Journal of Clinical Psychopharmacology • Volume 35, Number 3, June 2015
Letters to the Editors 10. Suzuki E, Nakai D, Yamamura N, et al. Inhibition mechanism of carbapenem antibiotics on acylpeptide hydrolase, a key enzyme in the interaction with valproic acid. Xenobiotica. 2011;41:958–963. 11. Bates D, Parkins M, Duggan K. Ertapenem-induced reduction in in valproate levels: case report and review of the literature. Can J Hosp Pharm. 2010;63:315–322.
Exacerbation of Tics After Combining Aripiprazole With Pimozide A Case With Tourette Syndrome To the Editors: ourette Syndrome (TS) is a neuropsychiatric disorder characterized by chronic motor and vocal tics, which have a waxing and waning course.1 There are many pharmacotherapeutic agents used in the treatment of tic disorders; antipsychotics are the drugs of choice.2 Although aripiprazole (ARI) is highly successful in treating positive symptoms in schizophrenia and manic symptoms in mania, and there is much data showing that tics are improved with ARI and its beneficial effect in tic disorders, it is mostly limited to case reports and open trials.2,3 Recently, Yoo et al4 reported that ARI was efficacious and safe in the short-term treatment of children and adolescents with TS when compared with placebo. We report an adolescent with TS whose tics were exacerbated after addition of ARI to pimozide.
T
CASE REPORT A 15-year-old male adolescent was first admitted to our child psychiatry unit 2 years ago because of his motor tics and attention problems. His motor tics were dominant in the shoulder and body. Furthermore, the patient himself and his family complained of marked impulsivity and aggression that led to serious problems in the family. He was born with induced vaginal delivery 10 days after the estimated birth date. His birth weight was 2500 g; he was discharged from the hospital 1 day after birth because he did not have any health problems. He had no history of hypoxia or jaundice. He was walking at his first birthday and speaking with short sentences when he was 2 years old. Tic problems were prevalent in his family history. His uncle had TS, his mother's uncle had motor tics, and his sister was diagnosed with Sydenham chorea. His health problems began with a seizure after a head trauma when he was 5 years old.
350
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Since his electroencephalographic examination had confirmed epileptiform abnormality, he was treated with valproic acid. His cranial magnetic resonance imaging was normal. One year after the initiation of valproic acid, risperidone treatment was added by the child neurologist for his behavioral problems and impulsivity. He was diagnosed with attention-deficit/ hyperactivity disorder (ADHD) when he was 6 years old, and risperidone was replaced with methylphenidate. After an allergic reaction to methylphenidate, risperidone was started again at 1 mg/d. His motor tics began when he was 8 years old, including shoulder shrugging, neck stretching, and scraping his hand across the wall. There were no simultaneous vocal tics. He was hospitalized by the child neurologist for the differential diagnosis of motor tics from conversion, Sydenham chorea, and Wilson disease when he was 8 years old. His echocardiography, electrocardiography, brain magnetic resonance imaging, electroencephalography, serum ceruloplasmin levels, eye inspection for Wilson disease, antistreptolysin-O, and C-reactive protein were all normal, and he was discharged with a risperidone regimen for chronic motor tic disorder. He had used several medications including haloperidol, pimozide, and atomoxetine in intervals until his admission to our clinic. Because he had problems related to chronic motor tic disorder and ADHD in his first admission to our clinic, he was treated with imipramine at 50 mg/d and pimozide at 2 mg/d. Pimozide dose was titrated to 3 mg/d for the control of motor tics. Five months after the first admission, he described a depressive episode and sertraline at 50 mg/d was initiated after the cessation of imipramine. He was on sertraline at 50 mg/d and pimozide at 3 mg/d for 10 months when a hypomanic episode occurred. He was suffering from sleep problems, irritability, decrease in academic performance, and severe anger. He also started to quarrel with his teachers, which he had never done before. The sertraline regimen was stopped, and he was started on ARI at 2.5 mg/d. Ten days after the initiation of ARI, the severity of the tics increased and vocal tics emerged with new motor tics. His Yale Global Motor Tic Severity Scale5 score increased from 11 to 19 after the addition of ARI. His vocal tic severity score was determined as 10. Although his irritability, psychomotor agitation, and other hypomania symptoms improved, ARI was discontinued. The severity of motor tics declined to its previous level gradually in 7 days after the cessation of ARI. Although the severity of vocal tics decreased after the termination of ARI, his vocal tic throat
clearing continued with multiple motor tics, which confirmed the diagnosis of TS in addition to ADHD and bipolar disorder.
