Movement disorder medications explained

What movement disorder medications are

Movement disorder medications in psychiatry are the treatments for a specific set of problems that mostly come from antipsychotics, or from Huntington disease. They aren't the medications used for Parkinson's disease itself (levodopa, dopamine agonists) or for essential tremor (propranolol, primidone). Those live in neurology.

The class covers three main groups.

VMAT2 inhibitors. These block a transporter that packages dopamine into vesicles for release. Turning down dopamine release quiets the involuntary movements of tardive dyskinesia, Huntington chorea, and related conditions. Valbenazine (Ingrezza) and deutetrabenazine (Austedo) were FDA-approved specifically for tardive dyskinesia in 2017. Tetrabenazine (Xenazine) is the older, first-in-class VMAT2 inhibitor, approved for Huntington chorea. Deutetrabenazine is a deuterated form of tetrabenazine with a longer half-life and generally better tolerability.

Anticholinergics. Benztropine and trihexyphenidyl block muscarinic acetylcholine receptors, which restores the dopamine-acetylcholine balance in the basal ganglia that's disrupted by dopamine blockade. They're used for antipsychotic-induced parkinsonism and, particularly, acute dystonic reactions. Diphenhydramine, the sedating antihistamine, has anticholinergic activity too and is used intramuscularly for acute dystonia.

Amantadine. An older antiviral medication that has NMDA antagonist and dopamine-releasing properties. It's used for antipsychotic-induced parkinsonism and, in the extended-release form (Gocovri), for levodopa-induced dyskinesia in Parkinson's disease.

Not every medication in this space is on PsychiatryRx. The ones covered here are deutetrabenazine, valbenazine, tetrabenazine, and amantadine. Benztropine, trihexyphenidyl, and diphenhydramine are widely used in psychiatric practice but don't currently have dedicated pages on the site.

How they work

VMAT2 inhibitors. The vesicular monoamine transporter type 2 (VMAT2) packages dopamine, norepinephrine, and serotonin into synaptic vesicles inside nerve terminals. Blocking VMAT2 reduces the amount of dopamine loaded into vesicles and released into the synapse. In tardive dyskinesia and chorea, that reduced dopamine release quiets the involuntary movements. VMAT2 inhibitors don't block dopamine receptors on the receiving cell (which is what antipsychotics do). They reduce dopamine release from the sending cell.

Deuterium modification. Deutetrabenazine is tetrabenazine with deuterium substituted for hydrogen at metabolic hot spots on the molecule. That slows metabolism and gives a longer half-life and steadier drug levels, which translates to less peak-related side effects. It's a chemistry trick that turned out to matter clinically.

Anticholinergics. Antipsychotics block dopamine D2 receptors in the basal ganglia, which shifts the balance so that cholinergic activity dominates. That's what produces parkinsonism (stiffness, tremor, slow movement) and dystonia (sudden muscle spasms). Anticholinergics restore the balance by blocking acetylcholine at muscarinic receptors. They're most effective for parkinsonism and dystonia, and less useful for akathisia.

Amantadine. Amantadine is an NMDA glutamate receptor antagonist and also enhances dopamine release. Both actions are thought to contribute to its effect on parkinsonism and dyskinesia. It has less anticholinergic burden than benztropine or trihexyphenidyl, which matters in older adults.

How the class developed

Tetrabenazine was developed as an antipsychotic in the 1950s but was overshadowed by chlorpromazine and haloperidol. It found a role in movement disorders, particularly Huntington chorea, and was used in Europe and Canada for decades before FDA approval in the U.S. in 2008 for Huntington chorea.

Deutetrabenazine and valbenazine were the first medications specifically approved for tardive dyskinesia, both in 2017. Before that, TD was treated with off-label tetrabenazine, dose reductions of the offending antipsychotic, or other approaches. The approval of two FDA-approved VMAT2 inhibitors for TD changed practice quickly.

Anticholinergics (benztropine and trihexyphenidyl) have been in use for decades for antipsychotic-induced parkinsonism and dystonia, going back to the earliest days of first-generation antipsychotics.

Amantadine (Symmetrel) was approved as an antiviral for influenza A in the 1960s. Its use for Parkinson's disease came from an accidental observation that a nurse taking it for flu felt her Parkinson's symptoms improve. Amantadine has since been repurposed several times, including for antipsychotic-induced EPS and, as extended-release amantadine (Gocovri), for levodopa-induced dyskinesia in Parkinson's disease.

