR TCA OR transcranial magnetic stimulation OR ketamine OR rTMS OR VNS OR

vagus nerve stimulation OR vagus nerve stimulator OR transcutaneous electric nerve stimulation

OR TENS)

Search Strategy: The Cochrane reports that an RCT filter is not required because all the records

are thoroughly and correctly indexed. Therefore, we only applied a randomized controlled trial

limit in our search. 18

Total Citations Located (no limits)—2,160

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Systematic Review and Meta-Analysis Protocol

Total Number (with RCT limits applied): 232

Clinical Trials.gov:

Dates: Inception thru December 31, 2015

Search Strategy: “suicide & prevention”

Results

o Three trials-no usable data

o Thirteen trials-ongoing/actively recruiting

Reference Review

Additional references located: Three

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Systematic Review and Meta-Analysis Protocol

Preliminary Abstracts

Abstract

Authors: Vijayakumar L, Jeyaseelan L, Kumar S, Mohanraj R, Devika S, Manikandan S. A

central storage facility to reduce pesticide suicides--a feasibility study from India. BMC Public

Health 2013; 13: 850.

Background: Pesticide suicides are considered the single most important means of suicide

worldwide. Centralized pesticide storage facilities have the possible advantage of delaying access

to pesticides thereby reducing suicides. We undertook this study to examine the feasibility and

acceptability of a centralized pesticide storage facility as a preventive intervention strategy in

reducing pesticide suicides.

Methods: A community randomized controlled feasibility study using a mixed methods

approach involving a household survey; focus group discussions (FGDs) and surveillance were

undertaken. The study was carried out in a district in southern India. Eight villages that engaged

in floriculture were identified. Using the lottery method two were randomized to be the

intervention sites and two villages constituted the control site. Two centralized storage

facilities were constructed with local involvement and lockable storage boxes were

constructed. The household survey conducted at baseline and one and a half years later

documented information on sociodemographic data, pesticide usage, storage and suicides.

Results: At baseline 4446 individuals (1097 households) in the intervention and 3307 individuals

(782 households) in the control sites were recruited while at follow up there were 4308

individuals (1063 households) in the intervention and 2673 individuals (632 households) in the

control sites. There were differences in baseline characteristics and imbalances in the prevalence

of suicides between intervention and control sites as this was a small feasibility study.The results

from the FGDs revealed that most participants found the storage facility to be both useful and

acceptable. In addition to protecting against wastage, they felt that it had also helped prevent

pesticide suicides as the pesticides stored here were not as easily and readily accessible. The

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Systematic Review and Meta-Analysis Protocol

primary analyses were done on an Intention to Treat basis. Following the intervention, the

differences between sites in changes in combined, completed and attempted suicide rates per

100,000 person-years were 295 (95% CI: 154.7, 434.8; p < 0.001) for pesticide suicide and 339

(95% CI: 165.3, 513.2, p < 0.001) for suicide of all methods.

Conclusions: Suicide by pesticides poisoning is a major public health problem and needs

innovative interventions to address it. This study, the first of its kind in the world, examined the

feasibility of a central storage facility as a means of limiting access to pesticides and, has

provided preliminary results on its usefulness. These results need to be interpreted with caution in

view of the imbalances between sites. The facility was found to be acceptable, thereby

underscoring the need for larger studies for a longer duration.

Confirmation Table

Category Inclusion Criteria Criteria Met

Study Design: RCTs and pooled analysis of RCT

RCTs.

Population Any adult age 18 and older Population in India at risk for

suicide including adults

Intervention: Interventions targeted at Centralized storage facility for

preventing death by suicide (or pesticide

suicidal behavior or ideation)

in a population

Comparison Usual care or placebo Usual care/No storage facility

condition (placebo or sham) or

waitlist

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Systematic Review and Meta-Analysis Protocol

Outcomes: Death by suicide Evaluated death by suicide as an

outcome

Page 19 of 23
Systematic Review and Meta-Analysis Protocol

Protocol Changes

Date

Section of Protocol Original version New version

Type of amendment* Justification

October 15, 2016 We searched Based on feedback from

Search Strategy Medline, Cochrane reviewers, we added these

-Included additional databases in Library, and additional databases and

including EMBASE and PsycINFO from revised our search strategy to

CINAHL in addition to Medline, inception through increase the likelihood that we

Cochrane Library and PsycINFO December 31, 2015 would capture all relevant

-expanded our search terms to studies. Because we located an

include the key word “suicide unfeasible number of citations

prevention” in all our electronic to manually search after

database searches (in the case of applying the aforementioned

EMBASE we used suicide search strategies, we also

prevention as an emtree term). incorporate recommended

“Suicide prevention” is not a highly sensitive search strategy

MeSH term in Medline so we for identifying RCTs in our

could only use it as a keyword. various electronic searches.