DISCUSSION Aripiprazole is a new generation antipsychotic drug that differs from other typical and atypical antipsychotics with its partial agonist action on dopamine D2 receptors, which is suggested to mediate its dopaminergic effect in hypodopaminergic conditions.6,7 Dopamine hypothesis for TS depends on an excess of nigrostriatal dopaminergic activity. Groups of striatal neurons are suggested to become abnormally active leading to dysinhibition of thalamocortical circuits in the pathogenesis of TS.1 Our patient was on pimozide treatment, a potent dopamine D2 receptor blocker, when ARI was added. It can be postulated that the exacerbation of tics was related to the partial agonistic effect of ARI on D2 receptors, which became prominent in the hypodopaminergic milieu of nigrostriatal pathways caused by pimozide. Aripiprazole has also been reported to worsen the psychotic symptoms, irritability, agitation, and aggression in patients diagnosed with schizophrenia and schizoaffective disorders when added to treatment regimen of dopamine antagonists with a high affinity for D2 and D3 receptors, and the D2 partial agonistic effect of ARI has been suggested to mediate this.8,9 Contrary to these reports, the hypomanic symptoms of our case improved whereas the severity of the tics were exacerbated. Several hypotheses can be proposed to explain this contradiction. First of all, it is known that ARI has functionally selective actions at different neuronal groups resulting from its unexpectedly robust pharmacological profile.6 Aripiprazole has a partial agonistic effect on 5HT1A and a partial antagonistic effect on 5HT2A receptors. Both of these receptors are found in large quantities in the prefrontal cortex.6 While 5HT1A receptors and 5HT2A receptors regulate dopamine release, they also regulate the glutamate system. 5HT1A receptors inhibit glutamate release and 5HT2A receptors stimulate the release of glutamate.10 Blockage of cortical 5HT2A receptors and functional 5HT1A receptor agonism are suggested to mediate the balance between excitatory and inhibitory inputs onto prefrontal pyramidal neurons.11 The neurobiological mechanism of mania is not definite yet, but the prefrontal cortex is suggested to play a central role in its pathophysiology.12 Not only dopamine but also other neurotransmitters, including glutamate, are suggested to play a role in the pathophysiology of mania.12,13 Although ARI does not directly affect the glutamatergic system, glutamatergic modulation through 5HT1A agonistic and 5HT2A antagonistic
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Journal of Clinical Psychopharmacology • Volume 35, Number 3, June 2015
actions of ARI might have mediated or contributed to the improvement of the hypomanic symptoms in our patient. Also, it can be postulated that different neurotransmitters and receptor systems might predominate in some patients with mania in relation to individual genetic differences. The binding properties of ARI on 5HT1A and 5HT2A receptors might also play a role in controlling aggression because several neurotransmitter systems, including dopaminergic, adrenergic, GABAergic, serotonergic, and glutamatergic mechanisms, are suggested to be related to aggression.14 Furthermore, Ishii et al15 reported that ARI may reverse MK-801– induced prepulse inhibition deficits through regulation of the mitogen-activated protein kinases pathway, a downstream signal transduction system that is common to both dopaminergic and N-methyl-D-aspartate systems. There are several possible mechanisms through which ARI might be effective on aggression, as mentioned previously.14 Secondly, this adolescent was hypomanic without any psychotic symptoms and the cases whose psychotic symptoms were exacerbated with ARI were all patients with schizophrenia and schizoaffective disorder.8 Aggression and/or agitation were all associated with psychotic symptoms such as delusions and hallucinations in these patients, suggesting psychotic agitation. The D2 receptor agonist action of ARI was considered to explain the worsening psychosis in these patients. Takeuchi and Remington suggested that there might be a small subgroup of patients with schizophrenia or schizoaffective disorder who are more liable to present with the exacerbation of psychotic symptoms and aggression if ARI is added to existing antipsychotic treatment.8 Furthermore, although ARI has been proven to be an effective antimanic agent, it also has been reported