SSRIs vs Clomipramine: Which Works Better for OCD and Depression?

When it comes to treating SSRIs, selective serotonin reuptake inhibitors, a class of antidepressants that increase serotonin levels in the brain. Also known as serotonin reuptake inhibitors, they are often the first choice for depression and obsessive-compulsive disorder. But there’s another option—clomipramine, a tricyclic antidepressant that affects serotonin and norepinephrine, and one of the few medications FDA-approved specifically for OCD. Both work on serotonin, but clomipramine hits more targets, which can mean stronger results—or more side effects. So why do doctors sometimes pick one over the other?

SSRIs like sertraline, fluoxetine, and escitalopram are usually tried first because they’re gentler on the body. They cause fewer dry mouth, dizziness, or heart rhythm issues compared to clomipramine. But if someone doesn’t improve after trying two or three SSRIs, clomipramine often comes up as the next step. Studies show it can be more effective for severe OCD, especially when intrusive thoughts are constant and overwhelming. It’s not a first-line drug because of its side effect profile—things like constipation, blurred vision, and weight gain are more common. But for people who’ve tried everything else, clomipramine can be the breakthrough they need.

There’s also the matter of dosing. SSRIs for OCD often need higher doses than what’s used for depression—sometimes double. Clomipramine doses start low and climb slowly, with many patients needing 150–250 mg daily to see results. Blood tests are sometimes used to make sure levels stay safe. And while SSRIs are generally safe long-term, clomipramine requires more monitoring, especially for heart function. It’s not for everyone, but for those who respond, the improvement can be life-changing.

What you won’t find in most doctor’s offices is a one-size-fits-all answer. Some people do great on an SSRI and never need to switch. Others bounce between meds until they find the right fit. That’s why the posts below dig into real-world dosing protocols, how side effects play out over time, and when switching from an SSRI to clomipramine actually makes sense. You’ll see what works for people with severe OCD, what doesn’t, and why some choose to stick with clomipramine despite the risks. This isn’t theory—it’s what happens in clinics, in homes, and in the lives of people who’ve been through it.