Craving and addictive potential of esketamine as side effects?

ABSTRACT

Introduction

Esketamine was approved for adults with treatment-resistant depression (TRD) in conjunction with an oral antidepressant, and for treating depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. However, evidence of great efficacy and safety of esketamine is accompanied by a widespread concern regarding its addictive potential.

Areas covered

A comprehensive review on the craving and addictive potential of ketamine and esketamine was carried out. In addition, a clinical case of a 34-year-old TRD woman treated with esketamine who experienced drug-seeking behaviors and craving symptomatology was described and critically discussed, with a particular focus on treatment strategies to manage craving in the short- and long term.

Expert opinion

Esketamine showed great efficacy and safety in treating TRD and MDD with acute suicidal ideation or behavior. Our clinical experience demonstrated the presence of an additive potential, which has been favorably managed with slow esketamine de-titration and combination with bupropion. However, literature so far published is scant and shows contradictory findings. Therefore, it is crucial to promptly detect and manage craving symptomatology in esketamine-treated TRD patients. In our experience, the use of bupropion to counteract craving and addictive symptoms was proven to be effective and safe.

KEYWORDS:

• Addictive
• addiction
• craving
• depression
• esketamine
• ketamine
• treatment-resistant depression

Article highlights

• Esketamine shows promise as an effective treatment for refractory major depressive disorder, despite some concerns in terms of its abuse liability

• Further longer-term studies of esketamine treatment should be implemented, by specifically focussing in collecting abuse liability, drug-seeking behaviors and craving symptomatology

• Clinicians should also be instructed on being watchful of requests for an increase in IN esketamine dose and/or dosing frequency, which may indicate early signs of abuse or addiction.

• There is the need to early detect and promptly manage the occurrence of drug-seeking behaviors and/or craving symptoms, even in those subjects without a previous positive history for substance and/or alcohol use.

Acknowledgments

We would like to thank Silvia Tempia Valenta for helping in collecting clinical data of the case report.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this manuscript has consulted to and received research funding from Janssen Pharmaceuticals, which developed intranasal esketamine. A separate peer reviewer on this manuscript reports honoraria, grants, and advisory for Janssen, Preceptive, Novartis, and Celon (terminated). The remaining peer reviewers on this manuscript have no relevant financial or other relationships to disclose.