What they treat

• Tardive dyskinesia. Valbenazine and deutetrabenazine are FDA-approved. Tetrabenazine is used off-label. The goal is to reduce involuntary movements, often of the face, mouth, tongue, limbs, or trunk, that developed during long-term antipsychotic treatment.
• Huntington disease chorea. Tetrabenazine, deutetrabenazine, and valbenazine are FDA-approved. Chorea is the dance-like involuntary movement that's a hallmark of Huntington disease.
• Antipsychotic-induced parkinsonism. Anticholinergics (benztropine, trihexyphenidyl) are commonly used. Amantadine is an alternative, especially in older adults. Reducing the antipsychotic dose or switching to one with less D2 blockade is often part of the strategy.
• Acute dystonic reactions. Intramuscular benztropine or diphenhydramine is the standard rescue treatment. These are sudden, painful muscle spasms of the neck, jaw, tongue, or eyes that can happen within hours to days of starting a high-potency antipsychotic.
• Levodopa-induced dyskinesia. Extended-release amantadine (Gocovri) is FDA-approved for this in people with Parkinson's disease.
• Akathisia. Not usually well-treated by any of these. First-line for akathisia is reducing the offending antipsychotic, switching, or adding propranolol, mirtazapine, or a benzodiazepine.

Individual medications in this class

• Deutetrabenazine (Austedo). VMAT2 inhibitor. Deuterated form of tetrabenazine. FDA-approved for tardive dyskinesia and Huntington chorea. Twice-daily dosing with immediate-release; once-daily with extended-release (Austedo XR).
• Valbenazine (Ingrezza). VMAT2 inhibitor. Once-daily dosing. FDA-approved for tardive dyskinesia and Huntington chorea.
• Tetrabenazine (Xenazine). The original VMAT2 inhibitor. FDA-approved for Huntington chorea. Used off-label for tardive dyskinesia (though the newer options are usually preferred). Requires CYP2D6 genotyping at higher doses because slow metabolizers are at higher risk of side effects.
• Amantadine (Gocovri, Osmolex ER, Symmetrel). NMDA antagonist with dopamine-releasing effects. Available in immediate-release, extended-release (Osmolex ER), and delayed-release/extended-release (Gocovri) forms. Gocovri is FDA-approved for levodopa-induced dyskinesia in Parkinson's disease. Used off-label for antipsychotic-induced EPS.

Benztropine (Cogentin), trihexyphenidyl (Artane), and diphenhydramine (Benadryl) are the anticholinergic mainstays for antipsychotic-induced EPS and acute dystonic reactions. They aren't currently on individual medication pages here but are covered in the antipsychotic-related content.

Common side effects across the class

VMAT2 inhibitors (valbenazine, deutetrabenazine, tetrabenazine).

• Sleepiness or sedation, especially early on.
• Fatigue.
• Parkinsonism (stiffness, slowed movement, tremor) at higher doses. This is the medication doing too much of what it does.
• Dry mouth.
• Nausea and mild GI upset.
• Depression and low mood. This is worth watching, particularly with tetrabenazine.
• Akathisia can occur, ironically, because turning down dopamine can produce it.

Anticholinergics (benztropine, trihexyphenidyl, diphenhydramine).

• Dry mouth, constipation, blurry vision, urinary retention.
• Confusion, especially in older adults.
• Sedation.
• Memory problems with long-term use.
• Increased risk of falls in older adults.

Amantadine.

• Livedo reticularis, a lacy purplish skin discoloration usually on the legs.
• Ankle swelling.
• Dry mouth.
• Insomnia, vivid dreams.
• Confusion or hallucinations, especially in older adults.
• Dose reduction is needed in kidney impairment.

Serious warnings across the class

VMAT2 inhibitors.

• Boxed warning on tetrabenazine and deutetrabenazine for depression and suicidality in people with Huntington disease. Valbenazine doesn't carry this specific boxed warning in the same form, but the concern about mood applies to all VMAT2 inhibitors.
• QT prolongation with valbenazine and deutetrabenazine, particularly at higher doses. Baseline ECG may be considered in people with heart disease or on other QT-prolonging medications.
• Parkinsonism at higher doses. Turning down dopamine release too far causes the same movement problem in reverse.
• Neuroleptic malignant syndrome has been rarely reported.

Anticholinergics.

• Anticholinergic burden. This is the accumulated effect of anticholinergic medications on cognition, especially in older adults. Long-term use of benztropine or trihexyphenidyl is associated with worse cognition and possibly increased dementia risk. The American Geriatrics Society Beers Criteria list first-generation anticholinergics as medications to avoid in older adults when possible.
• Acute angle-closure glaucoma. Anticholinergics can precipitate an attack.
• Urinary retention, particularly in men with prostate enlargement.
• Confusion and delirium, particularly in older adults.
• Anticholinergics don't help akathisia, and giving them for a symptom that isn't parkinsonism just adds burden without benefit.

Amantadine.

• Renal dosing. Amantadine is cleared by the kidneys, and dose reduction is required in kidney impairment. Full doses in someone with reduced kidney function can cause severe confusion and hallucinations.
• Psychosis and confusion, especially in older adults.
• Withdrawal syndrome if stopped abruptly at higher doses.
• QT prolongation, particularly at higher doses.

