Definitions and scope

Medication- or substance-induced neurocognitive impairment includes acute confusional states (intoxication, withdrawal, delirium) and longer-term cognitive deficits caused directly by toxic effects or indirectly via repeated exposure, metabolic disturbances or structural brain injury.

Common offending substances and medication classes

• Alcohol: acute intoxication, Wernicke encephalopathy (thiamine deficiency), and chronic Korsakoff syndrome causing persistent memory impairment.
• Benzodiazepines and sedative-hypnotics: acute sedation, impaired attention, risk of withdrawal seizures and persistent cognitive slowing with long-term use.
• Opioids: respiratory depression leading to hypoxic injury, acute delirium, and long-term cognitive effects with chronic misuse.
• Anticholinergics: delirium, confusion and memory impairment (e.g., older antihistamines, tricyclic antidepressants, some antipsychotics).
• Antipsychotics: sedation and cognitive blunting; extra caution in older adults with dementia.
• Antiepileptics & mood stabilisers: cognitive slowing (e.g., topiramate, valproate, phenobarbital).
• Illicit stimulants: methamphetamine and cocaine can cause psychosis, vascular events, and long-term executive dysfunction.
• Inhalants & solvents: direct neurotoxicity leading to chronic cognitive and motor deficits.
• Novel psychoactive substances: unpredictable neurocognitive effects; may not be detected on routine screens.

Presentation — acute vs chronic

• Acute intoxication/withdrawal: delirium, inattention, fluctuating consciousness, hallucinations, autonomic instability.
• Chronic exposure: persistent memory impairment, slowed processing, executive dysfunction, mood changes and social/occupational decline.
• Overlap: some patients present with both acute and chronic features (e.g., chronic alcohol use with acute delirium).

Assessment — clinical priorities

1. Immediate safety: ABC, treat life-threatening intoxication (naloxone for opioids), control seizures, airway protection.
2. Differentiating delirium from primary neurocognitive disorder: look for acute fluctuation, disturbed attention, and reversible causes.
3. Medication reconciliation: review all prescribed, OTC, herbal and recreational substances. Check recent changes or high-dose prescriptions.
4. Collateral history: family, carers, pharmacy records, primary care notes to determine timeline and exposures.
5. Laboratory and imaging: blood glucose, electrolytes, LFTs, renal function, toxicology, B12, thiamine level if indicated, CT/MRI for structural causes; ECG when cardiotoxic agents involved.
6. Neuropsychology: consider detailed testing when persistent impairment suspected to differentiate patterns and plan rehabilitation.

Management principles

Treat reversible causes, stop offending agents where safe, manage withdrawal, provide supportive care, and plan rehabilitation for persistent deficits.

Immediate measures

• Stabilise airway and circulation; administer antidotes when indicated (naloxone, flumazenil rarely used with caution).
• IV thiamine promptly if Wernicke encephalopathy suspected before glucose administration.
• Treat withdrawal syndromes with protocolised benzodiazepine regimens for alcohol or benzodiazepine withdrawal; use phenobarbital as adjunct in severe cases.

Medication review & deprescribing

• Stop or reduce anticholinergic burden, unnecessary sedatives and high-risk combinations (e.g., opioids + benzodiazepines).
• Taper medications safely—avoid abrupt cessation unless life-saving (assess seizure risk with benzodiazepine withdrawal).

Rehabilitation & long-term care

• Cognitive rehabilitation and compensatory strategies (memory aids, routines).
• Occupational therapy, physiotherapy and speech therapy as indicated.
• Substance use treatment services: detoxification, opioid agonist therapy, psychosocial interventions and relapse prevention.
• Mental health treatment for comorbid depression, anxiety or psychosis.

Prevention strategies

• Prescribing prudently—minimise anticholinergics and sedative load especially in older adults.
• Screen for substance use in primary care and offer early interventions.
• Public health measures: reduce harmful alcohol use, restrict access to high-risk combinations, education on safe medication use.

Key takeaways

• Substances and medications are common and potentially reversible contributors to cognitive impairment.
• Thorough medication reconciliation and collateral history are essential for diagnosis.
• Treat acute toxicity and withdrawal promptly; plan safe deprescribing and rehabilitation for persistent deficits.
• Prevention requires prudent prescribing, public health action and early screening for substance misuse.