The role of randomized trials in testing interventions for the prevention of youth suicide

Epidemiological considerations point to a small handful of prevention strategies that have the potential for dramatically reducing suicide rates. Nearly all of those prevention approaches involve population-based strategies to either find an increased number of individuals at high risk for suicide or to reduce the prevalence of risk factors in members of a population that, as a whole, has a relatively low rate of suicide. Few of these approaches have been evaluated in rigorous trials. We argue that there are rigorous randomized trial designs that are both feasible and ethical and can be used to test both programmes and implementation strategies for population-based suicide prevention. We review existing suicide prevention trials and introduce two new randomized trial designs that are likely to achieve sufficient statistical power. The 'dynamic wait-listed design' randomizes across different time periods and is now being used to test a gatekeeper training programme in 32 schools. It could also be used to examine suicide prevention programmes in rural areas. The multi-trial follow-up study builds on the large number of successful population-based preventive interventions aimed at reducing known risk factors for suicide in youths to see whether these also cause a reduction in rates of completed suicide.     

A systematic review of psychosocial suicide prevention interventions for youth

Youth suicide is a significant public health problem. A systematic review was conducted to examine the effectiveness of school, community and healthcare-based interventions in reducing and preventing suicidal ideation, suicide attempts and deliberate self-harm in young people aged 12–25 years. PsycInfo, PubMed and Cochrane databases were searched to the end of December 2014 to identify randomised controlled trials evaluating the effectiveness of psychosocial interventions for youth suicide. In total, 13,747 abstracts were identified and screened for inclusion in a larger database. Of these, 29 papers describing 28 trials fulfilled the inclusion criteria for the current review. The results of the review indicated that just over half of the programs identified had a significant effect on suicidal ideation (Cohen’s d = 0.16–3.01), suicide attempts (phi = 0.04–0.38) or deliberate self-harm (phi = 0.29–0.33; d = 0.42). The current review provides preliminary support for the implementation of universal and targeted interventions in all settings, using a diverse range of psychosocial approaches. Further quality research is needed to strengthen the evidence-base for suicide prevention programs in this population. In particular, the development of universal school-based interventions is promising given the potential reach of such an approach.     

HIV sexual risk-reduction interventions for youth: a review and methodological critique of randomized controlled trials

The authors review and provide a methodological critique of randomized controlled studies of HIV risk reduction interventions that measured sexual risk behavior outcomes with adolescents. Studies conducted in school, community, and health care settings were reviewed. Overall, 13 of 23 interventions (57%) were effective in reducing sexual risk behavior. Methodological strengths of extant studies included an emphasis on a theoretical framework, evaluation of both individualized and group-intervention formats, use of multiple assessments of risk behavior (including biological outcomes), and inclusion of efficacy and effectiveness trials. Methodological limitations included limited evaluation of theoretical mediators of risk reduction, failure to report effect sizes, and lack of sustained findings. Inconsistencies were found in data analytic procedures and reporting, including how nested designs, skewed data, and attrition were addressed. Recommendations for designing methodologically rigorous interventions are provided.     

Preventive interventions for youth suicide: a risk factor-based approach

OBJECTIVE: This review draws on current knowledge of risk for youth suicide to categorize strategies for intervention. Its goal is to identify areas of 'research need' and to provide an evidence base to identify 'best buy' preventive interventions for youth suicide. METHOD: The design, development, implementation and evaluation of prevention strategies ranging from clinical interventions to population-based universal approaches are considered within five risk factor domains: individual, family, community, school and peer. RESULTS: There is a paucity of evidence on the effects of interventions targeting depression and suicidal behaviour. Nevertheless, there are effective indicated, selective and universal interventions for important risk factors for depression and suicidal behaviour. Little evidence has emerged to support the efficacy of some traditional approaches to suicide prevention, such as school based suicide education programs and telephone hotlines. CONCLUSIONS: Youth suicide prevention strategies in Australia have generally employed traditional approaches that focus on clinical interventions for self-harmers, restricting access to lethal means, providing services to high risk groups and enhancing general practitioner responses. Both program development and research evaluation of interventions for many important risk and protective factors for suicide have been neglected.     

