Answering the Critical Question: What Medications Can Cause Hyperreflexia?

October 10, 2025 •

3 min read

The incidence of serotonin syndrome, a primary cause of medication-induced hyperreflexia, is estimated to be around 15% in patients who have overdosed on selective serotonin reuptake inhibitors (SSRIs). This highlights the importance of knowing what medications can cause hyperreflexia.

Quick Summary

A wide range of medications, particularly those that increase serotonin activity like antidepressants and stimulants, can cause hyperreflexia. This condition of overactive reflexes is a key sign of potentially serious drug-induced syndromes.

Key Points

Primary Cause: Hyperreflexia from medications is most often due to excessive activity of the neurotransmitter serotonin.
Common Culprits: Antidepressants (SSRIs, SNRIs, MAOIs), CNS stimulants, and certain opioids like tramadol are frequently implicated.
Serious Sign: The symptom is a key feature of serotonin syndrome, a potentially life-threatening condition also marked by agitation and autonomic instability.
High-Risk Combinations: Combining multiple serotonergic drugs, such as an SSRI with an MAOI or certain migraine medications, significantly increases the risk.
OTC and Supplements: Over-the-counter products like dextromethorphan (in cough syrup) and supplements like St. John's Wort can also contribute to hyperreflexia.
Diagnosis is Crucial: Diagnosis depends on a physical exam and a thorough review of the patient's medication history, as there is no specific lab test.
Treatment Focus: The most important step in management is to identify and discontinue the medication(s) causing the symptoms, with supportive care as needed.

What is Hyperreflexia?

Hyperreflexia is characterized by exaggerated or overactive reflexes, often indicating an issue with the central nervous system (CNS). When caused by medication, it's typically due to an imbalance in neurotransmitters.

The Link Between Medications and Hyperreflexia

The main reason medications cause hyperreflexia is increased serotonin activity in the nervous system. Serotonin is a key neurotransmitter, and various drugs can increase its levels by inhibiting reuptake (like SSRIs), increasing release (like amphetamines), inhibiting metabolism (like MAOIs), or directly stimulating serotonin receptors (like triptans and buspirone). Taking multiple drugs that affect serotonin increases the risk of severe symptoms.

Primary Medication Classes That Cause Hyperreflexia

Many drugs, particularly those that impact the CNS and serotonin levels, can cause hyperreflexia.

Antidepressants

This is a common group of medications linked to hyperreflexia and serotonin syndrome. Examples include SSRIs (fluoxetine, sertraline), SNRIs (venlafaxine), TCAs (amitriptyline), and MAOIs (phenelzine). Combining MAOIs with other serotonergic drugs is particularly risky.

CNS Stimulants

Prescription stimulants for conditions like ADHD (methylphenidate) and illicit substances such as cocaine and MDMA can cause CNS excitement and hyperreflexia.

Other Notable Medications

Other drug classes that can contribute include certain opioids (tramadol, fentanyl), antimigraine medications called triptans, OTC products like dextromethorphan and St. John's Wort, the antibiotic linezolid, and some antipsychotics and mood stabilizers.

Comparison of Medication-Induced Hyperreflexia Causes


Medication Class	Primary Mechanism	Common Examples	Associated Risk/Syndrome
Antidepressants (SSRIs, SNRIs, TCAs)	Inhibit serotonin reuptake	Fluoxetine, Venlafaxine, Amitriptyline	Serotonin Syndrome
Antidepressants (MAOIs)	Inhibit serotonin metabolism	Phenelzine, Selegiline	High risk of Serotonin Syndrome, especially when combined
CNS Stimulants	Increase serotonin release and CNS excitation	Methylphenidate, Amphetamines, Cocaine	Serotonin Syndrome, general CNS overstimulation
Opioids	Weak serotonin reuptake inhibition and increased release	Tramadol, Fentanyl, Meperidine	Serotonin Syndrome, especially with antidepressants
Triptans	Direct serotonin receptor activation	Sumatriptan, Rizatriptan	Serotonin Syndrome, especially with SSRIs/SNRIs
OTC/Supplements	Varies (e.g., MAO inhibition, reuptake inhibition)	Dextromethorphan, St. John's Wort	Serotonin Syndrome

Recognizing Associated Syndromes

Hyperreflexia is often part of a larger syndrome, most notably Serotonin Syndrome (SS). SS is a serious condition from excessive serotonin activity, presenting with neuromuscular hyperactivity (including hyperreflexia, clonus, tremor), autonomic instability (high blood pressure, fever), and altered mental status (agitation, confusion). Neuroleptic Malignant Syndrome (NMS), caused by dopamine blockers, can have similar symptoms but is more associated with severe rigidity and a slower onset.

Diagnosis and Management

If you experience hyperreflexia, medical attention is essential. Diagnosis involves a physical exam and a review of all medications. The main treatment is discontinuing the causative drug. Mild cases often improve within days with supportive care. More severe cases may require hospitalization, IV fluids, benzodiazepines, and potentially the antidote cyproheptadine.

Conclusion

Hyperreflexia is a significant symptom often caused by medications that increase serotonin, such as antidepressants and stimulants. It is a key indicator of serotonin syndrome, a condition requiring urgent medical care. Preventing and treating this requires careful medication management and open communication with healthcare providers about all substances being taken. If hyperreflexia or related symptoms occur after starting a medication, contact your doctor immediately.

For more information on neurological disorders, you can visit the National Institute of Neurological Disorders and Stroke.

Frequently Asked Questions

Antidepressants are the most common cause, especially SSRIs (e.g., fluoxetine, sertraline), SNRIs (e.g., venlafaxine), and MAOIs. CNS stimulants like methylphenidate and certain opioids like tramadol are also frequently responsible.

Not always, but it is a classic and very common sign of serotonin syndrome. It indicates an excess of serotonin activity, which is the underlying cause of the syndrome. It warrants immediate medical evaluation to rule out a serious condition.

Yes. The cough suppressant dextromethorphan and herbal supplements like St. John's Wort, ginseng, and L-tryptophan can all increase serotonin levels and potentially cause hyperreflexia, especially when combined with prescription medications.

The primary treatment is to stop the medication causing the issue. Mild cases often resolve within 24 to 72 hours. More severe cases may require hospitalization, supportive care like IV fluids, benzodiazepines for agitation, and an antidote called cyproheptadine.

Hyperreflexia is the state of having overactive reflexes. Clonus is a specific physical sign of severe hyperreflexia, characterized by involuntary, rhythmic, and repeated muscle contractions after a reflex is stimulated. Clonus is a very strong indicator of serotonin syndrome.

You should not stop any prescribed medication on your own. Contact your healthcare provider immediately to report your symptoms. They will determine the cause and advise you on the safest course of action, which may include stopping or changing your medication under medical supervision.

Prevention involves being cautious when taking multiple serotonergic medications. Always inform your doctor and pharmacist about all drugs, OTC products, and supplements you are taking. High-risk combinations, like an MAOI with an SSRI, should be avoided.