Tricyclics, MAOIs, and Psychotherapy: Legacy Options in MDD Treatment

In "Tricyclics, MAOIs, and Psychotherapy: Legacy Options in MDD Treatment," our experts turn to the agents that have quietly fallen out of the algorithm.

Dr. Alva notes that monoamine oxidase inhibitors and tricyclic antidepressants have not become less effective, only less convenient. He observes that a generation of prescribers has lost the muscle memory, and asks Dr. Clayton where these agents sit in her algorithm.

Dr. Clayton answers that she is old enough to have trained when tricyclics and MAOIs were the only options available. Her main objection to tricyclics is lethality, because patients can kill themselves with them and it does not take much to die. For anyone who is suicidal, she will not go there absent some compelling reason far down the line. She adds a practical problem, which is that almost nobody knows how to use them anymore. Levels are no longer checked, and EKGs matter, particularly around midlife. MAOIs she treats differently, because they offer a genuinely unique mechanism, and she argues unique options are exactly what the field needs. That reasoning is why she is interested in the newer mechanisms now emerging. She does still use MAOIs, and she favors the selegiline transdermal patch because it avoids the same dietary restrictions, is well tolerated, and works. When she needs an oral MAOI, she counsels extensively on what patients can and cannot eat. She tells patients plainly that if they overdose or disregard the restrictions, she will not continue prescribing it. In her experience, patients who are being helped are very reluctant to jeopardize that.

Dr. Alva then asks about psychotherapy and combination therapy as first-line treatment in moderate to severe cases. Dr. Clayton says psychotherapy performs about as well as medication in mild depression. Beyond mild, combination therapy outperforms any single modality alone. She adds that when deprescribing, CBT and similar approaches help patients hold their gains rather than slide into relapse.

Our next episode, "Rapid-Acting Glutamatergic Therapy in MDD: Mechanism and Trial Data," turns to a rapid-acting oral option and the trial data behind it.