Safety reporting in randomized trials of mental health interventions

OBJECTIVE: The authors aimed to evaluate the adequacy of the reporting of safety information in publications of randomized trials of mental-health-related interventions. METHOD: The authors randomly selected 200 entries from the PsiTri registry of mental-health-related controlled trials. This yielded 142 randomized trials that were analyzed for adequacy and relative emphasis of their content on safety issues. They examined drug trials as well as trials of other types of interventions. RESULTS: Across the 142 eligible trials, 103 involved drugs. Twenty-five of the 142 trials had at least 100 randomly chosen subjects and at least 50 subjects in a study arm. Among drug trials, only 21.4% had adequate reporting of clinical adverse events, and only 16.5% had adequate reporting of laboratory-determined toxicity, while 32.0% reported both the numbers and the reasons for withdrawals due to toxicity in each arm. On average, drug trials devoted 1/10 of a page in their results sections to safety, and 58.3% devoted more space to the names and affiliations of authors than to safety. None of the trials of nondrug interventions had adequate or even partially adequate reporting of either clinical adverse events or laboratory-determined toxicity. In multivariate modeling, long-term trials and trials conducted in the United States devoted even less space to safety, while schizophrenia trials devoted more space to safety than did trials in other areas. CONCLUSIONS: Safety reporting is largely neglected across trials of mental-health-related interventions, thus hindering the assessment of risk-benefit ratios for rational decision making in mental health care.     

Methods of youth suicide in New Zealand: trends and implications for prevention

OBJECTIVE: One commonly suggested approach to reducing suicide is to restrict access to potentially lethal means of suicide. This paper summarises recent trends in methods of suicide among young people in New Zealand and examines the feasibility of suicide prevention through restricting access to methods of suicide. METHOD: Data derived from official mortality statistics were used to examine trends, from 1977 to 1996, in methods of suicide among young people aged 15-24 years. RESULTS: During the last two decades, male youth suicide rates in New Zealand doubled, from 20.3 per 100,000 in 1977 to 39.5 per 100,000 in 1996. This increase was accounted for, almost entirely, by increased use of hanging (71% of total increase) and vehicle exhaust gas (26% of total increase). Suicide rates among young females also increased, from 4 per 100,000 in 1977 to 14.3 per 100,000 in 1996. As for males, the increased female suicide rate was largely accounted for by increased rates of hanging and vehicle exhaust gas. CONCLUSIONS: The marked increases in rates of youth suicide in New Zealand during the past two decades are accounted for, almost wholly, by increases in rates of suicide by hanging and, to a lesser extent, vehicle exhaust gas. In 1996 the majority (79.7%) of youth suicides were accounted for by these two methods: hanging (61.5%) and vehicle exhaust gas (18.2%). Both methods are widely available and difficult to restrict, implying that limiting access to means of suicide is a strategy which is unlikely to play a major role in reducing suicidal behaviour among young people in New Zealand.     

The role of vitamin E in the prevention of coronary events and stroke. Meta-analysis of randomized controlled trials

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the world. Vitamin E as an anti-oxidant vitamin, was suggested to have a role in the prevention of CVD. We did a meta-analysis, using the Cochrane Group Methodology, of all available randomized controlled trials (RCTs) to evaluate the role of vitamin E in the prevention of CVD. Nine studies met inclusion criteria, including 80,645 participants. Vitamin E supplementation was not associated with a reduction in total mortality or total CVD mortality, but it was associated with a small statistically significant reduction in non-fatal myocardial infarction in patients with pre-existing coronary artery disease. Prophylactic use of vitamin E in doses ranging between 50-800 IU was not associated with any increase in the incidence of serious side effects.     

