Therefore, it seems plausible that ketamine could produce both short- and long-term improvements in mood. Hallucinogenic drugs are thought to profoundly alter brain function through several mechanisms, including activating serotonin receptors, enhancing brain plasticity, and increasing brain connectivity.16
Psychiatric medications that are acutely reinforcing have significant potential for abuse. Antidepressants and mood stabilizers are not acutely rewarding. They don’t make patients feel good right away. Medications such as stimulants and opioids do, and must be used with extreme care because of their abuse potential. The problem with acutely reinforcing medications is that in the long run, they can worsen depression by decreasing the brain’s ability to produce endogenous opioids.17
4. No single solution?
A mental disorder is unlikely to have a single solution. Rather than regarding a new treatment as capable of rapidly alleviating every symptom of a patient’s illness, it should be viewed as a tool that can be helpful when used in combination with other treatments and lifestyle practices. In an interview with the web site STAT, Cristina Cusin, MD, co-director of the Intravenous Ketamine Clinic for Depression at Massachusetts General Hospital, said, “You don’t treat an advanced disease with just an infusion and a ‘see you next time.’ If [doctors] replace your knee but [you] don’t do physical therapy, you don’t walk again.”18 To sustain the benefits of a novel medication, patients with serious mental illnesses need to maintain strong social supports, see a mental health care provider regularly, and abstain from illicit drug and alcohol use.
5. Context matters
For a medication to obtain approval to treat a specific indication, the FDA usually require 2 trials that demonstrate efficacy. Off-label use of generic medications such as ketamine may have benefits, but it is unlikely that a generic drug would be put through a costly FDA-approval process.19
When learning about new medications, remember that patients might assume that these agents have undergone a thorough review process for safety and effectiveness. When our patients request such treatments—whether FDA-approved or off-label—it is our responsibility as physicians to educate them about the benefits, risks, effectiveness, and limitations of these treatments, as well as to evaluate the appropriateness of a treatment for a specific patient’s symptoms.
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