What’s best when a patient doesn’t respond to the maximum dose of an antidepressant?

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Clinical Inquiries

What’s best when a patient doesn’t respond to the maximum dose of an antidepressant?

J Fam Pract. 2010 March;59(3):173-175

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References

1. Paykel ES, Scott J, Teasdale JD, et al. Prevention of relapse in residual depression by cognitive therapy: a controlled trial. Arch Gen Psychiatry. 1999;56:829-835.

2. Schatzberg AF, Rush AJ, Arnow BA, et al. Chronic depression: medication (nefazodone) or psychotherapy (CBASP) is effective when the other is not. Arch Gen Psychiatry. 2005;62:513-520.

3. Thase ME, Friedman ES, Biggs MM, et al. Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Am J Psychiatry. 2007;164:739-752.

4. Ruhe HG, Huyser J, Swinkels JA, et al. Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry. 2006;67:1836-1855.

5. Rush AJ, Trevedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006;354:1231-1242.

6. Thase ME, Rush AJ, Howard RH, et al. Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression. Arch Gen Psychiatry. 2002;59:233-239.

7. Fava M, Rush AJ, Wisniewski SR, et al. A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report. Am J Psychiatry. 2006;163:1161-1172.

8. McGrath PJ, Stewart JW, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry. 2006;163:1531-1541.

9. Bauer M, Dopfmer S. Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. J Clin Psychopharmacol. 1999;19:427-434.

10. Crossley NA, Bauer M. Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta-analyses of randomized placebo-controlled trials. J Clin Psychiatry. 2007;68:935-940.

11. Nierenberg AA, Fava M, Trivedi MH, et al. A comparison of lithium and T3 augmentation following two failed medication treatments for depression: a STAR*D Report. Am J Psychiatry. 2006;163:1519-1530.

12. Trivedi MH, Fava M, Wisniewski SR, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354:1243-1252.

13. Papakostas GI, Shelton RC, Smith J, et al. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry. 2007;68:826-831.

14. Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2007;68:843-853.

15. Fava M. Augmentation and combination strategies in treatment-resistant depression. J Clin Psychiatry. 2001;62(suppl 18):S4-S11.

16. Institute for Clinical Systems Improvement (ICSI) Depression, Major, in Adults in Primary Care. Bloomington, Minn: Institute for Clinical System Improvement (ICSI); 2009. Available at: http://www.icsi.org/guidelines_and_more/gl_os_prot/behavioral_health/depression_5/depression__major__in_adults_in_primary_care_4.html. Accessed November 9, 2009.

17. American Psychiatric Association Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry. 2000;157(suppl 4):S1-S45.

When an SSRI fails…
A recent systematic review of 8 RCTs (including STAR*D) and 23 open studies concluded that after a first failure of a selective serotonin reuptake inhibitor (SSRI), any switch within or between classes of antidepressant is legitimate and equally effective.⁴

Switching within the same class of antidepressant. The STAR*D study, an unblinded RCT, reported that patients (N=238; median age 41 years) who were switched to sertraline (as much as 200 mg per day for 14 weeks) when they didn’t tolerate or respond adequately to citalopram had remission rates of 17.6% on the Hamilton Rating Scale for Depression (HAM-D) and 26.6% on the Quick Inventory of Depressive Symptomatology (QIDS).⁵

Switching to a different class of antidepressant. In a multisite study, outpatients who failed to respond to 12-week, double-blind treatment with either sertraline (n=117) or imipramine (n=51) were randomized to an additional 12 weeks of double-blinded treatment with the alternate medication. Investigators reported a 60% response rate in the sertraline switch group and a 44% response rate in the imipramine switch group.⁶

FAST TRACK

In 1 study, augmentation with cognitive therapy or medication worked equally well, but drugs produced a more rapid response.

In the STAR*D study, patients who didn’t tolerate or failed to respond to as many as 12 weeks of citalopram were switched to sustained-release (SR) bupropion, sertraline, or extended-release (ER) venlafaxine for as long as 14 weeks.⁵The bupropion-SR switch group (n=239, up to 400 mg per day) had remission rates of 21.3% (HAM-D) and 25.5% (QIDS); the sertraline switch group (n=238, up to 200 mg per day) had remission rates of 17.6% (HAM-D) and 26.6% (QIDS); and the venlafaxine-ER switch group (n=250, up to 375 mg per day) had remission rates of 24.8% (HAM-D) and 25% (QIDS). There were no clinically or statistically significant differences among the groups.

Response declines with multiple switches
Patients who didn’t respond to this treatment arm and were switched again to either mirtazapine (n=114, as much as 60 mg per day) or nortriptyline (n=121, as much as 200 mg per day) had a much less favorable response (mirtazapine 12.3% vs nortriptyline 19.8%; NNT nortriptyline-mirtazapine=13).⁷

Patients who failed to respond to this treatment arm were randomized to either tranylcypromine (n=58, mean 36.9 mg per day) or venlafaxine plus mirtazapine (n=51, mean 210.3 and 35.7 mg per day, respectively). Both groups had low remission rates (tranylcypromine 6.9%, venlafaxine plus mirtazapine 13.7%; NNT venlafaxine plus mirtazapine-tranylcypromine=15).⁸

Evidence-based answers from the Family Physicians Inquiries Network