Kopala L C
Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
Acta Psychiatr Scand Suppl. 1996;389:12-7. doi: 10.1111/j.1600-0447.1996.tb05943.x.
The extrapyramidal side-effects (EPS) of conventional neuroleptics are widely recognized. However, a substantial number of drug-naïve patients exhibit movement disorders which could be mistaken for EPS if drug therapy were started without a careful baseline assessment. Patients' experience of EPS during their first exposure to antipsychotic medication can have lasting effects on their attitudes to medication and compliance. Unmedicated, approximately 60% of patients will relapse in the first year after resolution of an acute psychotic episode, whereas prophylactic medication can reduce the relapse rate to less than 20%. The conventional neuroleptics produce antipsychotic effects at doses which differ little from those that induce EPS, and although anticholinergic medication helps to reduce the severity of EPS, it also causes side-effects, e.g. constipation, blurred vision, retention of urine, dry mouth and disturbances of sexual function. More importantly, anticholinergic drugs may worsen the psychosis and impair memory. Low or intermittent dose strategies with conventional neuroleptics may give patients relief from EPS, but they increase the relapse risk, and may also increase the risk of tardive dyskinesia. The serotonin-dopamine antagonist (SDA) antipsychotics, such as risperidone, produce both significant antipsychotic effects at doses which are lower than those that cause EPS, and also a lower level of EPS compared with conventional drugs. Clinical trials have shown that risperidone is effective in first-episode schizophrenia. In these trials the same doses were used as in chronic patients. However, clinical experience in Canada since the drug became generally available in 1993 suggests that first-episode patients require lower doses of risperidone than chronically ill patients who have had several acute psychotic episodes. More than 3 years of use has made it clear that risperidone should be seriously considered in first-episode patients, as it offers an opportunity to treat psychosis with minimal EPS. This in turn should lead to better compliance and a lower long-term relapse rate.
传统抗精神病药物的锥体外系副作用(EPS)已广为人知。然而,相当数量未使用过药物的患者存在运动障碍,如果在未进行仔细基线评估的情况下开始药物治疗,这些运动障碍可能会被误诊为EPS。患者首次接触抗精神病药物时对EPS的体验会对他们对药物治疗的态度和依从性产生持久影响。在未用药的情况下,约60%的患者在急性精神病发作缓解后的第一年就会复发,而预防性用药可将复发率降低至20%以下。传统抗精神病药物产生抗精神病作用的剂量与诱发EPS的剂量相差无几,尽管抗胆碱能药物有助于减轻EPS的严重程度,但它也会引起副作用,如便秘、视力模糊、尿潴留、口干和性功能障碍。更重要的是,抗胆碱能药物可能会使精神病症状恶化并损害记忆力。采用传统抗精神病药物的低剂量或间歇剂量策略可能会使患者从EPS中得到缓解,但会增加复发风险,还可能增加迟发性运动障碍的风险。5-羟色胺-多巴胺拮抗剂(SDA)类抗精神病药物,如利培酮,在低于引起EPS的剂量时就能产生显著的抗精神病作用,而且与传统药物相比,EPS的发生率也较低。临床试验表明,利培酮对首发精神分裂症有效。在这些试验中,使用的剂量与慢性患者相同。然而,自1993年该药物普遍上市以来,加拿大的临床经验表明,首发患者所需的利培酮剂量低于有过几次急性精神病发作的慢性病患者。超过3年的使用经验表明,首发患者应认真考虑使用利培酮,因为它提供了以最小的EPS治疗精神病的机会。这反过来又应能提高依从性并降低长期复发率。