CurrentmhnPolicy CP.PMN.197

Clomipramine (Anafranil)

Defines medical necessity and prior authorization criteria for clomipramine (Anafranil) for Medicaid members, including initial and continued therapy criteria for OCD and autistic disorder and related dosing limits.

Policy Summary

Payermhn

PolicyClomipramine (Anafranil)

Policy CodePolicy CP.PMN.197

Change TypeNo material change

Effective Date06.01.19

Next Review Date

Key ActionSubmit documentation (office chart notes, lab results, or other clinical information) showing the member has met all approval criteria for prior authorization.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2SSRI failures required for OCD prior authorization

250 mg/dayMaximum adult dose stated

12 monthsApproval duration for initial and continued therapy

25/50/75 mgProduct availability

Coverage Criteria for Clomipramine (Anafranil)

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Initial Approval - OCD: Diagnosis of obsessive-compulsive disorder (OCD); failure of 2 selective serotonin reuptake inhibitors (SSRIs), each used for at least 4 weeks at up to maximally indicated doses unless clinically significant adverse effects are experienced or all are contraindicated; member must use generic clomipramine unless contraindicated or clinically significant adverse effects are experienced; dose does not exceed 250 mg per day.

Initial Approval - Autistic Disorder (off-label): Diagnosis of autistic disorder; failure of a 4-week trial of fluoxetine at up to maximally indicated doses unless contraindicated or clinically significant adverse effects are experienced; member must use generic clomipramine unless contraindicated or clinically significant adverse effects are experienced; dose does not exceed 250 mg per day.

Initial Approval - Other diagnoses/indications: Either: (1) the drug has undergone a label change within the last 6 months (new indication, age expansion, new dosing) not yet reflected in this policy — refer to the applicable formulary/no-coverage or non-formulary policy (CP.PMN.255 or CP.PMN.16 for Medicaid); or (2) the requested use is not specifically listed under section III and criterion 1 does not apply — refer to the off-label use policy (CP.PMN.53 for Medicaid).

Continuation Therapy

Covered when ALL of the following are met for continuation:

Continued Therapy - all indications: Member is currently receiving medication via the Centene benefit, or documentation supports member has been receiving clomipramine for at least 30 days; member is responding positively to therapy; member must use generic clomipramine unless contraindicated or clinically significant adverse effects are experienced; if request is for a dose increase, the new dose does not exceed 250 mg per day.

Continued Therapy - Other diagnoses/indications: Either: (1) the drug has undergone a label change within the last 6 months not yet reflected in this policy — refer to CP.PMN.255 or CP.PMN.16 as applicable; or (2) the requested use is not specifically listed under section III and criterion 1 does not apply — refer to the off-label use policy CP.PMN.53 for Medicaid.

Non–FDA approved indications that are not specifically addressed in this policy are not authorized unless the request includes sufficient clinical documentation demonstrating efficacy and safety consistent with the Health Plan off‑label use policy CP.PMN.53 or other applicable evidence of coverage documents.

This clinical policy is intended as a guide to medical necessity and coverage decision‑making and does not constitute medical advice, medical treatment, or medical care. It is not a contract and does not guarantee payment or prescribe treatment; providers should exercise professional medical judgment and follow applicable coverage documents and regulatory requirements.

Within the document segment referenced for these criteria there are no explicit conditions identified as “not medically necessary” (NMN); determinations about NMN status should follow the explicit exclusions and off‑label documentation requirements described elsewhere in this policy and related Health Plan documents.

Policy governance and provider responsibilities

Policy-level statements and administrative coverage guidance

Administrative governance: Coverage decisions and administration of benefits are subject to the terms, conditions, exclusions, and limitations of the coverage documents and to state and federal requirements and applicable Health Plan-level administrative policies and procedures; for Medicaid members, state Medicaid provisions take precedence when conflicts exist.

Policy updates and reviews: Template and continued therapy revisions applied in 2022 and 2024 to allow continuity of care for all indications; annual reviews documented (2021–2025) with the 2Q 2025 review noting no significant changes.

Provider responsibility: Providers must exercise professional medical judgment; this clinical policy is a guide to medical necessity, does not constitute medical advice or dictate treatment, and does not guarantee payment. Providers are responsible for the medical advice and treatment of members.

Provider Requirements and Prior Authorization Actions

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must meet the initial or continued therapy criteria outlined in this policy to be approved. Providers must follow the Health Plan prior authorization processes and use the Health Plan’s PA submission system.

Approval durations: Initial and continued approvals are 12 months when criteria met
Dose limit: ≤ 250 mg/day for clomipramine

Step Therapy

Step Therapy for OCD

For Obsessive-Compulsive Disorder (OCD) requests, step therapy requires failure of two different SSRIs prior to approval. Each SSRI trial must be for ≥ 4 weeks at up to maximally indicated doses unless clinically significant adverse effects occur or the agent is contraindicated. Providers should document SSRI names, doses, start/stop dates, and reasons for discontinuation.

