In a recent publication in the Journal for Huntington's Disease, Tedroff and collaborators report that antidopaminergic (antipsychotic and tetrabenazine) drugs were associated with more rapid progression of Huntington's disease. Any study showing a factor associated with more rapid progression is important. However the question remains whether these medications "caused" the more rapid progression, or whether those on these medications had a more severe type of HD that would have progressed more rapidly with or without the medications.

What is the take home message from this study for individuals with HD who are taking these drugs?

Dopamine and Antidopaminergic Medications: Dopamine is an important brain chemical whose action is complex. Dopamine is a critical component of circuits that promote an action in one area of the brain, while inhibiting or stopping the action in another. In a healthy person, these circuits are balanced. However, in many brain diseases dopamine systems are not balanced. In HD this imbalance contributes both to involuntary movements like chorea, and to slowing of voluntary movement as in speed of walking or use of hands to perform tasks.

Antidopaminergic (anti-dopamine) medications include drugs like tetrabenazine, and antipsychotic medications like Haldol® or Zyprexa®. This type of medication is frequently used to treat chorea and behavioral symptoms like irritability or aggressive symptoms and psychosis in HD.

The Study: This study looked at data obtained on 651 individuals who were participants in the European HD Registry Study over a 2 year time interval [Tedroff J 2015]. Half were taking an antipsychotic medication or tetrabenazine, and the other half were not. The authors found that disease progression as measured by functional capacity and (involuntary) motor ability was faster for those on these medications than those who were not on them. Multiple analyses were performed to show that the two groups were well matched, but this type of retrospective study can only conclude that the drugs were associated with the difference, not that drugs caused the difference.

Another concern with this study is that the Registry population includes those who return for study visits; it does not include those who may have more severe disease. Consequently, the findings may not relate to the entire population of HD individuals.

The Take Home Message: With any medication used for any disease, it is about drug benefit and drug risk. Though not proven, we should pay attention to the extra risk that is suggested for these drugs. First, just as before this article: don't take these drugs if you don't need them. If you are taking this type of drug for anxiety, depression, insomnia or other symptoms, check with your doctor about an alternative.

  • For symptoms like irritability,anxiety, depression, a drug like Zoloft® (sertraline) or other types of antidepressants may be a better choice.
  • For various behavioral symptoms, a mood stabilizer seizure medication like depakote may be an alternative.
  • Don't use them for insomnia - good sleep hygiene or other drugs may be better choices.
  • For chorea, the benefit and risk must be considered. If chorea is severe, use care when starting any of these drugs, with the goal of decreasing chorea, not eliminating it. Keep dosages low.
  • Don't be afraid to use antipsychotics for more severe symptoms, where the benefit far outweighs the risk.

Though not definitive, this study is worrisome regarding use of these drugs, which have probably been over-prescribed in HD. This study should bring more caution regarding their use.

To conclude on a more positive note: We hope to have better news from the PRIDE-HD trial of pridopidine, which is a drug that may help balance dopamine action and motor symptoms. Further a recent study in a mouse model of HD suggests it may have potential to slow down disease progression [Squitieri F 2015].

References

Tedroff J, Waters S, Barker RA, Roos R, Squitieri F; EHDN Registry Study Group. Antidopaminergic Medication is Associated with More Rapidly Progressive Huntington's Disease. J Huntingtons Dis. 2015;4(2):131-40. doi: 10.3233/JHD-150143. PubMed abstract

Squitieri F, Di Pardo A, Favellato M, Amico E, Maglione V, Frati L. Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model. J Cell Mol Med. 2015 Nov;19(11):2540-8. doi: 10.1111/jcmm.12604. Epub 2015 Jun 22. PubMed abstract