Constantino J N, Liberman M, Kincaid M
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
J Child Adolesc Psychopharmacol. 1997 Spring;7(1):31-44. doi: 10.1089/cap.1997.7.31.
Low concentrations of the neurotransmitter serotonin and its 5-hydroxyindoleacetic acid metabolite in the central nervous system have been associated with increased aggressive behavior in animals and humans. Controlled clinical trials of serotonin agonists in depressed adults have suggested that aggressive behavior is less likely during treatment with these medications than with placebo, but there have been no previous studies of selective serotonin reuptake inhibitors (SSRIs) and aggression in children. We prospectively followed the course of aggressive behavior in 19 psychiatrically hospitalized adolescents (not selected for aggressiveness) who received open clinical trials of fluoxetine, paroxetine, or sertraline. The patients received standard doses (equivalent to fluoxetine 10-40 mg daily) for a minimum of 5 weeks. The starting dose was 15 +/- 5 mg, and dosages were raised at a mean rate of 5 mg every 4 days up to a mean dose of 25 +/- 10 mg daily. Results from trials of the three SSRIs were clustered because the sample sizes were not sufficient for separate analyses. Overall, there were no statistically meaningful improvements in the level of aggressive behavior, as measured on a modified version of the Overt Aggression Scale, over the course of these patients' SSRI trials. Symptoms of physical aggression toward others or self were manifest in 12 of the 19 patients while on SSRIs. Of the 19 patients, 13 were assessed both on and off SSRIs: verbal aggression (p = 0.04), physical aggression toward objects (p = 0.05), and physical aggression toward self (p < 0.02) occurred significantly more frequently on SSRIs than off; no increase was observed in physical aggression toward others. Patients with the highest baseline aggressivity scores did not show greater improvement during SSRI treatment. Further research is warranted, particularly to explore whether SSRIs may have therapeutic effects on aggression at higher (or lower) doses than were administered in this open trial.
中枢神经系统中神经递质血清素及其5-羟吲哚乙酸代谢物的低浓度与动物和人类攻击行为的增加有关。对成年抑郁症患者进行的血清素激动剂对照临床试验表明，与使用安慰剂相比，使用这些药物治疗期间攻击行为的可能性较小，但此前尚无关于选择性血清素再摄取抑制剂（SSRI）与儿童攻击行为的研究。我们前瞻性地跟踪了19名因精神问题住院的青少年（并非因攻击性而入选）的攻击行为过程，这些青少年接受了氟西汀、帕罗西汀或舍曲林的开放临床试验。患者接受标准剂量（相当于每日氟西汀10 - 40毫克），至少持续5周。起始剂量为15±5毫克，剂量以每4天平均增加5毫克的速度提高，直至平均每日剂量为25±10毫克。由于样本量不足以进行单独分析，三种SSRI试验的结果被汇总。总体而言，在这些患者的SSRI试验过程中，根据改良版的公开攻击量表测量，攻击行为水平没有统计学上有意义的改善。19名患者中有12名在服用SSRI期间出现了对他人或自身的身体攻击症状。在19名患者中，13名患者在服用和未服用SSRI时均接受了评估：言语攻击（p = 0.04）、对物体的身体攻击（p = 0.05）以及对自身的身体攻击（p < 0.02）在服用SSRI时比未服用时显著更频繁地发生；对他人的身体攻击未观察到增加。基线攻击得分最高的患者在SSRI治疗期间并未显示出更大的改善。有必要进行进一步的研究，特别是探讨SSRI在比本次开放试验中使用的剂量更高（或更低）时是否可能对攻击行为有治疗作用。
