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The use of bupropion is associated with a dose-related risk of seizures. While clinical data are lacking, there may be a theoretical risk of increased seizure potential when bupropion is used with central nervous system stimulants (e.g., amphetamines), particularly in patients who abuse or are addicted to this group of drugs. MANAGEMENT: Caution is advised if bupropion must be used with amphetamines or other agents with CNS stimulant activity. Low initial dosages and gradual increases of bupropion are recommended.

Several case reports suggest that patients treated with serotonin reuptake inhibitors (SRIs) may exhibit an increased sensitivity to sympathomimetic agents. The mechanism of interaction is unclear. The reaction has been reported when fluoxetine was used concomitantly with phentermine, amphetamine, or phenylpropanolamine. Additionally, some sympathomimetic agents (e.g., amphetamines) may possess serotonergic activity and should generally not be administered with SRIs because of the additive risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A receptors. The interaction occurred in a patient treated with dexamphetamine approximately 2 weeks after the addition of venlafaxine. The medications were discontinued and the patient was given cyproheptadine for suspected serotonin syndrome, whereupon symptoms promptly resolved. A second episode occurred when dexamphetamine was subsequently resumed and citalopram added. The patient improved following cessation of citalopram on his own, and residual symptoms were successfully treated with cyproheptadine. MANAGEMENT: In general, amphetamines should not be combined with serotonin reuptake inhibitors. Close monitoring for enhanced sympathomimetic effects is recommended if these agents must be used together. Patients should also be monitored for signs and symptoms of excessive serotonergic activity such as CNS irritability, altered consciousness, confusion, myoclonus, ataxia, abdominal cramping, hyperpyrexia, shivering, pupillary dilation, diaphoresis, hypertension, and tachycardia.