to precipitate a manic episode in certain patients.16,17 There might be some patients with individual genetic or environmental predisposing factors that make them prone to an unexpected response to ARI treatment. Finally, mood disorders are overrepresented among patients with TS.18 Although it is unclear why these 2 disorders frequently co-exist, dysfunctioning corticotstriatotalamocortical circuits exist in both of these disorders. Because ARI had paradoxical effects on the symptomathology of TS and bipolar disorder of the patient, it can be suggested that different neurotransmitter systems and receptors might predominate in the pathophysiology of these 2 disorders in cases where bipolar disorder and TS co-exist. In conclusion, ARI has a unique pharmacology that may mediate its selective effects in different disorders and comorbid situations. This is the first case report in
which ARI addition to a typical neuroleptic agent exacerbated motor tics and led to the emergence of vocal tics. We suggest that although ARI has promising effects on treatment of tics, clinicians should be cautious when combining it with potent antipsychotic agents. If ARI must be given in this regimen, it might be logical to combine it after an antipsychotic-free period when possible. This may not be practical in psychotic disorders but seems more logical for tic disorders, if the patient can continue with other psychiatric drug groups until the hypodopaminergic condition returns to its pretreatment levels. AUTHOR DISCLOSURE INFORMATION The authors have no conflicts of interest with any commercial or other associations and no financial ties to disclose in connection with the submitted article. This patient was presented in a poster presentation at the 6th International Congress on Psychopharmacology in Turkey, entitled “Exacerbation of Tics With Combining ARI to Pimozide: A Case With Tourette Syndrome.” The parents of the patient and the patient gave consent for this report to be published in the journal. Betül Mazlum, MD Department of Neuroscience Institute of Experimental Medical Research Istanbul University Istanbul, Turkey [email protected]
Sennur Zaimoğlu, MD Department of Child and Adolescent Psychiatry Institute for Neurological Sciences Marmara University Istanbul, Turkey
Didem Behice Öztop, MD Department of Child and Adolescent Psychiatry Faculty of Medicine Erciyes University Kayseri, Turkey
REFERENCES 1. Leckman JF, Bloch MH, Smith ME, et al. Neurobiological substrates of Tourette's disorder. J Child Adolesc Psychopharmacol. 2010;20(4):237–247.
Letters to the Editors 5. Leckman JF, Riddle MA, Hardin MT, et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry. 1989;28(4):566–573. 6. Shapiro DA, Renock S, Arrington E, et al. Aripiprazole, a novel atypical antipsychotic drug with unique and robust pharmacology. Neuropsychopharmacology. 2003;28(8): 1400–1411. 7. DeLeon A, Patel NC, Crismon ML. Aripiprazole: a comprehensive review of its pharmacology, clinical efficacy, and tolerability. Clin Ther. 2004;26(5):649–666. 8. Adan-Manes J, Garcia-Parajua P. Aripiprazole in combination with other antipsychotic drugs may worsen psychosis. J Clin Pharm Ther. 2009;34(2):245–246. 9. Takeuchi H, Remington G. A systematic review of reported cases involving psychotic symptoms worsened by aripiprazole in schizophrenia or schizoaffective disorder. Psychopharmacology (Berl). 2013;228(2):175–185. 10. Stahl SM. Antipsyhotic agents. Stahl's Essential Pychopharmacology-Neuroscientific Basis and Practical Applications. Cambridge: Cambridge University Press; 2008;327–451. 11. Martín-Ruiz R, Puig MV, Celada P, et al. Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism. J Neurosci. 2001;21:9856–9866. 12. Strakowski SM, Adler CM, Almedia J, et al. The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disord. 2012;14(4):313–325. 13. Ongür D, Jensen JE, Prescot AP, et al. Abnormal glutamatergic neurotransmission and neuronal-glial interactions in acute mania. Biol Psychiatry. 2008;64(8):718–726. 14. Comai S, Tau M, Pavlovic Z, et al. The psychopharmacology of aggressive behavior: a translational approach: part 2: clinical studies using atypical antipsychotics, anticonvulsants, and lithium. J Clin Psychopharmacol. 2012; 32(2):237–260. 15. Ishii D, Matsuzawa D, Kanahara N, et al. Effects of aripiprazole on MK-801-induced prepulse inhibition deficits and mitogen-activated protein kinase signal transduction pathway. Neurosci Lett. 2010;471(1):53–57.
