Monitoring a depressed patient’s daily activity patterns before trying the drug ketamine — being tested as a fast-acting antidepressant — may help physicians determine whether the drug will be effective or not, according to a new study published in the journal Biological Psychiatry.
During a depressive episode, many people experience reduced energy, a feeling of being slowed down and having less interest in activities. As their mood lifts, energy and activity return to their usual levels.
In the study, patients whose depressive symptoms improved in response to ketamine showed a particular level of activity before trying the drug: more activity earlier in the day and less activity later in the day. This finding suggests that activity patterns may help identify patients who would benefit from the drug.
“These findings are the first clinical results to suggest that trait-like circadian activity patterns are associated with rapid mood response to ketamine,” said first author Dr. Wallace Duncan from the Experimental Therapeutics and Pathophysiology Branch at the National Institute of Mental Health in Bethesda, Maryland.
For the study, the researchers used wristwatch activity monitors on 51 patients to examine measures of circadian timekeeping systems, including the timing and levels of activity. All of the patients had either major depressive disorder or bipolar disorder, and all had depressive symptoms that had not responded to any previous treatments.
The findings show that patients who responded to a single infusion of ketamine initially typically had more activity earlier in the day and lower activity later in the day than patients who did not respond to ketamine.
“In other words, their daily activity clock was shifted forward,” said Dr. John Krystal, editor of Biological Psychiatry.
Those patients who responded to ketamine also had advance-shifted timing of their activity on the first day after the treatment, and increased overall activity levels on the third day, consistent with the notion that activity levels are part of the clinical response to ketamine.
Altered measures of circadian timekeeping on the third day suggest that changes in circadian circuits may mediate ketamine’s continued effects on mood.
Furthermore, the differences in activity levels before and after treatment suggest biological differences in the circadian systems that regulate activity between people who respond to the drug and those who don’t. The researchers suggest that these underlying differences may help predict ketamine’s effects on mood.
“It would be nice if daily patterns of activity could be used clinically to identify people who might respond to ketamine and to monitor clinical improvement,” said Krystal.
According to Duncan, the findings are also important because they show that rapid-acting treatments such as ketamine can provide key insights into the associations between sleep and circadian rhythms, activity, and mood response.
The unique activity produced by ketamine suggests that the clock-gene mechanisms that control circadian rhythms may be linked to the type of depression that responds to ketamine.
In addition, depressive symptom scores were linked to decreased activity and increased sleep quality on the first night after the infusion, indicating that improved sleep quality may be key to ketamine’s rapid mood effects.