Comparison of common side effects from mood stabilizers and antipsychotics between pediatric and adult patients with bipolar disorder: a systematic review of randomized, double-blind, placebo-controlled trials

ABSTRACT

Introduction: To compare common side effects of mood stabilizers (MSs) and antipsychotics in pediatric and adult bipolar disorder (BD).

Area covered: MEDLINE, EMBASE, PsycINFO was searched for randomized, double-blind, placebo-controlled trials (RCTs) in the treatment of pediatric and adult BD. Twelve RCTs for pediatric patients and 30 for adult patients were included. The risk for the discontinuation due to adverse events, ≥7% weight gain, somnolence, akathisia, nausea and vomiting from a medication relative to placebo was estimated with absolute risk increase and the number needed to harm. The relative risk of these measures in pediatric and adult patients was compared.

Expert opinion: Overall, the relative risk for ≥7% weight gain, somnolence, nausea, or vomiting was higher, and akathisia was lower in pediatric patients than in adults. The magnitude of difference among MSs and antipsychotics and between pediatrics and adults varied widely. The risk for pediatric patients could be underestimated because in most pediatric studies, doses of studied medications were lower and flexibly dosed, and titration speeds were slower than in adult studies. Clinicians should pay attention to differences in study designs to understand the risk for common side effects when prescribing a medication for BD.

KEYWORDS:

• Akathisia
• bipolar disorder
• nausea
• pediatrics
• safety
• somnolence
• tolerability
• vomiting
• weight gain

Article highlights

• With the exception of oxcarbazepine in the treatment of pediatric mania, all other included medications were relatively well tolerated compared to placebo in both pediatric and adult patients with bipolar disorder (BD).

• Pediatric patients were more vulnerable to psychotropic-associated weight gain (WG), somnolence, nausea, and vomiting, but less likely to have akathisia than adults.

• The risk for WG, somnolence, akathisia, nausea, and vomiting varied widely among studied medications and between pediatric and adult patients.

• The risk for these common side effects could be underestimated in pediatric patients because in most pediatric studies, doses of studied medications were lower and flexibly dosed, and titration speeds were slower than in adult studies. The clinicians should pay attention to differences in study designs to understand the magnitude of differences between pediatric and adult patients.

• Both short-term side effects such as somnolence, akathisia, nausea, and vomiting and long-term side effects like WG and metabolic changes should be considered when prescribing a medication for BD.

Authors’ contributions

Conception and design (Y Bai, A Xu and K Gao), analysis and interpretation of the data (Y Bai and K Gao), drafting and revising of the paper (Y Bai, T Liu, A Xu, H Yang and K Gao), revising, final approval (Y Bai, T Liu, A Xu, H Yang and K Gao); and all authors agreed to be accountable for all aspects of the work.

Declaration of interest

K Gao was on an advisory board of Sunovion and Otsuka, is a member of a speakers bureau of AstraZeneca, Pfizer and Sunovion, and has received grant support from AstraZeneca, the Cleveland Foundation and the Brain and the Behavioral Research Foundation. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have been a consultant and/or a speaker and/or has received research grants from Allergan, Angelini, Apsen, Boheringer Ingelheim, Doc Generici, FB-Health, Italfarmaco, Janssen, Lundbeck, Mylan, Otsuka, Pfizer, Recordati, Sonofi Aventis, Sunovion and Vifor. All other peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was funded by the Sanming Project in Medicine of Shenzhen City, Guangdong, China (grant no. SZSM201612006).