Antidepressant Comparison Tool
Compare Antidepressants
Select antidepressants to compare and see key differences in effectiveness, side effects, and practical considerations for treatment decisions.
Comparison Results
| Attribute | Anafranil (Clomipramine) | Fluoxetine (Prozac) | Sertraline (Zoloft) | Venlafaxine (Effexor) | Duloxetine (Cymbalta) | Amitriptyline |
|---|---|---|---|---|---|---|
| Drug class | Tricyclic antidepressant | SSRI | SSRI | SNRI | SNRI | Tricyclic antidepressant |
| Primary FDA indications | OCD, MDD, Panic disorder | MDD, OCD, Bulimia | MDD, OCD, PTSD | MDD, Generalized anxiety | MDD, Diabetic neuropathy | MDD, Chronic pain |
| Typical starting dose | 25 mg daily | 20 mg daily | 50 mg daily | 37.5 mg daily | 30 mg daily | 25 mg daily |
| Weight impact | Weight gain (moderate) | Neutral to slight loss | Neutral | Neutral | Neutral | Weight gain (high) |
| Sexual dysfunction | Frequent | Common | Common | Common | Common | Frequent |
| Cardiac risk | Higher (QT prolongation) | Low | Low | Low | Low | Higher (arrhythmias) |
| Cost (US avg.) | $0.75 per tablet | $0.30 per tablet | $0.35 per tablet | $0.45 per tablet | $0.50 per tablet | $0.70 per tablet |
Decision Guidance
When Anafranil May Be Recommended
Choose Anafranil if you or your patient:
- Have severe OCD that hasn't responded to 2+ SSRIs
- Have comorbid depression with prominent symptoms
- Need broader anxiolytic coverage (dual serotonin/norepinephrine effect)
When to Avoid Anafranil
Consider avoiding Anafranil if:
- You have cardiac history or are taking other QT-prolonging drugs
- Cardiac monitoring isn't possible
- Side effects like dry mouth and sedation are problematic
- Weight gain is a major concern
When you or a loved one need to choose an antidepressant, the options feel endless. One drug that keeps popping up in discussions about obsessive‑compulsive disorder (OCD) and resistant depression is Clomipramine. But how does it really stack up against the newer SSRIs or SNRIs that most doctors prescribe first? This guide walks through the science, the side‑effect profile, and the practical pros and cons of Anafranil compared with the most common alternatives.
What is Anafranil (Clomipramine)?
Anafranil is the brand name for Clomipramine, a tricyclic antidepressant (TCA) that was first approved by the FDA in 1972. While most modern doctors start patients on selective serotonin reuptake inhibitors (SSRIs), Anafranil remains the gold‑standard for severe OCD and is also indicated for major depressive disorder (MDD) and panic disorder when other meds fail.
How does Clomipramine work?
Clomipramine blocks the reuptake of both serotonin and norepinephrine, increasing their levels in the synaptic cleft. It also has mild antagonism at muscarinic, histamine H1, and alpha‑1 adrenergic receptors, which explains many of its side effects. The drug is metabolized primarily by the liver enzyme CYP2D6; patients who are poor metabolizers can see higher plasma concentrations and need dose adjustments.
Clinical effectiveness: When does Anafranil shine?
In multiple double‑blind trials, Clomipramine reduced OCD symptoms by an average of 30‑40 % more than placebo, a gain that outperformed most SSRIs at similar doses. For MDD, the drug’s efficacy is comparable to other TCAs, but its onset of action can be slower than SSRI counterparts. In panic disorder, Clomipramine’s dual serotonin‑norepinephrine effect provides a broader anxiolytic coverage, especially when patients have co‑occurring depressive symptoms.
Side‑effect profile and safety considerations
Because Clomipramine hits many receptors, its side‑effects are broader than those of a typical SSRI. Common complaints include dry mouth, constipation, blurred vision, orthostatic hypotension, and weight gain. Sedation and sexual dysfunction are also frequent. The drug carries a higher risk of cardiac arrhythmias, especially in patients with existing heart disease or when combined with other QT‑prolonging agents. Regular ECG monitoring is advised for anyone on a dose above 150 mg per day.
