Clomipramine (Anafranil): dosage, uses, side effects

Most people have brief moments where they feel concerned about germs or contamination. Others may not be able to fall asleep until they double-check that they’ve locked their door. But for some people, these thoughts and behaviors become overwhelming, and a healthcare provider may diagnose them with obsessive compulsive disorder (OCD). 

If that’s the case, therapy and certain medications can help control their OCD. One such medication is clomipramine (brand name Anafranil). Keep reading for an overview of Anafranil, including its uses, dosage, side effects, and risks. 

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Clomipramine (Anafranil) is a generic antidepressant medication that’s available by prescription. It belongs to an older drug class called tricyclic antidepressants (TCAs), which are named for the three rings in their chemical structure and include medications like amitriptyline, imipramine, and nortriptyline (Mallinckrodt, 2019). 

The U.S. Food and Drug Administration (FDA) approved Anafranil, the brand-name version of clomipramine, back in 1989, and it was the first medication specifically approved to treat obsessive-compulsive disorder (OCD) (Wilson, 2021).

People often inappropriately use the term “OCD” as slang to describe someone who likes to keep things clean and organized. But, OCD is actually a mental health condition that involves unwanted, recurrent thoughts (obsessions) and repetitive behaviors or rituals (compulsions). These obsessions and compulsions can consume a significant amount of time and energy and may seriously affect a person’s ability to function in daily life and relationships (Fenske, 2015).

Fortunately, there are treatments available that can help, including antidepressant medications like clomipramine (Fenske, 2015). It isn’t known for sure how clomipramine works to treat OCD. What we do know is that the drug enhances the availability of serotonin (the “feel-good” hormone) in the brain (Mallinckrodt, 2019). 

The FDA approves clomipramine to treat obsessive-compulsive disorder (OCD) in adults and children ages 10 years and older (Mallinckrodt, 2019). 

While clomipramine is approved to treat OCD, it’s not usually the first-choice medication of healthcare providers for this diagnosis. Selective-serotonin reuptake inhibitors (SSRIs), often in high doses, are more popular treatments. 

SSRIs like fluvoxamine (brand name brand name Luvox or Luvox CR), paroxetine (brand name Brisdelle, Paxil), and sertraline (brand name Zoloft) typically cause fewer side effects than clomipramine. So, healthcare providers may prescribe clomipramine as a second-choice or add-on treatment for OCD that’s not well-controlled with other medications (Feske, 2015; Wilson, 2021). 

Sometimes, healthcare providers prescribe clomipramine “off-label” for other uses, meaning conditions that the FDA didn’t specifically approve it to treat. There are many off-label uses for clomipramine. Some examples include (Wilson, 2021):

• Depression and treatment-resistant depression

• Anxiety

• Cataplexy syndrome—sudden episodes of muscle weakness often triggered by strong emotions such as laughing or crying 

• Insomnia (trouble sleeping)

• Body dysmorphic disorder

• Premature ejaculation

• Bedwetting

• Trichotillomania (compulsive hair-pulling)

• Panic disorder, a condition that causes panic attacks 

• Chronic neuropathy (nerve-related pain)

Common side effects of clomipramine include (Mallinckrodt, 2019): 

• Dry mouth

• Constipation

• Nausea

• Indigestion

• Increased or decreased appetite

• Muscle twitching

• Drowsiness

• Dizziness

• Sexual dysfunction like changes in sex drive, failure to ejaculate, and erectile dysfunction

• Fatigue

• Sweating more than usual

Less commonly, people experience other side effects of clomipramine (Mallinckrodt, 2019):

• High blood pressure

• Fast heart rate or heart palpitations

• Confusion, psychosis, or hallucinations

• Urination problems

• Feeling irritable or restless 

• Hot flashes

• Increased body temperature

Because of the possibility of drowsiness and dizziness, it’s best to avoid driving while taking clomipramine until you see how it affects you. And drinking alcohol while taking this medication could make some of these side effects worse. If you have concerns about possible adverse effects of taking clomipramine, you can discuss them with your healthcare provider or pharmacist. 

