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When Antidepressants Fail, What Next?

Last month, we saw a flurry of new studies released related to the ground-breaking, large-scale depression study called STAR*D. STAR*D will likely provide data for researchers to continue to publish upon for many months to come.

Two of the studies dealt with what happens when an antidepressant treatment fails. What do people do next, and how much does the second treatment help them?

In the first study,

Treatment of major depressive disorder typically entails implementing treatments in a stepwise fashion until a satisfactory outcome is achieved. This study sought to identify factors that affect patients’ willingness to accept different second-step treatment approaches.

The researchers found that, when patients are given a choice after failing with a first-step medication treatment — in this case, Celexa — only 29% would opt to add psychotherapy (cognitive therapy, to be precise) to the mix. 71% would have nothing to do with psychotherapy. What factors might influence a person’s decision to try psychotherapy to help with their depression?

Those with higher educational levels or a family history of a mood disorder were more likely to accept cognitive therapy. Participants in primary care settings and those who experienced a greater side effect burden or a lower reduction in symptom severity with citalopram (Celexa) were more likely to accept a switch strategy as compared with an augmentation strategy.

In other words, well-educated people, people who saw their family doc, people who had nasty Celexa side effects, or found little anti-depressive benefits from the Celexa were all more willing to give psychotherapy a try. Those who had recurrent major depression or a drug abuse problem were less likely to do so.

Still, it’s a little depressing to read that so few people, when given the choice, choose not to try psychotherapy. I wish the researchers had asked the all-important question, “Why not?”

Meanwhile, Thase and his colleagues looked at what happens when people were assigned to either cognitive therapy or a different antidepressant, and whether both groups improve or not:

After an unsatisfactory response to citalopram (Celexa), patients who consented to random assignment to either cognitive therapy or alternative pharmacologic strategies had generally comparable outcomes. Pharmacologic augmentation was more rapidly effective than cognitive therapy augmentation of citalopram, whereas switching to cognitive therapy was better tolerated than switching to a different antidepressant.

Drugs work faster, psychotherapy works slower. Drugs have more side effects, while psychotherapy has few. Both were about equally as effective.

Which only goes to show you that (a) depression must not be as “biologically based” as some would have you believe (have you ever heard of psychotherapy doing much help in keeping blood sugar levels balanced in a diabetic?) and (b) psychotherapy is a very powerful treatment, working just as well as medications for most people.

Wisniewski SR et. al. (2007). Acceptability of second-step treatments to depressed outpatients: a STAR*D report. Am J Psychiatry. 164(5):753-60.

Thase ME, et. al. (2007). Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Am J Psychiatry. 164(5):739-52.

When Antidepressants Fail, What Next?

John M. Grohol, Psy.D.

Dr. John Grohol is the founder of Psych Central. He is a psychologist, author, researcher, and expert in mental health online, and has been writing about online behavior, mental health and psychology issues since 1995. Dr. Grohol has a Master's degree and doctorate in clinical psychology from Nova Southeastern University. Dr. Grohol sits on the editorial board of the journal Computers in Human Behavior and is a founding board member of the Society for Participatory Medicine. You can learn more about Dr. John Grohol here.

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APA Reference
Grohol, J. (2018). When Antidepressants Fail, What Next?. Psych Central. Retrieved on November 30, 2020, from
Scientifically Reviewed
Last updated: 8 Jul 2018 (Originally: 27 Jun 2007)
Last reviewed: By a member of our scientific advisory board on 8 Jul 2018
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