This is the first study to report an improvement in the timing of tablet intake in Parkinson's Disease (through any mechanism), but there was no change in Parkinson motor score, or quality of life scores. The response in timing adherence was however variable, between a 23% worsening and a 96% improvement in actively counselled patients, and control patients showed significantly worse overall medication timing. This may be due in part to waning novelty of the technique, between the first and second 3-month monitoring period. Deterioration in control group adherence figures post-intervention is reported elsewhere[26
]. The majority of patients found regularisation of medicine-taking difficult; reasons include forgetfulness and are well documented in PD[1
Timing adherence is based on a 24 hour day, rather than waking hours. This matches the concepts of the continuous dopaminergic theory, namely that smoother symptom control results from continuous, rather than pulsatile, drug delivery. Although patients frequently medicate preferentially in the daytime, which lowers their timing adherence, we did not adjust our results to account for this. The overnight problems of Parkinson symptoms, and the continuous dopaminergic theory, both argue against such an approach.
Drop-out from studies with electronic pill-bottle monitoring is expected[27
]. Although adverse events may contribute, this is commoner following therapy initiation[28
], while our patients were on established medication. Our monitoring was prolonged and repeated, typically encompassing several medications taken several times a day, which contrasts with studies of monotherapy or twice-daily medication[29
]. Limitations in our study are as follows. Firstly, a substantial proportion of patients were unable or unwilling to use MEMS containers (totalling 27 of 83 patients, 32.5%), which reduces adherence data for intention to treat analysis of the primary outcome. However, clinical scoring was continued in all of these cases. Secondly, the level at which sub-optimal adherence becomes clinically important in PD is not known, and our study does not assist in defining this. Thirdly, we underestimated the variability of timing adherence, which was unreported at the time of planning this study. This should be considered in designing further studies in this area.
Many interventions to improve therapy adherence have been tested[30
], but this is the first such study in Parkinson's disease. The vast majority of studies used pill counts, self report or physician/nurse assessment to measure adherence despite well-recognised shortcomings of these methods [31
]. Most interventions involve multiple components[30
], leaving uncertainty as to which aspects have a positive effect. We therefore chose an intervention with 3 components (verbal and written information, and tailored timing guidance) but had a single focus of improving timing adherence. The resulting timing adherence improvement was similar to that from individualised cue-dose training (linking medicine taking to daily activities) in diabetes[14
]. Another interventional approach is to inform the patient of their own prior dosing history from the electronically monitored data[32
In our study drugs taken once daily were taken more regularly than more complicated regimens, which is consistent with a systematic review of 76 electronic monitoring studies[33
]. Pharmaceutical development of more once daily antiparkinson preparations may help ease the process of medicine taking.
There was no significant difference in UPDRS 3 before and after the intervention. Quality of life deteriorated, but is more influenced by non-motor factors such as depression. We did not find an association between deterioration in domains of the PDQ score and UPDRS changes, in particular considering items which might respond to increasing, or regularising, dopaminergic therapy (bodily discomfort, mobility). Clinical improvement is reported in some adherence studies (e.g. epilepsy[34
]), but is by no means universal[14