Antipsychotics are a class of medications used primarily to manage symptoms of psychosis, such as those found in schizophrenia and bipolar disorder. These drugs work by altering the balance of neurotransmitters in the brain, most notably dopamine and serotonin. Taking more than the prescribed amount can overwhelm the body’s systems, and an overdose on these drugs can be fatal. Because the effects of an overdose can escalate rapidly, anyone suspected of having ingested an excessive amount needs immediate emergency medical care.
Factors Determining Overdose Severity
The severity of an antipsychotic overdose depends on multiple factors, including the specific drug and the patient’s individual health status. Antipsychotics are categorized into first-generation (typical) and second-generation (atypical) agents, which tend to have different overdose profiles. First-generation drugs, like chlorpromazine and haloperidol, are associated with a higher risk of severe cardiac complications and movement disorders at toxic doses.
Second-generation agents, such as quetiapine and olanzapine, are frequently involved in overdoses and can cause profound central nervous system depression and severe hypotension. Some atypical agents have a higher likelihood of causing major adverse outcomes, including coma and respiratory depression, compared to older drugs. The total amount ingested is a clear determinant of risk, with doses exceeding 1500 milligrams significantly increasing the chance of severe poisoning.
Polypharmacy, the co-ingestion of other substances alongside the antipsychotic, significantly escalates the danger. Combining antipsychotics with central nervous system depressants, such as alcohol, opioids, or benzodiazepines, dramatically increases the risk of severe respiratory failure and coma. Underlying health, particularly pre-existing heart conditions, makes patients more vulnerable to cardiovascular toxicity. Extended-release formulations also pose a delayed and prolonged risk, as the drug continues to be absorbed over many hours.
Mechanisms of Fatal Toxicity
Antipsychotics exert toxic effects by disrupting several physiological systems, primarily the cardiovascular and central nervous systems. The drugs interfere with ion channels in the heart, blocking potassium and sodium channels that regulate the heart’s electrical rhythm. This blockade causes a dangerous widening of the QT interval on an electrocardiogram (ECG).
QT prolongation raises the risk of a life-threatening arrhythmia called Torsades de Pointes, an irregular heart rhythm that prevents the heart from effectively pumping blood. Furthermore, some antipsychotics block alpha-1 adrenergic receptors, leading to widespread dilation of blood vessels. This action causes severe hypotension, which can progress to distributive shock and cardiac collapse if left untreated.
In the brain, the overdose effect is mediated by the potent blockade of histamine H1 and muscarinic receptors. This leads to profound central nervous system depression, causing extreme drowsiness, stupor, and deep coma. When a person is unconscious or has altered mental status, protective reflexes like coughing and swallowing are compromised. This creates a high risk of aspirating stomach contents into the lungs, leading to severe pneumonia and suffocation. Antipsychotics also lower the brain’s seizure threshold, leading to convulsions or status epilepticus, a medical emergency that can result in brain damage and death.
Recognizing the Signs of Overdose
Recognizing the signs of an antipsychotic overdose is necessary for seeking immediate help. The most common manifestation is a rapid change in mental status, often presenting as extreme drowsiness (somnolence) that progresses to stupor or coma. Paradoxically, some individuals may display agitation, confusion, or delirium due to the drug’s anticholinergic effects.
Cardiovascular signs include a rapid heart rate (tachycardia), which is the body’s attempt to compensate for low blood pressure. The skin may feel flushed and warm, and pupils may become dilated or pinpoint. Severe hypotension can cause a person to feel faint or dizzy before losing consciousness.
Neurological symptoms involve abnormal muscle movements, including acute dystonia (involuntary spasms of the face, neck, and back muscles). Tremors, muscle rigidity, and seizures can also occur. Other signs related to anticholinergic activity include dry mouth, blurred vision, and difficulty urinating.
Emergency Treatment and Prognosis
Any suspected antipsychotic overdose requires an immediate call to emergency services, as treatment must be provided in a hospital setting. Medical management focuses on aggressive supportive care to maintain the patient’s essential functions. This begins with securing the airway, which may involve intubation if respiratory depression or coma is severe.
Circulatory support is maintained with intravenous fluid boluses to counteract low blood pressure caused by vasodilation. If fluids are insufficient, vasopressor medications may be administered to constrict blood vessels. Continuous cardiac monitoring via ECG is mandatory to detect and manage dangerous arrhythmias. Torsades de Pointes is typically treated with an intravenous infusion of magnesium.
For recent ingestions, activated charcoal may be given to bind the remaining drug in the stomach and prevent its absorption. Seizures are managed using benzodiazepine medications, such as lorazepam. While most patients who receive rapid medical intervention recover fully, the prognosis is tied to the speed of treatment and the severity of complications. Delayed care, very large doses, or co-ingestion of multiple sedating drugs significantly worsens the outcome due to the increased likelihood of severe cardiac or neurological injury.