Analgesic treatments in people with dementia - how safe are they? A systematic review

Introduction: People with dementia may be unable to verbally express pain and suffer from untreated pain. Use of analgesics in people with dementia has increased during the last decade, in particular opioid analgesics with high potential for adverse effects.

Areas covered: This article presents a systematic review of the current evidence for safety and tolerability of analgesic drugs from randomized controlled trials in people with dementia. Relevant trials were identified by a literature search in the EMBASE, MEDLINE, and Cochrane databases from inception to November 2018. The search included the main terms ‘dementia’ and ‘analgesic’ or their subterms, and was filtered to limit results to clinical trials.

Expert opinion: Although pain treatment is increasingly recognized as an important clinical issue in people with advanced dementia, there is currently a lack of evidence to support safety evaluations of commonly used analgesics in this group. To inform treatment decisions and enable care providers to appropriately monitor patients at risk of adverse effects, it is necessary to conduct well-designed clinical trials to investigate the relative efficacy and safety of analgesics in people with dementia, with particular emphasis on harmful effects of long-term opioid use as well as short-term use of nonsteroidal anti-inflammatory drugs.     

Comparative analgesic efficacy of pregabalin administered according to either a prevention protocol or an intervention protocol in rats with cisplatin‐induced peripheral neuropathy

Chemotherapy‐induced peripheral neuropathy (CIPN) is a type of peripheral neuropathic pain that may be dose‐limiting in patients administered potentially curative cancer chemotherapy dosing regimens. In cancer survivors, persistent CIPN adversely affects patient quality of life and so adjuvant drugs (anticonvulsants eg pregabalin or antidepressants eg amitriptyline) are recommended for the relief of CIPN. However, most studies in rodent models of CIPN involve administration of single bolus doses of adjuvant drugs to assess pain‐relieving efficacy. Hence this study was designed to assess the efficacy of pregabalin administered to CIPN‐rats according to either a prevention or an intervention protocol. Groups of male Sprague‐Dawley rats received four single intraperitoneal bolus doses of cisplatin at 3 mg/kg at once‐weekly intervals to induce CIPN. For the prevention protocol, oral pregabalin (or vehicle) was administered to CIPN‐rats once‐daily for 21 consecutive days from day 0 to day 20 inclusive. For the intervention protocol, oral pregabalin was administered once‐daily for 21 consecutive days from day 28 to day 48, inclusive. Mechanical allodynia and mechanical hyperalgesia in the bilateral hindpaws were assessed just prior to each dose of cisplatin and at least once weekly until study completion (day 27, prevention protocol; or day 48, intervention protocol). Mechanical allodynia and mechanical hyperalgesia were also determined at the time of peak effect at about 2 hours post pregabalin/vehicle administration, once weekly until study completion. For the prevention protocol in CIPN‐rats, pregabalin alleviated mechanical hyperalgesia but not mechanical allodynia. For the intervention protocol, pregabalin alleviated both mechanical allodynia and mechanical hyperalgesia in the hindpaws.     

多中心、随机、双盲、安慰剂对照评价普瑞巴林添加治疗部分性癫癎发作的疗效和安全性

目的 评价普瑞巴林添加治疗部分性癫（癎）发作的疗效和安全性.方法采用随机、双盲、安慰剂对照、多中心平行设计添加治疗的方法,确诊为有部分性癫（癎）发作的225例癫（癎）患者,被随机分配入普瑞巴林治疗组（114例）与安慰剂组（111例）.在6周前瞻性基线期后,采用灵活剂量的普瑞巴林（150～600 mg·d-1）添加治疗成人部分性癫（癎）发作.主要疗效指标：部分性癫（癎）发作28 d-反应率.次要疗效指标：部分性癫（癎）发作28d-减少率、临床疗效评价、16周内癫（癎）无发作和发作减少率≥50％的病例比例、第13～16周癫（癎）无发作和发作减少率≥50％的病例比例以及临床疗效总评量表评分;并观察研究药物的安全性与不良反应情况.结果 普瑞巴林组部分性癫（癎）发作28 d-反应率（-40.24±37.88）％,显著高于安慰剂组（-22.84±37.61）％（F=15.063 9,P=0.000 l）.普瑞巴林组和安慰剂组的不良事件发生率分别为60.53％和47.75％,组间无显著差异;但普瑞巴林组的不良反应发生率较安慰剂组高（45.61％ vs 23.42％,P=0.000 7）,主要不良反应有头晕、嗜睡、视物模糊、乏力等.结论 普瑞巴林组的疗效显著优于安慰剂组.普瑞巴林作为部分性癫（痈）发作的添加药物有确定的疗效,安全耐受性较好,具有一定临床应用价值.