anafranil
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Synonyms | |||
Anafranil, known generically as clomipramine, is a tricyclic antidepressant (TCA) primarily used for obsessive-compulsive disorder (OCD). It’s one of those older agents that, frankly, we don’t reach for as a first-line for depression anymore due to side effects, but for OCD? It remains a cornerstone, arguably the most effective pharmacologic agent we have. Its mechanism is distinct, with potent serotonin reuptake inhibition that predates the SSRIs. I remember my first year in psychopharmacology, the attending told me, “If you want to understand OCD treatment, you start and end with clomipramine.” It’s not that simple, of course, but it highlights its foundational role.
1. Introduction: What is Anafranil? Its Role in Modern Medicine
So, what is Anafranil used for? Primarily, it’s indicated for the treatment of obsessions and compulsions in Obsessive-Compulsive Disorder. It’s a potent serotonin reuptake inhibitor, more so than many modern SSRIs, which is why it often works when other medications fail. Its role in modern medicine is that of a powerful, second-line or even first-line specialist tool for severe, treatment-resistant OCD. While newer agents like fluoxetine or sertraline are often tried first due to a more favorable side effect profile, Anafranil’s efficacy is often superior in head-to-head studies. It’s also used off-label for conditions like panic disorder, severe depression with obsessive features, and chronic pain syndromes like neuropathic pain. You don’t use it lightly, but when you need its specific power, it’s indispensable.
2. Key Components and Bioavailability Anafranil
The composition of Anafranil is straightforward: the active ingredient is clomipramine hydrochloride. It’s available in oral capsules, typically 10mg, 25mg, 50mg, and 75mg strengths. There’s no fancy delivery system or added components to enhance bioavailability like you see with some newer supplements. It’s the molecule itself that’s key. Clomipramine is a dibenzazepine derivative, closely related to imipramine. Its bioavailability is actually quite high after oral administration, but it undergoes significant first-pass metabolism in the liver. The parent compound, clomipramine, is a potent serotonin reuptake blocker, but its primary active metabolite, desmethylclomipramine, is a potent noradrenaline reuptake inhibitor. This dual, evolving action is part of what makes its pharmacodynamics so interesting—and its side effect profile so challenging. You’re essentially starting with a very serotonergic drug that becomes more noradrenergic over time as it’s metabolized.
3. Mechanism of Action Anafranil: Scientific Substantiation
How Anafranil works is a masterclass in psychopharmacology. Its primary mechanism of action is the potent inhibition of serotonin reuptake at the presynaptic neuronal membrane. By blocking the serotonin transporter (SERT), it increases the concentration of serotonin in the synaptic cleft, enhancing serotonergic neurotransmission. This is considered the cornerstone of its anti-obsessional effect. But it doesn’t stop there. As mentioned, its major metabolite, desmethylclomipramine, is a potent inhibitor of noradrenaline reuptake. So, you get a dual-action effect. Furthermore, like other TCAs, it has antagonistic effects at muscarinic M1, histaminic H1, and alpha-1 adrenergic receptors. This is the source of its classic anticholinergic side effects: dry mouth, constipation, blurred vision, and sedation. The scientific research is robust; its binding affinity for SERT is among the highest of any TCA, which is why its effect on OCD is so pronounced. It’s not just about increasing serotonin; it’s about a profound and sustained blockade that other agents can’t always match.
4. Indications for Use: What is Anafranil Effective For?
The official indications for use are quite specific, but its real-world application is broader.
Anafranil for Obsessive-Compulsive Disorder
This is its flagship indication. Multiple double-blind, placebo-controlled studies have consistently shown its superiority over placebo and often over other antidepressants for reducing Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. The effect isn’t just on compulsions; it truly dampens the intrusive, obsessive thoughts. I’ve seen patients who were housebound by contamination fears able to leave their homes after a 12-week course.
Anafranil for Depression
While it’s an effective antidepressant, its use for major depressive disorder has waned due to the side effect burden and risk in overdose compared to SSRIs and SNRIs. However, for depression with significant anxiety, agitation, or obsessive ruminations, it can be remarkably effective. It’s a treatment for severe, melancholic depression when other options have failed.
