Switching to monotherapy after failure with a first antidepressant resulted in no significant difference in efficacy and tolerability among bupropion, sertraline, and venlafaxine. In treatment-resistant depression, augmentation of previous treatment with bupropion did not result in significant differences in remission compared with switching to bupropion monotherapy, augmentation with aripiprazole, or augmentation with buspirone. Switching to bupropion monotherapy or augmentation with bupropion was associated with significantly higher incidence of anxiety, decreased appetite, dry mouth, and increased blood pressure, but lower incidence of increased appetite, increased weight, somnolence, akathisia, and laboratory test abnormality compared to augmentation with aripiprazole. Augmentation therapy with bupropion or aripiprazole may be a cost-effective option relative to switching to bupropion in treatment-resistant depression. Among the monotherapies, switching to vortioxetine appeared to be the most cost-effective option relative to other medications such as agomelatine, bupropion, venlafaxine, or sertraline; bupropion, venlafaxine, and sertraline monotherapies were not significantly different from one another in terms of cost-effectiveness.

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Direct and indirect evidence from 6 systematic reviews did not demonstrate a difference in treatment response or remission rates, or functional outcomes, with bupropion as compared to other antidepressants in adults with major depressive disorder. Direct and indirect evidence from 5 systematic reviews did not demonstrate a difference in overall adverse events, overall withdrawals, or withdrawals due to adverse events apart from a possible decreased risk of withdrawal due to adverse events with vortioxetine in a single indirect comparison. Direct and indirect evidence from 2 systematic reviews supports that the risk of sexual dysfunction may be lower with bupropion than other antidepressants (escitalopram, paroxetine, sertraline, and fluoxetine), while 1 systematic review showed no significant difference in sexual function scores between bupropion and venlafaxine. There is limited evidence supporting the cost-effectiveness of bupropion to augment citalopram, and dominance of vortioxetine compared to bupropion, for major depressive disorder with inadequate response to initial therapy. There is a lack evidence surrounding the comparative clinical or cost-effectiveness of bupropion in dysthymia.

People generally describe wanting access to carrier screening because knowing about the risk of passing along a genetic condition is considered important and supportive of their desires to be prepared. In the context of expanded carrier screening programs, this could mean that an increased number of people would want to access these programs. Supporting people who are considering carrier screening can be challenging and is likely to be more involved than simply sharing high-level descriptive information about testing details and potential outcomes. Descriptive information is important to help people understand the screening process and the types of results that could emerge from testing; however, programs might be more supportive of informed decision-making if the providers take a proactive role and are open to facilitating speculative conversations about potential ramifications in people’s actual lives. This is challenging given the expressed desire by health care providers, clinical geneticists in particular, to provide “neutral information” that patients would not experience as prescriptive. Given the challenge of supporting people making decisions about whether or not to pursue carrier screening, and the likely increase in people who would consider carrier screening if targeted programs were expanded to population-level screening, it is important to ensure that health care providers are both aware of jurisdictional carrier screening programs and competent in what carrier screening can offer their patients in terms of clinical actionability. Although this is particularly true for general practitioners who are often the primary point of contact with the health care system for their patients, it is also important for people who work in family planning clinics and women’s health clinics. Having the option to engage with carrier screening at the preconception stage was universally preferred by participants across the included studies. Compared with prenatal carrier screening, preconception carrier screening was seen as providing prospective parents with more reproductive options. Health care providers were concerned that offering carrier screening during pregnancy might lead pregnant people and their partners to confuse it with other prenatal testing which would limit people’s ability to be truly informed before deciding whether or not to pursue screening. However, if offered as a prenatal option, most people consider it important to do so as early as possible because it could be paired with other prenatal tests. Although not referred to specifically by any of the included studies, we note that offering carrier screening prenatally rather than at preconception, could place the responsibility to make the decision on cisgender women and non-binary or transgender people with uteruses. Sequentially designed carrier screening programs were the most common across the included studies; however, people moving through programs with this design found the interim period between receiving their positive carrier results and receiving their partners’ results difficult. This was particularly true for people who were already pregnant because this interim period forced them to reimagine both their relationship with the fetus and the future they had imagined with that child. Of course, this reimagining might be necessary if both partners’ screening results came back positive for the condition in question, but to stagger the return of the results could put undue anxiety on potential parents. Carrier screening will not affect everyone in the same way, and reproductive decision-making will still be complex and difficult. As such, the opportunity to engage with genetic counsellors on reproductive options following positive carrier status result is considered valuable.