Bipolar I Disorder
Efficacy
& Safety

LYBALVI (olanzapine and samidorphan) offers the efficacy demonstrated by olanzapine in adequate and well-controlled studies
Olanzapine has been proven to significantly reduce manic or mixed episodes in bipolar I disorder when used as monotherapy, maintenance monotherapy, and as adjunctive treatment to lithium or valproate1
The efficacy of LYBALVI in the treatment of adult patients with bipolar I disorder has been established based on adequate and well-controlled studies of orally-administered olanzapine.1 The following sections describe data from studies of olanzapine in patients with manic or mixed episodes associated with bipolar I disorder.
Monotherapy
- Olanzapine monotherapy was superior to placebo in reduction of mania (as measured by reduction of Young Mania Rating Scale [Y-MRS] total score)* in patients with bipolar I disorder with manic or mixed episodes in one 3-week trial and one 4-week trial1
- In an identically designed 3-week study conducted simultaneously with the first study, olanzapine demonstrated a similar treatment difference but, possibly due to sample size and site variability, was not shown to be superior to placebo on this outcome1
- The primary outcome in these studies was change from baseline in the Y-MRS total score1
Y-MRS, an 11-item clinician-rated scale traditionally used to assess the degree of manic symptomatology in a range from 0 (no manic features) to 60 (maximum score).1
Maintenance Monotherapy
- Patients with manic or mixed episodes who had responded during an initial open-label 2-week treatment phase to olanzapine 5 mg/day to 20 mg/day were randomized to either continuation of olanzapine at their same dose (n=225) or to placebo (n=136) for observation of relapse1
- In the randomized phase, approximately 50% of the patients had discontinued from the olanzapine group by Day 59 and 50% of the placebo group had discontinued by Day 23 of double-blind treatment1
- Patients receiving continued olanzapine experienced a significantly longer time to relapse (relapse was defined as an increase of the Y-MRS or HAM-D 21 total score to ≥15, or being hospitalized for either mania or depression)1
Adjunctive Treatment TO LITHIUM OR VALPROATE
Across two 6-week studies, olanzapine in combination with lithium or valproate was superior to either treatment alone in reduction of Y-MRS total scores in patients1:
- with inadequately controlled manic or mixed symptoms
- with or without psychotic symptoms
- with or without rapid cycling course
Adverse reactions with olanzapine in bipolar I disorder
Most common adverse reactions observed with oral olanzapine in bipolar I disorder
The safety of LYBALVI for the treatment of bipolar I disorder (manic or mixed) monotherapy and adjunct to lithium or valproate is based on adequate and well-controlled studies of olanzapine tablets in bipolar I disorder.1
- The most common adverse reactions (incidence of ≥5% of patients exposed to olanzapine and ≥2X the rate of placebo) from short-term trials of olanzapine (manic or mixed episodes) are somnolence, dry mouth, dizziness, asthenia, constipation, dyspepsia, increased appetite, and tremor1
- The most common adverse reactions (incidence of ≥5% of patients exposed to olanzapine and ≥2X the rate of placebo) from short-term trials of olanzapine as adjunct to lithium or valproate (manic or mixed episodes) are dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, and paresthesia1
The olanzapine in LYBALVI was shown to be bioequivalent to olanzapine alone2
The efficacy of LYBALVI in the treatment of adult patients with bipolar I disorder has been established based on adequate and well-controlled studies of orally-administered olanzapine.
STUDY DESIGN2
- Phase 1, single-center, open-label, randomized, crossover study to assess the relative bioavailability of olanzapine in LYBALVI, olanzapine and Zyprexa®
- Eligible healthy subjects were randomly assigned in a 1:1:1:1:1:1 ratio to 1 of 6 treatment sequences (n=8 subjects per sequence group), in which they received single doses of LYBALVI 10 mg/10 mg, olanzapine 10 mg, or Zyprexa 10 mg on the first day of each treatment period, with a 14-day washout period between doses. The study had 3 treatment periods for each subject. Each treatment period included a 4-day inpatient stay and a 5-day outpatient follow-up (9 days total). Subjects fasted for ≥10 hours before receiving a single dose of study drug on the morning of Day 1 of each treatment period. Subjects remained inpatients until 48 hours postdosing for pharmacokinetic and safety assessments and were asked to return for 4 outpatient follow-up visits on Days 4 to 6 and 8 for further pharmacokinetic and safety assessments1
Combining olanzapine with samidorphan does not affect the bioavailability of olanzapine1,2


Zyprexa® is a registered trademark of Eli Lilly and Company, its subsidiaries, or affiliates.
Zyprexa® is a registered trademark of Eli Lilly and Company, its subsidiaries, or affiliates.
References: 1. LYBALVI [prescribing information]. Waltham, MA: Alkermes, Inc.; 2021. 2. Sun L, McDonnell D, Liu J, von Moltke L. Bioequivalence of olanzapine given in combination with samidorphan as a bilayer tablet (ALKS 3831) compared with olanzapine-alone tablets: results from a randomized, crossover relative bioavailability study. Clin Pharm Drug Dev. 2019;8(4):459-466.