When you (or someone you care for) are facing obsessive‑compulsive disorder (OCD) or severe anxiety, picking the right pill can feel like a gamble. Anafranil is the brand name for clomipramine, a tricyclic antidepressant (TCA) that has been used for OCD since the 1970s. It works by blocking the re‑uptake of serotonin and norepinephrine, which lifts mood and reduces compulsive thoughts. Because it’s older and has a distinct side‑effect profile, many patients wonder whether newer drugs might be safer or more effective. This article walks through the key points you need to decide if clomipramine is right for you, and how it stacks up against the most common alternatives.
Quick Takeaways
- Clomipramine is the most evidence‑based TCA for OCD, but it carries more anticholinergic side effects than most SSRIs.
- SSRIs such as fluoxetine, sertraline, and fluvoxamine are first‑line because they are better tolerated.
- Cost on the NHS is comparable for most drugs; generic clomipramine is slightly cheaper.
- Switching between drugs should be done under medical supervision to avoid serotonin syndrome.
- Clomipramine comparison shows it excels in efficacy for treatment‑resistant cases but lags in safety for older adults.
How Clomipramine Works and What Makes It Unique
Clomipramine belongs to the tricyclic class, which predates the selective serotonin re‑uptake inhibitors (SSRIs). Its dual action on serotonin and norepinephrine gives it a stronger pull on the brain circuits that drive compulsions. Clinical trials from the 1990s onward consistently report response rates of 60‑70% in OCD patients, compared with 45‑55% for most SSRIs.
Key pharmacological attributes:
- Drug class: Tricyclic antidepressant (TCA)
- Primary mechanism: Serotonin and norepinephrine re‑uptake inhibition
- Typical adult dose for OCD: 100‑250mg daily, divided into 2 doses
- Half‑life: ~30hours, allowing once‑daily dosing after titration
- Common side effects: Dry mouth, constipation, blurred vision, weight gain, sexual dysfunction
Because of its anticholinergic load, clomipramine can cause dizziness and orthostatic hypotension in people over 65. That’s the main reason many clinicians reserve it for patients who have not responded to first‑line SSRIs.
Top Alternatives: SSRIs and Other Antidepressants
Below are the six most frequently prescribed alternatives. Each entry includes a short micro‑definition so search engines can recognise the entity.
Fluoxetine is a selective serotonin re‑uptake inhibitor (SSRI) approved for OCD, depression, and bulimia.
Sertraline is an SSRI commonly used as first‑line therapy for OCD and panic disorder.
Fluvoxamine is an SSRI with the strongest evidence for OCD among the SSRI class.
Escitalopram is an SSRI noted for its favorable side‑effect profile and high receptor selectivity.
Paroxetine is an SSRI that can cause more weight gain and sexual side effects than other SSRIs.
Duloxetine is a serotonin‑norepinephrine re‑uptake inhibitor (SNRI) used for depression and pain syndromes, occasionally off‑label for OCD.
Side‑by‑Side Comparison Table
| Attribute | Anafranil (Clomipramine) | Fluoxetine | Sertraline | Fluvoxamine | Escitalopram | Paroxetine |
|---|---|---|---|---|---|---|
| Drug class | Tricyclic (TCA) | SSRI | SSRI | SSRI | SSRI | SSRI |
| Primary mechanism | Serotonin+Norepinephrine re‑uptake inhibition | Serotonin re‑uptake inhibition | Serotonin re‑uptake inhibition | Serotonin re‑uptake inhibition | Serotonin re‑uptake inhibition | Serotonin re‑uptake inhibition |
| Typical OCD dose (mg) | 100‑250 | 20‑80 | 50‑200 | 50‑300 | 10‑20 | 20‑60 |
| Half‑life (hours) | ~30 | 2‑3 (active metabolite 4‑6) | 26 | 15‑20 | 27-32 | 21 |
| Response rate in OCD trials | 60‑70% | 45‑55% | 45‑55% | 50‑60% | 45‑55% | 40‑50% |
| Common side effects | Dry mouth, constipation, dizziness, weight gain | Nausea, insomnia, sexual dysfunction | Diarrhea, insomnia, sexual dysfunction | Nausea, insomnia, sexual dysfunction | Headache, nausea, mild sexual side effects | Weight gain, sexual dysfunction, drowsiness |
| Serious risk | Cardiac conduction changes (QT prolongation) in high doses | Serotonin syndrome (rare) | Serotonin syndrome (rare) | Serotonin syndrome (rare) | Serotonin syndrome (rare) | Serotonin syndrome (rare) |
| Cost on NHS (generic) | £0.10‑£0.15 per tablet | £0.12‑£0.18 per tablet | £0.13‑£0.20 per tablet | £0.14‑£0.22 per tablet | £0.15‑£0.23 per tablet | £0.13‑£0.19 per tablet |
When Clomipramine Beats the Rest
If you have tried two different SSRIs at therapeutic doses for at least 12 weeks each and still see only marginal improvement, the evidence suggests clomipramine may push you into the responder zone. Its stronger norepinephrine effect also helps patients whose anxiety has a marked physical component (e.g., tremor, rapid heart rate).
