Nunes E V, Deliyannides D, Donovan S, McGrath P J
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Psychiatr Clin North Am. 1996 Jun;19(2):311-27. doi: 10.1016/s0193-953x(05)70290-2.
General principles for treatment-resistant psychiatric disorders include reevaluation of diagnosis, search for hidden comorbidity, and systematic trials of alternative treatments and treatment combinations. For the combination of refractory depression and substance abuse, alternative approaches to both problems need to be tried, as suggested in the decision tree in Figure 1. Recognition of a previously unappreciated substance abuse problem or institution of more effective substance abuse treatment (see Table 2) can improve the outcome of depression. Hospitalization is often useful to enforce abstinence and to clarify the diagnosis of depression, and is particularly indicated if substance abuse is severe. If hospitalization is not possible then features of the history, such as relative onsets of depression and substance abuse, can be considered to support the diagnosis. TCAs and SSRIs have been studied in depressed substance abusers and should be the first lines of treatment. If these fail, other medications, medication combinations, or ECT should be considered, extrapolating from the general literature on treatment of refractory depression. In general, single agents should be preferred to combinations, as this reduces the odds of drug-drug interactions in patients who may abuse a variety of substances. Impairment by antidepressant agents of hepatic metabolism of other drugs should be considered, and sertraline, for example, might be preferred over fluoxetine for this reason. For each case, the known side effects and risks of a given antidepressant medication must be considered in the context of a patient's substance abuse pattern and medical problems. Such risk:benefit analyses are often difficult, as illustrated in the cases presented. Finally, although it is a rare occurrence, antidepressant medications that are anticholinergic or amphetamine-like may be abused, and this needs to be monitored. Alcohol or drug abuse history is a likely risk factor for benzodiazepine abuse, and benzodiazepines should, therefore, be avoided or used with caution. These recommendations for management of treatment-resistant depression with substance abuse are based upon clinical experience and extrapolation from the literature on treatment-resistant depression, treatment of substance abuse, and initial treatment of depression in substance abusers with TCAs and SSRIs. More treatment research is needed, particularly on Type IV patients where both depression and substance use are treatment resistant.
难治性精神障碍的一般治疗原则包括重新评估诊断、寻找潜在的共病情况，以及对替代治疗和治疗组合进行系统试验。对于难治性抑郁症与物质滥用并存的情况，需要尝试针对这两个问题的替代方法，如图1中的决策树所示。识别先前未被重视的物质滥用问题或采用更有效的物质滥用治疗方法（见表2）可以改善抑郁症的治疗效果。住院治疗通常有助于强制戒酒并明确抑郁症的诊断，尤其是在物质滥用严重的情况下。如果无法住院治疗，则可以考虑病史特征，如抑郁症和物质滥用的相对发病时间，以支持诊断。三环类抗抑郁药（TCAs）和选择性5-羟色胺再摄取抑制剂（SSRIs）已在患有物质滥用的抑郁症患者中进行了研究，应作为一线治疗药物。如果这些药物治疗失败，则应根据关于难治性抑郁症治疗的一般文献，考虑使用其他药物、药物组合或电休克治疗（ECT）。一般来说，应优先选择单一药物而非联合用药，因为这可以降低可能滥用多种物质的患者发生药物相互作用的几率。应考虑抗抑郁药对其他药物肝代谢的影响，例如，出于这个原因，舍曲林可能比氟西汀更受青睐。对于每个病例，必须根据患者的物质滥用模式和医疗问题，考虑特定抗抑郁药物已知的副作用和风险。正如所呈现的病例所示，这种风险效益分析往往很困难。最后，虽然很少见，但具有抗胆碱能或类似苯丙胺作用的抗抑郁药物可能会被滥用，需要对此进行监测。酒精或药物滥用史可能是苯二氮䓬类药物滥用的风险因素，因此应避免使用或谨慎使用苯二氮䓬类药物。这些关于难治性抑郁症合并物质滥用管理的建议基于临床经验以及从关于难治性抑郁症、物质滥用治疗以及使用三环类抗抑郁药和选择性5-羟色胺再摄取抑制剂对物质滥用者进行抑郁症初始治疗的文献中推断得出。需要更多的治疗研究，特别是针对IV型患者，这类患者的抑郁症和物质使用均具有难治性。
