After years of dormancy, psychiatric drug development is showing signs of life. There is the novel antipsychotic lumateperone, recently approved for adults with schizophrenia. Brexanolone was approved last year for postpartum depression. And perhaps generating the most attention lately among psychiatrists – and people with depression – is the use of ketamine and esketamine for depression.
Dr. J. John Mann
Columbia psychiatrist J. John Mann, MD, a professor of translational neuroscience and a mood disorder specialist, has been involved in several notable studies of ketamine in patients with depression. He and his colleagues’ recent research efforts include a randomized study into ketamine’s ability to reduce suicidal thoughts in bipolar depression and an MRI analysis illuminating the role that dosing plays in antidepressant effects.
Dr. Sederer: Nearly 20 million people in this country alone suffer from clinical depression every year. That means they have a functional impairment in addition to their suffering and are at risk of taking their own lives. Depression is a very prevalent, painful, and disabling condition. The psychopharmacologic treatments we’ve had have been more or less the same for the past 20 or 30 years.
Dr. Lloyd I. Sederer
We’ve asked Dr. Mann to … talk to us about ketamine and its nasal preparation esketamine, which is a novel psychopharmacologic treatment. Dr. Mann, please tell us about ketamine, its utility, and the yet-to-be-answered questions.
Dr. Mann: Ketamine and esketamine, which is a component of ketamine itself, is different from traditional antidepressant medications in three fundamental ways.
The first is that it acts very quickly. Traditional antidepressants take 4, 6, 8 weeks to work. This means that the patient has to put up with a great deal of suffering while waiting for a response. And the probability of the medication working isn’t that high. About 50%-70% of individuals will respond eventually at the end of this ride. But ketamine, when it works, does so in 2 hours. That’s a totally different timescale.
The second aspect is that, when it does work, it often works very robustly, even though it’s a quick-acting antidepressant. The patient often quickly feels distinctly better.
Very often when you’re using traditional antidepressants, it takes a while for the improvement to reach the point that the patient is confident that they are clearly better, and too often that does not happen.
Dr. Sederer: As the treating doctor, you’re trying to keep that patient’s hope alive, even though we don’t have substantial evidence that they’re going to respond.
Dr. Mann: Exactly. One of the difficulties of keeping patients on track with traditional antidepressants is that, after the first dose or two, they have all the side effects and yet no benefit has emerged. In many ways patients sometimes feel that they’re going backwards. They have all of their depression plus the side effects of the medication.
But with ketamine, it’s rather different. You come in, you have the treatment, and many patients feel improved in a couple of hours. And not just a bit improved, but in many cases distinctly improved.
It’s very important for clinicians to appreciate that ketamine will work in patients who have a classically described treatment-resistant depression, meaning they’ve tried several other types of antidepressant medications that haven’t worked.
A prerequisite for treatment with ketamine is that they have had a number of treatment failures. The labeling for the intranasal esketamine states that you should try the other antidepressants first and then use this if they don’t work. The fact that ketamine can work even when the other medications have failed is a huge advantage.