Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most notably obsessive–compulsive disorder but also many other disorders, including hyperacusis, panic disorder, major depressive disorder, trichotillomania,Swedo, S E et al. "A double-blind comparison of clomipramine and desipramine in the treatment of trichotillomania (hair pulling)." The New England Journal of Medicine Vol. 321,8 (1989): 497-501. doi:10.1056/NEJM198908243210803 body dysmorphic disorderAdebayo, Kazeem Olaide et al. "Body dysmorphic disorder in a Nigerian boy presenting as depression: a case report and literature review." International Journal of Psychiatry in Medicine Vol. 44,4 (2012): 367-72. doi:10.2190/PM.44.4.fPhillips, K.A., Albertini, R.S., Siniscalchi, J.M., Khan, A. and Robinson, M., 2001. "Effectiveness of pharmacotherapy for body dysmorphic disorder: a chart-review study." Journal of Clinical Psychiatry, 62(9), pp. 721-727.Pallanti, S. and Koran, L.M., 1996. "Intravenous, pulse-loaded clomipramine in body dysmorphic disorder: two case reports." CNS Spectrums, 1(2), pp. 54-57. and chronic pain. It has also been notably used to treat premature ejaculation and the cataplexy associated with narcolepsy.Shapiro, W. R. (1975). "Treatment of cataplexy with clomipramine." Archives of Neurology, 32(10), pp. 653-656.Dauvilliers Y, Siegel JM, Lopez R, Torontali ZA, Peever JH. "Cataplexy—clinical aspects, pathophysiology and management strategy." Nature Reviews Neurology. 2014 Jul, 10(7):386-95..
It may also address certain fundamental features surrounding narcolepsy besides cataplexy (especially hypnagogic and hypnopompic hallucinations).Chen C. N. (1980). "The use of clomipramine as an REM sleep suppressant in narcolepsy." Postgraduate Medical Journal, 56 Suppl 1, pp. 86–89. The evidence behind this, however, is less robust. As with other antidepressants (notably including selective serotonin reuptake inhibitors), it may paradoxically increase the risk of suicide in those under the age of 25, at least in the first few weeks of treatment.
It is typically taken by mouth, although intravenous preparations are sometimes used.Karameh, Wael Karameh, and Munir Khani. "Intravenous Clomipramine for Treatment-Resistant Obsessive-Compulsive Disorder." The International Journal of Neuropsychopharmacology Vol. 19,2 pyv084. 28 July 2015, doi:10.1093/ijnp/pyv084Sallee, F R et al. "Pulse intravenous clomipramine for depressed adolescents: double-blind, controlled trial." The American Journal of Psychiatry Vol. 154,5 (1997): 668-73. doi:10.1176/ajp.154.5.668
Common side effects include dry mouth, constipation, loss of appetite, sleepiness, weight gain, sexual dysfunction, and trouble urinating. Serious side effects include an increased risk of suicidal behavior in those under the age of 25, seizures, mania, and liver problems. If stopped suddenly, a withdrawal syndrome may occur with headaches, sweating, and dizziness. It is unclear if it is safe for use in pregnancy. Its mechanism of action is not entirely clear but is believed to involve increased levels of serotonin and norepinephrine.
Clomipramine was discovered in 1964 by the Swiss drug manufacturer Ciba-Geigy. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.
Medical uses Clomipramine has a number of uses in medicine, including in the treatment of:
Obsessive–compulsive disorder (OCD), which happens to be its only US -labeled indication. Other regulatory agencies (such as the TGA of Australia and the MHRA of the UK) have also approved clomipramine for this indication. A 2024 systematic review found that clomipramine is also effective in managing OCD in pediatric population. Major depressive disorder (MDD), a popular off-label use in the US. It is approved by the Australian TGA and the United Kingdom MHRA for this indication. In Japan it is also approved for depression. Some have suggested the possible superior efficacy of clomipramine compared to other antidepressants in the treatment of MDD,Danish University Antidepressant Group. (1990). Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. Journal of Affective Disorders, 18(4), 289-299. especially the more severe, although at the current time the evidence may be insufficient to more fully substantiate this claim.
As-with other tricyclic antidepressants, the antidepressant response specifically may be augmented, including in treatment-resistant cases, with triiodothyronine, at a dosage of 50 mcg. In the case of clomipramine specifically, this may also be the case with OCD.
