Dr. Ahmed Major depressive disorder (MDD) affects millions of people around the world and can greatly reduce their quality of life.
Researchers are constantly looking for better treatments, leading to different antidepressant medications.
Two such options are Auvelity, which combines dextromethorphan and bupropion, and Cymbalta, which contains duloxetine.
Although both are used to treat MDD, they work in different ways. This article will compare Auvelity and Cymbalta, explaining their similarities and differences to help the reader better understand these treatment choices.
Auvelity
Auvelity takes a unique approach to treating MDD by combining two main ingredients: dextromethorphan and bupropion.
Unlike typical antidepressants, it works in a different way. Dextromethorphan helps regulate mood by blocking NMDA receptors and balancing glutamate, a brain chemical linked to mood control.
Bupropion, meanwhile, increases norepinephrine and dopamine levels by preventing their reabsorption.
This combined effect is thought to be what makes Auvelity effective in treating depression.
Auvelity is currently approved by the FDA specifically for treating MDD (major depressive disorder) in adults.
Although its sole ingredients have other medical uses, the combination of dextromethorphan and bupropion is only prescribed for MDD.
This blend is believed to work together to create a faster and stronger antidepressant effect than either ingredient alone [ref].
Clinical trial data
In one study, a clinical trial studied Auvelity in 327 adults with major depressive disorder. Patients took either Auvelity or a placebo twice daily for six weeks.
Auvelity led to greater improvement in depression scores by Week 6 compared to placebo, with noticeable benefits as early as Week 1 and Week 2.
More patients on Auvelity reached remission at Week 2 and achieved significant symptom relief by Week 6. Auvelity also showed a faster effect compared to traditional antidepressants [ref].
Cymbalta
Cymbalta contains duloxetine as its active ingredient and is part of a group of antidepressants called serotonin-norepinephrine reuptake inhibitors (SNRIs).
It works by preventing the reabsorption of serotonin and norepinephrine in the brain, two neurotransmitters essential for mood regulation and pain signaling [ref].
This increases the availability of neurotransmitters, which helps reduce symptoms of depression and other conditions.
Cymbalta is approved for a wider range of conditions than Auvelity. It is used to treat major depressive disorder (MDD) and generalised anxiety disorder (GAD).
In addition, it helps manage chronic pain conditions like fibromyalgia and nerve pain in diabetic peripheral neuropathy [ref].
Its versatility comes from its impact on pain pathways, which are influenced by serotonin and norepinephrine in the central nervous system.
Duloxetine, the main active ingredient, is responsible for these multiple therapeutic benefits.
Clinical trial data
Cymbalta has been extensively studied for its effectiveness in treating MDD and physical pain symptoms.
In an 8-week multicenter trial study with 173 patients, duloxetine doses were titrated from 40 mg to 120 mg daily.
Duloxetine showed statistically significant improvement in depressive symptoms compared to placebo (p = .009). The estimated response and remission rates for duloxetine were 64% and 56%, respectively [ref].
Moreover, four acute phase trials involving doses of 40-60 mg/day duloxetine also confirmed its efficacy and safety over 9 weeks, showing consistent symptom improvement compared to placebo [ref]
Comparative Analysis
| Auvelity | Cymbalta | |
| Effectiveness | Auvelity has a faster onset of action, showing efficacy within one to two weeks, which is quicker than many traditional antidepressants. | Cymbalta does not have a specific fast onset, but it is effective in treating MDD and relieving physical pain symptoms. |
| Side effects | Some common side effects are higher blood pressure, an increased risk of seizure if taken in larger doses, manic episodes in people with bipolar disorder, and unusual thoughts or behavior. Auvelity is known to cause fewer sexual side effects compared to many other antidepressants, including Cymbalta. | Common side effects include nausea, drowsiness, and increased blood pressure. It also has a higher risk of causing sexual side effects and withdrawal symptoms. |
| Target Populations | Auvelity is approved specifically for MDD in adults and offers a fast onset of action. This makes it a good option for people looking for quick relief. Its fast-acting nature can be especially helpful for people who need rapid antidepressant effects. | Cymbalta is approved for a broader range of conditions, including chronic pain and generalised anxiety disorder, making it versatile for patients with comorbid conditions. It is suitable for those with multiple conditions, like chronic pain and depression. |
| Drug Interactions | Since Auvelity contains dextromethorphan and bupropion, it may interact with drugs that affect the CYP2D6 enzyme or those that raise the risk of seizure. | Known to interact with MAOIs, certain antidepressants, and medications that affect liver enzymes like CYP2D6. |
| Discontinuation Syndromes | There is limited information on withdrawal symptoms specific to Auvelity, but since it is a combination medication, stopping it suddenly may carry some risk of withdrawal effects. | Cymbalta is known to cause withdrawal symptoms upon discontinuation, including dizziness, nausea, and headaches. Gradual tapering is recommended to minimise these effects. |
Practical Considerations
Dosage and Administration:
- Auvelity:
- Auvelity is normally taken as one capsule twice a day, with a gap of at least 8 hours between doses. Each capsule has a combination of dextromethorphan and bupropion [ref].
- Availability and cost can vary depending on location and insurance coverage. Since it may be a newer medication, it may be more expensive than generic duloxetine.
- Cymbalta:
- The dosage of Cymbalta depends on the condition being treated, usually ranging from 30mg to 120mg per day. It can be taken once or twice a day. However, in clinical studies, doses higher than 60 mg weren’t found to be more effective than 60-mg doses [ref].
- Duloxetine is available in generic formulations, which generally offer lower costs. However, the brand name Cymblata may still be prescribed in some cases.
- Cost and Availability:
- The price of both medications varies based on factors such as insurance coverage, pharmacy, and prescribed dosage. It is always best to check with your insurance provider and local pharmacies for the most up-to-date pricing.
Patient Monitoring:
- Regular check-ups with the healthcare professional are essential for both Auvelity and Cymbalta. This helps assess how well the treatment is working, detect any side effects, and make a dosage adjustment if necessary.
- Both medications may affect mood, so patients should be closely monitored for any worsening of depression or suicidal thoughts, especially in the early stages of depression.
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