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Antidepressants get people better from depression, but what keeps them better? In this episode, Dr. Giovanni Fava suggests we may need to stop trying to stamp-out pathology and start finding ways to enhance well-being as patients recover.

Published On: 7/12/2021

Duration: 15 minutes, 42 seconds

Related Article: “Psychotherapy and Medication in Recurrent Depression,” The Carlat Psychiatry Report, June/July 2021

Antidepressants get people better from depression, but what keeps them better? In this episode, Dr. Giovanni Fava suggests we may need to stop trying to stamp-out pathology and start finding ways to enhance well-being as patients recover.

Welcome to The Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of The Carlat Psychiatry Report. And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

Dr. Aiken: It’s not easy to get patients with depression better, but it’s even harder to keep them well. Dr. Giovanni Fava learned in the lesson as he worked with depression in the 1990’s, and he has spent the past 3 decades researching ways to keep them well. That journey has taken him from antidepressants to cognitive behavior therapy to a new psychotherapy – well-being therapy – and recently to an innovative way of combining medication with psychotherapy called sequential treatment.

Other researchers have joined him in the search for better ways of preventing depression, and they now have enough studies out there to fill a meta-analysis. And those meta-analyses point to conclusions that are not exactly in line with the way we practice. Most people combine antidepressants and psychotherapy by starting both at the same time, but there’s little evidence that that kind of combination therapy does much to improve outcomes. Instead, we see a plateau effect – antidepressants help on their own, psychotherapy helps on its own, and combining the two rarely does any better than they did on their own.

Kellie Newsome: It’s like adding water to a sponge. You take a dry sponge, and pour a cup of water on it, and it’s going to soften up and get wet. But if you pour 2 cups of water on it, it doesn’t get any wetter – it reaches its plateau.

Giovanni Fava: When psychotherapy and antidepressants are done together from the very beginning – not in a sequential way, with every few exceptions we don’t see many advantages.

Dr. Aiken: There are exceptions to this – behavioral activation has successfully augmented antidepressants, and a unique kind of psychotherapy for chronic depression called the cognitive behavioral analysis system of psychotherapy or CBASP made nefazodone work better in patients with dysthymic disorder and chronic depression. But these are the exceptions.

Kellie Newsome: But Dr. Fava was able to show that psychotherapy can augment antidepressants, and he did it in a way that changes how we think about the two treatments – at least for me it did. Drawing from his early observations in the 1990’s, he speculated that antidepressants were very good at treating depression, but were not so good at preventing it. Psychotherapy, on the other hand, may not work as quickly as antidepressants, but it may do more to keep people well for the long haul. So he set out to develop a psychotherapeutic approach to depression prevention. He started with cognitive behavioral therapy, but found that it didn’t do enough to address the problem many patients with recurrent depression suffer from: Residual symptoms.

That’s when patients continue to have a few depressive symptoms, but not enough to meet criteria for a full episode. Residual symptoms tend to grow like a weed in a garden, most likely because they affect behavior in ways that might cause depression, such as through avoidance and interpersonal difficulties. The more the residual symptoms, the higher the chance of relapse. 

Dr. Aiken: And while residual symptoms put patients at risk for relapse, let’s keep in mind that these patients are already mostly well. And being well is something new for them, something they need to learn how to manage and maintain. So Dr. Fava decided that – rather than continue to target depressive thoughts and depressive behaviors like CBT does – he would develop a psychotherapy that helped recently depressed patients increase their well-being. Instead of making the bad stuff shrink, he was going to back the good stuff grow, and to do that he turned to an early pioneer in the positive psychology movement: Marie Jahoda.

Marie Jahoda and Positive Psychology

Kellie Newsome: Marie Jahoda “Ya-hoda” was a social psychologist whose work on prejudice, unemployment, and authoritarian personalities spans the decades of the 1930’s to the 1990’s. But perhaps her best known contribution was her 1958 book Current Concepts of Positive Mental Health, where she laid the groundwork for the positive psychology movement with this oft-quoted exhortation:

“The absence of mental illness is not a sufficient indicator of mental health.”

In that book Jahoda described the key characteristics of healthy people. They have a sense of control and mastery over their lives, and a consistent outlook or set of beliefs that guides their actions and feelings so that – ultimately – they can shape their future. They adapt flexibly and can tolerate stress, frustration and anxiety. They are active and productive. They work effectively with others and build meaningful relationships. They are realistic and accepting – in the way they view themselves and the world around them. 

When these ingredients are more or less in place, well-being is the result.

Dr. Aiken: Dr. Fava adapted these ideas into well-being therapy and designed a randomized controlled trial to compare it to standard CBT in people who had recovered from depression but continued to have residual symptoms. When it came to reducing residual symptoms, well-being therapy was the more effective of the two.

