From the Guidelines
Adding bupropion (Wellbutrin) to escitalopram (Lexapro) can be an effective strategy for treatment-resistant depression, particularly when patients experience incomplete response to escitalopram alone or have residual symptoms like fatigue or low motivation. This combination leverages complementary mechanisms of action, with escitalopram working primarily on serotonin and bupropion affecting dopamine and norepinephrine systems. When initiating this combination, start with bupropion SR 150 mg once daily for 4-7 days, then increase to 150 mg twice daily if tolerated. The maximum recommended dose is typically 400 mg daily (200 mg twice daily) 1. Some key points to consider when adding bupropion to escitalopram include:
- Monitoring patients closely for potential side effects including increased anxiety, insomnia, headache, dry mouth, and most importantly, an increased seizure risk (particularly at higher doses) 1.
- Contraindications for this combination include patients with seizure disorders, eating disorders, or those undergoing abrupt alcohol or benzodiazepine withdrawal 1.
- Drug interactions are another consideration, as both medications are metabolized by cytochrome P450 enzymes 1.
- The combination may be particularly beneficial for patients with depression accompanied by fatigue, low energy, sexual dysfunction, or weight gain from escitalopram, as bupropion often helps counteract these specific side effects while providing additional antidepressant efficacy through its distinct mechanism of action 1. It is essential to assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy and modify treatment if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder 1.
From the Research
Considerations for Adding Bupropion to Escitalopram
When considering adding bupropion (Wellbutrin) to escitalopram (Lexapro) in treatment-resistant patients, several factors should be taken into account:
- Serotonin Syndrome Risk: The combination of bupropion and selective serotonin reuptake inhibitors (SSRIs) like escitalopram may increase the risk of serotonin syndrome, a potentially fatal complication 2.
- Dose-Related Phenomena: High doses of bupropion (>450 mg/d) may be associated with an increased risk of mania in patients with bipolar affective disorder, although bupropion is generally considered to have a lower risk of inducing mania compared to other antidepressants 3.
- Efficacy and Tolerability: The combination of escitalopram and bupropion-SR has been shown to be effective and well-tolerated in patients with major depressive disorder, with response and remission rates higher than those typically seen with SSRI monotherapy 4.
- Extrapyramidal Symptoms: While escitalopram and other SSRIs may be associated with extrapyramidal symptoms, bupropion has been reported to be a suitable alternative in patients who experience these symptoms 5.
- Overdose Risk: Bupropion overdose has been associated with a higher risk of serious outcomes, including death, seizures, and hallucinations, compared to SSRI overdose 6.
Key Points to Consider
- Monitor patients closely for signs of serotonin syndrome when combining bupropion and escitalopram.
- Be cautious when using high doses of bupropion, especially in patients with bipolar affective disorder.
- The combination of escitalopram and bupropion-SR may be a viable option for patients with treatment-resistant major depressive disorder.
- Consider the potential for extrapyramidal symptoms when selecting an antidepressant.
- Evaluate the risk of overdose and the patient's propensity for self-harm when considering bupropion therapy.