-We used a highly sensitive

search strategy recommended by

Cochrane to identify RCTs in

Medline, EMBASE and

PsycINFO. We will use a search

strategy for identifying RCTs in

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Systematic Review and Meta-Analysis Protocol

CINAHL recommended by the

recommended by the Scottish

Intercollegiate Guidelines

Network.

*Amendments may include additions, deletions, changes, and/or clarifications

References

1. Centers for Disease Control and Prevention. National Center for Injury Prevention and

Control. Suicide facts at a glance, 2012

(http://www.cdc.gov/ViolencePrevention/pdf/Suicide_DataSheet-a.pdf).

2. Centers for Disease Control and Prevention. National Center for Injury Prevention and

Control. Web-based Injury Statistics Query and Reporting System (WISQARS), 2010

( http://wisqars.cdc.gov/:8080/costT/).

3. McLaughlin C, McGowan I, O’Neill S, Kernohan G. The burden of living with and

caring for a suicidal family member. J Ment Health 2014; 23: 236-240.

4. Ernst CL, Goldberg JF. Antisuicide properties of psychotropic drugs: a critical review.

Harv Rev Psychiatry 2004; 12: 14-41.

5. Bagley SC, Munjas B, Shekelle P. A systematic review of suicide prevention programs

for military or veterans. Suicide Life Threat Behav 2010; 40: 257-265.

6. Scott A, Guo B. For which strategies of suicide prevention is there evidence of

effectiveness? World Health Organization HEN Synthesis Report, 2012

(http://www.euro.who.int/__data/assets/pdf_file/0003/168843/HEN-Suicide-Prevention-

synthesis-report.pdf).

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Systematic Review and Meta-Analysis Protocol

7. 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.

8. Sareen J, Isaak C, Bolton SL, Enns MW, Elias B, Deane F, et al. Gatekeeper training for

suicide prevention in First Nations community members: a randomized controlled trial.

Depress Anxiety 2013; 10: 1021-29.

9. Husain N, Afsar S, Ara J, Fayyaz H, Rahman RU, Tomenson B, et al. Brief psychological

intervention after self-harm: randomized controlled trial from Pakistan. Br J Pyschiatry

2014; 6:462-70.

10. Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Designing Clinical

Research. Lippincott Williams & Wilkins, 2013.

11. Jacobs DG, Baldessarini RJ, Conwell Y, Fawcett JA, Horton L, Meltzer H, et al. Practice

Guidelines for the Assessment and Treatment of Patients with Suicidal Behaviors. APA,

2010

(http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/suicide

.pdf).

12. Glenn CR, Nock MK. Improving the short-term prediction of suicidal behavior. Am J

Prev Med 2014; 47: S176-80.

13. Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies, Box 6.4.c:

Cochrane Highly Sensitive Search Strategy for identifying randomized trials in

MEDLINE: sensitivity-maximizing version (2008 revision); Ovid format. In: Higgins

JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions

Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011.

(www.cochrane-handbook.org)

14. Lefebvre C, Manheimer E, Glanville J. Chapter 6.4.11.2 Search filters for identifying

randomized trials in EMBASE. In: Higgins JPT, Green S (editors). Cochrane Handbook

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for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The

Cochrane Collaboration, 2011. (www.cochrane-handbook.org)

15. Watson RJ, Richardson PH. Identifying randomized controlled trials of cognitive therapy

for depression: comparing the efficiency of Embase, Medline and PsycINFO

bibliographic databases. Br J Med Psychol 1999; 72(Pt 4): 535 - 42.

