Table 1
Medications With the Potential to Cause Tardive Syndromes
| Benzisothiazole (ziprasidone) |
| Benzisoxazole (iloperidone) |
| Butyrophenones (haloperidol, droperidol) |
| Calcium channel blockers (flunarizine, cinnarizine) |
| Dibenzazepine (loxapine, asenapine) |
| Dibenzodiazepine (clozapine, quetiapine) |
| Diphenylbutylpiperidine (pimozide) |
| Indolones (molindone) |
| Lithium |
| Phenothiazines (chlorpromazine, triflupromazine, thioridazine, mesoridazine, trifluoperazine, prochlorperazine, perphenazine, fluphenazine, perazine) |
| Pyrimidinone (risperidone, paliperidone) |
| Quinolinone (aripiprazole) |
| Substitute benzamides (metoclopramide, tiapride, sulpiride, clebopride, remoxipride, veralipride, amisulpride, levosulpiride) |
| Serotonin reuptake or serotonin norepinephrine reuptake inhibitors (duloxetine, citalopram) |
| Thienobenzodiazepine (olanzapine) |
| Thioxanthenes (chlorprothixene, thiothixene) |
| Tricyclic antidepressants (amoxapine) |
Table 2
Spectrum of Tardive Syndromes
| Classic Tardive Dyskinesia | Isolated or Predominant Oro-bucco-lingual Dyskinesia (stereotypy) |
|---|---|
| Tardive stereotypy | Seemingly purposeful, repetitive and coordinated movements in the limbs or trunk (if the face is mainly involved, would be considered as classic TD) |
| Tardive dystonia | Focal, segmental or generalized dystonia (classic features are retrocollis, opisthotonic trunk posturing, arm extension) |
| Tardive akathisia | Feeling of restlessness, inability to stay still, intense inner urge to move |
| Tardive tics (tardive tourettism) | Clinically indistinguishable from tics in Tourette syndrome but much older age of onset |
| Tardive tremor | Postural, kinetic, and rest tremor (typically high amplitude and low frequency) |
| Tardive myoclonus | Prominent postural myoclonic jerks in upper extremities |
| Tardive chorea | Usually accompanies classic TD in adult patient |
| Tardive parkinsonism | Rest tremor, bradykinesia, rigidity persisting for months/years after discontinuation of DRBAs; normal DAT SPECT |
| Withdrawal emergent syndrome | Generalized chorea (no or minimal involvement of oro-bucco-lingual region) in children after sudden discontinuation of DRBAs; self-limiting condition |
| Neuroleptic malignant syndrome | Fever, rigidity, mental status change, hyperthermia, elevated CK, leukocytosis |
| Tardive pain | Chronic painful oral and genital sensations |
Video 1.
Classic Tardive Dyskinesia.
A 77-year-old woman developed symptoms 2 weeks after sudden discontinuation of prochlorperazine 10 mg daily that she had been taking for a year. The video demonstrates classic oro-bucco-lingual stereotypy and mild extremity stereotypies.
Video 2.
Tardive Akathisia and Tardive Stereotypy.
A 34-year-old man with paranoid schizophrenia treated with haloperidol 10 mg daily for 2.5 years and lurasidone 80 mg daily for 6 months developed restlessness, inability to stay still, and abnormal hand movements. The video demonstrates extreme restlessness and hand-rubbing stereotypies.
Video 3.
Tardive Dystonia.
A 42-year-old man with mood disorder treated with ziprasidone 60 mg daily developed mild facial grimacing and tapered off ziprasidone over 2 weeks followed by worsening and generalization of abnormal movements. Video demonstrates cervical dystonia with retrocollis and torticollis to the left, jaw-opening dystonia, blepharospasm, truncal dystonia with opisthotonic trunk posturing, proximal arms dystonia with arm extension and internal rotation, and proximal legs dystonia.
Video 4.
Withdrawal Emergent Syndrome.
An 11-year-old boy with Tourette syndrome and behavioral problems treated with olanzapine 30 mg daily and fluphenazine 5 mg daily had all his medications suddenly discontinued, and 1–2 weeks later developed mild piano-playing finger movements with rapid progression to generalized chorea. The symptoms gradually resolved over the next 2 months with no treatment.
Video 5.
Tardive Tics and Tardive Tremor.
A 37-year-old man with history of gastroesophageal reflux disease treated with metoclopramide (20-30 mg/day) for 9 months developed facial tics and hands tremor (postural and kinetic) that persisted for 2 years after discontinuation of the medication. The patient also has left leg stereotypy.
Table 3
Treatment of Tardive Dyskinesia
| Medication | Starting Daily Dose | Daily Dose Range |
|---|---|---|
| Slow Taper of an Offending DRBA | ||
| Dopamine-depleting medications | ||
| Tetrabenazine67 | 12.5–25 mg | 25–200 mg (typical therapeutic dose 50–75 mg) |
| Reserpine86 | 0.25 mg | 0.75–8 mg |
| Amantadine86 | 100 mg | 100–300 mg |
| GABA agonistic medications | ||
| Clonazepam86 | 0.5 mg | 1–4 mg |
| Baclofen73 | 20–120 mg | |
| Valproic acid73 | 900–1500 mg | |
| Anticholinergic medications | ||
| Trihexyphenidyl87 | 1 mg | 4–20 mg |
| Less studied/might be effective medications (donepezil, lithium, antioxidants, zonisamide, vitamin B6, melatonin, zolpidem, propranolol) | ||
| Chemodenervation with botulinum toxin injections | ||
| Surgical treatment (deep brain stimulation) | ||