Anafranil for Panic Disorder
It’s highly effective for panic disorder, often aborting attacks completely. The initial side effects can be a barrier, but for treatment-resistant panic, it’s a powerful option.
Anafranil for Chronic Pain
Its use for neuropathic pain, like diabetic neuropathy or post-herpetic neuralgia, is a well-established off-label application. The mechanism is related to its noradrenergic activity, which modulates pain pathways in the descending inhibitory system of the central nervous system.
5. Instructions for Use: Dosage and Course of Administration
Dosing Anafranil is an art. You must start low and go slow to mitigate side effects. For outpatients with OCD, you typically initiate at 25 mg daily and increase gradually by 25 mg every 4-7 days as tolerated. The therapeutic range for OCD is usually between 150 mg and 250 mg per day, though some patients require less. It’s usually administered in divided doses to minimize peak-concentration side effects, but once a stable dose is reached, the entire dose can often be given at bedtime to capitalize on its sedating effects.
| Indication | Starting Dosage | Target Dosage | Administration Notes |
|---|---|---|---|
| OCD (Adult) | 25 mg daily | 100-250 mg/day | Titrate slowly; max 250 mg/day |
| OCD (Child/Adolescent) | 25 mg daily | 3 mg/kg/day or 100-200 mg/day | Very slow titration; close monitoring |
| Panic Disorder | 10-25 mg daily | 75-150 mg/day | Lower doses often effective |
| Depression | 25-50 mg daily | 100-200 mg/day | Divided or single nighttime dose |
The course of administration is long-term for chronic conditions like OCD. It often takes 4-6 weeks to begin seeing a significant response for obsessions and compulsions, and maximum benefit may not be seen for 12 weeks or longer. Abrupt discontinuation is not recommended due to risk of withdrawal symptoms (flu-like symptoms, insomnia, nausea).
6. Contraindications and Drug Interactions Anafranil
The list of contraindications is critical for safety. Absolute contraindications include known hypersensitivity to clomipramine or other TCAs, concomitant use with monoamine oxidase inhibitors (MAOIs) due to risk of serotonin syndrome, and during the acute recovery phase after a myocardial infarction. You also have to be very cautious with its use in patients with a history of seizures, as it lowers the seizure threshold, or with narrow-angle glaucoma or significant urinary retention due to its potent anticholinergic properties.
Drug interactions are a major concern. As mentioned, combining it with MAOIs is dangerous. It can potentiate the effects of CNS depressants like alcohol, barbiturates, and benzodiazepines. It’s highly protein-bound and can displace other drugs like warfarin, potentially increasing anticoagulant effect. The most dangerous interaction is with other serotonergic agents (e.g., other SSRIs, tramadol, linezolid, triptans) due to the risk of serotonin syndrome—a potentially fatal condition characterized by agitation, confusion, tachycardia, hyperthermia, and rigidity. Is it safe during pregnancy? It’s Category C, meaning risks cannot be ruled out, so it should only be used if the potential benefit justifies the potential risk to the fetus.
7. Clinical Studies and Evidence Base Anafranil
The clinical studies on Anafranil are some of the most robust in psychiatry for OCD. The landmark 1991 multi-center, double-blind, placebo-controlled study published in Archives of General Psychiatry by the Clomipramine Collaborative Study Group demonstrated a mean 38-44% reduction in Y-BOCS scores for clomipramine versus 3-5% for placebo. That’s a massive effect size. Subsequent meta-analyses have consistently placed clomipramine at the top for efficacy, even when compared directly to SSRIs like fluvoxamine and sertraline. A 2019 network meta-analysis in JAMA Psychiatry reaffirmed that clomipramine had the highest odds of response for OCD compared to all other pharmacotherapies. The scientific evidence for its use in panic disorder is also strong, with studies showing it to be as effective as alprazolam and more effective than imipramine in reducing panic attack frequency. The data is old, but it’s solid, which is why it remains in treatment guidelines worldwide.
