Repeated infusions of ketamine “rapidly and robustly” decreased chronic thoughts of suicide in half of patients with treatment-resistant depression, secondary analysis from a preliminary open-label study showed.
At the end of the series of infusions, 7 out of 14 patients — even those who were still depressed — had a score of zero on the Columbia-Suicide Severity Rating Scale [C-SSRS] for remission of suicidal ideation, Dawn Ionescu, MD, of Massachusetts General Hospital in Boston, and colleagues reported online in the Journal of Clinical Psychiatry.
This remission was maintained in two patients for at least 3 months after ketamine was stopped. Both patients also achieved depression remission with a Hamilton Depression Rating Scale [HDRS28] score of <7, the study showed.
Ketamine “provides promise for the rapid treatment of suicidal ideation in medicated outpatients with treatment-resistant depression and suicidal thoughts,” the researchers wrote. “Larger controlled studies (including more serious/acute patients in the emergency room) are necessary to study ketamine’s anti-suicidal effects and the relationship between antisuicidal and antidepressant effects.”
C-SSRS Ideation score fell by an average of -0.27 per patient after each infusion (P<0.01), and HDRS28-Suicidal Ideation scores also fell significantly during the acute treatment phase (P<0.001), they reported.
Although this treatment for depression is not FDA-approved, this is an important study with relevant preliminary findings, Mark Frye MD, director of the Mayo Clinic Depression Center in Rochester, Minn., told MedPage Today.
“There is increasing interest in looking at clinical designs to sustain the robust antidepressant response (with associated reduction in suicidal thinking) that is increasingly recognized with intravenous ketamine,” Frye, who wasn’t involved in the study, said in an email. “Further research is encouraged to confirm these findings and if so, how best to then implement this potentially life-saving treatment for patients struggling with depression.”
“Suicidal ideation can be treated and this is just one strategy,” Maria Oquendo, MD, of New York Presbyterian/Columbia University Medical Center, told MedPage Today in an email. “While repeat doses of ketamine as a treatment strategy is not ready for prime time, the data suggest that we will be able to find suitable treatments for acute suicidal crises in the near future.”
Importantly, these data emphasize that looking at suicidal ideation as a symptom of depression “is too limited,” Oquendo added.
“These findings confirm multiple observations about the utility of ketamine in decreasing suicidal ideation independently of any effect on mood symptoms,” she said. “That is important for many reasons, not the least of which is that the pathophysiology of suicidal ideation and behavior is separate from that of mood disorders.”
Although preclinical study findings raise serious questions about the safety of chronic ketamine use, newer intranasal versions of ketamine are being investigated, Oquendo noted, adding that the field “anxiously awaits the results.”
In the meantime, psychosocial treatments also can be used to directly address suicidal ideation, she said.
“Referring patients to Dialectical Behavioral Therapy or implementing Safety Planning can help patients and their families manage chronic suicidal ideation,” said Oquendo, who was not involved in the study.
In the study, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited between April 2012 and October 2013. All had current, stable suicidal thoughts of 3 months’ duration or longer. Over a period of 3 weeks, the patients received open-label ketamine infusions. The first 3 infusions consisted of 0.5 mg/kg over 45 minutes while the last 3 consisted of 0.75 mg/kg over 45 minutes.
Suicidal ideation was assessed 4 hours after ketamine infusion and after a follow-up of 3 months, using the C-SSRS and the HDRS28-SI.
Ionesco and colleagues pointed out that patients were recruited specifically for having thoughts of suicide, whereas in previous studies of ketamine, this was one of the criteria for exclusion. In addition, half of the patients were also taking benzodiazepines. Concomitant benzodiazepine use “may actually attenuate ketamine’s antidepressant effects, thereby making our preliminary significant findings of potential interest.”
Limitations of the trial included its small size, open-label design, lack of a placebo group, and the absence of mood ratings prior to infusions, the researchers said.