Antidepressant medication is used extensively to treat bipolar depression despite uncertain efficacy. The cytochrome P450 (CYP) 2C19 enzyme metabolize several antidepressants, and polymorphisms in the corresponding gene CYP2C19 influence plasma concentration and hence treatment outcomes in major depressive disorder. Here, we investigate if CYP2C19 polymorphisms are associated with antidepressant treatment patterns and the risk of mania when antidepressants are used in bipolar disorder. Two single nucleotide polymorphisms (rs4244285 and rs12248560) were used to classify 5019 bipolar disorder patients into CYP2C19 metabolic phenotypes ranging from poor to ultra-rapid metabolizers. We used Swedish national registry data 2005–2017 on dispensed medications and inpatient care to estimate risks for early-treatment persistence, treatment discontinuation, switching to a new antidepressant medication, and mania within 3 months of treatment initiation in patients treated with citalopram, escitalopram, sertraline, amitriptyline, and clomipramine. Metabolic phenotypes of CYP2C19 were not robustly associated with the investigated treatment outcomes based on dispense patterns. Slower metabolism was associated with an increased risk of treatment emergent mania for sertraline (hazard ratio [HR] = 1.3, 95% CI = 1.04–1.62, p = 0.02) and the tricyclic antidepressants amitriptyline and clomipramine (HR = 1.46, 95% CI = 1.05–2.02, p = 0.024). In a large study of the impact of CYP2C19 metabolic phenotypes on antidepressant treatment of bipolar depression, we found an association between slower CYP2C19 metabolism and higher risk of treatment emergent mania, which is a step towards personalized risk assessments. There were, however, no clear associations with early treatment persistence, treatment discontinuation, and switching to a new antidepressant.

尽管疗效不确定，但抗抑郁药物广泛用于治疗双相抑郁症。细胞色素 P450 (CYP) 2C19 酶代谢多种抗抑郁药，相应基因CYP2C19的多态性影响血浆浓度，从而影响重度抑郁症的治疗结果。在这里，我们调查CYP2C19多态性是否与抗抑郁药治疗模式相关，以及抗抑郁药用于双相情感障碍时躁狂症的风险。使用两个单核苷酸多态性（rs4244285 和 rs12248560）将 5019 名双相情感障碍患者分类为CYP2C19代谢表型从弱代谢者到超快代谢者不等。我们使用 2005-2017 年瑞典国家登记数据，了解配药和住院护理，以评估接受西酞普兰、艾司西酞普兰、舍曲林、阿米替林和氯米帕明。CYP2C19的代谢表型与基于分配模式的研究治疗结果没有密切关联。较慢的新陈代谢与舍曲林治疗引起的躁狂症风险增加有关（风险比 [HR] = 1.3，95% CI = 1.04–1.62，p = 0.02) 和三环类抗抑郁药阿米替林和氯米帕明 (HR = 1.46, 95% CI = 1.05–2.02, p  = 0.024)。在一项关于CYP2C19代谢表型对双相抑郁症抗抑郁治疗影响的大型研究中，我们发现 CYP2C19 代谢较慢与治疗突发躁狂症的风险较高之间存在关联，这是迈向个性化风险评估的一步。然而，早期治疗坚持、治疗中止和改用新的抗抑郁药之间没有明确的关联。