The study was performed in the health region of Lleida (Spain), a region with an active population of 206,603 people between the ages of 15 and 64years according to the central national health insurance registry in 2007. This registry includes all residents who are on the census list of a municipality in the region. In 2007 foreigners represented 13.5% of residents recorded in the census. Most of these foreigners were economic migrants from Eastern Europe, the Maghreb, Latin America, Sub-Saharan Africa and elsewhere.
Study population: population-based retrospective cohort of all subjects aged between 15 and 64years prescribed treatment with antidepressant drugs between 1 January 2007 and 31 December 2009.
The study included all individuals in the region who had received at least one pack of antidepressants in 2007 but who had not received antidepressants in the previous 12months. Subjects who had received ADT with amitriptyline alone were excluded, because of the habitual use of this drug in the treatment of other pathologies such as neuropathic pain or migraine. Individuals who moved to other regions or who died were also excluded from the analysis.
For each individual, age in 2007, sex, country of origin, units of antidepressants from the NO6A subgroup in the ATC classification system [5
] dispensed at pharmacies, the active ingredient, and month and year of dispensation were recorded.
The sociodemographic data were obtained from the Primary Care Information System. Data on exposure to drugs were obtained from the regional claims database. In Spain the public health system pays 90% of the price of antidepressant drugs officially prescribed to the population with statutory health insurance. Information on the packs dispensed per person is recorded in an individual database for each health region. We combined the information from these two databases using a common personal identifier; the information was then treated anonymously in the subsequent analysis.
For this study, immigrants were defined as those from low or middle-income countries according to the classification of the World Bank based on per capita GDP [6
]. If the country of origin was unknown, only those recorded in the central insurance registry before 1 January 2003, when the percentage of immigrants in the country was below 5%, were considered as natives. Otherwise, subjects whose country of origin was unknown were excluded from the study. The immigrants were grouped according to area of origin into Eastern Europe, Maghreb, Sub-Saharan Africa, Latin America, and Others.
Treatment duration was calculated for each patient as the number of months between the first dispensation in 2007 and the last during the study period. If patients did not withdraw medication during a period of six consecutive months this was considered as the end of the episode. Discontinuations of below six months, on the other hand, were included in the duration of the episode. If a patient had presented more than one episode during the study period, only the first one was included. Treatment duration for patients who had not completed treatment by the end of follow-up was considered as censored.
The use of the terms adherence and compliance was discussed by the research team and standardized. In the literature, the terms are often used interchangeably and the definitions used by different authors do not always coincide. Although in general the use of the term adherence is preferred because of its connotation of voluntary cooperation, in this case we define them as follows.
Treatment adherence was defined on the basis of the medication possession ratio. For each antidepressant the number of units per month that a patient needed according to the daily dose defined by the WHO Collaborating Centre for Drugs Statistics Methodology was recorded. On this basis, the ratio between the number of units obtained at the pharmacy and the theoretical number of units required according to the duration of the episode was obtained. Ratios of adherence above 80% were considered adequate.
By consensus, compliance was considered to be adequate in patients with a treatment duration of more than four months and an adherence of more than 80% until the end of treatment.
The cohorts characteristics with respect to the variables analysed were expressed as frequencies and percentages. The distribution of treatment duration was expressed by the means, medians, 25th and 75th percentiles and 95% confidence intervals (95%CI).
The distribution of treatment duration and the survival function were estimated using the Kaplan-Meier method. The survival curves were compared between groups using the Log-Rank test. To determine which factors were related to the treatment duration and the risk of abandonment/completion, a Cox multivariate model was applied. This model was used to estimate the hazard ratios (HR) and their corresponding 95%CI of ending/abandoning treatment. The same model was used to estimate the adjusted survival curves. The analysis of treatment duration was performed for the entire patient cohort and also for the subsample that completed the first month of treatment. P values below 0.05 were considered statistically significant.
This study was approved by the Ethical Committee of Clinical Research of the IDIAP J Gol (Primary Care Research Institute, Spain).