Highlights from ASCP 2026 – Clinical Pearls in Psychopharmacology

In a nutshell

• Highlights from the 2026 ASCP Annual Meeting in Miami: clinical pearls from interviews and posters.
• The through-line is individualized, rational prescribing.

The high-yield pearls

• Polypharmacy:
  • Do the “pharmacoarcheology” before changing a complex regimen
  • Reconstruct why each drug was started and whether that reason still holds, and judge the logic, not the length of the list (Dr. Goldberg).
• Antipsychotics:
  • Don’t let benign ethnic neutropenia rule out clozapine, and dose to the patient’s metabolism (Drs. Alam & Brown).
  • Reassure that first-trimester atypical-antipsychotic exposure carries a low, near-background malformation risk (Dr. Cohen).
• Montelukast: A non-psychiatric drug with psychiatric effects that may vary by developmental stage (Drs. Saleem & Khan).
  • Nightmares and sleep disturbance in children.
  • Depression, anxiety, and suicidal ideation in adolescents and adults.

Two further ASCP 2026 interviews — stimulant deprescribing in adult ADHD (Dr. Goodman) and treatment-resistant depression (Dr. Thase) — are coming soon as PI expert consultations.

Rational polypharmacy: reconstruct the regimen before you change it

Presentation context

• The question:
  • When a patient arrives on multiple psychotropics, how do you decide whether the regimen is rational, and how do you safely deprescribe?
• Joseph F. Goldberg, M.D., a member of the ASCP polypharmacotherapy/deprescribing task force, spoke in the workshop on rational versus irrational psychotropic combinations.

What we learned

• Reconstruct the regimen before you judge it
  • A long medication list is not automatically a problem; what matters is the logic behind it, not the number of medications.
  • Extensive polypharmacy in a still-symptomatic patient often functions as a proxy for treatment resistance, not carelessness.
  • Pharmacoarcheology means “going back in time and looking at the bones”
    • Trace the sequence of additions, what each drug was targeting, the response to each, and whether the original rationale still applies.
• Give the regimen a periodic “performance review,” drug by drug
  • Does each agent still earn its place, a clear purpose and measurable benefit, or should it be replaced?
  • Test the regimen for coherence: are components complementary or contradictory, redundant or non-redundant, each with an adequate trial behind it?
• Red flags that a regimen needs simplifying:
  • Redundant mechanisms
    • E.g., two SSRIs or an SSRI + SNRI; additive burden from stacked anticholinergics or alpha-1 antagonists.
  • Unmanaged drug–drug interactions
    • E.g., adding lamotrigine to valproate without halving the dose.
  • Agents not evidence-based for the indication
    • E.g., topiramate or gabapentin used as “mood stabilizers” in bipolar disorder.
  • “Pharmacological hoarding”
    • If no one can say why a drug is there.
• Distinguish elegant augmentation from accumulation
  • Rational combinations are non-redundant and mechanistically complementary, with an identifiable target.
    • E.g., a serotonergic agent plus a pro-dopaminergic agent for depression with prominent anxiety.
  • Done well, you can “see what the prescriber had in mind”, but elegance is only a hypothesis: name the target symptom, give it an adequate trial, and keep the combination only if it measurably works.
• Structure deprescribing hierarchically:
  • Make one change at a time where possible.
  • Triage by harm
    • Target harmful agents first (sedation, anticholinergic/antihistaminic burden, orthostasis).
    • Leave “benign but probably-not-helping” agents for later; they aren’t causing harm, and removing them yields less diagnostic information.
  • Treat each removal as an experiment whose result informs the next step.
    • E.g., before adding a stimulant for presumed ADHD, first remove the sedating anticholinergic that may be causing the cognitive dulling, then reassess.
  • Leave synergistic agents in place for now, and revisit them once the higher-priority changes are done.
    • E.g., bupropion used as a CYP2D6 inhibitor to raise a co-prescribed substrate’s level.
• Reassess the diagnosis in complex patients, and do so slowly.
  • “Speed is not the goal.”
  • Get collateral and prior records; treat it as a forensic reconstruction rather than reflexively pruning the list.
• Frame time as an investment, not a luxury.
  • Front-loading a comprehensive evaluation makes downstream 15-minute visits feel purposeful rather than random.
  • The task force is developing a semi-structured deprescribing interview and exploring a dedicated CPT code (consensus-statement work in progress).
  • The aspiration, à la Donald Klein: “If all goes well, I’ll see you a couple of times a year, like your dentist”
• Practical takeaways:
  • Take the time to know why every drug in a regimen is present; if you can’t say why, that’s where to start.
  • Hypothesize that each medication has a purpose, then judge whether it is still aligned to that purpose.

