How safe are antipsychotic medications -- that most often include Risperdal®, Zyprexa®, Seroquel® and Haldol® -- in Huntington's? This is an especially important question to address following the publication of two separate studies in highly respected medical journals earlier this month addressing risks of these drugs.

Though these are different types of studies and neither specifically addresses antipsychotic drug use in Huntington's, the stark results: that antipsychotic usage increases the risk of death -- nearly twice as much in one of the studies -- prompted strong expert recommendations for limiting the use of these drugs to severe neuropsychiatric symptoms.

It is important to remember that there is expert medical agreement for the use of antipsychotic drug treatment for severe neuropsychiatric symptoms. This applies to all disease situations including Huntington's and includes symptoms of aggression and those related to psychosis. In these situations, these drugs are first choice treatments and absolutely essential for safety for patients and families.

Simply Put

Antipsychotic drugs are frequently prescribed for many Huntington symptoms.

There is a greater risk of dying in those who use antipsychotic drugs.

There should be greater caution in the frequent use of these drugs for Huntington's.

The important question is whether antipsychotics should be used in treatment of less severe symptoms. How big might this problem be in Huntington's? Results from a recent survey of Huntington Expert Physicians from North America suggest that it could be a substantial problem. Survey results (presented in poster form at the Huntington Study Group Symposium in November 2008) indicate that antipsychotics are frequently used for treatment of less severe Huntington symptoms including irritability, insomnia, or chorea. In fact, survey results suggest that only antidepressants are used more frequently than antipsychotics for treatment of Huntington symptoms.

However based on results from the following medical studies, it is a very appropriate time to reconsider this treatment pattern in Huntington's

The Studies:

Study 1: Reported in Lancet Neurology [Ballard C 2009]: Study participants included about 150 Alzheimer patients residing in nursing homes in England who had placed on antipsychotic medication by their local doctors for at least 3 months. After entering the trial, half of the participants continued antipsychotic medications for a year, and the other half received placebo for a year. The Results: Those who remained on antipsychotic drugs had a greater risk of dying within 12 months (3 antipsychotic participants, 1 placebo). Though this was not as well studied as the first year, the even more alarming finding was that risk of dying increased dramatically over the subsequent year (7 antipsychotic participants, 1 placebo) with a 50% increased risk of dying at 3 years after entering the trial.

Study 2: Reported in New England Journal of Medicine [Ray WA 2009]: Using records from more than 80,000 Medicaid recipients using antipsychotic drugs (at any age for any cause) the authors surveyed records for only one cause of death: sudden death from a heart cause. They compared these results to matched controls or similar Medicaid individuals not using antipsychotic drugs. The Results: Those on antipsychotics had increased risk of sudden cardiac death, this risk increased with higher dosage and age of the patient. They also showed that the newer antipsychotic drugs were no safer than haldol in causing sudden death.

Discussion: Based on these study results the experts gave direct and strong recommendations to prescribing doctors:

  • Authors from the Alzheimer's Study 1: "Our opinion is that there is still an important but limited place for atypical antipsychotics in the treatment of severe neuropsychiatric manifestations (in Alzheimers) particularly aggression. However, the accumulating safety concerns, including the substantial increase in long-term mortality, emphasize the urgent need to put an end to unnecessary and prolonged prescribing."
  • From the editorial discussing Study 2 (that more directly applies to antipsychotic use in Huntington's): " . . in patient populations for whom the evidence of the efficacy of antipsychotic medications is limited and the risk of a fatal side effect is clear, prudence would suggest that the use of these drugs should be reduced sharply."

Editor's Comments: There is great concern among doctors and patients alike about the risks of Huntington's new drug Xenazine® (tetrabenazine). Yet at the same time, we (myself included) have been vastly less concerned about the risks of antipsychotic drugs -- even though there have been warning signals from several earlier medical studies. But there can be no excuse for lack of concern now: The results from these 2 recent studies and the expert recommendations that followed are clear, and should lead to a change in how these drugs are used for Huntington's.

  • Antipsychotic drugs should be used only for severe neuropsychiatric symptoms that include aggression and psychosis.
  • They should be considered risky treatment for the more minor symptoms of HD, and used only after safer alternatives are unsuccessful.
  • If antipsychotics are used there should be frequent attempts to lower dosage or discontinue these drugs after symptoms have been controlled. The experts suggest this should be done at least every 6 months.

References

Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, Gill R, Juszczak E, Yu LM, Jacoby R; DART-AD investigators. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol. 2009 Feb;8(2):151-7. doi: 10.1016/S1474-4422(08)70295-3. Epub 2009 Jan 8. PubMed abstract

Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009 Jan 15;360(3):225-35. doi: 10.1056/NEJMoa0806994. PubMed abstract