Drugs that Cause Movement

Disorders
October 1, 2008 Michele B. Kaufman, PharmD, BSc, RPh

Most of us learned in our professional training that neuroleptic agents cause movement
disorders, or extrapyramidal symptoms (EPS).1 Neuroleptics, the older class of antipsychotic
agents, which includes dopamine receptor blocking agents (DRBA), can cause tardive
dyskinesia (TD), dystonia, akathisia, and Parkinsonism.

We also learned that newer antipsychotic agents, the so-called second-generation

antipsychotics, do not cause EPS. However, dose-related EPS has been associated
with olanzapine and risperidone use (> 6 mg/day doses), and there have been two
reported cases of aripiprazole-induced EPS.2,3
So which symptoms indicate a drug-induced movement disorder (DIMD)? Patients
with DIMDs have difficulty with social functioning, motor-task performance,
interpersonal communication, and activities of daily living. They also are less likely
to adhere to a medication regimen, making disease relapse and rehospitalization
more likely.
Spending on diabetes drugs as a whole increased by 12% due to use of highercostmedications and drug inflation, yet utilization of these drugs increased by only
2.3%. Since diabetes has become an epidemic, more patients are being treated with
newer, higher-cost treatments, as well as, two- or three-drug regimens.
Some DIMDs are worse than others. Neuroleptic-induced TD, for example, is in
some cases irreversible and can lead to functional impairment so severe a patient
cannot feed himself, speak clearly, or breathe easily. In addition, removal of the
offending agent does not always resolve TD.4
Milder forms of neuroleptic-induced TD occur in about 20% of patients. In higher
risk groups, such as older patients, milder forms of neuroleptic-induced TD may
exceed 50%.
DIMDs often elude diagnosis by clinicians, partially because they look like other
medical conditions such as restless legs syndrome, agitation, or drug withdrawal.

Clinicians who understand the most likely DIMD culprits and the effect of each can
better manage their patients. Its also crucial for clinicians to pay attention to

Patient stress and anxiety levels, as both of these can exacerbate DIMD symptoms;

Patient drug history; and

Demographic information. Older women are most likely to develop tardive

dyskinesia. Young men more commonly experience dystonic reactions. The elderly are at
higher risk for Parkinsonism and akathisia.

Clinicians must watch for DIMD in any patient who has taken antipsychotics.
Symptoms can occur within hours to days (acute), weeks (subacute) or even months
to years (tardive) following exposure.

The Agents
Causative DRBAs include:

Haloperidol;

Thioridazine;

Perphenazine;

Droperidol;

Metoclopramide;

Prochlorperazine; and

Promethazine.

DIMDs can also occur from:

Lithium, which can cause tremors or chorea;

Stimulants (e.g., amphetamines), which can cause tremor, tics, dystonia, and
dyskinesia;

Selective-serotonin reuptake inhibitors (SSRIs), which can cause tremors, akathisia,

and possible dyskinesia, dystonia, and Parkinsonism;

Tricyclic antidepressants (TCAs) (e.g., amitriptyline, nortriptyline, etc), which can

cause myoclonus and tremors;

Valproic acid, which causes tremors; and

Cyclosporine A, which was implicated in one study as causing tremors and

Parkinsonism.6

Management
For neuroleptics, withdrawal of the offending agent may lead to partial improvement
in about half of patients. The outcome, of course, depends on the DIMD.
Early detection of TD is important to improve remission rates, which are inversely
related to the disorders duration and severity. To treat, gradually taper the patient
off the medication. It may take as long as two years after discontinuation for the
condition to resolve itself. Continually re-evaluate how much a patient needs this
agent. There may be another thats just as effective but with a lower TD incidence. 7
Treat acute dystonic reactions with a short course of a potent antimuscarinic agent
such as oral, intravenous (IV), or intramuscular benztropine, or diphenhydramine. If
the patients reaction is life-threatening, use IV administration of an antimuscarinic
agent and supportive measures. In some cases, you can use benzodiazepines in place
of antimuscarinic agents. For tardive dystonia, prevention is the most important
treatment since few pharmacologic treatments have proven efficacy.
Prevention also is the key to managing akathisia. To prevent this manifestation,
prescribe atypical antipsychotics or use a standardized dose titration to avoid
excessive dose escalation. In high-risk patients, consider prophylactic treatment with
diphenhydramine or benztropine. Other potentially useful agents include
benzodiazepines, propranolol, or cyproheptadine. For acute reactions, remove the
causative agent.
Treat drug-induced Parkinsonism by withdrawing the causative agent or reducing
the dose, switching to an atypical antipsychotic (if neuroleptic-induced), and possibly
prescribing a trial of amantadine, an antimuscarinic agent, a dopamine agonist, or
levodopa.
Though antiemetics and conventional antipsychotics are most commonly implicated,
other agents also cause DIMDs. To prevent and treat these disorders, clinicians need
to be particularly aware of the causative agents and symptoms. TH

Michele B. Kaufman, PharmD, BSc, RPh, is a registered pharmacist based in New

York City.