Meds That Increase Seizure Risk

Anesthetics: Seizures are usually self-limited or successfully treated with benzodiazepines.⁸

Anesthetics, local
(e.g., bupivacaine [Marcaine], lidocaine, etc)

Incidence is estimated to be about 0.1% with epidural administration (bupivacaine).¹⁰

Has been seen in infants within six hours of birth due to high serum concentrations likely due to unintentional intracranial injection during cervical blocks (procaine, lidocaine).¹⁰

Mechanism involves CNS stimulation.¹⁰

Propofol
(e.g., Diprivan)

Incidence of seizures is likely less than 1%.¹⁰

• Reports indicate as many as 24% to 40% of patients may experience EEG changes.⁶
  

Sevoflurane
(e.g., Ultane [U.S.]; Sevorane AF [Canada])

Incidence is rare and can occur as late as one day AFTER receiving anesthesia.¹⁰

• Reports indicate as many as 50% to 60% of patients may experience EEG changes.⁶
  
• Most common in children and young adults.¹⁰
  

Antibiotics/Anti-infectives: See our chart, CNS Adverse Effects of Antibiotics for more on seizures and other neurologic adverse effects.

Acyclovir
(e.g., Zovirax)

Incidence is estimated to be about 1% with intravenous administration.¹⁰

Occurs more commonly with high doses, in the elderly, and with impaired renal function.¹¹

Carbapenems
(e.g., imipenem/cilastatin [Primaxin], meropenem [Merrem], etc)

Incidence of seizures ranges from 0.4% to 5.9%.^4,10

• Most common in children, especially those three months of age or younger.¹⁰
  
• Increased likelihood with high doses or renal impairment.¹⁰
  

Cephalosporins
(e.g., cefepime, ceftazidime [Fortaz], etc)

Incidence of seizures is likely less than 1%.¹⁰

• Increased likelihood with high doses or renal impairment.¹⁰
  

Mechanism involves reduced GABA activity.^3,4

Can occur with any cephalosporin, but most commonly seen with cefepime and ceftazidime.⁴

Chloroquine
(e.g., Aralen)

Rare seizures have been seen with chloroquine.^10,11

Concomitant use of mefloquine may increase seizure risk.¹¹

Cycloserine (U.S.)

Rare seizures have been seen with cycloserine.¹⁰

Risk may be increased with serum levels ≥30 mcg/mL or consuming alcohol.^10,11

Concomitant vitamin B₆ (pyridoxine) 100 mg to 300 mg daily may reduce risk.¹⁰

Isoniazid

Incidence of seizures is rare, likely less than 1%.^4,11

Mechanism involves reduced GABA activity, by inhibiting GABA synthesis.^3,4

Concomitant lactic acidosis is common with seizures.^5,11

Seizure treatment involves intravenous followed by intramuscular vitamin B₆ (pyridoxine).^5,11

Metronidazole
(e.g., Flagyl)

Incidence is rare.¹¹

• Increased likelihood with high doses (e.g., >6 g/every other day) and prolonged use.¹¹
  

Mechanism unknown.⁴

Penicillin G

Incidence is rare.¹¹

Most often linked to high doses, rapid intravenous administration, or renal impairment.^10,11

Mechanism likely involves reduced GABA activity.⁴

Pyrimethamine
(e.g., Daraprim [U.S.])

Seizures may be seen with high doses.¹¹

Start with low doses in patients with a seizure disorder.¹¹

Quinolones
(e.g., ciprofloxacin [Cipro], etc)

Incidence of seizures is likely less than 1%.^4,10

• Increased likelihood in patients with impaired renal function.^4,11
  
• Highest risk appears to be with ciprofloxacin.⁴
  

Mechanism unknown, but may involve interference with GABA receptors and lowering seizure threshold.^4,11

Antidepressants: lower the seizure threshold²

Most SSRIs or SNRIs can be used safely in patients with epilepsy at therapeutic doses.^14,15

Low- to intermediate-risk antidepressants include doxepin, MAOIs (e.g., phenelzine, tranylcypromine), mirtazapine, SNRIs (e.g., venlafaxine), SSRIs (e.g., fluoxetine, paroxetine, sertraline), and trazodone.²

High-risk antidepressants include amoxapine, bupropion, clomipramine, and maprotiline.^2,14,15

The following antidepressants should be avoided in patients with epilepsy: amoxapine, bupropion, clomipramine, maprotiline.^14,15

Amoxapine (U.S.)

