TY - JOUR
AU - Repking,, Nicole
AB - Abstract Purpose The case of a patient taking high-dosage olanzapine who experienced parkinsonism after smoking cessation is reported. Summary A 73-year-old Caucasian woman with a recent diagnosis of Parkinson disease and a history of chronic obstructive pulmonary disease, hyperlipidemia, chronic osteoarthritis, and hypothyroidism was hospitalized for altered mental status, weakness, and ambulatory dysfunction. The diagnosis of Parkinson disease was made approximately four months prior. Despite initiation of carbidopa–levodopa, the patient’s symptoms did not improve, and her mental and physical status declined. The patient was taking olanzapine 30 mg daily for bipolar disorder and had a 40-pack-year history of smoking, but she quit smoking approximately four months before this hospitalization. The results of a neurologic evaluation suggested that the patient did not have Parkinson disease but was possibly experiencing olanzapine toxicity secondary to smoking cessation. Carbidopa–levodopa was discontinued. Psychiatry was consulted, and a monthlong cross-taper to discontinue olanzapine and initiate aripiprazole with a target dosage of 20 mg daily was recommended. During the course of therapy, the patient’s level of alertness and bradykinesia improved. Overall, it was noted that her extrapyramidal symptoms were gradually improving; two days before hospital discharge, she was noted to have no definite remaining evidence of parkinsonism. In this case, use of the Naranjo et al. adverse-drug-reaction probability scale and the drug interaction probability scale indicated that the adverse effects were probably related to the interaction between smoking and olanzapine. Conclusion A 73-year-old woman receiving high-dosage olanzapine for bipolar disorder developed parkinsonism after smoking cessation. Antipsychotic agents, Aripiprazole, Bipolar disorder, Carbidopa, Geriatrics, Levodopa, Olanzapine, Parkinsonian disorders, Smoking, Toxicity As an atypical antipsychotic, olanzapine is thought to have a favorable adverse-effect profile compared with first-generation antipsychotics, as it is less likely to cause extrapyramidal symptoms and tardive dyskinesia.1 Due to metabolic enzyme induction, diminished plasma concentrations of olanzapine have been reported in cigarette smokers.2 Despite this known interaction, few reports exist in the medical literature regarding changes in smoking status and resulting therapeutic effects in patients taking olanzapine. The exact effect of cigarette smoking on olanzapine levels is debatable; currently, no studies have examined the effects of smoking cessation on plasma olanzapine levels or olanzapine’s antipsychotic effects. Smokers have an estimated fivefold lower steady-state plasma olanzapine concentration than do nonsmokers, as the clearance of olanzapine is up to 98% greater in smokers.3 Based on this interaction, it has been recommended that prescribers increase the olanzapine dosage by 50–100% in patients who smoke.3,4 However, the drug’s package insert states that smoking increases olanzapine clearance by only 40% and does not recommend routine dosage increases in smokers.5 We report a probable case of olanzapine-induced parkinsonism resulting from high-dosage olanzapine therapy that was continued after smoking cessation. Case report A 73-year-old Caucasian woman with bipolar disorder who was recently diagnosed with Parkinson disease and movement disorder was admitted to our community hospital for altered mental status, weakness, and ambulatory dysfunction. Her medical history included chronic obstructive pulmonary disease, hyperlipidemia, chronic osteoarthritis, and hypothyroidism. Her medications (all given orally) included citalopram 20 mg daily, levothyroxine 100 μg daily, divalproex sodium 500 mg in the morning and 750 mg at bedtime, olanzapine 5 mg in the morning and 25 mg at bedtime, famotidine 10 mg three times daily as needed, and acetaminophen 300 mg with codeine 30 mg every four hours as needed. The patient also received inhaled albuterol two puffs every four hours as needed. The diagnosis of Parkinson disease had been made approximately four months before hospital admission, with decreasing functional capacity noted for the previous two months. Despite the initiation of carbidopa–levodopa, the patient’s symptoms did not exhibit much clinical improvement, and her mental and physical status had declined, including numerous falls and hallucinations. She had a 40-pack-year history of smoking but quit approximately four months before hospital admission. Approximately one week before her arrival at our hospital, she was evaluated by a neurologist, who concluded that she likely did not have Parkinson disease but could be experiencing extrapyramidal symptoms secondary to olanzapine use. Carbidopa–levodopa was discontinued at this time. At hospital admission, the patient was comfortable but a mental status examination showed her to be oriented only to her name and displayed poor immediate