Antipsychotic prescribing: metabolism and reproductive safety

Ethnopsychopharmacology: Personalizing antipsychotic choice and dose

Presentation context

• The question:
  • Do race and ethnicity shape antipsychotic utilization, response, and safety — and what should clinicians do differently?
• The data:
  • Misbah Alam, M.D. and Jasmyn Brown (The Valley Health System) — Poster T86, “A systematic literature review on anti-psychotic utilization in minority populations and key clinical considerations” ^[1]

What we learned

• Antipsychotic prescribing is not one-size-fits-all
  • Attending to ethnicity-linked pharmacokinetics and pharmacodynamics is part of precision psychiatry.
• Disparities run in both directions: over- and under-use, depending on agent and context.
  • Overprescribing: first-generation (FGA) long-acting injectables, especially in Black patients (where more literature was available) ^[2]
  • Underprescribing: clozapine, especially in Black and Hispanic patients ^[3]
• Benign ethnic neutropenia (BEN) and clozapine access
  • Benign ethnic neutropenia (BEN) is a constitutionally lower baseline neutrophil count tied to ancestral alleles, commonly of African or Middle-Eastern descent.
    • The Duffy-null / ACKR1 phenotype.
    • BEN does not lower immunity or raise infection risk ^[4–6]
  • Clinical pearls:
    • Compare any drop to the patient’s own baseline, not the population threshold, and apply BEN-adjusted ANC thresholds.
    • Don’t withhold or stop a gold-standard drug for a constitutionally low ANC (in some countries clozapine is used first-line and routinely) ^[7]

BEN-adjusted ANC monitoring thresholds

Step	General population	Benign ethnic neutropenia (BEN)
Minimum baseline ANC to start clozapine	≥ 1500	≥ 1000
Normal range; continue, routine monitoring	≥ 1500	≥ 1000
Reduced but continue clozapine; monitor ANC 3×/week until recovery	1000–1499 (mild neutropenia)	500–999 (BEN neutropenia)
Interrupt treatment and work up	500–999 (moderate neutropenia)	— (no interrupt tier)
Stop for suspected clozapine-induced neutropenia; don’t rechallenge unless benefit outweighs risk	< 500 (severe neutropenia)	< 500 (BEN severe neutropenia)

The FDA removed the formal Clozapine REMS on February 24, 2025; ANC monitoring at these frequencies — and the BEN-adjusted thresholds — remain recommended in the prescribing information, and severe-neutropenia warnings stay in the Boxed Warning. ^[8,9]

Prescribing patterns and treatment response by population

Population	Prescribing disparities	Response / pharmacology	Clinical action
Black / African American	– Clozapine under-prescribed – More often started on a first-gen LAI without a prior SGA trial	– Better adherence on LAI vs. oral risperidone – Fewer positive symptoms on LAI risperidone	– Offer clozapine when indicated – Trial an SGA before a first-gen LAI – LAI risperidone is a reasonable option [2,3,10–12]
Hispanic	– Clozapine under-prescribed	– Limited risperidone response in studies, likely later presentation with more severe illness, not pharmacologic non-response	– Consider a higher initial dose or a different agent – Don’t mislabel as “treatment-resistant” after under-dosed trials. [3,12]
East Asian / South Asian	– Non-white patients overall more likely to receive LAIs	– Paliperidone LAI well tolerated across dosing	– Paliperidone LAI is reasonable – Keep LAI use a shared decision, not a default [10,11,13]

Pharmacogenetics, metabolism, and dosing by population

Population	Genetic / metabolic factor	Dosing implication
Sub-Saharan African ancestry	– Faster risperidone metabolism (CYP2D6*17) – The *29 allele behaves like no-function	– Don’t infer “poor metabolizer” from genotype – Standard phenotyping can misclassify these patients [14]
East Asian	– Slower metabolizer of several SGAs – More adverse reactions to standard clozapine titration.	– Start low and titrate slowly. – Aripiprazole is tolerated at standard dose. [7,15–17]

• Practical takeaways:
  • Factor ethnic/pharmacogenetic differences in metabolism into dosing and titration.
  • Treat these ancestry findings as considerations, not deterministic rules.
  • Mind the evidence gap for South Asian, Native American, and Pacific Islander populations.