A randomized controlled trial of postcrisis suicide prevention

OBJECTIVE: This study tested the hypothesis that professionals' maintenance of long-term contact with persons who are at risk of suicide can exert a suicide-prevention influence. This influence was hypothesized to result from the development of a feeling of connectedness and to be most pertinent to high-risk individuals who refuse to remain in the health care system. METHODS: A total of 3,005 persons hospitalized because of a depressive or suicidal state, populations known to be at risk of subsequent suicide, were contacted 30 days after discharge about follow-up treatment. A total of 843 patients who had refused ongoing care were randomly divided into two groups; persons in one group were contacted by letter at least four times a year for five years. The other group-the control group-received no further contact. A follow-up procedure identified patients who died during the five-year contact period and during the subsequent ten years. Suicide rates in the contact and no-contact groups were compared. RESULTS: Patients in the contact group had a lower suicide rate in all five years of the study. Formal survival analyses revealed a significantly lower rate in the contact group (p=.04) for the first two years; differences in the rates gradually diminished, and by year 14 no differences between groups were observed. CONCLUSIONS: A systematic program of contact with persons who are at risk of suicide and who refuse to remain in the health care system appears to exert a significant preventive influence for at least two years. Diminution of the frequency of contact and discontinuation of contact appear to reduce and eventually eliminate this preventive influence.     

Comparison of large versus smaller randomized trials for mental health-related interventions

OBJECTIVE: The extent of disagreement between large and smaller randomized, controlled trials on mental health issues is unknown. The authors aimed to compare the results of large versus smaller trials on mental health-related interventions. METHOD: The authors screened 161 Cochrane and 254 Database of Abstracts of Reviews of Effectiveness systematic reviews on mental health-related interventions. They identified 16 meta-analyses with at least one "large" randomized trial with sample size >800 and at least one "smaller" trial. Effect sizes were calculated separately for large and smaller trials. Heterogeneity was assessed between all studies, within each group (large and smaller studies), and between large and smaller studies. RESULTS: Significant between-study heterogeneity was seen in five meta-analyses. By random-effects calculations, the results of large and smaller trials differed beyond chance in four meta-analyses (25%). In three of these disagreements (effect of day care on IQ, discontinuation of antidepressants, risperidone versus typical antipsychotics for schizophrenia), the smaller trials showed greater effect sizes than the large trials. The inverse was seen in one case (olanzapine versus typical antipsychotics for schizophrenia). With fixed-effects models, disagreements beyond chance occurred in five cases (31%). In four meta-analyses, the effect size differed over twofold between large and smaller trials. Various quality and design parameters were identified as potential explanations for some disagreements. CONCLUSIONS: Large trials are uncommon in mental health. Their results are usually comparable with the results of smaller studies, but major disagreements do occur. Both large and smaller trials should be scrutinized as they offer a continuum of randomized evidence.     

The statistical pitfalls of the partially randomized preference design in non-blinded trials of psychological interventions

In a partially randomized preference trial (PRPT) patients with no treatment preference are allocated to groups at random, but those who express a preference receive the treatment of their choice. It has been suggested that the design can improve the external and internal validity of trials. We used computer simulation to illustrate the impact that an unmeasured confounder could have on the results and conclusions drawn from a PRPT. We generated 4000 observations ("patients") that reflected the distribution of the Beck Depression Index (DBI) in trials of depression. Half were randomly assigned to a randomized controlled trial (RCT) design and half were assigned to a PRPT design. In the RCT, "patients" were evenly split between treatment and control groups; whereas in the preference arm, to reflect patient choice, 87.5% of patients were allocated to the experimental treatment and 12.5% to the control. Unadjusted analyses of the PRPT data consistently overestimated the treatment effect and its standard error. This lead to Type I errors when the true treatment effect was small and Type II errors when the confounder effect was large. The PRPT design is not recommended as a method of establishing an unbiased estimate of treatment effect due to the potential influence of unmeasured confounders.     

