Journal of Clinical Psychopharmacology • Volume 35, Number 2, April 2015
Psychosis Associated With Guanfacine To the Editors: 5-year-old African American boy with attention-deficit/hyperactivity disorder presented with new-onset visual and tactile hallucinations of snakes. The symptoms first manifested when he awoke from sleep in the middle of the night. He was communicative and coherent but agitated during these episodes, which persisted into the daytime. The patient had restarted 1 mg of longacting guanfacine by mouth daily 2 weeks before presentation. Six days prior, the dose had been increased to 2 mg by mouth daily. After the onset of symptoms, the patient's mother had reduced the dose to 1 mg and then brought him to the hospital. Basic metabolic panel, serum and urine toxicology screens, as well as electrocardiogram all showed normal results. The patient had no prior history of hallucinations. He had no other neurological findings and no family history of mental illness. Magnetic resonance imaging of the brain was normal. For the first 24 hours of presentation, the patient received total doses of 3.5 mg of haloperidol and 1.5 mg of lorazepam. On admission to the medical floor, the patient's long-acting guanfacine, which has a half-life of 17 hours, was stopped, and his psychotic symptoms resolved for the subsequent 3 days. After the first night of admission, he did not require any further pro re nata. There have been only 3 other case reports of psychotic symptoms associated with α-agonists in the pediatric population. One case involved a 10-year-old African American boy who developed visual hallucinations of frogs and snakes in the middle
A
Letters to the Editors
of the night after initiation of both dextroamphetamine and guanfacine.1 Another case involved a girl taking clonidine and dextroamphetamine, who developed hallucinations after missing a dose of clonidine.2 Both of these cases involved concomitant use of psychostimulants, which are known to be potential hallucinogens. The third case involved a boy who developed auditory hallucinations while taking guanfacine in conjunction with paroxetine, lamotrigine, and trazodone.3 There have been more case reports of hallucinations and/or delirium in adults treated with α-agonists (Table 1). The α-adrenergic agonists were first used as antihypertensive agents. Clonidine and guanfacine subsequently have been found to have psychiatric indications, including attention-deficit/hyperactivity disorder and tic disorder. The most common adverse effects include xerostomia, fatigue, somnolence, constipation, and dizziness. Less common, more severe adverse effects include depression, anxiety, insomnia, and agitation. The psychoactive properties of the α-adrenergic agonists derive from their effects on the noradrenergic system. αAgonists can suppress arousal via stimulation of presynaptic autoreceptors in the locus coeruleus. An acute alteration in arousal may elicit anxiety and hallucinations. There has also been speculation that the visual hallucinations, in particular, may be a form of hypnopompic hallucinations, deriving from rebound hyperarousal in the middle of the night.1 All 4 of these pediatric case reports are characterized by acute onset after initiation or recent dose increase, duration of symptoms which is curtailed by discontinuation of the medication, and a complete
TABLE 1. Case Reports of Hallucinations and/or Delirium in Adults Treated With α-Agonists Demographic
Medication 4
54-year-old man
40-year-old woman5 68-year-old woman6 31-year-old woman6 50-year-old woman6 34-year-old man7 68-year-old man8 53-year-old man9 53-year-old man10
Indication
Adverse Effect
Polypharmacy
Clonidine
Hypertension
Yes
Clonidine
Hypertension
Clonidine
Hypertension
Hallucinations, delusions Hallucinations, delirium Hallucinations
Clonidine
Hypertension
Visual hallucinations
Clonidine
Hypertension
Not specified Not specified Yes
Auditory Yes hallucinations Clonidine Hypertension Hallucinations, Not specified delusions, delirium Brimonidine Glaucoma Paranoia, auditory Yes tartrate hallucinations Clonidine Hypertension Delirium Yes Clonidine Nightmares and Auditory Yes flashbacks hallucinations
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
