Mounting clinical evidence supports the use of intravenous (IV) ketamine for the rapid treatment of depression and anxiety disorders. Over the past decade and a half, physicians have continually noted the drug’s robust antidepressant quality, which provides very rapid near instantaneous symptom relief. In comparison to traditional antidepressant drugs that often take weeks to months to take effect (if they do at all), ketamine’s effect is felt after only a single dosage. In this way, infusion therapy offers new hope for those suffering from the most acute and treatment-resistant forms of these disorders. The therapy can be applied in these cases as a stabilizing intervention—allowing patients to survive long enough to seek further treatment and recover.
Empirical clinical evidence supports an IV ketamine protocol of 6 infusions over a 3 week period. In our own experience, the majority of our patients selected for this treatment regimen saw immediate improvements in their condition. However, what remains an ongoing topic of clinical interest is the efficacy of ketamine infusion therapy long term. Numerous studies are currently underway investigating means of extending and maintaining the clinical response of ketamine therapy using other therapeutic agents.
These studies look to identify potential drugs that may have a synergistic effect with ketamine. These drugs may operate on the same glutamatergic receptors as ketamine or other downstream mechanisms. One such study is currently underway at Mount Sinai Medical School. Investigators there believe oral lithium may help maintain the long-term response of ketamine by inhibiting the glycogen synthase kinase 3 (GSK3) intracellular signaling pathway—a cellular pathway that has been identified as critical in the antidepressant action of both drugs. Preliminary data from the experiment appears to be promising—we, however, will have to wait another few months to a year before the final paper is published.
Another study published this past year by Kantrowitz et al. investigated the use of D-cycloserine for maintaining ketamine’s response. D-cycloserine is a FDA-approved anti-tuberculosis drug, which, like ketamine, is a partial NMDA receptor antagonist. D-cycloserine is of particular interest to researchers because of its clinical advantages: it can be delivered orally and the drug has established safety and tolerability long-term. In their small-scale study of bipolar individuals, D-cycloserine was shown to prevent relapse of symptomology after initial ketamine therapy. The majority of participants experience full remission throughout the 8-week observation period.
While both of these potential treatment avenues are still in their nascent phases, they exemplify the kind of rapid advancements being made to develop and refine IV ketamine therapy. More generally, these studies fit into a growing body of research on ketamine as an antidepressant and speak to the excitement surrounding ketamine in the clinical psychiatric community.
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