TARDIVE DYSKINESIA WITH ARIPIPRAZOLE - – A CASE REPORT Ijmas 558
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This case report describes a 46-year-old woman who developed tardive dyskinesia after taking the atypical antipsychotic aripiprazole for 10 months to treat schizophrenia. She began experiencing involuntary orofacial movements. While aripiprazole is generally considered to have a low risk of tardive dyskinesia, this case suggests it may cause the condition in some patients, especially those with risk factors like longer treatment duration. The report adds to limited evidence that aripiprazole can potentially induce tardive dyskinesia and cautions doctors to monitor patients carefully when prescribing it long-term.
![INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES
E-ISSN:2320-3137
www.earthjournals.org Volume 3, Issue 4, 2014
129
not be attributed to the use of any other medications in the regime.Controversy does not cease
to exist as regarding the use of aripiprazole both for and against as regards to treatment of
tardive dyskinesia. Nearly all of the published data is in the form of case reports. We then
conducted a literature review of aripiprazole-induced TD. Zacher and Hatchett (2006) used
aripiprazole 20 mg to treat a case of bipolar illness. Pseudoparkinsonism ensued soon after
starting the drug, and rabbit syndrome (characterized by rhythmic movements of the mouth)
was considered to be a dystonic event but not necessarily TD15
Sajbel and Evcimen and their colleagues16,17
reported two
cases of aripiprazole-induced TD in two patients,both being cases of schizo -affective
disorder. Both patients were receiving 20 mg/day. After 10 days of discontinuing
aripiprazole in one of the patients,his abnormal tongue movements ceased.
In other case reports, aripiprazole was used to treat and alleviate TD induced by other
neuroleptic agents in patients with bipolar and schizo-affective illnesses. It is difficult to
determine whether aripiprazole acted as a treatment or whether stopping the previous higher-
potency neuroleptic agent allowed the remission of TD18-21
.
Risk of TD with aripiprazole can be explained by one probable mechanism as has
been proposed by recent studies as regards to its ‘functionally selective’ action at the D2
receptors.It can act as an agonist or partial agonist or even an antagonist on the D2 receptors
depending on the cellular milieu22
.This property of aripiprazole may result in it behaving as
potent first generation antipsychotics with blockade of upto 90 percent of D2 receptors23
.But
still though,which strata of the aripiprazole receiving patients are at a potential risk of
developing TD is still a matter that can only be disclosed by further research.In our case of
Mrs JS,she fulfils the aforementioned risk factors of developing TD i.e female gender and
long antipsychotic treatment duration.This report suggests that physicians should be alert and
observant enough when starting on Aripiprazole in a patient with stated risk factors.
REFERENCES
1. Al Hadithy AF, Ivanova SA, Pechlivanoglou P, Semke A, Fedorenko O, Kornetova E, et al.
Tardivedyskinesia and DRD3, HTR2A and HTR2C gene polymorphisms in Russian psychiatric
inpatients from Siberia. Prog Neuropsychopharmacol Biol Psychiatry. Apr 30 2009;33(3):475-81.
[Medline].
2. Liou YJ, Lai IC, Liao DL, Chen JY, Lin CC, Lin CY, et al. The human dopamine receptor D2 (DRD2)
gene is associated with tardive dyskinesia in patients with schizophrenia. Schizophr Res. Sep
2006;86(1- 3):323-5. [Medline].
3. Bakker PR, van Harten PN, van Os J. Antipsychotic-induced tardive dyskinesia and the Ser9Gly
polymorphism in the DRD3 gene: a meta analysis. Schizophr Res. Apr 2006;83(2-3):185-92.
[Medline].
4. Lafuente A, Bernardo M, Mas S, Crescenti A, Aparici M, Gassó P, et al. Dopamine transporter (DAT)
genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics. Schizophr
Res. Feb 2007;90(1-3):115-22. [Medline].
5. Galecki P, Pietras T, Szemraj J, Florkowska K, Florkowski A, Zboralski K. [Functional polymorphism
of manganese superoxide dismutase (MnSOD) gene correlates with schizophrenia in Polish
population]. Pol Merk ur Lek arsk i. Mar 2006;20(117):329-32. [Medline].
6. Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of aripiprazole as adjunctive
therapy in major depressive disorder : A multicenter, randomized, double-blind, placebo-controlled
study. J Clin Psychiatry 2007;68(6):843–853.
