The  Depression roared back with a vengeance: three visits in three weeks to the emergency department of a busy inner-city hospital in downtown Toronto. The third time she was actively suicidal; and is whisk away to the psychiatric crisis unit on the bright and airy fifth floor. I was a medical student at the time; doing a rotation in psychiatry, and is giving the task of spending time each day with Mary (I’m using a pseudonym here) to monitor her symptoms;p her insight into her illness, and the goals of her care. Nothing the medical team tried seemed to work.

Experimental trial

She was on the maximum dose of her antidepressant, a selective serotonin re uptake inhibitor (SSRI). An experimental trial of deep-brain stimulation months earlier had little effect. By definition, our 52-year-old patient met the criteria for treatment-resistant depression. At the time I couldn’t quite understand Mary’s condition or our futility in treating it. I spent hours each evening searching for something that might help Mary; returning the next day with a new idea: a gratitude journal; spending time in the fifth-floor garden; or revisiting the cognitive behavioral therapy that she had tried before.

Mary seemed grateful for my earnestness; but it was unlikely that the strategies I suggested would make a significant long-term difference. Mary never really eased, and she would likely return to the hospital after she was discharged. The psychiatry toolbox was empty. This openness to new treatments is a signal to the medical community that best practices can and must change. It’s also a signal that practitioners must be train to supervise “the trip.”

Depression symptoms

In clinical trials, esketamine improved depression symptoms within a few hours. It’s believe that the drug acts on what’s call the NMDA/glutamate pathway; a different mechanism than the way SSRIs work, though the exact mechanism of action on the neurotransmitters involve in depression are unknown.

Breakthrough drugs for mental health disorders, and particularly depression; are rare none since the approval of SSRIs in 1987. Other modalities have instead emerged: deep brain stimulation (which has mixed-reviews); and a helmet that delivers repetitive transcranial magnetic stimulation. As it stands; esketamine is poised to drastically change how psychiatric care is delivered it will soon be rolled out in VA system.

Psychiatric medication

Yet in its approval of esketamine, the FDA overlooked one essential issue: while psychiatrists provide “talk therapy” and others dispense medications, it’s almost unheard of for a doctor to dispense a psychiatric medication and supervise the reaction for up to two hours. In a mental health care system where waitlists are already weeks long, will the system adapt to allow for this additional period to supervise the immediate effect of the medication?
Ketamine is something of a Jekyll-and-Hyde drug. It has been used effectively as an intravenous anesthetic for more than 50 years, even though it is associated with side effects such increased heart rate and blood pressure, nausea, and what’s called the emergence reaction: After a procedure; some people awaken terrified and combative, occasionally requesting they never be given the drug again.