From the Guidelines
For a patient with depression and PTSD who has not responded well to sertraline and venlafaxine, I recommend trying bupropion (Wellbutrin) as an alternative medication. Start with 150 mg once daily in the morning for the first week, then increase to 150 mg twice daily if tolerated. The target dose is typically 300 mg per day, but can be increased to a maximum of 450 mg per day if needed. Bupropion works differently from the SSRIs and SNRIs previously tried, as it primarily affects norepinephrine and dopamine rather than serotonin. This different mechanism of action may be beneficial for patients who haven't responded to serotonergic drugs. Bupropion has shown efficacy in treating both depression and PTSD symptoms, as supported by studies such as the STAR*D trial 1. Common side effects include dry mouth, nausea, insomnia, and agitation. It's essential to note that bupropion lowers the seizure threshold, so it should be used with caution in patients with a history of seizures or eating disorders. In addition to medication, strongly consider referring the patient for trauma-focused cognitive behavioral therapy (TF-CBT), which is a first-line treatment for PTSD and can also help with depressive symptoms. The combination of medication and psychotherapy often yields better results than either treatment alone, as suggested by the American College of Physicians guideline 1. Some key points to consider when prescribing bupropion include:
- Monitoring the patient closely for the first few weeks after starting bupropion, as the risk of side effects and potential worsening of symptoms is highest during this period.
- If there's no improvement after 6-8 weeks at the target dose, consider alternative strategies such as augmentation with mood stabilizers or consultation with a psychiatrist for more specialized care.
- Discussing adverse event profiles with the patient before selecting a medication, as different SGAs have varying rates of adverse effects, such as sexual dysfunction and suicidality 1. Overall, bupropion is a reasonable alternative for patients who have not responded to sertraline and venlafaxine, and its use should be considered in conjunction with psychotherapy for optimal treatment outcomes.
From the Research
Alternative Medications for Depression and PTSD
For a patient with depression and post-traumatic stress disorder (PTSD) who has previously taken sertraline (Selective Serotonin Reuptake Inhibitor, SSRI) and venlafaxine (Serotonin-Norepinephrine Reuptake Inhibitor, SNRI), alternative medications can be considered.
- Bupropion-SR: A study published in 2 found that bupropion-SR, sertraline, or venlafaxine-XR can be effective after failure of SSRIs for depression. Remission rates as assessed by the HRSD-17 and the QIDS-SR-16 were 21.3 percent and 25.5 percent for sustained-release bupropion.
- Mirtazapine: Research suggests that mirtazapine can be an effective option for treatment-resistant depression 3. The combination of mirtazapine plus venlafaxine has shown to reduce immobility in the forced swim test and does not inhibit female sexual behavior.
- Other SSRIs: Although the patient has previously taken sertraline, other SSRIs can be considered as an alternative, as they have similar efficacy and tolerability profiles 4, 5.
Considerations for Alternative Medications
When considering alternative medications, it is essential to weigh the benefits and risks of each option.
- Venlafaxine: While venlafaxine can be effective, it has been associated with a higher risk of cardiovascular adverse effects and fatal overdoses compared to most SSRIs 5.
- Mirtazapine and Venlafaxine Combination: The combination of mirtazapine and venlafaxine may be an effective option for treatment-resistant depression, but its safety and efficacy need to be carefully evaluated 3.
- Bupropion-SR: Bupropion-SR has been shown to be effective after failure of SSRIs for depression, but its tolerability and adverse event profile should be considered 2.