According to the National Institute of Mental Health, an estimated 21 million adults in the US experienced at least one major depressive episode in 2021. However, treatment failure is common, with around 60% of people not responding to the first antidepressant they use.
For many people, two options often come up–Wellbutrin and Lexapro. But how do you know which one is right for you or whether taking both might be more effective? Finding the right antidepressant can feel like trial and error.
In the sections that follow, we’ll break down how Wellbutrin vs. Lexapro differ, how they’re each used, what side effects to expect, and whether they can be safely taken together.
Comparing Lexapro and Wellbutrin’s Effectiveness
Both Lexapro and Wellbutrin are effective antidepressants, but they work differently and often serve different patient needs. Here’s a breakdown of how they compare in terms of effectiveness for depression and related conditions:
Wellbutrin vs. Lexapro for Anxiety
Lexapro is FDA-approved for generalized anxiety disorder (GAD) and is often used as a first-line treatment. Wellbutrin, on the other hand, is not approved for GAD, and many doctors are cautious about prescribing it due to its potential to make anxiety symptoms worse.
Still, emerging research suggests that Wellbutrin may be a reasonable alternative in some cases, particularly if you’re concerned about side effects like sexual dysfunction, which is common with Lexapro.
In a 2008 pilot study, the extended-release version of Wellbutrin (XL) was found to be just as effective as Lexapro in easing anxiety symptoms among adults with GAD. But because the study had a limited sample size, further research is still needed.
A broader analysis of 10 high-quality clinical trials examined outcomes in people with anxious depression, a combination of major depression and high anxiety. It compared the effectiveness of SSRIs vs. Wellbutrin.
Results indicated that SSRIs, including Lexapro, had a slight advantage, but the difference was minimal. For every 17 individuals treated with an SSRI instead of Wellbutrin, only one was likely to experience better results. The remaining 16 would likely have done just as well with Wellbutrin.
More recent data from 8,457 patients tracked changes in anxiety levels over 6 and 12 weeks. Initially, individuals taking Wellbutrin had higher anxiety scores.
However, after adjusting for factors like age, sex, symptom severity, and other clinical variables, both the SSRI (47% patients on Lexapro) and Wellbutrin groups showed similar improvements. In fact, there was no clear evidence that Wellbutrin made anxiety worse over time.
Wellbutrin vs. Lexapro for Depression
Lexapro and Wellbutrin are FDA-approved to treat major depressive disorder (MDD). Wellbutrin also covers seasonal affective disorder and is sometimes prescribed off-label for depression linked to bipolar disorder.
In one study, researchers compared Wellbutrin XL and Lexapro in adults with depression. After 8 weeks of treatment, both groups saw a reduction in depression scores.
People taking Wellbutrin XL had their scores drop by an average of 14.5 points. Those on Lexapro saw a slightly greater drop, 15.4 points on average, but the difference wasn’t large enough to be considered significant.
When looking at how many people responded to treatment, about 70% of those on Wellbutrin XL experienced at least a 50% improvement in symptoms. For Lexapro, it was around 73%.
Remission rates were also similar. Close to 40% of those on Wellbutrin XL had minimal or no remaining symptoms. For Lexapro, it was roughly 47%. These findings suggest that both medications are similarly effective for treating depression.
Another study focused on individuals with MDD who also struggled with memory and daily functioning, not just low mood. It found no major difference between the two treatments as well. Both were linked to improved memory and better psychosocial functioning.
Wellbutrin vs. Lexapro’s Mechanism of Action
Lexapro contains escitalopram, which is an SSRI (Selective Serotonin Reuptake Inhibitor). It primarily works by:
This makes Lexapro effective for both depression and generalized anxiety disorder, as it helps balance emotional and stress-related brain activity.
Meanwhile, Wellbutrin contains bupropion, which is an atypical antidepressant, often grouped under the broader term NDRI (norepinephrine-dopamine reuptake inhibitor). It works by:
Unlike Lexapro, Wellbutrin does not significantly affect serotonin levels, which is why it’s not typically used for anxiety and may even worsen it in some people.