Panic disorder with or without agoraphobia. Body dysmorphic disorder Repetitive self-injurious/self-harming behaviours in those with intellectual disability specifically. The subtype of systemised paranoia characterised by somatic phenomena. Compulsive nail-biting (onychophagia). Cataplexy associated with narcolepsy. This is a TGA and MHRA-labeled indication for clomipramine. Self-bloodlettingMestermann S, Rudtke L, Brazdis RM, Tsaktanis T, Kornhuber J, Thürauf N. Successful Pharmacologic Treatment of Self-Bloodletting with Factitious Chronic Anemia (Lasthénie de Ferjol Syndrome) with High-Dose Serotonergic Medication: A Case Report. Behav Sci (Basel). 2024 Mar 14;14(3):237. doi: 10.3390/bs14030237. PMID 38540540. Premature ejaculation, where it may be more effective than paroxetineWaldinger, M. D., Zwinderman, A. H., & Olivier, B. (2004). On-demand treatment of premature ejaculation with clomipramine and paroxetine: a randomized, double-blind fixed-dose study with stopwatch assessment. European urology, 46(4), 510–516. https://doi.org/10.1016/j.eururo.2004.05.005 Depersonalization-derealization disorder Chronic pain with or without organic disease, particularly headache of the tension type. Developmental stuttering Sleep paralysis, with or without narcolepsy Enuresis (involuntary urinating in sleep) in children. The effect may not be sustained following treatment, and alarm therapy may be more effective in both the short-term and the long-term. Combining a tricyclic (such as clomipramine) with anticholinergic medication may be more effective for treating enuresis than the tricyclic alone. Trichotillomania In combination with lithium and tryptophan for severe, particularly treatment-resistant depression. This combination, in a similar vein, has also been used for clomipramine-resistant obsessive-compulsive disorder. When electro-convulsive therapy is performed alongside this treatment-regime (as may be the case in severe depression and accompanied with thyroxine,) however, great care must be taken with lithium. The overall risk of seizures may have to be weighted against the refractory severity of the current illness and necessity of the amalgamation of treatment(s). Isolated cataplexy unto itself (i.e., in the absence of characteristically associated narcolepsy), admittedly a rare conditionMandagere, V. and Rayment, D., 2024. Atypical isolated cataplexy: two case reports and a mini-review. Neurocase, pp.1-3. There is anecdotal and tentative, as-yet-undocumented information suggesting that clomipramine may address certain core features of hyperacusis, and possibly misophonia. In the case of hyperacusis, this appears to be especially the case at doses > 150 mg/d. As-with obsessive-compulsive disorder, a full response to any one dose may not be experienced for up to 12–16 weeks.
Although lithium is most-associated with the treatment of bipolar disorder (where it is known for its general mood-stabilising features and to be especially useful in treating and preventing mania), it may have a certain place in the management of treatment-resistant depression (which is often of higher severity than other depressions which have not been addressed with ECT). In these cases it is often prescribed alongside SSRIs (e.g., fluoxetine, paroxetine), venlafaxine and various of the tricyclics (e.g., clomipramine, amitriptyline, nortriptyline, maprotiline), which is why it may feature sometimes in the discussion of depression being managed with clomipramine. Lithium also significantly reduces the long-term risk of suicide in general. In any case, it is not necessary to have a diagnosis of bipolar affective disorder (manic-depressive illness), or even to be considered to have subtle elements of it ("soft bipolarity"), to benefit from lithium in the context of treatment with clomipramine.
In a meta-analysis of various trials involving fluoxetine (Prozac), fluvoxamine (Faverin/Luvox), and sertraline (Zoloft) to test their relative efficacies in treating OCD, clomipramine was found to be significantly more effective.Wilson, M., & Tripp, J. (2022). Clomipramine. In StatPearls. StatPearls Publishing. Other studies have borne similar results even when risk of bias is eliminated. A potentially significantly greater inherent side-effect profile, however, makes it a second-line choice in the treatment of OCD. SSRIs are generally better-tolerated but appear to be inferior in terms of actual clinical efficacy.
Contraindications Contraindications include:
Known hypersensitivity to clomipramine, or any of the excipients or cross-sensitivity to tricyclic antidepressants of the dibenzazepine group Recent myocardial infarction Any degree of heart block or other cardiac arrhythmias Mania Severe liver disease Narrow angle glaucoma Untreated urinary retention It must not be given in combination or within 3 weeks before or after treatment with a monoamine oxidase inhibitor. (Moclobemide-included; however, clomipramine may be initiated sooner at 48 hours following discontinuation of moclobemide.)
Pregnancy and lactation Clomipramine use during pregnancy is associated with congenital heart defects in the newborn. It is also associated with reversible withdrawal effects in the newborn. Clomipramine is also distributed in breast milk and hence nursing while taking clomipramine is advised against.
Side effects Clomipramine has been associated with the side effects listed below:
Very common (>10% frequency):
Accommodation defect Blurred vision Nausea Dry mouth (Xerostomia) Constipation Fatigue Dizziness Tremor Headache Myoclonus Drowsiness Somnolence Restlessness Micturition disorder Sexual dysfunction (erectile dysfunction and loss of libido) Hyperhidrosis (profuse sweating)
Common (1–10% frequency):
Weight loss Dystonia Cognitive impairment Orthostatic hypotension Sinus tachycardia Clinically irrelevant ECG changes (e.g. T- and ST-wave changes) in patients of normal cardiac status Palpitations Tinnitus (hearing ringing in one's ears) Mydriasis (dilated pupils) Vomiting Abdominal disorders Diarrhoea Decreased appetite Increased transaminases Increased Alkaline phosphatase Speech disorders Paraesthesia Muscle hypertonia Dysgeusia Memory impairment Muscular weakness Disturbance in attention Confusional state Disorientation Hallucinations (particularly in elderly patients and patients with Parkinson's disease) Anxiety Agitation Sleep disorders Mania Hypomania Aggression Depersonalization Insomnia Nightmares Aggravation of depression Delirium Galactorrhoea (lactation that is not associated with pregnancy or breastfeeding) Orgasms triggered by yawning Hot flush Dermatitis allergic (skin rash, urticaria) Photosensitivity reaction Pruritus (itching)
Uncommon (0.1–1% frequency): Convulsions Ataxia Arrhythmias Elevated blood pressure Activation of psychotic symptoms
Very rare (<0.01% frequency):
Pancytopenia – an abnormally low amount of all the different types of blood cells in the blood (including platelets, white blood cells and red blood cells). Leukopenia – a low white blood cell count.