Section - Expert Consultations

02. Antipsychotic Blood Levels, Part 2: Active Moieties, LAIs, and Special Populations

Published on June 26, 2026 Certification expiration date: June 26, 2029 DOI: 10.64239/PI-EC10102

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Key Points

• For risperidone TDM, measure both risperidone and paliperidone. Paliperidone (9-hydroxy risperidone) represents about five-sixths of the active moiety.
• Aripiprazole trough level is approximately 11 times the oral dose. Use this ratio to confirm whether the prescribed dose matches your plasma level target.
• A subtherapeutic plasma level, in the absence of other explanations, signals non-adherence. When non-adherence is confirmed, strongly consider switching to a long-acting injectable.

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Managing High Plasma Levels

Flavio Guzman, M.D.: An olanzapine level comes back about 110 ng/mL above the alert threshold, but the patient has no symptoms. How do you approach that?

John Kane, M.D.: Examining the patient is particularly important in this situation.

If that dose was arrived at as the dose to which the patient is responding and they are not experiencing significant adverse effects, then a plasma level higher than expected is less concerning.

It really depends on the clinical examination and understanding the entire clinical picture.

Active Moieties — Risperidone and Aripiprazole

Flavio Guzman, M.D.: Risperidone and aripiprazole require measuring the active moiety. Why does that matter clinically, and how often is it missed in practice?

John Kane, M.D.: With risperidone, the active metabolite is 9-hydroxy risperidone — also known as paliperidone — which has been marketed as a separate drug in both an oral form and a

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Table of Contents

Learning Objectives

After completing this activity, the learner will be able to:

Apply correct therapeutic drug monitoring sampling principles—including 12-hour post-dose timing, steady-state requirements, and repeat testing—to obtain interpretable antipsychotic plasma levels.
Assess subtherapeutic or undetectable levels to distinguish non-adherence and pseudo-resistance from true treatment resistance, and integrate this finding into decisions about clozapine and long-acting injectable therapy.
Explain drug-specific TDM considerations across antipsychotics—including the clozapine algorithm and smoking effects, active-moiety measurement for risperidone and aripiprazole, the haloperidol therapeutic threshold, and monitoring in pregnancy.

Activity

Original Release Date: June 26, 2026
Expiration Date: June 26, 2029
Expert: John M. Kane, M.D.
Medical Editor: Flavio Guzmán, M.D.

Relevant Financial Disclosures:

John M. Kane, M.D. declares the following interest:
– JMK has received consultant or speaker fees from AbbVie, Alkermes, Boehringer-Ingelheim, Bristol Meyers-Squibb, Cerevel, Click Therapeutics, Dainippon Sumitomo, , HealthRhythms, HLS Therapeutics, Intra-Cellular, Janssen, Johnson & Johnson, LB Pharmaceuticals, Lundbeck, Mapi, Maplight, Merck, Minerva, Neurocrine, Newron, Novartis, NW PharmaTech, Otsuka, Saladax, Sunovion, Terran, and Teva; has grant support from Bristol Meyers-Squibb, Janssen, Lundbeck, Otsuka, Sunovion; receives royalties from UpToDate; and holds stock or stock options for Health Rhythms, LB Pharmaceuticals, Medincell, North Shore Therapeutics, NW Pharmatech, Reviva, Saladax, Terran, and Vanguard Research Group.: JMK has received consultant or speaker fees from AbbVie, Alkermes, Boehringer-Ingelheim, Bristol Meyers-Squibb, Cerevel, Click Therapeutics, Dainippon Sumitomo, , HealthRhythms, HLS Therapeutics, Intra-Cellular, Janssen, Johnson & Johnson, LB Pharmaceuticals, Lundbeck, Mapi, Maplight, Merck, Minerva, Neurocrine, Newron, Novartis, NW PharmaTech, Otsuka, Saladax, Sunovion, Terran, and Teva; has grant support from Bristol Meyers-Squibb, Janssen, Lundbeck, Otsuka, Sunovion; receives royalties from UpToDate; and holds stock or stock options for Health Rhythms, LB Pharmaceuticals, Medincell, North Shore Therapeutics, NW Pharmatech, Reviva, Saladax, Terran, and Vanguard Research Group.

All the relevant financial relationships listed above have been mitigated by Medical Academy and the Psychopharmacology Institute.

None of the other faculty, planners, and reviewers for this educational activity has relevant financial relationships to disclose during the last 24 months with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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Artificial Intelligence (AI) Use Disclosure

Artificial intelligence (AI) tools may have been used in limited stages of developing this activity (e.g., drafting or language refinement). The specific tool, version, and date of use are documented internally. AI is used solely as an editorial support mechanism and does not replace human expertise. AI does not determine clinical recommendations. All content is reviewed, verified, and approved by the listed experts and medical editors, and reflects independent human clinical judgment consistent with ACCME Standards for Integrity and Independence in Accredited Continuing Education.