Compounded Ketamine Formulations: Lozenges, Troches, and Creams

What Are Compounded Ketamine Formulations?

Compounded ketamine formulations are custom-prepared versions of ketamine made by compounding pharmacies according to a prescriber's specifications. Unlike commercially manufactured pharmaceutical products, which are mass-produced in standardized forms, compounded formulations are individually prepared to meet specific patient needs — including unique dosages, delivery forms, and ingredient combinations not available in commercial products.

The growth of ketamine therapy for psychiatric and pain conditions has driven significant demand for compounded formulations. Because the only commercially available forms of ketamine are generic injectable solutions (approved for anesthesia) and Spravato nasal spray (approved for depression), prescribers who wish to offer oral, sublingual, or topical ketamine must rely on compounding pharmacies. This has made compounded ketamine one of the most frequently prepared psychiatric compounds in the United States.

Types of Compounded Formulations

Sublingual Troches and Lozenges

Sublingual troches (also spelled "trochees") and lozenges are the most commonly prescribed compounded ketamine formulations for psychiatric use. These are solid dosage forms designed to be held under the tongue or between the cheek and gum, allowing ketamine to be absorbed through the oral mucosa directly into the bloodstream.

Key characteristics:

• Dosing range: Typically 50 to 300 mg per troche, though higher doses are sometimes prescribed
• Bioavailability: Approximately 25-35% when administered sublingually, though this varies based on the duration of mucosal contact, whether saliva is swallowed or expectorated, and individual mucosal absorption
• Onset: Effects typically begin within 10 to 20 minutes
• Duration: Psychoactive effects generally last 45 to 90 minutes
• Flavoring: Compounding pharmacies typically add flavoring agents to improve palatability, as ketamine has a bitter taste

Troches and lozenges are frequently prescribed for at-home use under clinical guidance. Patients are typically instructed to hold the troche under the tongue for 10 to 15 minutes to maximize mucosal absorption, then either swallow or spit out the remaining saliva. The portion of the dose that is swallowed undergoes significant first-pass hepatic metabolism, reducing its effective bioavailability.

Rapid Dissolve Tablets (RDTs)

Rapid dissolve tablets are a newer compounded formulation designed for sublingual administration. They dissolve more quickly than traditional troches, potentially improving mucosal absorption and patient experience. RDTs may achieve slightly higher bioavailability than standard troches due to enhanced dissolution and mucosal contact, though comparative pharmacokinetic data are limited.

Nasal Sprays

Compounded intranasal ketamine sprays deliver ketamine through the nasal mucosa. This route avoids first-pass metabolism and offers higher bioavailability (approximately 25-50%) than oral administration, with a faster onset of action (5-15 minutes).

Compounded nasal sprays differ from Spravato (esketamine nasal spray) in several important ways:

• They typically contain racemic ketamine rather than esketamine alone
• They are not FDA-approved for any specific indication
• They are not subject to the REMS program requirements that govern Spravato
• Dosing and concentration vary by prescription and pharmacy
• They are generally less expensive than Spravato

Topical Creams and Gels

Topical ketamine formulations — creams, gels, and ointments — are primarily prescribed for pain management rather than psychiatric indications. They are applied directly to the skin over painful areas, with the goal of delivering ketamine to peripheral nerves and local tissue.

Common topical applications include:

• Neuropathic pain conditions (complex regional pain syndrome, diabetic neuropathy, post-herpetic neuralgia)
• Musculoskeletal pain
• Post-surgical pain
• Chronic wound pain

Topical ketamine concentrations typically range from 2% to 10%, and may be compounded in combination with other analgesic agents such as gabapentin, baclofen, diclofenac, or lidocaine. Systemic absorption from topical application is minimal, meaning that these formulations do not produce psychoactive or dissociative effects.

Oral Solutions and Suspensions

Some compounding pharmacies prepare ketamine in liquid oral form — solutions or suspensions that are swallowed. Oral ketamine has the lowest bioavailability (approximately 17-24%) of any commonly used route, as it undergoes extensive first-pass metabolism in the liver. However, the primary metabolite — norketamine — has its own pharmacological activity and may contribute to the therapeutic effect.

Oral formulations are sometimes used for chronic pain management or as a longer-acting, lower-intensity maintenance option for patients who have responded to initial IV or IM ketamine treatment.

