clomipramine

Adjunctive therapy

Brands: Anafranil

Last reviewed 2025-10-05

Reviewed by PsychMed Editorial Team.

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Quick answers

What is clomipramine?
Clomipramine (brand Anafranil) is a serotonin-preferring tricyclic antidepressant (TCA) approved in 1990 for obsessive-compulsive disorder (OCD); it remains a key option when maximized SSRI therapy is ineffective or poorly tolerated.
What is Anafranil?
Anafranil is a brand name for clomipramine.
What is Anafranil (clomipramine) used for?
Label indications include: Obsessive-compulsive disorder; depression when other treatments fail.
What drug class is Anafranil (clomipramine)?
Tricyclic antidepressant; potent serotonin reuptake inhibition.
What strengths does Anafranil (clomipramine) come in?
Capsules: 25 mg, 50 mg, 75 mg (Anafranil; typically divided 2–3 times daily).

Snapshot

Class: Adjunctive therapy
Common US brands: Anafranil
Therapeutic drug monitoring recommended; reference range 150–300 ng/mL.
Last reviewed: 2025-10-05

Label indications

Obsessive-compulsive disorder; depression when other treatments fail.

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Clinical Highlights

Clomipramine (brand Anafranil) is a serotonin-preferring tricyclic antidepressant (TCA) approved in 1990 for obsessive-compulsive disorder (OCD); it remains a key option when maximized SSRI therapy is ineffective or poorly tolerated. Desmethylclomipramine, the active metabolite, adds norepinephrine reuptake inhibition and broadens efficacy in treatment-resistant depression but increases anticholinergic and cardiovascular burden, making therapeutic drug monitoring critical.

Despite strong efficacy in OCD and select treatment-resistant depression cases, clomipramine use is constrained by anticholinergic burden, seizure risk at higher plasma concentrations, and the need for ECG and therapeutic drug monitoring. Many clinicians reserve it for specialty care or after SSRI/SNRI trials.
The compare view, clomipramine evidence feed, and clomipramine print page can support counseling and shared decision-making; the bipolar disorder hub summarizes antidepressant switch and mania-risk considerations.
Obsessive-compulsive disorder (FDA 1990)
Generic: Generic clomipramine is supplied by multiple manufacturers (e.g., Teva, Mylan/Viatris, Sun).
Generic: Brand Anafranil remains available; liquid preparations require compounding.

Dosing & Formulations

Capsules: 25 mg, 50 mg, 75 mg (Anafranil; typically divided 2–3 times daily). Generic capsules/tablets: 25 mg, 50 mg, 75 mg; largest portion usually given at bedtime to limit daytime sedation.

No long-acting, liquid, or parenteral formulations are marketed in the United States.
Typical initiation is 25 mg at bedtime; increase by 25 mg every 3–4 days as tolerated.
Typical OCD target 100–250 mg/day divided two or three times; outpatient maximum 250 mg/day (300 mg/day inpatient).
The largest portion is often given at bedtime to reduce daytime sedation and orthostasis.

Monitoring & Risks

Boxed warning: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults—monitor closely during initiation and dose changes. Sedation: Up to 40%; bedtime dosing and gradual titration lessen daytime somnolence.

Anticholinergic effects: Dry mouth, constipation, blurred vision, and urinary hesitancy are frequent and dose-related.
Orthostasis and tachycardia: Alpha-1 blockade causes dizziness or palpitations, particularly during titration.
Weight gain: Average 1–2 kg over 12 weeks; diet and activity strategies may help.
Sexual dysfunction: Delayed orgasm or anorgasmia in 30–40% of patients.

Drug Interactions

Contraindicated with MAOIs or within 14 days of discontinuation (serotonin syndrome, hypertensive crisis). Strong CYP2D6 or CYP3A4 inhibitors (fluoxetine, fluvoxamine, paroxetine, ritonavir, ketoconazole) raise levels—reduce dose and monitor concentrations closely.

CYP inducers (carbamazepine, rifampin, phenytoin, St. John’s wort, cigarette smoking) lower levels—dose adjustments may be required.
Additive serotonergic agents (SSRIs, SNRIs, triptans, linezolid) increase serotonin syndrome risk—monitor for clonus, hyperreflexia, and autonomic instability.
Additive QTc prolongation with class Ia/III antiarrhythmics, macrolides, certain antipsychotics, and other TCAs.
Combined anticholinergic burden with antihistamines, bladder antimuscarinics, or low-potency antipsychotics heightens constipation and cognitive adverse effects.

Practice Notes

Baseline ECG and electrolytes are typically obtained before titration, with repeats after major dose increases or if symptoms emerge. Therapeutic drug monitoring (goal 150–300 ng/mL combined) helps balance efficacy with seizure and arrhythmia risk; draw trough after 3–4 weeks on a stable dose.

Bowel regimens are often needed; hydration and fiber intake can help prevent ileus and constipation.
Because overdose is highly lethal, limited quantities are often dispensed in patients at acute suicide risk, with counseling on secure storage.
Bipolar disorder screening is important before initiation, and emergent hypomania or mania is monitored during treatment.

References

Anafranil (clomipramine) prescribing information — DailyMed (2024)
APA Clinical Practice Guideline FOR THE Treatment OF Patients With Obsessive Compulsive Disorder — American Psychiatric Association (2020)
Evidence Based Pharmacotherapy FOR Obsessive Compulsive Disorder — International Clinical Psychopharmacology (2020)
Sertraline versus clomipramine in pediatric OCD — American Journal of Psychiatry (1998)
Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology — Pharmacopsychiatry (2018)