What medications lower the seizure threshold?

From the Guidelines

Medications that can lower the seizure threshold include antipsychotics, antidepressants, stimulants, antibiotics, analgesics, and certain anesthetics, as well as other medications such as theophylline, baclofen withdrawal, and immunosuppressants like cyclosporine, as noted in a recent study 1.

Key Medications that Lower Seizure Threshold

• Antipsychotics: particularly clozapine, chlorpromazine, and olanzapine
• Antidepressants: especially bupropion, tricyclics like amitriptyline, and SSRIs at high doses
• Stimulants: methylphenidate, amphetamines, cocaine
• Antibiotics: carbapenems, quinolones, isoniazid
• Analgesics: tramadol, meperidine
• Certain anesthetics: enflurane, ketamine

Mechanisms and Patient Considerations

These medications lower the seizure threshold through various mechanisms, including altering neurotransmitter balance, affecting sodium channels, or causing metabolic disturbances, as discussed in a study on smoking cessation 1. Patients with epilepsy, history of seizures, brain injury, or other neurological conditions are at higher risk when taking these medications.

Prescribing Considerations

When prescribing these drugs to at-risk patients, consider starting at lower doses, increasing slowly, monitoring closely, and avoiding combinations of multiple threshold-lowering medications, as recommended in a guideline on pharmacological interventions for adults with obesity 1. In some cases, concurrent use of an antiepileptic medication might be necessary to prevent seizures while using these medications for their intended therapeutic purposes.

From the FDA Drug Label

• Drugs that lower seizure threshold: Dose bupropion hydrochloride extended-release tablets (XL) with caution. ( 5.3,7.3) The meds that lower seizure threshold are not explicitly listed in the label, but it is mentioned that bupropion should be dosed with caution when used with such drugs 2.

• Key point: Bupropion should be used with caution with drugs that lower seizure threshold.
• The label does not provide a list of specific medications that lower seizure threshold.

From the Research

Medications that Lower Seizure Threshold

• Antipsychotic medications, such as clozapine, can lower the seizure threshold, increasing the chances of seizure induction 3
• Certain antidepressants, including bupropion, maprotiline, and clomipramine, have a relatively high seizurogenic potential 4
• First-generation antipsychotic medications, such as chlorpromazine, can also lower the seizure threshold, with chlorpromazine appearing to be associated with the greatest risk of seizure provocation 3
• The combination of medications that lower the seizure threshold, such as clozapine and bupropion, may have additive or synergistic effects, increasing the risk of seizures 5

Factors that Increase Seizure Risk

• History of seizure activity
• Concurrent use of other drugs that lower seizure threshold
• Rapid dose titration
• Slow drug metabolism
• Metabolic factors
• Drug-drug interactions 3, 4

Safe Treatment Options

• Serotonin reuptake inhibitors are preferred for treating depression in patients with epilepsy 6
• Safer agents that do not lower the seizure threshold should be utilized whenever possible 5