8. Comparing Anafranil with Similar Products and Choosing a Quality Product
When comparing Anafranil with similar products, you’re mainly comparing it to SSRIs (fluoxetine, sertraline, fluvoxamine, paroxetine, citalopram). The question of “which is better” is nuanced. For pure efficacy in OCD, Anafranil often wins. But the SSRIs have a much more favorable side effect profile—less anticholinergic effects, less sedation, less orthostatic hypotension, and a much safer profile in overdose. So, the choice often comes down to a risk-benefit calculation: use an SSRI first for better tolerability, and reserve Anafranil for more severe or treatment-resistant cases. There’s no “quality” issue with the brand Anafranil versus generic clomipramine; they are bioequivalent. The key is ensuring it’s prescribed by a knowledgeable clinician who can manage its complexities.
9. Frequently Asked Questions (FAQ) about Anafranil
What is the recommended course of Anafranil to achieve results?
For OCD, a therapeutic trial should be at least 10-12 weeks at an adequate dose (usually 150-250 mg/day for adults) before determining it’s ineffective. This is a long-term maintenance treatment, not a short-course therapy.
Can Anafranil be combined with SSRIs?
Generally, no. This combination dramatically increases the risk of serotonin syndrome and other pharmacokinetic interactions. This should only be done in rare, refractory cases by specialists with very close monitoring.
How long do side effects like dry mouth and drowsiness last?
The initial sedative and anticholinergic side effects are often worst in the first 1-2 weeks and tend to diminish somewhat as the body adapts. However, for many patients, some degree of dry mouth or mild sedation can persist long-term.
Is weight gain a common side effect?
Yes, significant weight gain is a very common and problematic long-term side effect of Anafranil, more so than with most SSRIs. It’s important to counsel patients on diet and exercise from the outset.
10. Conclusion: Validity of Anafranil Use in Clinical Practice
In conclusion, the validity of Anafranil use in clinical practice remains high for specific, severe conditions, particularly treatment-refractory OCD. Its risk-benefit profile is characterized by superior efficacy balanced against a significant burden of side effects and safety concerns. It is not a first-line agent for most situations today, but it is an essential tool in the psychiatric armamentarium. For the right patient, under careful supervision, it can be a life-changing intervention where other treatments have failed. Its role is secure as a powerful, evidence-based option for severe obsessive-compulsive disorder.
I’ll never forget Sarah, a 42-year-old librarian. She’d been through three SSRIs and CBT for her horrific contamination OCD. Her hands were cracked and bleeding from washing, she couldn’t touch a doorknob. We were at an impasse. I brought up clomipramine in our team meeting, and the pushback was immediate. My senior colleague, Dr. Evans, was adamant. “The side effect profile is a nightmare, John. The anticholinergics, the weight gain, the cardiac stuff. It’s a step back.” I argued that we’d exhausted the “friendly” options. We had a real disagreement; he thought I was being reckless. We settled on a compromise: a painfully slow titration, starting at just 10mg, with weekly ECG monitoring because she was otherwise healthy. The first month was rough. Sarah called me twice a week, miserable with dry mouth and so drowsy she could barely work. I almost pulled the plug, honestly. I thought Evans was right. But around week 7, at 150mg, she left me a voicemail. She’d taken a book from the returns cart without gloves. For anyone else, nothing. For her, a mountain. That was the turning point. A year later, she’s maintained on 175mg. She gained 15 pounds, which we manage, and she still needs a mouthful of water to get through a conversation, but she’s back to work full-time, she can hug her nieces. We saw her for a follow-up last month, and she said, “I feel like I got my life back from a monster.” That’s the thing with this drug. It’s messy, it’s difficult, it’s not elegant. But for some people, it’s the only thing that fights the monster. Evans and I had coffee last week, and he admitted, “You were stubborn, but you were right for her.” That’s the hard-earned insight—the textbook doesn’t always capture the individual battle, and sometimes the older, dirtier tool is the only one that does the job.