Evidence-based Synthesis Program Department of Veterans Affairs

Health Services Research & Development Service

March 2012

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Quality Enhancement Research Initiative

Health Services Research & Development Service

Washington, DC 20420

Prepared by:

Evidence-based Synthesis Program (ESP) Center

Portland VA Medical Center

Portland, OR

Devan Kansagara, M.D., M.C.R., Director

Suicide Prevention Interventions 

and Referral/Follow-up Services:

A Systematic Review

Investigators:

Principal Investigator: 

Maya Elin O’Neil, Ph.D., M.S.

Co-Investigators and Research Associates: 

Kimberly Peterson, M.S.

Allison Low, B.A.

Susan Carson, M.P.H.

Lauren M Denneson, Ph.D.

Elizabeth Haney, M.D.

Paulo Shiroma, M.D.

Devan Kansagara, M.D., M.C.R.
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PREFACE

Quality Enhancement Research Initiative’s (QUERI) Evidence-based Synthesis Program 

(ESP) was established to provide timely and accurate syntheses of targeted healthcare topics 

of particular importance to Veterans Affairs (VA) managers and policymakers, as they work to 

improve the health and healthcare of Veterans. The ESP disseminates these reports throughout 

VA.

QUERI provides funding for four ESP Centers and each Center has an active VA affiliation. The 

ESP Centers generate evidence syntheses on important clinical practice topics, and these reports 

help:

• develop clinical policies informed by evidence,

• guide the implementation of effective services to improve patient outcomes 

and to support VA clinical practice guidelines and performance measures, 

and 

• set the direction for future research to address gaps in clinical knowledge.

In 2009, the ESP Coordinating Center was created to expand the capacity of QUERI Central 

Office and the four ESP sites by developing and maintaining program processes. In addition, 

the Center established a Steering Committee comprised of QUERI field-based investigators, 

VA Patient Care Services, Office of Quality and Performance, and Veterans Integrated Service 

Networks (VISN) Clinical Management Officers. The Steering Committee provides program 

oversight, guides strategic planning, coordinates dissemination activities, and develops 

collaborations with VA leadership to identify new ESP topics of importance to Veterans and the 

VA healthcare system.

Comments on this evidence report are welcome and can be sent to Nicole Floyd, ESP 

Coordinating Center Program Manager, at nicole.floyd@va.gov.

Recommended citation: O’Neil ME, Peterson K, Low A, Carson S, Denneson LM, Haney E, 

Shiroma P and Kansagara D. Suicide Prevention Interventions and Referral/Follow-up Services: 

A Systematic Review. VA-ESP Project #05-225; 2012.

This report is based on research conducted by the Evidence-based Synthesis Program 

(ESP) Center located at the Portland VA Medical Center, Portland OR funded by the 

Department of Veterans Affairs, Veterans Health Administration, Office of Research and 

Development, Quality Enhancement Research Initiative. The findings and conclusions 

in this document are those of the author(s) who are responsible for its contents; the 

findings and conclusions do not necessarily represent the views of the Department 

of Veterans Affairs or the United States government. Therefore, no statement 

in this article should be construed as an official position of the Department of 

Veterans Affairs. No investigators have any affiliations or financial involvement 

(e.g., employment, consultancies, honoraria, stock ownership or options, expert 

testimony, grants or patents received or pending, or royalties) that conflict with 

material presented in the report.
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EXECUTIVE SUMMARY

INTRODUCTION

Suicide is the tenth leading cause of death in the United States (US), with nearly 100 suicides 

occurring each day and over 36,000 dying by suicide each year.1

 Among Veterans and current 

military, suicide is a national public health concern. Recent estimates suggest current or former 

military represent 20 percent of all known suicides in the US2

 and the rate of suicides among 

Veterans utilizing Veterans Health Administration (VHA) services is estimated to be higher than 

the general population.3

 The enormity of the problem has led to several major public health 

initiatives and a growth in research funding for suicide prevention.4-7

Despite recent suicide prevention efforts, the suicide rate in the US has changed relatively little 

over the past 100 years.8

 The body of research on suicide prevention approaches has been reviewed 

previously by Gaynes and colleagues,9 and Mann and colleagues,9, 10 and recent, similar work 

exists in the form of draft self-harm guidelines from the National Institute for Health and Clinical 

