Kabul,S; Alatorre,C; Montejano,LB; Farr,AM; Clemow, DB.

CNS Neuroscience & Therapeutics 21 (2015) 936–942.

This study describes a large prescription database survey of dosing patterns of atmoxetine, between January 2006 and December 2001, in adults with ADHD. 12,412 adults >= 18 y.o. met inclusion criteria of: 1) having at least one claim coded for ADHD, 2) having continuous medical and prescription benefits for the 6 months prior and 12 after the index (initial atomoxetine prescription) and 3) having been treated with atomoxetine monotherapy. The survey examined dosing patterns and the average daily dose of atomoxetine prescribed in the 31 to 365 days following the index prescription of atomoxetine (to allow titration). Adults were divided into four dosing cohorts: 1) suboptimal (average daily dose < 80 mg/day) (n=4548, 36.6%) , recommended (80-100 mg/day) (n=3323, 26.8%) , above-recommended (> 100 mg/day) (n=213, 1.7%) and fluctuating (adults who could not be classified readily into one of the above three cohorts as their dose changed commonly during the treatment period). The fluctuating dose cohort (n=4328, 34.9%) was excluded from subsequent analyses of patient characteristics.

The suboptimal and recommended cohorts were quite similar in patient characteristics, with the exception of a somewhat higher proportion of younger patients (aged 25-44 years) in the recommended vs. the suboptimal group (45.3% vs. 40.6%); the suboptimal group had somewhat higher percentage of females (53.5% vs. 44%) and lower rates of use of ADHD medication prior to the survey period (16.8% vs. 20.0%) versus the recommended dosing cohort. Rates of co-morbid psychiatric disorders were generally the same in these two groups. The overall dose after titration in the three cohorts was 43 mg/day. Slightly greater than 90% of patients discontinued atomoxetine during the one year observation period.

Conclusions drawn from this trial should be tempered by the retrospective, survey based nature of the investigation. Additionally, the assignment of 80 mg/day as the recommended dose is purely based upon the atomoxetine label, whereas the clinical trials examined doses in the 40 to 100 mg/day range. Additionally the four month average treatment period with atomoxetine might have led to an under-estimation of final dosing as a percentage of patients were not titrated to final dosing. However, even with these caveats, there are several important findings for clinicians. Atomoxetine in this claims database seems to be at the lower register of recommended ranges; clinicians should attempt to titrate atomoxetine to optimal dosing based on observed side effects and potential side effects. Adherence to atomoxetine treatment in this claim database was poor, as has been reported in several other studies of ADHD medications in general (stimulants and non-stimulants). Clinicians should make all attempts to improve adherence to medication treatment and attempt to mitigate potential reasons for non-adherence, as patients will only get better if they take their medications.