2. Roessner V, Schoenefeld K, Buse J, et al. Pharmacological treatment of tic disorders and Tourette Syndrome. Neuropharmacology. 2013;68:143–149.
16. Findling RL, Nyilas M, Forbes RA, et al. Acute treatment of pediatric bipolar 1 disorder, manic or mixed episode, with aripiprazole: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2009;70(10):1441–1451.
3. Kirino E. Efficacy and safety of aripiprazole in child and adolescent patients. Eur Child Adolesc Psychiatry. 2012;21(7):361–368.
17. Donohue A. First manic episode in a 55-year-old man after initiation of aripiprazole. Psychiatry (Edgmont). 2010;7(4):37–39.
4. Yoo HK, Joung YS, Lee JS, et al. A multicenter, randomized, double-blind, placebo-controlled study of aripiprazole in children and adolescents with Tourette's disorder. J Clin Psychiatry. 2013;74(8):e772–e780.
18. Robertson MM. Mood disorders and Gilles de la Tourette's syndrome: an update on prevalence, etiology, comorbidity, clinical associations, and implications. J Psychosom Res. 2006;61(3):349–358.
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.psychopharmacology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
351
Letters to the Editors 10. Suzuki E, Nakai D, Yamamura N, et al. Inhibition mechanism of carbapenem antibiotics on acylpeptide hydrolase, a key enzyme in the interaction with valproic acid. Xenobiotica. 2011;41:958–963. 11. Bates D, Parkins M, Duggan K. Ertapenem-induced reduction in in valproate levels: case report and review of the literature. Can J Hosp Pharm. 2010;63:315–322.
Exacerbation of Tics After Combining Aripiprazole With Pimozide A Case With Tourette Syndrome To the Editors: ourette Syndrome (TS) is a neuropsychiatric disorder characterized by chronic motor and vocal tics, which have a waxing and waning course.1 There are many pharmacotherapeutic agents used in the treatment of tic disorders; antipsychotics are the drugs of choice.2 Although aripiprazole (ARI) is highly successful in treating positive symptoms in schizophrenia and manic symptoms in mania, and there is much data showing that tics are improved with ARI and its beneficial effect in tic disorders, it is mostly limited to case reports and open trials.2,3 Recently, Yoo et al4 reported that ARI was efficacious and safe in the short-term treatment of children and adolescents with TS when compared with placebo. We report an adolescent with TS whose tics were exacerbated after addition of ARI to pimozide.
T
CASE REPORT A 15-year-old male adolescent was first admitted to our child psychiatry unit 2 years ago because of his motor tics and attention problems. His motor tics were dominant in the shoulder and body. Furthermore, the patient himself and his family complained of marked impulsivity and aggression that led to serious problems in the family. He was born with induced vaginal delivery 10 days after the estimated birth date. His birth weight was 2500 g; he was discharged from the hospital 1 day after birth because he did not have any health problems. He had no history of hypoxia or jaundice. He was walking at his first birthday and speaking with short sentences when he was 2 years old. Tic problems were prevalent in his family history. His uncle had TS, his mother's uncle had motor tics, and his sister was diagnosed with Sydenham chorea. His health problems began with a seizure after a head trauma when he was 5 years old.
