Tardive dyskinesia and iatrogenic motor instability

Specialty: Geriatrics.

• pharmacological involuntary orofacial movements
• iatrogenic parkinsonism in the elderly
• iatrogenic extrapyramidal tremor

Why it occurs

• Prolonged or chronic use of first (haloperidol) or second generation antipsychotics (risperidone, olanzapine) for the behavioral control of dementia
• Inappropriate prescription of antiemetics or prokinetics with blocking action of central dopaminergic receptors (metoclopramide, clebopride, alizapride)
• Prolonged use of calcium channel blockers used inappropriately for the treatment of vertigo (flunarizine, cinnarizine)
• Physiological loss of dopaminergic neurons in the nigrostriatal pathway associated with intrinsic aging
• Complex drug interactions that increase serum levels of active antipsychotics (e.g., cytochrome CYP2D6 inhibitors)

Initial workup

Systematic application of the Abnormal Involuntary Movement Scale (AIMS); blood work including complete blood count, serum electrolytes, kidney function, liver function, and serum CK levels; 12-lead electrocardiogram to quantify the QTc interval if rotation or deprescription of neuroleptics is planned; brain imaging study (CT or MRI) to rule out acute structural lesions in the basal ganglia (lacunar infarcts in the putamen or caudate).

Standard management

• Extremely gradual reduction and suspension, if the baseline psychopathological condition allows it, of the offending drug — for example, gradual tapering of metoclopramide or haloperidol over several weeks to avoid dyskinesia withdrawal syndrome
• Rotation to antipsychotics with lower central D2 affinity, such as Quetiapine — starting with 12.5 mg orally at night, titrating slowly according to response) or Clozapine (in severe and refractory cases, requiring strict monitoring of the leukocyte count due to the risk of agranulocytosis
• Tetrabenazine (12.5 mg to 25 mg orally per day as a reversible inhibitor of the vesicular monoamine transporter VMAT2, indicated only in cases of severe and disabling tardive dyskinesias that do not respond to other measures, monitoring the appearance of depression and secondary parkinsonism).