Evaluation of the current data on guanfacine extended release for the treatment of ADHD in children and adolescents

ABSTRACT

Introduction: Attention-deficit/hyperactivity disorder (ADHD) commonly occurs in children, adolescents, and adults. Although symptoms of ADHD often respond robustly to treatment with stimulants (amphetamine or methylphenidate), not all patients are appropriate candidates for treatment with these drugs. Guanfacine extended-release (GXR) is a non-stimulant alternative drug approved for the treatment of ADHD in the United States (U.S.), Canada, and Europe.

Areas covered: The chemistry, pharmacokinetics, mechanism of action and dosage of GXR are presented. Efficacy and safety data obtained in clinical trials with subjects aged 6–17 years for both GXR monotherapy and use in combination with stimulants are described. Meta-analyses comparing GXR to other drugs are presented. MedWatch surveillance data collected for GXR since approval in the U.S. are also discussed.

Expert opinion: Although GXR is effective for the treatment of ADHD and has a different side effect profile than stimulants, it is not as impressive in reducing symptoms. Despite the availability of multiple pharmacological treatments for ADHD, there remains an unmet need for formulations as potent as stimulants but with fewer adverse effects. Several pharmacological agents for ADHD treatment are in development. It is not clear that any of these compounds will replace currently available formulations as first-line alternatives.

KEYWORDS:

• Attention-deficit/hyperactivity disorder
• ADHD
• guanfacine extended-release
• pharmacological treatment
• non-stimulants

Article Highlights

• Guanfacine extended-release (GXR) monotherapy is effective in treatment of ADHD in children and adolescents in doses of 1 mg to 7 mg daily

• GXR is effective in reducing ADHD symptoms in children and adolescents as add-on therapy in patients who have partial response to stimulants in doses of 1 mg to 4 mg daily

• GXR may be dosed at any time of day

• GXR concentrations increase by approximately 75% when taken with a high-fat meal compared to dosing when fasting

• GXR is metabolized by CYP3A4 and CYP3A5 and dosing should be adjusted when administered with moderate to strong CYP3A4 inducers or inhibitors

Declaration of interest

A Childress has received research support from: Allergan, Aevi Genomic Medicine, Akili Interactive Labs, Alcobra Pharma, Allergan, Arbor Pharmaceuticals, LLC, Eli Lilly and Company, Forest Laboratories, Ironshore Pharmaceuticals & Development, Inc., KemPharm, Inc., Lundbeck, Neos Therapeutics, Neurovance, Inc., Noven, Otsuka America Pharmaceutical, Inc., Pearson, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Shire, Sunovion Pharmaceuticals, Inc., Supernus Pharmaceuticals, Inc., and Tris Pharma. She is also an advisory board member/consultant for Akili Interactive Labs, Arbor Pharmaceuticals, LLC, Cingulate Therapeutics, Ironshore Pharmaceuticals & Development, Inc., Neos Therapeutics, Neurovance, NLS Pharma, Noven, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Shire, Sunovion Pharmaceuticals, Inc., Supernus Pharmaceuticals, Inc., and Tris Pharma and serves on the Speakers bureau for Arbor Pharmaceuticals, LLC, Ironshore Pharmaceuticals & Development, Inc., Neos Therapeutics, Pfizer, Shire, Takeda Pharmaceutical Company Ltd., and Tris Pharma. A Childress has also received writing support from Arbor Pharmaceuticals, LLC, Ironshore Pharmaceuticals & Development, Inc., Neos Therapeutics, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Shire, Sunovion Pharmaceuticals, Inc. and Tris Pharma. 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

One referee, in the past, has been a site investigator for Shire studies on safety and efficacy of guanfacine for the treatment of ADHD. He has also been a co-author on scientific presentations of the data related to the safety and efficacy of guanfacine for treating ADHD. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.