Antipsychotic drugs are frequently prescribed for several symptoms of Huntington's disease (HD). Does it make any difference which one is used? While there is no clinical trial evidence for HD, early clinical trials in schizophrenia suggested that one is not that much better than another. However more recent reviews and studies make the important point that older ones -- like Haldol® -- appear to have more unwanted side effects than the newer ones, side effects that may further impair gait, balance and cognition in HD.

Antipsychotic drugs are a class of psychiatric medications that were developed primarily to treat schizophrenia, a mental illness characterized by hallucinations (seeing or hearing things that aren't present) or delusions (thoughts not based in reality). Though lacking FDA approval for their use in other situations, these drugs are prescribed for other situations including treatment for several HD symptoms. Indeed, there is general agreement that these drugs are helpful in the treatment of chorea, irritable and aggressive behaviors, agitation, and psychotic symptoms in HD. Unfortunately several new studies suggest that these drugs also have significant side effects, ones that can worsen some symptoms already present in HD: impaired cognition, apathy, or bradykinesia (Parkinson's disease like symptoms), walking and balance problems, and swallowing problems.

Does it make a difference which antipsychotic is used for HD? There has been essentially no quality study comparing treatment effects or side effects among different antipsychotic drugs for any symptom in HD. There is only one study in HD, and several studies in other diseases that might help inform us:

  • HD: in a new study from France [Désaméricq G 2014] that followed the course of 968 HD patients for 8 years, a commonly used older antipsychotic drug was associated with more cognitive decline than the newer antipsychotics.
  • Schizophrenia: In the new study [Leucht S 2013] which analyzed results from 212 high quality clinical trials in more than 43,000 schizophrenia patients, authors compared efficacy, or how well each drug worked, and side effects for 15 different antipsychotic drugs. Most important for HD, the newer antipsychotic drugs olanzapine (Zyprexa®), risperidone (Risperdal®), quetiapine (Seroquel®), and aripiprazole (Abilify®) had fewer Parkinsonism side effects than older drugs like haloperidol (Haldol®).
  • Home-dwelling dementia patients: In a large study of almost 27,000 dementia outpatients, authors report a higher risk of death if an older drug like haloperidol was prescribed rather than a newer drug like risperidone [Langballe EM 2014]. This was also seen in another large study of veterans [Rossom RC 2010].
  • Nursing home dementia residents: Though not all studies are in agreement, it appears there is greater risk of death among those on the older antipsychotic drugs than the newer ones [Aparasu RR 2012] [Huybrechts KF 2012]. Antipsychotic drugs impair cognition [Vigen CL 2011].
  • Parkinson's disease: Studies in this disease suggest that except for clozapine, a drug not often utilized due to blood-related side effects, and quetiapine (Seroquel®), all the others worsen motor symptoms of Parkinson's [Goldman JG 2011].

Why antipsychotic drug choice may make a difference for HD: At least in the past, older drugs like haloperidol or fluphenazine have been utilized for chorea usually at a point when bradykinesia symptoms are not prominent in HD. But too often these drugs are continued, then increased in dosage over the course of the disease if behavioral symptoms occur. This can result in more motor impairment than that caused by the disease alone. Because we have no clinical evidence base to inform us, we should take the lessons learned from other disease study to guide us: older antipsychotic drugs are associated with more risk of death, and more Parkinson's like symptoms which would worsen impairments caused by bradykinesia of HD. My advice: if an antipsychotic is needed, start -- and stay -- with a newer drug.

References

Désaméricq G, Dolbeau G, Verny C, Charles P, Durr A, Youssov K, Simonin C, Azulay JP, Tranchant C, Goizet C, Damier P, Broussolle E, Demonet JF, Morgado G, Cleret de Langavant L, Macquin-Mavier I, Bachoud-Lévi AC, Maison P. Effectiveness of anti-psychotics and related drugs in the Huntington French-speaking group cohort. PLoS One. 2014 Jan 15;9(1):e85430. doi: 10.1371/journal.pone.0085430. eCollection 2014. PubMed abstract

Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013 Sep 14;382(9896):951-62. doi: 10.1016/S0140-6736(13)60733-3. Epub 2013 Jun 27. PubMed abstract

Langballe EM, Engdahl B, Nordeng H, Ballard C, Aarsland D, Selbæk G. Short- and long-term mortality risk associated with the use of antipsychotics among 26,940 dementia outpatients: a population-based study. Am J Geriatr Psychiatry. 2014 Apr;22(4):321-31. doi: 10.1016/j.jagp.2013.06.007. Epub 2013 Sep 7. PubMed abstract

Rossom RC, Rector TS, Lederle FA, Dysken MW. Are all commonly prescribed antipsychotics associated with greater mortality in elderly male veterans with dementia?. J Am Geriatr Soc. 2010 Jun;58(6):1027-34. doi: 10.1111/j.1532-5415.2010.02873.x. Epub 2010 May 7. PubMed abstract

Aparasu RR, Chatterjee S, Mehta S, Chen H. Risk of death in dual-eligible nursing home residents using typical or atypical antipsychotic agents. Med Care. 2012 Nov;50(11):961-9. doi: 10.1097/MLR.0b013e31826ec185. PubMed abstract

Huybrechts KF, Gerhard T, Crystal S, Olfson M, Avorn J, Levin R, Lucas JA, Schneeweiss S. Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ. 2012 Feb 23;344:e977. doi: 10.1136/bmj.e977. PubMed abstract

Vigen CL, Mack WJ, Keefe RS, Sano M, Sultzer DL, Stroup TS, Dagerman KS, Hsiao JK, Lebowitz BD, Lyketsos CG, Tariot PN, Zheng L, Schneider LS. Cognitive effects of atypical antipsychotic medications in patients with Alzheimer's disease: outcomes from CATIE-AD. Am J Psychiatry. 2011 Aug;168(8):831-9. doi: 10.1176/appi.ajp.2011.08121844. Epub 2011 May 15. PubMed abstract

Goldman JG, Vaughan CL, Goetz CG. An update expert opinion on management and research strategies in Parkinson's disease psychosis. Expert Opin Pharmacother. 2011 Sep;12(13):2009-24. doi: 10.1517/14656566.2011.587122. Epub 2011 Jun 2. PubMed abstract