Does this patient’s history of binging and purging make it unsafe to start bupropion?

Your patient is a 25 yo woman in a current major depressive episode. She was treated with escitalopram first, and then switched to sertraline. Each medication helped her depression and caused anorgasmia, which caused her to stop them.  She is moderately depressed, and wants to know if there is anything that she can take for depression that won’t cause sexual side effects. 

In terms of her past medical history, she has a history of anorexia nervosa in her teens and bulimia in her early 20s.  She has not had disordered eating behaviors for 3 years.  Her BMI is 23.  She does not want to take mirtazapine because of the higher risk of weight gain.  You know that unlike most antidepressants, bupropion (like mirtazapine) is unlikely to cause sexual side effects.  Does this patient’s history of binging and purging make it unsafe to start bupropion? The FDA labeling states: “Wellbutrin is contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa because of a higher incidence of seizures noted in such patients treated with Wellbutrin.”

Before diving into this case, let’s think about the risk factors associated with seizures and medications.  There are 2 groups of risk factors for seizures:

1) Drug risk factors, which include the intrinsic convulsant potential of the drug, the drug dose and plasma concentration, and the rate of drug titration.

2) Patient risk factors, which include having epilepsy, traumatic brain injury, encephalitis, and electrolyte abnormalities from disordered eating behaviors like purging or laxative use.

The rates of seizures in people taking SSRIs and SNRIs is in the 0.1-0.3% range (fluoxetine 0.2%, paroxetine 0.1%, sertraline <0.1%, venlafaxine 0.26%).  Bupropion is associated with a dose-dependent risk of seizures that is highest at the time of peak plasma concentrations.  The initial formulation of bupropion (immediate-release) was rapidly absorbed, with high peak plasma concentrations that led to a notably higher incidence of seizures than other antidepressants.  The FDA warnings about seizures from bupropion were based on data from the use of immediate release bupropion.

Subsequent bupropion formulations — bupropion sustained release (SR), and bupropion extended release (XL) — have lower peak plasma concentrations than the immediate release bupropion.  The peak plasma concentration from a single dose of bupropion SR or bupropion XL is much lower than the same dose of the immediate release bupropion. Data from an open-label prospective, drug-company sponsored study (N=3,100) demonstrated a seizure incidence of 0.10% in patients receiving bupropion SR at doses up to 150mg BID.  In other words, the rate of seizures on bupropion SR 150mg BID is no higher than the rate of seizures on SSRIs or SNRIs.  The same is likely true for bupropion XL 300mg daily.

To summarize, at total daily doses of bupropion 300mg or less, using the sustained release (SR) 150mg BID dosing or extended release (XL) 300mg daily dosing, the rate of seizures with bupropion is no higher than with SSRIs or SNRIs. 

Bupropion FormMaximum Daily DoseMaximum Single Dose
Bupropion
  (immediate release)
450mg
(dosed 150mg TID)
150mg
Bupropion SR
(sustained release)
400 mg
(dosed 200mg BID)
200mg
Bupropion XL
(extended release)
450mg
(dosed 450mg daily)
450mg
Practical tips for prescribing bupropion:  

Don’t exceed the maximum single dose of bupropion for any of the formulations above. A patient who takes bupropion SR 300mg daily instead of bupropion SR 150mg BID has peak plasma concentrations of bupropion that put them at a higher risk of seizures. I tell patients who are unsure if they took their bupropion one day, it’s better to accidentally skip the day than to accidentally take too much. If they missed a day, they should not double their dose the next day.  

Avoid evening dosing: The bupropion XL formulation is dosed once daily in the morning, making it easier for patients to take as prescribed. Bupropion SR at doses over 200mg needs to be dosed BID. To decrease insomnia from bupropion SR, take the first dose in the morning and the second one 8 hours later in the mid-afternoon.   

Don’t split or crush bupropion SR or bupropion XL pills or they will lose their controlled release, leading to higher peak levels and a higher risk of seizures.

Avoid the need for prior authorizations
by prescribing Bupropion XL 450mg daily as two pills: Bupropion XL 150mg + Bupropion XL 300mg daily (taken at the same time). The bupropion XL 450mg pill (branded Forfivo XL has a retail cost of more than $400/month), while the combination of Bupropion XL 150mg + Bupropion XL 300mg daily costs around $100/month.   

Returning to our patient, a 25 yo woman in a major depressive episode who stopped 2 SSRI trials due to sexual side effects. Is it ok to prescribe bupropion for depression despite her history of an eating disorder (currently at a normal BMI, with no purging for 3 years)?

Yes!

And even if she had more significant patient-related seizure risks, it is as safe to prescribe bupropion XL up to 300mg daily as it is to prescribe an SSRI like fluoxetine.  


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