Clomipramine (Anafranil) was engineered from imipramine in the early 1960s. It was approved for treatment of depression in Europe in 1970, but not available in the US until 1990. This delay was because the FDA considered it just a “me too” drug of imipramine. Eventually, the FDA approved it for obsessive-compulsive disorder (OCD).
Clomipramine is the only available TCA not approved for depression. It has been established as effective for panic disorder, off-label.
Clomipramine was considered the gold standard for treatment of OCD due to potent serotonergic activity. The other medication approved for OCD but not for depression is the SSRI fluvoxamine (Luvox), which is also highly serotonergic.
Due to side effects, clomipramine is considered a third-line OCD treatment after two trials of high-dose SSRIs have failed (Robert Hudak, MD). It may be somewhat more effective than SSRIs for OCD.
Clomipramine may be the safest TCA. Of 680 single-drug exposures to clomipramine reported to Poison Control, there were no deaths and only 44 major serious outcomes (Nelson & Spyker, 2017). Protriptyline (Vivactil) may be safer, but the sample size was small (77 exposures).
Dosing: For OCD start 25 mg QD, increase by 25 mg QD every 4–7 days for maximum of 200 mg in the first 2 weeks, then to FDA maximum maintenance dose of 250 mg. Give in divided doses with food during initial titration. Taper gradually to discontinue.
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