7. Papakostas GI, Shelton RC, Smith J, Fava M. Augmentation of antidepressants with atypical
antipsychotic medications for treatment- resistant major depressive disorder: A meta-analysis. J Clin
Psychiatry 2007;68(6):826–831.
8. Seeman P. An update of fast-off dopamine D2 atypical anti -psychotics. Am J Psychiatry
2005;162:1984–1985.](https://image.slidesharecdn.com/ijmas558-180626161059/85/TARDIVE-DYSKINESIA-WITH-ARIPIPRAZOLE-A-CASE-REPORT-Ijmas-558-3-320.jpg)
TARDIVE DYSKINESIA WITH ARIPIPRAZOLE - – A CASE REPORT Ijmas 558
- 1. INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES E-ISSN:2320-3137 www.earthjournals.org Volume 3, Issue 4, 2014 127 Case Report TARDIVE DYSKINESIA WITH ARIPIPRAZOLE - – A CASE REPORT Dhrubajyoti Bhuyan1 , Partha Pratim Saikia2 1. Assistant Professor, 2. Post Graduate Trainee Department of Psychiatry, Assam Medical College, Dibrugarh, Assam. Corresponding Author: Dr.Dhrubajyoti Bhuyan,Assistant professor,Department Of Psychiatry,Assam Medical College,Dibrugarh,Assam. Abstract : Aripiprazole,a novel antipsychotic agent is the latest addition to the class of atypical antipsychotics. It is a partial dopamine agonist and has been advocated for treatment of many psychiatric disorders including schizophrenia, bipolar affective disorder, irritability associated with autism and as an augmentation therapy for Major Depressive disorder. This drug is known for its minimal extrapyramidal side effects. Till now, aripiprazole has been regarded as a relatively safe agent when it comes to the risk of developing TD. Rather on the contrary, aripiprazole is known to have been used as a treatment of tardive dyskinesia. Here, in the case report that follows, we document a case of a 46 year old lady developing tardive dyskinesia manifesting as involuntary orofacial movements after continuous use of the drug in the dose of 15 mg once daily for 10 months. Key words: Aripiprazole, Tardive Dyskinesia, Schizophrenia INTRODUCTION Tardive dyskinesia is a syndrome characterized by abnormal involuntary movements, typically involving the orofacial region, limbs, and trunk. Essential features of tardive dyskinesia include involuntary movements of the tongue, face, and jaw. Though most Tardive dyskinesia cases are mild, severe oral dyskinesia may result in dental and denture problems that can progress to ulceration and infection of the mouth as well as muffled or unintelligible speech. Also, gait disturbances due to limb dyskinesia may leave patients vulnerable to falls and injuries. Traditionally,first generation antipsychotics are considered to have higher risk of Tardive Dyskinesia when used in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Also,they occasionally occur in other patients,as people with fetal alcohol syndrome, developmental disabilities, and other brain disorders as well. Risk factors of TD include increasing age, preexisting parkinsonism, previous brain damage, antipsychotic treatment duration, and exposure to FGAs. TD has been associated with polymorphisms of both the dopamine receptor D2 (DRD2) gene1 , TaqI A and TaqI B and associated haplotypes2 , and of the dopamine receptor D3 (DRD3) gene1,3 , the dopamine transporter(DAT) gene, and the manganese superoxide dismutase (MnSOD) gene. It was also proposed that a dysfunction of the dopamine transporter is responsible for causing tardive dyskinesia. However, no evidence of involvement of a polymorphism with a variable number of tandem repeats(VNTD) in the DAT gene (SLC6A3) in dyskinesias induced by antipsychotics could be associated by a
- 2. INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES E-ISSN:2320-3137 www.earthjournals.org Volume 3, Issue 4, 2014 128 research done by Lafuente et al.4 Thus, further research is needed to investigate the role of the dopamine transporter in the development and maintenance of TD.Galecki et al reported the possibility of a polymorphism of the manganese superoxide dismutase (MnSOD) gene behind causation of TD.5 With the advent of the second-generation (atypical) anti-psychotic agents (SGAs), all of which utilize a serotonin-2 receptor (5-HT2) blockade, the risk of TD has apparently decreased, thereby allowing clinicians to treat schizophrenia with less possibility of a side- effect burden. The off-label use of SGAs also continues to increase in the form of augmented therapies for resistant depression and anxiety6,7 . In fact, the FDA recently approved aripiprazole as the first augmentation (add-on) strategy for the treatment of unipolar