Samidorphan for the treatment of weight gain associated with olanzapine in patients with schizophrenia and bipolar disorder

ABSTRACT

Introduction

Olanzapine (OLZ) is one of the most effective antipsychotic agents, however, its clinical utility has been limited by weight gain. Samidorphan (SAM) is a μ-opioid receptor antagonist and it can reduce the weight gain associated with OLZ. A combination of OLZ and SAM (OLZ/SAM) has been developed to provide the antipsychotic efficacy of OLZ, while mitigating OLZ-associated weight gain.

Areas covered

A comprehensive literature search was conducted in PubMed. Key search terms included SAM and weight gain associated with OLZ. The pharmacological action, clinical efficacy, and safety of SAM were reviewed.

Expert opinion

OLZ can lead to weight gain. SAM is a new drug that acts as an opioid receptor antagonist that can decrease weight gain. SAM mitigates OLZ-associated weight gain while preserving the antipsychotic efficacy of OLZ. Clinical trials have confirmed that OLZ/SAM significantly improved psychotic symptoms, and resulted in significantly less weight gain than OLZ. OLZ/SAM was well tolerated. Therefore, it is a potential new treatment option for schizophrenia.

KEYWORDS:

• Μ-opioid antagonist
• olanzapine
• samidorphan
• schizophrenia
• weight gain

Article highlights

• SAM is aμ-opioid receptor antagonist and it can reduce the weight gain associated with OLZ.

• The exposure to SAM increased with increasing dose. The volume of distribution of SAM is 341 L, plasma clearance rate is 33.7L/h, and elimination half-life is 7-8 h.

• The initiate dose of OLZ/SAM is 5 mg/10 mg or 10 mg/10 mg orally once daily, the maintenance dose is 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg once daily.

• The common adverse reactions were weight gain, somnolence, dry mouth.

• Clinical trial: Phase 1: NCT00800319; Phase 2: NCT01903837; Phase 3: NCT02634346, NCT02669758, NCT02694328, NCT02873208.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed receiving manuscript or speaker’s fees from Astellas, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Elsevier Japan, Janssen Pharmaceuticals, Kyowa Yakuhin, Lundbeck, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Nihon Medi-Physics, Novartis, Otsuka Pharmaceutical, Shionogi, Shire, Tsumura, Wiley Japan, and Yoshitomi Yakuhin; and research grants from Dainippon Sumitomo Pharma, Eisai, Mochida Pharmaceutical, Meiji Seika Pharma and Shionogi. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Information resources

The regulatory documents including drug labels and scientific reviews of the Food and Drug Administration can be accessed online[10] . Sun L et al. carried out an important pharmacokinetic and pharmacodynamic study[34]. The pivotal clinical trials were NCT01903837[39], NCT02634346 (ENLIGHTEN-1)[40], (NCT02669758) [41], NCT02694328 (ENLIGHTEN-2)[42].

Additional information

Funding

This paper was not funded.