Incidence is estimated to be about 1%.¹⁰

Appears to be dose-dependent.^14,15

Bupropion

Incidence is dose-dependent and ranges from 0.1% (300 mg/day) to 0.4% (450 mg/day).^4,9,10

• Highest risk among available antidepressants.¹⁰
  

Contraindicated in patients with anorexia and bulimia, due to risk of seizures.^10,16

Clomipramine
(e.g., Anafranil)

Incidence may be as high as 10% at high doses.²

• May be dose-dependent (>250 mg/day), and may also be related to duration of therapy.^10,11
  

Seizures have also been associated with withdrawal.¹¹

Maprotiline

Incidence is estimated to be about 1%.¹⁰

• Occurs more commonly in children compared to adults.¹⁰
  

SNRIs (e.g., duloxetine [Cymbalta], venlafaxine [Effexor XR], etc)

Venlafaxine is most common SNRI linked to seizures, and often associated with overdose.⁵

SSRIs (e.g., citalopram [Celexa], fluoxetine [Prozac], etc)

Citalopram is most common SSRI linked to seizures, and often associated with overdose.⁵

Antiepileptics: drug interactions may lower effectiveness of some antiseizure medications. See our toolbox, Drug Interactions: A Practical Approach and chart, Comparison of Antiepileptic Drugs, for a better understanding of the individual agents and guidance on ways to avoid drug interactions.

Barbiturates (e.g., phenobarbital, etc)

Seizures linked to abrupt discontinuation, especially of high doses.^3,10

Carbamazepine
(e.g., Tegretol)

Most frequent antiseizure medication associated with seizure activity.²

Seizures linked to abrupt discontinuation.¹⁰

May worsen complex partial seizures, especially atypical absence or generalized convulsions.¹¹

Use with caution in patients with complex partial or mixed seizure disorders.¹¹

Phenytoin (e.g., Dilantin)

More common with serum concentrations of 50 mcg/mL or higher.¹⁰

Tiagabine (e.g., Gabitril [U.S.])

Seizures may occur with overdose or abrupt discontinuation.^10,11

Valproic acid or divalproex sodium (e.g., Depakote [U.S.], Depakene)

Seizure risk highest in patients with severe hepatic impairment or toxic encephalopathy.²

Vigabatrin (e.g. Sabril)

Seizures may occur more frequently with high doses.¹⁰

Antihistamines: mechanism involves CNS stimulation¹⁰

Diphenhydramine (e.g., Benadryl)

Incidence is rare, and occurs more commonly with overdoses.^5,10

Famotidine
(e.g., Pepcid)

Incidence of seizures is rare, likely less than 1%.^10,11

Risk may be increased in patients with impaired kidney function.¹⁰

Second-generation antihistamines
(e.g., loratadine [Claritin], etc)

Less likely to cause seizures compared to first-generation antihistamines (e.g., diphenhydramine).¹²

Antipsychotics: lower the seizure threshold^2,13

Low- to intermediate-risk antipsychotics include fluphenazine, haloperidol, pimozide, risperidone, thioridazine, and trifluoperazine.²

High-risk antipsychotics include chlorpromazine and clozapine.²

Avoid antipsychotic depot injections in patients with a history of seizures, due to inability to quickly withdraw the drug should seizures develop.¹³

Chlorpromazine

Incidence of seizures ranges from 0.5% to 9% (≥1,000 mg/day).²

Risk highest with doses ≥1,000 mg/day.²

Clozapine
(e.g., Clozaril)

Incidence of seizures ranges from 1% to 4%.⁶

Risk highest with doses ≥600 mg/day.²

Chemotherapy

Alkylating agents
(e.g., chlorambucil [Leukeran], busulfan [Myleran], etc)

Incidence is rare, but can occur with therapeutic doses, pulse-dosing regimens, and with overdose.¹⁰

Seizures have been seen as late as six to 90 days after beginning therapy (chlorambucil).¹¹

Seizures have been seen with both intravenous and oral doses (busulfan).¹¹

• Prophylactic phenytoin is recommended with intravenous doses and can be considered with oral doses.¹¹
  

Cytarabine
(e.g., DepoCyt)

Rare seizures have been seen with high-dose cytarabine.¹⁰

More common with liposomal formulation.¹¹

Appear most often either during or shortly after infusions.¹⁰

Vincristine

Seizures have been reported, often seen with concomitant hypertension.¹¹

May reduce phenytoin concentrations and increase risk for seizures.¹¹

Immunosuppressives

Cyclosporine
(e.g., Sandimmune)

Incidence of seizures ranges from 0.5% to 5%.^6,10

Risk may be increased with concomitant high-dose corticosteroids (e.g., methylprednisolone).^10,11

Methotrexate (e.g., Otrexup [U.S.]; Metoject [Canada])

Associated with intravenous or intrathecal administration, especially at high doses.^10,11

Tacrolimus
(e.g., Prograf)

Reported with systemic use (not topical).^10,11

Increased risk with high serum levels or impaired liver function.¹⁰

Narcotics/Analgesics

Fentanyl
(e.g., Duragesic)

Incidence is estimated to be ≥1%.¹⁰

Seizures have been seen with intravenous use.⁴

Mefenamic acid (e.g., Ponstel [U.S.]; Ponstan [Canada])

Incidence is rare.¹⁰

Meperidine
(e.g., Demerol)

Incidence of seizures estimated at about 2.1%.⁶

• Increased likelihood in patients with impaired hepatic or renal function.^4,11
  

Mechanism likely related to neurotoxic metabolite, normeperidine.^4,11

Morphine

Seizures more likely to be associated with epidural or intrathecal administration compared to intravenous.⁴

Pentazocine (e.g., Talwin [U.S.])