16. Identifying RCTs in PsycINFO. Search strategy, amended to ProQuest format.

(http://work.cochrane.org/psycinfo)

17. Scottish Intercollegiate Guidelines Network Healthcare Improvement. Search Filters.

http://www.sign.ac.uk/methodology/filters.htm#random

18. Cochrane Work. RCT filters for different databases. (http://work.cochrane.org/rct-filters-

different-databases)

Page 23 of 23
Appendix DS2

Excluded Studies

Table 1: Randomized trials comparing an intervention versus active control for suicide prevention. (horizontal position)

Study Number of suicides Study arm

Author, year N Study Population Intervention Comparison Significance
Duration by study arm favored

Psychotherapy

Rogerian
Cognitive
Cottraux, 20085 65 BPD 24 months Supportive No events Neither NS
Therapy
Therapy

BPD, PTSD & self-

Harned, 20141 26 15 months DBT + PE DBT DBT – 1 Neither NS
injury

Breast cancer plus Behavioral

Hopko, 20134 80 24 months PST No events Neither NS
MDD Activation

CBT for Cognitive

Klingberg, 20122 198 Schizophrenia 12 months No events Neither NS
psychosis remediation

Arm 2: DBT-I
BPD plus ≥2 SA
Linehan, 20153 99 24 months DBT-S Arm 3: Standard Standard DBT - 1 Neither NS
&/or NSSI
DBT
Antidepressants
Moderate-Severe
Perroud, 20096 811 Unipolar 3 months Escitalopram Nortriptyline Nortriptyline – 1 Neither NS
Depression
Rucci, 20117 291 Nonpsychotic MDD 4 months IPT Escitalopram No events Neither NS

Arm 2: Bupropion
SR plus
Nonpsychotic
Escitalopram Escitalopram;
Zisook, 20118 665 chronic &/or 7 months No events Neither NS
plus placebo Arm3:
recurrent MDD
Venlafaxine XR
plus Mirtazapine

Antipsychotics

Schizophrenia &
Paliperidone Daily oral
Alphs, 20159,a 450 history of 15 months No events Neither NS
palmitate antipsychotics*
incarceration

Low dose Ultra-low dose

Seen in ER after
Battaglia, 199910,b 58 6 months Fluphenazine Fluphenazine No events Neither NS
recent SA
decanoate decanoate

Schizophrenia or Physician’s LAI-R – 1;

Buckley, 201511,c 305 30 months LAI-R Neither NS
SCAD choice oral SGA SGA – 1

Arm 2:
Aripiprazole – 1;
Crespo-Facorro, First Episode Ziprasidone
202 12 months Aripiprazole Ziprasidone – 1; Neither NS
201412 Schizophrenia Arm 3:
Quetiapine - 2
Quetiapine

Meltzer, 2003 Schizophrenia and Clozapine – 5;

980 24 months Clozapine Olanzapine Neither NS
(InterSePT) 13 high risk for suicide Olanzapine – 3

ITT: RR 1.19
Schizophrenia (0.61-2.31)
Strom, 201114 18,154 (seen in naturalistic 12 months Ziprasidone Olanzapine Time on assigned Neither NS
practice) treatment
RR: 1.37 (0.66 – 2.85)
Thomas, 201015 9,858 Schizophrenia 14,147 PY Sertindole Risperidone HR 0.72 (0.36 – 1.41) Neither NS

Mood Stabilizers

Bipolar Disorder Lithium– 0;

Oquendo, 201116 98 30 months Lithium Valproate Neither NS
plus prior SA Valproate - 0

Arm 2:
Thies-Flechtner, Lithium– 0;
MDD, Bipolar Amitriptyline;
1996d 378 30 months Lithium Carbamazepine - 4; Lithium NS
Disorder or SCAD Arm3:
(MAP Study) 17 Other medications – 5
Carbamazepine

BPD = Borderline Personality Disorder; CBT = Cognitive Behavioral Therapy; DBT = Dialectical Behavior Therapy; DBT-S: DBT skills training; DBT-I: DBT individual therapy; ER = Emergency Room
HR = hazard ratio; IPT = Interpersonal psychotherapy; InterSePT = International Suicide Prevention Trial; ITT = Intention to treat; LAI-R = Long-acting injectable risperidone;
MDD = Major Depressive Disorder; NS = Not statistically significant; NSSI = non-suicidal self-injury; PE = Prolonged exposure; PST = problem solving therapy; PTSD = Post-traumatic stress disorder;
PY = person years; RR = Risk Ratio; SA = Suicide Attempt; SCAD = Schizoaffective Disorder; SGA = Second generation antipsychotics (physician’s choice); SR = sustained release; XR = extended
a. Oral antipsychotics may have included aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine, and risperidone
b. Low dose included 12.5 milligram monthly injections of fluphenazine decanoate; Ultra-low dose included 1.5 milligram monthly injections of fluphenazine decanoate
c. SGA may have included aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, paliperidone, asenapine, and iloperidone
d. The authors report that other medications may have included antidepressants, neuroleptics or no medications
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Therapy Prolonged Exposure protocol for suicidal and self-injuring women with borderline personality disorder and PTSD. Behav Res Ther 2014;55:7-

