Opioid analgesics are often required for management of painful diabetic neuropathy (DPNP) because of insufficient efficacy or side effects of other agents. We examined the efficacy of a constant release opioid Buprenorphine Transdermal Delivery System (BTDS, NORSPAN® patch) in DPNP. The study (ACTRN12609000647235) was a double-blind, randomised, placebo controlled multicentre trial approved by relevant ethics committees. Participants included subjects with neuropathy ≥ 3 on the Michigan Neuropathy Screening Instrument and DPNP of duration >6 months and severity of ≥4/10 on a Numerical Rating Scale (NRS). The active group (n=93) received 5mcg/hr patch of BTDS titrated to a maximum of 40mcg/hr over 12wks by the investigator using a flexible dosing schedule according to pain and side effects while other analgesics were kept constant. The placebo (PL) group (n=93) received matching patches. Primary Endpoint was the proportion of participants who achieved at least a 30% reduction of DPNP at wk12. Secondary Endpoints included 50% DPNP reduction at wk12, DPNP during the study, Patient/Clinician Global Impression of Change (PGIC/CGIC) and various questionnaires. Analysis was according to Intention To Treat (ITT) or Per Protocol (PP) using Logistic Regression and Wilcoxon tests. Results are summarised in Table and Figure.
As in many studies on pain, there were significant dropouts which negatively impact on the power of the study. BTDS treated group achieved the arbitrary primary endpoint of pain reduction more than PL, although the difference was only significant in the PP analysis. BTDS was also superior for 50% pain reduction, average pain intensity at all post-baseline time-points as measured by the NRS scale and PGIC, but not CGIC and had no consistent effects on the other indices measured. Our findings suggest that BTDS which provides sustained analgesic release can be beneficial, particularly in patients who can tolerate opioid therapy without problematic side effects.