Head‑to‑head comparison with major alternatives
Below is a quick reference that lines up key attributes of Anafranil against the most widely prescribed antidepressants. The table uses Fluoxetine, Sertraline, Venlafaxine, Duloxetine, and Amitriptyline for quick visual comparison.
| Attribute | Anafranil (Clomipramine) | Fluoxetine (Prozac) | Sertraline (Zoloft) | Venlafaxine (Effexor) | Duloxetine (Cymbalta) | Amitriptyline |
|---|---|---|---|---|---|---|
| Drug class | Tricyclic antidepressant | SSRI | SSRI | SNRI | SNRI | Tricyclic antidepressant |
| Primary FDA indication | OCD, MDD, Panic disorder | MDD, OCD, Bulimia | MDD, OCD, PTSD | MDD, Generalized anxiety | MDD, Diabetic neuropathy | MDD, Chronic pain |
| Typical starting dose | 25 mg daily | 20 mg daily | 50 mg daily | 37.5 mg daily | 30 mg daily | 25 mg daily |
| Half‑life | ≈30 h | ≈4‑6 days | ≈26 h | ≈5 h (active metabolite 11 h) | ≈12 h | ≈10‑50 h (varies) |
| Weight impact | Weight gain (moderate) | Neutral to slight loss | Neutral | Neutral | Neutral | Weight gain (high) |
| Sexual dysfunction | Frequent | Common | Common | Common | Common | Frequent |
| Cardiac risk | Higher (QT prolongation) | Low | Low | Low | Low | Higher (arrhythmias) |
| Cost (US avg.) | $0.75 per tablet | $0.30 per tablet | $0.35 per tablet | $0.45 per tablet | $0.50 per tablet | $0.70 per tablet |
Decision criteria: When to pick Anafranil over an SSRI or SNRI
- Severity of OCD: If a patient has tried at least two SSRIs at therapeutic doses without meaningful improvement, guidelines suggest moving to Clomipramine.
- Comorbid depression: Clomipramine’s dual action can help when depressive symptoms are pronounced and other agents have failed.
- Metabolic considerations: Patients who are CYP2D6 ultra‑rapid metabolizers may see reduced efficacy from Clomipramine; genetic testing can guide dosing.
- Cardiac health: Anyone with a history of arrhythmias, uncontrolled hypertension, or taking other QT‑prolonging drugs should usually avoid Anafranil.
- Side‑effect tolerance: If dry mouth and sedation are unacceptable, an SSRI like Fluoxetine may be a smoother choice.
Practical tips for switching to or from Anafranil
- Consult a psychiatrist before any change; abrupt discontinuation can cause withdrawal symptoms.
- If moving from an SSRI, taper the SSRI over 2‑4 weeks while introducing a low dose of Clomipramine.
- Start at 25 mg daily, split into morning and evening doses to lessen dizziness.
- Schedule an ECG after reaching 150 mg/day, especially for patients over 50 or with cardiac risk factors.
- Monitor blood pressure weekly for the first month; clomipramine can cause orthostatic drops.
- Encourage patients to stay hydrated and chew sugar‑free gum to alleviate dry mouth.
- Re‑evaluate symptom scores (Y‑BOCS for OCD, PHQ‑9 for depression) after 6‑8 weeks to decide on dose adjustments.
Frequently asked questions
Can I take Clomipramine with an SSRI?
Combining two serotonergic agents raises the risk of serotonin syndrome. If a doctor decides an SSRI‑plus‑Clomipramine regimen is necessary, the SSRI dose is usually lowered and the patient is watched closely for agitation, high fever, or muscle rigidity.
How long does it take for Anafranil to work for OCD?
Most patients notice a reduction in intrusive thoughts after 8‑12 weeks at an effective dose. Full response can take up to 6 months, so patience and regular therapy sessions are key.
Is Clomipramine safe during pregnancy?
Animal studies show no major teratogenic effects, but human data are limited. Most clinicians reserve Clomipramine for severe cases where benefits outweigh potential risks, and they switch to a safer SSRI if possible.
What are the biggest differences between TCAs and SSRIs?
TCAs like Clomipramine affect multiple neurotransmitters and bind to several receptor types, leading to more side effects (dry mouth, cardiac effects). SSRIs target only serotonin reuptake, so they’re generally better tolerated but may be less potent for certain anxiety disorders.
Do I need genetic testing before starting Clomipramine?
Testing for CYP2D6 variants can help predict plasma levels, especially if the patient has a history of unusual drug reactions. It’s not mandatory, but many specialists order it when planning a TCA regimen.
Choosing the right antidepressant is rarely a one‑size‑fits‑all decision. Anafranil offers unparalleled strength for stubborn OCD and can rescue patients who haven’t responded to newer drugs. Yet its side‑effect baggage and cardiac warnings mean it should be prescribed thoughtfully, with clear monitoring plans. By weighing symptom severity, medical history, and personal tolerance, clinicians and patients can land on a treatment that genuinely improves daily life.
Felix Chan
October 19, 2025 AT 13:11Hey folks, just wanted to say that starting on Anafranil doesn’t have to feel like stepping off a cliff. Most people begin with a low 25 mg dose and gradually work their way up, which gives the body time to adapt. The dry‑mouth and drowsiness issues are usually manageable with a glass of water and chewing sugar‑free gum. Keep an eye on your blood pressure the first few weeks, and ask your doc for an ECG if you’re hitting the higher end of the dose range. With a bit of patience, many find the OCD symptoms melt away faster than with an SSRI.