Abstract
To the Editor:
A 6-
Significant inattention and distractibility were noted and guanfacine extended-release (XR) (Intuniv XR®) was prescribed. Ten days after dose titration started with 1 mg daily and after the first 2 mg dose, she began to display manic symptoms including decreased need for sleep, excessive energy, giddiness, grandiosity, pressured speech, hypersexuality, increased self-harm (hair pulling, head banging, skin picking, and scratching), and aggression toward her younger sibling and unit staff (hitting, kicking, and punching). Guanfacine XR was titrated down and discontinued. Despite sleeping adequately at night, her mood continued to be elevated and aggressive. A diagnosis of bipolar disorder, unspecified, was made. After consideration of several mood-stabilizing medications (i.e., lithium, divalproex, or aripiprazole), the family consented to a trial of lithium.
Manic symptoms took 7 weeks to settle. Over the final 2 weeks in hospital, symptoms improved with lithium treatment. With the combination of lithium and clonidine, our patient was better able to regulate and manage her mood and sleep. The patient's discharge medications were lithium 600 mg at bedtime and clonidine 0.05 mg at bedtime. At 3 months postdischarge, the patient's mood remained relatively stable; however, there continued to be sleep difficulties and corresponding periods of mood dysregulation.
Discussion
Manic reactions have been previously reported in children with guanfacine immediate-release (IR) (Horrigan and Barnhill 1999). To our knowledge, this is the first published report of a manic reaction with guanfacine XR. There was an increase in dysregulation after initiation of guanfacine XR 1 mg, and in retrospect this may have signaled an impending manic switch. The likelihood of this adverse event being related to guanfacine XR treatment was assessed as probable (Naranjo et al. 1981).
The Canadian Intuniv XR product monograph contains a warning regarding emergence of new psychotic or manic symptoms (Shire Pharma Canada ULC 2015), as does the U.S. prescribing information for guanfacine IR (Tenex®) (Promius Pharma, LLC 2013) but not the U.S. prescribing information for guanfacine XR (Intuniv) (Shire US, Inc. 2015). Given the earlier marketing of guanfacine XR (marketed in 2009 in the United States, late 2013 in Canada) and larger population, it is surprising there have not been reports of manic reactions to guanfacine before ours. The current Canadian Intuniv XR product monograph warns that screening for personal or family history of bipolar disorder should occur before starting treatment with guanfacine XR, and if such a history is identified, “particular care” should be taken regarding this prescription because of a concern for induction of a mixed/manic episode in such patients (Shire Pharma Canada ULC 2015). However, this warning was not present in the Intuniv XR product monograph at the time of the initial approval of guanfacine XR by Health Canada in July 2013 (Shire Canada, Inc. 2013) and was only added to the product monograph in January 2015, with update notification of this change reported to have been communicated to healthcare providers in February 2015 (Personal communication with Shire Pharma Canada ULC 2016). Awareness of the possibility of a manic switch after treatment with guanfacine XR appears to remain low among prescribers and pharmacists.
Conclusion
Treatment with guanfacine XR at a dosage of up to 2 mg/day for 12 days led to a manic episode in a 6-year-old girl. Resolution of the manic symptoms occurred over the following 7 weeks. Discontinuation of guanfacine XR and lithium initiation was required.
Footnotes
Disclosures
No competing financial interests exist.