Center for Psychopharmacology, Diakonhjemmet Hospital, PO Box 85 Vinderen, Oslo 0319, Norway.
Center for Psychopharmacology, Diakonhjemmet Hospital, PO Box 85 Vinderen, Oslo 0319, Norway; Norwegian National Advisory Unit on Aging and Health, Vestfold Hospital Trust, Tønsberg, Norway.
Eur Neuropsychopharmacol. 2020 Aug;37:64-69. doi: 10.1016/j.euroneuro.2020.06.007. Epub 2020 Jun 25.
Nonadherence to oral antipsychotic drugs is a major issue in clinical psychiatry giving rise to treatment failure. Further, polypharmacy is common in the treatment of psychotic disorders due to insufficient treatment effect during monotherapy. As a potential circuit problem, we hypothesized that antipsychotic polypharmacy is associated with increased risk of nonadherence. To investigate this, in terms of 'complete' nonadherence, the rates of undetectable serum drug concentrations during prescribing of doses used in psychotic disorders were compared during antipsychotic 'monotherapy' vs 'polypharmacy' treatment using therapeutic drug monitoring (TDM) data of 24,239 patients. A complete nonadherence patient was objectively defined as the detection of at least one event of undetectable serum concentration of a prescribed antipsychotic drug. The rate of complete nonadherence patients was compared between antipsychotic monotherapy and polypharmacy by multivariate logistic regression analyses. The overall rate of complete nonadherence in the population was 6.8% (n = 1,644; 95%CI: 6.5-7.1). Compared to monotherapy patients, the rate of nonadherence increased significantly with the number of co-prescribed antipsychotic drugs. After adjusting for sex (p = 0.091) and age (p < 0.001) as covariates, the rates of nonadherence vs monotherapy were 1.69-fold (95% CI: 1.48-1.92; p < 0.001) for two, 2.60-fold (95% CI: 1.88-3.59; p < 0.001) for three, and 3.54-fold (95% CI: 1.46-8.58; p = 0.005) for four or more co-prescribed antipsychotics, respectively. The present naturalistic study shows that antipsychotic polypharmacy significantly increases the rate of complete nonadherence, which is positively correlated with increasing number of concurrently used antipsychotic drugs. Thus, the intended clinical benefit of combining oral antipsychotic drugs may probably be reduced by increased nonadherence.
抗精神病药物不依从是临床精神病学中的一个主要问题，导致治疗失败。此外，由于单药治疗时疗效不足，抗精神病药物的多药治疗在精神障碍的治疗中很常见。作为一种潜在的电路问题，我们假设抗精神病药物的多药治疗与不依从的风险增加有关。为了研究这一点，根据“完全”不依从的情况，我们使用治疗药物监测（TDM）数据比较了 24239 名患者在抗精神病药物“单药治疗”与“多药治疗”期间，处方剂量时血清药物浓度不可检测的发生率，以评估精神障碍患者的多药治疗与不依从之间的关系。完全不依从的患者被客观定义为检测到至少一次规定的抗精神病药物血清浓度不可检测的事件。通过多变量逻辑回归分析比较了抗精神病药单药治疗和多药治疗之间完全不依从患者的比例。该人群的完全不依从率总体为 6.8%（n=1644；95%CI：6.5-7.1）。与单药治疗患者相比，不依从率随着合用抗精神病药物数量的增加而显著增加。在校正性别（p=0.091）和年龄（p<0.001）作为协变量后，与单药治疗相比，不依从的发生率分别为 2 种药物时 1.69 倍（95%CI：1.48-1.92；p<0.001），3 种药物时 2.60 倍（95%CI：1.88-3.59；p<0.001），4 种或更多同时使用的抗精神病药物时 3.54 倍（95%CI：1.46-8.58；p=0.005）。本自然主义研究表明，抗精神病药物的多药治疗显著增加了完全不依从的发生率，且与同时使用的抗精神病药物数量呈正相关。因此，联合使用口服抗精神病药物的预期临床获益可能会因不依从而降低。
