Weekly Oral Risperidone (LYN‑005): Breakthrough in Schizophrenia Treatment?
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Published: July 2025 in The Lancet Psychiatry
Study: Long-acting oral weekly risperidone (LYN-005) for schizophrenia in the USA (STARLYNG-1): a multicentre, open-label, non-randomised phase 3 trial.
📌 Study Summary:
This phase 3, open‑label, non‑randomised US study assessed the pharmacokinetic equivalence and clinical stability of LYN‑005, a once‑weekly oral capsule formulation of risperidone, compared with standard daily risperidone.
🔬 Design Highlights:
- Participants (n=83): Adults with stable schizophrenia or schizoaffective disorder (mean age 49.3, 75% male, 81% Black/African American)
- Run-in Period: 7 days of daily immediate‑release risperidone (2 mg or 6 mg), depending on prior dosing
- Intervention: LYN‑005 once weekly (15 mg or 45 mg) for 5 weeks (total 5 doses) with supplemental half-dose risperidone in Week 1
- Primary Endpoints: Pharmacokinetic measures—Cₘᵢₙ (weeks 1 & 5), Cₘₐₓ, and Cₐᵥg (week 5), compared to daily oral risperidone
💊 Pharmacokinetic Outcomes: Geometric mean ratios of LYN-005 versus immediate-release risperidone were:
- Cmin at week 1: 1·02 (90% CI 0·93–1·12)
- Cmin at week 5: 1·04 (90% CI 0·87–1·23)
- Cmax at week 5: 0·84 (0·77–0·92)
- Cavg at week 5: 1·03 (0·93–1·13)
- Steady therapeutic levels maintained across the week
⚠️ Safety & Tolerability:
- Adverse events: Mild gastrointestinal symptoms in 66% of participants; one serious event (esophagitis)
👍 Clinical Stability:
- PANSS scores remained unchanged; most participants judged stable
💬 Clinical Commentary
This trial marks the first successful phase 3 validation of a long‑acting oral antipsychotic. The once-weekly dosing of LYN‑005 could bridge the gap between daily pills and injectable long-acting injectables (LAIs), especially for patients preferring oral formulations over injections
Potential Benefits:
- Improved adherence: Less dosing frequency may reduce missed doses and associated relapse risk
- Stable plasma levels: Lower peak concentrations could mean fewer side effects related to dopamine fluctuation
- Patient autonomy: Eliminates frequent reminders, enhances self-management, and likely reduces stigma
Clinical Considerations:
- Short study duration (5 weeks): Long-term adherence, relapse prevention, and safety—especially GI effects—need further evaluation
- Controlled setting: Inpatient/residential phase may not reflect real-world outpatient adherence or acceptance
- Pharmacokinetic vs clinical outcomes: Although PK equivalence is promising, efficacy and tolerability in broader outpatient settings remain to be demonstrated
📚 Comparison with Existing Modalities
- Daily oral risperidone: Convenient but prone to non-adherence and plasma level fluctuations
- LAI antipsychotics: Already reduce relapse risk, but involve clinic visits and injection aversion
- LYN‑005: Promises the convenience of oral dosing with adherence advantages of LAIs—without injections
✅ Conclusion
The STARLYNG‑1 trial confirms that weekly LYN‑005 delivers stable, therapeutic risperidone levels and is well-tolerated over 5 weeks in stable patients. This novel oral long-acting platform offers a compelling new option for schizophrenia care. Pending confirmatory outpatient trials and long-term data, LYN‑005 could reshape antipsychotic adherence strategies—especially for patients resistant to daily or injectable regimens.
🛠 Next Steps
- Outpatient, relapse-prevention trials over 6–12+ months
- Patient-reported outcomes on satisfaction and quality of life
- Head-to-head comparisons with LAIs to assess relapse rates, side-effect profiles, and overall cost-effectiveness
📚 References
Citrome, Leslie et al. The Lancet Psychiatry, Volume 12, Issue 7, 504 – 512 (article)
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