Taylor Matthew J, Rudkin Lisa, Bullemor-Day Philippa, Lubin Jade, Chukwujekwu Christopher, Hawton Keith
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
Cochrane Database Syst Rev. 2013 May 31;2013(5):CD003382. doi: 10.1002/14651858.CD003382.pub3.
Sexual dysfunction (including altered sexual desire, orgasmic and ejaculatory dysfunction, erectile and other problems) is a relatively common side effect of antidepressant medication. These sexual side effects may compromise a person's lifestyle and result in a lack of compliance with the prescribed antidepressant to the detriment of the person's mental health. A wide range of management strategies are possible to address this problem, including behavioural, psychological and pharmacological approaches.
We searched the Cochrane Depression, Anxiety and Neurosis Group's Specialized Register (CCDANCTR, to 1 January 2013), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). Additional searches were carried out by the author team on the same biomedical databases (using terms for 'sexual dysfunction' only) together with CINAHL (1982 to Jan 2012). The reference lists of reports of all included studies were screened.
We included randomised controlled trials that compared management strategies for antidepressant-induced sexual dysfunction versus placebo or any alternative strategy.
Two authors independently extracted data and assessed trial quality. Study authors were contacted for additional information.
We included 23 trials involving 1886 people in this updated review. Twenty-two of these trials investigated the addition of medication to treat the identified dysfunction, with most agents studied in only single studies. One study investigated switching to an alternative antidepressant.In men, data for the phosphodiesterase inhibitors sildenafil (three studies, 255 participants) and tadalafil (one study, 54 participants) indicated they led to a greater improvement in erectile function than placebo. Combined data from three sildenafil studies found benefit over placebo on International Index of Erectile Function ratings of ability to achieve (MD 1.04, 95% CI 0.65 to 1.44), and maintain erections (MD 1.18, 95% CI 0.78 to 1.59). A single point improvement on these ratings is equivalent to an improvement in frequency from 'sometimes' to 'most times'. Men receiving tadalafil were more likely to report improved erectile function (RR 11.50, 95% CI 3.03 to 43.67). For women it remains uncertain whether sildenafil is more effective than placebo. Unpublished data could reduce this uncertainty.Data from three studies in men and women of bupropion 150 mg twice daily indicate a benefit over placebo on rating scale scores (SMD 1.60, 95% CI 1.40 to 1.81), but response rates in two studies of bupropion 150 mg once daily demonstrated no statistically significant difference in effect (RR 0.62, 95% CI 0.09 to 4.41).Other augmentation strategies failed to demonstrate significant improvements in sexual dysfunction compared with placebo.One trial involving 75 people with sexual dysfunction due to sertraline assessed the effect of changing antidepressant. Switching to nefazodone was significantly less likely to result in the re-emergence of sexual dysfunction than restarting sertraline (RR 0.34, 95% CI 0.19 to 0.60), however, nefazodone is no longer available for clinical use.There is an absence of randomised trials assessing the effects of switching to currently-available antidepressant agents with lower rates of adverse sexual effects, the role of psychological or mechanical interventions, or of techniques such as drug holidays.We identified no data for any of the strategies included in the trials assessed that indicated that they led to a worsening of psychiatric symptoms. However, the relatively small numbers assessed for many of the interventions studied means that the possibility of such an effect cannot confidently be excluded in all cases.Given the small numbers of studies assessing most of the strategies assessed, the presence of any unpublished trials could have substantial effects on estimates of effect. In some cases, only results from particular items or subscales within ratings scales are available. It is likely that this could act to bias estimates of effect obtained, increasing apparent effectiveness.
AUTHORS' CONCLUSIONS: The evidence currently available is rather limited. For men with antidepressant-induced erectile dysfunction, the addition of sildenafil or tadalafil appears to be an effective strategy. For women with antidepressant-induced sexual dysfunction the addition of bupropion at higher doses appears to be the most promising approach studied so far.
性功能障碍(包括性欲改变、性高潮和射精功能障碍、勃起及其他问题)是抗抑郁药物相对常见的副作用。这些性方面的副作用可能会影响一个人的生活方式,并导致不遵守规定的抗抑郁药物治疗,从而损害其心理健康。解决这一问题有多种管理策略,包括行为、心理和药理学方法。
我们检索了Cochrane抑郁、焦虑和神经症小组的专业注册库(CCDANCTR,截至2013年1月1日),其中包括来自以下书目数据库的相关随机对照试验:Cochrane图书馆(所有年份)、EMBASE(1974年至今)、MEDLINE(1950年至今)和PsycINFO(1967年至今)。作者团队在相同的生物医学数据库上进行了额外检索(仅使用“性功能障碍”相关术语),同时检索了CINAHL(1982年至2012年1月)。对所有纳入研究报告的参考文献列表进行了筛选。
我们纳入了比较抗抑郁药所致性功能障碍管理策略与安慰剂或任何替代策略的随机对照试验。
两位作者独立提取数据并评估试验质量。与研究作者联系以获取更多信息。
在本次更新的综述中,我们纳入了23项试验,涉及1886人。其中22项试验研究了添加药物治疗已确定的功能障碍,大多数药物仅在单一研究中进行了研究。一项研究调查了换用另一种抗抑郁药的情况。在男性中,磷酸二酯酶抑制剂西地那非(三项研究,255名参与者)和他达拉非(一项研究,54名参与者)的数据表明,它们在改善勃起功能方面比安慰剂更有效。三项西地那非研究的合并数据显示,在国际勃起功能指数的勃起能力评分(MD 1.04,95%CI 0.65至1.44)和维持勃起评分(MD 1.18,95%CI 0.78至1.59)上优于安慰剂。这些评分上提高一分相当于频率从“有时”提高到“大多数时候”。接受他达拉非治疗的男性更有可能报告勃起功能改善(RR 11.50,95%CI 3.03至43.67)。对于女性,西地那非是否比安慰剂更有效仍不确定。未发表的数据可能会减少这种不确定性。三项关于每日两次服用150mg安非他酮的男性和女性的研究数据表明,在评分量表得分上优于安慰剂(SMD 1.60,95%CI 1.40至1.81),但两项关于每日一次服用150mg安非他酮的研究中的有效率未显示出统计学上的显著差异(RR 0.62,95%CI 0.09至4.41)。与安慰剂相比,其他增效策略未能显示出性功能障碍有显著改善。一项涉及75名因舍曲林导致性功能障碍的患者的试验评估了更换抗抑郁药的效果。换用奈法唑酮导致性功能障碍再次出现的可能性明显低于重新服用舍曲林(RR 0.34,95%CI 0.19至0.60),然而,奈法唑酮已不再用于临床。目前缺乏评估换用具有较低性不良反应发生率的现有抗抑郁药、心理或机械干预的作用或药物假期等技术效果的随机试验。我们未发现所评估试验中包含的任何策略导致精神症状恶化的数据。然而,许多所研究干预措施的评估人数相对较少,这意味着不能完全排除在所有情况下出现这种影响的可能性。鉴于评估大多数所评估策略的研究数量较少,任何未发表试验的存在可能会对效应估计产生重大影响。在某些情况下,仅可获得评分量表中特定项目或子量表的结果。这可能会使所获得的效应估计产生偏差,增加明显的有效性。
目前可得的证据相当有限。对于患有抗抑郁药所致勃起功能障碍的男性,添加西地那非或他达拉非似乎是一种有效的策略。对于患有抗抑郁药所致性功能障碍的女性,较高剂量添加安非他酮似乎是迄今为止研究中最有前景的方法。