Does Sleep Quality Change After Switch From Wellbutrin SR to Wellbutrin XL in Patients With Major Depressive Disorder?

Overview

Wellbutrin (bupropion) is an effective antidepressant (Thase, M 2005). It exists in instant release (IR), sustained release (SR) and extended release (XL) forms. The IR formulation was never approved for use in Canada. The XL formulation allows for once daily dosing. Wellbutrin is both a norepinephrine and dopamine reuptake inhibitor, and as such increases the synaptic concentration of both neurotransmitters. This adds to its positive effects on cognition, apathy, tiredness and executive functioning. The increased activation may be also responsible for some of its side effects such as initial insomnia and reduced sleep efficiency, especially when taken at night.

Wellbutrin SR formulation cannot be given as more than 150 mg as a single dose and higher doses are commonly required for the treatment of depression; they also have to be given at least 8 hours apart in order to avoid peak plasma concentrations and to reduce the risk of seizures (incidence of 0.1% at doses £ 300 mg). The twice a day dosing may result in complaints of insomnia and may necessitate discontinuing the medication or adding a sleep promoting agent. The benefit of once-daily dosing cannot be understated given treatment adherence is typically lower in depressed patients than their non-depressed counterparts; further, the 8 h dosing interval of bupropion SR is likely to have lower adherence compared with traditional bid dosing (i.e., morning and evening); thus, it is not difficult to imagine patients missing 30-50% of their second dose given the difficulty of recalling to take the second dose at work or school. The review of Fava et al. (2005) plots the relative PK profiles of XL and SR and notes the significantly lower bupropion concentration at bedtime, which is likely to reduce the occurrence of insomnia. Therefore, Wellbutrin XL may improve adherence by eliminating the second dose and Wellbutrin XL also avoids the high plasma drug concentrations at bedtime, as seen with bupropion SR, which are associated with insomnia. Further, the smoother pharmacokinetic profile of Wellbutrin XL may improve overall tolerability compared with Wellbutrin SR.