9 Steps for Treatment-Resistant Depression

Dr Shock
August 30, 2007


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 MayoClinic.com about Treatment-resistant depression

 

3 Responses to “9 Steps for Treatment-Resistant Depression”

  1. 08 09 ‘22

    As an ex school doctor I think often in educational terms.
    To me it’ s amazing that the author calls a depression already “treatment resistant” TRD if the psychiatrists only has tried different medicines or ECT.
    It seems he gives only a little bit benefit of doubt that psychotraumatic events or pedagogical misunderstandings can cause very resistant depressions.

    I think lack of a solid basis of self respect can be very depressing for some characters

    I think too that electroconvulsive therapy alas almost only is applyed as a black box.
    Long ago my teacher suggested that the period of amnesia following ECT has to be filled with fresh friendly communications. New and correcting experiences have to replace old bad ones.
    Has this vision ever been disproved?

    We don’t know how poor, cold and bad our communications are. Even if we are very nice.
    How much we are trained to recognise and assist human beings starving for understanding and respect, for getting kindness or the possibility to give kindness?

    I think we need to get and to give three levels of respect and appreciation, animal, psychological and transcendent. Getting or giving to little can be very depressing.

  2. Ton Postmes on September 23rd, 2008 at 11:59 am
  3. [...] The choice of strategies appears hard to justify. Why choose buproprion and buspirone as initial augmentation strategies when there appears better evidence for augmentation with lithium? For other and better options as well as a better treatment algorithm read: 9 steps for treatment resistant depression [...]

  4. STAR*D Trial Sheds Little Light on how to manage Depression in Clinical Practice | Dr Shock MD PhD on January 3rd, 2009 at 10:49 am
  5. [...] can they do about Treatment-Resistant Depression? Besides the 9 steps for treatment resistant depression described in an earlier post on this blog systematic treatment algorithms do decrease inappropriate [...]

  6. Treatment Resistant Depression and Algorithm Guided Treatment | Dr Shock MD PhD on July 21st, 2009 at 8:48 am
  1. 08 09 ‘22

    As an ex school doctor I think often in educational terms.
    To me it’ s amazing that the author calls a depression already “treatment resistant” TRD if the psychiatrists only has tried different medicines or ECT.
    It seems he gives only a little bit benefit of doubt that psychotraumatic events or pedagogical misunderstandings can cause very resistant depressions.

    I think lack of a solid basis of self respect can be very depressing for some characters

    I think too that electroconvulsive therapy alas almost only is applyed as a black box.
    Long ago my teacher suggested that the period of amnesia following ECT has to be filled with fresh friendly communications. New and correcting experiences have to replace old bad ones.
    Has this vision ever been disproved?

    We don’t know how poor, cold and bad our communications are. Even if we are very nice.
    How much we are trained to recognise and assist human beings starving for understanding and respect, for getting kindness or the possibility to give kindness?

    I think we need to get and to give three levels of respect and appreciation, animal, psychological and transcendent. Getting or giving to little can be very depressing.

  2. Ton Postmes on September 23rd, 2008 at 11:59 am
  3. [...] The choice of strategies appears hard to justify. Why choose buproprion and buspirone as initial augmentation strategies when there appears better evidence for augmentation with lithium? For other and better options as well as a better treatment algorithm read: 9 steps for treatment resistant depression [...]

  4. STAR*D Trial Sheds Little Light on how to manage Depression in Clinical Practice | Dr Shock MD PhD on January 3rd, 2009 at 10:49 am
  5. [...] can they do about Treatment-Resistant Depression? Besides the 9 steps for treatment resistant depression described in an earlier post on this blog systematic treatment algorithms do decrease inappropriate [...]

  6. Treatment Resistant Depression and Algorithm Guided Treatment | Dr Shock MD PhD on July 21st, 2009 at 8:48 am
  1. 08 09 ‘22

    As an ex school doctor I think often in educational terms.
    To me it’ s amazing that the author calls a depression already “treatment resistant” TRD if the psychiatrists only has tried different medicines or ECT.
    It seems he gives only a little bit benefit of doubt that psychotraumatic events or pedagogical misunderstandings can cause very resistant depressions.

    I think lack of a solid basis of self respect can be very depressing for some characters

    I think too that electroconvulsive therapy alas almost only is applyed as a black box.
    Long ago my teacher suggested that the period of amnesia following ECT has to be filled with fresh friendly communications. New and correcting experiences have to replace old bad ones.
    Has this vision ever been disproved?

    We don’t know how poor, cold and bad our communications are. Even if we are very nice.
    How much we are trained to recognise and assist human beings starving for understanding and respect, for getting kindness or the possibility to give kindness?

    I think we need to get and to give three levels of respect and appreciation, animal, psychological and transcendent. Getting or giving to little can be very depressing.

  2. Ton Postmes on September 23rd, 2008 at 11:59 am
  3. [...] The choice of strategies appears hard to justify. Why choose buproprion and buspirone as initial augmentation strategies when there appears better evidence for augmentation with lithium? For other and better options as well as a better treatment algorithm read: 9 steps for treatment resistant depression [...]

  4. STAR*D Trial Sheds Little Light on how to manage Depression in Clinical Practice | Dr Shock MD PhD on January 3rd, 2009 at 10:49 am
  5. [...] can they do about Treatment-Resistant Depression? Besides the 9 steps for treatment resistant depression described in an earlier post on this blog systematic treatment algorithms do decrease inappropriate [...]

  6. Treatment Resistant Depression and Algorithm Guided Treatment | Dr Shock MD PhD on July 21st, 2009 at 8:48 am

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