Here’s a side-by-side comparison of how they work:
| Feature | Lexapro | Wellbutrin |
|---|---|---|
| Main brain chemical | Serotonin | Dopamine and norepinephrine |
| How it works | Keeps serotonin active longer to improve mood | Keeps dopamine and norepinephrine active longer to increase drive and focus |
| Best for | Depression with anxiety, mood swings | Depression with low energy or lack of motivation |
| Helps with anxiety? | Yes | In some cases, but it might also make it worse for some people |
Side Effects of Wellbutrin and Lexapro
Lexapro and Wellbutrin are both generally well-tolerated. They may cause similar side effects, including insomnia, nausea, and sweating.
According to a study mentioned earlier, the overall rate of side effects was comparable. But, nausea was more common with Lexapro (18.7%) than with Wellbutrin (10.5%).
Lexapro’s Side Effects
Because they act on different brain chemicals, each has a distinct side effect profile. With Lexapro, you’re more likely to experience sexual issues such as reduced libido, delayed ejaculation, or difficulty reaching orgasm. You might also notice fatigue or drowsiness.
Some side effects, though less common, are more serious. If you’re taking Lexapro, be aware of these potential risks:
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- Serotonin syndrome – a dangerous reaction linked to high serotonin levels, especially if you’re using other serotonergic medications.
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- QT prolongation – an irregular heart rhythm that can become serious, particularly in older adults or those with heart problems.
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- Hyponatremia – low sodium levels, most often seen in older adults, which can cause confusion, muscle weakness, or even seizures.
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- Withdrawal symptoms – you may feel dizzy, fatigued, or nauseated if you stop the medication abruptly.
Wellbutrin’s Side Effects
Wellbutrin is often chosen by people who want to avoid sexual side effects. Unlike Lexapro, it doesn’t affect sexual function. However, you might experience the following:
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- Dry mouth
- Dizziness
- Sore throat
- Abdominal discomfort
- Restlessness or irritability
- Anxiety
- Tremors
- Palpitations
- Tinnitus (ringing or buzzing in the ears)
- Muscle pain
- Appetite suppression
- Frequent urination
- Skin rash
Serious concerns include:
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- Seizures, especially at higher doses or if you have a history of seizure disorders
- Elevated blood pressure or heart rate
- Worsening of suicidal thoughts
- Persistent itching or other skin reactions
Comparing Weight Changes on Wellbutrin and Lexapro
Another point to consider is weight gain.
In a recent study analyzing data from over 183,000 people across eight US health systems, those on Wellbutrin lost an average of 0.5 lbs and were 15% less likely to gain significant weight (defined as 5% or more of their starting weight). In contrast, Lexapro and several other antidepressants were linked to a 10-15% increased risk of that level of weight gain.
Earlier research involving overweight and obese women found that, after 24 weeks, participants taking Wellbutrin lost an average of 12.9% of their body weight, with most of the reduction coming from fat mass rather than muscle or bone.
Another long-term study evaluated the sustained-release form (Wellbutrin SR). After 48 weeks, those taking 300 mg maintained a 7.5% weight reduction, and those on 400 mg averaged an 8.6% loss. The medication was considered safe and well-tolerated throughout the study.
If weight gain is especially bothersome to you, Wellbutrin may be the more suitable choice.
Approved Indications of Lexapro and Wellbutrin
Lexapro is FDA-approved to treat major depressive disorder (MDD) in adults and teens aged 12 to 17. It’s used during both the initial phase and for ongoing management. More recently, the FDA also authorized its use for generalized anxiety disorder (GAD) in adults and in children as young as 7 years old.
In contrast, Wellbutrin’s extended-release formulation (XL) is approved for managing MDD and for preventing seasonal affective disorder (SAD). The sustained-release version (SR) is indicated only for MDD.
Unlike Lexapro, Wellbutrin has not been evaluated for safety or effectiveness in children. Prescribing Wellbutrin SR or XL for a child or adolescent would rely entirely on your healthcare provider’s clinical judgment.
Safety of Taking Wellbutrin and Lexapro Together
Starting treatment for MDD usually involves taking an SSRI alone. But for many people, that’s not enough. Less than a third reach full remission with just one medication. When this happens, doctors often try a combination of Lexapro and Wellbutrin to help improve results.
In a small 12-week study, researchers examined how safe and effective Wellbutrin SR and Lexapro might be for people with long-term or recurring depression. Everyone began with 10 mg of Lexapro each day. A week later, 150 mg of Wellbutrin SR was added. Over time, the doses went up to 20 mg of Lexapro and 400 mg of Wellbutrin SR.
