Auvelity: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on Oct 4, 2023.

1. How it works

• Auvelity is a combination extended-release tablet containing dextromethorphan 45mg and bupropion 105mg which may be used to treat severe depression in adults.
• Auvelity works in several different ways because it contains two different ingredients, dextromethorphan and bupropion, although the exact way it works for depression is unknown. The dextromethorphan component targets the NMDA receptor (N-methyl-D-aspartate), the serotonin transporter (SERT), the norepinephrine transporter (NET), and the sigma-1 receptor, to regulate levels of glutamate and other neurotransmitters such as serotonin and norepinephrine. It has a similar effect to ketamine, but the main problem with dextromethorphan is that it is quickly metabolized. To slow the metabolism of dextromethorphan, Auvelity also contains bupropion which inhibits cytochrome P450 2D6 enzymes. By inhibiting these enzymes, less dextromethorphan is metabolized, prolonging its effect. Bupropion also has antidepressant effects and primarily acts through the NET and the dopamine transporter (DAT).
• NMDA receptors are located on nerve cells, mostly at excitatory synapses, and research has shown that they can become overstimulated when glutamate levels are high. Previous studies have shown that NMDA receptor antagonists can have antidepressant effects.
• Auvelity is classed as a miscellaneous antidepressant because it has a different way of working than other currently available antidepressants. Specifically, it is a norepinephrine and dopamine reuptake inhibitor (bupropion component) and an N-methyl D-aspartate (NMDA) receptor antagonist (dextromethorphan component).

2. Upsides

• May be used to treat major depressive disorder (MDD) in adults.
• Usually taken twice a day after an initial titration period.
• Orally administered (taken by mouth).
• Available in one strength: 45mg/105mg dextromethorphan/bupropion.
• May be taken with or without food.
• Contains both dextromethorphan and bupropion, both of which have antidepressant effects.
• Rapid-acting. Starts working within one to two weeks. Currently, Auvelity is the only antidepressant that significantly improves depressive symptoms (compared to placebo) starting at week 1.
• Auvelity is the first oral NMDA receptor antagonist approved for the treatment of MDD and provides the first new oral mechanism of action for depression in more than 60 years.
• Research has not found any association with psychotomimetic effects (such as hallucinations or delusions) or weight gain, and it may be less likely than some other antidepressants to cause sexual dysfunction.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Dizziness (16%), nausea (13%), headache (8%), diarrhea (7%), drowsiness (7%), dry mouth (6%), sexual dysfunction (6%), and increased sweating (5%) are the most common side effects reported with Auvelity.
• Auvelity, like other antidepressants, may increase the risk of suicidal thoughts and actions in some children, adolescents, and young adults, especially within the first few months of treatment or when the dose is changed. Auvelity is not approved for use in children and young adults.
• May also increase the risk of high blood pressure, manic episodes in people with bipolar disorder, angle-closure glaucoma, and unusual thoughts and behaviors.
• There is a risk of seizures during treatment with Auvelity. The risk is higher in people who take higher dosages, with certain medical problems (such as severe head injury, brain tumors, or severe stroke), or who take other medications that lower the seizure threshold (such as antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids). Contraindicated in people with seizure disorders.
• Should not be taken by people with a known hypersensitivity to bupropion, dextromethorphan, or any of the inactive ingredients in Auvelity.
• The dosage of Auvelity will need to be reduced in those with moderate kidney disease or in people who are poor metabolizers of CYP2D6. Avoid use in severe kidney or severe liver disease.
• Contraindicated in people with a history of eating disorders, such as bulimia or anorexia nervosa; by people who are likely to abruptly discontinue alcohol, benzodiazepines, barbiturates, or antiepileptics; by people taking MAOIs or within 14 days of stopping treatment with Auvelity or an MAOI. Screen patients for eating disorders, bipolar disorder, mania or hypomania, and check for possible drug interactions before starting Auvelity.
• Not recommended during pregnancy because it may harm an unborn baby. Adequate contraception should be used. If a woman inadvertently becomes pregnant while taking Auvelity consider registering them with the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or online. Breastfeeding is not recommended with Auvelity and for 5 days after the last dose because bupropion passes into breast milk.
• No generic is available.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

• Auvelity is an oral combination antidepressant tablet containing bupropion and dextromethorphan that has a novel way of working to treat adults with severe depression. Research has shown it is rapid-acting, and can have an effect within one to two weeks. Auvelity may not be suitable for some people including those with head injuries, eating disorders, or a history of stroke or seizures. It interacts with many other medications.

