Auvelity

Treatment of Major Depressive Disorder

Auvelity is specifically approved for the treatment of major depressive disorder (MDD) in adults. It is a combination medication containing dextromethorphan and bupropion, designed to help manage the symptoms of clinical depression.

Healthcare providers may prescribe this medication when a patient requires a treatment that may work more quickly than traditional antidepressants. Clinical studies have shown that some individuals may begin to see an improvement in their depressive symptoms within the first one to two weeks of starting the medication.

This medication is intended to address various symptoms associated with major depressive disorder, including:

• Persistent feelings of sadness, hopelessness, or emptiness
• Loss of interest or pleasure in hobbies and activities
• Changes in appetite or weight
• Sleep disturbances, such as insomnia or sleeping too much
• Loss of energy or increased fatigue
• Difficulty thinking, concentrating, or making decisions
• Feelings of worthlessness or inappropriate guilt

How Auvelity Works

Auvelity contains two active ingredients, dextromethorphan and bupropion, which work together to treat major depressive disorder. Unlike many traditional antidepressants that primarily target serotonin, this medication works through the glutamate system in the brain.

The Role of Dextromethorphan

Dextromethorphan is the component that directly affects mood-regulating pathways. It acts as an NMDA receptor antagonist and a sigma-1 receptor agonist. These actions help modulate glutamate, a neurotransmitter essential for healthy brain communication and mood stability.

The Role of Bupropion

In this combination, bupropion serves a specific purpose: it increases and sustains the levels of dextromethorphan in the blood. It does this by blocking a specific enzyme in the liver called CYP2D6, which would otherwise break down the dextromethorphan too quickly for it to be effective for depression. While bupropion is also an antidepressant, its primary job here is to boost the effectiveness of the dextromethorphan.

A Different Approach to Treatment

Because it targets different pathways than older antidepressants, Auvelity may work more quickly. While many treatments take several weeks to show results, the glutamate-targeting mechanism of this medication has been shown to improve symptoms in some people as early as one to two weeks after starting treatment.

Common Side Effects

The most frequently reported side effects of Auvelity include:

• Dizziness
• Headache
• Diarrhea
• Sleepiness or drowsiness
• Dry mouth
• Sexual function problems
• Increased sweating

Serious Side Effects

Contact a healthcare provider immediately if you experience any of the following serious symptoms:

• Seizures: The risk of seizures is higher at doses above the recommended amount or in people with certain medical conditions.
• High Blood Pressure: This medication can cause an increase in blood pressure that may require regular monitoring.
• Mood or Behavior Changes: This includes mania, hallucinations, or feelings of extreme agitation and confusion.
• Impulse Control Problems: Some people experience intense urges to gamble, spend money, or eat that they cannot control.
• Visual Changes: Eye pain, swelling, or changes in vision can be signs of angle-closure glaucoma.
• Severe Allergic Reactions: Symptoms may include a severe rash, itching, or swelling of the face, tongue, or throat.

Suicidal Thoughts and Behaviors

Auvelity carries a boxed warning, the most serious warning required by the FDA. Antidepressants may increase the risk of suicidal thoughts and behaviors in children, adolescents, and young adults. It is important to monitor for any new or worsening changes in mood, behavior, or thoughts during treatment.

Seizure Risk

The bupropion component of this medication increases the risk of seizures. This risk is dose-related. This medication is generally contraindicated in individuals with a history of seizure disorders, current or prior diagnosis of bulimia or anorexia nervosa, or those undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.

Blood Pressure and Cardiovascular Effects

Treatment with this medication can cause an increase in blood pressure. Monitoring blood pressure is recommended before starting treatment and periodically during therapy. The risk may be higher when used in combination with other medications that increase blood pressure or in patients with existing hypertension.

Mental Health and Neuropsychiatric Reactions

Several neuropsychiatric concerns are associated with this medication:

• Activation of Mania/Hypomania: In patients with bipolar disorder, antidepressants may trigger a manic or hypomanic episode. Screening for bipolar disorder is recommended before starting treatment.
• Psychosis and Other Reactions: Bupropion has been associated with neuropsychiatric signs and symptoms, including hallucinations, delusions, paranoia, and confusion.
• Serotonin Syndrome: A potentially life-threatening condition called serotonin syndrome may occur, especially when this medication is used with other serotonergic drugs.

Other Precautions

• Angle-Closure Glaucoma: This medication may cause pupillary dilation, which can trigger an angle-closure attack in patients with anatomically narrow angles who do not have a functional iridectomy.
• Impulse Control: Some medications used for mental health conditions have been linked to impulse control problems, such as intense urges to gamble, spend money, or binge eat.
• Dizziness and Falls: The medication can cause dizziness, which may increase the risk of accidental falls.

Pregnancy

There are no adequate or well-controlled studies on the use of Auvelity in pregnant individuals to determine if there is a drug-associated risk of major birth defects, miscarriage, or other adverse outcomes. While some research on bupropion, one of the active ingredients, has not shown a clear increase in the risk of birth defects, other data remain inconclusive. Healthcare providers may suggest monitoring through a pregnancy exposure registry if the medication is used during pregnancy to track the health of both the parent and the baby.

Breastfeeding

Bupropion and its metabolic byproducts are known to pass into human breast milk. Because of the potential for serious side effects in a nursing infant, breastfeeding is not recommended during treatment with Auvelity. It is typically advised to avoid breastfeeding during treatment and for at least five days after the final dose is taken. If you are breastfeeding or planning to breastfeed, it is important to discuss alternative treatment options or feeding methods with your healthcare provider.

Available Forms

Auvelity is supplied as an oral medication in the following form:

• Extended-release tablet

This medication is designed to be swallowed whole. Breaking, crushing, or chewing the tablet may interfere with how the medicine is released into the body.

FDA Approval and Indication

The U.S. Food and Drug Administration (FDA) approved Auvelity in August 2022. It is indicated specifically for the treatment of major depressive disorder (MDD) in adults. It represents a new class of antidepressant treatment, combining dextromethorphan and bupropion to target different pathways in the brain than traditional SSRIs or SNRIs.

Boxed Warning

Auvelity contains a boxed warning, which is the FDA's most serious warning for prescription drugs. This warning highlights the increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults. Because of this risk, healthcare providers must monitor patients closely for any worsening of depression or emergence of suicidal tendencies, especially during the first few months of treatment or following dosage changes.

Regulatory Status and Safety

Auvelity is a prescription-only medication and is not classified as a controlled substance. While it is approved for adults, its safety and effectiveness have not been established for pediatric patients, and it is not FDA-approved for use in anyone under the age of 18. The FDA also monitors the individual components of the drug, such as bupropion, for potential risks related to seizure activity and blood pressure changes.

Brand-Name Status

Auvelity is a brand-name medication. At this time, there is no generic version of this specific combination drug available. Brand-name drugs typically cost more than generic alternatives.

Insurance Coverage

The amount you pay for Auvelity often depends on your insurance plan. Some plans may place Auvelity on a higher tier of their formulary, which can result in a higher copay. In some cases, insurance companies may require prior authorization, meaning your doctor must provide additional information to the insurer to justify the use of the medication before it is covered.

Savings and Assistance

Patients may be able to reduce their out-of-pocket expenses through manufacturer-sponsored programs. These may include:

• Copay Savings Cards: These are often available for patients with commercial insurance to lower the cost at the pharmacy counter.
• Patient Assistance Programs: These programs may provide the medication at a lower cost or for free to individuals who meet specific income requirements and do not have insurance coverage.

It is helpful to consult with a pharmacist or contact your insurance provider directly to determine the exact cost under your specific plan.