0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letters   |    
Atomoxetine-Induced Vocal Tics in a Patient With Schizophrenia
Dhanya Raveendranathan, M.D.; Mukund G Rao, M.D.; Shivarama Varambally, M.D; Ganesan Venkatasubramanian, M.D.; Bangalore N Gangadhar, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2012;24:E45-E46. doi:10.1176/appi.neuropsych.11110333
View Author and Article Information
Senior Residents
Associate Professors
Professor
Department of Psychiatry
National Institute of Mental Health And Neurosciences (NIMHANS)
Bangalore, India

Corresponding author: Dr. Dhanya Raveendranathan e-mail: dhanya.ravi@gmail.com

To the Editor: Atomoxetine is a potent inhibitor of the presynaptic norepinephrine transporter (NET) and has minimal affinity for other neurotransmitter transporters and neuronal receptors. As per currently available evidence, atomoxetine has demonstrated efficacy in improving attention-deficit hyperactivity disorder (ADHD) symptoms in children with comorbid tics and has also significantly improved comorbid tic symptoms.1 Hence, it has been considered as an appropriate choice in patients with ADHD and comorbid tics, or with a history of possible medication-induced tics.

However, here have been a few reports of atomoxetine-induced tics25 when used in children with ADHD.

Atomoxetine, through its mechanism of being an NET inhibitor, may selectively increase dopamine (DA) in the prefrontal cortex (PFC) while not increasing DA in subcortical areas. Accordingly, since persons with schizophrenia are thought to have a deficit of DA in the PFC, and excessive subcortical DA function, an NET inhibitor such as atomoxetine may increase DA-dependent, PFC-mediated neurocognitive functioning and reduce negative symptoms associated with this disorder without worsening the positive symptoms of schizophrenia.6 Hence, there is a rationale and some preliminary evidence for its possible use in schizophrenia.

A 17-year-old, single young man, temperamentally “slow to warm up,” was initially noticed at age 15 to show decline in his academic performance and become socially withdrawn. Gradually, he was observed to have delusions of persecution and 2nd- and 3rd-person auditory hallucinations, in the absence of any previous medical or psychiatric history. The psychotic symptoms improved with olanzapine 10mg/day. This was reduced to 7.5 mg because of excessive sedation. The patient continued to report impairment in attention, concentration, and overall difficulty in studies, due to which academic decline continued. Because of persistent reports of difficulty in attention and concentration, a neuropsychological evaluation of his cognitive abilities was done. This showed inadequacy in motor speed, mental speed, visuo-spatial memory, working memory, verbal memory, set-shifting, and concept-formation. An impression of frontal and bitemporal involvement was made. The patient was started on atomoxetine 10 mg with the aim of reducing his cognitive impairment and enhancing subsequent overall functioning. One month after atomoxetine was started, he was noted to be producing ticking sounds from his throat. The frequency of these sounds, which were initially not noticed by the family, gradually began to increase over the next few months. These would occur numerous times throughout the day, but were absent during sleep. At consultation, a detailed physical examination revealed repeated ticking sounds from the throat, which patient would try to suppress by drinking water and swallowing repeatedly, but he was only partially successful. No other involuntary movements or coprolalia were observed. A complete hemogram and routine biochemical investigations, including blood sugars, renal, liver, and thyroid functions, were within normal limits. An impression of “vocal tics” was made. Since the onset of the vocal tics had begun after the start of atomoxetine therapy, a suspicion of atomoxetine-induced tics was noted, and a decision to stop atomoxetine was made. Within 5 days of stopping atomoxetine, the sounds from the throat subsided and stopped. The patient continues to remain symptom-free after more than 3 months of atomoxetine discontinuation. He has been advised to undergo cognitive remediation training to handle the cognitive deficits.

The animal models of noradrenergic dysfunction have shown deficits in sustained attention and shifting attention, which are also known to exist in schizophrenia, and these deficits were shown to be reversed by drugs that improve noradrenergic transmission.7 Atomoxetine has been known to increase the concentration of extracellular norepinephrine and dopamine threefold in the prefrontal cortex (PFC) by blocking the NET, where it has been shown that DA is predominately taken up nonselectively by NET. It does not increase extracellular dopamine or other monoamine concentrations in the subcortical areas.6

In adults with ADHD, there is some evidence that atomoxetine improves response inhibition8 and executive functioning.9 Because of the mechanism of selective increase of dopamine in the PFC and widespread increase of NE, it has been theorized that atomoxetine might also have a role in enhancement of cognitive functioning in patients with schizophrenia. There have been a few studies with conflicting results on cognitive-function improvement with atomoxetine. In two double-blind, placebo-controlled studies, no improvement in overall cognition as compared with placebo was noted in schizophrenia patients,10,11 but, in one study, the atomoxetine group showed significantly greater increase in working memory-related activation in the left dorsolateral prefrontal cortex.11

There have been a few reports of atomoxetine-induced tics25 when used in children with ADHD. Many had a history of medication-induced tics; also, the possibility of comorbid Tourette’s disorder in ADHD has to be considered. In this case, use of the adverse drug reaction probability scale by Naranjo et al.12 (score of 6) indicated that the adverse effect was probably related to atomoxetine.

As per our knowledge, this is the first case report of atomoxetine-induced vocal tic in an adult having schizophrenia with no previous history of ADHD or movement disorder who was given atomoxetine as an agent for cognitive enhancement. This case highlights the possibility that atomoxetine, like other stimulants, probably poses an independent risk of inducing tics and hence may not be ideal in patients with tic disorders.

