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 examine 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, with all studies 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/or systematic reviews. Of these 11 studies, 8 reported clinical regression, 2 reported economic regression, and 1 reported both; treatment adherence was mostly measured using medication possession rate (MPR). The specific consequences of non-adherence to antidepressant treatment, when combined with the available evidence, include: Clinical regression 1. Risk of relapse/recurrence: 8-fold higher for non-adherence Two studies examined the association between treatment adherence and risk of relapse/recurrence in separate Asian populations. 2011, a large retrospective cohort study in South Korea that included 117,087 individuals showed that patients who adhered to antidepressant treatment had a higher risk of relapse and The risk of relapse and relapse was more than half in patients who adhered to antidepressant treatment compared with those who stopped early (6 months) (HR=0.42, CI=0.40C0.44, p<0.0001). In contrast, a Hong Kong study (n=189) in 2007 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). In 2011, a US study of 8,521 subjects showed that patients who were compliant with duloxetine treatment had a 14% lower risk of hospital admission and a 20% lower risk of emergency room visits than non-compliers; in 2011, another US retrospective database analysis study (n=14,190) showed that patients who were compliant with duloxetine treatment had a 14% lower risk of hospital admission and a 20% lower risk of emergency room visits than non-compliers. A third retrospective analysis that included 9417 individuals over 65 years of age showed that older patients who were compliant with antidepressant therapy 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. . Three studies evaluated the effect of adherence on treatment 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 adherence group than in the non-adherence group (p<0.001). The 2006 study also showed higher remission rates and longer mean time from treatment response to relapse among treatment adherents, but treatment adherence in this study was not associated with relapse rates. A study conducted 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 weeks 6 and 12 follow-up (p<0.01). A US study of 488 employees showed that non-adherents to antidepressant treatment spent significantly more on medication than adherents ($2822 vs. $1060); after adjusting for confounders, White et al. found that non-adherents also spent significantly more on medication in the first 6 months of antidepressant treatment than adherents. 2. Treatment costs: also higher for non-adherents Treatment costs in this case refer to all depression and non-depression related treatment, emergency room, hospitalization and other medical related costs. The results of the three studies examining 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 included medication costs and consultation costs. 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 review of the literature suggests a negative impact of non-adherence to antidepressant treatment on clinical and economic regression. In fact, the quality of the studies included in this review was generally moderate to high, and this evidence is sufficient to draw a causal association. The above information is instructive for physician advocacy and for future programs to improve adherence.