It is well known that poor adherence to antipsychotic medication has been a major challenge in the treatment of schizophrenia. In fact, non-adherence to antidepressant treatment in patients with depression may be even more severe and equally harmful. In a systematic review published online Dec. 25 in the Journal of Affective Disorders, researchers examined the clinical and economic consequences of poor adherence to antidepressant treatment.
The investigators systematically reviewed studies addressing non-adherence to antidepressant treatment and correlates of diversion in PubMed, EMBASE, DARE, CINAH, PsycINFO, the Cochrane Clinical Research Centre Register, and the Cochrane Library of Systematic Reviews through March 31, 2015, all of which were required to be available in full English. The investigators assessed the quality of the 11 studies included in this literature review using the NewcastleCOttawa scale, a common tool for assessing the quality of non-randomized studies in meta-analyses and systematic reviews. Of these 11 studies, 8 reported clinical regression, 2 reported economic regression, and 1 reported both, with treatment adherence mostly measured using medication possession rate (MPR).
Combining the available evidence, specific consequences of antidepressant treatment nonadherence include
Clinical regression
1. Risk of relapse/recurrence: may be 8-fold higher in non-adherence
In 2011, a large retrospective cohort study in Korea that included 117,087 individuals showed that patients who adhered to antidepressant treatment had more than half the risk of relapse and relapse compared to those who stopped early (6 months) (HR=0.42, CI=0.40C0.44, p<0.0001).
A 2014 Hong Kong study (n=189), on the other hand, showed that the risk was more than eight times higher in those not on continuous antidepressant treatment than in those on continuous medication (OR=8.42, CI=3.30C21.47).
2. Risk of hospital admissions and emergency room visits: increased frequency and longer duration
In 2011, a U.S. study of 8,521 subjects showed that patients who were compliant with duloxetine had a 14% lower risk of hospital admission and a 20% lower risk of emergency room visits than non-compliant patients.
In 2003, another retrospective database analysis study in the United States (n=14,190) showed that adherents had fewer hospitalizations and shorter emergency department visits than non-adherents (p=0.0037).
A third retrospective analysis that included 9417 individuals over 65 years of age showed that older patients who were compliant with antidepressant treatment had a 26% lower risk of hospitalization for coronary heart disease (HR=0.74,CI=0.60C0.93), but this effect was not present in younger depressed patients.
3. Symptom severity, response and remission rates: non-adherents had more severe symptoms and lower response and remission rates
Two studies conducted by Akerblad and co-workers in 2003 and 2006 showed the same results: the response rate (MADRS minus ≥50%) was significantly higher in the treatment-adherent group than in the non-adherent group (p < 0.001). 2006 also showed that treatment-adherent patients had a higher remission rate, with a longer mean time from treatment response to Relapse took longer on average, but treatment adherence in that study was not associated with relapse rates.
A study conducted by Warden in 2014 (n=567) showed that non-adherence to antidepressant treatment was not associated with change in depressive symptoms or response/remission rates, while a post-hoc analysis conducted by Sirey et al. for an RCT showed that treatment adherents had lower total HDRS scores at week 6 and week 12 follow-up (p<0.01).
Economic regression
1. Non-adherents were more costly for medications
Medication costs: In 2010, a US study of 488 employees showed that medication costs were much higher for non-adherents to antidepressant treatment than for adherents ($2822 vs. $1060).
After adjusting for confounders, White et al. found that nonadherents also spent significantly more on medications in the first 6 months of antidepressant treatment than did adherents.
2. Cost of medical treatment: non-adherents were also higher
Medical costs in this context refer to all depression- and non-depression-related visits, emergency room visits, hospitalizations, and other medical-related costs. The results of the three studies exploring this topic were generally consistent: non-adherents were higher than adherents, and two of them were statistically significant.
3. Total medical costs: mixed results
Total medical costs include the cost of medication and treatment. The results of the three studies varied, with one (n=14,190) being higher among nonadherents, another (n=488) being higher among adherents, and the third (n=22,947) not being significantly different between the two groups.
4. Inpatient and outpatient costs: no significant difference?
Only one study showed no significant difference between adherents and non-adherents for either component of medical costs.
The investigators concluded that, overall, this literature review suggests a negative impact of non-adherence to antidepressant treatment on clinical and economic outcomes. In fact, the studies included in this review were generally of moderate to high quality, and this evidence is sufficient to draw causal associations. This information is instructive for future programs to improve adherence.