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Ketamine: Repeated Infusion Protocol, Tolerance, and Non-Responders

Although just a single infusion of ketamine has been shown to have anti-depressive effects within a few hours, the research shows that completing a series of repeated infusions is superior at reducing symptoms for treatment resistant depression. Ketamine infusions have been found to have maximal antidepressant effects at 24 hours. The repeated infusion protocol consists of either six ketamine infusions administered 3 times weekly for 2 weeks, or 1 to 2 times weekly over 3-4 weeks. Interestingly, it has been found that repeated infusions do not show evidence of tolerance, meaning that patients experience similar antidepressant responses with repeated infusions. This differs from other traditional antidepressant medication’s where patients may fail to respond with repeated similar dosages of a medication.

Furthermore, it has been found that the anti-depressive effects of ketamine are cumulative, meaning that depressive symptoms may further decrease in severity after each infusion. So, what about patients who do not initially respond to ketamine? Are they immediately considered non-responders? Not necessarily. Some patients require three or even more infusions before meeting response criteria, indicating that individuals who initially fail to respond to a single infusion may still respond after repeated administration.

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