Are 24-hour motor activity patterns associated with continued rapid response to ketamine?

Patients with major depressive disorder who had a brief antidepressant response to ketamine (lasting 24-48 hours) showed blunted 24-hour wrist activity amplitude from baseline through three days post-infusion and a phase advance of activity on day one that returned to baseline by day three. Those with a continued response (over 72 hours) had phase-advanced activity at baseline and day one, plus increased amplitude on days one and three. Nonresponders did not show these patterns. The time course of antidepressant response to ketamine appears linked to underlying biological differences in motor activity timekeeping, which may involve circadian system mechanisms.

Study at a glance

Abstract

PURPOSE: This study examined the links between 24-hour activity patterns (specifically, amplitude and timing of wrist activity) and the persisting qualities of clinical antidepressant response to the glutamatergic modulator ketamine. METHODS: Twenty-four-hour activity patterns were compared across 5 days of 24-hour activity rhythms in patients with major depressive disorder who displayed either a brief antidepressant response (24-48 hours), a continued antidepressant response (>72 hours), or no antidepressant response to ketamine. These postinfusion-response profiles were then used retrospectively to examine cohort-specific fitted parameters at baseline, postinfusion day 1 (D1), and postinfusion D3. RESULTS: Relative to the nonresponders, the cohort experiencing a brief antidepressant response had blunted 24-hour amplitude that extended from baseline through D3 and postketamine phase advance of activity on D1 that reverted to baseline on D3. Relative to the nonresponders, the cohort experiencing a continued antidepressant response to ketamine had phase-advanced activity at both baseline and D1, as well as increased amplitude on D1 and D3. CONCLUSION: Taken together, the results suggest that the time course of antidepressant response to ketamine is influenced by underlying biological differences in motor activity timekeeping. These differences may provide clues that link durable mood response with the molecular machinery of the circadian system, thus leading to more effective interventions. In addition, biomarkers of preinfusion motor activity (eg, amplitude, timing) may be useful for recommending future individualized treatment interventions, to the extent that they help identify patients who may relapse quickly after treatment.