THERAPEUTICS

Brands

• Nitoman, Xenazine

Generic?

• No

Class

• Monoamine-depleting agent

Commonly Prescribed for

(FDA approved in bold)

• Chorea in Huntington's disease (HD)

• Tardive dyskinesia

• Psychosis

• Hemiballism

• Dystonia (especially tardive)

• Myoclonus

• Gilles de la Tourette syndrome (GTS) or tics

• Hypertension

How the Drug Works

• Depleting agent that reversibly inhibits vesicular monoamine transporter type 2 (VMAT2) resulting in depletion of monoamines, primarily dopamine but less effect on others (norepinephrine, serotonin, and histamine), from nerve terminals. It also weakly blocks postsynaptic D2 receptors. Effectiveness is likely related to dopamine depletion. Sedation and depression are probably due to histamine and serotonin/norepinephrine depletion, respectively

How Long Until It Works

• Rapid onset, lasting 5–6 hours

If It Works

• In neurological conditions, continue to assess effect of the medication, determine if still needed, and adjust to optimal dose

If It Doesn't Work

• Chorea: consider benzodiazepines and AEDs (valproate). Neuroleptics are usually effective. Reserpine is an alternative depleting agent

• Generalized dystonia: anticholinergics, baclofen, or benzodiazepines may be effective. Surgical treatments (including pallidotomy, thalamotomy, deep brain stimulation, myotomy, rhizotomy, or peripheral denervation) are reserved for refractory cases

• GTS/tics: neuroleptics and α2-adrenergic agonists are often effective

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Chorea: combine with AEDs, neuroleptics, or benzodiazepines

• Dystonia: combine with anticholinergics or benzodiazepines

• GTS/tics: combine with neuroleptics for refractory cases

Tests

• At doses of 50mg or greater, test patients for the CYP2D6 gene to determine if they are poor, intermediate, or extensive metabolizers

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Related to monoamine depletion

Notable AEs

• Drowsiness, fatigue, dizziness, depression, anxiety, insomnia

• Parkinsonism, akathisia, orthostatic hypotension, nausea

• Upper respiratory tract infection, dyspnea, dysuria

• Slight increase in liver function tests