return to premorbid functioning. One of the case reports noted that it is unclear whether symptoms would have resolved even if the α-agonist had been continued.1 Although admittedly rare, it is important that psychotic symptoms be considered as a potential adverse effect, particularly given that α-agonist medications seem to be prescribed more regularly now. Of note, previous case reports involved polypharmacy, whereas in this case, the patient was not on any other psychopharmacologic agents. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Rosa K. Kim, MD Division of Child and Adolescent Psychiatry Medical College of Wisconsin and Children's Hospital of Wisconsin Milwaukee, WI [email protected]
Robert Chayer, MD Child and Adolescent Services Department of Psychiatry and Behavioral Medicine Medical College of Wisconsin and Child and Adolescent Psychiatry Children's Hospital of Wisconsin Milwaukee, WI
REFERENCES 1. Luthra V, Markov D, Ambrosini P. Does guanfacine cause hallucinations in children? [letter]. J Child Adolesc Psychopharmacol. 1999;9:313–314. 2. Cantwell DP, Swanson J, Connor DF. Case study: adverse response to clonidine. J Am Acad Child Adolesc Psychiatry. 1997;36:539–544. 3. Boreman CD, Arnold LE. Hallucinations associated with initiation of guanfacine. J Am Acad Child Adolesc Psychiatry. 2003;42:1387. 4. Enoch MD, Hammad GE. Acute hallucinosis due to clonidine. Curr Med Res Opin. 1997;4: 670–671. 5. Elizur A, Liberson Z. An acute psychotic episode at the beginning of clonidine therapy. Prog Neuropsychopharmacol. 1980;4:211–212. 6. Brown MJ, Salmon D, Rendell M. Clonidine hallucinations. Ann Intern Med. 1980;93: 456–457. 7. Hoffman WF, Ladogana L. Delirium secondary to clonidine therapy. N Y State J Med. 1981;81: 382–383. 8. Kim DD. A case of suspected alphagan-induced psychosis. Arch Ophthalmol. 2000;118: 1132–1133. 9. Delaney J, Spevack D, Doddamani S, et al. Clonidine-induced delirium [letter]. Int J Cardiol. 2006;113:276–278. 10. Bestha DP, Madaan V. Clonidine and auditory hallucinations. Innov Clin Neurosci. 2012;9:10–13.
www.psychopharmacology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
213
Psychosis Associated With Guanfacine To the Editors: 5-year-old African American boy with attention-deficit/hyperactivity disorder presented with new-onset visual and tactile hallucinations of snakes. The symptoms first manifested when he awoke from sleep in the middle of the night. He was communicative and coherent but agitated during these episodes, which persisted into the daytime. The patient had restarted 1 mg of longacting guanfacine by mouth daily 2 weeks before presentation. Six days prior, the dose had been increased to 2 mg by mouth daily. After the onset of symptoms, the patient's mother had reduced the dose to 1 mg and then brought him to the hospital. Basic metabolic panel, serum and urine toxicology screens, as well as electrocardiogram all showed normal results. The patient had no prior history of hallucinations. He had no other neurological findings and no family history of mental illness. Magnetic resonance imaging of the brain was normal. For the first 24 hours of presentation, the patient received total doses of 3.5 mg of haloperidol and 1.5 mg of lorazepam. On admission to the medical floor, the patient's long-acting guanfacine, which has a half-life of 17 hours, was stopped, and his psychotic symptoms resolved for the subsequent 3 days. After the first night of admission, he did not require any further pro re nata. There have been only 3 other case reports of psychotic symptoms associated with α-agonists in the pediatric population. One case involved a 10-year-old African American boy who developed visual hallucinations of frogs and snakes in the middle
A
Letters to the Editors
