By Rajnish Mago, MD (bio)
Question from a Member:
I’m wondering who has recommended 15 to 30 mg/day of aripiprazole? This is a high dose. Typically, very low doses of antipsychotics are used for augmentation in OCD.
Answering this question is not only clinically important because use of adjunctive antipsychotics for OCD is very common, but also helps us to better understand how to interpret and apply research findings.
Tip on methodology
To decide what is the optimal dose of a medication for a disorder, what is ideally needed is a double-blind, FIXED-dose, controlled clinical trial that compares different doses to each other.
Fixed-dose—rather than flexible-dose—because when the dose can be changed by the clinician, we don’t know for sure whether the person would have improved even if the dose had not been increased.
What do the guidelines say?
(Optional to read: The American Psychiatric Association practice guideline (2007) only mentioned the very small, open-label study done prior to its publication. The 2013 update of the American Psychiatric Association practice guideline referred to several studies but didn’t give a clear opinion as to the recommended dose. It did say that a “limitation” of one of the studies was the 15 mg maximum dose. The WFSBP guideline (Bandelow et al., 2008) was published before most of the aripiprazole studies were done. So, I am disregarding that guideline as well.)
A Canadian practice guideline (Fineberg et al., 2015) noted (emphasis added):
The antipsychotic dose range noted to be effective includes … aripiprazole (15–30 mg/day) (reviewed in Fineberg et al. (2012).
What do the clinical trials say?
But, to answer our colleague’s question with greater confidence, let’s go to the primary sources and look at what doses of aripiprazole were used in clinical trials in adult patients with OCD that had not responded adequately to a serotonergic antidepressant alone—both uncontrolled (open-label) and controlled trials (listed chronologically).
Connor et al. (2005): No control group, flexible dose. Aripiprazole was started at 10 mg/day and increased to 15 to 30 mg/day. The mean dose actually used was not described in the paper.
Pessina et al. (2009): No control group, flexible dose. The protocol-allowed dose of aripiprazole was 5 to 20 mg. The mean (standard deviation) dose actually used was 11.2 +/- 5.2 mg/day.
Ak et al. (2011): No control group, flexible dose. The protocol-allowed dose range for aripiprazole was 5 to 30 mg/day. The mean (standard deviation) of the dose actually used was 15.9 +/- 7.9 mg/day.
Selvi et al. (2011): Single-blind, risperidone and placebo control groups. Aripiprazole was given at 15 mg/day, but details of the dosing were not provided in the paper.
Muscatello et al. (2011): Double-blind, placebo-controlled. Aripiprazole was supposedly given at 15 mg/day but further details were not provided in the paper.
Important! It seems that these studies tended to start aripiprazole at relatively high doses (10 mg/day or more) and/or to titrate it up relatively rapidly without waiting to see if the lower dose might be enough. Both of these issues (giving a high dose and titrating rapidly) are common in clinical trials because the investigators have limited time to do the study and they are eager to show that the medication was effective.
Bottom line regarding clinical trials on this topic: As of April 2019, there is no controlled clinical trial that can answer the question of the optimal dose of aripiprazole for the adjunctive treatment of OCD.
Combining the above sources with my own clinical experience and the clinical experience of experts in the psychopharmacology of OCD whom I consulted on this question suggests the following:
1. To improve tolerability, start aripiprazole at low doses—about 2 mg/day (or even 1 mg/day, which is half of a 2 mg tablet). Yes, I know that is a really low dose to start with, but let’s remember that we are in this for the long haul.
2. We should also remember that several antidepressants can increase aripiprazole levels through CYP450 drug-drug interactions.
3. Titrate up slowly—at one- to four-week intervals-–both for better tolerability and because some patients will have adequate improvement at 5 or 7.5 mg/day of aripiprazole.
4. But, if a cautious and adequate trial of a lower dose of aripiprazole does not produce an adequate response, the patient does not have unacceptable side effects, and a drug interaction that increases aripiprazole levels is not present, I think it may not be a good idea to conclude that aripiprazole did not work and should be tapered off.
If lower doses of aripiprazole given for several weeks are not effective or only partially effective, we should try to go to higher doses. It may be better to complete the trial of aripiprazole by increasing the dose cautiously to 15 mg/day or even higher than that.
Clinical trials (uncontrolled or controlled)
Ak M, Bulut SD, Bozkurt A, Ozsahin A. Aripiprazole augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a 10-week open-label study. Adv Ther. 2011 Apr;28(4):341-8. doi: 10.1007/s12325-011-0011-7. Epub 2011 Mar 21. PubMed PMID: 21437763. Uncontrolled clinical trial
Connor KM, Payne VM, Gadde KM, Zhang W, Davidson JR. The use of aripiprazole in obsessive-compulsive disorder: preliminary observations in 8 patients. J Clin Psychiatry. 2005 Jan;66(1):49-51. PubMed PMID: 15669888. Uncontrolled (open-label), only eight patients.
Ercan ES, Ardic UA, Ercan E, Yuce D, Durak S. A Promising Preliminary Study of Aripiprazole for Treatment-Resistant Childhood Obsessive-Compulsive Disorder. J Child Adolesc Psychopharmacol. 2015 Sep;25(7):580-4. doi: 10.1089/cap.2014.0128. PubMed PMID: 26375768. Uncontrolled clinical trial in children.
Muscatello MR, Bruno A, Pandolfo G, Micò U, Scimeca G, Romeo VM, Santoro V, Settineri S, Spina E, Zoccali RA. Effect of aripiprazole augmentation of serotonin reuptake inhibitors or clomipramine in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. J Clin Psychopharmacol. 2011 Apr;31(2):174-9. doi: 10.1097/JCP.0b013e31820e3db6. PubMed PMID: 21346614.
Pessina E, Albert U, Bogetto F, Maina G. Aripiprazole augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a 12-week open-label preliminary study. Int Clin Psychopharmacol. 2009 Sep;24(5):265-9. doi: 10.1097/YIC.0b013e32832e9b91. PubMed PMID: 19629012. Uncontrolled clinical trial
Sayyah M, Sayyah M, Boostani H, Ghaffari SM, Hoseini A. Effects of aripiprazole augmentation in treatment-resistant obsessive-compulsive disorder (a double blind clinical trial). Depress Anxiety. 2012 Oct;29(10):850-4. doi: 10.1002/da.21996. Epub 2012 Aug 29. PubMed PMID: 22933237. Study from Iran; not considered in this article.
Selvi Y, Atli A, Aydin A, Besiroglu L, Ozdemir P, Ozdemir O. The comparison of aripiprazole and risperidone augmentation in selective serotonin reuptake inhibitor-refractory obsessive-compulsive disorder: a single-blind, randomised study. Hum Psychopharmacol. 2011 Jan;26(1):51-7. PubMed PMID: 21308781.
Copyright 2019, Rajnish Mago, MD. All rights reserved. May not be reproduced in any form without express written permission.
Disclaimer: The content on this website is provided as general education for medical professionals. It is not intended or recommended for patients or other lay persons or as a substitute for medical advice, diagnosis, or treatment. Patients must always consult a qualified health care professional regarding their diagnosis and treatment. Healthcare professionals should always check this website for the most recently updated information.