Clomipramine is the most serotonergic tricyclic, and adding fluvoxamine, a CYP1A2 inhibitor, keeps more of it in that serotonergic form, in theory giving more of the activity that helps OCD. The price is strong anticholinergic effects, QTc prolongation, heavy sedation and weight gain: not necessarily the greatest choice, but one to consider when it is viable.
Side effects and safety
It brings strong anticholinergic effects, QTc prolongation, heavy sedation and weight gain. Not necessarily the greatest choice, but if it is viable, you can consider it.
“Strong anticholinergic effects, QTC prolongation, very sedating. weight gain. So not necessarily the greatest choice, but if it's viable, you can consider it”
27:57Practical OCD Psychopharmacology: Evidence‑Based (& Non Evidence-Based) Medication ApproachAug 2025
Pearls
It is the most serotonergic tricyclic. CYP1A2 breaks it down into norclomipramine, a secondary tricyclic that is less serotonergic.
“clomipramine is the most serotonergic TCA. So it consists of clomipramine, and then it's broken down by CYP1A2 into norclomipramine. So... Norclomiprimine is a secondary TCA, so it's less serotonergic”
26:04Practical OCD Psychopharmacology: Evidence‑Based (& Non Evidence-Based) Medication ApproachAug 2025 Fluvoxamine inhibits CYP1A2, so adding it raises the ratio of serotonergic clomipramine and, in theory, gives more of the serotonergic activity that is better for OCD.
“fluvoxamine is a CYP1A2 inhibitor. So if you inhibit CYP1A2, you're going to increase the ratio of the serotonergic clomipramine and theoretically get more of that serotonergic activity that's better for OCD”
28:58Practical OCD Psychopharmacology: Evidence‑Based (& Non Evidence-Based) Medication ApproachAug 2025
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From these episodes
Every point above is something said on the Psychofarm podcast, with the words as spoken and a link to the moment in the episode. It is education, not medical advice, and an episode reflects what we thought when we recorded it.