350
www.psychopharmacology.com
Since his electroencephalographic examination had confirmed epileptiform abnormality, he was treated with valproic acid. His cranial magnetic resonance imaging was normal. One year after the initiation of valproic acid, risperidone treatment was added by the child neurologist for his behavioral problems and impulsivity. He was diagnosed with attention-deficit/ hyperactivity disorder (ADHD) when he was 6 years old, and risperidone was replaced with methylphenidate. After an allergic reaction to methylphenidate, risperidone was started again at 1 mg/d. His motor tics began when he was 8 years old, including shoulder shrugging, neck stretching, and scraping his hand across the wall. There were no simultaneous vocal tics. He was hospitalized by the child neurologist for the differential diagnosis of motor tics from conversion, Sydenham chorea, and Wilson disease when he was 8 years old. His echocardiography, electrocardiography, brain magnetic resonance imaging, electroencephalography, serum ceruloplasmin levels, eye inspection for Wilson disease, antistreptolysin-O, and C-reactive protein were all normal, and he was discharged with a risperidone regimen for chronic motor tic disorder. He had used several medications including haloperidol, pimozide, and atomoxetine in intervals until his admission to our clinic. Because he had problems related to chronic motor tic disorder and ADHD in his first admission to our clinic, he was treated with imipramine at 50 mg/d and pimozide at 2 mg/d. Pimozide dose was titrated to 3 mg/d for the control of motor tics. Five months after the first admission, he described a depressive episode and sertraline at 50 mg/d was initiated after the cessation of imipramine. He was on sertraline at 50 mg/d and pimozide at 3 mg/d for 10 months when a hypomanic episode occurred. He was suffering from sleep problems, irritability, decrease in academic performance, and severe anger. He also started to quarrel with his teachers, which he had never done before. The sertraline regimen was stopped, and he was started on ARI at 2.5 mg/d. Ten days after the initiation of ARI, the severity of the tics increased and vocal tics emerged with new motor tics. His Yale Global Motor Tic Severity Scale5 score increased from 11 to 19 after the addition of ARI. His vocal tic severity score was determined as 10. Although his irritability, psychomotor agitation, and other hypomania symptoms improved, ARI was discontinued. The severity of motor tics declined to its previous level gradually in 7 days after the cessation of ARI. Although the severity of vocal tics decreased after the termination of ARI, his vocal tic throat
clearing continued with multiple motor tics, which confirmed the diagnosis of TS in addition to ADHD and bipolar disorder.
DISCUSSION Aripiprazole is a new generation antipsychotic drug that differs from other typical and atypical antipsychotics with its partial agonist action on dopamine D2 receptors, which is suggested to mediate its dopaminergic effect in hypodopaminergic conditions.6,7 Dopamine hypothesis for TS depends on an excess of nigrostriatal dopaminergic activity. Groups of striatal neurons are suggested to become abnormally active leading to dysinhibition of thalamocortical circuits in the pathogenesis of TS.1 Our patient was on pimozide treatment, a potent dopamine D2 receptor blocker, when ARI was added. It can be postulated that the exacerbation of tics was related to the partial agonistic effect of ARI on D2 receptors, which became prominent in the hypodopaminergic milieu of nigrostriatal pathways caused by pimozide. Aripiprazole has also been reported to worsen the psychotic symptoms, irritability, agitation, and aggression in patients diagnosed with schizophrenia and schizoaffective disorders when added to treatment regimen of dopamine antagonists with a high affinity for D2 and D3 receptors, and the D2 partial agonistic effect of ARI has been suggested to mediate this.8,9 Contrary to these reports, the hypomanic symptoms of our case improved whereas the severity of the tics were exacerbated. Several hypotheses can be proposed to explain this contradiction. First of all, it is known that ARI has functionally selective actions at different neuronal groups resulting from its unexpectedly robust pharmacological profile.6 Aripiprazole has a partial agonistic effect on 5HT1A and a partial antagonistic effect on 5HT2A receptors. Both of these receptors are found in large quantities in the prefrontal cortex.6 While 5HT1A receptors and 5HT2A receptors regulate dopamine release, they also regulate the glutamate system. 5HT1A receptors inhibit glutamate release and 5HT2A receptors stimulate the release of glutamate.10 Blockage of cortical 5HT2A receptors and functional 5HT1A receptor agonism are suggested to mediate the balance between excitatory and inhibitory inputs onto prefrontal pyramidal neurons.11 The neurobiological mechanism of mania is not definite yet, but the prefrontal cortex is suggested to play a central role in its pathophysiology.12 Not only dopamine but also other neurotransmitters, including glutamate, are suggested to play a role in the pathophysiology of mania.12,13 Although ARI does not directly affect the glutamatergic system, glutamatergic modulation through 5HT1A agonistic and 5HT2A antagonistic
