Of the 66 expert clinicians contacted, 49 (75%) responded. Not all respondents answered all individual questions. Of these 49 experts, 21 were from Europe, 26 from North America, and 3 from Australia. Most respondents were neurologists (33) or psychiatrists (14), and 2 were double boarded in neurology and psychiatry. Most respondents reported seeing at least 50 HD patients per year; there were only 8 who reported seeing fewer than this number. Fourteen reported seeing 50-100 patients annually; 9 reported seeing 100-150 and 18 more than 150 patients per year.
Behavioral Interventions: The first questions concerned non-pharmacological interventions for OCBs; specifically, respondents were asked treatment practice using cognitive behavioral therapy (CBT) in patients with either mild, moderate, or severe cognitive impairment. There was also a query about the perceived benefit of family education. Many respondents (23%) indicated having no experience with CBT for HD patients, but others (50%) reported that CBT was at least somewhat effective, but only in those with mild cognitive impairment. It was not endorsed for patients with moderate or severe cognitive impairment. However, 83% of respondents endorsed family education on OCBs.
Practice patterns by drug/drug class: The next set of treatment questions concerned drug selection and was phrased as follows: “Assuming there are no comorbid symptoms to influence your decision, what is your practice pattern with the use of [drug or drug class] for the treatment of OCBs in Huntington’s disease?”
An SSRI was first choice of most respondents for treatment of OCBs when no comorbid symptoms influenced treatment decisions. CMI was the next most frequently endorsed first choice, followed by APDs and AEDs. Considering all monotherapy choices (first and alternative) SSRIs were most frequently endorsed (89%). CMI also rated highly and was endorsed as monotherapy by 63% of respondents who had experience with this drug. The BZDs, TCAs (excluding clomipramine) and lithium were not chosen as first choice agent by any respondent. APDs and AEDs were often utilized as augmenting and adjunctive therapies. BZDs were most often used as adjunctive therapy when anxiety was a comorbid factor.
Figure 1. Choice of drug from OCBs across all geographic regions. Vertical axis is number of responses. See box 3 for abbreviations.
Figure 2. Choice of drug for OCBs, European respondents. Vertical axis is number of responses. See box 3 for abbreviations.
Figure 3. Choice of drug for OCBs, North American and Australian respondents. Vertical axis is number of responses. See box 3 for abbreviations.
Table 1. Choice of drug for treating OCBs across all geographic regions. N is number of responses. Percentages are relative to N. See box 3 for abbreviations.
Perceived efficacy of drug choice: Most experts indicated that SSRIs are the most effective drug choice for treating OCBs in HD. For respondents experienced with clomipramine, efficacy ratings for this drug were similar to SSRIs. Table 1 summarizes expert views about the relative efficacy of the surveyed drugs.
Table 2. Expert opinion of drug efficacy for treating OCBs. N is number of responses. Percentages are relative to N. See box 3 for abbreviations.
Perceived benefit of high dose SSRI optimization: Respondents were also asked about SSRI dosing optimization for treating OCBs in HD to upper limits of manufacturer recommended dosage for depression. Though all respondents perceived a level of increased effectiveness with higher dosing, the degree of perceived effect varied widely. Seven respondents reported beneficial results in selected patients using dosage exceeding that recommended by the manufacturer. Subsequent to the survey, the Federal Drug Administration issued a directive to change manufacturer recommended high dosage of citalopram from 60 mg to 40 mg per day due to increase in heart arrhythmias and lack of benefit of the higher dose for treating depression. However, seven respondents reported beneficial results for treating OCBs in selected patients using doses higher than that recommended for depression.
Dosing interval choices: The respondents were asked about dose titration intervals for the drug/drug class alternatives. For both SSRI and CMI, the top two pharmacological agents for monotherapy, more of respondents reported they would increase from initial dose after 4-6 weeks, followed by 2-4 weeks as the second most endorsed option (Table 3).
Table 3. Choice of dosing titration intervals for drugs used to treat OCBs. N is number of responses. Percentages are relative to N. See box 3 for abbreviations.
Adding or switching drugs for inadequate response to initial drug choice
: The next set of iterative questions regarded strategies for either adding or switching drug when an initial drug failed to adequately treat OCBs in HD. The most notable result to this set of questions is that no consistent pattern was demonstrated. When SSRI was chosen as initial monotherapy but gave no or only partial benefit, the next step in management varied: switch to another SSRI (23%), switch to CMI (18%), add CMI (16%) or an APD (16%), switch to serotonin and norepinephrine reuptake inhibitor (SNRI) (14%). Less common choices (5% each) were: switch to an APD or add BZD. When CMI was chosen as initial monotherapy but gave no or only partial benefit, next step choices also varied and included: add an APD (41%), switch to SSRI (26%), add SSRI (11%), add an AED (11%), or switch to an APD (7%). Fewer than 5% chose any other option. In response to separate questions regarding APDs, AEDs, BZDs or TCAs (other than clomipramine), the majority of those surveyed reported they used all of these agents most frequently as adjunctive therapy.
Table 4. Alternate choice of drug for treating OCBs when inadequate response to initial therapy. N is number of responses. Percentages are relative to N. Alternate listed only if chosen by 5% or more of respondents. See box 3 for abbreviations.
Specific drugs favored within class: Respondents were asked about preferred drugs within class for treating OCBs in HD. Preferred drugs included the SSRIs: citalopram (35%), sertraline (25%), paroxetine (15%), fluoxetine (11%), the APDs: olanzapine (52%), risperidone (34%), quetiapine (23%), aripiprazole (21%), the AEDs: valproate derivatives (70%), carbemazepine (22%), lamotrigene (16%), topiramate (11%). When using BZDs, favored drugs were: clonazepam (60%), alprazolam (28%), lorazepam (27%). For a separate query regarding Lithium, most respondents reported insufficient experience using this agent for OCBs in HD (56%). Another 29% felt it was not an appropriate alternative. Only 14% reported using it as monotherapy.
Preferred drug for OCBs given comorbid psychiatric symptoms: Respondents were asked, for each of the medication classes (SSRI, CMI, APBs, AEDs, BZDs, TCAs, lithium) about how selection of that drug would be affected by the presence of a given comorbid symptom occurring with OCBs. Comorbid symptoms queried included depression, anxiety, psychotic behaviors, aggressive or threatening behaviors, impulsivity, insomnia, or hypersexuality. Given comorbid depression, anxiety, impulsivity, or hypersexuality, SSRI drugs were most frequently chosen. Antipsychotic drugs were chosen when comorbid psychotic or aggressive behaviors occurred. See figure 4 and table 5.
Figure 4. Choice of drug for treating OCBs that occur with a given comorbid symptom. Blue bars indicate the number of experts who selected the drug as first choice; red bars indicate the number who selected the drug as alternative monotherapy. See box (more ...)
Table 5. Choice of drug for treating OCBs that occur with a given comorbid symptom. Percentages are relative to the number of experts who provided information for any symptom x drug combination (47). The last column is the sum of the previous two; the percentages do not always match precisely because of roundoff. The table only includes drugs chosen by 10% or more of the experts. See box 3 for abbreviations.