What medications, such as Selective Serotonin Reuptake Inhibitors (SSRIs) or antipsychotics, can cause hyperreflexia as a side effect?

Medications That Can Cause Hyperreflexia as a Side Effect

Several medications, particularly serotonergic agents, can cause hyperreflexia as a side effect, with the most common being selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and other medications that increase serotonin levels in the central nervous system. 1

Serotonergic Medications Associated with Hyperreflexia

Hyperreflexia is most commonly associated with serotonin syndrome, a potentially life-threatening condition characterized by excessive serotonergic activity in the central nervous system. The following medications can cause hyperreflexia through this mechanism:

Antidepressants

• SSRIs (fluoxetine, paroxetine, sertraline, citalopram, fluvoxamine) 2, 1
• SNRIs (venlafaxine, duloxetine) 1
• Tricyclic antidepressants (amitriptyline, nortriptyline, desipramine) 2, 1
• MAOIs (phenelzine, isocarboxazid, moclobemide, isoniazid) 2, 1
• Other antidepressants (bupropion, mirtazapine, trazodone) 2, 3

Other Medications

• Opioids (tramadol, meperidine, methadone, fentanyl) 2, 1
• Stimulants (amphetamines, methylphenidate) 2, 3
• Over-the-counter medications containing dextromethorphan or chlorpheniramine 2, 1
• Antimigraine drugs (triptans) 1
• Antiemetics (ondansetron, metoclopramide) 1
• Antibiotics (linezolid - acts as an MAOI) 2, 1
• Herbal supplements (St. John's wort, L-tryptophan) 2

Medication Combinations with Highest Risk

The risk of hyperreflexia significantly increases when combining multiple serotonergic medications, particularly:

1. MAOI + any serotonergic drug (highest risk combination) 2, 1
2. Multiple SSRIs or an SSRI with another serotonergic agent 1
3. Antidepressants + opioids with serotonergic effects 2, 1
4. Antidepressants + illicit drugs (ecstasy, methamphetamine, cocaine, LSD) 2, 4

Clinical Presentation of Hyperreflexia in Serotonin Syndrome

When hyperreflexia occurs as part of serotonin syndrome, it is typically accompanied by:

• Mental status changes (confusion, agitation, anxiety)
• Neuromuscular abnormalities (tremor, clonus, rigidity)
• Autonomic hyperactivity (hypertension, tachycardia, hyperthermia)
• In severe cases: fever >38°C, seizures, and potentially death 1, 5

Risk Factors for Developing Hyperreflexia

Certain factors increase the risk of developing hyperreflexia from medications:

• Advanced age (older adults have higher risk) 6
• Higher medication doses (dose-dependent relationship) 6
• Combination therapy with multiple serotonergic agents 6
• Drug interactions affecting metabolism of serotonergic medications 1
• Recent dose increases or medication changes 2

Management of Medication-Induced Hyperreflexia

If hyperreflexia is detected:

1. Discontinue all serotonergic agents immediately 1
2. Provide supportive care including IV fluids 1
3. Administer benzodiazepines for agitation control 1
4. Consider cyproheptadine (12 mg initially, max 32 mg daily) for moderate to severe cases 1
5. Monitor for complications such as rhabdomyolysis, metabolic acidosis, and renal failure 1

Prevention Strategies

To prevent medication-induced hyperreflexia:

• Avoid combining MAOIs with any other serotonergic medications 2, 1
• Exercise caution when combining two or more non-MAOI serotonergic drugs 2, 1
• Start second serotonergic medications at low doses and increase slowly 2
• Monitor closely for symptoms in the first 24-48 hours after medication changes 2
• Educate patients about early signs of serotonin syndrome 1

Important Caveats

• Hyperreflexia can occur with monotherapy but is much more common with combination therapy 4
• Symptoms typically develop within 24-48 hours after starting or increasing the dose of a serotonergic medication 1
• Without proper treatment, mortality rate can reach approximately 11% 1
• Physical restraints should be avoided as they may worsen hyperthermia 1