Altered mental status (AMS) is a broad medical term used to describe a sudden or gradual change in a person’s usual brain function, which affects their attention, awareness, and cognition. This is not a diagnosis itself, but rather a symptom indicating a disruption in the brain’s normal activity. The manifestations of AMS can range widely, from mild confusion and disorientation to severe delirium, stupor, or coma.
The brain’s function relies on a delicate chemical balance, and many substances, whether prescribed medications, over-the-counter drugs, or illicit compounds, can interfere with this balance. Drug-induced AMS typically occurs by either slowing down brain activity, overstimulating it, or indirectly disrupting the metabolic environment the brain needs to function correctly. Understanding how different classes of drugs affect specific neurotransmitter systems can help explain the diverse ways AMS presents.
Central Nervous System Depressants
Central Nervous System (CNS) depressants reduce neuronal activity in the brain, often leading to effects like sedation, lethargy, slurred speech, and confusion. In high doses, these substances can progress to stupor, respiratory failure, or coma. The primary mechanism of action for many of these drugs is the enhancement of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
GABA reduces the excitability of neurons. When a depressant drug binds to the GABA-A receptor complex, it increases the effectiveness of naturally occurring GABA. This opens the receptor’s chloride channel, allowing negatively charged chloride ions to flow into the neuron. The resulting hyperpolarization makes the neuron less likely to fire an action potential, thus reducing overall brain activity.
Common examples of CNS depressants include opioids, alcohol, benzodiazepines (prescribed for anxiety or sleep), and barbiturates. The AMS caused by these drugs is characterized by slowed response times, difficulty maintaining attention, and a reduced level of consciousness, reflecting general suppression of the central nervous system.
Anticholinergic and Deliriogenic Agents
Anticholinergic drugs block the action of the neurotransmitter acetylcholine (ACh) throughout the central and peripheral nervous systems. Acetylcholine is important for cognitive functions, including memory, learning, and attention. When these drugs cross the blood-brain barrier and block ACh receptors, the disruption can lead to a specific and severe form of AMS known as anticholinergic delirium.
The symptoms of anticholinergic delirium are often described by a classic triad: hyperthermia (“hot as a hare”), pupil dilation (“blind as a bat”), and acute confusion with hallucinations (“mad as a hatter”). This state is marked by profound disorientation, agitation, incoherent speech, and memory impairment. First-generation antihistamines, found in many over-the-counter sleep aids and cold medications, are frequent culprits because they readily enter the brain and block these cholinergic receptors.
Other medications with strong anticholinergic properties include certain older antidepressants, some antipsychotics, and specific drugs used to treat bladder overactivity or Parkinson’s disease. The risk of developing AMS from these agents is elevated in older adults, whose brains are more sensitive to the effects of muscarinic receptor inhibition.
Psychoactive and Sympathomimetic Drugs
Psychoactive and sympathomimetic drugs cause AMS through hyperstimulation, opposite to the effect of depressants. These agents mimic or enhance the body’s sympathetic nervous system, or “fight-or-flight” response, by increasing the availability of catecholamines like norepinephrine and dopamine. The resulting overactivity manifests as agitation, psychosis, paranoia, and elevated body temperature.
Illicit stimulants, such as cocaine and methamphetamine, are powerful sympathomimetics that increase the concentration of these stimulating neurotransmitters in the synaptic cleft. They achieve this by blocking the reuptake of dopamine and norepinephrine or by stimulating their release from nerve terminals. This surge of catecholamines floods the brain, leading to alertness, manic behavior, and altered perception that characterize the resulting AMS.
Certain prescription drugs can also inadvertently cause hyper-stimulated AMS, most notably Serotonin Syndrome. This occurs when medications that boost serotonin levels, such as specific antidepressants, are taken in combination or at high doses. The excessive serotonin activity leads to a rapid onset of confusion, agitation, neuromuscular hyperactivity, and hyperthermia.
Non-Psychiatric Medications Affecting Metabolism
Drugs can cause AMS indirectly by disrupting the systemic metabolic balance required for normal brain function, rather than by directly interacting with neurotransmitter receptors. The brain depends on a constant supply of energy and stable electrolyte concentrations to maintain its electrical and chemical processes. When a medication interferes with this homeostasis, cognitive impairment can rapidly follow.
A prime example is the use of insulin or sulfonylurea medications for diabetes, which can cause severe hypoglycemia (low blood sugar). Since glucose is the brain’s primary fuel source, a significant drop in blood sugar quickly leads to confusion, dizziness, and even coma.
Some cardiac medications or diuretics can cause hyponatremia, a condition of low sodium concentration in the blood. Sodium is fundamental to nerve cell communication and regulating fluid balance, so a significant imbalance can cause brain swelling and AMS symptoms like lethargy and seizures. Certain antibiotics, such as fluoroquinolones, have also been linked to neurotoxicity, causing symptoms like confusion and hallucinations.