Med/Psych Update

How to target psychiatric symptoms of Huntington’s disease

Current Psychiatry. 2012 September;11(9):34-39

References

1. Harper PS. The epidemiology of Huntington’s disease. Hum Genet. 1992;89(4):365-376.

2. Paulsen JS, Ready RE, Hamilton JM, et al. Neuropsychiatric aspects of Huntington’s disease. J Neurol Neurosurg Psychiatry. 2001;71(3):310-314.

3. Thompson JC, Harris J, Sollom AC, et al. Longitudinal evaluation of neuropsychiatric symptoms in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2012;24(1):53-60.

4. Beglinger LJ, Langbehn DR, Duff K, et al. Probability of obsessive and compulsive symptoms in Huntington’s disease. Biol Psychiatry. 2007;61(3):415-418.

5. Naarding P, Janzing JG, Eling P, et al. Apathy is not depression in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2009;21(3):266-270.

6. Ho AK, Gilbert AS, Mason SL, et al. Health-related quality of life in Huntington’s disease: which factors matter most? Mov Disord. 2009;24(4):574-578.

7. Hamilton JM, Salmon DP, Corey-Bloom J, et al. Behavioural abnormalities contribute to functional decline in Huntington’s disease. J Neurol Neurosurg Psychiatry. 2003;74(1):120-122.

8. Hubers AA, Reedeker N, Giltay EJ, et al. Suicidality in Huntington’s disease. J Affect Disord. 2012;136(3):550-557.

9. Videnovic A, Leurgans S, Fan W, et al. Daytime somnolence and nocturnal sleep disturbances in Huntington disease. Parkinsonism Relat Disord. 2009;15(6):471-474.

10. Craufurd D, Thompson JC, Snowden JS. Behavioral changes in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(4):219-226.

11. Duff K, Paulsen JS, Beglinger LJ, et al. “Frontal” behaviors before the diagnosis of Huntington’s disease and their relationship to markers of disease progression: evidence of early lack of awareness. J Neuropsychiatry Clin Neurosci. 2010;22(2):196-207.

12. Tsuang D, Almqvist EW, Lipe H, et al. Familial aggregation of psychotic symptoms in Huntington’s disease. Am J Psychiatry. 2000;157(12):1955-1959.

13. Holl AK, Wilkinson L, Painold A, et al. Combating depression in Huntington’s disease: effective antidepressive treatment with venlafaxine XR. Int Clin Psychopharmacol. 2010;25(1):46-50.

14. Killoran A, Biglan KM. Therapeutics in Huntington’s disease. Curr Treat Options Neurol. 2012;14(2):137-149.

15. Ranen NG, Peyser CE, Folstein SE. ECT as a treatment for depression in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 1994;6(2):154-159.

16. Rosenblatt A, Ranen NG, Nance MA, et al. A physician’s guide to the management of Huntington’s disease. 2nd edition. http://www.hdsa.org/images/content/1/1/11289.pdf. Published 1999. Accessed July 27, 2012.

17. Squitieri F, Cannella M, Piorcellini A, et al. Short-term effects of olanzapine in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(1):69-72.

18. Johnston TG. Risperidone long-acting injection and Huntington’s disease: case series with significant psychiatric and behavioural symptoms. Int Clin Psychopharmacol. 2011;26(2):114-119.

19. Alpay M, Koroshetz WJ. Quetiapine in the treatment of behavioral disturbances in patients with Huntington’s disease. Psychosomatics. 2006;47(1):70-72.

20. Lin WC, Chou YH. Aripiprazole effects on psychosis and chorea in a patient with Huntington’s disease. Am J Psychiatry. 2008;165(9):1207-1208.

21. Oulis P, Mourikis I, Konstantakopoulos G, et al. Aripiprazole in the treatment of olanzapine-resistant psychotic and motor symptoms of Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2010;22(3):352c.e4-352c.e5.

22. van Vugt JP, Siesling S, Vergeer M, et al. Clozapine versus placebo in Huntington’s disease: a double blind randomised comparative study. J Neurol Neurosurg Psychiatry. 1997;63(1):35-39.

23. Verhagen Metman L, Morris MJ, Farmer C, et al. Huntington’s disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Neurology. 2002;59(5):694-699.

24. Lucetti C, Del Dotto P, Gambaccini G, et al. IV amantadine improves chorea in Huntington’s disease: an acute randomized, controlled study. Neurology. 2003;60(12):1995-1997.

25. O’Suilleabhain P, Dewey RB, Jr. A randomized trial of amantadine in Huntington disease. Arch Neurol. 2003;60(7):996-998.