Clomipramine comes as an oral capsule that is available in three strengths: 25 milligrams (mg), 50 mg, and 75 mg (Mallinckrodt, 2019).

For OCD, the typical starting dose of clomipramine is 25 mg per day. Healthcare providers might increase your dose over time, up to a maximum of 250 mg per day. It is important to know that clomipramine takes a while to start working. It may take 6 to 12 weeks of treatment with clomipramine to see improvement in OCD symptoms (Wilson, 2021). 

Your healthcare provider may adjust your dose based on how well you tolerate and respond to the medication. Always consult your healthcare provider before changing your dose or stopping any prescription medications.

The FDA requires clomipramine and other antidepressants to carry a boxed warning due to their rare but serious risk of suicidal tendencies. An increased risk of suicidal thoughts and behaviors mainly affects children, adolescents, and young adults aged 24 or younger, especially in the early stages of treatment or after dose increases. 

People who notice negative changes in their thoughts and behaviors since starting clomipramine should tell their healthcare provider right away or seek urgent medical care (Mallinckrodt, 2019).

Other precautions

Clomipramine isn’t safe for everyone. Your healthcare provider will go over your medical history with you before they consider prescribing it. The following conditions could raise the risk for serious side effects (Mallinckrodt, 2019):

• High blood pressure or heart disease

• Bipolar disorder, schizophrenia, or other mental health disorder

• Seizure disorder

• Urination problems

• Overactive thyroid

• Liver or kidney disease

• Glaucoma

• Older adults (ages 65+) due to the risk of hyponatremia (low sodium levels in the blood)

• Alcohol use

• Pregnant or breastfeeding

• Past allergic reaction to clomipramine or other tricyclic antidepressants (TCAs), such as amitriptyline, imipramine, and nortriptyline.

Several types of medications can interact with clomipramine. Some drug interactions can lead to severe side effects. 

If you take them with clomipramine, certain medications can raise the levels of serotonin; a “feel good” brain chemical that regulates your mood. In rare cases, serotonin syndrome can occur. Symptoms of serotonin syndrome vary and range from mild to life-threatening. Taking the following medications with clomipramine can increase the risk of serotonin syndrome (Mallinckrodt, 2019):

• Monoamine oxidase inhibitor (MAOI) drugs such as phenelzine, tranylcypromine, linezolid, rasagiline, and methylene blue.

• Other antidepressants including other tricyclic antidepressants (such as amitriptyline, doxepin, imipramine and nortriptyline); SSRIs (such as citalopram, escitalopram, fluoxetine, and fluvoxamine); and SNRIs (such as duloxetine; and venlafaxine)

• Triptans, a drug class used to treat migraine headaches

• Painkillers fentanyl and tramadol

• Herbal supplements like St. John's wort and tryptophan

• Buspirone, an anti-anxiety medication

• Lithium, a mood stabilizer drug

Certain medications can increase or decrease clomipramine’s levels and effects, such as:

• Methylphenidate, a medication used for attention deficit hyperactivity disorder (ADHD)

• Haloperidol, a drug for schizophrenia or other mental health conditions

• Cimetidine, an antacid

Clomipramine can also affect other medications from working as they should. One example is clonidine, a drug prescribed to treat high blood pressure or ADHD. Clomipramine may also increase the levels and side effects of drugs like warfarin, a blood thinner, and digoxin, a heart medication.

This list does not include all of clomipramine’s possible interactions. Before taking clomipramine, your healthcare provider or pharmacist will check for interactions with your other medications, so be sure to tell them everything you take. They can offer you personalized medical advice on managing drug interactions and side effects.

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How we reviewed this article

Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

Current version

November 05, 2021

Written by

Patricia Weiser, PharmD

Fact checked by

Felix Gussone, MD

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About the medical reviewer

Felix Gussone, MD, Ro

Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.