major depression. At a therapeutic dose, it is noteworthy that aripiprazole has one of the highest D2 receptor affinities; however, because of its partial agonist properties, it has a lower risk of causing acute EPS and, probably, TD.8-11 Till now, aripiprazole has been regarded as a relatively safe agent when it comes to the risk of developing TD. In fact few have reported aripiprazole to be therapeutic for TD. However, by contrast, there is slowly increasing published data which associates aripiprazole with TD.12-14 CASE Mrs J. S.,a 46 yr old married female from Amolapatty ,Dibrugarh came to our hospital(ASSAM MEDICAL COLLEGE,DIBRUGARH),on 28/07/2012 with the chief complaints of disturbed sleep,suspiciousness,fearfulness and irrelevant talking for a duration of 6 months. She had history of similar illness in the past. The significant findings during her Mental Status Examination were delusion of reference,delusion of persecution, and auditory hallucinations. She was diagnosed as a case of schizophrenia paranoid type and so was prescribed TAB ARIPIPRAZOLE 15 mg once daily at bed time and TAB TRIHEXYPHENIDYL 2mg in the morning. In her next visit on 01/09/2012,her symptoms had improved and she was directed to continue the same treatment.Mrs sonowal was maintaining well on the same treatment until she came to our OPD having developed symptoms of chewing movements around the lips on 25/05/2013.She was complaining of orofacial involuntary movements for the past one month.she was prescribed tab vitamin E 800 mg after which she showed improvement.She maintained well for a year without reccurence of symptoms and revisited the OPD with complaints of the orofacial movements having started again for the past 2 weeks.She was prescribed tab Tetrabenzene 25 mg for two days and then subsequently increased to 50 mg in two divided doses as maintenance dose.When she was reviewed on 12/07/2014 ,she had improved much and was maintaining well. DISCUSSION The case that we discussed above is a clear example of new-onset oromandibular TD arising during the use of the atypical neuroleptic agent aripiprazole when used at the time for treating schizophrenia in this middle aged woman. A few important observations did not go unnoticed in the above described patient. First, above patient was antipsychotic medications naïve till she took aripiprazole although she had a similar type of illness in the past . Second, she developed classical TD like abnormal involuntary movements in the orofacial region within 10 months of starting therapy with aripiprazole 15 mg.The symptoms moreover could
- 3. INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES E-ISSN:2320-3137 www.earthjournals.org Volume 3, Issue 4, 2014 129 not be attributed to the use of any other medications in the regime.Controversy does not cease to exist as regarding the use of aripiprazole both for and against as regards to treatment of tardive dyskinesia. Nearly all of the published data is in the form of case reports. We then conducted a literature review of aripiprazole-induced TD. Zacher and Hatchett (2006) used aripiprazole 20 mg to treat a case of bipolar illness. Pseudoparkinsonism ensued soon after starting the drug, and rabbit syndrome (characterized by rhythmic movements of the mouth) was considered to be a dystonic event but not necessarily TD15 Sajbel and Evcimen and their colleagues16,17 reported two cases of aripiprazole-induced TD in two patients,both being cases of schizo -affective disorder. Both patients were receiving 20 mg/day. After 10 days of discontinuing aripiprazole in one of the patients,his abnormal tongue movements ceased. In other case reports, aripiprazole was used to treat and alleviate TD induced by other neuroleptic agents in patients with bipolar and schizo-affective illnesses. It is difficult to determine whether aripiprazole acted as a treatment or whether stopping the previous higher- potency neuroleptic agent allowed the remission of TD18-21 . Risk of TD with aripiprazole can be explained by one probable mechanism as has been proposed by recent studies as regards to its ‘functionally selective’ action at the D2 receptors.It can act as an agonist or partial agonist or even an antagonist on the D2 receptors depending on the cellular milieu22 .This property of aripiprazole may result in it behaving as potent first generation antipsychotics with blockade of upto 90 percent of D2 receptors23 .But still though,which strata of the aripiprazole receiving patients are at a potential risk of developing TD is still a matter that can only be disclosed by further research.In our case of Mrs JS,she fulfils the aforementioned risk factors of developing TD i.e female gender and long antipsychotic treatment duration.This report suggests that physicians should be alert and observant enough when starting on Aripiprazole in a patient with stated risk factors. REFERENCES 1. Al Hadithy AF, Ivanova SA, Pechlivanoglou P, Semke A, Fedorenko O, Kornetova E, et al. Tardivedyskinesia and DRD3, HTR2A and HTR2C gene polymorphisms in Russian psychiatric inpatients from Siberia. Prog Neuropsychopharmacol Biol Psychiatry. Apr 30 2009;33(3):475-81. [Medline]. 