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Depression - remission, relapse, and getting a grip


Clinical bottom line

Getting on top of depression early is important because it predicts less likelihood of depression returning later. A minority of patients will do well on any single treatment, and several may have to be tried to find one that does the job. The best sequence is unknown.


AJ Rush et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. American Journal of Psychiatry 2006 163: 1905-1917.


STAR*D is a study on sequences treatment alternatives to relieve depression. It used one or more active treatment steps to achieve symptom remission in the short term, using vigorous and timely dose adjustments and changes in treatment when remission was not attained. Patients in reemission, and with a lesser degree of treatment response, were able to enter a 12-month naturalistic follow up phase where management was by clinician judgement, with recommendations to continue previously effective acute treatment medications.

Definitions used in the study were:

The overall design is shown in Figure 1. Patients with at least moderate depression all went into step 1, citalopram. If that failed, then up to three additional steps were available with different antidepressants, or cognitive therapy, or combinations, or lithium or T3 supplementation. The outcomes were remission and response in the acute steps, and remission in the follow on phase.

Figure 1: Design of Star D - acute and follow up phases


Of 4,014 patients enrolled, 3,671 had a postbaseline assessment. Table 1 shows that the proportion with remission and response declined with each additional step, while the proportion with intolerable adverse events increased. Overall, the theoretical maximum remission rate was 67%, assuming no dropouts.

Table 1: Remission, response, and intolerable adverse events in steps 1-4 in the acute phase

Step 1
Step 2
Step 3
Step 4
Total number at entry
Remission (%)
Response (%)
Intolerable AE (%)


Relapse rates in the follow up phase depended on level of response and number of steps taken in the acute phase. There was more relapse in those in remission at entry than those with a level of response less than remission. There was a more relapse where more steps had been taken to get remission. Of these two factors, being in remission on entry to the follow up phase appeared to be the more important (Figure 2).

Figure 2: Relapse rate in follow up phase according to degree of benefit and number of steps taken in the acute phase


These findings have profound clinical importance. Remission is associated with better function and prognosis, and probably less overall cost to health services. The study shows that getting remission in the early stage of treating depression is important, because it predicts longer term response and less likelihood of relapse. That might mean accepting that a sequence of steps is needed for a sensible acute phase care pathway, and an unwillingness to accept lesser degrees of benefit.

We don't know the best sequence of treatments that will provide the best overall result, but it is likely that those that get more remission sooner will feature highly in any effective care pathway.