In a recent study published in BMC Medicine, researchers evaluate real-world acceptability, tolerability, and efficacy of concomitant antidepressant and statin treatment using data from QResearch, a big United Kingdom (UK) primary care database.

Background

There are over 350 million patients with clinical depression worldwide, a mood disorder that requires pharmacological interventions. Clinical guidelines recommend antidepressant treatments; nonetheless, nearly 50% of them don’t reply to these treatments. Furthermore, over 25% of individuals with depressive disorders discontinue antidepressant treatment.

Pre-clinical and clinical studies, including randomized clinical trials (RCTs), have examined the consequences of antidepressants and located that statins are promising drugs to mix with conventional antidepressant medications.

A meta-analysis of placebo-controlled RCTs showed that concurrent statin and antidepressant use were more efficacious in participants with depression versus patients taking an antidepressant plus placebo, and this treatment markedly reduced depressive symptoms at two months.

Most clinical trials are adequately powered to evaluate the efficacy of medication; nonetheless, those using small sample sizes and shorter follow-ups generate imprecise results for end result measures apart from drug efficacy, limiting the generalizability of those findings to clinical practice.

Quite the opposite, observational studies following similar methodological principles as clinical trials (e.g., having specified follow-up duration and data-analysis plan) can overcome these limitations and supply complementary evidence using randomized data.

In regards to the study

In the present cohort study using observational design, researchers investigated anonymized electronic healthcare records (EHRs) of greater than 35 million patients from 1,574 general practices (GPs) in England to discover patient groups receiving only antidepressants and statin+antidepressant treatment within the QResearch database.

All included patients were 18 to 100 years old, had registered with the GPs within the QResearch database between January 1998 and August 2020, and remained registered for a minimum of a yr. All of them were diagnosed with depressive disorder for the primary time and had initiated treatment with an antidepressant.

The researchers assessed the consequences of antidepressant treatment discontinuations on depressive symptoms at 2, 6, and 12 months post-discontinuation.

Discontinuation implied considered one of the next for a patient: i) over a 30-day gap between the termination and begin of antidepressant prescription, considering the typical prescription duration of 28-30 days; ii) switching to a different antidepressant; or iii) a patient being prescribed a further antidepressant, mood stabilizer or antipsychotic.

The outcomes of interest were the drug’s acceptability, tolerability, and efficacy.

The researchers measured acceptability because the ratio of discontinuations (because of any cause) from initiation of antidepressant treatment, tolerability because the ratio of discontinuations from antidepressant treatment inside 30 days from any antagonistic event, and efficacy outcomes as response, remission, and alter in depression rating, measured using the Patient Health Questionnaire (PHQ)-9.

The researchers performed unadjusted and adjusted analyses for every end result, reporting results for full set (primary) and complete case (sensitivity) analyses, adjusting for several confounding variables, corresponding to age, gender, and ethnicity, to call just a few.

Further, they performed an intention-to-treat evaluation (ITT) to explore all study outcomes. Moreover, they used the ‘vce(cluster clustvar)’ function to account for within-group correlation for every GP (e.g., hospital, clinics) and computed odds ratios (ORs) for all dichotomous outcomes.

In addition they deduced mean differences (MDs) with 99% confidence intervals (99% CIs) for continuous outcomes.

Finally, the researchers performed a subgroup evaluation on a subset of patients within the 65+ age group and a sensitivity evaluation.

Results

The ultimate cohort comprised 673,177 patients, of which 46,482 patients were receiving an antidepressant with statin and 626,335 were antidepressant-only. 

These patients had moderate to severe depression, as reflected in average PHQ-9 scores of 17.09±4.95, and 85.7% of them received selective serotonin reuptake inhibitors (SSRI), a definite class of antidepressant drugs.

Regression analyses model adjusted for baseline differences between the 2 groups.

These differences suggested that the antidepressant + statin receiving group had more male patients (56.18% vs. 41.90%) who were older (mean age 67.1 years vs. 40.9 years), were taking other medications, and had more comorbidities, especially metabolic, neoplastic, and cardiovascular diseases. 

In comparison with the antidepressant-only group, they were also the least socioeconomically deprived and were more prone to have minor depression.

Lower all-cause discontinuation of antidepressant treatment within the group using antidepressant+statin showed higher acceptability in comparison with the antidepressant-only group in any respect time points. These results remained consistent even after adjusting for confounders.

Quite the opposite, tolerability was consistently poor within the antidepressant + statin group for each datasets within the unadjusted analyses. Furthermore, primary evaluation didn’t confirm this association, suggesting higher tolerability for the antidepressant+statin treatment at two and 6 months.

Efficacy didn’t significantly vary across study groups.

Additional analyses confirmed that concurrent antidepressant + statin treatment was acceptable in any respect time points, had higher tolerability at two months, and comparable efficacy outcomes.

Conclusions

Overall, concomitant antidepressant and statin use in individuals with clinical depression was correlated to lower antidepressant treatment discontinuations. Nonetheless, it didn’t enhance the efficacy of antidepressant medications. 

Further studies are needed to make clear these observations. More importantly, clinicians should monitor adherence to antidepressant treatment, especially amongst those not taking concurrent medications corresponding to statins.