Why Do Doctors Prescribe Lexapro and Wellbutrin Together?

Lexapro and Wellbutrin are two common antidepressants with different effects on the nervous system. Combining different types of antidepressants can be beneficial due to their synergistic effects on mood, particularly in patients who do not get better with a single antidepressant. So why do doctors prescribe Lexapro and Wellbutrin together? This blog discusses the scientific evidence of why doctors prescribe Lexapro and Wellbutrin together.
Klara Hatinova

Klara Hatinova

Klara is postgraduate researcher in experimental psychology at the
University of Oxford.

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Doctors often prescribe Lexapro and Wellbutrin together to enhance their effectiveness in treating depression. This combination can provide a more comprehensive approach to managing symptoms, as Lexapro works by increasing serotonin levels, while Wellbutrin targets dopamine and norepinephrine. Taking them together can offer greater benefits than taking them individually, as they address different aspects of the brain's neurotransmitter balance.

What are Lexapro and Wellbutrin?

Lexapro and Wellbutrin are both antidepressants that contain the active substances escitalopram and bupropion, respectively. They have slightly different antidepressant properties, making them suitable to be prescribed together.

What Is Lexapro?

Lexapro, containing the active substance escitalopram, belongs to a group of antidepressants called selective serotonin reuptake inhibitors (SSRIs).

Lexapro is commonly prescribed for depression and anxiety, but antidepressants like Lexapro should not be used for ADHD [1]. It's worth noting that Lexapro doesn't cure depression, but it can help manage the symptoms. 

How Does Lexapro Work?

Lexapro improves mood by increasing serotonin levels in your brain –  a critical regulator of mood, appetite, and alertness. This is done by blocking serotonin's reuptake (re-absorption) and increasing the brain's serotonin. Due to the role of serotonin in the brain, increasing serotonin can improve mood and reduce anxiety [2].

As a benefit compared to other antidepressants, Lexapro can act as an allosteric modulator of serotonin reuptake, which makes it better tolerated than other SSRIs [2].

What Is Wellbutrin?

Wellbutrin is an antidepressant brand name that contains the active substance bupropion. It is primarily prescribed to treat major depressive disorder (MDD) and prevent seasonal affective disorder (SAD) [3].

In addition to its primary uses, Wellbutrin is also sometimes used to help people quit smoking, treat episodes of depression in patients with bipolar disorder, and manage attention deficit hyperactivity disorder (ADHD) [4]. 

How Does Wellbutrin Work?

Wellbutrin belongs to a group of drugs known as norepinephrine and dopamine reuptake blockers. Therefore, Wellbutrin stabilises mood by affecting the balance of norepinephrine and dopamine in the brain, which differs from Lexapro and other SSRIs [3]. This makes Wellbutrin an excellent antidepressant for combination therapy, as it can complement the serotonergic activity of SSRIs

In 2012, Wellbutrin was incorrectly marketed to help with weight loss and sexual dysfunction, which resulted in a fine for the manufacturer, GlaxoSmithKline. Nonetheless, there is preliminary evidence that Wellbutrin could be a peptide to help with weight loss and sexual dysfunction, but it is not yet approved for these purposes [5].

Why Do Doctors Prescribe Lexapro and Wellbutrin Together?

Doctors prescribe the combination of bupropion (Wellbutrin) and escitalopram (Lexapro) for the treatment of the major depressive disorder (MDD), and has been looked at in several studies.

For example, Lexapro and Wellbutrin could be prescribed together if you show signs that your antidepressant dose is too low

Speed Of Remission Prescribing Lexapro and Wellbutrin

One study found that the combination of Lexapro and Wellbutrin from the onset of treatment was superior to either drug alone in terms of speed of onset of remission. The remission rate at week 12 of combination treatment was higher (15/28) compared to Wellbutrin monotherapy (7/26), although not statistically different from escitalopram monotherapy (11/31) [6]. 

Response Rates Prescribing Lexapro and Wellbutrin 

Another study found that the combination of Lexapro and Wellbutrin resulted in response rates of 62% and remission rates of 50% at study exit, significantly higher than is typical for SSRI monotherapy [7].

In a study of patients with both major depressive disorder and internet gaming disorder,

Wellbutrin showed greater effects than Lexapro on reducing impulsivity and attentional symptoms. The study also found that decreased brain connectivity between the salience network and the default mode network was associated with improved symptoms of excessive internet gaming disorder and impulsivity [8].

However, it's important to note that not all studies found the combination therapy superior. One study did not see that dual therapy outperformed both monotherapies in either the timing of remission or remission rate [9].

Treatment Tolerability Prescribing Lexapro and Wellbutrin

In terms of tolerability, one study found that the combination of escitalopram and bupropion was well tolerated, with a low level of adverse events that could be directly tracked to the drug. Only 3 participants (6%) discontinued treatment due to side effects [7].

Critically, combining two drugs may be linked to an increased chance of side effects since these could come from either of the drugs. Luckily for Lexapro and Wellbutrin, the side effects rate was comparable to when they were taken together, which is why doctors prescribe them together. Common side effects of Lexapro and Wellbutrin combination therapy were sexual dysfunction (41%), insomnia (22%), lack of energy (15%), and mild tremor-like dyskinesia (11%) [10]. Promisingly, one study found Wellbutrin could reduce Lexapro-induced sexual dysfunction, demonstrating the complementary effects of combining these two antidepressants [11].

Summary: Why Do Doctors Prescribe Lexapro and Wellbutrin Together

To summarise, Lexapro and Wellbutrin are two different types of antidepressant drugs that are prescribed together for faster and more effective treatment of major depression. Even as a combination therapy, they do not significantly increase the risk of side effects, making their combination popular among doctors.

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Klara Hatinova

Klara Hatinova

Klara is a postgraduate researcher in experimental psychology at the University of Oxford. She has worked across a spectrum of hot topics in neuroscience, including her current project measuring reinforcement learning strategies in Parkinson’s disease. Previously, she studied the efficacy of psilocybin as a therapy for critical mental health conditions and examined molecular circadian rhythms of migraine disorders. She completed her undergraduate degree in Neuroscience at the University of Glasgow and participated in a year abroad at the University of California, where she worked on a clinical trial for spinal cord injury.