Table 1.
Overview of cognitive function studies evaluating OAB antimuscarinic agents in adults
| References | Study design, tests and patients | Treatments | Key outcomes |
|---|---|---|---|
| Multiple-dose studies | |||
| Kay et al. (47) | Randomised, double-blind, parallel group, multicentre study (3 weeks of treatment) Computerised CFT (10 tests) performed at baseline and weeks 1, 2 and 3 150 healthy men and women (60–83 years) | Darifenacin (n=49): 7.5 mg/day (weeks 1 and 2) then 15 mg/day (week 3) Oxybutynin ER (n=50): 10 mg/day (week 1), 15 mg/day (week 2), 20 mg/day (week 3) Placebo (n=51): weeks 1–3 | Delayed recall (NFAT) at week 3 not significantly different between darifenacin and placebo Delayed recall (NFAT) at week 3 significantly impaired with oxybutynin (p < 0.05 vs. placebo or vs. darifenacin) comparable to 16 years of brain ageing No between-group differences in self-rated memory (i.e. subjects unaware of memory deterioration) |
| Kay and Wesnes (45) | Randomised, double-blind, 4-way cross-over study (7-day treatment and 7-day washout periods) Computerised CFT (12 variables) and EEG recordings performed at baseline and day 7 of each treatment 23 healthy men (19–44 years) | Darifenacin 7.5 mg/day Darifenacin 15 mg/day Dicyclomine (positive control: M1 selective antimuscarinic) 20 mg qid Placebo | No significant effect on CFT with either dose of darifenacin and no clinically relevant effects on EEG Impaired performance on 5/12 variables at 2 h postdose with dicyclomine accompanied by EEG slowing |
| Lipton et al. (46) | Randomised, double-blind, 3-period crossover study (14-day treatment and 7-day washout periods), each subject receiving 3 of 5 treatments Computerised CFT (5 tests) at baseline and week 2 of each treatment period 129 healthy men and women (65–84 years) | Darifenacin 3.75 mg/day (n=65) Darifenacin 7.5 mg/day (n=70) Darifenacin 15 mg/day (n=61) Darifenacin IR* 5 mg tid (n=65) Placebo (n=66) | Darifenacin not significantly different from placebo for primary end-points of CFT (MSS, SCRT, WRS) at any dose No changes in self-rated alertness or contentment with darifenacin vs. placebo |
| Kay et al. (47) | Randomised, double-blind, crossover study (2 × 3-week treatment periods with 7 days of washout) Computerised CFT performed at baseline and 3 weeks 22 healthy men and women (mean age 63 years) | Tolterodine ER 4 mg/day (weeks 1–3, with sham titration) Oxybutynin ER: 10 mg/day (week 1), 15 mg/day (week 2), 20 mg/day (week 3) | No significant change in delayed recall (NFAT) or other outcome measures from baseline to week 3 of tolterodine treatment Delayed recall (NFAT) at week 3 significantly impaired with oxybutynin vs. baseline comparable to 20 years of ageing Delayed recall performance significantly worse with oxybutynin ER than tolterodine ER at week 3 but not at earlier time points No awareness of changes in memory at any time point |
| Nagels et al. (49) | Randomised, double-blind, crossover study (2 × 8-week treatment periods) CFT included PASAT and ADAS-Cog tests; MACFIMS and MMSE were also assessed 14 patients with MS (ages not specified) | Oxybutynin IR 2.5 mg tid Tolterodine IR 2 mg bid | Tolterodine was associated with a trend to better performance on PASAT than oxybutynin ADAS-Cog and MMSE did not differ between treatment periods |
| Single-dose studies | |||
| Katz et al. (50) | Randomised, double-blind, placebo-controlled cross-over study (single doses with 1-week washout) Combination of pencil and paper, interview and computerised CFT (15 tests lasting 1 h), starting 90 min postdose 12 healthy men and women (75–76 years) | Oxybutynin HCl† 5 mg Oxybutynin HCl† 10 mg Diphenhydramine HCl† (positive control: antihistamine with known anticholinergic and cognitive effects) 50 mg Placebo† | Oxybutynin at both doses caused significant decrements on 7/15 cognitive measures Diphenhydramine caused significant decrements on 5/15 cognitive measures Effects of oxybutynin remained significant after Bonferroni correction |
| Diefenbach et al. (52) | Randomised, double-blind, placebo-controlled, cross-over study (single doses with 8-day washout) Sleep study with additional assessment of reaction time (ZVT) and attention (d2 test) 1 h postdose 24 healthy men and women (51–65 years) | Trospium 45 mg Oxybutynin IR 15 mg Tolterodine IR 4 mg Placebo | No significant differences between any drug and placebo in reaction time on ZVT, or number of items completed/mistakes or target items missed in d2 test |
| Diefenbach et al. (51) | Randomised, double-blind, placebo-controlled, cross-over study (single doses with 8-day washout) Sleep study with additional assessment of reaction time (ZVT) and attention (d2 test) 1 h postdose 24 healthy men and women (22–36 years) | Trospium 45 mg Oxybutynin IR 15 mg Tolterodine IR 4 mg Placebo | No significant differences between any drug and placebo in reaction time on ZVT, or number of items completed/mistakes or target items missed in d2 test |
*
Non-marketed formulation. †Administered as liquids diluted to 100 ml in fruit juice. ADAS-Cog, Alzheimer’s disease assessment scale, cognitive subscale; bid, twice daily; CFT, cognitive function tests; ER, extended release; HCl, hydrochloride salt; IR, immediate release; MACFIMS, Minimal Assessment of Cognitive Function in Multiple Sclerosis; MMSE, Mini-Mental State Examination; MS, multiple sclerosis; MSS, memory scanning sensitivity; NFAT, name–face association test; PASAT, paced auditory serial addition test; qid, four times daily; SCRT, speed of choice reaction time; tid, three times daily; WRS, word recognition sensitivity; ZVT, Zahlen–Verbindungs test.