SSRIs are first-line medications for the treatment of obsessive-compulsive disorder (OCD). What pharmacological treatments may be tried if a full trial of an SSRI fails to produce any improvement or produces only partial improvement?
Switch or augment?
If there is significant but not full improvement, consider adding exposure and response prevention and/or another medication to “augment” the SSRI.
On the other hand, if there is minimal or no improvement with the SSRI at full or at higher than usual dose, we should probably switch treatments. If switching to another medication, it is recommended t hat we switch to another SSRI before switching to clomipramine.
What to switch to?
While in the treatment of major depressive disorder, we can consider switching to an SNRI after non-response to an SSRI, this strategy is not recommended for OCD because for OCD, SNRIs are not more effective than SSRIs.
If switching to a second SSRI does not work, consider switching to clomipramine.
Note: The use of MAO inhibitors for OCD has not been studied and it is not recommended at this time. We cannot extrapolate from their use in major depression because in major depression there seems to be an advantage in using a medication that enhances activity of multiple neurotransmitters. OCD, on the other hand, appears to benefit only from enhancing serotonergic activity.
What to augment with?
1. Add a second-generation antipsychotic (aripiprazole or risperidone) to the SSRI or clomipramine. Addition of other second-generation antipsychotics is not recommended. For a discussion of this topic, click HERE.
2. Consider a combination of an SSRI and clomipramine
Severe and “treatment-resistant” cases
The person should be referred to a specialist or a specialty center for potential treatment with:
1. Intravenous clomipramine. The rationale for IV use is that this bypasses first-pass metabolism.
2. Deep-brain stimulation
Should clomipramine be a first-line treatment for OCD?
High-dose SSRIs for OCD?
BEST books for patients with OCD
Castle D, Bosanac P, Rossell S. Treating OCD: what to do when first-line therapies fail. Australas Psychiatry. 2015 Aug;23(4):350-3. doi: 10.1177/1039856215590027. Review. PubMed PMID: 26104775.
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Mazhar golewale says
I have used clomipramine with low dose fluvoxamine (25 to 50 mg). Fluvoxamine inhibits the conversion of clomipramine to desmethyl clomipramine. I try to keep the ratio of clomipramine to desmethylclomipramine to 2:1. Desmethyl clomipramine (DMC) has higher NE effect. As you all know, OCD responds to serotonin mechanism and not to NE or DA mechanism. My goal is try and keep higher ratio of clomipramine versus DMC.
Rajnish Mago, MD says
Thank you, Dr. Golewale! I agree that a higher clomipramine to desmethylclomipramine ratio is desirable in patients with OCD. We had discussed this at the following link: https://simpleandpractical.com/clomipramine-desmethylclompramine-level/
Demetris Gousis says
What is your opinion regarding augmentation of an SSRI with memantine for treatment resistant OCD?
Marianne Bernadino says
I have never augmented an SSRI with a TCA due to concern for serotonin syndrome. Can you address and advise on dosing? Also, we can now add TMS as another alternative treatment for OCD.