Ketamine monotherapy reduces suicidal ideation in adults with depression
In adults with treatment-resistant depression, ketamine monotherapy significantly reduced suicidal ideation compared with adjunctive ketamine, according to a retrospective study in Journal of Psychiatric Research.
“Ketamine has been almost exclusively studied as an antidepressant adjunct to other antidepressants, most commonly monoaminergic agents such as SSRIs,” Joshua D. Di Vincenzo, of University of Toronto’s University Health Network and Brain and Cognition Discovery Foundation and the Canadian Rapid Treatment Center of Excellence (CRTCE), and colleagues wrote. “Due to the dearth of high-quality clinical data on the safety and efficacy of ketamine as an antidepressant monotherapy, the majority of clinicians continue to prescribe ketamine to patients with the condition that they remain on a stable dose of one or more antidepressant drugs for the duration of treatment.”
Researchers analyzed data of 220 adults with treatment-resistant depression (TRD) who had four to six IV ketamine infusions for major depressive disorder at the CRTCE between August 2018 and May 2021.
They classified 39 participants (17.7%) not currently using other antidepressants, with the exception of psychostimulants and sedatives, as the monotherapy group and 181 participants (82.3%) using at least one other antidepressant drug as the adjunctive group.
Participants self-reported suicidal ideation and overall depressive symptom severity at baseline and after four infusions; anxiety and functional impairment were reported at baseline for 10 patients, after the third infusion for seven and after the fourth for seven others. If Quick Inventory for Depressive Symptomatology-Self Report 16-Item (QIDS-SR16) scores for overall symptoms did not improve after two infusions, dosage increased from 0.5 mg/kg of actual body weight to 0.75 mg/kg. This occurred mostly among younger patients.
The monotherapy group had a significantly greater reduction of its mean QIDS-SR16 subscore for SI (0.91 points, SD = 0.9) than the adjunct therapy group (0.37 points, SD = 0.8). There was no significant difference in improvement between monotherapy and adjunctive groups for anxiety, functional impairment or general depressive symptoms.
“Importantly, baseline QIDS-SR16 SI subscores were significantly higher in the monotherapy group, so a greater decrease on the QIDS-SR16 SI in this group compared to the adjunctive group may be expected,” Di Vincenzo and colleagues noted.
In both groups, ketamine infusion had a significant large effect on overall depressive symptoms and anxiety, and a significant medium effect on suicidal ideation and functional impairment.
Limitations included retrospective design, absence of controls, use of a TRD population and incomplete data due to dropouts and participants not completing assessments. Di Vincenzo and colleagues indicated a need for larger study populations and suggested characterizing patients who will benefit from monotherapy.
“Future research should endeavor to determine which patients are most likely (or less likely) to benefit from combination treatment versus monotherapy in persons with MDD,” they wrote. “Moreover, whether a specific combination of ketamine and monoaminergic-based antidepressant is optimal also awaits empirical confirmation.”