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disorder. Psychother Psychosom 2008; 78: 307-16.

6. Perroud N, Uher R, Marusic A, Rietschel M, Mors O, Henigsberg N, et al. Suicidal ideation during treatment of depression with escitalopram and

nortriptyline in Genome-Based Therapeutic Drugs for Depression (GENDEP): a clinical trial. BMC Medicine 2009; 7: 60.

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unipolar major depression with SSRI pharmacotherapy or interpersonal psychotherapy in a randomized clinical trial. Depress Anxiety 2011; 28: 303-9.
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behavior in a randomized trial: An exploratory report from the combining medications to enhance depression outcomes study. J Clin Psychiatry 2011; 72:

1322-32.

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multiple suicide attempters in the emergency department. Int Clin Psychopharmacol 1999;14:361-72.

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psychosis: a randomized comparison of aripirazole, quetiapine and ziprasidone over 1 year. Psychopharmacology 2014; 231: 357-66.

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14. Strom BL, Eng SM, Faich G, Reynolds RF,D’Agostino R, Ruskin J, et al. Comparative mortality associated with ziprasidone and olanzapine in real-

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193-201.

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sertindole cohort prospective study (SCoP). Acta Psychiatr Scand 2010; 122: 345-355.
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affective disorders: data from a randomized prospective trial. Pharmcopsychiat 1996; 29: 103-107.
 PRISMA 2009 Checklist Riblet et al. Suicide Prevention Meta-Analysis

Reported
Section/topic # Checklist item
on page #
TITLE
Title 1 Identify the report as a systematic review, meta-analysis, or both. 1
ABSTRACT
Structured summary 2 Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, 2
participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and
implications of key findings; systematic review registration number.

INTRODUCTION
Rationale 3 Describe the rationale for the review in the context of what is already known. 3
Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, 3
outcomes, and study design (PICOS).
METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide 3
registration information including registration number.
Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, 3-4
language, publication status) used as criteria for eligibility, giving rationale.
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify 4
additional studies) in the search and date last searched.
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be App 1
repeated.
Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, 5
included in the meta-analysis).
Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes 5
for obtaining and confirming data from investigators.
Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and 5
simplifications made.
Risk of bias in individual 12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was 5
studies done at the study or outcome level), and how this information is to be used in any data synthesis.
Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means). 5-6
Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency 5-6
(e.g., I2) for each meta-analysis.
Page 1 of 2
 PRISMA 2009 Checklist Riblet et al. Suicide Prevention Meta-Analysis

Reported
Section/topic # Checklist item
on page #
Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective 7
reporting within studies).
Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating 6-7
which were pre-specified.
RESULTS
Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at 7
each stage, ideally with a flow diagram.
Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and 7, Table1
provide the citations. eTable2
Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). eTable2
Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each 8-9,
intervention group (b) effect estimates and confidence intervals, ideally with a forest plot. eTable2
Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency. 8-9, Fig 2
and Fig3
Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15). 8,
eTable2
Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]). 8-10
DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to 11-13
key groups (e.g., healthcare providers, users, and policy makers).
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of 13
identified research, reporting bias).
Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research. 14
FUNDING
Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the 1
systematic review.

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(6): e1000097.
doi:10.1371/journal.pmed1000097
For more information, visit: www.prisma-statement.org.
Page 2 of 2
Strategies to prevent death by suicide: meta-analysis of
randomised controlled trials
Natalie B. V. Riblet, Brian Shiner, Yinong Young-Xu and Bradley V. Watts
BJP published online April 20, 2017 Access the most recent version at DOI: 10.1192/bjp.bp.116.187799

Supplementary Supplementary material can be found at:

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