TOPLINE:

Twice-weekly intravenous (IV) ketamine over a 4- to 5-week induction period for severe treatment-resistant depression (TRD) was associated with a faster and greater reduction in symptoms than intranasal (IN) esketamine, although overall tolerability was similar, a new retrospective study showed.

METHODOLOGY:

• Researchers conducted a retrospective chart review of 153 patients aged 18-78 years diagnosed with severe TRD who did not respond to at least two adequate antidepressant therapies and presented with baseline scores ≥ 16 on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16).
• The cohort included 111 patients treated with IV racemic ketamine and 42 with IN esketamine; both groups had comparable depression severity at baseline.
• Patients received eight treatment sessions administered twice weekly over 4-5 weeks. IV ketamine was initiated at 0.5 mg/kg over 40 minutes, with gradual and conservative dose escalation permitted up to 1.0 mg/kg. IN esketamine typically began at 56 mg before escalating the dose to 84 mg. QIDS-SR scores were recorded at baseline and immediately prior to each treatment session.

TAKEAWAY:

• QIDS‑SR16 scores were significantly lower after the first session with IV ketamine (P < .001 for each session), but the IN esketamine group did not show significant improvement until after the second session (P = .342 after the first session; P = .014 after the second; P < .001 for sessions 3-8).
• For sessions 3-8, presession QIDS‑SR16 scores were consistently lower with IV ketamine than with IN esketamine (P < .05 for all).
• The overall decrease in QIDS-SR16 scores from baseline through the final treatment was 49.8% vs 39.5% with IV ketamine vs IN ketamine.
• Dropout rates and side‑effect profiles were similar between groups.

IN PRACTICE:

“The results suggest both IN esketamine and IV ketamine are important tools in the evolving neuropsychiatric tool kit,” investigator said in a press release.

“The differences observed are important, but their substantive meaning is likely contingent on a holistic set of clinical and logistical factors. For some patients, one tool may be more appropriate than the other, and careful and comprehensive consultation is important,” investigator added.

SOURCE:

The study was led by Robert Meisner, MD, medical director of the Ketamine Service, and Shuang Li, MD, PhD, both of the Psychiatric Neurotherapeutics Program at McLean Hospital, Belmont, Massachusetts. It was published online on September 22 in The Journal of Clinical Psychiatry.

LIMITATIONS:

The study was limited by its retrospective, nonrandomized design and the lack of a well-controlled comparator. The lack of randomization may have introduced selection bias and confounding — for example, through socioeconomic factors affecting access. Patients continued or modified their regimens of antidepressants and psychotherapy during treatment, which may have influenced outcomes. The IV ketamine protocol allowed dose adjustments rather than fixed dosing, complicating comparison with the IN esketamine protocol. Unequal group sizes limited statistical precision, although baseline demographics were similar.

DISCLOSURES:

The study reported receiving no funding. The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.