Clomipramine vs Prozac: Key Differences and What Works for You

When you're trying to find the right antidepressant, Clomipramine, a tricyclic antidepressant originally developed for depression and later found effective for OCD. Also known as Anafranil, it works by balancing serotonin and norepinephrine in the brain. On the other hand, Prozac, a selective serotonin reuptake inhibitor (SSRI) approved in the 1980s as one of the first SSRIs. Also known as fluoxetine, it mainly boosts serotonin levels without affecting norepinephrine. Both are used for depression, but only Clomipramine is FDA-approved for treating obsessive-compulsive disorder (OCD) in adults and children over 10. Prozac also treats OCD, but it’s often tried first because of its milder side effect profile.

Clomipramine hits harder and faster for severe OCD, but it comes with more side effects—dry mouth, dizziness, weight gain, and a higher risk of heart rhythm issues. Prozac tends to be gentler: nausea and insomnia are common at first, but most people adjust within weeks. If you’ve tried other SSRIs like Zoloft or Lexapro and they didn’t help, your doctor might suggest Clomipramine. It’s not a first-line choice for depression alone because of its safety profile, but for stubborn OCD, it’s often the most effective option. People on Clomipramine need regular ECGs to monitor heart function, while Prozac users rarely need that level of monitoring. Both can cause sexual side effects, but Prozac is more likely to cause emotional numbness in some users, while Clomipramine can make you feel foggy or overly tired.

Neither drug works overnight. It takes 4 to 8 weeks to see real changes, and skipping doses can undo progress. If you’re switching from one to the other, you’ll need a careful taper—mixing them can cause serotonin syndrome, a rare but dangerous condition. Your doctor will look at your history: if you have heart problems, Clomipramine might be off the table. If you’re young and worried about weight gain, Prozac might be a better fit. Both are available as generics, so cost isn’t usually a deciding factor. What matters is how your body responds. The posts below compare real experiences, side effect patterns, and what works when other meds fail—so you can make a smarter choice with your doctor.