Clomipramine is a tricyclic antidepressant that is used for the treatment of obsessive-compulsive disorder. The generic is relatively cheap while the branded Anafranil® is very expensive (about $1800 per month for 150 mg/day).
On this page, we address two questions:
1. Is clomipramine more efficacious than SSRIs?
2. Can clomipramine be considered a first-line alternative to SSRIs for the treatment of OCD?
It is unclear whether clomipramine is more efficacious than SSRIs
Clinical trials that directly (“head-to-head”) compare clomipramine to an SSRI generally do not find clomipramine to be more efficacious (American Psychiatric Association, 2007).
However, when these data were combined in meta-analyses (references below), some of them found clomipramine may be more efficacious than SSRIs. The most recent meta-analysis (Skapinakis et al., 2016), however, did not find clomipramine to be more efficacious than SSRIs.
The combination of these observations suggests that the difference in efficacy, if any, is probably not large.
Clomipramine is associated with more adverse effects than are the SSRIs
Clomipramine is associated with some troublesome adverse effects like dry mouth, dizziness, etc., and also with potential cardiovascular adverse effects. At higher doses, it usually requires doing periodic ECGs and measurements of serum level.
Notably, clomipramine is associated with significantly more weight gain than SSRIs, even more than paroxetine, the SSRI that is associated with the greatest weight gain. In a 2.5-year follow-up study, clomipramine was associated with the greatest increase in weight increase and fluoxetine and sertraline with the least (Maina et al., 2004). The percentage of patients who gained 7% of more of their baseline weight were: clomipramine 35%, fluoxetine 9%, sertraline 5%.
Bottomline
Since it is not clear that clomipramine is substantially more efficacious than SSRIs and clomipramine has more adverse effects than SSRIs, the American Psychiatric Association’s Practice guideline for the treatment of patients with obsessive-compulsive disorder (2007) recommends that SSRIs should be used as first-line treatments for OCD rather than clomipramine.
Related Pages
High-dose SSRIs for OCD?
BEST books for patients with OCD
References
American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Arlington, VA: American Psychiatric Association, 2007. Available online at http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/ocd.pdf. Guideline Watch (2013) available at http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/ocd-watch.pdf
Maina G, Albert U, Salvi V, Bogetto F. Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors. J Clin Psychiatry. 2004 Oct;65(10):1365-71. PubMed PMID: 15491240.
Meta-analyses
Abramowitz JS. Effectiveness of psychological and pharmacological treatments for obsessive-compulsive disorder: a quantitative review. J Consult Clin Psychol. 1997 Feb;65(1):44-52. PubMed PMID: 9103733.
Ackerman DL, Greenland S. Multivariate meta-analysis of controlled drug studies for obsessive-compulsive disorder. J Clin Psychopharmacol. 2002 Jun;22(3):309-17. PubMed PMID: 12006902.
Eddy KT, Dutra L, Bradley R, Westen D. A multidimensional meta-analysis of psychotherapy and pharmacotherapy for obsessive-compulsive disorder. Clin Psychol Rev. 2004 Dec;24(8):1011-30. PubMed PMID: 15533282.
Greist JH, Jefferson JW, Kobak KA, Katzelnick DJ, Serlin RC. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis. Arch Gen Psychiatry. 1995 Jan;52(1):53-60. PubMed PMID: 7811162.
Kobak KA, Greist JH, Jefferson JW, Katzelnick DJ, Henk HJ. Behavioral versus pharmacological treatments of obsessive compulsive disorder: a meta-analysis. Psychopharmacology (Berl). 1998 Apr;136(3):205-16. PubMed PMID: 9566805.
Skapinakis P, Caldwell DM, Hollingworth W, Bryden P, Fineberg NA, Salkovskis P, Welton NJ, Baxter H, Kessler D, Churchill R, Lewis G. Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2016 Aug;3(8):730-9. PubMed PMID: 27318812; PubMed Central PMCID: PMC4967667.
Head-to-head comparisons
Freeman CP, Trimble MR, Deakin JF, Stokes TM, Ashford JJ. Fluvoxamine versus clomipramine in the treatment of obsessive compulsive disorder: a multicenter, randomized, double-blind, parallel group comparison. J Clin Psychiatry. 1994 Jul;55(7):301-5. PubMed PMID: 8071291.
Koran LM, McElroy SL, Davidson JR, Rasmussen SA, Hollander E, Jenike MA. Fluvoxamine versus clomipramine for obsessive-compulsive disorder: a double-blind comparison. J Clin Psychopharmacol. 1996 Apr;16(2):121-9. PubMed PMID: 8690827.
López-Ibor JJ Jr, Saiz J, Cottraux J, Note I, Viñas R, Bourgeois M, Hernández M, Gómez-Pérez JC. Double-blind comparison of fluoxetine versus clomipramine in the treatment of obsessive compulsive disorder. Eur Neuropsychopharmacol. 1996 May;6(2):111-8. PubMed PMID: 8791036.
Milanfranchi A, Ravagli S, Lensi P, Marazziti D, Cassano GB. A double-blind study of fluvoxamine and clomipramine in the treatment of obsessive-compulsive disorder. Int Clin Psychopharmacol. 1997 May;12(3):131-6. PubMed PMID: 9248868.
Mundo E, Maina G, Uslenghi C. Multicentre, double-blind, comparison of fluvoxamine and clomipramine in the treatment of obsessive-compulsive disorder. Int Clin Psychopharmacol. 2000 Mar;15(2):69-76. PubMed PMID: 10759337.
Ravizza L, Barzega G, Bellino S, Bogetto F, Maina G. Drug treatment of obsessive-compulsive disorder (OCD): long-term trial with clomipramine and selective serotonin reuptake inhibitors (SSRIs). Psychopharmacol Bull. 1996;32(1):167-73. PubMed PMID: 8927668.
Zohar J, Judge R. Paroxetine versus clomipramine in the treatment of obsessive-compulsive disorder. OCD Paroxetine Study Investigators. Br J Psychiatry. 1996 Oct;169(4):468-74. PubMed PMID: 8894198.
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Thanks! I’d love to know if there is actually evidence around augmentation of an SSRI with clomipramine or SGA. Foa et al had an article I recall reading a few years back that were less excited about the addition of risperodone versus side effects but this gets discussed so often as a possible next step.