East Asian Arch Psychiatry 2024;34:87-8 | https://doi.org/10.12809/eaap2404

CASE REPORT

Delirium secondary to inadvertent administration of naltrexone in patient with opioid dependence syndrome: a case report

Kritika Aggarwal, Rajeev Ranjan, Sulagna Mallik, Harshit Hemant Salian, Saurabh Shekhar


Kritika Aggarwal, Department of Psychiatry, All India Institute of Medical Sciences, Patna, India
Rajeev Ranjan, Department of Psychiatry, All India Institute of Medical Sciences, Patna, India
Sulagna Mallik, Department of Psychiatry, All India Institute of Medical Sciences, Patna, India
Harshit Hemant Salian, Department of Psychiatry, All India Institute of Medical Sciences, Patna, India
Saurabh Shekhar, Department of Psychiatry, All India Institute of Medical Sciences, Patna, India

Address for correspondence: Dr Sulagna Mallik, Department of Psychiatry, All India Institute of Medical Sciences, Patna, 801507, India. Email: sulagnamallik2014@gmail.com

Submitted: 15 January 2024; Accepted: 22 April 2024


pdf Full Paper in PDF

Introduction

Opioid withdrawal arises from the abrupt cessation, therapeutic discontinuation, or dosage reduction of opioids (μ-receptor agonists). It can also occur after administering an opioid antagonist or partial opioid agonist to people who are physically dependent on opioids.1 Precipitated opioid withdrawal induced by antagonists such as naloxone can be severe and abrupt, triggering psychological and physiological responses. It can lead to life-threatening complications such as myocardial infarction, respiratory distress, seizures, and, rarely, delirium.2 Precipitated opioid withdrawal is more common after administering naloxone than longer-acting antagonists such as naltrexone and nalmefene.3 There are limited guidelines available for the safe and efficient management of precipitated opioid withdrawal, particularly relating to delirium.4

Case presentation

In June 2023, a 24-year-old man presented to the emergency department of the All India Institute of Medical Sciences with an abrupt onset of restlessness, uneasiness, agitation, palpitations, severe body aches, multiple episodes of vomiting, and profuse sweating.

A family member reported that these symptoms occurred after taking prescribed naltrexone 25 mg in tablet form. The symptoms progressed to irrelevant speech, visual hallucinations, and psychomotor agitation in the form of pacing. The patient had a history of injecting buprenorphine 2 mg mixed with promethazine and had been treated for opioid dependence (with clonidine, non- steroidal anti-inflammatory drugs, and anti-motility drugs) on an outpatient basis for the previous 20 days. After 20 days of opioid abstinence (as confirmed by the patient), naltrexone 25 mg/day was prescribed in the morning of the current presentation. The patient had no history of head trauma, seizure, infection, or psychiatric illness (personal or familial). His only other substance abuse issue was regular chewable tobacco use.

Physical examination revealed disorientation to time and place. Blood pressure was 136/84 mmHg; pulse rate was 130 beats per minute; and temperature was normal. Multiple prominent thrombosed veins were observed in both forearms. His pupils were dilated. There was bilateral plantar flexor response. Postural tremor was noted. The patient had no signs of focal neurological abnormality or meningism. Test results of the abdominal, respiratory, and cardiovascular systems were normal.

On mental status examination, the patient had increased psychomotor activity, irrelevant speech, irritable affect, disorganised thoughts, visual hallucinations, and inattention. The patient’s Clinical Opioid Withdrawal Scale score was 23, which indicates moderate withdrawal. Non- contrast computed tomography of the head was normal, as was blood test results. A urine drug screen tested positive for buprenorphine.

The patient received intravenous diazepam 10 mg and deep intramuscular haloperidol 2.5 mg for treatment of agitation, but agitation persisted. He was then given diazepam 60 mg, haloperidol 15 mg, metoclopramide 10 mg, and intravenous fluids over 6 hours, but the patient became drowsy. In the following day, his orientation improved and his Clinical Opioid Withdrawal Scale score decreased to 4. He was maintained on oral diazepam 20 mg/day, pantoprazole 40 mg/day, and diclofenac 50 mg (as required). On questioning, the patient admitted to using buprenorphine before taking naltrexone. On day 3, he was transitioned to oral diazepam 15 mg/day and clonidine 150 mg/day. He was discharged on day 7. Diazepam was gradually stopped.

Discussion

Naltrexone (4-hour half-life) is metabolised to 6β-naltrexol (13-hour half-life); both act as opioid receptor antagonists. Their strongest activity is at μ receptors; they outcompete opioids such as methadone in reducing mesolimbic dopamine and opioid euphoria. Initiation of naltrexone requires 7 opioid-free days to avoid severe withdrawal; immediate administration of naltrexone without abstinence of opioid can cause life-threatening withdrawal symptoms. There are limited case reports of opioid withdrawal delirium; its diagnosis involves exclusion of metabolic, structural, traumatic, and toxicological causes.