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Journal of Clinical Psychopharmacology • Volume 35, Number 3, June 2015
actions of ARI might have mediated or contributed to the improvement of the hypomanic symptoms in our patient. Also, it can be postulated that different neurotransmitters and receptor systems might predominate in some patients with mania in relation to individual genetic differences. The binding properties of ARI on 5HT1A and 5HT2A receptors might also play a role in controlling aggression because several neurotransmitter systems, including dopaminergic, adrenergic, GABAergic, serotonergic, and glutamatergic mechanisms, are suggested to be related to aggression.14 Furthermore, Ishii et al15 reported that ARI may reverse MK-801– induced prepulse inhibition deficits through regulation of the mitogen-activated protein kinases pathway, a downstream signal transduction system that is common to both dopaminergic and N-methyl-D-aspartate systems. There are several possible mechanisms through which ARI might be effective on aggression, as mentioned previously.14 Secondly, this adolescent was hypomanic without any psychotic symptoms and the cases whose psychotic symptoms were exacerbated with ARI were all patients with schizophrenia and schizoaffective disorder.8 Aggression and/or agitation were all associated with psychotic symptoms such as delusions and hallucinations in these patients, suggesting psychotic agitation. The D2 receptor agonist action of ARI was considered to explain the worsening psychosis in these patients. Takeuchi and Remington suggested that there might be a small subgroup of patients with schizophrenia or schizoaffective disorder who are more liable to present with the exacerbation of psychotic symptoms and aggression if ARI is added to existing antipsychotic treatment.8 Furthermore, although ARI has been proven to be an effective antimanic agent, it also has been reported to precipitate a manic episode in certain patients.16,17 There might be some patients with individual genetic or environmental predisposing factors that make them prone to an unexpected response to ARI treatment. Finally, mood disorders are overrepresented among patients with TS.18 Although it is unclear why these 2 disorders frequently co-exist, dysfunctioning corticotstriatotalamocortical circuits exist in both of these disorders. Because ARI had paradoxical effects on the symptomathology of TS and bipolar disorder of the patient, it can be suggested that different neurotransmitter systems and receptors might predominate in the pathophysiology of these 2 disorders in cases where bipolar disorder and TS co-exist. In conclusion, ARI has a unique pharmacology that may mediate its selective effects in different disorders and comorbid situations. This is the first case report in
which ARI addition to a typical neuroleptic agent exacerbated motor tics and led to the emergence of vocal tics. We suggest that although ARI has promising effects on treatment of tics, clinicians should be cautious when combining it with potent antipsychotic agents. If ARI must be given in this regimen, it might be logical to combine it after an antipsychotic-free period when possible. This may not be practical in psychotic disorders but seems more logical for tic disorders, if the patient can continue with other psychiatric drug groups until the hypodopaminergic condition returns to its pretreatment levels. AUTHOR DISCLOSURE INFORMATION The authors have no conflicts of interest with any commercial or other associations and no financial ties to disclose in connection with the submitted article. This patient was presented in a poster presentation at the 6th International Congress on Psychopharmacology in Turkey, entitled “Exacerbation of Tics With Combining ARI to Pimozide: A Case With Tourette Syndrome.” The parents of the patient and the patient gave consent for this report to be published in the journal. Betül Mazlum, MD Department of Neuroscience Institute of Experimental Medical Research Istanbul University Istanbul, Turkey [email protected]
Sennur Zaimoğlu, MD Department of Child and Adolescent Psychiatry Institute for Neurological Sciences Marmara University Istanbul, Turkey
Didem Behice Öztop, MD Department of Child and Adolescent Psychiatry Faculty of Medicine Erciyes University Kayseri, Turkey
REFERENCES 1. Leckman JF, Bloch MH, Smith ME, et al. Neurobiological substrates of Tourette's disorder. J Child Adolesc Psychopharmacol. 2010;20(4):237–247.
