A 43-year-old man with a BMI of 33 presents to the PMHNP with complaints of being depressed, difficulty falling asleep, loss of motivation, diminished concentration, and decreased sexual desire. Based on this scenario, which of the following medications would be most appropriate as an initial treatment?

Choice A reason: Mirtazapine is a sedating antidepressant that can cause significant weight gain and increased appetite. Given the patient’s elevated BMI, this side effect profile may worsen his metabolic status and is not ideal as a first-line option. Choice B reason: Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and is generally weight-neutral or mildly weight-reducing. However, it can cause sexual dysfunction, which is already a concern for this patient. It may also exacerbate insomnia in some individuals. Choice C reason: Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) that is activating and can improve energy, motivation, and concentration. It is associated with weight loss and has a lower risk of sexual side effects compared to SSRIs, making it the most appropriate initial choice for this patient’s symptom profile and BMI. Choice D reason: Nortriptyline is a tricyclic antidepressant with anticholinergic side effects and potential for weight gain. It is not typically used as a first-line agent due to its side effect burden and cardiovascular risks, especially in patients with metabolic concerns.