Bloch  MH;  Panza  KE;  Landeros-Weisenberger  A  et al:  Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders.  J Am Acad Child Adolesc Psychiatry 2009; 48:884–893
[CrossRef] | [PubMed]
 
Sears  J;  Patel  NC:  Development of tics in a thirteen-year-old male following atomoxetine use.  CNS Spectr 2008; 13:301–303
[PubMed]
 
Párraga  HC;  Párraga  KL;  Harris  DK  et al:  Abdominal tics during atomoxetine treatment in a child with ADHD: evaluation and differential diagnosis.  CNS Spectr 2008; 13:E1
 
Ledbetter  M:  Atomoxetine use associated with onset of a motor tic.  J Child Adolesc Psychopharmacol 2005; 15:331–333
[CrossRef] | [PubMed]
 
Lee  TS;  Lee  TD;  Lombroso  PJ  et al:  Atomoxetine and tics in ADHD.  J Am Acad Child Adolesc Psychiatry 2004; 43:1068–1069
[CrossRef] | [PubMed]
 
Bymaster  FP;  Katner  JS;  Nelson  DL  et al:  Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder.  Neuropsychopharmacology 2002; 27:699–711
[CrossRef] | [PubMed]
 
Friedman  JI;  Stewart  DG;  Gorman  JM:  Potential noradrenergic targets for cognitive enhancement in schizophrenia.  CNS Spectr 2004; 9:350–355
[PubMed]
 
Chamberlain  SR;  Del Campo  N;  Dowson  J  et al:  Atomoxetine improved response inhibition in adults with attention deficit/hyperactivity disorder.  Biol Psychiatry 2007; 62:977–984
[CrossRef] | [PubMed]
 
Faraone  SV;  Biederman  J;  Spencer  T  et al:  Atomoxetine and Stroop Task performance in adult attention-deficit/hyperactivity disorder.  J Child Adolesc Psychopharmacol 2005; 15:664–670
[CrossRef] | [PubMed]
 
Kelly  DL;  Buchanan  RW;  Boggs  DL  et al:  A randomized, double-blind trial of atomoxetine for cognitive impairments in 32 people with schizophrenia.  J Clin Psychiatry 2009; 70:518–525
[CrossRef] | [PubMed]
 
Friedman  JI;  Carpenter  D;  Lu  J  et al:  A pilot study of adjunctive atomoxetine treatment to second-generation antipsychotics for cognitive impairment in schizophrenia.  J Clin Psychopharmacol 2008; 28:59–63
[CrossRef] | [PubMed]
 
Naranjo  CA;  Busto  U;  Sellers  EM  et al:  A method for estimating the probability of adverse drug reactions.  Clin Pharmacol Ther 1981; 30:239–245
[CrossRef] | [PubMed]
 
References Container
+

References

Bloch  MH;  Panza  KE;  Landeros-Weisenberger  A  et al:  Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders.  J Am Acad Child Adolesc Psychiatry 2009; 48:884–893
[CrossRef] | [PubMed]
 
Sears  J;  Patel  NC:  Development of tics in a thirteen-year-old male following atomoxetine use.  CNS Spectr 2008; 13:301–303
[PubMed]
 
Párraga  HC;  Párraga  KL;  Harris  DK  et al:  Abdominal tics during atomoxetine treatment in a child with ADHD: evaluation and differential diagnosis.  CNS Spectr 2008; 13:E1
 
Ledbetter  M:  Atomoxetine use associated with onset of a motor tic.  J Child Adolesc Psychopharmacol 2005; 15:331–333
[CrossRef] | [PubMed]
 
Lee  TS;  Lee  TD;  Lombroso  PJ  et al:  Atomoxetine and tics in ADHD.  J Am Acad Child Adolesc Psychiatry 2004; 43:1068–1069
[CrossRef] | [PubMed]
 
Bymaster  FP;  Katner  JS;  Nelson  DL  et al:  Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder.  Neuropsychopharmacology 2002; 27:699–711
[CrossRef] | [PubMed]
 
Friedman  JI;  Stewart  DG;  Gorman  JM:  Potential noradrenergic targets for cognitive enhancement in schizophrenia.  CNS Spectr 2004; 9:350–355
[PubMed]
 
Chamberlain  SR;  Del Campo  N;  Dowson  J  et al:  Atomoxetine improved response inhibition in adults with attention deficit/hyperactivity disorder.  Biol Psychiatry 2007; 62:977–984
[CrossRef] | [PubMed]
 
Faraone  SV;  Biederman  J;  Spencer  T  et al:  Atomoxetine and Stroop Task performance in adult attention-deficit/hyperactivity disorder.  J Child Adolesc Psychopharmacol 2005; 15:664–670
[CrossRef] | [PubMed]
 
Kelly  DL;  Buchanan  RW;  Boggs  DL  et al:  A randomized, double-blind trial of atomoxetine for cognitive impairments in 32 people with schizophrenia.  J Clin Psychiatry 2009; 70:518–525
[CrossRef] | [PubMed]
 
Friedman  JI;  Carpenter  D;  Lu  J  et al:  A pilot study of adjunctive atomoxetine treatment to second-generation antipsychotics for cognitive impairment in schizophrenia.  J Clin Psychopharmacol 2008; 28:59–63
[CrossRef] | [PubMed]
 
Naranjo  CA;  Busto  U;  Sellers  EM  et al:  A method for estimating the probability of adverse drug reactions.  Clin Pharmacol Ther 1981; 30:239–245
[CrossRef] | [PubMed]
 
References Container
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Related Content
Books
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 12.  >
Dulcan's Textbook of Child and Adolescent Psychiatry > Chapter 46.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 4.  >
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 38.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 12.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles
[Disorders comorbid to attention deficit hyperactivity syndrome in children]. Zh Nevrol Psikhiatr Im S S Korsakova 2007;107(7):30-5.
Atomoxetine-induced vocal tics in a patient with schizophrenia. J Neuropsychiatry Clin Neurosci 2012;24(4):E45-6.