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1
Question:

A 47-year-old man with a long history of schizoaffective disorder comes to the clinic with his wife.  After a difficult course requiring several psychiatric hospitalizations and poor response to multiple antipsychotics and mood stabilizers, the patient's condition has been relatively stable for the past 3 years with high doses of lithium and risperidone.  Lowering his dose of risperidone resulted in worsening psychotic symptoms, so the dose was subsequently increased.  The patient's wife states that his psychiatric symptoms have improved with the current medications, but they are both concerned about new abnormal movements he has begun to make.  He has no other medical conditions and takes no other medications.  The patient does not use tobacco, alcohol, or illicit drugs.  Blood pressure is 120/70 mm Hg, pulse is 72/min, and respirations are 12/min.  Lithium level is 1.2 mEq/L (range: 0.8-1.2).  During examination, the patient repeatedly taps his foot, protrudes his tongue, and smacks his lips.  The rest of the examination shows no abnormalities.  The patient is treated with sequential trials of valbenazine and deutetrabenazine but shows no significant improvement in abnormal movements at follow-up.  Which of the following is the most appropriate next step in management of this patient?

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Explanation:

Tardive dyskinesia

Clinical features

  • Abnormal involuntary movements due to prolonged use of antipsychotics or metoclopramide
  • Orofacial dyskinesia (tongue protrusion, lip smacking, grimacing)
  • Limb dyskinesia (dystonic postures, foot tapping, chorea)
  • Trunk dyskinesia (rocking, thrusting, shoulder shrugging)
  • Greater risk with first-generation antipsychotics

Management

  • Discontinue causative medication if feasible
  • Switch to second-generation antipsychotic (quetiapine, clozapine) if continued antipsychotic is required
  • Treat with valbenazine or deutetrabenazine 

This patient's movements are most consistent with tardive dyskinesia (TD), an involuntary hyperkinetic movement disorder resulting from prolonged exposure to dopamine receptor-blocking drugs, including antipsychotics (eg, risperidone) and metoclopramide.  Management options for TD include:

  • Reducing the antipsychotic dose, which may not be possible as it can worsen psychosis (as in this patient).
  • Using valbenazine or deutetrabenazine, reversible inhibitors of the vesicular monoamine transporter 2 (VMAT2) recently approved by the FDA for use in TD.
  • Switching (cross-tapering) to an antipsychotic with a lower tendency to cause TD, such as quetiapine or clozapine.  In patients with a history of poor response to multiple antipsychotics, clozapine is the preferred option.

In addition to TD, other side effects of first- and second-generation antipsychotics include extrapyramidal symptoms (dystonias, parkinsonism, akathisia), which can be treated with anticholinergics or, in the case of akathisia, beta blockers.  Anticholinergics and beta blockers do not treat TD.

(Choices A and B)  Benztropine can treat drug-induced parkinsonism (eg, gradual-onset tremor, rigidity, bradykinesia) and acute dystonia (muscle spasms/stiffness, torticollis, opisthotonus, oculogyric crisis).  Diphenhydramine (an antihistamine with strong anticholinergic properties) can also be used to treat dystonias.  These medications have not been shown to improve the abnormal movements of TD (and anticholinergics may even worsen them).

(Choice C)  Propranolol, a beta blocker, is used to treat akathisia, a subjective feeling of restlessness that compels patients to move constantly (eg, repeated leg crossing, weight shifting, pacing) and that can occur at any time during treatment with antipsychotics.  This patient's movements are not consistent with akathisia, and beta blockers do not treat TD.

(Choice D)  Although lithium can cause tremors, it does not cause other involuntary movements.  It would be an unlikely explanation for the abnormal movements in this patient who has a normal lithium level and no other signs of lithium toxicity.

Educational objective:
Tardive dyskinesia occurs after prolonged exposure to antipsychotic drugs and is characterized by abnormal involuntary movements of the mouth, tongue, face, trunk, or extremities.  When antipsychotic dose reduction or discontinuation is not feasible, using valbenazine or deutetrabenazine or switching to clozapine should be considered.