SSRIs + Bupropion - Drug Interactions

There are isolated reports of psychosis, mania and seizures associated with use of bupropion and fluoxetine and an isolated report of serotonin syndrome with bupropion and sertraline.Hypersexuality has also been reported with bupropion and fluoxetine or sertraline.

The day after stopping fluoxetine 60mg daily,a 41-year-old man was started taking 75mg and later 100mg of bupropion three times daily. After 10 days he became edgy and anxious and after 12 days he developed myoclonus. After 14 days he became severely agitated and psychotic,with delirium and hallucinations. His behaviour returned to normal 6 days after bupropion was stopped (See reference number 1). Another patient taking lithium carbonate for bipolar disorder developed anxiety,panic and eventually mania a little over a week after stopping fluoxetine and starting bupropion (See reference number 2).

A 35-year old woman taking fluoxetine 40mg daily was given low-dose bupropion (100 mg daily) to treat fluoxetine-induced sexual dysfunction. Despite a good initial response,hypersexuality developed leading to discontinuation of bupropion (See reference number 4).

A 62-year-old woman treated with therapeutic doses of bupropion and sertraline experienced upper extremity tremor,clumsiness and gait difficulties, with fluctuating symptoms of confusion, forgetfulness, and alternating agitation and lethargy, which started after a few days on this regimen. Venlafaxine was then added and clinical picture worsened with deterioration of mental status, hallucinations, insomnia, myoclonic jerks, postural and balance difficulties, incoordination and incontinence. The medications were discontinued and symptoms, which were indicative of serotonin syndrome, gradually resolved (See reference number 5).

An isolated case describes spontaneous orgasm with combined use of bupropion and sertraline. Bupropion had been successfully used to treat SSRI-induced impaired sexual function,but after 6 weeks of combined therapy she experienced a sudden-onset, spontaneous orgasm; this occurred again on rechallenge with bupropion (See reference number 6).

Several mechanisms have been proposed. Bupropion inhibits cytochrome P450 isoenzyme CYP2D6, which may interfere with metabolism of some SSRIs, causing an increase in plasma levels and increased toxicity. However,a small study found no statistically significant changes in plasma levels of fluoxetine or paroxetine when combined with bupropion (See reference number 7). An in vitro study demonstrated that several SSRIs (paroxetine, sertraline, norfluoxetine, and fluvoxamine) could inhibit CYP2B6, isoenzyme involved in bupropion hydroxylation,(See reference number 8)and in one of cases described above it was suggested that residual fluoxetine may have inhibited metabolism of bupropion, leading to toxic levels (See reference number 1). A pharmacodynamic mechanism has also been proposed. Bupropion can cause seizures and antidepressants may further lower seizure threshold, see Bupropion + Miscellaneous interaction.

Information is very limited but these reports suggest that if concurrent or sequential use is thought appropriate, outcome should be well monitored and reduced doses should be considered. The UK and US manufacturers recommend that drugs that are metabolised by CYP2D6 should be given with bupropion with caution and initiated at lower end of dose range. If bupropion is added to treatment of a patient already taking a drug metabolised by CYP2D6, need to decrease dose of this drug should be considered (See reference number 9,10). The UK manufacturers specifically name paroxetine and US manufacturers additionally name fluoxetine and sertraline. In addition, manufacturers advise extreme caution if bupropion is given with antidepressants that lower seizure threshold(See reference number 10) and recommend reducing dose of bupropion to a maximum of 150mg daily (See reference number 9).

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