It is estimated that about 15-30% of patients with depression continue to experience symptoms despite multiple medication trials, meeting definition of treatment resistant depression (TRD). This can be a dark and scary place especially considering there has not been much movement in terms of revolutionary new antidepressants.
Of the Food and Drug Administration (FDA ) approved non pharmacological interventions for TRD, electroconvulsive therapy (ECT), continues to play an important role, especially is setting of suicidal ideation but may not appeal to some. Transcranial magnetic stimulation (TMS) is newer, with mixed results, one of the drawbacks being the daily time commitment over the course of several weeks.
In recent years ketamine has surfaced as a potential treatment for TRD. Interest in ketamine lies around the fact that unlike other antidepressants that work on the monoamine system (think serotonin and dopamine), ketamine works on a completely different mood altering pathway at the NMDA receptor. Ketamine is a commonly used anesthetic in the operating room. It has not been approved by FDA for TRD however off label use is beginning to gain some traction. It can be administered in a clinic, ideally set up with a means to monitor cardiovascular and respiratory activity. The doses used for depression, infused by IV over 40mins, are significantly lower than those for anesthesia, with patients experiencing a significant improvement in mood and alleviation of suicidal ideation almost right away, peaking at 72hrs. The effects however, are not long lasting, and while in clinical practice patients receive 2-3 treatments a week, there are no studies that look at the long term effects of ketamine. The sides effects tend to include increased blood pressure and heart rate, and a dissociative woozy feeling which wears off within a couple of hours.
So why would anyone even consider ketamine if the results are so transient? Well, for someone struggling with a resistant depression or suicidal ideation, even the smallest amount of relief may be enough to generate a sense of hope and mobilization. For others, it may provide the missing piece or boost to their existing regimen. Whatever one’s personal reasons may be for considering ketamine infusions for depression, it is important to be aware of the limitations and risks, including the potential for abuse, and lack of data on long term efficacy and safety.
Murrough JW. Ketamine as a Novel Antidepressant: From synapse to behavior. Clin Pharm & Theraputics. 9;2 (303-309) 2012
Sanacora G et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA psychiatry. 74;4 (399-405).2017