and delayed recall. The patient was a poor historian but denied fever, cough, sharp chest pain, and dysuria. She was noted to have a slight shuffling gait and mild bradykinesia. She denied alcohol or illicit drug use. Her valproic acid level was checked at admission and was within normal range, and repeated measures of these levels throughout her admission remained within therapeutic range. An evaluation by a neurologist, including a computed tomography scan of the patient’s head and an electroencephalogram, found no neurologic cause for the patient’s deficit. Based on the patient’s dose of olanzapine and her recent smoking cessation, olanzapine toxicity was considered. We proposed that cigarette smoking had reduced plasma olanzapine levels, causing an increase in the patient’s olanzapine requirement while actively smoking. Once the patient stopped smoking, the olanzapine dose was too high, leading to drug-induced parkinsonism (DIP). This theory was supported by the fact that her symptoms began shortly after she quit smoking. Psychiatry was consulted, and a monthlong cross-taper to discontinue olanzapine and initiate aripiprazole with a target dosage of 20 mg daily was recommended. The patient remained hospitalized for 11 days and reached an aripiprazole dosage of 15 mg daily. Olanzapine had been decreased to 5 mg daily with the intent to discontinue olanzapine within three weeks of discharge. During this cross-taper, the patient’s level of alertness improved, though she still had evidence of dementia. Her bradykinesia improved, though she continued to have some difficulty with gait and required the use of a walker. Her extrapyramidal symptoms gradually improved; 2 days before hospital discharge, she had no definite remaining evidence of parkinsonism. At discharge, the patient was placed in a nursing home to address her needs for physical and occupational therapy until she was able to return to her assisted-living facility. Discussion Olanzapine is extensively metabolized by direct N-glucuronidation; minor metabolic pathways include cytochrome P-450 (CYP) isoenzymes 1A2 and 2D6.2 Olanzapine’s pharmacokinetics is affected by many factors, including genetic variability, sex, smoking status, and drug interactions.2 Cigarette smoking produces polycyclic aromatic hydrocarbons due to incomplete combustion.3 These hydrocarbons are potent inducers of CYP1A2; thus, patients taking olanzapine who smoke tobacco products have decreased serum concentrations of the medication because of increased drug clearance. It is important to note that only the smoking of tobacco products will produce this effect; chewing tobacco does not produce polycyclic aromatic hydrocarbons. Potential toxicities with antipsychotics such as olanzapine include extrapyramidal symptoms that often resemble Parkinson disease. DIP is a potentially reversible condition that commonly causes parkinsonism in the elderly population. The actual prevalence of DIP is not known due to underrecognition and subsequent underreporting of DIP and a lack of epidemiologic studies focusing on DIP itself rather than the broader category of parkinsonism or drug-induced movement disorders.6 Janno et al.7 evaluated the frequency of movement disorders induced by neuroleptic agents among 99 institutionalized patients with schizophrenia and found that 23.2% had neuroleptic-induced parkinsonism. A definitive diagnosis of DIP is elusive, which can lead to a misdiagnosis of Parkinson disease and unnecessary treatment with antiparkinson drugs.6 One case–control study found that, compared with nonusers, patients treated with neuroleptics were roughly five times more likely to receive initial treatment with antiparkinson medications and had a more than twofold increased risk of beginning therapy with a dopaminergic agent for idiopathic Parkinson disease.8 A detailed medication history is crucial for diagnosing DIP; special consideration should be given to those agents most commonly implicated in DIP, including typical and some atypical antipsychotics, antiemetic agents, and certain anti-depressants and anticonvulsants.6,9 Antipsychotics are commonly implicated in DIP due to their inhibition of dopamine transmission. While atypical antipsychotics (e.g., olanzapine) are thought to have a lower risk of causing extrapyramidal symptoms compared with typical antipsychotics, DIP with these agents, particularly at high dosages, has been reported.6 The risk of DIP is greater in older patients and women; other risk factors include preexisting movement disorder, dementia, human immunodeficiency virus infection, and familial Parkinson disease.6,9 DIP is usually characterized by bilateral and symmetrical symptoms and has a subacute onset.6,9 Neuroleptic-induced DIP may be characterized by concurrent orofacial and limb dyskinesia, akathisia, and perioral tremor.6 These characteristics may help clinicians distinguish between Parkinson disease and DIP. A 2004 case report illustrated the effects of increased cigarette smoking in a 30-year-old