¹⁶ The HDSA guide notes psychostimulants may worsen irritability in HD and have a high potential for abuse. ECT appears to have little effect on apathy.¹⁵

Anxiety. A small, open-label study of 11 patients found that olanzapine, 5 mg/d, significantly improved depression, anxiety, irritability, and obsessive behavior in HD patients.¹⁷

The HDSA guide suggests treating anxiety and obsessive-compulsive symptoms as you would in patients without HD. For anxiety, SSRIs and possibly a short-term trial of a low-dose benzodiazepine (ie, lorazepam, clonazepam) are suggested.¹⁶ Benzodiazepines may increase the risk of falls and delirium in this population. Anecdotally, buspirone is helpful in some patients, with a starting dose of 5 mg 2 to 3 times per day and increased to 20 to 30 mg/d in divided doses.¹⁶ For obsessive-compulsive symptoms, SSRIs are recommended; atypical antipsychotics are reserved for severe or refractory symptoms.¹⁶

Disinhibition and impulsivity. There’s no research on treating disinhibition and impulsivity in HD. In our clinical experience, atypical antipsychotics are the most helpful. Factors regarding choosing an agent and dosing levels are similar to those for psychotic symptoms.

Psychotic symptoms. Most studies of typical and atypical antipsychotics for HD psychosis have shown beneficial effects.^14,16-21 Neurologists frequently use these agents for managing chorea. Both neurologic and psychiatric features of the patient’s presentation must be considered when selecting a drug because treatment directed at 1 component of the disease may inadvertently exacerbate another. Specifically, higher potency antipsychotics (eg, haloperidol) are effective for chorea but can dramatically worsen bradykinesia; lower potency agents (eg, quetiapine) are less helpful for chorea but do not significantly worsen rigidity symptoms.

Olanzapine has been shown to improve chorea, anxiety, irritability, depression, sleep dysfunction, and weight loss in addition to psychotic symptoms.^14,17 We find that olanzapine treats a constellation of symptoms common among HD patients, and we prescribe it frequently. Because olanzapine is considered a mid-potency agent, we find it’s best suited for concurrent control of psychotic symptoms and mild to moderate chorea in patients with minimal bradykinesia. Start olanzapine at 2.5 mg/d and gradually increase to 5 to 10 mg/d as tolerated.¹⁴

Clinical Point

Olanzapine has been shown to improve chorea, anxiety, irritability, depression, and sleep dysfunction in HD patients

Risperidone is effective for treating psychosis and chorea. It can be started at 0.5 to 1 mg/d, and gradually increased to 6 to 8 mg/d.¹⁴ The depot formulation of risperidone has been shown to be effective in HD, which may help patients adhere to their medication.¹⁸ Risperidone is a mid-high potency antipsychotic, and in our experience is best used to control psychotic symptoms in patients with moderate chorea and few or no symptoms of bradykinesia or rigidity.

Quetiapine reduces psychotic symptoms, agitation, irritability, and insomnia without worsening bradykinesia or rigidity,¹⁹ but it is not beneficial for chorea. It can be started at 12.5 mg/d and gradually increased for effect as tolerated, up to 600 mg/d (depending on indication), in 2 or 3 divided doses.¹⁴

Haloperidol is a high-potency typical antipsychotic and may help psychotic patients with severe chorea; it should not be used in patients with bradykinesia. Start haloperidol at 0.5 to 1 mg/d and gradually increase to 6 to 8 mg/d as tolerated.¹⁴ Because of higher likelihood of side effects with typical antipsychotics, we often reserve its use for patients whose psychosis does not respond to atypical agents.

Other antipsychotics. Aripiprazole in HD has been examined in only 2 single- patient case reports^20,21; the drug appeared to reduce psychosis and possibly chorea. Clozapine’s effectiveness for HD psychosis is not well known. It does not appear to be helpful for chorea and can cause agranulocytosis.²²

Because one of the hallmarks of HD is dementia, it is worth noting that the FDA has issued a “black-box” warning on the use of antipsychotic drugs in patients with dementia because of concerns regarding increased mortality. However, drawing specific conclusions is difficult because the FDA warning is based on studies that looked primarily at Alzheimer’s disease and vascular dementia, not HD.

Other pharmacotherapies

Clinical Point

Tetrabenazine is FDA-approved for HD but can increase the risk of depression and suicidality

Tetrabenazine is the only FDA-approved drug for treating HD. However, it carries a “black-box” warning for increased risk of depression and suicidal ideation and is contraindicated in suicidal patients and those with untreated or inadequately treated depression.

Although several small trials have had conflicting results regarding its benefit, amantadine sometimes is used to treat chorea.^23-25 For more information about tetrabenazine and amantadine, see Box 3.

Box 3