Scheltema Beduin Albertine, de Haan Lieuwe
Department of Psychiatry, Academic Medical Centre, Amsterdam, The Netherlands.
Psychopharmacol Bull. 2010;43(3):45-81.
Impulse regulation disorders and substance abuse disorders have considerable consequences for treatment and prognosis of comorbid psychiatric disorders. Second generation antipsychotics (SGA) are frequently prescribed off-label for these disorders. This off label use of SGA entails some systematic problems, such as lack of knowledge about their long-term efficacy and effects, including side-effects, and unclarity about doses in certain disorders and patient groups, for example children and adolescents. In this review we describe the evidence that supports off-label use of the second generation antipsychotics risperidone, olanzapine, clozapine, ziprasidone, quetiapine and aripiprazole in impulse regulation disorders and substance abuse disorders. We discuss these disorders together since we argue that the central feature of impulsivity in both disorders is a possible target for antipsychotic medication. Subsequently we discuss the adverse effects of these agents and we consider some hypotheses about the mechanism of action in these disorders. Several double-blind randomised placebo-controlled trials have proven that risperidone is effective in attention-deficit and disruptive behavior disorders in children and adolescents, in behavioral problems and subaverage intelligence and in tic disorders. Some double-blind randomised placebo-controlled trials, open-label studies and case reports find efficacy of olanzapine in tic disorders and pervasive developmental disorder. Risperidone and olanzapine are found to be ineffective in substance use disorders. In tic disorders two double-blind randomised placebo-controlled trials show inefficacy of clozapine and efficacy of ziprasidone. Some open-label studies found no benefit of quetiapine in pervasive developmental disorder. Single-blind and open-label studies argue the benefit of clozapine, quetiapine and aripiprazole in substance abuse and dependence. A few open-label studies and case reports suggest efficacy of quetiapine, aripiprazole and ziprasidone in attention-deficit and disruptive behavior disorders in children and adolescents and in tic disorders. Metabolic side effects such as hyperglycaemia and diabetes mellitus, weight gain and hyperlipidaemia are reported in all SGA, but especially in clozapine and olanzapine. In children they seem to be more pronounced than in adults. The most reported side effect in off-label SGA use in children, adolescents and adults is sedation. More double-blind randomised placebo-controlled trials into the long-term efficacy and safety of second generation antipsychotics are needed. Moreover head to head comparison of SGA against each other and against first-generation antipsychotic medication is still needed to determine the superiority of specific agents in treatment of specific disorders.
冲动调节障碍和物质使用障碍对共病精神障碍的治疗和预后有相当大的影响。第二代抗精神病药物（SGA）经常被超说明书用于治疗这些障碍。SGA的这种超说明书使用存在一些系统性问题，比如对其长期疗效和影响（包括副作用）缺乏了解，以及在某些障碍和患者群体（如儿童和青少年）中剂量不明确。在本综述中，我们描述了支持第二代抗精神病药物利培酮、奥氮平、氯氮平、齐拉西酮、喹硫平和阿立哌唑超说明书用于冲动调节障碍和物质使用障碍的证据。我们将这些障碍放在一起讨论，因为我们认为这两种障碍中冲动性的核心特征可能是抗精神病药物治疗的靶点。随后我们讨论了这些药物的不良反应，并考虑了一些关于这些障碍作用机制的假说。多项双盲随机安慰剂对照试验已证明，利培酮对儿童和青少年的注意力缺陷与破坏性行为障碍、行为问题与智力低于平均水平以及抽动障碍有效。一些双盲随机安慰剂对照试验、开放标签研究和病例报告发现奥氮平对抽动障碍和广泛性发育障碍有效。利培酮和奥氮平在物质使用障碍中被发现无效。在抽动障碍方面，两项双盲随机安慰剂对照试验显示氯氮平无效而齐拉西酮有效。一些开放标签研究发现喹硫平对广泛性发育障碍无益处。单盲和开放标签研究认为氯氮平、喹硫平和阿立哌唑对物质滥用和依赖有益。一些开放标签研究和病例报告表明喹硫平、阿立哌唑和齐拉西酮对儿童和青少年的注意力缺陷与破坏性行为障碍以及抽动障碍有效。所有SGA都有代谢副作用的报告，如高血糖和糖尿病、体重增加和高脂血症，但在氯氮平和奥氮平中尤为明显。在儿童中，这些副作用似乎比在成人中更显著。在儿童、青少年和成人中，超说明书使用SGA最常报告的副作用是镇静作用。需要更多关于第二代抗精神病药物长期疗效和安全性的双盲随机安慰剂对照试验。此外，仍需要对SGA相互之间以及与第一代抗精神病药物进行头对头比较，以确定特定药物在治疗特定障碍方面的优势。