Don’t stop an effective antipsychotic just because of pregnancy

Presentation context

• The question:
  • Does first-trimester exposure to atypical antipsychotics increase the risk of major malformations?
• The data:
  • Lee S. Cohen, M.D., Adele C. Viguera, M.D., M.P.H., and colleagues (Massachusetts General Hospital, Ammon-Pinizzotto Center for Women’s Mental Health) — “Risk of Major Malformations Following Fetal Exposure to Atypical Antipsychotics — Update 2026,” from the National Pregnancy Registry for Psychiatric Medications (NPRPM): a prospective pharmacovigilance registry (4,324 enrolled as of April 2026; potential malformations adjudicated by a dysmorphologist blinded to diagnosis and exposure) ^[18]

What we learned

• First-trimester SGA exposure carries a low absolute malformation risk^[18,19]
  • About 2.45% with first-trimester exposure vs. 1.58% unexposed, both near the ~2–3% general-population background ^[20,21]
• Atypical antipsychotics do not appear to be major teratogens
  • The adjusted odds ratio was 1.425 (95% CI 0.841–2.416, not significant), consistent with the registry’s 2021 estimate (OR 1.48, 95% CI 0.63–3.52). ^[18,19]
• Clinical pearls:
  • Don’t reflexively stop an effective antipsychotic for pregnancy.
  • The malformation risk is close to the general-population background; weigh it against the real harms of untreated psychiatric illness.
  • Per-drug estimates are still maturing, and the registry is actively recruiting a larger, more diverse cohort.

Montelukast’s neuropsychiatric effects: from nightmares to depression

Presentation context

• The question:
  • Could montelukast be causing a patient’s new psychiatric symptoms, and does the picture differ by age?
• The data:
  • Interviewees Saba Saleem, D.O. and A. Rakin Khan (Valley Health System, Las Vegas) — Poster T116, “From Nightmares to Depression: Age-Stratified Neuropsychiatric Effects of Montelukast” (co-authors: Saleem, Ali Abbas, Rabail Abbas, Mujeeb Shad, Faisal Suba) ^[22]

What we learned

• Montelukast (Singulair) carries a 2020 FDA boxed warning for neuropsychiatric effects^[23,24]
  • It is among the top-20 most-prescribed US medications (~26–30 million prescriptions/year) and is FDA-approved from 6 months of age.
• Central hypothesis: the same neurochemical disruption may present differently by developmental stage ^[25]
  • In younger children: a sleep/arousal phenotype (nightmares, night terrors, insomnia, behavioral change).
  • In adolescents and adults: an affective/internalizing phenotype (depression, anxiety, irritability, suicidal ideation).
• Proposed mechanisms:^[26]
  • Leukotrienes are inflammatory signaling molecules.
    • Blocking them may perturb neuroimmune regulation of mood, sleep, and cognition in vulnerable individuals
  • A more permeable immature blood–brain barrier in young children may increase CNS exposure.
  • Corticolimbic/glutamatergic remodeling (PFC maturation, synaptic pruning) makes adolescence vulnerable to affective dysregulation, anxiety, and psychotic symptoms.
• The evidence is mixed
  • Large registry/cohort studies find no significant association ^[27,28]
  • Pharmacovigilance signals, case reports, other cohort studies, and a meta-analysis detect neuropsychiatric effects of varying magnitude ^[29–34]
  • Transient symptoms (nightmares, behavioral change) may never reach datasets because families discontinue before any psychiatric evaluation.
• Practical takeaways for clinicians:
  • Non-psychiatric drugs can cause psychiatric symptoms
    • When montelukast appears on a patient’s medication list, consider whether it might explain new sleep disturbance, mood symptoms, or suicidal ideation before treating them as a “primary” psychiatric disorder.
  • Assess causality before attributing symptoms to a primary disorder
    • Timing of onset after starting, improvement on stopping (dechallenge), recurrence on restarting (rechallenge), and competing explanations.
    • The age pattern is a clue to what to look for:
      • In children: sleep/arousal symptoms.
      • In adolescents and adults: mood and internalizing symptoms, including suicidal ideation.