Bioavailability Comparison

Understanding the bioavailability of different formulations is essential for appropriate dosing:

These values are approximate and subject to significant individual variability. For detailed dosing guidance, see the weight-based dosing guidelines. Factors such as mucosal integrity, gastrointestinal motility, liver function, body composition, and concurrent medications all influence absorption.

Clinical Uses of Compounded Formulations

At-Home Psychiatric Treatment

The most prominent current use of compounded ketamine is for at-home psychiatric treatment. Prescribers — often psychiatrists or other mental health providers working through telehealth platforms or in-person clinics — prescribe sublingual troches or lozenges for patients to take at home, typically with clinical guidance regarding dosing, frequency, and safety protocols.

At-home protocols generally include:

• An initial evaluation (often in-person or via telehealth) to establish diagnosis and candidacy
• Prescription of a specific formulation and dose
• Instructions for a treatment sitter (a sober, responsible adult present during sessions)
• Remote monitoring through follow-up appointments
• Clear guidelines for when to contact the prescriber or seek emergency care

Chronic Pain Management

Compounded ketamine in topical, oral, and sublingual forms is widely used for chronic pain management, particularly for conditions that have not responded to conventional analgesics. The multi-modal analgesic properties of ketamine — including NMDA receptor blockade, anti-inflammatory effects, and opioid-sparing activity — make it a versatile addition to pain management regimens.

Transitional and Maintenance Therapy

For patients who have responded to initial IV or IM ketamine treatment, compounded sublingual or intranasal formulations can serve as maintenance therapy — allowing continued treatment outside of an infusion clinic. This approach can reduce cost, improve convenience, and support long-term adherence, though it involves the trade-off of lower bioavailability and less clinical oversight.

Quality and Regulatory Considerations

Compounding Pharmacy Standards

Compounding pharmacies in the United States are regulated at both the state and federal levels. Key regulatory frameworks include:

• State boards of pharmacy — Each state has its own regulations governing compounding practices, including facility standards, documentation requirements, and practitioner oversight
• USP standards — The United States Pharmacopeia publishes standards for compounding, including USP <795> for non-sterile compounding and USP <797> for sterile compounding
• FDA oversight — Under the Drug Quality and Security Act of 2013, compounding pharmacies that prepare large quantities of medications without individual prescriptions (outsourcing facilities, or 503B pharmacies) are subject to FDA registration and inspection

Quality Variability

A significant concern with compounded formulations is quality variability. Studies have shown that some compounded medications deviate from the labeled potency, meaning patients may receive more or less ketamine than prescribed. Selecting a reputable compounding pharmacy that adheres to current USP standards and undergoes regular third-party testing is an important consideration for both prescribers and patients.

Legal Considerations

The legal landscape for compounded ketamine is complex and evolving. While prescribers can legally prescribe compounded ketamine off-label, the regulatory environment surrounding at-home prescribing has been subject to increased scrutiny. Federal and state agencies have expressed concern about the safety of unsupervised ketamine use, particularly when prescribed via telehealth without an in-person evaluation. Several states have enacted or proposed regulations specifically addressing at-home ketamine prescribing practices.

Choosing Between Formulations

The selection of a compounded formulation depends on multiple factors:

• Clinical indication — Psychiatric conditions typically call for sublingual or intranasal formulations, while pain conditions may benefit from topical or oral preparations
• Desired bioavailability — Higher-bioavailability routes provide more predictable dosing but may produce more intense psychoactive effects
• Clinical setting — At-home use necessitates formulations that can be safely self-administered
• Patient preference — Some patients prefer the convenience of troches, while others find intranasal sprays more acceptable
• Cost — Compounded formulations are generally less expensive than Spravato but more expensive than generic injectable ketamine used for IV infusion

Note: This article is for educational purposes only and does not constitute medical advice. Compounded ketamine should only be used under the supervision of a qualified healthcare provider, and patients should ensure their compounding pharmacy meets appropriate quality standards. For a comparison with FDA-approved options, see our guide to racemic ketamine vs esketamine.

References

• FDA: Drug Information — U.S. Food and Drug Administration resource on drug compounding regulations and safety
• StatPearls: Ketamine — Clinical reference on ketamine pharmacology and formulation considerations
• Ketamine Pharmacology: An Update — NIH review of ketamine bioavailability across different administration routes
• MedlinePlus: Ketamine Injection — National Library of Medicine drug information on ketamine's clinical applications