Seizures have been rarely reported. May be more likely in patients with other risks for seizures.¹⁰

Tramadol
(e.g., Ultram)

Increased risk when combined with alcohol or medications that lower the seizure threshold.^4,10

Most cases related to higher doses (e.g., 400 mg/day immediate-release [300 mg/day for patients

≥75 years old], 300 mg/day extended-release [or lower in elderly]) and chronic use.^6,10

May be more common in the elderly.¹

Seizures possible at therapeutic doses, especially in patients with a seizure disorder (e.g., epilepsy).⁶

Stimulants

Mechanism involves lowering the seizure threshold.¹⁰

Most common in patients with previous seizure disorder, EEG abnormalities, or with an overdose.¹⁰

Seizures often precipitated by tremors, agitation, hallucinations, or tachycardia.⁵

Amphetamine (e.g., Adzenys [U.S.])

Incidence is rare.¹⁰

Amphetamine/Dextroamphetamine
(e.g., Adderall)

Incidence is rare.¹⁰

Atomoxetine (e.g., Strattera)

Incidence is estimated to be about 0.1% (adults) and 0.2% (pediatrics).¹⁰

More common in patients that are poor metabolizers.¹⁰

Cocaine

Mechanism involves lowering the seizure threshold.¹⁰

Seizures often precipitated by tremors, agitation, hallucinations, or tachycardia.⁵

Dextroamphetamine (e.g., Dexedrine)

Incidence is rare.¹⁰

Lisdexamphetamine (e.g., Vyvanse)

Incidence is rare.¹⁰

Methylphenidate (e.g., Concerta)

Incidence is rare.¹⁰

Pemoline (e.g., Cylert [U.S.])

Incidence is rare.¹⁰

Pseudoephedrine
(e.g., Sudafed)

Seizures may be seen, especially in patients with renal dysfunction or excessive doses.¹⁰

Incidence may be more common in elderly patients.¹¹

Other

Baclofen
(e.g., Lioresal)

Mechanism is not clear, though baclofen is structurally similar to GABA.¹⁷

Can occur at normal doses, but more common with overdoses or abrupt discontinuation.¹⁰

Most commonly associated with intrathecal administration (e.g., 0.5% to 10%).^10,11

Beta-blockers

May mask symptoms of hypoglycemia, which could present with seizures if left untreated.¹⁰

Has been seen with overdose, especially with highly lipophilic beta-blockers (e.g., carvedilol, propranolol).¹⁸

Ethanol

Seizures linked to withdrawal of high doses and chronic use.³

Lindane

Mechanism involves CNS stimulation.¹⁰

No longer recommended first-line for head lice due to risk of neurotoxicity, including seizures.¹¹

Increased risk with repeated applications or prolonged therapy.¹¹

Avoid use in premature infants, or in patients with a seizure disorder or a skin condition that could increase absorption (e.g., atopic dermatitis).¹¹

Lithium (e.g., Lithobid [U.S.];
Lithane [Canada])

Incidence is rare.^10,11

Seizures have been noted even at therapeutic levels, but occur more often with toxic levels.^2,11

Mexiletine

Incidence of seizures is likely less than 1%.¹⁰

Naloxone

Seizures may occur with use as a result of opioid reversal.¹⁰

Pertussis vaccine (e.g., Boostrix)

Seizures are more likely in children, especially those with a history of or family history of seizures.¹⁰

Radio contrast agents

Mechanism may involve hypotension.²⁰

Incidence of seizures is likely less than 0.5%, but may be higher in patients with CNS abnormalities.¹⁹

Sodium phosphate bowel preps

Mechanism involves electrolyte disturbances and low serum osmolality.¹⁰

Use caution in patients with existing electrolyte abnormalities (e.g., diuretic use, heart failure).¹⁰

Theophylline
(e.g., Uniphyl)

Seizures often last longer than other drug-induced seizures and may not respond well to treatment.⁵

Seizures with serum concentrations <20 mcg/mL are usually less severe than with higher levels.¹⁰

Triptans (e.g., sumatriptan, etc)

Incidence of seizures is likely less than 1%.¹⁰

Zolpidem (e.g., Ambien [U.S.]; Sublinox [Canada])

Seizures can be associated with abrupt discontinuation.¹¹

Supplements

Ginkgo

More common with seeds than leaves (or products made from leaves) due to higher content of ginkgotoxin in the seeds.⁷

• Ingestion more than about ten seeds can induce seizures.⁷
  

Ephedra (Ma Huang, etc)

Common dietary supplement linked to seizure activity, especially in patients with an underlying disorder.⁷

May interfere with anticonvulsant medication activity.⁷

St. John’s wort

Increases metabolism of phenobarbital and phenytoin, reducing effectiveness, and possibly inducing seizures.⁷

Concomitant use with tramadol associated with serotonin syndrome and possible seizures.⁹