Ameller A, Gorwood P
Département de psychiatrie, hôpital Louis-Mourier, AP-HP, 92700 Colombes, France; Inserm U894, centre de psychiatrie et neurosciences (CPN), Paris, France.
Inserm U894, centre de psychiatrie et neurosciences (CPN), Paris, France; Université Paris-Descartes, Paris-Sorbonne-Cité, 75005 Paris, France; Clinique des maladies mentales et de l'encéphale (CMME), groupe hospitalier Sainte-Anne, 100, rue de la Santé, 75014 Paris, France.
Encephale. 2015 Apr;41(2):174-83. doi: 10.1016/j.encep.2015.02.002. Epub 2015 Mar 30.
There are numerous risk factors involved in poor (incomplete) compliance to pharmacological treatment, and the associated relapse risk, for patients with schizophrenia. Comorbid substance use disorders are considered as among the most important ones, although how much their presence increase the risk of poorer observance (and higher risk of relapse) has not been yet assessed. This measure would be important, especially if the published literature on the topic provides sufficient material to perform a meta-analysis and to assess different potential biases such as those related to time (new studies are easier to publish when positive) or sample size (small samples might drive the global positive conclusion).
A PubMed(®) search was made, screening the following terms between 1996 and august 2014 "Addiction AND (Observance OR Adherence) AND schizophrenia AND (French OR English [Language])" and "(Substance Abuse OR substance dependance) AND Outcome AND schizophrenia AND (French OR English [Language])". Studies were included if they describe two patients groups (schizophrenia with and without present substance use disorder) and assess the studied outcome. MetaWin(®) version 2 was used for the meta-analysis, while publication time bias relied on non-parametric correlation and the one linked to sample size was assessed through normal quantile plots. An attributable risk was also computered, on the basis of the odds-ratio derived from the meta-analysis and the prevalence of the analyzed trait (associated substance use disorder).
Eight studies could be included in the meta-analysis, showing that the presence of a substance use disorder significantly increases the risk of poor observance to pharmacological treatment (OR=2.18 [1.84-2.58]), no significant bias being detected, either linked to time (rho=0.287, P=0.490) or sample size (Kendall's Tau=-0.286, P=0.322). The related attributable risk is 18.50%. Only three studies could be used for the meta-analysis of the risk of relapse associated with the presence of substance use disorders. The corresponding odds-ratio is 1.52 [1.19-1.94], and the attributable risk is 31.20%, but the search for biases could not be performed because of the small number of studies.
These results shed light on the importance of comorbid substance use disorder to explain the poor observance frequently observed in patients with schizophrenia. Indeed, having an associated substance use disorder double the risk of poor compliance to pharmacological treatment, this comorbidity explaining a fifth of all factors involved. Although the number of available studies does not allow definite conclusions, the meta-analysis of prospective studies focusing this time of the risk of relapse requiring hospitalization is also in favor of a significant role of associated substance use disorder. These results argue in favor of developing specific strategies to better treat patients with dual diagnoses, i.e. schizophrenia and substance use disorder.
精神分裂症患者药物治疗依从性差(不完全依从)及相关复发风险涉及众多危险因素。共病物质使用障碍被认为是最重要的因素之一,尽管其存在会增加较差依从性(及较高复发风险)的程度尚未得到评估。这一评估很重要,特别是如果关于该主题的已发表文献提供了足够材料来进行荟萃分析,并评估不同的潜在偏倚,如与时间相关的偏倚(阳性研究更容易发表)或样本量偏倚(小样本可能导致整体得出阳性结论)。
在PubMed(®)数据库进行检索,筛选1996年至2014年8月期间的以下检索词:“成瘾与(依从性或坚持性)与精神分裂症与(法语或英语[语言])”以及“(物质滥用或物质依赖)与结局与精神分裂症与(法语或英语[语言])”。如果研究描述了两组患者(有和无当前物质使用障碍的精神分裂症患者)并评估了所研究的结局,则纳入研究。使用MetaWin(®) 2版本进行荟萃分析,出版时间偏倚通过非参数相关性评估,与样本量相关的偏倚通过正态分位数图评估。还根据荟萃分析得出的优势比和所分析特征(相关物质使用障碍)的患病率计算了归因风险。
八项研究可纳入荟萃分析,结果显示物质使用障碍的存在显著增加了药物治疗依从性差的风险(优势比=2.18 [1.84 - 2.58]),未检测到与时间(rho = 0.287,P = 0.490)或样本量(肯德尔tau系数=-0.286,P = 0.322)相关的显著偏倚。相关归因风险为18.50%。仅有三项研究可用于对与物质使用障碍存在相关的复发风险进行荟萃分析。相应的优势比为1.52 [1.19 - 1.94],归因风险为31.20%,但由于研究数量少,无法进行偏倚搜索。
这些结果揭示了共病物质使用障碍对于解释精神分裂症患者中常见的依从性差的重要性。确实,存在相关物质使用障碍会使药物治疗依从性差的风险加倍,这种共病解释了所有相关因素的五分之一。尽管现有研究数量不足以得出明确结论,但此次对关注需要住院治疗的复发风险的前瞻性研究进行的荟萃分析也支持相关物质使用障碍起重要作用。这些结果支持制定特定策略以更好地治疗双重诊断患者,即精神分裂症和物质使用障碍患者。