Excellence (NICE) in 2011.11 As requested by the Veterans Affairs (VA)/Department of Defense 

(DoD) Evidence Based Practice Working Group (EBPWG) on suicide prevention, we examined 

recent research on suicidal self-directed violence as defined by Crosby et al. 2011.12 We update the 

work of Gaynes et al. and Mann et al. by systematically reviewing relevant literature that was not 

included in either report, and was published in 2005 through November 18, 2011. Though the focus 

of the report is on suicide prevention, we include as outcomes any type of suicidal self-directed 

violence, defined as “Behavior that is self-directed and deliberately results in injury or the potential 

for injury to oneself. There is evidence, whether implicit or explicit, of suicidal intent.”12, 13

The key questions were:

Key Question #1. What is the effectiveness of specific interventions for reducing rates of suicidal 

self-directed violence in military and/or Veteran populations?

Key Question #2. What lessons can be learned from suicidal self-directed violence prevention 

intervention research conducted outside of Veteran or military settings that can be applied to 

Veteran and/or military populations?

Key Question #3. What is the effectiveness of referral and follow-up services (e.g., strategies 

designed to provide referrals, improve referral follow-through and attendance, etc.) for reducing 

rates of suicidal self-directed violence in military and/or Veteran populations?

Key Question #4. What lessons can be learned from research on suicidal self-directed violence 

referral and follow-up services conducted outside of Veteran or military settings that can be 

applied to Veteran and/or military populations?

METHODS

The VA/DoD suicide prevention Evidence Based Practice Workgroup (EBPWG) requested a 

systematic review of literature related to suicidal self-directed violence published since two 

prior reports on the topic by Mann et al. and Gaynes et al.9, 10 The workgroup requested a review 
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focused on countries and populations of interest due to their similarity to US Veteran and military 

populations. Though a previous systematic review was conducted by Shekelle and colleagues in 

2009,14 the EBPWG requested that the current review include studies of pharmacotherapy and 

psychotherapy interventions, which were largely excluded from this previous report; and, therefore, 

we used the end search date from the Mann et al. review as the starting point for the current 

search. We identified relevant systematic reviews and controlled trials by searching PubMed, 

PsycINFO, the Cochrane Database of Systematic Reviews®, and the Cochrane Central Register 

of Controlled Trials® from 2005 to November 18, 2011. We used suicide and related terminology, 

and included interventions, military, Veterans as search terms (Appendix A). We limited the 

search to peer-reviewed articles involving human subjects and published in the English language 

that were not included in the previously published systematic reviews on the topic.9, 10 We also 

report results from these two older systematic reviews, as well as results from a draft systematic 

review on self-harm,11 comparing and combining findings across the three reports to the findings 

in this current report. Additional citations were identified from reference lists, consultation with 

content experts, and web sources. Titles, abstracts, and articles were reviewed by doctoral level 

investigators and project research associates trained in the critical analysis of literature; all articles 

were reviewed in duplicate. Quality assessment of all included primary studies and systematic 

reviews was performed in duplicate by investigators and research associates. We assessed study 

quality of systematic reviews using Oxman and Guyatt criteria.15 We assessed the risk of bias of 

primary studies using the tool described in version 5.1.0 of the Cochrane Handbook for Systematic 

Reviews of Interventions.

16 Data on study characteristics, patient characteristics, and outcomes were 

extracted by trained research associates under the supervision of the Principal Investigator, a VA 

clinical psychologist. All data were narratively summarized.

DATA SYNTHESIS

We constructed evidence tables showing study, patient, and intervention characteristics; 

methodological quality; and outcomes, organized by key question, intervention type, and 

comparison group. We analyzed studies to compare their characteristics, methods, and findings. 

We graded strength of evidence based on the guidance established for the Evidence-based 

Practice Center (EPC) Program of the Agency for Healthcare Research and Quality (AHRQ).17

We compiled a summary of findings for each question based on qualitative and semi-quantitative 

synthesis of the findings. We identified and highlighted findings from VA and DoD populations.

