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

By

Vincent Lo, MD

Lauren Maggio, MS(LIS), MA

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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.

EVIDENCE-BASED ANSWER

FIRST, CONSIDER POSSIBLE CAUSES OF THE INADEQUATE RESPONSE, then weigh treatment options in light of the characteristics of the individual patient and therapy. When managing a patient with nonpsychotic depression and inadequate response to the maximum dose of a single antidepressant, the physician should first identify factors that may contribute to the poor response, such as suboptimal dosage resulting from nonadherence, inadequate duration of therapy, and comorbid medical and psychiatric conditions (strength of recommendation [SOR]: C, expert opinion).

The literature supports several treatment alternatives, including augmentation with cognitive therapy, switch therapy, and combination-augmentation therapy; not enough studies exist to recommend the best treatment. All options reviewed produced a 20% to 50% remission rate (SOR: B, systematic reviews and randomized controlled trials [RCTs]).

Physicians should consider the patient’s clinical history and preferences, along with drug toxicity, potential drug interactions, and cost when making treatment decisions (SOR: C, expert opinion).

Evidence summary

A recent study randomized 158 patients who didn’t respond to antidepressant therapy to either cognitive therapy with clinical management or clinical management alone.¹The cognitive therapy group had a 29% cumulative relapse rate at 68 weeks, compared with 47% in the clinical management control group (number needed to treat [NNT]=6).

A crossover RCT compared 12 weeks of the cognitive behavioral analysis system of psychotherapy (CBASP) in 61 patients who had failed to respond to a 12-week course of nefazodone with 12 weeks of nefazodone treatment in 79 patients who hadn’t responded to 12 weeks of CBASP.²Remission rates were comparable in the 2 crossover groups (28% for nefazodone vs 25% for CBASP; P=.92).

FAST TRACK

The literature supports several treatment alternatives, but there is no single best option.

Drugs may produce a faster response
The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial compared augmentation with as many as 16 sessions of cognitive therapy with pharmacologic augmentation and switch strategy among 65 patients who had failed to respond to 14 weeks of citalopram.³

The investigators concluded that augmentation with cognitive therapy or pharmacologic therapy was equally effective, but pharmacologic augmentation produced a more rapid response (mean time to first remission for cognitive therapy=53.3 days, compared with 40.1 days for pharmacologic therapy; P=.022). Patients who were switched to cognitive therapy had similar outcomes to patients who were switched to alternative antidepressants (remission rates=25% and 27.9%, respectively; P=.6881), but reported fewer adverse effects (0% vs 48%).

Evidence-based answers from the Family Physicians Inquiries Network