Real-world effectiveness of repeated ketamine infusions for treatment resistant depression during the COVID-19 pandemic

Rosenblat and colleagues frame the study against the backdrop of the COVID-19 pandemic and the public health measures that followed—closure of non‑essential services, prolonged social isolation and quarantines—which have been associated with increased risk of adverse mental health outcomes, particularly among people with pre‑existing mood disorders. The authors note that social support is important for mental health and that pandemic‑related stressors (loneliness, circadian disruption, isolation) could plausibly attenuate the effectiveness of antidepressant treatments. Intravenous (IV) ketamine is described as a rapid‑acting, in‑person treatment option for adults with treatment‑resistant depression (TRD) that also rapidly reduces suicidal ideation in some patients. This paper therefore aims to evaluate whether the antidepressant effectiveness of repeated IV ketamine infusions was altered during the COVID‑19 period of public health restrictions. Specifically, the investigators compare outcomes following a standard course of four ketamine infusions delivered in an outpatient clinic during the pandemic (March 2020–February 2021) versus the year prior to the pandemic (March 2019–February 2020). The comparison seeks to inform whether restrictions on in‑person social interaction were associated with attenuated clinical response to ketamine in a real‑world treatment setting.

The study is a retrospective case series analysis of adult patients who received four outpatient IV ketamine infusions (0.5–0.75 mg/kg) over approximately two weeks for treatment‑resistant depression. Patients treated during the COVID‑19 period (cases: March 2020–February 2021; n = 107) were compared with patients treated in the prior year (controls: March 2019–February 2020; n = 160). The authors state that the full treatment protocol has been published elsewhere. Clinical operations during COVID‑19 followed provincial public health guidance: initial and follow‑up psychiatric consultations were conducted virtually by telephone or telemedicine, PPE was required for staff and patients, arrival screening and handwashing procedures were instituted, and clinic flow was altered to minimise waiting‑room contact. Treatment capacity and booking times were reduced briefly (March–April 2020) with phased resumption of new and out‑of‑province patients by May 2020; PPE availability constrained capacity early on. Outcome measurement included depressive symptoms assessed with the Quick Inventory of Depressive Symptomatology‑Self Report 16 (QIDS‑SR16), suicidal ideation using the QIDS‑SR16 SI item, anxiety with the Generalized Anxiety Disorder‑7 (GAD‑7) scale, and functional disability via the Sheehan Disability Scale (SDS) total score. Depressive symptoms and SI were measured pre‑treatment and after each infusion up to post‑infusion 4; anxiety and functioning were analysed from pre‑treatment to post‑infusion 3 and post‑infusion 4. Statistical analyses used mixed models with an autoregressive covariance structure, adjusting for age, sex, number of past antidepressant trials, and baseline symptom severity. Bonferroni corrections were applied for multiple post‑hoc comparisons. Analyses were performed in SPSS v26. The analysis received approval from a community research ethics board.

A total of 267 patients were included: 107 treated during the COVID‑19 period (mean age 44.5, SD 13.3; 52.0% female) and 160 treated before the pandemic (mean age 46.2, SD 15.2; 56.3% female). Level of treatment resistance was comparable between groups, with a mean of 8 past antidepressant trials (SD = 5) in both groups. Mixed model analyses found no statistically significant overall difference in response to IV ketamine between patients treated during the pandemic and those treated before it. Across the pooled sample, repeated ketamine infusions produced significant improvements in primary clinical measures: depressive symptoms (F(4, 630) = 48.73, p < .001), suicidal ideation (F(4, 627) = 17.34, p < .001), anxiety (F(2, 344) = 52.84, p < .001), and functional impairment (SDS total score; F(2, 318) = 36.17, p < .001). A significant group‑by‑infusion interaction was observed for GAD‑7 anxiety scores. Pairwise comparisons indicated a significantly greater reduction in anxiety from baseline to post‑infusion 3 in the pre‑COVID control group compared with the COVID‑period group (p = .044). However, by post‑infusion 4 the between‑group difference in anxiety reduction was not statistically significant (p = .078). The extracted text does not report additional subgroup or adverse‑event data.

Rosenblat and colleagues interpret their findings as indicating that four outpatient IV ketamine infusions produced comparable symptomatic improvements in adults with TRD whether delivered during the COVID‑19 pandemic or in the prior year. The authors emphasise that, despite widespread restrictions on in‑person social interactions—which could plausibly blunt therapeutic response—ketamine’s effectiveness was not meaningfully attenuated in this real‑world clinic sample. They note the practical implication that clinicians and patients should weigh the risk of potential COVID‑19 exposure against the benefits of an in‑person, potentially life‑saving treatment, rather than assume diminished antidepressant efficacy during periods of social restriction. The authors also suggest, more tentatively, that effective treatment of serious mental illness might reduce adverse COVID‑19 outcomes in this vulnerable population, though they frame the latter point as conjecture rather than established evidence. Finally, they acknowledge that generalisability to other psychiatric disorders or treatment modalities is unknown and remains to be determined. The extracted text does not provide an extended limitations section or additional qualification beyond the limits on generalisability.