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Early response to ketamine infusions for depression: comparison between genders.

Sheela Vaswani

Northeast Ohio Medical University


Introduction: Major Depressive Disorder is characterized by depressed mood, decreased energy, changes in sleep and appetite, anhedonia and suicidal ideation. FDA-approved antidepressants, which modulate monoamine neurotransmitters take several weeks to provide therapeutic relief. Recently, ketamine, a non-competitive NMDA receptor antagonist, has been used for treatment-resistant depression. Unlike other antidepressants, it is characterized by a rapid onset of action. Several studies have shown that a single-dose infusion of ketamine can rapidly decrease suicidal ideation and provide anti-depressant effects. From studies done on rodents, ketamine was found to be metabolized differently between females and males. Females had greater concentrations of ketamine over the first 30 minutes in both the brain and plasma due to slower clearance rates and longer half-lives. In addition, it is thought that due to the presence of estrogen and progesterone, females are more sensitive to the effects of ketamine. Estrogen’s role in the mesolimbic dopamine system, may account for the rewarding effects of ketamine with the repeated low dose infusions. Very few studies have examined the role of gender in response to ketamine in the clinical setting. Our hypothesis is females will see a more significant early response to ketamine treatment. Methods: The study was approved by the Institutional Review Board and Participants signed consent. Patients (n=16, 8 male, 8 females) received 0.5 mg/kg continuous intravenous infusion of ketamine over 40 minutes for treatment-resistant depression at on a biweekly schedule as standard of care. Treatment response was measured using the clinician rated Montgomery Asberg Depression Rating Scale (MADRS) and the self-reported Patient Health Questionnaire-9. Scores at the 2nd visit (2-5 days after the 1st injection) were compared to scores at baseline. Results: The average MADRS scores decreased 12.6% for men (from 36.5±9 to 31.9±10.5) and 25.9% for women (from 33.6±7.6 to 24.9±7) between the 1st and 2nd assessments. After one injection, 37.5% of women and 0% men had a decreased in MADRS score >50%, defined as response to treatment. Conclusion: Analysis of data from this small sample suggests that females may have a higher rate of early response to low-dose ketamine infusion than men. This will need to be confirmed with a larger sample for statistical significance.

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