Delirium during early abstinence from street heroin: An uncommon but probable withdrawal feature?

To the Editor,

Complications such as convulsions and delirium are seen in alcohol withdrawal. Such presentations are rarely seen in opioid withdrawal.[1] A comparative study involving 136 opioid users in India and Nepal identified seven cases of opioid withdrawal delirium.[2] A PubMed search through February 2025 with ‘opioid’, ‘withdrawal,’ and ‘delirium’ in the title retrieved only nine case reports.[1,3,4,5,6,7,8,9,10] We hereby report a case of opioid dependence presenting with delirium during withdrawal.

CASE SUMMARY

A 22-year-old male was presented to the Outpatient Department (OPD) of a psychiatric hospital with chief complaints of regular intake of brown sugar in a dependence pattern for 4 years, confusion, and not recognizing family members for the past 3 days after abrupt cessation of heroin use. Other chief complaints were occasional intake of cannabis (Ganja) and alcohol with their last intake 4 months and 2 months ago, respectively. His family members corroborated the pattern of his use of substances during the assessment. The index patient was admitted to the deaddiction center for inpatient management. History revealed that the index patient started and increased consuming brown sugar over the past 4 years to currently 2 grams/day often in the morning and multiple times with friends throughout the day. He always consumed brown sugar by ‘chasing’ and denied ever using it via the intravenous route. He never tried to quit it because if he did not consume it, he would feel very restless and irritable and would also complain of body aches and runny nose, so to avoid all these symptoms, he would always indulge in heroin. After repeated advice and pressure from his parents, he stopped using brown sugar once for 1 day. Following this, within 24 hours of last intake of brown sugar, he started having severe body aches, lacrimation, runny nose, restlessness, and irritability. With passage of time, his family members noticed that gradually over the next 24 hours, he was unable to recognize his family members and appeared confused at times. He was talking irrelevantly and did not recognize the family members. He would also be seen trying to catch hold of things in the air or walls as if something was there. At times he would behave normally, but at times he would be confused. When these symptoms persisted for another day, guardians brought him to the OPD of the institute. There was no similar history or any significant family history. On examination at the time of OPD visit, the patient was afebrile and was not oriented to time and person. General survey and systemic examination did not suggest any foci of infection or reveal signs of dehydration. He was responding to verbal commands inconsistently and talking irrelevantly. His pupils were dilated and reactive. The severity score on the Clinical Opioid Withdrawal Scale (COWS)[11] was 14, indicating moderate withdrawal. His biochemical and hematological investigation reports are shown in Table 1. Electrocardiogram (ECG) did not reveal any abnormalities.

Table 1.

Physical investigations and laboratory investigations of the patient

Parameter	Result	Parameter	Result
Pulse	74 bpm	BP	114/80 mm Hg
Hb	13.9 g/dl	Total bilirubin	0.63 mg/dl
WBC	10.1 x 10^3/ul	Total protein	6.83 g/dl
RBC	4.73 x 10^6/ul	AST	20.5 u/l
Platelet	127 x 10^3/ul	ALT	23.7 u/l
Neutrophils	75.8%	Triglycerides	103.1 mg/dl
Lymphocytes	22.3%	Cholesterol	131 mg/dl
Eosinophils	1.2%	HDL	27.0 mg/dl
FBS	92 mg/dl	VLDL	21 mg/dl
Urea	23.6 mg/dl	LDL	83.8 mg/dl
Creatinine	0.67 mg/dl	Albumin and Globulin ratio	1.54
Sodium	137.90 mmol/l	Potassium	3.36 mmol/l

Hb- Hemoglobin, WBC – white blood corpuscle, RBC- red blood corpuscle, BP- blood pressure, AST- Aspartate transaminase, ALT- Alanine transaminase, HDL- high-density lipoprotein, VLDL- very low-density lipoprotein, LDL- low-density lipoprotein

He was started on parenteral haloperidol 2.5 mg BID and injection lorazepam 2 mg TID. Detoxification was started with oral clonidine 100 mcg TID with gradual tapering 50 mcg every 3 days and nonsteroidal anti-inflammatory medication on an SOS basis. His confusion started to show improvement, and on day 3 after admission, he was fully oriented to time, place, and person and was not confused. Parenteral haloperidol was stopped, and injection lorazepam was switched to oral lorazepam, which was gradually tapered off. The patient was detoxified over a period of two and half weeks since his visit to OPD. He was offered motivational enhancement therapy (MET) and started on Tab Naltrexone as an anti-craving agent.

DISCUSSION

Absence of fever, head injury, and use of alcohol or benzodiazepines pointed toward delirium, probably due to illicit opioid withdrawal in our patient. Delirium is caused by an array of psychopathologies arising from multiple etiologies. Among them, the neurotransmitter imbalance pathway is relevant in delirium due to drug use.[12] The most implicated neurotransmitter imbalances are reduced acetylcholine (Ach), with excess dopamine (DA), norepinephrine (NE), and glutamate (Glu).[13] Long-term opioid use causes increased sensitivity of dopaminergic, cholinergic, and serotonergic neurotransmission. The effect of opioids on noradrenergic neurotransmission is the primary mediator of the symptoms of opioid withdrawal. Thus, opioid dependence evokes a compensatory homeostatic mechanism within the neurons, which results in rebound hyperactivity during opioid withdrawal.[14] Preclinical and clinical studies have found increased activity of dopaminergic and adrenergic neurotransmission during opioid withdrawal.[15,16] This neurotransmitter imbalance might precipitate delirium during opioid withdrawal in such cases. Although these speculate that opioids can cause delirium during early abstinence, due to nonavailability, the etiology of delirium could not be confirmed by urine drug screening, thin-layer chromatography, or gas chromatography–mass spectrometry (GC-MS) report in our patient. In contrast to existing reports, our patient was a young man rather than elderly with comorbidities and had moderate severity of opioid withdrawal. During opioid withdrawal, symptoms like frequent vomiting and diarrhea can cause electrolyte imbalance, dehydration, and eventually heart failure with deadly results. Our patient did not have any such feature as well. Evidence exists for another potential cause for delirium during opioid withdrawal. An alternative explanation may be the presence of impurities in street heroin used which may lead to delirium.[8,17] High concentrations of benzodiazepines and barbiturates have been found as adulterants in street heroin worldwide including in India.[17,18,19,20] Thus, a more plausible but concerning explanation of delirium in our patient was benzodiazepine or barbiturate present as impurities and adulterants in street heroin our patient was dependent on. These adulterations and impurities can pose a significant threat to opioid users and those who suffer from opioid use disorder during early abstinence. Clinicians should keep this in mind and be watchful for delirium as a presenting feature of opioid withdrawal.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.