Guanfacine

Guanfacine is a selective α2A receptor agonist.

Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison.[Pubmed:28258319]

Eur Child Adolesc Psychiatry. 2017 Aug;26(8):875-897.

This study compared the clinical efficacy and safety of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in children and adolescents 6-17 years of age. A systematic literature review was conducted to identify randomized controlled trials (RCTs) of pharmacologic monotherapies among children and adolescents with ADHD. A Bayesian network meta-analysis was conducted to compare change in symptoms using the ADHD Rating Scale Version IV (ADHD-RS-IV), Clinical Global Impression-Improvement (CGI-I) response, all-cause discontinuation, and adverse event-related discontinuation. Thirty-six RCTs were included in the analysis. The mean (95% credible interval [CrI]) ADHD-RS-IV total score change from baseline (active minus placebo) was -14.98 (-17.14, -12.80) for lisdexamfetamine dimesylate (LDX), -9.33 (-11.63, -7.04) for methylphenidate (MPH) extended release, -8.68 (-10.63, -6.72) for Guanfacine extended release (GXR), and -6.88 (-8.22, -5.49) for atomoxetine (ATX); data were unavailable for MPH immediate release. The relative risk (95% CrI) for CGI-I response (active versus placebo) was 2.56 (2.21, 2.91) for LDX, 2.13 (1.70, 2.54) for MPH extended release, 1.94 (1.59, 2.29) for GXR, 1.77 (1.31, 2.26) for ATX, and 1.62 (1.05, 2.17) for MPH immediate release. Among non-stimulant pharmacotherapies, GXR was more effective than ATX when comparing ADHD-RS-IV total score change (with a posterior probability of 93.91%) and CGI-I response (posterior probability 76.13%). This study found that LDX had greater efficacy than GXR, ATX, and MPH in the treatment of children and adolescents with ADHD. GXR had a high posterior probability of being more efficacious than ATX, although their CrIs overlapped.

The impact of adjunctive guanfacine extended release on stimulant adherence in children/adolescents with attention-deficit/hyperactivity disorder.[Pubmed:28118752]

J Comp Eff Res. 2017 Mar;6(2):109-125.

AIM: To assess stimulant adherence among children/adolescents with attention-deficit/hyperactivity disorder (ADHD) augmenting stimulants with Guanfacine extended-release (GXR). PATIENTS & METHODS: Inclusion criteria: 6-17 years, >/=1 ADHD diagnosis, >/=1 long-acting and/or short-acting stimulant with GXR augmentation. Modified medication possession ratio (mMPR; days medication available/days in period, excluding medication holidays) was assessed; mMPR <0.80 nonadherent. Regression models assessed change in mMPR adjusting for demographic and clinical characteristics. RESULTS: Among patients nonadherent to stimulants pre-augmentation (n = 165), unadjusted mean (SD) pre- and post-stimulant mMPRs were 0.68 (0.11) and 0.87 (0.16). Adjusted mean change in mMPR was 0.20 for long-acting versus 0.18 for short-acting stimulants (p = 0.34). CONCLUSION: Among patients nonadherent to stimulants, GXR augmentation was associated with increased stimulant adherence.

Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial.[Pubmed:28165762]

J Child Adolesc Psychopharmacol. 2017 Feb;27(1):29-37.

OBJECTIVE: This is a feasibility study evaluating the safety, tolerability, and potential anxiolytic efficacy of the alpha2 agonist Guanfacine extended-release (GXR) in children and adolescents with generalized anxiety disorder (GAD), separation anxiety disorder (SAD), or social phobia/social anxiety disorder. METHODS: Youth aged 6-17 years with a primary diagnosis of GAD, SAD, and/or social anxiety disorder were treated with flexibly dosed GXR (1-6 mg daily, n = 62) or placebo (n = 21) for 12 weeks. The primary aim of this study was to determine the safety and tolerability of GXR in youth with anxiety disorders, which involved the analysis of treatment-emergent adverse events (TEAEs), the emergence of suicidal ideation and behaviors, vital signs, and electrocardiographic/laboratory parameters. Exploratory efficacy measures included dimensional anxiety scales (Pediatric Anxiety Rating Scale [PARS] and Screen for Child Anxiety Related Emotional Disorders [SCARED]), as well as the Clinical Global Impression-Improvement (CGI-I) scale. As this was an exploratory study, no inferential statistical analyses were performed. RESULTS: GXR was safe and well tolerated. Treatment-related mean +/- standard deviation changes in heart rate (GXR: 1.8 +/- 12 beats per minute [bpm] decrease; placebo: 0.5 +/- 11 bpm decrease), systolic blood pressure (GXR: 2.3 +/- 11 mm Hg decrease; placebo: 1.7 +/- 11 mm Hg decrease), or diastolic blood pressure (GXR: 1.3 +/- 9 mm Hg decrease; placebo: 0.9 +/- 7 mm Hg increase) were similar between treatment groups. TEAEs, including headache, somnolence/fatigue, abdominal pain, and dizziness, were consistent with the known safety profile of GXR. No differences were observed between treatment groups for PARS and SCARED scores, although at endpoint, a higher proportion of subjects receiving GXR versus placebo demonstrated CGI-I scores

[An update on the pharmacological treatment of attention deficit hyperactivity disorder: lisdexamphetamine and extended-release guanfacine].[Pubmed:28272733]

Rev Neurol. 2017 Mar 13;64(s02):S1-S8.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders in the child population. Its treatment is complex and must include psychoeducational, environmental and pharmacological measures. In recent years, the main novelties as regards its pharmacological treatment have been the appearance of lisdexamphetamine and extended-release Guanfacine. AIMS: The increase in the number of drugs available for the treatment of ADHD makes it possible to treat and cover a very wide range of different clinical situations. The purpose of this review is to perform an analysis of the literature on the two drugs. DEVELOPMENT: The study determines the strong points of both treatments, with special attention given to their mechanism of action, their tolerability and their efficacy. CONCLUSIONS: Extended-release Guanfacine enables the professional to treat situations that are poorly covered by stimulants, such as children with irritability and tics, with a significant profile characterised by moderate efficacy and good tolerability and safety. The appearance of lisdexamphetamine has brought about a very important change because, according to the literature, it is a drug that, from the clinical point of view, is both complete and effective in improving the symptoms of ADHD. Moreover, it has a good safety profile.