Older adults with cardiac histories should avoid clomipramine unless the benefits clearly outweigh the risks. In such cases, an SSRI with a clean cardiac profile-like escitalopram-is generally safer.
Practical Considerations: Dosing, Monitoring, and Switching
- Starting dose: Begin with 25mg at night to minimize anticholinergic side effects.
- Titration: Increase by 25mg every 2‑3 weeks until you reach the target 100‑150mg for most patients.
- Blood monitoring: Baseline ECG is recommended for anyone over 60 or with known heart disease. Repeat after reaching 200mg.
- Drug interactions: Avoid simultaneous use of MAO inhibitors, tramadol, or other serotonergic agents without a wash‑out period of at least 14 days.
- Switching to an SSRI: Gradually taper clomipramine over 2‑4 weeks while starting the SSRI at a low dose. This reduces the chance of serotonin syndrome.
Patients often report that the “sedating start” of clomipramine fades after the first month, making it a viable long‑term option when other drugs fail.
Best‑Fit Scenarios: Who Should Choose Which Drug?
- First‑line for most new OCD diagnoses: Sertraline or fluvoxamine - they are well‑tolerated and have the strongest guideline support.
- Patients with co‑existing chronic pain: Duloxetine may address both mood and pain pathways.
- Treatment‑resistant OCD (failed two SSRIs): Switch to clomipramine.
- Older adults or those with cardiac risk: Choose escitalopram or sertraline.
- Women of child‑bearing age: Fluoxetine or sertraline have the most safety data in pregnancy.
Frequently Asked Questions
Can I take clomipramine and an SSRI together?
Combining a TCA with an SSRI dramatically raises the risk of serotonin syndrome, a potentially life‑threatening condition. Doctors only do this when the benefit is clear and the patient is closely monitored, usually with a very low SSRI dose and a gradual taper of clomipramine.
How long does it take for clomipramine to work for OCD?
Most patients notice a reduction in compulsive thoughts after 4‑6 weeks at a therapeutic dose, but full response can take up to 12 weeks. Patience and steady titration are key.
Is clomipramine safe for pregnant women?
Clomipramine is classified as Category B in the UK, meaning animal studies haven’t shown risk but human data are limited. Most clinicians prefer an SSRI like fluoxetine if a patient becomes pregnant while on treatment.
What are the main differences in side‑effects between clomipramine and sertraline?
Clomipramine often causes dry mouth, constipation, and occasional dizziness due to its anticholinergic action. Sertraline’s most common complaints are gastrointestinal-nausea and diarrhea-plus occasional insomnia. Sexual dysfunction can occur with both, but it’s typically milder with sertraline.
Do I need regular blood tests while on clomipramine?
Routine blood work isn’t required for most patients, but a baseline liver function test and ECG are advised, especially for doses above 200mg or in patients with cardiac history.
Next Steps for Anyone Considering a Switch
1. Schedule an appointment with your GP or psychiatrist and bring a list of all current meds.
2. Discuss whether you’ve completed an adequate trial of at least two SSRIs (12 weeks each, at max dose).
3. If the answer is yes, ask about a clomipramine trial, emphasizing the need for ECG monitoring if you’re over 60.
4. Ask for a clear taper plan if you need to stop an existing SSRI.
5. Keep a symptom diary for the first 8 weeks; note any side effects, sleep changes, or new anxiety patterns.
Switching meds can feel daunting, but with a step‑by‑step plan you’ll know exactly what to expect and when to call your prescriber.
Choosing the right OCD medication isn’t a one‑size‑fits‑all decision. By weighing efficacy, safety, cost, and personal health factors, you can land on the option that gives you the most relief with the fewest unwanted effects.
Comments (1)
Brad Tollefson October 14 2025
Clomipramine works, but the dry mouth can be a real pain.