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Thursday, August 30, 2007

9 Steps for Treatment-Resistant Depression

50 to 60 % of patients with a depressive disorder fail to respond to their first antidepressant. These rates increase in clinical practice setting to 65 to 85%. Estimates of TRD prevalence varies greatly depending on treatment setting. The lowest TRD prevalence is in primary care and progressevily higher rates occur in outpatient psychiatric settings, inpatients settings and academic tertiairy setting.

Compared to non-TRD, TRD patients have been reported to have significantly higher outpatient medical costs, and to be approximately twice as likely to be hospitalized, either medically or psychiatrically
From: Nemeroff CB. J Clin Psychiatry. 2007;68 Suppl 8:17-25.
Prevalence and management of treatment-resistant depression. Abstract

What is Treatment-Resistant Depression?
An inadequate response to an adequate course of treatment in a patient meeting criteria for major depressive disorder. Treatment is usually antidepresssants. Depression is not bipolar depression. This diagnoses needs a different approach. An adequate course is a course of an adequate dosage of the antidepressant for at least 6 weeks. This has been operationalized in criteria for different stages of TRD:

Stage 1. Failure of an adequate trial of 1 class of antidepressant

Stage 2. Failure of adequate trials of 2 distinctly different classes of antidepressants

Stage 3. Stage 2 plus failure of a third class of antidepressant, including a tricyclic antidepressant

Stage 4. Stage 3 plus failure of an adequate trial of a monoamine oxidase inhibitor

Stage 5. Stage 4 plus failure of an adequate course of electroconvulsive therapy

From: Thase ME, Rush AJ. J Clin Psychiatry. 1997;58 Suppl 13:23-9.When at first you don't succeed: sequential strategies for antidepressant
nonresponders. Abstract

What can they do about Treatment-Resistant Depression?

1. Be sure they diagnosed the depression properly, subtype of depression

2. Exclude somatic illness

3. Exclude comorbid psychiatric illness

4. Evaluate antidepressant treatment for compliance, tolerabillity, duration, and dosage. If necessary optimize by increasing dosage or extending the duration.

5. Switch to an other antidepressant if previous measures failed

6. Augment the antidepressant

7. After cessation of all antidepressants start a monoamine oxidase inhibitor

8. Reconsider diagnoses and use Electroconvuslive therapy

9. Don't forget cognitive therapy, Interpersonal psychotherapy, running therapy, family therapy.

Treatment algorithm for Treatment-Resistant Depressed Inpatients

In a recent study some of these steps were studied in a treatment algorithm with depressed patients admitted to a depression unit.

Step 0: Washout, Diagnostic phase, and placebo run-in (1 week)

Step 1: Antidepressant monotherapy (imipramine or fluvoxamine; 6 weeks)

Step 2: Lithium addition (5 weeks)

Step 3: Nonselective monoamine oxidase inhibitor (MAOI; phenelzine or tranylcypromine; 5 weeks)

Step 4: Electroconvulsive therapy (flexible number of weeks)

Results of a treatment algorithm for treatment-resistant depression

149 patients (50%) were included in the 4-step algorithm. Of the 56 patients who were excluded from
step 1 because of proven refractoriness to antidepressants during the index episode, 54 were enrolled directly into step 3 of the algorithm. Only 4 (7%) of these 54 patients had received lithium addition. Ten patients needed immediate ECT.

At the end of the algorithm, 129 (87%) of 149 patients achieved response. Complete remission was achieved by 89 of 149 (60%) patients. Three patients switched into
hypomania during the algorithm: 2 receiving a combination of imipramine and lithium and 1 patient receiving phenelzine. These patients were considered both as responders and remitters. Overall dropout of the algorithm amounted to 24 (16%) of 149 patients. When including patients who entered the algorithm at step 3 (treatment with a nonselective MAOI) the figures are as follows: 165 (81%) of 203 responded during the algorithm and 101 (50%) achieved remission. Overall dropout, including the 54 additional patients, was 30 of 203, i.e., 15%.

These results emphasizes the importance of persisting with stepwise antidepressant treatment in non-responders to the first antidepressant. Important is to note that this trial was done on a depression unit in a academic/tertiary centre.

From: Birkenhäger TK, van den Broek WW, Moleman P, Bruijn JA. J Clin Psychiatry. 2006 Aug;67(8):266-71. Outcome of a 4-step treatment algorithm for depressed inpatients. Abstract

I was inspired by an article from the about Treatment-resistant depression

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