Lipka L J, Lathers C M
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129.
J Clin Pharmacol. 1987 Mar;27(3):169-83. doi: 10.1002/j.1552-4604.1987.tb02180.x.
Major tranquilizers as well as antidepressant agents have been associated with clinical seizures in patients administered these agents. The incidence of such seizures is generally low when these drugs are administered in therapeutic doses. However, administration of large doses of these agents has been associated with many cases of convulsion production. The effects that these drugs have on animal models of epilepsy have been examined. It appears that the phenothiazines act as convulsant agents at lower doses, whereas, at higher doses, they act as anticonvulsant drugs. Antidepressants, on the other hand, appear to exert an anticonvulsant effect at low doses and convulsant effects at high doses. The mechanism by which these agents alter the seizure threshold is not yet known. Clinically, drugs of lower seizure production potential should be substituted for those drugs with greater potential in treating epileptic patients for psychiatric ailments. The problem of sudden death in epileptic patients is one that must be confronted. Sudden death has most frequently been attributed to autonomic dysfunction and cardiac arrhythmia in these patients. The contribution of stress in sudden death production also must be taken into account. In addition, some psychoactive agents have been associated with sudden death as well as cardiac arrhythmia and seizure production. Thus, in light of the possible additivity of the factors involved in the production of sudden death, the administration of a psychoactive agent to an epileptic patient should be approached with caution. Those agents that do not alter cardiac rhythm or seizure threshold should be administered if a psychoactive agent is deemed necessary for the management of psychiatric illness in the epileptic patient.
大剂量镇静剂以及抗抑郁药与服用这些药物的患者出现临床癫痫发作有关。当以治疗剂量服用这些药物时，此类癫痫发作的发生率通常较低。然而，大剂量服用这些药物与许多惊厥病例有关。人们已经研究了这些药物对癫痫动物模型的影响。似乎吩噻嗪类药物在较低剂量时起惊厥剂的作用，而在较高剂量时则起抗惊厥药物的作用。另一方面，抗抑郁药似乎在低剂量时发挥抗惊厥作用，而在高剂量时发挥惊厥作用。这些药物改变癫痫发作阈值的机制尚不清楚。在临床上，对于患有精神疾病的癫痫患者，应使用癫痫发作可能性较低的药物替代那些可能性较高的药物。癫痫患者的猝死问题必须加以面对。在这些患者中，猝死最常归因于自主神经功能障碍和心律失常。还必须考虑压力在猝死发生中的作用。此外，一些精神活性药物与猝死、心律失常以及癫痫发作有关。因此，鉴于猝死发生中涉及的因素可能具有叠加性，向癫痫患者施用精神活性药物时应谨慎行事。如果认为精神活性药物对于癫痫患者的精神疾病治疗是必要的，则应施用那些不改变心律或癫痫发作阈值的药物。
