A common painkiller triggered hallucinations mistaken for schizophrenia

A recent case report published in the medical journal Cureus describes how a man was mistakenly diagnosed with schizophrenia after developing hallucinations. The episodes, both visual and auditory, began shortly after he increased his prescribed dose of Norco, a combination of hydrocodone and acetaminophen, to manage chronic back pain. According to the patient’s account, the hallucinations stopped entirely when he discontinued the medication, raising questions about how often opioid-induced side effects are misinterpreted as signs of a serious psychiatric disorder.

This case provides a window into how the effects of prescription opioids can sometimes mimic primary psychotic disorders. It also illustrates how clinical context—such as medication history, timing of symptom onset, and prior psychiatric status—can help distinguish between drug-induced symptoms and conditions like schizophrenia.

The patient, a 67-year-old African American man, had a wide range of serious medical conditions. His history included congestive heart failure, coronary artery disease, hypertension, peripheral artery disease, chronic hepatitis C (complicated by hepatic coma), gastroesophageal reflux disease, chronic midline back pain, and spinal stenosis at the L4-L5 level. He was also a chronic tobacco user and reported very occasional cannabis use—only one or two hits every couple of months. His daily medications included baclofen, pantoprazole, metoprolol, gabapentin, and trazodone.

He had no known psychiatric history and no family history of mental illness or dementia. That changed at age 63, when he was hospitalized for a seizure. Roughly 20 days after the seizure, he began experiencing visual hallucinations—he reported seeing people trying to attack him and animals that weren’t present. He also exhibited paranoia. These symptoms led to his diagnosis with schizophrenia, unspecified, and he was admitted to an inpatient psychiatric facility for stabilization.

He responded well to treatment with Seroquel (quetiapine), an antipsychotic. A dose of 100 mg at bedtime helped reduce his symptoms and also aided his sleep. After two years of stability, the dose was lowered to 50 mg per night. He remained psychiatrically stable for a time and had no ongoing hallucinations.

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That changed when he presented again to the psychiatry clinic with a new wave of symptoms. He described feeling like someone was following him and hearing voices that were constantly in the background. These voices made derogatory comments and seemed intent on putting him down. While distressing, they never instructed him to harm himself or others. He also experienced visual hallucinations, including seeing small worms crawling across the roof of his house. He explicitly denied using marijuana or any recreational substances during this time.

He did, however, report that his chronic back pain had worsened. In response, he increased his intake of Norco—an opioid painkiller composed of hydrocodone and acetaminophen—to four tablets per day, which was still within the prescribed range. He noticed a clear correlation: the more Norco he took, the more vivid and intense the hallucinations became.

Recognizing the possibility of a medication-related issue, he decided on his own to stop taking Norco. After discontinuing the opioid, his hallucinations completely resolved. He has not experienced any further episodes of paranoia, auditory hallucinations, or visual hallucinations since stopping the medication.

This sequence of events—hallucinations emerging only after increasing his opioid dosage and disappearing after stopping the drug—suggests that the symptoms were not a recurrence of schizophrenia but rather an adverse effect of the opioid medication. Notably, the patient had been psychiatrically stable on a low dose of Seroquel, and there had been no other changes to his medication regimen or lifestyle that might have explained the sudden onset of hallucinations.

This pattern suggests the episodes were likely not a recurrence of schizophrenia but rather an adverse reaction to the opioid medication. Yet the symptoms were serious enough to warrant concern, highlighting how difficult it can be to tease apart psychiatric illness from medication effects, especially in medically complex patients.

It is important to note that case reports describe the experience of a single individual. This format lacks the statistical power to establish causality or generalize findings across populations. Case reports do not control for confounding variables, nor can they definitively rule out alternative explanations.

Still, case reports serve an essential role in medicine by drawing attention to rare or underrecognized phenomena. They can prompt further research, guide clinical awareness, and help prevent misdiagnosis. In this case, the authors suggest that greater attention to a patient’s medication history—including the use of opioids—could help clinicians avoid mistakenly labeling drug-induced symptoms as chronic psychiatric conditions.

Although not commonly discussed, hallucinations are a documented side effect of various opioid medications. Previous studies have reported that up to 6% of patients using fentanyl for postoperative pain experienced hallucinations. These may be underreported due to stigma, fear of being perceived as mentally ill, or because the hallucinations are mild and transient.

Opioids, especially when taken at higher doses or over long periods, can affect the brain’s dopamine system, which plays a role in perception and reward. Dopamine dysregulation has been implicated in both opioid-induced hallucinations and in conditions such as schizophrenia. This shared mechanism may partly explain the overlap in symptoms, even though the underlying causes differ.

Research also indicates that different opioids may have different risks. Morphine has been the most commonly reported opioid linked to hallucinations, but others—including hydromorphone, tramadol, methadone, and buprenorphine—have also been implicated. The neurotoxic effects may arise from the opioid itself or from its metabolites, which can vary in how they interact with brain receptors.

In some cases, changing the type of opioid—a process known as opioid rotation—can eliminate hallucinations while still managing pain. Other strategies include dose reduction or the addition of non-opioid pain treatments. When hallucinations do occur, they can sometimes be managed with antipsychotic medications, though this may not be ideal if the underlying problem is a reversible drug effect.

The authors of the case study point out that schizophrenia is typically a disorder of early adulthood, with most diagnoses occurring before the age of 40. A sudden onset of hallucinations and paranoia in a man in his mid-60s, especially without a family history of mental illness, should raise suspicion about alternative causes.

The patient’s first experience of hallucinations followed a seizure, which may have triggered postictal psychosis—a known but temporary condition. His more recent hallucinations appeared only after increasing his Norco dose and resolved completely after stopping it. These details suggest the need for caution when diagnosing a lifelong psychiatric disorder based on symptoms that may have other explanations.

This case also touches on the broader issue of polypharmacy in older adults, who often take multiple medications for various chronic conditions. Interactions between drugs, along with age-related changes in metabolism and brain function, can increase the risk of adverse effects, including neuropsychiatric symptoms.

The report, “Opioid-Induced Hallucinations: A Case Report,” was authored by Arvind Dhanabalan, Sall Saveen, Christina Singh, Ramona Ramasamy, and Keerthiga Raveendran.