of the night after initiation of both dextroamphetamine and guanfacine.1 Another case involved a girl taking clonidine and dextroamphetamine, who developed hallucinations after missing a dose of clonidine.2 Both of these cases involved concomitant use of psychostimulants, which are known to be potential hallucinogens. The third case involved a boy who developed auditory hallucinations while taking guanfacine in conjunction with paroxetine, lamotrigine, and trazodone.3 There have been more case reports of hallucinations and/or delirium in adults treated with α-agonists (Table 1). The α-adrenergic agonists were first used as antihypertensive agents. Clonidine and guanfacine subsequently have been found to have psychiatric indications, including attention-deficit/hyperactivity disorder and tic disorder. The most common adverse effects include xerostomia, fatigue, somnolence, constipation, and dizziness. Less common, more severe adverse effects include depression, anxiety, insomnia, and agitation. The psychoactive properties of the α-adrenergic agonists derive from their effects on the noradrenergic system. αAgonists can suppress arousal via stimulation of presynaptic autoreceptors in the locus coeruleus. An acute alteration in arousal may elicit anxiety and hallucinations. There has also been speculation that the visual hallucinations, in particular, may be a form of hypnopompic hallucinations, deriving from rebound hyperarousal in the middle of the night.1 All 4 of these pediatric case reports are characterized by acute onset after initiation or recent dose increase, duration of symptoms which is curtailed by discontinuation of the medication, and a complete
TABLE 1. Case Reports of Hallucinations and/or Delirium in Adults Treated With α-Agonists Demographic
Medication 4
54-year-old man
40-year-old woman5 68-year-old woman6 31-year-old woman6 50-year-old woman6 34-year-old man7 68-year-old man8 53-year-old man9 53-year-old man10
Indication
Adverse Effect
Polypharmacy
Clonidine
Hypertension
Yes
Clonidine
Hypertension
Clonidine
Hypertension
Hallucinations, delusions Hallucinations, delirium Hallucinations
Clonidine
Hypertension
Visual hallucinations
Clonidine
Hypertension
Not specified Not specified Yes
Auditory Yes hallucinations Clonidine Hypertension Hallucinations, Not specified delusions, delirium Brimonidine Glaucoma Paranoia, auditory Yes tartrate hallucinations Clonidine Hypertension Delirium Yes Clonidine Nightmares and Auditory Yes flashbacks hallucinations
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
return to premorbid functioning. One of the case reports noted that it is unclear whether symptoms would have resolved even if the α-agonist had been continued.1 Although admittedly rare, it is important that psychotic symptoms be considered as a potential adverse effect, particularly given that α-agonist medications seem to be prescribed more regularly now. Of note, previous case reports involved polypharmacy, whereas in this case, the patient was not on any other psychopharmacologic agents. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Rosa K. Kim, MD Division of Child and Adolescent Psychiatry Medical College of Wisconsin and Children's Hospital of Wisconsin Milwaukee, WI [email protected]
Robert Chayer, MD Child and Adolescent Services Department of Psychiatry and Behavioral Medicine Medical College of Wisconsin and Child and Adolescent Psychiatry Children's Hospital of Wisconsin Milwaukee, WI
REFERENCES 1. Luthra V, Markov D, Ambrosini P. Does guanfacine cause hallucinations in children? [letter]. J Child Adolesc Psychopharmacol. 1999;9:313–314. 2. Cantwell DP, Swanson J, Connor DF. Case study: adverse response to clonidine. J Am Acad Child Adolesc Psychiatry. 1997;36:539–544. 3. Boreman CD, Arnold LE. Hallucinations associated with initiation of guanfacine. J Am Acad Child Adolesc Psychiatry. 2003;42:1387. 4. Enoch MD, Hammad GE. Acute hallucinosis due to clonidine. Curr Med Res Opin. 1997;4: 670–671. 5. Elizur A, Liberson Z. An acute psychotic episode at the beginning of clonidine therapy. Prog Neuropsychopharmacol. 1980;4:211–212. 6. Brown MJ, Salmon D, Rendell M. Clonidine hallucinations. Ann Intern Med. 1980;93: 456–457. 7. Hoffman WF, Ladogana L. Delirium secondary to clonidine therapy. N Y State J Med. 1981;81: 382–383. 8. Kim DD. A case of suspected alphagan-induced psychosis. Arch Ophthalmol. 2000;118: 1132–1133. 9. Delaney J, Spevack D, Doddamani S, et al. Clonidine-induced delirium [letter]. Int J Cardiol. 2006;113:276–278. 10. Bestha DP, Madaan V. Clonidine and auditory hallucinations. Innov Clin Neurosci. 2012;9:10–13.
www.psychopharmacology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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