Luykx Jurjen J, Corbeil Olivier, Kärkkäinen Olli, Tanskanen Antti, Mittendorfer-Rutz Ellenor, Tiihonen Jari, Taipale Heidi
Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands.
GGZ inGeest Mental Health Care, Amsterdam, The Netherlands.
Mol Psychiatry. 2025 Jul 1. doi: 10.1038/s41380-025-03080-3.
Attention-deficit hyperactivity disorder (ADHD) is frequently comorbid with schizophrenia spectrum disorders (SSDs) and is associated with poorer outcomes. Yet, its pharmacological treatment in patients with SSDs has been hampered by safety concerns. We therefore examined whether psychiatric, cardiovascular and other medical outcomes are associated with the use of ADHD medications in people with SSDs (N = 131,476). The main outcome was all-cause hospitalization/mortality. Secondary outcomes were hospitalization for psychosis, somatic hospitalization, and cardiovascular hospitalization. Adjusted hazard ratios (aHRs) were calculated for the association between the outcomes and the different exposure categories (compared with non-use of ADHD medication) using within-individual Cox regression analyses. Lisdexamphetamine was associated with a decreased risk of all-cause hospitalization/mortality (aHR = 0.89, 95%CI = 0.84-0.94) and methylphenidate with a slightly increased risk (aHR = 1.04 [1.01-1.08]), while for the other exposures the 95%CI of the HRs encompassed 1. Atomoxetine was associated with a reduced risk of hospitalization for psychosis (aHR = 0.87 [0.78-0.98]), lisdexamphetamine with a reduced risk of somatic hospitalizations (aHR = 0.70 [0.58-0.84]), and ADHD polytherapy with an increased risk of somatic hospitalizations (aHR = 1.37 [1.07-1.74]). No other statistically significant associations were found between the exposures and outcomes (including cardiovascular hospitalizations). Furthermore, increased all-cause hospitalization/mortality risks for methylphenidate were only found with doses ≥95 mgs/day (aHR 1.08 [1.03-1.14]) or during use periods of this agent without concomitant use of an antipsychotic (aHR = 1.06 [1.01-1.12]). Finally, for methylphenidate and lisdexamphetamine, we found evidence of U-shaped associations between doses used and risks of all-cause hospitalization/mortality and psychosis. In conclusion, we find that for people with SSDs, the use of ADHD medication (particularly lisdexamphetamine in all dosages and long-acting methylphenidate in low to medium doses) is safer than generally conceived. The benefits of its use for patients with SSD and comorbid ADHD should therefore be weighed against the risks in a shared decision-making process aimed at improving patients' chances of recovery.
注意力缺陷多动障碍（ADHD）常与精神分裂症谱系障碍（SSD）共病，且与较差的预后相关。然而，对患有SSD的患者进行药物治疗时，安全性问题一直是个障碍。因此，我们研究了患有SSD的人群（N = 131476）使用ADHD药物是否与精神、心血管及其他医疗结局相关。主要结局是全因住院/死亡。次要结局包括因精神病住院、躯体疾病住院和心血管疾病住院。使用个体内Cox回归分析计算结局与不同暴露类别（与未使用ADHD药物相比）之间关联的调整风险比（aHR）。赖右苯丙胺与全因住院/死亡风险降低相关（aHR = 0.89，95%CI = 0.84 - 0.94），哌甲酯风险略有增加（aHR = 1.04 [1.01 - 1.08]），而其他暴露的HR的95%CI包含1。托莫西汀与因精神病住院风险降低相关（aHR = 0.87 [0.78 - 0.98]），赖右苯丙胺与躯体疾病住院风险降低相关（aHR = 0.70 [0.58 - 0.84]），ADHD联合治疗与躯体疾病住院风险增加相关（aHR = 1.37 [1.07 - 1.74]）。在暴露与结局（包括心血管疾病住院）之间未发现其他具有统计学意义的关联。此外，仅在哌甲酯剂量≥95毫克/天（aHR 1.08 [1.03 - 1.14]）或该药物使用期间未同时使用抗精神病药物时（aHR = 1.06 [1.01 - 1.12]），才发现其全因住院/死亡风险增加。最后，对于哌甲酯和赖右苯丙胺，我们发现所使用剂量与全因住院/死亡及精神病风险之间存在U型关联的证据。总之，我们发现对于患有SSD的人群，使用ADHD药物（特别是所有剂量的赖右苯丙胺和低至中等剂量的长效哌甲酯）比一般认为的更安全。因此，在旨在提高患者康复几率的共同决策过程中，应权衡其对患有SSD和共病ADHD患者使用的益处与风险。