Death by hanging: implications for prevention of an important method of youth suicide

AIM: The aim of this study was to identify factors associated with deaths by hanging among young people in Queensland, Australia. METHOD: An examination of coroner's reports for all deaths by hanging of people under 25 years of age that occurred in Queensland in the years 1995 and 1996. RESULTS: All cases were recorded as suicides. Most were males and a quarter were indigenous persons. Half the deaths occurred in regional or rural areas. Unemployment, the experience of personal loss, psychiatric illness and alcohol use were possible precipitating agents. Early warning signs were the onset of uncharacteristic behaviours and threats of suicide. CONCLUSIONS: The private nature of hanging means that there are rarely opportunities to prevent it in the period immediately before the fatal event. Earlier interventions will have to be considered. To prevent hanging as a means of suicide, we need to understand more about the difficulties experienced by some young men who are living in rural areas. We need more information about the cultural problems experienced by indigenous youths in their teenage years. Young people in the justice system may need personal support. There is a pressing need to determine if young people, especially in rural areas, have adequate access to the professional expertise needed to diagnose and treat mental disorders.     

Psychosocial interventions for the prevention of relapse in bipolar disorder: systematic review of controlled trials

BACKGROUND: Pharmacological interventions alone do not provide sufficient benefit for some individuals with bipolar disorder. AIMS: To determine the effectiveness of psychosocial interventions for the prevention of relapse in bipolar disorder. METHOD: A systematic review and meta-analysis of randomised or quasi-randomised controlled trials were conducted. RESULTS: Cognitive-behavioural therapy or group psychoeducation may be effective for relapse prevention in stable individuals. Family therapy was no more or less effective than individual psychosocial therapy or crisis management. There is no evidence that care management or integrated group therapy is effective in the prevention of relapse. CONCLUSIONS: Cognitive-behavioural therapy, group psychoeducation and possibly family therapy may be beneficial as adjuncts to pharmacological maintenance treatments.     

Pharmacological interventions for acute bipolar mania: a systematic review of randomized placebo-controlled trials

OBJECTIVES: We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials in acute bipolar mania to summarize available data on drug treatment of mania. METHODS: We included trials of medications licensed in the USA or UK for the treatment of any phase of bipolar disorder. Outcomes investigated were changes in mania scores, attrition, extrapyramidal effects and weight change. Data were combined through meta-analyses. RESULTS: We included 13 studies (involving 3,089 subjects) and identified 2 studies for each of the following medications: carbamazepine, haloperidol, lithium, olanzapine, quetiapine, risperidone, valproate semisodium and aripiprazole. All drugs showed significant benefit compared with placebo for reduction in mania scores. Compared with placebo, for all antipsychotics pooled, response to treatment (> or =50% reduction in Young Mania Rating Scale scores) was increased more than 1.7 times [relative risk (RR) = 1.74, 95% confidence interval (CI) = 1.54, 1.96]; for all mood stabilizers pooled, response to treatment was doubled (RR 2.01, 95% CI = 1.66, 2.43). Overall withdrawals were 34% fewer (24-43%) with antipsychotics, and 26% fewer (10-39%) with mood stabilizers. However, for carbamazepine, aripiprazole and lithium an increase in risk of withdrawal could not be excluded. Small but significant increases in extrapyramidal side effects occurred with risperidone and aripiprazole. CONCLUSIONS: Antipsychotics and mood stabilizers are significantly more effective than placebo for the treatment of acute mania. Their effect sizes are similar. Small differences between effect sizes may be due to differences in the patients included in the studies or to chance. Carbamazepine and lithium may be more poorly tolerated, and antipsychotics cause more extrapyramidal side effects.     

Adherence to multidomain interventions for dementia prevention: Data from the FINGER and MAPT trials

IntroductionMultidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable.MethodsWe studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2-year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3-year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega-3 supplement or placebo.ResultsAdherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega-3 supplement, and lowest for unsupervised computer-based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms.DiscussionReducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face-to-face contacts, and taking into account participant characteristics may increase adherence in future trials.     

Evaluation of imminent danger for suicide among youth

Problems with current strategies for assessing suicide risk are discussed and a two-tier method for evaluating imminent danger among adolescents is proposed. First, statistically-based data on suicide risk factors are collected; second, coping ability is assessed by having youths promise in writing not to try suicide, compliment themselves and others, assess their feelings; and develop a plan for dealing with suicidal circumstances.