WASHINGTON — Even neurologists are missing the diagnosis of drug-induced parkinsonism, according to an informal study of patients at one movement disorder clinic presented at the World Parkinson Congress.

Overall 8% (23 of 304 patients) of all cases of new patients with parkinsonian symptoms seen at the Emory University movement disorders clinic between January 2004 and January 2006 were diagnosed with drug-induced parkinsonism (DIP), said Dr. Stewart A. Factor, director of the movement disorders program at Emory University.

The age at diagnosis ranged between 49 and 97 years; the age at onset ranged between 48 and 96 years. Patients were predominantly female (73%). Records were available for 22 patients with DIP.

“Seventeen of the 22 patients had been seen previously by neurologists, and yet only 2 of them were diagnosed with drug-induced parkinsonism,” said Dr. Factor. Of these, 10 were misdiagnosed with Parkinson's disease (PD) and were treated with antiparkinsonian drugs. Seven patients had no clear diagnosis.

DIP, defined by Dr. Factor to include tardive dyskinesia, is misdiagnosed frequently; it has been estimated variously that only 1 in 16 cases and 2 in 12 patients with DIP are correctly diagnosed. “What I'm seeing is that even neurologists are missing this diagnosis.”

The older, conventional antipsychotic drugs have been most commonly associated with DIP. It has been assumed that the risk of DIP was reduced with the introduction of atypical antipsychotic drugs. However, Dr. Factor's experience has been just the opposite. Only three patients in his clinic developed DIP in response to typical antipsychotics (haloperidol, trifluoperazine, and amoxapine). In contrast, 12 cases were caused by atypical antipsychotics (3 from risperidone, 6 from olanzapine, 1 from ziprasidone, and 2 from aripiprazole). Five cases were caused by metoclopramide and two were caused by drug combinations (metoclopramide/reserpine, metoclopramide/ziprasidone).

In terms of clinical features, 11 patients had tardive dyskinesia (including 5 with respiratory dyskinesia), 2 had akathisia, 19 had tremor (17 with resting tremor and 6 with asymmetric tremor, alone or in combination), and 3 had akinetic rigidity. Clinically, 11 patients had psychiatric diagnoses—primarily mood disorders (9 patients)—and 6 patients had neurologic diagnoses (dementia, Huntington's chorea, hydrocephalus). Of the 13 patients who stopped the drug and returned for follow-up, 12 showed an improvement in symptoms within about 6 months. DIP has a subacute onset and all of the cardinal features of Parkinson's disease—tremor, rigidity, bradykinesia, and abnormalities of posture, gait, and balance—can be seen. Akinetic rigidity (without tremor) is seen in more than half of patients with DIP. Drug-use history and tardive dyskinesia appear to be key to the differential diagnosis.

Several other factors can also help differentiate DIP from PD, including subacute onset, bilateral features, more postural tremor than resting tremor, and the presence of other extrapyramidal signs.

Among psychiatric patients, 90% of DIP cases have their onset in the first 3 months of drug use or within 3 months of a dosage increase. The condition may reverse spontaneously, though this is rare. The condition may also be chronic and progressive. Most importantly, withdrawal of the drug does not lead to immediate improvement of symptoms, typically taking up to 6 months to resolve.

Metoclopramide, an antiemetic drug used primarily for gastrointestinal disorders, has also been implicated in DIP. Though the drug is intended for short-term use (2–8 weeks), many patients are treated long term with this drug. “With chronic use, they develop drug-induced parkinsonism or tardive dyskinesia,” said Dr. Factor.

The prevalence of DIP among psychiatric patients on metoclopramide may be as great as 25%, according to estimates. Women tend to be affected more frequently than men, particularly older women. Among patients with metoclopramide-induced parkinsonism, up to 70% have tremor, 70% have postural instability, and 40% have tardive dyskinesia. Once the drug is stopped, improvement typically takes 4 months.

In addition to neuroleptics and metoclopramide, there have been reports of a number of other drugs associated with DIP. These include SSRIs, dopamine depleters, bupropion, phenelzine, lithium, valproate, some cardiac drugs (amiodarone, captopril, verapamil, diltiazem, amlodipine, manidipine, methyldopa), and estrogens.

There are a number of risk factors for developing DIP. In particular, women appear to be twice as likely as men to develop the disorder. Older age (older than age 65) is associated with a five times greater risk. Greater drug potency or dose also plays a role. Less frequently described potential risk factors include prior brain injury, dementia, HIV infection, certain psychiatric disorders (mood disorders in particular), the presence of tardive dyskinesia, and a family history of PD.

“Recognition is the key to proper management because if you recognize that the drug causes it, you stop the drug if you can and the symptoms will reverse in most patients.”

In addition, amantadine and anticholinergics are frequently used to treat symptoms. Other potential treatments include levodopa, electroconvulsive therapy, propranolol, and clozapine.

Drug-Induced Parkinsonism Frequently Missed : Of 17 DIP patients seen by a neurologist, only 2 were correctly diagnosed, according to an informal study.