References

1. Brown, J., Alam, M., Tupu, M., Tran, E., Nguyen, J., Chua, J., Alam, M., Hazari, Z., Khan, A., Saleem, S., Shad, M., & Suba, F. A Systematic Literature Review on Antipsychotic Utilization in Minority Populations and Key Clinical Considerations [Poster T86]. American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, Miami, FL.(2026). CNS Pulse. Retrieved June 9, 2026, from https://cnspulse.com/abstracts/369-t86-a-systematic-literature-review-on-anti-psychotic-utiliza/

2. Pesa, J., Liu, Z., Fu, A. Z., Campbell, A. K., & Grucza, R. (2023). Racial disparities in utilization of first-generation versus second-generation long-acting injectable antipsychotics in Medicaid beneficiaries with schizophrenia. Schizophrenia Research, 261, 170–177. https://doi.org/10.1016/j.schres.2023.09.033

3. Barry, S. et al. (2024). Racial disparities in clozapine prescription patterns among patients with schizophrenia. Psychiatric Services, 75(8), 733–739. https://doi.org/10.1176/appi.ps.20230226

4. Ahmed, S., Beyene, E., Bisrat, M., et al. (2025). Incidence and demographic patterns of neutropenia in clozapine-treated patients with schizophrenia: A 20-year retrospective cohort study. Journal of the National Medical Association. https://doi.org/10.1016/j.jnma.2025.11.010

5. Brandt, A. S., Nucifora, F. C., Zandi, P. P., & Margolis, R. L. (2024). The timing and severity of clozapine-associated neutropenia in the US: Is the risk overstated? Schizophrenia Research, 272, 104–109. https://doi.org/10.1016/j.schres.2024.08.018

6. Xie, S., Glassman, M., Vyas, G., Nwulia, E., & Kelly, D. L. (2025). Longitudinal analysis of absolute neutrophil count (ANC) variability and neutropenia incidence in African American schizophrenia patients by ACKR1 genotype. Schizophrenia Research, 285, 124–131. https://doi.org/10.1016/j.schres.2025.09.011

7. de Leon, J., Schoretsanitis, G., Smith, R. L., et al. (2022). An international adult guideline for making clozapine titration safer by using six ancestry-based personalized dosing titrations, CRP, and clozapine levels. Pharmacopsychiatry, 55(2), 73–86. https://doi.org/10.1055/a-1625-6388

8. U.S. Food and Drug Administration. (2025). Clozapine prescribing information: Absolute neutrophil count (ANC) monitoring, benign ethnic neutropenia (BEN) thresholds, and Boxed Warning for severe neutropenia. FDA prescribing information (clozapine / CLOZARIL label).

9. U.S. Food and Drug Administration. (2025). FDA removes the Risk Evaluation and Mitigation Strategy (REMS) program for the antipsychotic drug clozapine. FDA / CDER drug safety announcement.

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11. Bell Lynum, K. S., Henderson, D. C., Wright, H. J., Gogate, J. P., & Kim, E. (2021). Treatment effect with paliperidone palmitate compared with oral antipsychotics in black/african american patients with schizophrenia and a history of criminal justice system involvement: A post hoc analysis of the PRIDE study. The Journal of Clinical Psychiatry, 82(2), 20m13356. https://doi.org/10.4088/JCP.20m13356

12. Novacek, D. M., Subotnik, K. L., Ventura, J., et al. (2025). Positive symptoms and medication adherence in response to oral versus long-acting injectable risperidone in black, latino, and white first-episode psychosis patients. Schizophrenia Research, 284, 160–166. https://doi.org/10.1016/j.schres.2025.08.004