PEER REVIEW

A draft version of this report was reviewed by eight technical experts, as well as clinical 

leadership. Reviewer comments were addressed and our responses were incorporated in the final 

report (Appendix AA).

RESULTS

We reviewed 16,518 titles and abstracts from the electronic and hand searches. Applying our 

inclusion/exclusion criteria eliminated studies published prior to 2005; studies that did not report 

suicidal self-directed violence as an outcome; studies that were not randomized controlled trials 
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(RCTs); and studies conducted in countries other than Australia, Canada, New Zealand, the 

United Kingdom, and the United States. We rejected 16,110 at the abstract level, and performed a 

more detailed full-text review on 408 articles. From these, we identified 38 RCTs (reported in 47 

publications) and 23 systematic reviews (reported in 25 publications) that addressed at least one 

of the key questions.

We classified studies as pharmacotherapy interventions, psychotherapy interventions, or referral 

and follow-up services. We defined interventions as interventions designed to treat a condition, 

symptom, or behavior. Referral and follow-up services were any services that were provided 

to patients that were primarily designed to facilitate access to interventions rather than treat a 

condition, symptom, or behavior. Because many interventions include components designed to 

increase adherence and attendance, we classified any study describing an intervention component 

as an “intervention” study rather than a “referral and follow-up services” study even if it also 

included components of referral and follow-up services. Therefore, the studies designated as 

referral and follow-up services were described by the authors as solely designed to increase 

access to, attendance at, and adherence to other interventions not included in the study design.

Key Question #1. What is the effectiveness of specific interventions for reducing 

rates of suicidal self-directed violence in military and/or Veteran populations?

We found no RCTs of self-directed violence prevention interventions in military and/or VA 

health care settings.

Key Question #2. What lessons can be learned from suicidal self-directed violence prevention intervention research conducted outside of Veteran or military 

settings that can be applied to Veteran and/or military populations?

Pharmacotherapy Results

Findings from other systematic reviews with similar key questions report that pharmacotherapy 

findings are based on few studies with limited sample sizes, some methodological quality 

concerns, and short term follow-up assessment periods;9-11 therefore, pharmacotherapy findings 

should be interpreted with caution. All three reports found that available evidence from 

antidepressant trials does not show a benefit for reducing suicide, but caution that rates of suicide 

may have been too low to detect differences. Although observational studies show a correlation 

between increasing prescription rates and decreasing suicide rates, this evidence is considered 

lower strength than evidence obtained from RCTs or meta-analyses. The three systematic reviews 

included different studies of antipsychotic medications. Overall, they report positive findings 

from trials of flupenthixol, clozapine, and fluphenazine, though caution that findings are based 

on small samples of patients in very few studies. Finally, the systematic reviews report different 

results related to mood stabilizing medications. Gaynes et al. report no reduction in suicide 

rates based on one trial of lithium, whereas Mann et al. and NICE report some non-significant 

reductions in suicide rates for patients receiving lithium.9-11

Primary studies included in the current report evaluated antidepressants, atypical antipsychotics, 

mood stabilizers, and omega-3 supplements and reported their efficacy in prevention of 

suicidal self-directed violence in civilian populations. Findings from antidepressant trials in 

civilian populations were consistent with previous reviews on the topic, and did not provide 
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sufficient evidence to make a strong conclusion about the effectiveness of antidepressants in 

reducing suicides and suicide attempts. We identified nine trials (reported in 10 publications) 

that evaluated antidepressant medications. Comparisons included various combinations 

of antidepressant medications versus placebo;18-23 one antidepressant versus another;24, 25

antidepressant therapy versus cognitive behavioral therapy (CBT);23 and antidepressant therapy 

with and without CBT.19, 21, 26, 27 Many studies had no suicides in either group. Because of the 

short duration and low participant numbers, many of these studies would not have had the 

statistical power and duration of follow-up to allow the medication to effect a change in suicide 

rates. Therefore, they are felt to be of low strength, and are insufficient for determining the 

effectiveness of various combinations of antidepressant medications for reducing suicidal selfdirected violence. 

