The STAR*D trials II: Switching antidepressants [Classics Series]

Classics Series, Landmark Trials in Medicine

1. In cases where citalopram fails or cannot be tolerated, approximately 1 in 4 patients will experience remission of their depression symptoms by switching to sustained-release buproprion, sertraline, or extended-release venlafaxine.

Original Date of Publication: March 2006

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trials explored the management of patients who had refractory depression despite treatment with a selective serotonin-reuptake inhibitor (SSRI). Two papers were published based on data from the STAR*D trials in NEJM in 2006, which involved outpatients with nonpsychotic major depression who had not experienced remission with citalopram alone. In both papers, the primary outcome measure was remission with a score of <7 on the Hamilton Rating Scale for Depression (HRSD-17), while secondary outcome measurement of remission and response was done using the Quick Inventory of Depressive Symptomatology (QIDS-SR-16). Patients in this study were given the option to 1) augment their therapy by adding other agents or 2) switch to another therapy.

Study Rundown: In patients suffering from refractory depression after a trial of citalopram, switching to another medication resulted in approximately 1 in 4 patients experiencing remission of their symptoms with sustained-release buproprion, sertraline, or extended-release venlafaxine. A strength of the STAR*D studies is the few criteria for inclusion and exclusion, which suggests that these findings may be very generalizable to an outpatient population. Limitations include the lack of a placebo control group and the fact that treatment delivery was unblinded. Interestingly, the rates of remission with switching medications were lower than the remission rates observed with augmenting therapy. Part of this may be attributed to the differences in patient pools seen in the two studies (i.e., the “medication switch” study having a larger proportion of patients who could not tolerate citalopram) and the inadequate doses/treatment durations. Nevertheless, this study demonstrates clinically meaningful remission rates when switching to other antidepressants.

Click to read study in NEJM

In-Depth [randomized, controlled trial]: Apart from augmentation, switching to a different anti-depressant represents another option for managing patients who do not experience depression remission despite treatment with an SSRI. In this study, 727 outpatients with nonpsychotic depression were enrolled – all had been previously treated with citalopram and had not experienced remission or could not tolerate citalopram. Patients were randomized to switch from citalopram to 1) sustained-release buproprion (a norepinephrine-dopamine reuptake inhibitor, NDRI), 2) sertraline (another SSRI), or 3) extended-release venlafaxine (a serotonin-norepinephrine reuptake inhibitor, SNRI).

Remission rates were not significantly different between the three treatment groups, as measured by HSRD-17 scores (21.3% in the buproprion group, 17.6% in the sertraline group, 28.4% in the venlafaxine group). Moreover, the three groups were not significantly different with regards to response/remission rates, or time to response/remission, as measured by QIDS-SR-16 scores, nor were they significantly different in terms of their rates of side effects or serious adverse events.

Image: PD

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