Frequently Asked Questions

Repeated IV ketamine produced a larger reduction in depressive symptoms than intranasal esketamine during the 8-treatment induction phase. The overall decrease in QIDS-SR16 scores from baseline to the eighth treatment was 49.82% in the IV ketamine group versus 39.55% in the intranasal esketamine group. Mean QIDS-SR16 scores fell from 19.23 b1 0.23 to 9.65 b1 0.48 with IV ketamine and from 19.52 b1 0.39 to 11.80 b1 0.65 with intranasal esketamine.

Yes. In this chart review, IV ketamine showed a faster antidepressant response than intranasal esketamine. QIDS-SR16 scores decreased significantly after the first IV ketamine treatment, with all comparisons to baseline reported as P < .001. In contrast, the decrease became significant after the second intranasal esketamine treatment; the first posttreatment comparison was not significant (P = .342), and the second was significant (P = .014).

The groups began to separate after the second treatment. The authors reported that after the second treatment, the two groups began to demonstrate a significant difference in QIDS-SR16 scores. From the third through the eighth treatment, pretreatment QIDS-SR16 scores were significantly lower in the IV ketamine group than in the intranasal esketamine group, with all P values < .05.

Both treatments were delivered as 8 induction treatments given twice weekly over 435 weeks. IV racemic ketamine started at 0.5 mg/kg infused over 40 minutes, with gradual conservative escalation allowed up to 1.0 mg/kg; the average final dose was 0.67 mg/kg. Intranasal esketamine usually started at 56 mg with prompt escalation to 84 mg; the average final dose was 82.67 mg.

No. Dropout before the eighth treatment was similar between groups. Eighty-eight of 111 patients in the IV ketamine group and 35 of 42 patients in the intranasal esketamine group completed the full induction course. Terminal dropout rates were 21% for IV ketamine and 17% for intranasal esketamine, and this difference was not statistically significant (P = .654).

Both treatments were described as generally well tolerated with similar side-effect profiles, but the study was not designed to quantify adverse effects in detail. The most clinically salient reported effects for both treatments were transient dissociation, anxiety, nausea, dizziness, ability to tolerate oral intake, and increased blood pressure.

The study included 153 eligible outpatients aged 1878 years with major depressive disorder and treatment-resistant depression. All patients had failed at least 2 adequate antidepressant trials and had a pretreatment QIDS-SR16 score of 16 or higher. Patients treated as inpatients were excluded, and the service generally did not treat patients with a history of psychosis, concerning substance use, or relevant uncontrolled medical illness.

Baseline depression severity was similar, and most demographic and clinical characteristics did not differ significantly between groups. The authors found no significant baseline difference in QIDS-SR16 scores and no significant differences in age, body mass index, gender, marital status, race, education, employment, concomitant psychiatric disorders, or prior ketamine, ECT, or TMS exposure. One exception was concomitant antipsychotic use for antidepressant augmentation, which was more common in the intranasal esketamine group than in the IV ketamine group (51.4% vs 26.2%, P < .05).

No. This study found that IV ketamine was associated with greater and faster symptom improvement during induction, but its retrospective design limits definitive treatment recommendations. The authors noted that the study lacked randomization and a controlled comparison group, and treatment choice may have been influenced by confounding factors such as insurance coverage, background treatment changes, and different dosing approaches. They concluded that future randomized controlled trials are needed to confirm comparative efficacy.

• It was a retrospective chart review, so the analysis was observational and not randomized.
• There was no well-controlled comparison group, which increases the risk of selection bias and confounding.
• Patients could continue or modify antidepressants and psychotherapy during treatment, so other treatment changes may have influenced outcomes.
• The IV ketamine protocol allowed dose adjustments up to 1.0 mg/kg, making direct route-to-route comparisons more complex.
• The sample sizes were imbalanced, with 111 patients receiving IV ketamine and 42 receiving intranasal esketamine.