Aripiprazole Induced Akathisia with Parkinsonism

• A case series

Pallav Pareek M.D.

Background

• SGA’s* are being increasingly prescribed1

• Aripiprazole is considered 3rd generation (different MOA from other SGA’s)

• Partial DA agonist• Agonist at 5HT1A• Antagonist at 5HT2A• Metabolized via the CYP2D6 & CYP3A4

1: Cáceres MC, Peñas-Lledó EM, de la Rubia A, Llerena A. Increased use of second generation antipsychotic drugs in primary care: potential relevance for hospitalizations in schizophrenia patients. Eur J Clin Pharmacol. 2008 Jan;64(1):73-6.

Aripiprazole: one of the safer medications?

• Akathisia is frequent but EPS with parkinsonism is rare

• Extra Pyramidal Side-effects 16% are comparable to Placebo 14%2 when Schizophrenia and Schizoaffective disorder were the primary diagnoses.

• Previous trials have consistently demonstrated the incidence of EPS to be comparable to placebo 3

2: Kane JM, Barnes TR, Correll CU, Sachs G, Buckley P, Eudicone J, McQuade R, Van Tran Q, Pikalov A 3rd, Assunção-Talbott S: Evaluation of akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder: a post hoc analysis of pooled data from short- and long-term aripiprazole trials. J Psychopharmacol. . [Epub ahead of print]

3. Gupta, S, Masand, P: Aripiprazole: review of its pharmacology and therapeutic use in psychiatric disorders. Ann Clin Psychiatry 2004;16: 155–166.

Previous Case Reports• Citing adverse effects

1. Maytal et al 20064 reported the development of Tardive dyskinesia with 9 mo therapy

2. Sajbel et al 20055 reported lingual dyskinesia3. Sharma6, and Lua7 et al at different times have reported

Parkinsonism4. Zacher et al 20068 reported combination of lingual dyskinesia

and parkinsonism

4: Maytal G, Ostacher M, Stern TA: Aripiprazole-related tardive dyskinesia. CNS Spectr. 2006;11(6):435-95: Sajbel TA, Cheney EM, DeQuardo JR: Aripiprazole-associated dyskinesia. Ann Pharmacother. 2005;39:200-16: Sharma A, Sorrell JH: Aripiprazole-induced Parkinsonism: Int Clin Psychopharmacol 2006;21:127-297: Lua LL, Zhang L. Development of Parkinsonism following exposure to aripiprazole: two case reports: J Med Case Reports.

2009 Mar 10;3:6448.8: Zacher JL, Hatchett AD. Aripiprazole-induced movement disorder. Am J Psychiatry. 2006;163:160–161.

Previous Reports : contd:

• As Rx for adverse effects

1. Duggal et al 20039 reported resolution of haloperidol induced EPS.

2. Chen et al in 200910 reported improvement in risperidone related tardive parkinsonism.

9: Duggal: Aripiprazole-induced improvement intardive dyskinesia. Can J Psychiatry 2003;48:771-2.

10: Chen CK, Wu JH: Improvement of risperidone related tardive parkinsonism with a switch to aripiprazole : Prog Neuropsychopharmacol Biol Psychiatry, 2009;33: 1279-80

CASE REPORT : Patient #1

1. GR is a 20 y/o CM with velo-cardio-facial syndrome

2. Congenital heart condition: interrupted aortic arch with VSD

3. No previous psychiatric hx

4. No family psych hx

Patient 1 Contd:

• Referred by his neurologist, with one year hx of auditory hallucinations: increased with stress and lack of sleep, alleviated with rest and sleep.

• No paranoia, delusions, or other s/s of psychosis.• Dose 5 →15 mg QHS, developed akathisia, stiff

muscles, and mask like facies• Aripiprazole d/c, started Benztropine 1 mg BID• Prompt resolution of the Extrapyramidal symptoms• Currently maintained on 5 mg QHS, and 7.5 mg QHS on

alternate days. No active symptoms, and no S/E reported at the time compilation of this report

Patient #2

• LG is a 28 y AAF

• 9 year history of Bipolar disorder NOS

• First psychiatric admission at age19 with acute mania, subsequently multiple admissions in and around Detroit

• Past medications included neuroleptic medications including depot neuroleptics

• 6 mo Hx of noncompliance and symptom free period one week prior to being seen at the clinic

Patient 2 Hx Contd:

• Developed Paranoia, delusions of persecution, and auditory hallucinations.

• No agreeable to any other antipsychotic• Started 5 →30 mg PO QDAY• 3rd Wk of her Rx started exhibiting anxiety and

akathisia progressing onto muscle stiffness, pill rolling tremor and cogwheel rigidity

• Benztropine → resolution of EP symptoms within hours.

• Continues to be stable on 20 mg QHS. No EPS

Patient #3

• 25 yo CM with a diagnosis of Cannabis induced psychotic disorder (abusing since age 14)

• Psychotic Sx started with AH and proceeding to frank psychosis with Paranoia towards family and neighbors & delusions. Pt seen after 2 mo of symptoms.

• 5→30 mg QD.• Subjective restlessness, not reported

Patient 3 Hx Contd:

• Later developed muscle stiffness, cogwheel rigidity and mask like facies.

• Brought himself, administered Benztropine, prompt resolution of symptoms

• Later Benztropine was d/c • Currently maintained on 10 mg QDAY.• Continues to be Sx and S/E free at the time of

this report.

Conclusions

• This report describes the emergence of EPS and Akathisia with the trial of ARI.

• The absence of EPS before aripiprazole, no concurrent antipsychotic, temporal difference from the administration of another antipsychotic, and resolution of the symptoms with the administration of anticholinergic medication, points towards the EPS and Akathisia as s/e of ARI.

• A recent case report by Lungu et al 2009 11 reported TD in patients with a diagnosis of PTSD and Fragile X syndrome

• The evolution of the EPS was also atypical in all three cases: beginning with anxiety and Akathisia & gradually evolving into Parkinsonian symptoms

11: Lungu C, Aia PG, Shih LC, Esper CD, Factor SA, Tarsy D: Tardive dyskinesia due to aripiprazole: report of 2 cases.. J Clin Psychopharmacol. 2009 Apr;29(2):185-6.

Conclusions Contd:

• Prescribers need to exercise caution while prescribing ARI because

1. Considered a relatively safe medication2. Very few reported Extrapyramidal s/e in

literature3. Often used as an augmentation agent4. EPS is more frequent in atypical

presentation

Possible preventive measures

• Need to monitor medication schedule

• Patients should be educated

• Monitor the emergence of side effects

• Should be promptly reported to Physicians

QUESTIONS ????