Clinical Depression and Treatment Planning

Michael E. Thase, MD: If we talk about a syndrome and the syndrome having a weight, the weight can be measured by the number of symptoms and the intensity of each symptom. And so, you can use a standard rating scale to basically estimate the severity that the person is suffering from. Now, obviously some symptoms are more severe and worrisome than others. Strong suicidal ideation, for example.

Nevertheless, the more symptoms, the stronger the symptoms, the more likely it is that the person is not functioning well. And so, when you initiate a treatment, you want to have a baseline measure of the weight of the depressive syndrome, and then at key time points—ideally every other week, but even if that’s not possible, monthly. The same measure of the same signs and symptoms to see what progress has been made. Almost always, you need to have about a 50% reduction in the weight of the symptoms to declare that the person is significantly better. A little better isn’t good enough. Significantly better is a starting place, because then you know you’re on the right track with the treatment. Ideally, you’re aiming to help the person achieve what we call a remission, which basically means an almost complete reduction of the signs and symptoms of the depressive episode.

When you’re initiating a treatment, you want symptom relief to occur pretty quickly. But even before that, if the treatment’s a medication, you want to make sure that the treatment is reasonably well tolerated.

A first time-limited goal in a management plan would be to pick a medication that is affordable, can be taken without worrisome adverse effects or annoying adverse effects, and can start to put the antidepressant treatment process into motion. That’s a goal for the first 2 weeks of treatment, to accomplish those things. That’s the first time-limited goal.

A second time-limited goal would be to get that first substantial symptom relief. And so, let’s aim to see that by 4 weeks. Ideally, we’d want to see it at 2 weeks, if we could. Some treatments work a little faster than others, but generally, if you’re not seeing that kind of reduction in the first 4 weeks, you may have to pick a different treatment for the depression.

To get to the end of the acute phase of treatment, that would be the third time-limited goal, that’s generally between the 6th and 12th week of treatment. That’s when you’ve declared victory with this particular treatment plan, or turn to another treatment plan, for which you’re resetting your time-limited goals.

There are all sorts of different guidelines to help physicians stay on track with their treatment efforts, and there are guidelines for various different kinds of disorders. For the depressive disorders in the United States, the American Academy of Family Physicians and the American Psychiatric Association have practice guidelines, as does the [US Department of] Veterans Affairs medical system. So depending where you’re practicing, there is a coherent set of guidelines available for you. I think the first American Psychiatric Association practice guidelines came out in 1993. I’m pretty sure they were revised again around the year 2000, and I think the third edition came out in 2010. The third edition is the most recent one, in part because the American Psychiatric Association has slowed its efforts with guideline development. It’s still weighing the impact of their experts’ relationships with the pharmaceutical industry. They’re very concerned and cautious that patients perceive that their treatment is being guided as much by experts’ opinions as experts’ relationships with pharmaceutical companies. This is a controversial area. You can’t have guidelines written by people who aren’t experts, but if you limit the guidelines to only people who have no relationships with the pharmaceutical industry, you have few experts left to write the guidelines. So we’ve not come to a good peace with that.

My favorite current practice guideline is the one that our Canadian colleagues, from their mood disorders consortium, does. There’s a 2016 version that is almost perfectly well suited for practitioners in the United States.

If we were going to take the Canadian guidelines and use them to update the American Psychiatric Association practice guidelines, we’d have the newest antidepressants. Medications like vortioxetine and vilazodone would be added. The whole value of using newer-generation antipsychotic medication for adjunctive therapy of major depressive disorder, that has mostly come online since the last edition of the American Psychiatric Association practice guidelines. But even the Canadian guidelines don’t have a full, up-to-date assessment of the newest therapies that have been introduced in the United States, including Spravato, which is the intranasal form of esketamine. And then the newest medicine approved for postpartum depression, brexanolone, which is a very interesting GABA [gamma-aminobutyric acid]-acting medicine called a neurosteroid, basically, which is another kind of rapid novel treatment for a condition that previously we had no specific medications indicated for.

Transcript edited for clarity.