We found three trials that reported on the effectiveness of quetiapine (1 trial)28 or adjunctive 

aripiprazole (2 trials in 3 publications)29-31 in reducing suicide deaths. These trials were six 

to eight weeks in duration and none had any suicides reported during the follow-up period. 

The quetiapine trial reported one suicide attempt in each group (treatment and intervention). 

Therefore, we concluded there was insufficient evidence to determine antisuicidal benefit. 

Notably, the previous review by Mann and colleagues reported an antisuicidal effect of 

clozapine, an atypical antipsychotic medication.10

The two trials of mood stabilizers compared lithium versus valproate (2.5 years)32 and lithium 

versus citalopram (8 weeks).33 These trials reported no instances of suicidal self-directed violence 

for the duration of either study. The previous report by Mann et al., however, found an antisuicidal 

effect for lithium compared to carbamazepine and amitriptyline.10 Thus, trials conducted since 

the Mann et al. report provided insufficient evidence to draw conclusions about the comparative 

effectiveness of mood stabilizers in preventing suicide attempts. One study conducted outside a 

country within the scope of this review was suggested for inclusion by reviewers.34 This study, had 

it been included in our results, provided insufficient evidence for the effectiveness of lithium in 

prevention of suicidal self-directed violence when compared to placebo.

Finally, one trial of omega-3 fatty acid supplementation for 12 weeks did not have any suicide 

deaths in either group.35

Psychotherapy Results

Three previously published systematic reviews on this topic all report an overall insufficient 

to low strength of evidence for the effectiveness of any psychotherapeutic interventions in 

prevention of self-directed violence.9-11 In one report (NICE 2011), the authors combined 

findings from multiple psychotherapy studies with treatment as usual comparison groups, and 

describe low strength evidence of the effectiveness of these interventions in prevention of selfdirected violence.11 Individual psychotherapy results reported in the three reports include mixed 

findings related to cognitive therapies, positive findings related to Dialectical Behavior Therapy 

(DBT) for people with Borderline Personality Disorder, positive findings for interpersonal 

psychotherapy, null findings for outpatient day hospitalization, positive findings for problemsolving therapy, positive findings for psychoanalytically oriented partial day hospitalization 

for people with Borderline Personality Disorder, and positive findings for transference-focused 

psychotherapy. Notably, these results were presented in the previous reports as coming from 
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very few studies with small sample sizes, many methodological flaws, and short-term follow-up 

assessment periods, suggesting that all findings are of insufficient to low strength and should be 

interpreted with caution.

All psychotherapy trials meeting criteria for inclusion in this review were sufficiently 

heterogeneous in terms of type of treatment, duration of treatment, and population characteristics 

to preclude combination or quantitative comparison. Therefore, psychotherapy trials are 

grouped for discussion by population: those conducted in patients with Borderline Personality 

Disorder, recent suicide attempts, a psychotic spectrum disorder, and depression or dysthymia. 

The strongest evidence (moderate strength) comes from a trial of problem-solving treatment in 

addition to usual care versus usual care alone for patients with recent suicide attempts.36 This 

trial showed no significant benefit of the intervention compared to usual care for the overall 

group of patients presenting to the hospital after engaging in self-harm behaviors; however, a 

significant benefit was noted for a sub-population of patients limited to people who had multiple 

hospitalizations for self-harm prior to the intervention. The other trials of psychotherapy 

provided insufficient or low strength evidence to draw definitive conclusions, often because of 

limitations in quality and insufficient statistical power to detect intervention effects on low baserate outcomes of suicidal self-directed violence.

Three RCTs provided insufficient evidence to draw conclusions about prevention of suicide 

deaths in populations with Borderline Personality Disorder, largely because no or very few 

suicides occurred during the trials. One trial showed a significant reduction in suicide attempts 

with Mentalization Based Treatment (MBT) compared to Structured Clinical Management 

(SCM),37 as did a trial comparing DBT with community treatment by experts.38 Three other 

studies showed no significant benefit in suicide attempt prevention for Systems Training for 

