Rivastigmine transdermal patches in the treatment of dementia in Alzheimer's disease in adults with Down syndrome‐pilot study

Numerous studies have now been published demonstrating the association between dementia in Alzheimer’s disease (DAD) and Down syndrome (DS). The use of anti-dementia drugs in the DS population has been the subject of the Cochrane Database of Systematic Reviews (Mohan et al., 2009). A significant problem with oral anti-dementia medication has been their high side-effect rate and poor compliance. Novartis Pharma (East Hanover, NJ, USA) has developed a rivastigmine transdermal patch as a means of overcoming these problems. Rivastigmine transdermal patches provide 24-h continuous drug delivery with similar efficacy to the highest recommended dose of oral rivastigmine (Dhillon, 2011). Contact dermatitis, nausea and vomiting are the commonest side effects of the patches. Compliance to treatment in DAD and caregiver preference appears to be better for transdermal patches (Darreh-Shori and Jelic, 2010. This is the first report to investigate the efficacy, tolerability and compliance of adults with DS with DAD for rivastigmine transdermal patches. Case notes of DS patients with DAD, diagnosed according to ICD-10 (WHO, 1993) criteria and treated with rivastigmine patches were audited. Baseline assessments, Time 1 (T1) of (i) global functioning was made using the Dementia Questionnaire for Mentally Retarded Persons (DMR) (ii) non-cognitive and behavioural problems, using the Neuropsychiatric Inventory (NPI). During the first 2weeks, patients were prescribed 1.5-mg rivastigmine orally, increasing to twice a day for a further 4 weeks. Over the rest of the 6-month treatment period, subjects were treated with 4.6mg/24 h rivastigmine patches. At 6months, the baseline neuropsychological tests were repeated; Time 2 (T2). The findings for the patients treated with rivastigmine (N=10) were compared with findings of DS persons with DAD untreated (N=13) and treated with oral rivastigmine (N=17; Prasher et al., 2005). Age was distributed normally (Kolmogorov–Smirnov Test p=0.2). There was no statistically significant difference for age (untreated group= 54.9 years; oral rivastigmine group= 53.2 years and rivastigmine patches group= 56.2 years; one-way ANOVA=1.1, p=0.37). Analysis of co-variance for the DMR, comparing T2-T1 score but controlling for T1 score, showed no difference between the three groups (F= 2.1, p= 0.14). With the use of the same analysis, findings were (i) non-treated versus oral medication (F= 3.9, p= 0.06); (ii) non-treated versus patches (F= 2.7, p= 0.11); (iii) oral versus patches (F= 0.7, p= 0.41); and (iv) untreated versus oral and patches (F= 4.2; p= 0.048). Analysis of co-variance for the NPI, comparing T2-T1 score but controlling for T1 score, showed borderline difference between the three groups (F=3.3, p=0.05). NPI findings for other results were (i) non-treated versus oral medication (F=5.3, p=0.03); (ii) non-treated versus patches (F=4.1, p=0.06); (iii) oral versus patches (F=0.98, p=0.37); and (iv) untreated versus oral and patches (F=5.2; p=0.03). The side-effects found with rivastigmine patch in this study were erythema, rash, tinnitus and diarrhoea. Three out of 10 patients were reported to develop these side-effects within 6months. One of these three patients developed facial erythema, which subsided on discontinuation of the patch. Another patient developed tinnitus with rash and diarrhoea was reported in the third patient. There were no difficulties reported with compliance. However, patches had to discontinue in three of 10 patients beyond the study period that is, between 6 and 12months of starting. Two of these patients had developed an advanced stage of the illness, and antidementia medication was deemed unnecessary. One patient repeatedly peeled off the patch. In this study, individuals treated with rivastigmine (oral and patches) had borderline significantly less of a decline over the 6-month period in cognitive and global functioning (DMR), as compared with the untreated group. Further, neuropsychiatric symptomotology (NPI) declined significantly less over the 6-month period for those treated with rivastigmine (oral or patches). There was no significant difference between oral rivastigmine or rivastigmine patches. The effect size may be greater and not fully observed because of the small sample size and the use of 4.6mg not 9.5mg of patches, rather than rivastigmine not being more effective. However, rivastigmine patches were found to have better patient compliance and less significant side-effects in the DS population, as compared with oral medication.