Naranjo C A, Herrmann N, Mittmann N, Bremner K E
Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
Drugs Aging. 1995 Sep;7(3):184-202. doi: 10.2165/00002512-199507030-00004.
Psychopharmacotherapy of the elderly must take into account the effects of age-related changes in the structure and function of the brain and various organs. In general, older people are more sensitive than young people to both the therapeutic and toxic effects of psychotropic medications, necessitating lower doses and longer dosage intervals. This holds true for the treatment of 5 major types of psychiatric illness (depression, bipolar disorder, anxiety, psychotic disorders and dementia). The tricyclic antidepressants, although efficacious, inexpensive, and backed by 30 years of experience, are less well tolerated by the elderly than are newer antidepressants such as the selective serotonin uptake inhibitors. Problems with monoamine oxidase (MAO) inhibitors, including orthostatic hypotension and restrictions in diet and other medication use, have been overcome by the advent of reversible selective inhibitors of MAO-A, but the efficacy of these in the elderly has yet to be proven in clinical trials. Lithium remains the mainstay for the treatment of bipolar disorder. However, careful dosing and monitoring of plasma lithium concentrations are required in the elderly due to changes in pharmacokinetics and pharmacodynamics which make older patients very sensitive to the toxic effects of this medication. Similarly, age-related changes in the pharmacokinetics and pharmacodynamics of the benzodiazepines, the most frequently prescribed medications for anxiety in the elderly, result in recommendations for lower doses and preferential use of those agents metabolised by conjugation (e.g. oxazepam). Buspirone, a partial serotonin 5-HT1A-agonist which is better tolerated than benzodiazepines in the elderly, may be used as an alternative. The elderly are extremely sensitive to extrapyramidal adverse effects which the typical antipsychotics (neuroleptics) exhibit to varying extents. The selection of a suitable agent for the treatment of a psychotic disorder should be based upon the adverse effect profile of the drug and the specific symptoms and situation of the patient. The newer atypical antipsychotics, clozapine and risperidone, have yet to be well-studied in the elderly. Dementia, exemplified by Alzheimer's disease, is almost exclusively an illness of the elderly. Only one medication, tacrine, has been approved for its treatment, based on extensive basic research and positive results of several clinical trials. Its long-term benefits have yet to be determined and it has several adverse effects, including a tendency to increase liver enzymes to the extent that the medication has to be discontinued.(ABSTRACT TRUNCATED AT 400 WORDS)
老年人的心理药物治疗必须考虑到与年龄相关的大脑及各器官结构和功能变化所产生的影响。一般来说,老年人比年轻人对精神药物的治疗作用和毒性作用更为敏感,因此需要更低的剂量和更长的给药间隔。这适用于5种主要类型的精神疾病(抑郁症、双相情感障碍、焦虑症、精神障碍和痴呆症)的治疗。三环类抗抑郁药虽然有效、价格低廉且有30年的使用经验,但与新型抗抑郁药如选择性5-羟色胺再摄取抑制剂相比,老年人对其耐受性较差。单胺氧化酶(MAO)抑制剂存在体位性低血压以及饮食和其他药物使用受限等问题,不过可逆性选择性MAO-A抑制剂的出现克服了这些问题,但这些药物在老年人中的疗效尚未在临床试验中得到证实。锂盐仍然是治疗双相情感障碍的主要药物。然而,由于药代动力学和药效学的变化,老年人对这种药物的毒性作用非常敏感,因此需要仔细调整剂量并监测血浆锂浓度。同样,苯二氮䓬类药物是老年人最常用的抗焦虑药物,其药代动力学和药效学的年龄相关变化导致推荐使用更低剂量,并优先选用通过结合代谢的药物(如奥沙西泮)。丁螺环酮是一种5-羟色胺1A部分激动剂,在老年人中比苯二氮䓬类药物耐受性更好,可作为替代药物使用。老年人对典型抗精神病药物(神经阻滞剂)不同程度表现出的锥体外系不良反应极为敏感。治疗精神障碍时合适药物的选择应基于药物的不良反应情况以及患者的具体症状和病情。新型非典型抗精神病药物氯氮平和利培酮在老年人中的研究尚不充分。以阿尔茨海默病为例的痴呆症几乎完全是老年人的疾病。基于广泛的基础研究和多项临床试验的阳性结果,只有他克林一种药物被批准用于治疗痴呆症。其长期益处尚未确定,且有多种不良反应,包括使肝酶升高,严重时不得不停药。(摘要截选至400词)