The clinical presentation of our patient indicated delirium. The absence of head injury, loss of consciousness, or high fever, coupled with no history of other substance abuse, suggested delirium secondary to naltrexone-induced opioid withdrawal, which was supported by laboratory results. Treatments involve benzodiazepines for agitation, antiemetics for nausea and vomiting, airway protection, fluid replenishment, non-opioid analgesia for musculoskeletal pain, and clonidine (0.1-0.2 mg every 6 hours) for anxiety, tremor, and sweating.

A study reported two cases of delirium secondary to naltrexone-induced opioid withdrawal.1 In the first case, a patient experienced sudden agitation and watery diarrhoea after consuming naltrexone 50 mg in addition to prescribed 100 mg/day methadone dose. Management involved intravenous injection of fluids and midazolam 80 mg for 24 hours. In the second case, a patient on a daily methadone regimen had a sudden onset of agitation and severe diarrhoea after taking naltrexone provided by a family member. Delirium was resolved after taking lorazepam. In addition, a case series reported precipitated opioid withdrawal secondary to improper use of naltrexone.2 In all five cases, withdrawal was caused by deviation from the treatment protocol; patients took naltrexone before the recommended 10 opiate-free days. Of the five patients, two involved withdrawal seizures and delirium and one had a fatal outcome. All patients were treated in the intensive care unit with benzodiazepines (intramuscular or intravenous), along with symptomatic management. In a patient with precipitated opioid withdrawal after taking naltrexone 100 mg 8 hours after a dose of heroin, symptoms improved only after administration of clonidine.3

The most common symptoms after taking naltrexone in patients with active opioid use are agitation and altered levels of consciousness, followed by nausea, vomiting, and abdominal pain.5 Agitation is the most difficult to manage. The dose of naltrexone is not associated with the presence of these symptoms, except for agitation. In a 17-year-old woman who received extended-release naltrexone for opioid dependence, she developed precipitated opioid withdrawal with mild intoxication several days after taking oxycodone.6

Naltrexone-induced opioid withdrawal requires prompt and aggressive management. Antagonism of the κ opioid receptor by naltrexone could lead to increased dopamine release in the medial prefrontal cortex and could trigger psychotic symptoms such as delirium.7

Conclusion

Clinicians should ensure the duration of abstinence of opioid before prescribing naltrexone; a naloxone challenge test can be conducted. Clinicians should refrain from prescribing naltrexone if recent opioid use is suspected.

Contributors

All authors designed the study, acquired the data, analysed the data, drafted the manuscript, and critically revised the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

Conflicts of interest

All authors have disclosed no conflicts of interest.

Funding/support

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

All data generated or analysed during the present study are available from the corresponding author on reasonable request.

Ethics approval

The patient was treated in accordance with the tenets of the Declaration of Helsinki. The patient provided written informed consent for all treatments and procedures and for publication.

References

  1. Miles I, Kestler A, Scheuermeyer FX. Diarrhea and delirium from naltrexone-precipitated opioid withdrawal. Can J Emerg Med 2020;22:121-2. Crossref
  2. Iovcheva M, Zlateva S, Asparuhova M. Precipitated withdrawal reaction to opiates in cases of improper use of naltrexone. Addict Biol 2007;1:75-7.
  3. Kurmi J, Choudhury HA. Life threatening opioid withdrawal syndrome due to inadvertent naltrexone administration and lifesaving result by clonidine. Indian J Psychiatry 2020;62:742. Crossref
  4. National Institute for Health and Care Excellence. Drug misuse in over 16s: opioid detoxification. Accessed 15 January 2024. Available from: https://www.nice.org.uk/guidance/cg52/re10sources/drug-misuse-in-over-16s-opioid-detoxification-pdf-975504131269.
  5. Hassanian-Moghaddam H, Afzali S, Pooya A. Withdrawal syndrome caused by naltrexone in opioid abusers. Human Exp Toxicol 2014;33:561-7. Crossref
  6. Fishman M. Precipitated withdrawal during maintenance opioid blockade with extended release naltrexone. Addiction 2008;103:1399-401. Crossref
  7. Margolis EB, Lock H, Chefer VI, Shippenberg TS, Hjelmstad GO, Fields HL. κ opioids selectively control dopaminergic neurons projecting to the prefrontal cortex. Proceed Natl Acad Sci 2006;103:2938-42. Crossref
View My Stats