TCPR: I think that a lot of psychiatrists, myself included, could use a refresher course on Parkinson disease and how to distinguish its symptoms from those induced by antipsychotics (parkinsonism). What exactly is parkinsonism?
Dr. Kaufman: Parkinsonism is a clinical syndrome comprised primarily of rigidity, tremor, and bradykinesia (slowed movements). The most common cause of parkinsonism is Parkinson disease, but parkinsonism also can occur from the use of any medication that blocks the D2 (dopamine type 2) receptor. Those include antipsychotics but can also include non-psychiatric medicines, particularly metoclopramide (Reglan), an anti-nausea medicine. So, we see parkinsonism in people who are being treated for nausea and vomiting associated with prolonged migraines, chemotherapy, and pregnancies. In addition, vesicular monoamine transporter 2 (VMAT2) inhibitors such as deutetrabenazine (Austedo), tetrabenazine (Xenazine), and valbenazine (Ingrezza)—medications that reduce tardive dyskinesia, chorea in Huntington disease, or both—have recently been reported to induce parkinsonism as an adverse effect.
TCPR: What other disorders might cause parkinsonism?
Dr. Kaufman: In addition to parkinsonism being related to antipsychotics and other medications, psychiatrists need to consider the possibility that parkinsonism can be a manifestation of neurologic illnesses, including Lewy body dementia, Wilson disease, drug abuse, or Huntington disease, at least its juvenile form. These particular illnesses are especially important because they cause mood and thought disorders, as well as parkinsonism, and thus a patient developing one of them may see a psychiatrist before any other specialist.
TCPR: Can you tell us more about how we determine diagnostically whether parkinsonism is due to the use of antipsychotics or Parkinson disease? Could it be both?
Dr. Kaufman: It could be both, especially in older adults. If older patients have been receiving antipsychotics and develop parkinsonism, a psychiatrist might consider that these patients may have been developing idiopathic Parkinson disease and that the psychiatric symptoms may have been related. It is not always easy to tell the difference between the disease and its adverse effects. The first thing to do, if possible, is to stop the antipsychotic agent and wait 3 weeks to 3 months to see if the symptoms resolve. If the psychiatrist cannot discontinue the antipsychotic, the next strategies would be to reduce the dose, switch to a second-generation antipsychotic, or use clozapine. In equivocal cases, or when there is urgency, there is a new nuclear medicine test called a dopamine transporter scan (DaT) that usually can reliably distinguish between Parkinson disease and medication-induced parkinsonism (Bhattacharjee S, Ng KL, Indian J Nucl Med 2016;31(4):320–321).
TCPR: How should we examine a patient who appears to have parkinsonism?
Dr. Kaufman: To start, observe whether the patient has reduced facial and limb expressions and gestures. For example, there may be decreased smiling and decreased affect. The patient will not make any hand gestures. There will also be characteristically fewer eye blinks and a tendency to stare, which neurologists call a “reptilian stare.” In most cases, a patient with parkinsonism will have a tremor of one or both hands. If it is unilateral or asymmetric, a resting tremor suggests idiopathic Parkinson disease, but if it is symmetric, we really cannot say whether it is idiopathic or medication-induced.
TCPR: After we make those observations, what should we do next?
Dr. Kaufman: Neurologists rotate the hand around the wrist and see if there is cogwheel resistance. Both wrists need to be tested. In individuals who have a tremor on one side, that wrist ought to have rigidity, and the other one will not. Another maneuver is the so-called “pull test.” With the patient standing, the physician stands behind the patient, hands on the patient’s shoulders, and says, “At the count of 3, I’m going to pull you back a little.” During this, a normal healthy patient will take a step back or bend the shoulders backwards to maintain balance. In contrast, someone with Parkinson disease will either take many steps backwards (“retropulsion”) or just topple over like a statue (“falling en bloc”). Another simple thing we do is watch people walk to see if they have normal arm swing. A lack of normal swinging on one or both sides is consistent with parkinsonism.
TCPR: Interesting. How do you suggest we evaluate tremors in these patients? And can you clarify the difference between intention tremors and resting tremors?
Dr. Kaufman: Parkinson disease is usually associated with a resting tremor. That is, a tremor of 4–6 Hertz (Hz, cycles per second) in one or both hands, in which the fingers and the hand repeatedly flex. Although this tremor is present at rest, patients actually can suppress it for several seconds to several minutes. We ask patients, “Please stop the shaking as I count to 10.” Patients will also have a diminished tremor when we ask them, “Take your finger and move it from your nose to my finger, then go back and forth.” And, when a patient is holding the hands in fixed positions against gravity—say, straight out—the tremor will be reduced compared to when the patient holds the hands at rest.
TCPR: So, in parkinsonism we would see a resting tremor. When would we see an intention tremor?
Dr. Kaufman: A common intention tremor is “essential tremor,” which is more frequent, develops in younger individuals, and frequently has developed in a patient’s family members. This tremor is a more rapid tremor and is not present when patients have their hands in their lap, but is present when the arms are held in fixed positions against gravity—for example, when the patient sticks out both hands for 10 seconds.