Use of Acute and Maintenance Intravenous Ketamine in Outpatients With Depression

In real-world patients with treatment-resistant depression (TRD), long-term intravenous (IV) ketamine therapy is well tolerated and is associated with modest improvement in the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR₁₆) score. A retrospective chart review was conducted among patients with TRD who were being treated on an outpatient basis at the Intravenous Ketamine Clinic for Depression at Massachusetts General Hospital (MGH) in Boston, Massachusetts. Results of the study were published in the Journal of Affective Disorders.

The investigators sought to examine outcomes experienced among outpatients treated at the MGH ketamine clinic between October 2018 and November 2019. A total of 85 patients with TRD were enrolled in the study. At every visit prior to administration of IV ketamine, participants’ symptom severity was measured via use of the QIDS-SR₁₆.

Patients’ initial dose of ketamine was typically 0.5 kg/mg. which was infused over 40 minutes. In the induction phase, IV ketamine was administered 2 times weekly for 3 weeks. This was followed by a maintenance phase, in which a variable dose and administration schedule were used. Response to IV ketamine was defined as a ≥50% reduction in the total QIDS-SR₁₆ score from baseline.

Overall, 47.1% (40 of 85) of the patients who initiated treatment discontinued during or immediately following the induction phase. At the time this report was published, 3.5% (3 of 85) of the participants were still on induction therapy, and 49.4% (42 of 85) of patients had transitioned to the maintenance phase after having completed the induction phase. Among these participants, 16.5% discontinued treatment during the maintenance period and 28 continued on maintenance therapy.

During maintenance therapy, the mean ketamine dosage was 0.91 ± 0.28 mg/kg. In total, 18.3% (15 of 82) of participants responded to induction therapy and 7.3% (6 of 82) of them remained in responder status during the maintenance phase — that is, at the time of data analysis. Discontinuation of ketamine because of side effects was reported in 3 patients.

The study has several limitations including the fact that this is a retrospective chart review and patients were followed naturalistically, with the possibility to continue or change antidepressants and their psychotherapy regimen according to recommendations from the treating psychiatrist. Also, the high dropout rate may have been influenced by the cost of ketamine infusions, since this treatment is not currently covered by insurance.

The investigators concluded that notwithstanding the considerable out-of-pocket costs incurred and the low response rates in QIDS-SR₁₆ scores, nearly half of all the real-world outpatients with TRD continued maintenance treatment with ketamine because of the perceived significant improvement. Large comparative effectiveness studies on the subject are warranted, in order to identify the role played by ketamine in the depression treatment algorithm, as well as to better distinguish the optimal dosing and frequency of treatment needed in patients with TRD.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Sakurai H, Jain F, Foster S, et al. Long-term outcome in outpatients with depression treated with acute and maintenance intravenous ketamine: A retrospective chart review. J Affect Disord. 2020;276:660-666. doi:10.1016/j.jad.2020.07.089