By the end of the study, 62% of people showed clear improvement, and 50% had no more depression symptoms at all. These numbers were better than what’s usually seen with Lexapro by itself. Side effects were mild for most. Only 3 people out of 48 stopped because of them.
Still, the authors emphasized the need for larger, well-controlled trials to validate the findings.
Another research found that taking Wellbutrin and Lexapro together may improve symptoms faster than monotherapy.
In that study, 5 of 28 participants in the combination group had improved by week 2, whereas no early improvements were seen in the groups receiving either Wellbutrin or Lexapro alone. The advantage of combined treatment persisted through week 12.
Insights from Real Life Experiences
Some people who combined Wellbutrin and Lexapro shared that the combination worked better than Lexapro alone. One person said they felt extreme fatigue and had no motivation while taking only Lexapro. They were close to taking leave from work.
After adding Wellbutrin, the fatigue went away, and they felt more like themselves. They did notice some mild restless leg symptoms at bedtime but said it didn’t affect their sleep.
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Another person had been on 20 mg of Lexapro and felt emotionally numb. Their doctor added Wellbutrin, and although the first two weeks came with headaches, the change was worth it. They said their depression lifted, and they were finally able to feel emotions again.
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Dosage and Administration of Lexapro versus Wellbutrin
Lexapro is only available as a once-daily formulation, and it’s designed to work consistently throughout the day. Wellbutrin, on the other hand, has multiple versions (IR, SR, XL). However, the immediate-release (IR) formulation of Wellbutrin is no longer available.
Here’s how they compare in terms of dosage and administration:
| Medication | Indication | Initial Dose | Target Dose | Max Dose | Timing |
|---|---|---|---|---|---|
| Lexapro | MDD and GAD | 10 mg once daily for both adults and pediatric patients | 10 mg once daily | 20 mg once daily | Morning or evening, with or without food |
| Wellbutrin SR | MDD | 150 mg once daily | 300 mg/day (150 mg twice daily) | 400 mg/day (200 mg twice daily) | Twice daily (8 hrs apart), with or without food. Wait at least 3 days after starting the initial dose before increasing it. |
| Wellbutrin XL | MDD | 150 mg once daily | 300 mg once daily | 300 mg once daily | Morning, with or without food. Wait at least 4 days after starting the initial dose before increasing it. |
| Wellbutrin XL | SAD | 150 mg once daily, start treatment in the autumn prior to the onset of symptoms | 300 mg once daily | 300 mg once daily, treatment should be continued through the winter season | Morning, with or without food. Wait at least 1 week after starting the initial dose before increasing it. |
Cost of Lexapro vs. Wellbutrin
If you’ve been prescribed Wellbutrin XL, the cost may come as a surprise. A 30-day supply of the 150 mg strength can cost around $1,700, while the 300 mg dose may exceed $2,500. Wellbutrin SR tends to be less expensive, averaging around $500 for 60 tablets of the 150 mg dose. Lexapro can also be costly, with a month’s supply of the 10 mg tablets often priced above $400.
Generic options are available and generally more affordable. However, if you prefer to stay with the brand-name version, you still have options to reduce your out-of-pocket cost. One such option is purchasing your medication through a Canadian pharmacy.
Pharma Giant, an online Canadian pharmacy partner, offers significantly lower prices on these same medications. You can obtain 90 tablets of Wellbutrin XL 150 mg for $155, or the 300 mg strength for $195. Lexapro’s highest dose is available at $150 for a month’s supply.
Additional savings are also available through bulk purchases, coupon codes, and a 10% discount for new customers.
These are the same formulations that were approved by the FDA in the US. The price difference is due to Canada’s national pricing regulations, which benchmark costs against rates in other developed nations such as France, Germany, and the UK.
In Summary
Lexapro and Wellbutrin are both effective for treating depression, but they work differently. Lexapro is better for anxiety and is approved for more age groups, while Wellbutrin may be more helpful if low energy, weight concerns, or sexual side effects are a problem.
Studies show their overall effectiveness for depression is similar, and combining them can be useful when one alone doesn’t work well.
The best choice depends on your symptoms, treatment goals, and how you handle side effects. Always consult your doctor before starting or combining these medications.
Frequently Asked Questions
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