Table 1.
Drugs used in Huntington’s disease
| Drug | Indication | Mean standard daily dose in adults | Major relevant side effects | Contraindications/restrictive application | Main drug interaction | Special points |
|---|---|---|---|---|---|---|
| Antipsychotic drugs (APDs) | ||||||
| Risperidone | Psychosis, mania, aggression | 1–2 mg/d (max 6 mg/d) | Headache, insomnia, agitation, anxiety, extrapyramidal symptoms, QT prolongation | Hepatic and renal dysfunction, Parkinson syndrome, prolactin disturbances, cardiovascular diseases, diabetes, dementia, QT prolongation | Carbamazepine, dopamine agonists, alcohol, liver enzyme-inducing drugs, phenthiazine, tricyclic antidepressiva, fluoxetin, paroxetin, cimetidin, ranitidine, drugs inducing QT prolongation, antihypertensiva, furosemid | Improvement of motor and psychiatric symptoms; depot formulation of risperidone has been shown to be effective in HD |
| Olanzapine | Psychosis, mania, chorea | 5–15 mg/d | Somnolence, weight gain, speech disturbances, eosinophilia, increased glucose, triglyceride, and cholesterol levels, vertigo, hypotension, extrapyramidal symptoms, malignant neuroleptic syndrome, QT prolongation | Breast-feeding, dementia, Parkinson syndrome, prostatic hypertrophy, ileus, hepatic dysfunction, neutropenia, bone marrow suppression, epilepsy, QT prolongation | Carbamazepine, smoking, Fluvoxamine, CYP4501A2-inhibitors, dopamine agonists, valproat, sedativa, alcohol | Improvement of motor function (chorea), behavioral/psychiatric symptoms, overall function; improvement of chorea; choose if psychosis is predominant and loss of weight |
| Tiapride | Chorea, tardive dyskinesia | 300–1,000 mg/d | Vertigo, headache, extrapyramidal symptoms, hypersalivation, akathisia, somnolence, fatigue, elevated plasma prolactin levels | Renal failure (reduced dosage), QT prolongation, pregnancy, breast-feeding | L-DOPA | Improvement of chorea; conflicting data |
| Haloperidol | Psychosis, chorea | 0.5–8 mg/d | Extrapyramidal symptoms, heart rhythm disturbances, insomnia, QT prolongation | Parkinson syndrome, epilepsy, disturbance of the hematopoietic system, anticoagulants, bradycardia, QT prolongation, pregnancy, breast-feeding, elderly with dementia | QT prolongation-inducing drugs, CYP3A4 and CYP2D6 isoenzymes, alcohol | Reserved use for patients whose psychosis does not respond to atypical agents; improvement of chorea; choose if psychosis is predominant |
| Quetiapine | Irritability, agitation, delusions, chorea | 12.5 mg/d up to 300 mg/d in 2–3 doses chorea: 600 mg/d | Somnolence, headache, agitation, hypotension, weight gain, dry mouth, increased trigylceride and cholesterol levels, hyperglycemia, neutropenia, extrapyramidal symptoms, malignant neuroleptic syndrome, pancreatitis, suicidality, QT prolongation | Cardio- and cerebrovascular diseases, QT prolongation | CYP450–3A4 inhibitors, HIV protease inhibitors, azol antifungals, erthyromycine, clarithromycine, nefazodon, grapefruit juice | Psychotic features; for chorea higher doses |
| Aripiprazole | Psychosis, mania depression, chorea | 2.5–15 mg/d (max 30 mg/d) | Vertigo, somnolence, headache, extrapyramidal symptoms, akathisia, hypersalivation, weight gain, lowered plasma prolactin levels, QT prolongation | Hepatic dysfunction, epilepsy, QT prolongation, suicidality, cardio- and cerebrovascular diseases | QT prolongation-inducing drugs, CYP3A4 and CYP2D6 isoenzymes | Improvement of chorea and psychiatric symptoms |
| Tetrabenazine (TBZ) | ||||||
| Tetrabenazine(monoamine-depleting agent) | Chorea, tardive dyskinesia | 12.5 mg/d, max 100 (200) mg/d | Depression, suicidal tendency, anxiety, agitation, confusion, akathisia, insomnia, vertigo, dysphagia, elevated plasma prolactin levels, extrapyramidal symptoms, parkinsonism, malignant neuroleptic syndrome | Depression, suicidality | MAO inhibitors, haloperidol, chlorpromazin, metoclopramid, CYP2D6 inhibitors, L-DOPA | Cognitive function can decline, cave: CYP2D6 slow metabolizer (dose reduction) |
| Benzodiazepine | ||||||
