Thursday, 20 April 2017

Re: Ginkgo Supplements Have Low Patient Persistence for Treating Dementia in Germany

Date: 12-31-2013HC# 121321-487

Czeche S, Schüssel K, Franzmann A, Burkart M, Schulz M. Dosage strength is associated with medication persistence with Ginkgo biloba drug products: a cohort study of ambulatory drug claims data in Germany. BMC Complement Altern Med. 2013;13(1):278. doi: 10.1186/1472-6882-13-278.

Dementia is a non-specific syndrome that results in decreases in several areas of cognitive function, including memory, attention, and problem solving. It is much more common in people over 65 years of age, and, in some cases such as Alzheimer's disease, is degenerative with no cure. Dementia is most often treated with cholinesterase inhibitors (ChEIs) and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists such as memantine. Ginkgo (Ginkgo biloba) is used to enhance memory and cognitive function, and, in Germany, is prescribed as a treatment for dementia. Clinical trials have shown that ginkgo, when used as an anti-dementia treatment, must be taken over long periods of time (≥ 24 weeks) to be effective. The authors collected data from the national prescription database (DAPI) of Germany to measure the effect of ginkgo dosage on the length and consistency with which patients with dementia maintained ginkgo usage.
Ginkgo is only prescribed for dementia under the German healthcare system (SHI) and, as such, the authors assumed with reasonable certainty that ginkgo prescriptions found within the DAPI were used to treat dementia. The DAPI, which maintains records from 80% of the community pharmacies in Germany, was searched for ginkgo prescriptions in 2008. Records found were divided into the following three categories: capsules of 240 mg ginkgo extract, 120 mg extract, and less than 120 mg extract. Records were excluded if the patient had a prescription for ginkgo in the previous year. The following information was also collected for each record: specialty of prescribing physician, geographic region, insurance membership status, pretreatment with anti-dementia medications, antidepressants, nootropics, and drugs indicating a coexisting disease. Persistence, the duration and consistency of ginkgo use, was determined for each patient. The duration of time that the prescription should last and whether the prescription was refilled within 20% of the original prescription duration were recorded. If the ginkgo prescription was not refilled within this time, the therapy was considered discontinued. Medians were calculated for each parameter. Log-rank tests were used to compare persistence between dosages and Cox proportional hazard models were used to identify and control for factors associated with non-persistence.
A large sample population (n = 13,810) was found with 430 patients in the 240 mg per capsule dosage group, 7,070 in the 120 mg per capsule dosage, and 6,310 in the < 120 mg per capsule dosage. The smaller sample size in the 240 mg group of patients is likely due to the fact that this dosage strength only became available in 2008, and physicians were not accustomed to prescribing this dosage yet. Patients were more likely to continue taking ginkgo in the highest dosage (P < 0.0001). The authors hypothesize that this is because only one capsule is taken per day at this dosage strength, making it easier for patients and caregivers to incorporate it into the daily regime (even though the label and package insert instructions for the 240 mg tablets are to split the tablet and take one half twice daily). Also, neurologists were more likely to prescribe the highest dosage strength of ginkgo than other medical specialties and had the highest compliance and persistence with their patients. At six months, 22.8% of patients in the highest dosage strength were still taking the ginkgo prescription, as compared to 5.7% and nearly zero in the 120 mg group and less than 120 mg group, respectively. These rates had fallen to 8.4% and 2.1% in the higher and middle dosage strength groups, respectively, at the end of 12 months.
Based on previous clinical trials, only patients who were prescribed a 240 mg daily dose would benefit from ginkgo prescriptions for treating dementia. Thus, the highest dosage strength is preferable, in part, because these patients were more likely to take ginkgo in large enough quantities and for long enough duration for an effect to occur. The rates of obtaining at least one ginkgo prescription refill after treatment initiation were 52.8% for the highest strength, 45.3% for 120 mg strength, and 34.1% for lower strengths. Rates of prescription refills were not high with other anti-dementia medications either. ChEIs had the highest compliance with a rate of 44%, while memantine prescriptions were only refilled 15% of the time.
The study had a number of inherent assumptions that limit the conclusions that can be drawn. Firstly, it was assumed that the patients took all of the ginkgo capsules as prescribed and only refilled the prescription when the original prescription was gone. Secondly, the authors assumed that patients had no external source of ginkgo. This may be erroneous since ginkgo extracts are available without prescription in Germany. Lastly, there may be unmeasured sources of bias, e.g. socioeconomic class, age, and patient education at the time of prescription.
The authors conclude that patient persistence is, in general, too low for ginkgo to benefit most patients with dementia, and that increases in dosage strength are likely to increase persistence.
Cheryl McCutchan, PhD