The University of Southampton
University of Southampton Institutional Repository

Sleep-associated adverse events during the methylphenidate treatment of attention-deficit/hyperactivity disorder: A meta-analysis

Sleep-associated adverse events during the methylphenidate treatment of attention-deficit/hyperactivity disorder: A meta-analysis
Sleep-associated adverse events during the methylphenidate treatment of attention-deficit/hyperactivity disorder: A meta-analysis
Objective: Sleep disturbances are a feature of attention deficit/hyperactivity disorder (ADHD) and an adverse event (AE) of methylphenidate (MPH) treatment. We sought to clarify MPH-associated sleep problems and how studies are affected by confounding factors.

Data Sources: Published studies in English collected via online databases and unpublished data from www.clinicaltrials.gov and FDA websites. Sources were searched from inception to August 2017.

Study Selection: We included blinded placebo-controlled studies of youth with ADHD conducted in naturalistic settings. This led to 35 studies yielding 75 observations of sleep-related AEs. These studies comprised 3079 drug-exposed and 2606 placebo-treated patients.

Data Extraction: Two PhD reviewers reviewed each study for inclusion. Four PhD/PharmD reviewers extracted data in duplicate. Discrepancies were resolved by discussion or, if needed, by the senior author.

Results: We found increased pooled relative risks (RRs) for MPH-associated sleep-related AEs for insomnia, initial insomnia, middle insomnia, combined insomnia, and sleep disorder. Several sample or study design features were significantly associated with the RR for sleep-related AEs and the MPH formulation studied. After correcting for confounding, we found significant differences among drugs. We show that the RR, and its interpretation, is constrained by the placebo AE rate.

Conclusions: Several types of insomnia and sleep problems are associated with MPH treatment. Study design and sample features influence the RR statistic. By showing that the rate of placebo AEs impacts the RR, we provide the field with a useful covariate for adjusting RR statistics.
0160-6689
Faraone, Stephen V.
1ac67756-6c14-477a-8e38-84a735a2d030
Po, Michelle D.
104534e4-ff38-4145-98bf-ea91c2e94a0d
Komolova, Marina
8792ff1a-8613-4dd6-86e4-7255b96cc6ff
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb
Faraone, Stephen V.
1ac67756-6c14-477a-8e38-84a735a2d030
Po, Michelle D.
104534e4-ff38-4145-98bf-ea91c2e94a0d
Komolova, Marina
8792ff1a-8613-4dd6-86e4-7255b96cc6ff
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb

Faraone, Stephen V., Po, Michelle D., Komolova, Marina and Cortese, Samuele (2018) Sleep-associated adverse events during the methylphenidate treatment of attention-deficit/hyperactivity disorder: A meta-analysis. The Journal of Clinical Psychiatry. (In Press)

Record type: Article

Abstract

Objective: Sleep disturbances are a feature of attention deficit/hyperactivity disorder (ADHD) and an adverse event (AE) of methylphenidate (MPH) treatment. We sought to clarify MPH-associated sleep problems and how studies are affected by confounding factors.

Data Sources: Published studies in English collected via online databases and unpublished data from www.clinicaltrials.gov and FDA websites. Sources were searched from inception to August 2017.

Study Selection: We included blinded placebo-controlled studies of youth with ADHD conducted in naturalistic settings. This led to 35 studies yielding 75 observations of sleep-related AEs. These studies comprised 3079 drug-exposed and 2606 placebo-treated patients.

Data Extraction: Two PhD reviewers reviewed each study for inclusion. Four PhD/PharmD reviewers extracted data in duplicate. Discrepancies were resolved by discussion or, if needed, by the senior author.

Results: We found increased pooled relative risks (RRs) for MPH-associated sleep-related AEs for insomnia, initial insomnia, middle insomnia, combined insomnia, and sleep disorder. Several sample or study design features were significantly associated with the RR for sleep-related AEs and the MPH formulation studied. After correcting for confounding, we found significant differences among drugs. We show that the RR, and its interpretation, is constrained by the placebo AE rate.

Conclusions: Several types of insomnia and sleep problems are associated with MPH treatment. Study design and sample features influence the RR statistic. By showing that the rate of placebo AEs impacts the RR, we provide the field with a useful covariate for adjusting RR statistics.

Text
180630 MPH Sleep AE Meta Analysis UNF_SC - Accepted Manuscript
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 20 November 2018

Identifiers

Local EPrints ID: 426418
URI: https://eprints.soton.ac.uk/id/eprint/426418
ISSN: 0160-6689
PURE UUID: eb379a52-5cb4-4718-8aec-d0411e2fa3f0
ORCID for Samuele Cortese: ORCID iD orcid.org/0000-0001-5877-8075

Catalogue record

Date deposited: 27 Nov 2018 17:30
Last modified: 14 Mar 2019 01:32

Export record

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×