2. Liou YJ, Lai IC, Liao DL, Chen JY, Lin CC, Lin CY, et al. The human dopamine receptor D2 (DRD2) gene is associated with tardive dyskinesia in patients with schizophrenia. Schizophr Res. Sep 2006;86(1- 3):323-5. [Medline]. 3. Bakker PR, van Harten PN, van Os J. Antipsychotic-induced tardive dyskinesia and the Ser9Gly polymorphism in the DRD3 gene: a meta analysis. Schizophr Res. Apr 2006;83(2-3):185-92. [Medline]. 4. Lafuente A, Bernardo M, Mas S, Crescenti A, Aparici M, Gassó P, et al. Dopamine transporter (DAT) genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics. Schizophr Res. Feb 2007;90(1-3):115-22. [Medline]. 5. Galecki P, Pietras T, Szemraj J, Florkowska K, Florkowski A, Zboralski K. [Functional polymorphism of manganese superoxide dismutase (MnSOD) gene correlates with schizophrenia in Polish population]. Pol Merk ur Lek arsk i. Mar 2006;20(117):329-32. [Medline]. 6. Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder : A multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2007;68(6):843–853. 7. Papakostas GI, Shelton RC, Smith J, Fava M. Augmentation of antidepressants with atypical antipsychotic medications for treatment- resistant major depressive disorder: A meta-analysis. J Clin Psychiatry 2007;68(6):826–831. 8. Seeman P. An update of fast-off dopamine D2 atypical anti -psychotics. Am J Psychiatry 2005;162:1984–1985.
- 4. INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES E-ISSN:2320-3137 www.earthjournals.org Volume 3, Issue 4, 2014 130 9. Seeman P, Tallerico T. Antipsychotic drugs which elicit little or no Parkinsonism bind more loosely than dopamine to brain D2 receptor, yet occupy high levels of these receptors. Mol Psychiatry 1998;3:123–134. 10. Lublin H, Eberhard J, Levander S. Current therapy issues and unmet clinical needs in the treatment of schizophrenia: A review of the new generation antipsychotics. Int Clin Psychopharmacol.2005;20:183– 198. 11. Grunder G, Carisson A, Wong DF. Mechanism of new anti - psychotic medications: Occupancy is not just antagonism. Arch Gen Psychiatry 2003;60:974–977. 12. Hall DA, Agarwal P, Griffith A, Segro V, Seeberger LC. Movement disorders associated with aripiprazole use: a case series. Int J Neurosci 2009;119:2274-2279. 13. Peña MS, Yaltho TC, Jankovic J. Tardive dyskinesia and other movement disorders secondary to aripiprazole. Mov Disord 2011;26:147-152. 14. Wang LJ, Ree SC, Chen CK. Courses of aripiprazole associated tardive dyskinesia: report of two cases. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:743-744. 15. Zacher JL, Hatchett AD. Aripiprazole-induced movement disorder. Am J Psychiatry 2006;163(1):160– 161. 16. Sajbel TA, Cheney EM, DeQuardo JR. Aripiprazole-associated dyskinesia. Ann Pharmacother 2005;39(1):200–201. 17. Evcimen YA, Evcimen H, Holland J. Aripiprazole-induced tardive dyskinesia: The role of tamoxifen. Am J Psychiatry 2007;164(9): 1436–1437. 18. Grant MJ. Baldessarini RJ. Possible improvement of neurolepticassociated tardive dyskinesia during treatment with aripiprazole. Ann Pharmacother 2005;39(11):1953. 19. Witschy JK, Winter AS. Improvement in tardive dyskinesia with aripiprazole use. Can J Psychiatry 2005;50(3):188. 20. Duggal HS. Aripiprazole-induced improvement in tardive dys kinesia. Can J Psychiatry 2003;48(11):771–772. 21. Rizos E, Douzenis A, Gournellis R. Tardive dyskinesia in a patient treated with quetiapine. World J Biol Psychiatry 2007;1–4 (electronic version). Available at: www.informaworld.com/smpp/ title~content=t713721967~db=all. Accessed December 3, 2007. 22. Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu LX, Sibley DR, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology.Neuropsychopharmacology 2003;28:1400-1411. 23. Mace S, Taylor D. Aripiprazole: dose-response relationship in schizophrenia and schizoaffective disorder. CNS Drugs 2009;23:773-780.