SSRIs are a first-line treatment option for obsessive-compulsive disorder (OCD), along with exposure and response prevention therapy. Unfortunately, many persons with OCD either do not respond or have an incomplete response even with a full dose of an SSRI.
In such situations, clinicians often, off-label, use higher doses of SSRIs than are recommended in the FDA-approved Prescribing Information. Is there research evidence for such use? Before answering that question, here are three preliminary facts:
1. The American Psychiatric Association (APA) Practice Guideline for OCD (2007) noted that some patients with OCD require higher than the standard doses of antidepressants (e.g, sertraline 400 mg/day, fluvoxamine 450 mg/day, paroxetine 100 mg/day, etc.).
2. The Guideline Watch (2013), i.e., update, noted that the standard dose of citalopram should not be exceeded because of the FDA’s warning about potential QTc prolongation with high doses. In addition, I recommend not exceeding standard doses for fluoxetine and escitalopram without ECG monitoring.
3. In major depressive disorder, there is not a very clear dose-response relationship. But in OCD, a meta-analysis of studies (Bloch et al., 2010) showed that higher doses are more efficacious.
Now coming to the main question of whether it makes sense to increase the dose of an SSRI above the usual maximum dose when standard doses have failed to produce an adequate improvement in the OCD. In a randomized, controlled trial (Ninan et al., 2006), those who did not respond to 200 mg/day of sertraline taken for 16 weeks were randomized to either:
1. Continue the sertraline 200 mg/day, or to
2. Increase the dose to 250 to 400 mg/day (i.e., above the FDA-approved dose range) for another 12 weeks.
Those whose dose was increased showed a greater improvement than those in the control group.
Important: The improvement in the increased dose did not become apparent until 6 to 8 weeks after increasing the dose. So, if this strategy is used, the trial should last for 12 weeks.
American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Arlington, VA: American Psychiatric Association, 2007. Available online at http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/ocd.pdf. Guideline Watch (2013) available at http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/ocd-watch.pdf
Bloch MH, McGuire J, Landeros-Weisenberger A, Leckman JF, Pittenger C. Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder. Mol Psychiatry. 2010 Aug;15(8):850-5. PubMed PMID: 19468281; PubMed Central PMCID: PMC2888928.
Ninan PT, Koran LM, Kiev A, Davidson JR, Rasmussen SA, Zajecka JM, Robinson DG, Crits-Christoph P, Mandel FS, Austin C. High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial. J Clin Psychiatry. 2006 Jan;67(1):15-22. PubMed PMID: 16426083.
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