What is a suitable alternative to Sertraline (selective serotonin reuptake inhibitor) and Vilazodone (partial serotonin receptor agonist) for a patient with intolerance and inadequate response?

From the Guidelines

For a patient who did not tolerate sertraline due to weight gain, sedation, and sexual dysfunction and is not responding well to vilazodone, bupropion (Wellbutrin) would be a good medication option. Bupropion is typically started at 150 mg once daily for 3-7 days, then increased to 150 mg twice daily if tolerated. The maximum dose is usually 450 mg per day, divided into multiple doses. Bupropion works differently from SSRIs like sertraline, acting primarily on norepinephrine and dopamine rather than serotonin. This unique mechanism of action often results in fewer sexual side effects, less sedation, and is generally weight-neutral or may even promote modest weight loss, as supported by the American College of Physicians guideline 1. Bupropion is particularly effective for depression with prominent fatigue, low energy, or concentration difficulties. However, it should be used cautiously in patients with seizure disorders, eating disorders, or those at risk for seizures, as it can lower the seizure threshold. It's also important to monitor for potential side effects such as insomnia, anxiety, headache, and dry mouth, which typically improve over time. The American College of Physicians recommends discussing adverse event profiles with patients before selecting a medication, and bupropion has a favorable profile in this regard, with a lower rate of sexual adverse events compared to fluoxetine and sertraline 1.

Some key points to consider when prescribing bupropion include:

• Starting with a low dose and gradually increasing as needed and tolerated
• Monitoring for potential side effects and adjusting the dose or discontinuing the medication if necessary
• Being aware of the potential for bupropion to lower the seizure threshold and using caution in patients with seizure disorders or those at risk for seizures
• Discussing the potential benefits and risks of bupropion with the patient and involving them in the decision-making process, as recommended by the American College of Physicians guideline 1.

Overall, bupropion is a reasonable alternative for patients who have not responded to or tolerated other antidepressant medications, and its unique mechanism of action and favorable side effect profile make it a good option for patients with depression and prominent fatigue, low energy, or concentration difficulties.

From the FDA Drug Label

The recommended initial dose is 15 mg daily (7.5 mg b.i.d.) To achieve an optimal therapeutic response, at intervals of 2 to 3 days the dosage may be increased 5 mg per day, as needed. In clinical trials allowing dose titration, divided doses of 20 mg to 30 mg per day were commonly employed

Buspirone may be a good medication option for a patient who did not tolerate sertraline due to weight gain, sedation, and sexual dysfunction and is not responding well to Vilazodone, as it has a different side effect profile.

• The patient should be started on a low dose of 15 mg daily and titrated up as needed.
• Buspirone does not typically cause weight gain, sedation, or sexual dysfunction, making it a potential alternative for patients who have experienced these side effects with other medications 2.

From the Research

Alternative Medication Options

Given the patient's intolerance to sertraline due to weight gain, sedation, and sexual dysfunction, and a poor response to vilazodone, alternative medication options can be considered.

• Bupropion is a dopamine-norepinephrine reuptake inhibitor that has been shown to be effective in treating major depressive disorder with a lower risk of sexual dysfunction and weight gain compared to SSRIs 3, 4, 5.
• Mirtazapine is an antidepressant that enhances norepinephrine and serotonin neurotransmission, but it may not be the best option for this patient due to its potential for increased appetite and weight gain 3.
• Trazodone is a 5-HT2A and 5-HT2C receptor antagonist and selective serotonin reuptake inhibitor that has been used off-label for various conditions, including insomnia and anxiety, but its efficacy in treating depression is similar to SSRIs 3.
• Vortioxetine is a novel antidepressant that combines direct serotonin transporter inhibition and 5-HT1A receptor modulation, but it may have similar side effects to SSRIs, such as nausea and sexual dysfunction 3, 6.

Bupropion as a Potential Option

Bupropion has been shown to be an effective and well-tolerated option for treating major depressive disorder, with a lower risk of sexual dysfunction and weight gain compared to SSRIs 4, 5. It is available in various formulations, including immediate release, sustained release, and extended release, and has been used to treat a range of conditions, including depression, smoking cessation, and attention-deficit/hyperactivity disorder 4, 7.

• The most common side effects of bupropion include dry mouth, insomnia, and headaches, but it has a lower risk of sexual dysfunction and weight gain compared to SSRIs 3, 4, 5.
• Bupropion has been shown to be effective in treating depression, with improvement in symptoms noted at 2 weeks and full therapeutic effect observed at 4-6 weeks 3, 4.