Irritability is one of the very common symptoms in Huntington's, occurring in greater than 60% of individuals when observed over a one month time period [Paulsen JS 2001]. Symptoms of irritabilty include extreme sensitivity to people, quick excitability, and overreaction to feelings or events. Irritability can lead to aggressive behaviors when the emotional response escalates and cannot be controlled. This symptom can occur in both early and later stages of disease [Thompson JC 2002].

Irritability Treatments: As much as possible, it is important to identify and avoid situations of stress or "triggers" that can exacerbate irritability and set off more aggressive behaviors. When reassurance and other supportive measures are not effective, drugs from several classes may be useful. Though the experts are not in full agreement, SSRI antidepressant medications are used as first line treatment for mild and moderately severe irritability -- even when depression is not present. When symptoms are more severe and urgent treatment is needed, antipsychotic medications should be utilized. However, antipsychotic drugs should not be the first choice drug for milder forms of irritability due to greater side effects.

When symptoms are either more severe or are not controlled by antidepressants, antipsychotic medications and mood stabilizer drugs can be added. As with other drug classes used for Huntington's, evidence for benefit comes mostly from studies in other conditions like Parkinson's disease.

Mood Stabilizer Drugs: In other diseases, this class of drugs is used most often for control of seizures and treatment of manic depressive or bipolar psychiatric illness. In Huntington's, these drugs are used to treat several behavioral symptoms including irritability and agitation. It is always best to use the lowest dose that is helpful.

Commonly Used Mood Stabilizer Medications for Irritability

Valproate (Depakene®) or divalproex (Depakote®): Dosages start at 125 mg twice a day, gradually increasing to an effective dose (usually about 500 mg twice daily). Blood tests are necessary to check for liver and blood side effects. Other side effects include sleepiness, dizziness, nervousness, nausea, diarrhea, and weakness.

Carbamazepine (Tegretol®): Dosages start at 100-200 mg/day and are gradually increased to a usual dose of 800-1200 per day. Blood tests are necessary to check for liver and blood side effects. Other side effects include nausea, dizziness, sleepiness, and fluid retention.

Oxcarbazepine (Trileptal) is a drug similar to carbamazepine, but does not require as frequent blood testing. Dosage starts at 150 mg once or twice daily, and is increased gradually as needed up to 600 mg twice daily.

Lamotrigine (Lamictal®): This drug is a more recent addition to this drug class. It may be the preferred drug due to fewer side effects than others. Regular blood testing is not necessary for this drug. In addition this drug is used to treat depression that is resistant to other drugs. Side effects include dizziness, sleepiness, and frequent rash. Dosing starts at 50 mg/day, and increases by 50 mg each two week period till a maximum of 300 mg dose is reached.

An algorithm for treatment of irritability in HD can be downloaded from the web that summarizes various treatments and is in a form that may be useful to take to your doctor [Groves M 2011].

References

Paulsen JS, Ready RE, Hamilton JM, Mega MS, Cummings JL. Neuropsychiatric aspects of Huntington's disease. J Neurol Neurosurg Psychiatry. 2001 Sep;71(3):310-4. PubMed abstract

Thompson JC, Snowden JS, Craufurd D, Neary D. Behavior in Huntington's disease: dissociating cognition-based and mood-based changes. J Neuropsychiatry Clin Neurosci. 2002 Winter;14(1):37-43. PubMed abstract

Groves M, van Duijn E, Anderson K, Craufurd D, Edmondson MC, Goodman N, van Kammen DP, Goodman L. An International Survey-based Algorithm for the Pharmacologic Treatment of Irritability in Huntington's Disease. PLoS Curr. 2011 Aug 30;3:RRN1259. PubMed abstract