In the head-to-head trial, 62% responded to exposure therapy, 42% to clomipramine, 70% to both, 8% to placebo
122 adults with OCD, three centres, 12 weeks, four arms. Exposure and ritual prevention alone did not differ from exposure plus clomipramine, and both beat clomipramine alone. Among completers: 86%, 48%, 79% and 10%.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: One trial, 122 people, one drug. Thirty-eight percent of people who started the therapy did not respond, and the treated-versus-completer gap shows dropout. The combination had the highest treated response even though the difference from therapy alone was not significant. The therapy was intensive, which most clinics do not deliver.
The one randomised trial that put the therapy, the drug, the combination and a placebo pill in the same room.
Significant findings
Foa and colleagues randomised 122 adult outpatients with OCD to intensive exposure and ritual prevention (four weeks of intensive sessions, then eight weekly maintenance sessions), clomipramine for 12 weeks to a maximum of 250 mg a day, both, or pill placebo. The three centres were chosen so that one was expert in drugs, one in the therapy and one in both.
"At week 12, the effects of all active treatments were superior to placebo. The effect of exposure and ritual prevention did not differ from that of exposure and ritual prevention plus clomipramine, and both were superior to clomipramine only."
The response rates, for everyone treated and then for people who completed: exposure and ritual prevention 62% and 86%; clomipramine 42% and 48%; the combination 70% and 79%; placebo 8% and 10%.
The conclusion: "Intensive exposure and ritual prevention may be superior to clomipramine and, by implication, to monotherapy with the other SRIs."
The other direction
Sixty-two percent responded to the therapy, which means 38 percent of the people who started it did not, after twelve weeks of the intensive version. The gap between treated and completer rates (62% against 86%) says a fair number of people did not finish. The combination arm had the highest treated response, 70%, even though the difference from therapy alone was not statistically significant. And the therapy tested was intensive, four weeks of concentrated sessions, which is more than most clinics offer.
What this does not show
It is 122 people and one drug. The last sentence of the abstract reaches the other SRIs "by implication", not by testing them. It does not say whether any one person should take, keep or stop clomipramine or anything else; that is a decision with a prescriber.
Worth asking
What does the intensive version of exposure and response prevention look like, and is it available to me?
Source
Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder — Foa EB, Liebowitz MR, Kozak MJ, Davies S, Campeas R, Franklin ME, Huppert JD, Kjernisted K, Rowan V, Schmidt AB, Simpson HB, Tu X (2005)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1176/appi.ajp.162.1.151
DOI: 10.1176/appi.ajp.162.1.151
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Funding not disclosed
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 122
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 29, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 62 out of 100 on our published rubric. One caveat travels with that badge: One trial, 122 people, one drug. Thirty-eight percent of people who started the therapy did not respond, and the treated-versus-completer gap shows dropout. The combination had the highest treated response even though the difference from therapy alone was not significant. The therapy was intensive, which most clinics do not deliver. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder — Foa EB, Liebowitz MR, Kozak MJ, Davies S, Campeas R, Franklin ME, Huppert JD, Kjernisted K, Rowan V, Schmidt AB, Simpson HB, Tu X (2005). Published in: Top-tier peer-reviewed journal. DOI: 10.1176/appi.ajp.162.1.151. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Randomised controlled trial. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is clomipramine (Anafranil), anafranil FDA approved?
Yes — this medication carries FDA approval. Approval is always for a specific indication, not for every use it is prescribed for.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.