man with schizophrenia treated with olanzapine.2 The authors described a decrease in olanzapine levels that correlated with an increased number of cigarettes smoked per day, consistent with findings that the CYP1A2-inducing effect of smoking appears to be dose dependent. The patient’s psychotic symptoms worsened when he suddenly and dramatically increased his cigarette consumption. Zullino et al.10 reported the case of a 25-year-old man with bipolar disorder who was a known smoker of cigarettes and cannabis. Olanzapine 30 mg orally daily was initiated; after five weeks of olanzapine treatment, the patient decided to reduce his daily smoking from 40 to 10 cigarettes. He subsequently developed a parkinsonism syndrome with hallmark symptoms. After his olanzapine dosage was reduced to 20 mg daily, the patient’s symptoms improved. Our patient’s risk factors for DIP included her age, sex, and high-dose atypical antipsychotic use. Although she was taking divalproex sodium, this was felt to be an unlikely cause of DIP in this patient because of her therapeutic drug levels. Her symptoms were more likely caused by high-dosage olanzapine. After successful smoking cessation, the subsequent lack of enzyme induction may have led to excessive levels of olanzapine, resulting in toxicity. We did not obtain olanzapine levels to aid in the diagnosis but made the diagnosis based on clinical suspicion. The Naranjo et al.11 causality scale for adverse drug reactions indicated a probable correlation between olanzapine and parkinsonism in this patient (score = 5). Use of the drug interaction probability scale yielded a score of 7, indicating a probable drug interaction, with olanzapine as the object drug and cigarette smoking as the precipitant.12 This case illustrates the need for awareness of the impact of cigarette smoking on medications such as olanzapine. The number of cigarettes smoked daily should be assessed at each health care provider visit for patients who smoke and take medications commonly associated with DIP. Changes in smoking status or significant changes in the number of cigarettes smoked per day may necessitate increased monitoring and possible dosage adjustment. Conclusion A 73-year-old woman receiving high-dosage olanzapine for bipolar disorder developed parkinsonism after smoking cessation. Footnotes The authors have declared no potential conflicts of interest. References 1 Volavka J Czobor P Sheitman B et al. . Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder . Am J Psychiatry 2002 ; 259 : 255 – 62 . Google Scholar Crossref Search ADS WorldCat 2 Chiu C Lu M Huang M et al. . Heavy smoking, reduced olanzapine levels, and treatment effects . Ther Drug Monit 2004 ; 26 : 579 – 81 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Kroon L . Drug interactions with smoking . Am J Health-Syst Pharm 2007 ; 64 : 1917 – 21 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Gex-Fabry M Balant-Gorgia A Balant L . Therapeutic drug monitoring of olanzapine: the combined effect of age, gender, smoking, and comedication . Ther Drug Monit 2003 ; 25 : 46 – 53 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Zyprexa (olanzapine) package insert Indianapolis : Eli Lilly and Company ; 2009 . WorldCat COPAC 6 Thanvi B Treadwell S . Drug induced parkinsonism: a common cause of parkinsonism in older people . Postgrad Med J 2009 ; 85 : 322 – 6 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Janno S Holi M Tuisku K et al. . Prevalence of neuroleptic-induced movement disorders in chronic schizophrenia inpatients . Am J Psychiatry 2004 ; 161 : 160 – 3 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Avorn J Bohn RL Mogun H et al. . Neuroleptic drug exposure and treatment of parkinsonism in the elderly: a case-control study . Am J Med 1995 ; 99 : 48 – 54 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Gershanik OS . Drug-induced parkinsonism in the aged: recognition and prevention . Drugs Aging 1994 ; 5 : 127 – 32 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Zullino DF Delessert D Eap CB et al. . Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or olanzapine . Int Clin Psychopharmacol 2002 ; 17 : 141 – 3 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Naranjo CA Busto U Sellers EM et al. . A method for estimating the probability of adverse drug reactions . Clin Pharmacol Ther 1981 ; 30 : 239 – 45 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Horn J Hanston P Chan L . Proposal for a new tool to evaluate drug interaction cases . Ann Pharmacother 2007 ; 41 : 674 – 80 . Google Scholar Crossref Search ADS PubMed WorldCat Copyright © 2011, American Society of Health-System Pharmacists, Inc. All rights reserved.
TI - Olanzapine-induced parkinsonism associated with smoking cessation
JF - American Journal of Health-System Pharmacy
DO - 10.2146/ajhp100258
DA - 2011-03-01
UR - https://www.deepdyve.com/lp/oxford-university-press/olanzapine-induced-parkinsonism-associated-with-smoking-cessation-MOu7AgkJWV
SP - 399
VL - 68
IS - 5
DP - DeepDyve
ER -