Letters to the Editors 5. Leckman JF, Riddle MA, Hardin MT, et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry. 1989;28(4):566–573. 6. Shapiro DA, Renock S, Arrington E, et al. Aripiprazole, a novel atypical antipsychotic drug with unique and robust pharmacology. Neuropsychopharmacology. 2003;28(8): 1400–1411. 7. DeLeon A, Patel NC, Crismon ML. Aripiprazole: a comprehensive review of its pharmacology, clinical efficacy, and tolerability. Clin Ther. 2004;26(5):649–666. 8. Adan-Manes J, Garcia-Parajua P. Aripiprazole in combination with other antipsychotic drugs may worsen psychosis. J Clin Pharm Ther. 2009;34(2):245–246. 9. Takeuchi H, Remington G. A systematic review of reported cases involving psychotic symptoms worsened by aripiprazole in schizophrenia or schizoaffective disorder. Psychopharmacology (Berl). 2013;228(2):175–185. 10. Stahl SM. Antipsyhotic agents. Stahl's Essential Pychopharmacology-Neuroscientific Basis and Practical Applications. Cambridge: Cambridge University Press; 2008;327–451. 11. Martín-Ruiz R, Puig MV, Celada P, et al. Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism. J Neurosci. 2001;21:9856–9866. 12. Strakowski SM, Adler CM, Almedia J, et al. The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disord. 2012;14(4):313–325. 13. Ongür D, Jensen JE, Prescot AP, et al. Abnormal glutamatergic neurotransmission and neuronal-glial interactions in acute mania. Biol Psychiatry. 2008;64(8):718–726. 14. Comai S, Tau M, Pavlovic Z, et al. The psychopharmacology of aggressive behavior: a translational approach: part 2: clinical studies using atypical antipsychotics, anticonvulsants, and lithium. J Clin Psychopharmacol. 2012; 32(2):237–260. 15. Ishii D, Matsuzawa D, Kanahara N, et al. Effects of aripiprazole on MK-801-induced prepulse inhibition deficits and mitogen-activated protein kinase signal transduction pathway. Neurosci Lett. 2010;471(1):53–57.
2. Roessner V, Schoenefeld K, Buse J, et al. Pharmacological treatment of tic disorders and Tourette Syndrome. Neuropharmacology. 2013;68:143–149.
16. Findling RL, Nyilas M, Forbes RA, et al. Acute treatment of pediatric bipolar 1 disorder, manic or mixed episode, with aripiprazole: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2009;70(10):1441–1451.
3. Kirino E. Efficacy and safety of aripiprazole in child and adolescent patients. Eur Child Adolesc Psychiatry. 2012;21(7):361–368.
17. Donohue A. First manic episode in a 55-year-old man after initiation of aripiprazole. Psychiatry (Edgmont). 2010;7(4):37–39.
4. Yoo HK, Joung YS, Lee JS, et al. A multicenter, randomized, double-blind, placebo-controlled study of aripiprazole in children and adolescents with Tourette's disorder. J Clin Psychiatry. 2013;74(8):e772–e780.
18. Robertson MM. Mood disorders and Gilles de la Tourette's syndrome: an update on prevalence, etiology, comorbidity, clinical associations, and implications. J Psychosom Res. 2006;61(3):349–358.
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.psychopharmacology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
351
