Psychiatry Classics #5: Major depression remission rates in the STAR*D trial

A key question in the treatment of depression is: what is the probability that a given treatment will lead to a sustained remission of symptoms?

One of the largest, most famous studies to address this is called the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

From what I understand, the researchers designed the trial to mimic what might happen in a realistic clinical setting.

A patient diagnosed with major depressive disorder (MDD) might be first started on a first-line drug (citalopram). If that didn’t work (because the side effects were untolerable, or the symptoms persisted), then another drug would be chosen, and so on. Here is their algorithm:

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They used a unique randomization strategy, as participants in Level 2 could choose to opt out of the randomization blocks that entailed a) switching off of citalopram, b) augmenting citalopram with a different drug, and/or c) using cognitive therapy.

From the numbers above, you can see that most common option was for participants to opt out of cognitive therapy. This is probably in part accounted for by a selection bias for participants who would enter the citalopram-based trial in the first level.

One of the main outcomes was the remission rates from depression (defined as QIDS-SR16 score of <= 5) at the various stages:

  • For step 1, the remission rate for those not treated for their current episode was 43%, vs 36% for those already treated for their current episodes
  • For step 2, the remission rate was 30%
  • For step 3, the remission rate was 14%
  • For step 4, the remission rate was 13%
  • Assuming that none of the participants existed the study and stayed in treatment, the theoretical remission rate after a maximum of four treatment steps was 67%

They also looked at the 12-month follow up of these same participants. Of those, the proportion without a relapse (defined as QIDS-SR16 >= 11) was ~50% in the participants who had a remission of symptoms following step 1, and ~ 33% in the participants who had a remission of symptoms following step 2.

This data set has been analyzed in many other ways. For example, after unsuccessful treatment with the SSRI citalopram, there was no difference in the remission rates of buproprion, sertraline, and venlafaxine. On the other hand, augmenting citalopram with buproprion led to a greater reduction in symptoms and had fewer side effects compared with augmenting with buspirone.