A multi-site randomized clinical trial to reduce suicidal ideation in suicidal adult outpatients with Major Depressive Disorder: Development of a methodology to enhance safety

Abstract

Background/Aims Suicide is a major public health concern, yet there are very few randomized clinical trials that have been conducted to reduce suicidal ideation in patients at risk for suicide. We describe the rationale and refinements of such a trial that is designed to assess the effect of a hypnotic medication on suicidal ideation in adult outpatients currently experiencing suicidal ideation. Methods “Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT)” is a multi-site randomized clinical trial that includes 3 recruiting sites and one data management site. This 4-year study is in its second year of recruitment. The purpose of the study is to compare hypnotic medication versus placebo as an add-on treatment to a selective serotonin reuptake inhibitor as a means of reducing suicidal ideation in depressed adult outpatients with insomnia and suicidal ideation. The safety features of the study follow the 2001 NIH guidelines for studies that include patients at risk of suicide. Results Five hundred and eighty-four potential participants have undergone telephone screening; 67% of these failed the phone screen, most often due to an absence of expressed suicidal ideation (26% of the telephone screen fails). One hundred and twelve persons appeared for a face-to-face baseline assessment, and 40 of these had completed a taper of their ineffective psychotropic medications before the baseline assessments. Sixty-four% of those who completed baseline assessments failed to proceed to randomization, most commonly because of no clinically significant suicidal ideation (51% of those excluded at baseline). One participant was offered and accepted voluntary psychiatric hospitalization in lieu of study participation. Thus far, 40 participants have been randomized into the study, 88.7% of scheduled visits have been attended, with 93.8% adherence for the SSRI and 91.6% adherence for the randomized hypnotic versus placebo. None of the randomized participants have required hospitalization or had a suicide attempt. Conclusions By carefully considering the inclusion and exclusion criteria and other safety features, the safe conduct of randomized clinical trials in suicidal adult patients is possible, including the inclusion of participants who have undergone a prescribed tapering of psychotropic medications prior to baseline assessment.

Sleep problems and suicidal behaviors in college students

“…Sleep is modifiable, and some students may be more willing to seek help for sleep problems than for depression or suicidal behaviors specifically (McCall and Black, 2013, Woznica et al, 2015). Further, there is evidence that cognitive behavioral therapy for insomnia (CBT-I) not only improves sleep functioning, but also reduces suicidal ideation among adults with both low or high levels of depression (Manber et al, 2011; see also McCall et al, 2015).…”

An Update on the Use of Sedative-Hypnotic Medications in Psychiatric Disorders

“…Also, a controlled study to examine effects of sedative-hypnotics on suicidal ideation requires a very thoughtful study design to protect the safety of research participants. To help clarify the potential role of sedative-hypnotics in the management of suicidal ideation, a carefully crafted, multi-site randomized clinical trial of open-label SSRI with zolpidem ER versus placebo in depressed adult outpatients with insomnia and suicidal ideation has been developed, and is currently recruiting participants with funding from the National Institutes of Mental Health (15). We eagerly anticipate the results of this Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT) study, as it is very likely to significantly impact the standard of care in psychiatry.…”

Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA

“…This hypothesis is presently being tested in a multi-site, randomized clinical trial. (5) In the meantime, the proposition of routinely prescribing hypnotics to suicidal depressed patients is countered by the fact that hypnotics can be part of an intentional overdose, or may induce or aggravate suicide. The latter possibility has public health significance as 3% of non-institutionalized adult Americans reported using a hypnotic in the last month.…”