He went on to show that well-being therapy helped prevent depressive episodes, and improved recovery in generalized anxiety disorder and cyclothymic disorder. That last one is remarkable because it is the only randomized controlled trial with positive results in cyclothymic disorder I know of – that’s right, there are no controlled trials of medication in this mild but chronic version of bipolar disorder – instead, psychotherapy is the best studied treatment.

Kellie Newsome: Next, Dr. Fava tested well-being therapy as part of a new model of treatment for recurrent depression – the sequential treatment model. In this model, patients start with an antidepressant to get them out of the depression. Once they are largely recovered, well being therapy is added on to reduce residual symptoms and help them develop new habits to stay well. The sequential addition of well-being therapy helped patients stay well longer, and it even helped them come off their antidepressant successfully. In other words, 8 sessions of well-being therapy worked as well as continuing the antidepressant, and with fewer side effects. 

Dr. Aiken: That idea may seem counter-intuitive – to taper off an antidepressant in a patient who continues to have residual symptoms. But Dr. Fava explained it like this – the antidepressant has done as much as it could, and is no longer helping – and why not taper it off and add something that is will treat the remaining symptoms – especially if it is causing side effects.

Giovanni Fava: So if the medication didn’t do that much and they have still have the residual symptoms, how do we expect that the medication worked on the symptom? And it’s also another way of empowering the patient saying, “Okay, we are taking this off. But be careful. You have to do your 50%, otherwise everything collapses.”

Kellie Newsome: Dr. Fava is not alone in this research, and neither is well-being therapy. Others have explored this model of sequential treatment using mindfulness-based CBT, or a preventive model of CBT with similar results. Like well-being therapy, preventive CBT also guides patients to keep their eyes on the positive. Instead of simply challenging negative believes, patients are encouraged to come up with ideal beliefs that represent their best self, like “I’m a good friend and a loving father,” and to flesh that out with questions like “What would you be doing if you were a good friend and a loving father?”

Whether you use mindfulness, preventive CBT, or well-being therapy, this sequential approach is a shift from usual practice, where antidepressants are continued indefinitely, with or without psychotherapy. And it made me realize that something is missing in psychiatry. We don’t distinguish acute treatments from preventative treatments like other medical fields do.

Giovanni Fava: We work with oversimplified, unsupported claims, and one of these claims for instance is that the medication that made you feel better is the best and keeping them. This assumption is in medicine – there are many examples of what to use for an acute hypertensive crisis which may be quite different from what to use for essential hypertension. So there are a lot of things and mostly, however, is the neglect of the use of psychotherapy.

Dr. Aiken: In our online interview, Dr. Fava talks more about when to use antidepressants or psychotherapy in recurrent depression, tips on managing antidepressant withdrawal, and how to weave well-being therapy into a brief medication visit. 

Kellie Newsome: Here’s a hint – one of the key steps in well-being therapy is to ask the patient to watch for times when they feel well in the coming week, even if it was brief and rare. Then, when they come back with an example, you don’t focus on what was going on that created that optimal state – instead you ask what caused that good feeling to go away. It leads to some revealing answers. 

22:29

Giovanni Fava: So to summarize, use the antidepressants until the patient is no longer depressed. You work with psychotherapy and the great Jerome Frank used to write about psychotherapy is nothing else than guided self-therapy. 

So psychotherapy, lifestyle modification may bring you to a state of euthymia, which is a step above the limbo of no symptomatic state. And the state of euthymia may give you more resistance to stress, to environmental circumstances, and may make relapses less likely.

Dr. Aiken: Dr. Giovanni Fava is a Clinical Professor of Psychiatry at the State University of New York at Buffalo and Editor-in-Chief of the journal Psychotherapy and Psychosomatics. Under his leadership, that journal has risen its influence and now has an impact factor that lands it in the top 4 journals in psychology as well as in psychiatry. His book, Discontinuing Antidepressant Medications, is due from Oxford University Press later this year. 

And now for the word of the day…. Tetracyclic antidepressants

Kellie Newsome: Who put the tri- in tricyclic? Or the tetra- in tetracyclic? The answer has to do with the number of atomic rings in the chemical structure – tricyclics have 3, while the lesser known tetracyclics have 4 rings. There are 3 tetracyclics in the US, but two of them are often classified with the tricyclics – maprotiline, released in 1974, and amoxapine, a relative new-comer released in the US in 1992. Compared to the tricyclics, these two are more selective for norepinephrine than serotonin. And then there is mirtazapine – yes, mirtazapine (Remeron), released in 1996, is also classified as a tetracyclic, though its unique pharmacodynamic profile really puts it in a class of its own. In this month issue we have an important research update on mirtazapine in PTSD, and next we’ll bring you 5 more updates from this year’s crop of clinically relevant studies on mirtazapine.

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