| Clonazepam | Sleep disorders, anxiety, epilepsy, chorea | 0.5–2 mg/d | Sleepiness, somnolence, dizziness, ataxia | Hepatic and renal dysfunction, ataxia, alcohol | Lithium, antipsychotics, hypnotics | Only in addition if psychiatric stress worsens chorea |
| Serotonergic reuptake inhibitors, antidepressants, and agonists | ||||||
| Citalopram (SSRI) | Major depression | 20 mg/d | Somnolence, headache, agitation, tremor, nausea, dry mouth, obstipation, asthenia, concentration problems, sexual disturbances | QT prolongation, long-QT syndrome, bleeding anomalies, diabetes mellitus, epilepsy, renal insufficiency | MAO inhibitors, anticoagulants, drugs with effect on blood coagulation, neuroleptics, metoprolol, cimetidin, desipramin | SSRIs (eg, Citalopram, sertraline or paroxetine) are commonly used |
| Mirtazapine(NaSSA) | Major depression, anxiety, restlessness, insomnia | 15–45 mg/d at bedtime | Somnolence in the beginning, headache, dry mouth, weight gain, elevated plasma prolactin levels | Breast-feeding, epilepsy, hepatic and renal dysfunction, hypotension, diabetes, suicidal behavior, schizophrenia, mania, elderly hyponatremia, glaucoma, voiding dysfunction | Sedativa, serotonergic drugs, CYP3A4-inhibitors, and inductors, cimetidin, warfarin | Effective with high dosage in severe depression in suicidal HD |
| Venlafaxine(SNRI) | Major depression | 75 mg/d; 225 mg | Ulcera, thrombozytopenia, hyponatremia, insomnia, suicide, hypotension, tachycardia, nausea, irritability, apathy, weight changes | Hepatic and pancreatic dysfunction, suicidal behavior, cardiac diseases | MAO inhibitors, caution with NSARs, Warfarin, CYP3A3/4-inhibitors | Improvement of depression scores |
| Buspirone(serotonin-agonist) | Anxiety, aggression | 15–30 mg/d in 2–3 doses | Dizziness, hedache, somnolence | Metabolic acidosis, diabetes, liver and renal dysfunction | CYP3A4, MAO inhibitors, haloperidol, carbamazepine, nefazodone, rifampicin, itraconalzole, grape fruit juice | Reduction of aggressive and perseverative behavior |
| Amantadine | ||||||
| Amantadine(NMDA antagonist) | Rigor, tremor, akinesis, chorea | 200–400 mg/d | Agitation, anxiety or nervousness, difficulty concentrating, headache, edema, diarrhea, irritability, loss of appetite, nausea, skin changes, sleeping disturbances | Psychosis, depression, renal dysfunction, seizure disorders, edema, hypotension | Drugs with anticholinergic properties | Improvement of motor function; decline of cognitive functions has been reported; conflicting data |
| Riluzole | ||||||
| Riluzole | Chorea | 50–200 mg | Headache, nausea, somnolence, paresthesia, neutropenia, elevated liver enzymes, nonspecific interstitial pneumonia | Liver dysfunction, elevated liver enzymes | CYP1A2 inhibitors: elevated levels; CYP1A2 inductors (smoking cigarettes!): lowered levels | Improvement of chorea, (restricted to high doses [200 mg]) |
| Mood-stabilizing antiepileptic drug (AED) | ||||||
| Valproic acid | Mood stabilizer, epilepsy, myoclonus | 20 mg/kg in 2–4 doses | Nausea, vomiting, abdominal pain, weight gain, somnolence, headache, blood dyscrasia, hyperammonemia, dizziness, fatal hepatotoxicity, pancreatitis | Hepatic and pancreatic dysfunction, pregnancy, carnitin-palmitoyl-transferase type II deficiency | Plasma levels decrease; cytochrome P450 inducers | Improvement of irritability; myoclonus and seizures in JHD |
| Levetiracetam | Epilepsy | 2×750 mg/d | Nasopharyngitis, somnolence, headache, sleepiness, dizziness | Hepatic and renal dysfunction, suicidal tendency, hemodialysis, hematologic abnormalities pregnancy | Baclofen, duloxetine, trazodone | Improvement of chorea |
Notes: Listed drugs are not complete. Details of drugs are mainly based on ROTE LISTE®/Fachinfo (http://www.online.rote-liste.de; http://www.fachinfo.de),109,110 copyright © 2014, ROTE LISTE®/Fachinfo; European Medicine Agency (http://www.ema.europa.eu);111 or drug information of the Food and Drug Administration (FDA, http://www.fda.gov).112
Abbreviations: d, day; HD, Huntington’s disease; JHD, juvenile Huntington’s disease; NaSSA, noradrenergic and specific serotonergic antidepressant; NMDA, N-methyl-D-aspartate; NSAIDs, nonsteroidal anti-inflammatory drugs; SNRI, serotonin-norephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.