What tips the choice within the class

Tardive dyskinesia. Either valbenazine or deutetrabenazine is a reasonable first choice. Both work. Valbenazine offers once-daily dosing from the start; deutetrabenazine has a twice-daily immediate-release and a once-daily extended-release. Cost, insurance coverage, and side-effect fit typically drive the choice. Reducing the offending antipsychotic when possible, or switching to one with less TD risk, is part of the plan alongside the VMAT2 inhibitor. Tetrabenazine is a cheaper option but has a heavier side-effect profile and CYP2D6 dosing considerations.

Huntington chorea. Deutetrabenazine and valbenazine are generally better tolerated than tetrabenazine. The boxed warning on depression matters in Huntington disease because depression is common in Huntington disease. Careful monitoring, sometimes with prophylactic antidepressant treatment, is part of the plan.

Antipsychotic-induced parkinsonism. First move is usually to reduce the antipsychotic dose or switch to one with less D2 blockade (an atypical if on a first-gen; a lower-D2 atypical like quetiapine if on a higher-D2 one; clozapine in refractory cases). If a rescue anticholinergic is needed, benztropine or trihexyphenidyl. In older adults, amantadine has less anticholinergic burden and may be preferred, with attention to kidney function.

Acute dystonic reaction. This is an emergency (or urgent), and IM benztropine or IM diphenhydramine is the standard rescue. Oral anticholinergic prophylaxis may follow.

Akathisia. Not usually well-treated by VMAT2 inhibitors or anticholinergics. First-line is dose reduction or switch. Propranolol, mirtazapine, or a benzodiazepine can help.

Older adults. Anticholinergic burden is a major concern. Amantadine may be preferred over benztropine or trihexyphenidyl, with kidney dosing. VMAT2 inhibitors are used in tardive dyskinesia in older adults but with attention to sedation, parkinsonism, and QT.

Common questions

What is tardive dyskinesia and how is it treated? Tardive dyskinesia (TD) is a movement disorder that can develop after months to years of taking an antipsychotic. It involves involuntary, repetitive movements, often of the face, mouth, or tongue (lip smacking, tongue movements, grimacing), and sometimes the limbs or trunk. TD can be permanent, though it sometimes improves after reducing or stopping the antipsychotic. FDA-approved treatments are the VMAT2 inhibitors valbenazine (Ingrezza) and deutetrabenazine (Austedo). Alongside the VMAT2 inhibitor, the offending antipsychotic is often reduced or switched when possible. Regular AIMS (Abnormal Involuntary Movement Scale) screening helps catch TD early, when it may be more reversible.

Why do anticholinergics help antipsychotic-induced Parkinsonism but not tardive dyskinesia? Because they're different problems mechanistically. Antipsychotic-induced parkinsonism comes from acute D2 blockade in the basal ganglia, which shifts the balance so cholinergic activity dominates. Anticholinergics restore the balance and help. Tardive dyskinesia comes from long-term changes in dopamine receptor sensitivity that develop with prolonged D2 blockade. Adding an anticholinergic doesn't fix that and can actually make TD worse. Anticholinergics are for parkinsonism and dystonia. VMAT2 inhibitors are for tardive dyskinesia.

What is akathisia and how is it treated? Akathisia is an intense feeling of inner restlessness, often with an urge to move. People pace, shift their weight, can't sit still, and describe the feeling as almost intolerable. It's a common antipsychotic side effect and can be very distressing. It's linked to worse outcomes in schizophrenia and to suicidal thoughts. Treatment usually starts with reducing the antipsychotic dose or switching. Propranolol is often used, sometimes mirtazapine at low doses (5 mg to 15 mg), and benzodiazepines can help short-term. Anticholinergics generally don't help akathisia and shouldn't be reflexively added.

Are VMAT2 inhibitors safe long-term? The evidence so far, going back to approval in 2017, suggests they're generally well tolerated for years of use. The main concerns to monitor for are mood (depression), parkinsonism if the dose is too high, QT prolongation, and sedation. Tardive dyskinesia often needs ongoing treatment, so long-term use is expected. Trials of drug holidays or discontinuation to see if TD returns aren't well studied. Continuing the medication as long as it's helping is the usual approach.

Why is amantadine used for movement problems if it was originally an antiviral? Amantadine's usefulness in movement disorders was an accidental discovery. In the 1960s, a nurse taking amantadine for influenza noticed her Parkinson's symptoms improved. The mechanism was worked out later: amantadine antagonizes NMDA glutamate receptors and also enhances dopamine release. Both actions help parkinsonism and dyskinesia. Amantadine is now used more for movement disorders than for its original antiviral indication (and it's no longer recommended for influenza because of resistance).

Sources

This guide draws on current prescribing information and public health references. It's reviewed for clinical accuracy and updated as guidance changes. This is educational content and isn't medical advice.

1. U.S. Food and Drug Administration. Prescribing information.
2. MedlinePlus, U.S. National Library of Medicine.
3. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia (movement disorder appendix).
4. American Academy of Neurology. Practice guidelines related to tardive syndromes and Huntington disease.
5. American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.