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What’s the Best Way to Treat a First Bout of Depression?


Oct. 25, 2018 Psychology Today

In the midst of these difficulties, a person faces an important decision: What is the best way to treat my depression? Options include talking with close friends and family members, self-help books and apps, over-the-counter remedies, psychotherapy, and prescription medication, among others. Many people find these choices overwhelming and are not sure where to begin, especially because it’s their first time dealing with depression.

Thankfully many people have thought really carefully about this decision, and none more than psychologist Robert J. DeRubeis of the University of Pennsylvania. I recently interviewed Rob to discuss the current state of the science in depression treatment research.

Do I Have a Chemical Imbalance?

First, let’s think about what causes depression, which may affect choice of treatment. An explanation that seems to have saturated popular culture is that depression is caused by a “chemical imbalance.” Most often the imbalance is said to involve too little serotonin—with the understanding that a drug is needed to fix it. I asked Rob for his perspective on this theory:

Seth J. Gillihan: What causes depression? Is it a chemical imbalance?

Robert J. DeRubeis: The chemical imbalance theories that came around in the 1950s were quite intriguing and they captured the imagination of the profession. There’s no doubt that whenever we are in a particular mood or when we come out of that mood, there are associated events in the brain. That’s a given and we all understand that.

But theories that led some to talk about a ‘chemical imbalance’ as a rather simple matter have really not panned out. There’s nothing simple about the neurotransmitters and their relation to depression. The brain’s a very complicated organ, and current thinking is more focused on the regulatory systems in the brain that are more active in some people than in others.

SJG: And yet that simple account of a chemical imbalance has been surprisingly persistent given how little data there have been to support it.

RJD: Yes, and of course it’s connected to the predominant treatments in the US and many other Western countries for people with mood difficulties—that is, the antidepressant medications. And so there are some kind of interesting links between what we think the antidepressant medications are doing and what we know about what happens at the synapses in certain areas of the brain, but the connections are not very tight, strong, or well understood. And indeed as I’ve read these literatures and contributed a bit to them, it’s common enough that what we find about a given neurotransmitter system is the opposite of what was first proposed.”

Can Psychotherapy Really Help with Severe Depression?

The lack of evidence for a chemical imbalance in depression might call into question whether the condition requires a chemical solution. I asked Rob about existing research comparing the effectiveness of meds and psychotherapy, particularly for severe cases of depression.

SJG: When I started in my doctoral program at Penn in 2001, the idea was that medication was like a key that fit in the lock of your chemical imbalance, which fed the idea that the real treatment for real depression was medication. Someone I interviewed with at Penn actually predicted that in a study you were doing at the time, ‘the meds were going to beat up on the therapy’ in the head-to-head comparison of CBT and an SSRI. So I wanted to get your perspective on why it was widely assumed that medication was better than the best therapy for treating severe depression.

RJD: In the 1970s and ’80s, the possibility that we could correct a simple imbalance was very exciting, and the medications that were being used were more effective than placebo pills, on average, for people with substantial depression. So the idea was that ‘Here we have a real and serious treatment for depression.’

Then along came a relatively small study—but an intriguing one—that found that cognitive therapy outperformed medication in that randomized trial. This was surprising to many who believed that ‘real’ depression needs a ‘real,’ physical treatment, and there were many skeptics, as there should have been. But then a couple of other studies showed very similar kinds of effects that were encouraging about the benefits of cognitive therapy in comparison to medication.

And then in what was thought to be a large study comparing medications with cognitive behavioral therapy, there were reports that medications outperformed CBT for those with the most severe symptoms [Elkin et al., 1989—a study that’s been cited over 3200 times]. This finding confirmed preexisting notions among the psychiatric community, and also spread to the public. The belief was that ‘now that we’ve done the real study and we’ve looked at more severe depression, we can see that we were too optimistic to think that CBT could work as well as meds.'”

This 1989 study did indeed seem to have a lot of sway over the depression treatment field; it was frequently cited as evidence for the superiority of medication over psychotherapy. But as Rob explains, the implications of that study’s findings appear to have been overblown.

RJD: It turns out that in that study, the comparison that everyone was excited about and took very seriously was a comparison of 27 patients in each group. Now, that’s not nothing, and it certainly is data that one needs to take into account. In the 1999 paper we wrote, those 27 patients who got medication in that trial did significantly better than those in cognitive therapy, but it turned out that study was unusual in that regard. Clinical science is a larger enterprise than one study, and when we were able to look across several studies, there was no advantage of the medications at all in the short run. Cognitive therapy and medications, on average, performed essentially exactly the same.

Does Medication Work Faster Than Psychotherapy?

While CBT and medication appear to be equivalent in their short-term effectiveness, some have suggested that medication works faster, and thus can lead to quicker relief.

SJG: One of the other common arguments for giving antidepressant medications right away is that they work faster than psychotherapy. Is that the case?

RJD: They don’t. And this belief again somehow meets up with preconceptions, but in the analyses we’ve done, there really isn’t a difference in speed of the effects, and if there are any, they’re really slight. Of course, it’s going to depend a bit on what the medication is and how active and directive and potent the psychotherapy is. But if you’re talking about an effective antidepressant and an effective cognitive behavioral therapy, the rates of change are pretty much on top of each other, on average.

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