Unit for Psychiatric Research, Aalborg Psychiatric Hospital, Aarhus University Hospital, Aalborg, Denmark.
CNS Drugs. 2011 Jun 1;25(6):473-90. doi: 10.2165/11587800-000000000-00000.
Several antipsychotics are associated with the ventricular tachycardia torsade de pointes (TdP), which may lead to sudden cardiac death (SCD), because of their inhibition of the cardiac delayed potassium rectifier channel. This inhibition extends the repolarization process of the ventricles of the heart, illustrated as a prolongation of the QT interval on a surface ECG. SCD in individuals receiving antipsychotics has an incidence of approximately 15 cases per 10,000 years of drug exposure but the exact association with TdP remains unknown because the diagnosis of TdP is uncertain. Most patients manifesting antipsychotic-associated TdP and subsequently SCD have well established risk factors for SCD, i.e. older age, female gender, hypokalaemia and cardiovascular disease. QT interval prolongation is the most widely used surrogate marker for assessing the risk of TdP but it is considered somewhat imprecise, partly because QT interval changes are subject to measurement error. In particular, drug-induced T-wave changes (e.g. flattening of the T-wave) may complicate the measurement of the QT interval. Furthermore, the QT interval depends on the heart rate and a corrected QT (QTc) interval is often used to compensate for this. Several correction formulas have been suggested, with Bazett's formula the most widely used. However, Bazett's formula overcorrects at a heart rate above 80 beats per minute and, therefore, Fridericia's formula is considered more appropriate to use in these cases. Several other surrogate markers for TdP have been developed but none of them is clinically implemented yet and QT interval prolongation is still considered the most valid surrogate marker. Although automated QT interval determination may offer some assistance, QT interval determination is best performed by a cardiologist skilled in its measurement. A QT interval >500 ms markedly increases the risk for TdP and SCD, and should lead to discontinuation of the offending drug and, if present, correction of underlying electrolyte disturbances, particularly serum potassium and magnesium derangements. Before prescribing antipsychotics that may increase the QTc interval, the clinician should ask about family and personal history of SCD, presyncope, syncope and cardiac arrhythmias, and recommend cardiology consultation if history is positive.
几种抗精神病药物可通过抑制心脏延迟钾整流通道，导致尖端扭转型室性心动过速（TdP），进而引发心源性猝死（SCD）。这种抑制作用会延长心脏心室的复极过程，表现为体表心电图上 QT 间期延长。接受抗精神病药物治疗的个体发生 SCD 的发病率约为每 10000 年用药 15 例，但 TdP 的确切关联仍不清楚，因为 TdP 的诊断不确定。大多数表现出抗精神病药相关 TdP 并随后发生 SCD 的患者都有明确的 SCD 危险因素，即年龄较大、女性、低钾血症和心血管疾病。QT 间期延长是评估 TdP 风险最广泛使用的替代标志物，但它被认为有些不精确，部分原因是 QT 间期变化受测量误差的影响。特别是，药物引起的 T 波变化（例如 T 波平坦）可能会使 QT 间期的测量变得复杂。此外，QT 间期取决于心率，通常使用校正 QT（QTc）间期来补偿这一点。已经提出了几种校正公式，其中最广泛使用的是 Bazett 公式。然而，Bazett 公式在心率超过 80 次/分钟时过度校正，因此，在这种情况下，Fridericia 公式被认为更适合使用。已经开发了几种其他 TdP 的替代标志物，但它们都尚未在临床上实施，QT 间期延长仍然被认为是最有效的替代标志物。尽管自动 QT 间期测定可能会提供一些帮助，但最好由熟练测量的心脏病专家进行 QT 间期测定。QT 间期>500ms 会显著增加发生 TdP 和 SCD 的风险，应导致停用引起 TdP 的药物，如果存在，纠正潜在的电解质紊乱，特别是血清钾和镁紊乱。在开可能会增加 QTc 间期的抗精神病药物之前，临床医生应询问 SCD、先兆晕厥、晕厥和心律失常的家族和个人史，如果病史阳性，建议进行心脏病学咨询。
