Rankings / Mood, Anxiety & Stress

Olanzapine + samidorphan (Lybalvi)

Mood, Anxiety & Stress · Antipsychotic + opioid antagonist

Tier B-

atypical-antipsychoticdopamineopioid-antagonistschizophreniaprescription
6 / 10
Tier B-
Ev 8 Bn 6.5 Sf 3.5

Bottom line

Read Off Label grades Olanzapine + samidorphan (Lybalvi) as B- (6.0/10) based on strong evidence, med-high benefit magnitude, and a med-high-risk safety profile.

Alkermes (Lybalvi).

Typical use: Oral once daily (olanzapine 5-20 mg + samidorphan 10 mg) — Rx.

What this is

Alkermes (Lybalvi). FDA-approved for schizophrenia and bipolar I. Samidorphan attenuated olanzapine-associated weight gain in registration trials (ENLIGHTEN-2); the open question is whether the metabolic-mitigation signal holds in real-world use. Industry-sponsored.

Mechanism

Fixed-dose olanzapine plus the opioid antagonist samidorphan, designed to retain olanzapine efficacy while blunting its characteristic weight gain via central opioid-receptor blockade.

Dose & route

Oral once daily (olanzapine 5-20 mg + samidorphan 10 mg)

Citations

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Common questions

Does Olanzapine + samidorphan (Lybalvi) work?
Read Off Label rates the evidence for Olanzapine + samidorphan (Lybalvi) as Strong and the benefit magnitude as med-high, producing an overall grade of B- (6.0/10). Alkermes (Lybalvi).
Is Olanzapine + samidorphan (Lybalvi) safe?
Olanzapine + samidorphan (Lybalvi) has a med-high risk profile in published human data. Legal status: Rx (FDA-approved: schizophrenia, bipolar I). This is not medical advice — see the disclaimer.
What is the typical dose for Olanzapine + samidorphan (Lybalvi)?
Oral once daily (olanzapine 5-20 mg + samidorphan 10 mg)
How does Olanzapine + samidorphan (Lybalvi) work?
Fixed-dose olanzapine plus the opioid antagonist samidorphan, designed to retain olanzapine efficacy while blunting its characteristic weight gain via central opioid-receptor blockade.

This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.