Tolerability of duloxetine in the elderly and in younger adults: a systematic review and individual patient data meta-analysis of randomized controlled trials versus placebo.

Duloxetine is a medication which has been approved for a wide range of pathologies by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), namely major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, chronic musculoskeletal pain and stress urinary incontinence. These diseases represent a major public health burden for elderly population (1). Several guidelines recommend the use of duloxetine as a first-line medication for these diseases in the elderly (2-6) while some formally proscribe its use (7).
As a matter of fact, good practice guidelines of duloxetine use are under debate, notably because of mixed evidence for a favorable risk-benefit balance in older populations (5, 8). For instance, duloxetine has been associated with both the highest response rate for major depressive disorder in old-age population compared to other serotoninergic antidepressants (antidepressant drugs that involve serotonin, a chemical that carries messages between the brain and other parts of the body to enhance satisfaction, happiness and optimism), and the highest risk of adverse events (AE, i.e. undesired effects of a drug) (9), supported by several meta-analyses which concluded to a disfavoring risk-benefit balance for duloxetine compared to placebo (10, 11). More precisely, the European Public Assessment Report of duloxetine warns of an increased amount of falls and hyponatremia (low concentration of sodium in the blood) in the elderly. However, many subgroup analyses of pilot trials did not find differences in tolerability between old and young adults, maybe due to the small effective of elderly participants within these studies. Altogether, it seems that the tolerability of duloxetine needs clarification especially if AE are more frequent in elderly compare to adults. The scope of this meta-analysis is intended to inform clinical decision-making for a wide range of conditions for the elderly population. Therefore, we would like to determine whether old age is significantly associated to a higher risk of AE under duloxetine than younger adults, by an individual participant meta-analysis of randomized controlled trials of any condition with an FDA or EMA approval of use of duloxetine.