5. Tips

• The usual initial recommended dose is 1 tablet once daily in the morning, which is increased to 1 tablet twice daily after 3 days. Take Auvelity exactly as your doctor prescribes it. Do not take more than 2 tablets in 24 hours.
• Swallow the tablets whole: do not chew, divide, or crush the tablets. Separate each dose by at least 8 hours.
• May be taken with or without food.
• If you miss a dose, do not take an extra dose to make up for the dose you missed. Wait and take your next dose at the regular time. Do not take more than 1 dose of this medicine at a time.
• Before taking Auvelity, tell your doctor about all your health conditions, including if you have had a head injury, seizures, or convulsions, have had a stroke, have kidney problems, or have diabetes. Auvelity may not be suitable for people with certain health conditions, or there may be an increased risk of side effects with these conditions.
• Keep your appointments with your healthcare provider. Your blood pressure will need regular monitoring and your doctor will also want to monitor you for other side effects.
• If you have a seizure during treatment, stop taking this medicine and call your healthcare provider right away. Do not take this medicine again if you have a seizure.
• Call your healthcare provider right away if you feel your mood has declined further while taking Auvelity or develop suicidal thoughts or actions.
• Tell your doctor about all the medicines you take, including herbal medicines and supplements. Some may increase the risk of side effects and a potentially life-threatening problem called serotonin syndrome can happen if you take Auvelity with certain other medicines. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of serotonin syndrome such as agitation, seeing or hearing things that are not there (hallucinations), confusion, fast heartbeat, high body temperature (hyperthermia), shaking (tremors), stiff muscles or muscle twitching, or nausea, vomiting, or diarrhea.
• May cause dizziness and drowsiness, affecting your ability to drive or operate machinery, and increasing your risk of falls. Do not drive a car or use heavy machinery until you know how this medicine affects you.
• May increase the risk of angle-closure glaucoma in people with certain other eye conditions. Call your healthcare provider if you have eye pain, changes in your vision, or swelling or redness in or around the eye.
• Do not stop using Auvelity suddenly. Talk to your doctor first before stopping it, if you decide you no longer wish to take it. The dosage may need to be gradually discontinued.
• Auvelity may cause false positive results on a drug-screening urine test. If you require a drug test, tell the laboratory staff that you are taking this medicine, and they may be able to do a more specific drug test.
• Tell your healthcare provider if you are pregnant or plan to become pregnant. Auvelity is not recommended during pregnancy because it may harm your unborn baby. If you become pregnant or think you are pregnant during treatment, tell your healthcare provider right away and consider registering with the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or online. Breastfeeding is not recommended with Auvelity and for 5 days after the last dose because bupropion passes into breast milk

6. Response and effectiveness

• Trials have also shown that Auvelity works faster than other antidepressants, with rapid symptom improvement being noted in as early as 1 week. In addition, more people experienced symptom remission by week 2 than those taking a placebo. Continued effects were seen through to week 6. Symptom improvement was based on the overall change in a depression symptom scale that evaluated: sadness, inner tension, reduced sleep and appetite, difficulty concentrating or doing daily activities, lack of interest, lack of energy/motivation and ability to feel, pessimism, and thoughts of suicide.
• The percentage of patients who achieved symptoms that were “very much improved / much improved” at one week was 22% for Auvelity vs. 13% for placebo, a significant effect. In studies, over 50% of patients achieved a clinical response by the 6th week of treatment.
• Auvelity worked significantly better than Wellbutrin (bupropion) at relieving symptoms of depression in a small randomized double-blind, parallel trial that lasted for 6 weeks. It also had a faster onset of effect, with improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) score being observed as early as week 1 and differences being statistically significant by week 2.
• 43 people prescribed Auvelity experienced an overall decrease in their Montgomery-Åsberg Depression Rating Scale (MADRS) score of 13.7 points after 6 weeks compared to a decrease of 8.8 points in the 37 people prescribed bupropion (least-squares mean difference=-4.9; 95% CI=-3.1, -6.8).
• The change in the MADRS score and remission rates with Auvelity were also significantly greater than with bupropion at week 2 and every time point thereafter (-12.5 vs. -7.8, least-squares mean difference=-4.7; 95% CI=-0.6, -8.8).
• 60.5% of people taking Auvelity had at least a 50% decrease in their MADRAS score at week 6 compared with only 40.5% prescribed bupropion (least-squares mean difference=19.9%, 95% CI=-1.6, 41).
• Most other outcomes favored Auvelity.

7. Interactions

Medicines that interact with Auvelity may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Auvelity. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Over 620 medications interact with Auvelity. Common medications that may interact include:

• antibiotics such as ciprofloxacin
• antifungals, such as ketoconazole
• benzodiazepines or sedatives-hypnotics (sleep medicines)
• CNS stimulants
• corticosteroids, such as betamethasone, prednisone, or dexamethasone
• digoxin
• dopaminergic drugs such as bromocriptine, cabergoline, lisuride, or pramipexole
• interferon
• ketamine
• MAOIs (contraindicated within 14 days)
• medicines used to treat mood, anxiety, psychotic, or thought disorders, including selective serotonin reuptake inhibitors (SSRIs)
• nicotine
• opiates, such as fentanyl, morphine, and oxycodone
• oral diabetes medicines such as glipizide or insulin
• other medicines containing bupropion (found in some smoking cessation treatments or antidepressants) or dextromethorphan (found in some cough medicines)
• street (illicit) drugs
• strong inhibitors of CYP 2D6, such as paroxetine, thioridazine, and fluoxetine
• strong inducers of CYP2B6 such as clotrimazole, phenytoin, and carbamazepine
• substrates of CYP 2D6, such as most TCADs, SSRIs, venlafaxine, and duloxetine
• supplements that contain 5-hydroxytryptophan, black cohosh, or St. John's Wort
• tamoxifen
• tricyclic antidepressants (TCAs)
• theophylline
• warfarin.

Alcohol can interact with bupropion which is an ingredient of Auvelity, increasing the risk of neuropsychiatric side effects and reducing a person's tolerance to alcohol. Avoid or minimize alcohol consumption during treatment with Auvelity.

Note that this list is not all-inclusive and includes only common medications that may interact with Auvelity. You should refer to the prescribing information for Auvelity for a complete list of interactions.

References

• Auvelity Prescribing Information. Revised December, 2022. https://www.axsome.com/auvelity-prescribing-information.pdf

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Auvelity only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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