Clinical Review

Is Ketamine the New Wonder Drug for Treating Suicide?

Although the initial findings involving the use of ketamine in suicidal patients are promising, further research is needed on the short- and long-term effects of this medication.

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In 2014 the suicide rate in the U.S. was 13/100,000, the highest recorded in 28 years.1 Suicide is now considered the 10th leading cause of death for all ages, and the rate has increased every year from 2000 to 2014 among both women and men and in every age group except those aged ≥ 75 years.1-3 For those aged 15 to 44 years, suicide is among the top 3 causes of death worldwide.4-6


In 2013, more than 490,000 hospital visits related to suicide attempts were reported in the U.S.4 Health care expenditures related to suicide are estimated at $56.9 billion in combined medical and work loss costs annually and an unmeasurable cost to the affected families.7 The mental health care community is desperate for ways to address this epidemic, and the National Academies of Medicine (NAM) has declared that research that directly addresses comparative effectiveness of treatment strategies following a suicide attempt should be a national priority.8

The most recent reports from 2014 indicate that the suicide rates are higher for male veterans than for male nonveterans (32.1 vs 20.9 per 100,000, respectively) and are much higher for female veterans than for female nonveterans (28.7 vs 5.2 per 100,000, respectively).3 Suicide rates also may be associated with veteran-specific comorbidities, such as higher rates of depression, anxiety, posttraumatic stress disorder (PTSD), and war-related trauma.3 According to the VHA, the suicide rate for veterans aged > 30 years also is rapidly increasing, and VHA has echoed the calls from NAM to make suicide prevention research a national priority.3

The VA has tried to stem the tide of suicides in veterans by implementing many advances in suicide prevention, including hiring suicide prevention coordinators at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services. Yet the suicide rates for veterans continue to rise and remain higher than the rates in the general population.3

About 90% of deaths by suicide are by persons who have a treatable psychiatric disorder, most commonly a mood disorder, such as depression.4 However, most studies show that antidepressant therapy does not provide rapid or significant relief of suicidal ideation (SI).4 Therefore, the current standard of care for the treatment of acutely suicidal patients includes a combination of hospitalization, cognitive behavioral therapy or psychotherapy, case management, antidepressant medications, and electroconvulsive therapy (ECT).4 Even though these therapies have become more widely available over the past decade, rates of suicide continue to increase.1,4 These interventions have limited effectiveness in acute settings. Although both intensive outpatient follow-up and routine outpatient care have been studied in relation to the decrease of suicidal behavior, neither intervention has been shown to immediately reduce suicidal behavior significantly in patients.

Suicidality Interventions

Therapy and case management require patients to be well enough to make office visits and follow through with care for periods as long as 1 year, which is often not possible for individuals with severe depression.5 One-third of patients who attended 6 months of outpatient therapy consistently still met the criteria for major depressive disorder (MDD), a major risk for suicide attempt.9 Antidepressant medications take a minimum of 4 weeks to reach full efficacy, and many patients stop taking the medications before that point because of concern that the medication is not helping or because of adverse effects (AEs), such as sleep disturbance, sexual dysfunction, or weight gain.9

Electroconvulsive therapy has been shown to be an effective treatment for patients with depression and suicidal behavior, but adherence with 12 weeks of recommended therapy has been a barrier for this intervention. Additionally, ECT may not provide reduction in SI for 1 to 2 weeks.4,10 A review of research studies showed that nearly 50% of patients with high-expressed SI did not complete the prescribed amount of ECT due to the length of time to complete the recommended 12 sessions.10 Therefore, current treatment barriers for suicidal patients include: (1) long periods in treatment for therapy, medication, and ECT before any relief of symptoms is noted; (2) high recidivism rates for MDD symptoms and risk of suicide following treatment; and (3) high treatment dropout rates.

Pharmacologic treatments currently used in suicidal patients have not fared much better. Many have received FDA approval for treatment of associated mental health diagnoses such as bipolar disorder, schizophrenia, or MDD, but there are no approved treatments that specifically target suicidal behavior. Lithium is approved for reducing the long-term risk of SI primarily because it reduces the risk of mood disorders associated with SI, but lithium has not been shown to be effective in acute settings.11 Clozapine is approved for reducing the long-term risk of recurrent suicide in patients with schizophrenia or schizoaffective disorder.4 Clozapine has not been shown to be effective in patients with mood disorders, which make up the majority of patients who attempt suicide.4 Additionally, both medications are plagued by the same barriers listed earlier, such as long time to effect (it takes an average 4 weeks to reach efficacy), lack of efficacy in acute settings, and AEs (eg, sleep problems, weight gain, and sexual dysfunction).9 Thus finding better pharmacologic interventions for suicidal patients is a priority for current research.

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