Emotional Predictability and Problem Solving (STEPPS) versus treatment as usual,39 CBT 

specific to Cluster B personality disorders versus treatment as usual,40, 41 or DBT versus general 

psychiatric management.42

Few trials reported on prevention of suicide deaths as the outcome of psychotherapy 

interventions, and of those that did, most were insufficiently powered to detect an effect of the 

intervention. One study conducted a comparison among people with recent suicide attempts, 

self-harm incidents, or imminent risk.43 This trial had several design flaws that contribute to a 

high potential for bias: non-randomization, baseline differences among the groups, non-blinding, 

and differing drop-out rates among the groups. Therefore, there was insufficient evidence to 

draw conclusions about the psychotherapy comparison. Two other studies of people presenting 

with repeat self-harm reported no suicide events in either treatment or control groups for group 

therapy,44 and for intensive case management.45 Other studies evaluated inventions in similar 

populations (prior suicide). A study of Attachment-Based Family Therapy versus Enhanced 

Usual Care showed a reduction in suicide attempts, though design flaws limit the ability to draw 

a firm conclusion about the results.46 Likewise, studies comparing Collaborative Assessment and 

Management of Suicidality (CAMS) versus Enhanced Care As Usual (E-CAU) and skills-based 

intervention versus a supportive therapy control condition did not use sufficient methodological 

rigor to enable firm conclusions about effectiveness.47, 48 Notably, a study of adolescent group 

therapy compared to routine care resulted in fewer instances of self-harm in the routine care 

group indicating the possibility of iatrogenic effects in the group treatment condition; however, 
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design flaws in this study preclude the ability to draw firm conclusions based on the results.49

Finally, one study compared three conditions, CBT, problem-solving therapy, and treatment 

as usual. This study had few patients and methodological limitations, and therefore provides 

insufficient evidence related to any of the interventions being investigated.50

One study comparing CBT versus supportive counseling in patients with a psychotic spectrum 

disorder had an unacceptably high risk of bias because therapists were not blinded and delivered 

both interventions to the participants.51 Another trial compared the Improving Mood: Promoting 

Access to Collaborative Treatment (IMPACT) intervention (including a comprehensive 

depression case management and treatment component) versus usual care in people with 

depression or dysthymia used methods resulting in an unclear risk of bias.52 Each of these trials 

provides insufficient evidence to draw definitive conclusions about the effectiveness of the 

interventions.

Key Question #3. What is the effectiveness of referral and follow-up services 

(e.g., strategies designed to provide referrals, improve referral follow-through and 

attendance, etc.) for reducing rates of suicidal self-directed violence in military 

and/or Veteran populations?

We did not find any RCTs of suicidal self-directed violence prevention referral and follow-up 

services in military and/or VA health care settings.

Key Question #4. What lessons can be learned from research on suicidal selfdirected violence referral and follow-up services conducted outside of Veteran or 

military settings that can be applied to Veteran and/or military populations?

The three previously published reports on this topic all report overall insufficient to low strength 

of evidence for the effectiveness of any referral and follow-up services in prevention of selfdirected violence.9-11 Specific findings from the three reports include positive results from studies 

on case management/care coordination and 24-hour contact with a mental health professional. 

Mixed reports of findings came from studies on emergency contact cards and postal contact. Null 

findings were reported from studies investigating intensive psychosocial follow-up, telephone 

follow-up, and video education plus family therapy. Notably, these results were presented in the 

previous reports as coming from very few studies with small sample sizes, many methodological 

flaws, and short-term follow-up assessment periods, suggesting that all findings are of 

insufficient to low strength and should be interpreted with caution.

Findings from primary studies included in this report include three studies of postcard 

interventions to decrease repeated suicidal self-directed violence, which showed mixed 

results.53-55 Two studies of Youth-Nominated Support Team (YST) interventions combined with 

usual care did not significantly reduce risk of suicide attempts or death in suicidal adolescents.56,57

One study of assertive community treatment compared with community mental health care in 

difficult-to-engage adults with serious mental illness showed no reduction in suicide deaths or 

deliberate self-harm incidents.58 Finally, one trial of a depression care management program 

resulted in no significant changes in the suicide mortality rate of older adults in primary care 

settings.59 However, all these studies were given low strength of evidence ratings and thus limit 

conclusions about the effectiveness of these interventions.