Objective
Depression relapse after electroconvulsive therapy (ECT) is common (40% at 6 months). Ketamine has a robust antidepressant effect, but there are no reported studies of ketamine for depression relapse prevention. This pilot trial (NCT02414932) was designed to assess feasibility of the proposed trial protocol, including examining reasons for nonrecruitment, nonrandomization, and dropout.
Methods
Patients with unipolar depression referred for ECT were monitored weekly for therapeutic response, using the 24-item Hamilton Rating Scale for Depression (monitoring phase). Those who met standard response criteria were invited to be randomized to a course of 4 once-weekly infusions of ketamine (0.5 mg/kg) or the active comparator, midazolam (0.045 mg/kg), over 40 minutes to examine trial processes (treatment phase). Participants were followed up for 6 months after ECT to assess for relapse.
Results
One hundred seventy-five referrals were screened over 18 months, and 68% of eligible participants (n = 43) were recruited to the monitoring phase; 60.5% of participants met ECT response criteria (n = 26), but only 26% (6) of these consented to take part in the treatment phase. These were randomized (3 to ketamine and 3 to midazolam), and no participant completed the 4-week treatment protocol. Information was gathered on reasons for nonrecruitment, nonrandomization, and dropout, which included practical aspects of infusions and lack of interest in further treatment after response to ECT.
Conclusions
The proposed treatment protocol is not suitable for a definitive trial in our center. Information collected on reasons for dropout may inform future clinical trials of intravenous ketamine.
Trial registration: www.clinicaltrials.gov NCT02414932.
Vulnerable groups are often excluded from clinical research on the basis of scientific, ethical and practical reasons. Although intended to protect vulnerable people and maintain study integrity, exclusion of vulnerable groups from research through use of standard exclusion criteria may not always be necessary and may result in findings that are not generalisable. Achieving a balance between the competing needs to protect vulnerable people and to make progress in our understanding of disorders and their management through research requires a reconsideration of exclusion criteria and consent processes to ensure vulnerable people are appropriately represented in clinical research. Reasons for development of broad exclusion criteria include both concrete barriers and intangible discouraging factors. This paper examines this situation and its consequences, perceived and real barriers to inclusion of vulnerable people in research, and suggests methods for overcoming these barriers and applying thoughtful exclusion criteria.
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