Evidence of heterogeneity in the opioid withdrawal syndrome: Spontaneous and precipitated withdrawal

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI:10.1016/j.pbb.2026.174153

Suky Martinez , Jermaine D. Jones , Kelly E. Dunn , Andrew Huhn , Joshua A. Lile , Thomas P. Shellenberg , Laura Brandt

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引用次数: 0

Abstract

Aims

This study characterized the heterogeneity of opioid withdrawal by comparing naturally occurring withdrawal during opioid abstinence (spontaneous withdrawal) with abrupt, pharmacologically induced naloxone-precipitated withdrawal in adults with Opioid Use Disorder (OUD).

Methods

A secondary analysis was conducted on de-identified data from 86 adults meeting DSM-5 criteria for moderate-to-severe OUD. Participants either presented in spontaneous withdrawal (n = 28) or underwent naloxone challenge to precipitate withdrawal (n = 58). Withdrawal symptoms were rated using the Wang procedure. Principal Component Analysis (PCA) of binary symptom data was performed to identify dominant patterns of symptom co-occurrence. Separate PCAs were then conducted for the withdrawal syndrome types to delineate group-specific symptom clusters.

Results

In the combined sample, four principal components together accounted for 55.6% of the variance in withdrawal symptoms, with the highest loadings observed on autonomic (e.g., temperature change, sweating) and somatic (e.g., restlessness, yawning) domains. Subgroup analyses revealed distinct symptom-loading patterns: the spontaneous withdrawal group displayed a more pronounced autonomic profile dominated by temperature dysregulation and muscle aching, whereas the precipitated withdrawal group exhibited greater variability, with notable gastrointestinal (vomiting, stomach pain) and somatic features. Across analyses, inter-individual variability was substantial, underscoring the multidimensional nature of opioid withdrawal.

Conclusion

These findings suggest spontaneous and precipitated withdrawal are distinct clinical phenomena: the former emerges gradually, the latter produces diverse, acute symptoms, though both display heterogeneity. Moreover, relying solely on naloxone-challenge paradigms for treatment development may overlook key aspects of “real-world” spontaneous withdrawal, reinforcing the importance of broader experimental models and individualized care.

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阿片类戒断综合征异质性的证据：自发戒断和沉淀戒断。

目的：本研究通过比较阿片类药物使用障碍（OUD）成人阿片类药物戒断期间自然发生的戒断（自发戒断）和药物诱导的纳洛酮沉淀戒断，来表征阿片类药物戒断的异质性。方法：对符合DSM-5中度至重度OUD标准的86名成人的去识别数据进行二次分析。参与者要么表现为自发戒断（n = 28），要么接受纳洛酮刺激以沉淀戒断（n = 58）。戒断症状采用Wang程序评定。对二元症状数据进行主成分分析（PCA），以确定症状共现的主要模式。然后对戒断综合征类型进行单独的pca，以描述组特异性症状群。结果：在综合样本中，四个主要成分共同占戒断症状方差的55.6%，其中自主神经（如体温变化、出汗）和躯体（如烦躁不安、打哈欠）领域的负荷最高。亚组分析揭示了不同的症状负荷模式：自发戒断组表现出更明显的自主神经特征，以温度失调和肌肉疼痛为主，而沉淀戒断组表现出更大的可变性，有显著的胃肠道（呕吐、胃痛）和躯体特征。在分析中，个体间的差异是实质性的，强调了阿片类药物戒断的多维性。结论：自发性戒断和沉淀性戒断是两种不同的临床现象，自发性戒断是逐渐出现的，而自发性戒断则表现为不同的急性症状，但两者均具有异质性。此外，仅仅依靠纳洛酮挑战范式来开发治疗可能会忽视“现实世界”自发戒断的关键方面，从而加强了更广泛的实验模型和个性化护理的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacology Biochemistry and Behavior 医学-行为科学

CiteScore

6.40

自引率

2.80%

发文量

122

审稿时长

38 days

期刊介绍： Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.