Abstract：
BACKGROUND: Withdrawal syndrome (WDS) has been described after discontinuation of antipsychotics. WDS could be the consequence of an over-activation of the dopaminergic pathway. Antipsychotics with a higher affinity for dopamine D2 receptors could be associated with a higher risk of WDS. This study aims to address this statement and evaluate the risk difference for withdrawal syndrome between antipsychotics based on pharmacovigilance data.
METHODS: We collected individual reports registered in Vigibase® between 01/01/2000 and 31/12/2022 of patients treated with antipsychotics and who had presented WDS. A disproportionality analysis was performed to evaluate the risk of reporting WDS with each antipsychotic compared to all other antipsychotics. We performed a correlation analysis to assess the correlation between the risk of reporting WDS for each antipsychotic in relation with their pKi for D2 and 5HT2A receptors.
RESULTS: The most frequent psychiatric withdrawal symptoms after antipsychotic discontinuation were insomnia, anxiety and depression. Tremor, headache and dizziness were among the most frequently reported neurologic withdrawal symptoms. Tiotixene had the highest risk of reporting WDS (ROR 7.08; 95%CI 3.49 - 14.35) followed by pimozide (ROR 4.35; 95%CI 1.93 - 9.77), quetiapine (ROR 4.24; 95%CI 3.87 - 4.64), thioridazine (ROR 4.17; 95%CI 2.50-6.98) and ziprasidone (ROR 2.98; 95%CI 2.41-3.67). We found a poor correlation between D2/5HT2A binding affinity and the risk of reporting withdrawal syndrome (R2 = 0,094).
CONCLUSIONS: Our results suggest that there might be a risk difference for WDS between antipsychotics. Tiotixene, pimozide and quetiapine were associated with a higher risk of reporting a WDS whereas this risk was lower with chlorpromazine, clozapine and fluphenazine. We could not address the issue of withdrawal psychosis, withdrawal dyskinesia, rebound psychosis or supersensitivity psychosis due to the lack of specific WHO medDRA coded terms to identify potential cases.
METHODS: We collected individual reports registered in Vigibase® between 01/01/2000 and 31/12/2022 of patients treated with antipsychotics and who had presented WDS. A disproportionality analysis was performed to evaluate the risk of reporting WDS with each antipsychotic compared to all other antipsychotics. We performed a correlation analysis to assess the correlation between the risk of reporting WDS for each antipsychotic in relation with their pKi for D2 and 5HT2A receptors.
RESULTS: The most frequent psychiatric withdrawal symptoms after antipsychotic discontinuation were insomnia, anxiety and depression. Tremor, headache and dizziness were among the most frequently reported neurologic withdrawal symptoms. Tiotixene had the highest risk of reporting WDS (ROR 7.08; 95%CI 3.49 - 14.35) followed by pimozide (ROR 4.35; 95%CI 1.93 - 9.77), quetiapine (ROR 4.24; 95%CI 3.87 - 4.64), thioridazine (ROR 4.17; 95%CI 2.50-6.98) and ziprasidone (ROR 2.98; 95%CI 2.41-3.67). We found a poor correlation between D2/5HT2A binding affinity and the risk of reporting withdrawal syndrome (R2 = 0,094).
CONCLUSIONS: Our results suggest that there might be a risk difference for WDS between antipsychotics. Tiotixene, pimozide and quetiapine were associated with a higher risk of reporting a WDS whereas this risk was lower with chlorpromazine, clozapine and fluphenazine. We could not address the issue of withdrawal psychosis, withdrawal dyskinesia, rebound psychosis or supersensitivity psychosis due to the lack of specific WHO medDRA coded terms to identify potential cases.
摘要：
背景：已经描述了停用抗精神病药物后的戒断综合征（WDS）。WDS可能是多巴胺能途径过度激活的结果。对多巴胺D2受体具有较高亲和力的抗精神病药可能与较高的WDS风险有关。本研究旨在解决这一问题，并根据药物警戒数据评估抗精神病药之间戒断综合征的风险差异。
方法：我们收集了2000年1月1日至2022年12月31日在Vigibase®注册的接受抗精神病药物治疗并出现WDS的患者的个人报告。进行了不相称性分析，以评估与所有其他抗精神病药物相比，每种抗精神病药物报告WDS的风险。我们进行了相关性分析，以评估每种抗精神病药报告WDS的风险与D2和5HT2A受体的pKi之间的相关性。
结果：抗精神病药物停药后最常见的精神戒断症状是失眠，焦虑和抑郁。震颤,头痛和头晕是最常见的神经系统戒断症状。Tiotixene报告WDS的风险最高（ROR7.08;95CI3.49-14.35），其次是匹莫齐特（ROR4.35;95CI1.93-9.77），喹硫平（ROR4.24；95CI3.87-4.64），硫利达嗪(ROR4.17;95CI2.50-6.98)和齐拉西酮(ROR2.98;95CI2.41-3.67)。我们发现D2/5HT2A结合亲和力与报告戒断综合征的风险之间的相关性较差（R2=0,094）。
结论：我们的结果表明，抗精神病药物之间可能存在WDS的风险差异。Tioxene,吡莫齐特和喹硫平报告WDS的风险较高，而氯丙嗪报告WDS的风险较低，氯氮平和氟奋乃静.我们无法解决戒断性精神病的问题，戒断运动障碍,由于缺乏特定的WHOmedDRA编码术语来识别潜在病例，导致反弹精神病或超敏性精神病。
方法：我们收集了2000年1月1日至2022年12月31日在Vigibase®注册的接受抗精神病药物治疗并出现WDS的患者的个人报告。进行了不相称性分析，以评估与所有其他抗精神病药物相比，每种抗精神病药物报告WDS的风险。我们进行了相关性分析，以评估每种抗精神病药报告WDS的风险与D2和5HT2A受体的pKi之间的相关性。
结果：抗精神病药物停药后最常见的精神戒断症状是失眠，焦虑和抑郁。震颤,头痛和头晕是最常见的神经系统戒断症状。Tiotixene报告WDS的风险最高（ROR7.08;95CI3.49-14.35），其次是匹莫齐特（ROR4.35;95CI1.93-9.77），喹硫平（ROR4.24；95CI3.87-4.64），硫利达嗪(ROR4.17;95CI2.50-6.98)和齐拉西酮(ROR2.98;95CI2.41-3.67)。我们发现D2/5HT2A结合亲和力与报告戒断综合征的风险之间的相关性较差（R2=0,094）。
结论：我们的结果表明，抗精神病药物之间可能存在WDS的风险差异。Tioxene,吡莫齐特和喹硫平报告WDS的风险较高，而氯丙嗪报告WDS的风险较低，氯氮平和氟奋乃静.我们无法解决戒断性精神病的问题，戒断运动障碍,由于缺乏特定的WHOmedDRA编码术语来识别潜在病例，导致反弹精神病或超敏性精神病。