13. Chung, Y. C., Yang, Y. K., Sulaiman, A. H., Bergmans, P., & Tan, W. (2022). Asian subgroup analysis of the REMISSIO study: A long-term efficacy and safety study of paliperidone palmitate 3-month formulation in patients with stable schizophrenia. Clinical Psychopharmacology and Neuroscience, 20(3), 427–439. https://doi.org/10.9758/cpn.2022.20.3.427

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18. Cohen, L. S., Freeman, M. P., Barest, P., Grassi, E. J., Murphy, B., Cork, L., Scoggins, S. E., Dineen, H., Slaby, E., Manuelian, A., Gaccione, P., Chitayat, D., Hernández-Díaz, S., & Viguera, A. C. The national pregnancy registry for psychiatric medications: The National Pregnancy Registry for Psychiatric Medications: Risk of Major Malformations Following Fetal Exposure to Atypical Antipsychotics — Update 2026 [Poster]. American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, Miami, FL.generation antipsychotics. (2026). CNS Pulse. Retrieved June 9, 2026, from https://cnspulse.com/abstracts/384-t101-the-national-pregnancy-registry-for-psychiatric-medicat/

19. Viguera, A. C., Freeman, M. P., Kobylski, L. A., Rossa, E. T., Gaccione, P., Chitayat, D., Hernández-Díaz, S., & Cohen, L. S. (March/April 2023). Risk of Major Malformations Following First-Trimester Exposure to Olanzapine: Preliminary Data From the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications. Journal of Clinical Psychopharmacology, 43(2), 106. https://doi.org/10.1097/JCP.0000000000001665

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22. Saleem, S., Abbas, A., Abbas, R., Shad, M., & Suba, F. From Nightmares to Depression: Age-Stratified Neuropsychiatric Effects of Montelukast [Poster T116]. American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, Miami, FL.(2026). CNS Pulse. Retrieved June 9, 2026, from https://cnspulse.com/abstracts/399-t116-from-nightmares-to-depression-age-stratified-neuropsych/

23. U.S. Food and Drug Administration. (2022). FDA requires Boxed Warning about serious mental health side effects for the asthma and allergy drug montelukast (Singulair). FDA Drug Safety Communication. https://www.fda.gov/drugs/fda-requires-boxed-warning-about-serious-mental-health-side-effects-asthma-and-allergy-drug

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27. Wintzell, V., Brenner, P., Halldner, L., Rhedin, S., Gong, T., & Almqvist, C. (2025). Montelukast Use and the Risk of Neuropsychiatric Adverse Events in Children. JAMA Pediatrics, 179(4), 418–427. https://doi.org/10.1001/jamapediatrics.2024.5429

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31. Jumaili, W. A., Gburi, N. A., Chaudhary, N., Brown, K., & Jain, S. (2024). Two Cases of Montelukast-Associated Psychosis in Children. The Primary Care Companion for CNS Disorders, 26(3), 23cr03694. https://doi.org/10.4088/PCC.23cr03694

32. Jordan, A., Toennesen, L. L., Eklöf, J., Sivapalan, P., Meteran, H., Bønnelykke, K., Ulrik, C. S., & Stæhr Jensen, J.-U. (2023). Psychiatric Adverse Effects of Montelukast-A Nationwide Cohort Study. The Journal of Allergy and Clinical Immunology. In Practice, 11(7), 2096–2103.e1. https://doi.org/10.1016/j.jaip.2023.03.010

33. Sobczak, M., & Pawliczak, R. (2025). Montelukast: Risk of mental disorders vs. Efficacy–a meta-analysis. Frontiers in Pharmacology, 16, 1659852. https://doi.org/10.3389/fphar.2025.1659852

34. Tunca, S., Yilmaz, O., Ocalan, M., Arga, M., Cavkaytar, O., Ozceker, D., Kiliç, M., Duksal, F., Can, D., Sancakli, O., Kaya, M. Ş., Ercan, N., Gunaydin, N. C., Aydogan, M., Demir, E., Sancak, R., Karadag, S. İ. K., Sapan, N., Demir, A. U., … Yüksel, H. (2025). Potentially Overlooked Risk for Neuropsychiatric Symptoms in Children: Montelukast Treatment. Journal of Paediatrics and Child Health, 61(8), 1287–1294. https://doi.org/10.1111/jpc.70092