Interaction between CYP2D6 inhibitor antidepressants and codeine: is this relevant?

Introduction: Co-occurring pain impairs depression's prognosis. Selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) are first-line pharmacotherapies for depression and inhibit many cytochrome 2D6 enzymes. Codeine is a first-line treatment for pain and needs to be metabolized into morphine by cytochrome 2D6 to exert its analgesic effect. Concomitant prescription of both pharmacotherapies leads to inadequate analgesia. Areas covered: We performed a systematic review of the literature to amalgamate the current knowledge regarding the clinical effect of this association and quantified its prevalence in clinical practice in the French Pays de la Loire area using a retrospective observational cohort study design. Expert opinion: The literature review highlighted that antidepressants with moderate-to-strong inhibition of CYP2D6 should be avoided in patients receiving codeine. However, 0.44% of the 12,296 sampled patients received concomitant codeine and CYP2D6 inhibitor between January 2015 and June 2015. Switching drugs in both painful and depressive patients depends on the pain and depression subtypes. Promising drugs that both show an effect on pain and depression are currently being studied but are not usable in clinical practice. Until then, tailored communication reinforcement toward health-care professionals is needed to prevent these problematic occurrences of concomitant prescription administration.