Required SSRI failures: 2 agents, each ≥ 4 weeks at maximally indicated doses
Therapeutic alternatives listed in Appendix B may be considered (e.g., fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram)

Documentation Required

Required Documentation and Denial Triggers

Documentation must be submitted to support that the member meets all approval criteria. Acceptable documentation includes office chart notes, medication history (including prior SSRI trials and dosing), laboratory results, and any records demonstrating current use and clinical response when requesting continued therapy. Requests lacking sufficient documentation or for indications not addressed in this policy may be denied unless adequate off‑label justification is provided per CP.PMN.53.

For continued therapy: evidence member has received medication for at least 30 days and is responding to therapy
For Anafranil requests: use of generic clomipramine must be documented or a contraindication/adverse effect noted
Denial triggers: missing documentation, unaddressed indications without off‑label support

Note

Professional Judgment and Coverage Considerations

Providers are expected to exercise professional medical judgment in treating members. This policy is guidance only and does not replace individualized clinical decision-making. Coverage decisions remain subject to the terms, conditions, exclusions, and limitations of the member’s benefit documents.

Providers are solely responsible for medical advice and treatment decisions
This policy does not constitute medical advice or an authorization guarantee

Coding, Dosing Limits, and Product Availability

Codes referencedmixed

none listed

No specific CPT/HCPCS/ICD-10/NDC codes are listed in this policy text.

inv-09: Maximum daily dose (adult) — 250 mg/day

Maximum adult daily dose250 mg/day

Initial adult titrationStart 25 mg PO QD; increase as tolerated to 100 mg during first 2 weeks

Adult dosing for autistic disorderInitially 25 mg PO QD; may increase to 75–100 mg as needed

Formulations notedCapsules available (25, 50, 75 mg) per product availability references

inv-10: Pediatric maximum dose — 3 mg/kg/day or specified mg/day limits per indication

Pediatric weight-based maximum3 mg/kg/day (or 100–200 mg/day as specified per indication)

Pediatric initial titration (all indications)Start 25 mg PO QD; increase as tolerated to 3 mg/kg or 100 mg, whichever is smaller, during first 2 weeks

Pediatric maximum for autistic disorder3 mg/kg/day or 200 mg/day, whichever is smaller

Pediatric note for OCD vs autismOCD pediatric max: 3 mg/kg/day or 200 mg/day; autistic disorder pediatric max: 3 mg/kg/day or 200 mg/day per dosing table

Pharmacotherapy

Pharmacotherapy: Clomipramine is a tricyclic serotonin reuptake inhibitor used pharmacologically to treat obsessive-compulsive disorder and, off-label, to target repetitive behaviors in autism spectrum disorder; SSRIs are generally preferred prior to clomipramine due to a more favorable safety profile, and clomipramine and fluoxetine have randomized controlled trial evidence for reducing repetitive behaviors in autism.

Definitions

inv-20: Clomipramine (Anafranil) — definition and indication

Drug class and trade nameClomipramine (Anafranil) — a tricyclic antidepressant

FDA-approved indicationIndicated for treatment of obsessions and compulsions in patients with obsessive-compulsive disorder (OCD)

Clinical roleUsed for OCD and for targeting repetitive behaviors in autism spectrum disorder (off-label) per guideline evidence

inv-21: SSRI — definition and role as first-line therapy for OCD

DefinitionSSRI = selective serotonin reuptake inhibitor

Role in OCD therapySSRIs are first-line therapies for OCD and are generally preferred prior to clomipramine due to a better safety profile

Therapeutic alternativesPreferred SSRIs listed in Appendix B include fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, escitalopram with specific dosing limits

inv-22: Health Plan — definition of the Health Plan adopting this policy

Health Plan definitionHealth Plan means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan's affiliates

Purpose of policyProvides a guide to medical necessity to assist in making coverage decisions and administering benefits; not a contract or guarantee of payment

Governance noteCoverage decisions subject to terms, conditions, exclusions, limitations of coverage documents and applicable state/federal requirements

Background

Clomipramine (Anafranil) is a tricyclic antidepressant indicated for treatment of obsessions and compulsions in obsessive‑compulsive disorder (OCD). Selective serotonin reuptake inhibitors (SSRIs) are generally preferred prior to clomipramine because of a more favorable safety and tolerability profile; clomipramine is reserved for cases where SSRIs are ineffective, not tolerated, or contraindicated and has evidence supporting efficacy, including use off‑label for repetitive behaviors in autistic disorder.