Clomipramine

Pronunciation: kloe-MIP-ra-meen.

Generic name: clomipramine hydrochloride
Brand names: Anafranil (most countries), APO-Clomipramine, Clomipramine-Teva, Clomipramine-WGR (generic, various countries)
Drug class: Tricyclic antidepressant (TCA) with potent serotonin-reuptake-inhibiting activity
Form: Capsule or tablet, 10 mg, 25 mg, 50 mg, or 75 mg depending on brand and market
Route: Oral
Legal status: Prescription-only in all markets reviewed.

Availability and supply rules vary by country

Trade names by country: United States · United Kingdom · Canada · Australia · New Zealand

Australia: Anafranil (5), APO-Clomipramine (5) · Full directory

Boxed warning: Increased risk of suicidal thinking and behaviour in children, adolescents, and young adults

Clomipramine carries a boxed warning (the US FDA's strongest safety warning), shared with antidepressants as a class: antidepressants increased the risk, compared with placebo, of suicidal thinking and behaviour in short-term studies in children, adolescents, and young adults (under 25 years of age). In pooled analyses of over 4,400 paediatric and 77,000 adult patients, this worked out to about 14 additional cases of suicidal thinking or behaviour per 1,000 patients treated under age 18, and about 5 additional cases per 1,000 treated aged 18 to 24. Short-term studies did not show this increased risk in adults over 24, and showed a reduction in suicidality risk in adults 65 and older. Anyone starting clomipramine -- and their family or caregivers -- should watch closely for new or worsening depression, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, restlessness, unusual changes in behaviour, or thoughts of suicide or self-harm, especially during the first few months of treatment and whenever the dose is changed. Report any such changes to the prescriber immediately, especially if they are severe, sudden, or were not part of the person's condition before starting treatment. (1)

What clomipramine hydrochloride is and how it works

Clomipramine is a tricyclic antidepressant that increases the amount of certain natural chemical messengers (mainly serotonin, and to a lesser extent noradrenaline) in the brain. In the United States it is approved specifically for obsessive-compulsive disorder (OCD); in the United Kingdom and several other countries it is also approved for depression, obsessional and phobic states, and as an add-on treatment for cataplexy in narcolepsy. (1) (2)

Like all antidepressants, clomipramine carries a genuine boxed warning for an increased risk of suicidal thinking and behaviour in children, adolescents, and young adults under 25, especially in the first few months of treatment and after dose changes -- close monitoring by family, caregivers, and the prescriber is essential during this time. Clomipramine also carries a real, dose-related seizure risk, a serious risk of drug interactions with MAOI antidepressants and other serotonergic medicines, and effects on heart rhythm -- always take it exactly as prescribed and never stop or change your dose without your prescriber's guidance, since stopping abruptly can cause withdrawal symptoms.

Mechanism of action: how clomipramine hydrochloride works

Clomipramine is a tricyclic antidepressant that potently inhibits neuronal reuptake of serotonin (and, via its active desmethyl-metabolite, noradrenaline), increasing synaptic availability of these neurotransmitters. It also has anticholinergic, antihistaminic, and alpha-adrenergic-blocking activity, accounting for much of its side-effect profile. (1) (2)

What clomipramine hydrochloride is used for

Obsessive-compulsive disorder (OCD)

Treats obsessions and compulsions in OCD that cause marked distress, take up significant time, or significantly interfere with social or work functioning. This is the sole approved US indication. (1)

Depression

Treats symptoms of depressive illness, particularly where a sedating antidepressant is appropriate. (2)

Obsessional and phobic states

Treats obsessional and phobic states, similar to the OCD indication approved in the United States. (2)

Cataplexy associated with narcolepsy (add-on treatment)

Used as an adjunctive (add-on) treatment for cataplexy -- sudden muscle weakness triggered by strong emotion -- in people with narcolepsy. (2)

Before taking clomipramine hydrochloride

Do not take / not appropriate for

Do not take clomipramine if you have taken a monoamine oxidase inhibitor (MAOI) antidepressant in the last 2-3 weeks, or if you plan to start one -- this combination is contraindicated because of a serious risk of serotonin syndrome and hypertensive crisis. (all countries) (1) (2)
Do not take clomipramine if you have recently had a heart attack, have heart block, or have a cardiac arrhythmia. (United Kingdom, European Union) (2) (1)
Do not take clomipramine if you have narrow-angle glaucoma, urinary retention, mania, or severe liver disease. (United Kingdom, European Union) (2)
Do not take clomipramine with linezolid or intravenous methylene blue. (United States) (1)
Do not take clomipramine if you have a known allergy to clomipramine or other tricyclic antidepressants. (all countries) (1) (2)

Tell your clinician about

Any personal or family history of seizures, or any condition that increases seizure risk.
Any heart problems, including irregular heartbeat, heart block, or a recent heart attack.
Any history of glaucoma, urinary retention, or difficulty emptying your bladder.
Any personal or family history of bipolar disorder or mania.
All other medicines and supplements you take, especially other antidepressants (including SSRIs and other TCAs), MAOIs, triptans, tramadol, lithium, and St John's Wort, since these increase the risk of serotonin syndrome.
Whether you are pregnant, plan to become pregnant, or are breastfeeding.
Whether you or a family member has ever had thoughts of suicide or self-harm.

(1) (2)

How to take clomipramine hydrochloride

Take clomipramine exactly as your prescriber directs -- your dose is started low and increased gradually over the first few weeks.
Doses are often taken with meals during the titration period, and the full daily dose may be taken once at bedtime after titration, since it can cause drowsiness.
Do not stop taking clomipramine suddenly without talking to your prescriber -- abrupt discontinuation can cause withdrawal symptoms such as dizziness, nausea, vomiting, headache, sleep disturbance, and irritability. Your prescriber will taper your dose gradually if you need to stop.
It may take several weeks of treatment before you notice the full benefit.

(1) (2)

Procedures and treatment changes

Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1) (2) (3) (4) (5) (6)

Missed dose

If you miss a dose, contact your pharmacist or prescriber for guidance rather than doubling your next dose. Do not stop or change your dosing schedule on your own.

Overdose

Clomipramine overdose can be fatal and requires emergency medical attention immediately, even if you feel well at first -- symptoms can appear within 4 hours and peak around 24 hours later, with risk continuing for several days. Call emergency services or go to the nearest emergency department right away; in the United States, you can also contact a poison control centre at 1-800-222-1222. (1) (2)