Caroff Stanley N, Gutman Alisa R, Northrop John, Leong Shirley H, Berkowitz Rosalind M, Campbell E Cabrina
Behavioral Health Service, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Clin Psychopharmacol Neurosci. 2021 May 31;19(2):355-360. doi: 10.9758/cpn.2021.19.2.355.
Although evidence implicates striatal cholinergic impairment as a mechanism underlying tardive dyskinesia, trials of nonspecific cholinergic agents have been inconclusive. As a partial agonist at specific nicotinic receptor subtypes, varenicline reduces drug-induced dyskinesias in animal models suggesting promise as a treatment for tardive dyskinesia.
Three schizophrenia patients with tardive dyskinesia who were smokers underwent an open trial of varenicline. After a 2-week baseline, subjects received varenicline 1 mg twice daily. Changes from baseline on the Abnormal Involuntary Movement Scale were measured after a 4-week varenicline stabilization period, and 6 weeks after the smoking quit date in one patient.
Varenicline had no effect on mean Abnormal Involuntary Movement Scale scores after 4 weeks. Although smoking decreased after 4 weeks on varenicline and diminished further in one patient after 10 weeks, this also appeared to have no effect on ratings of tardive dyskinesia.
In contrast to animal models, no significant change in tardive dyskinesia occurred in response to varenicline replacement in three schizophrenia patients. Further investigations of cholinergic mechanisms in tardive dyskinesia are worthwhile as agents for specific cholinergic targets become available for treatment. In addition, treatment trials of tardive dyskinesia should control for smoking status, while patients on antipsychotics receiving nicotine replacement therapies for smoking should be studied further for changes in movement.
尽管有证据表明纹状体胆碱能损害是迟发性运动障碍的潜在机制，但非特异性胆碱能药物的试验结果尚无定论。作为特定烟碱受体亚型的部分激动剂，伐尼克兰可减轻动物模型中的药物性运动障碍，提示其有望用于治疗迟发性运动障碍。
对三名患有迟发性运动障碍的精神分裂症吸烟患者进行了伐尼克兰的开放试验。在为期2周的基线期后，受试者每天两次服用1毫克伐尼克兰。在4周的伐尼克兰稳定期后，以及一名患者戒烟日期6周后，测量异常不自主运动量表相对于基线的变化。
4周后，伐尼克兰对异常不自主运动量表的平均得分没有影响。尽管服用伐尼克兰4周后吸烟量减少，且一名患者在10周后进一步减少，但这似乎对迟发性运动障碍的评分也没有影响。
与动物模型不同，三名精神分裂症患者在使用伐尼克兰替代治疗后，迟发性运动障碍没有明显变化。随着针对特定胆碱能靶点的药物可用于治疗，对迟发性运动障碍中胆碱能机制进行进一步研究是值得的。此外，迟发性运动障碍的治疗试验应控制吸烟状态，同时对于接受尼古丁替代疗法戒烟的抗精神病药物患者，应进一步研究其运动变化情况。
