What depression med works the fastest? Exploring new rapid-acting treatments

October 10, 2025 •

2 min read

For decades, traditional antidepressants have notoriously taken weeks or even months to show a significant effect. However, recent breakthroughs have introduced new treatments that offer a much faster path to relief, prompting many to ask: what depression med works the fastest?

Quick Summary

The fastest-acting depression medications, such as the nasal spray esketamine (Spravato) and the oral tablet Auvelity, can offer symptom relief in days or weeks, unlike traditional antidepressants that take months. This guide provides a detailed look at these newer treatments, how they work, and their suitability for different conditions, emphasizing the importance of medical guidance.

Key Points

Ketamine and Esketamine are the fastest: The nasal spray esketamine (Spravato) can produce relief within 24-72 hours, particularly for treatment-resistant depression and suicidal ideation, and IV ketamine can work within hours.
Rapid action involves unique mechanisms: Unlike older antidepressants that target serotonin, faster-acting medications like ketamine, esketamine, and Auvelity modulate the glutamate system to quickly alter brain connections.
Auvelity offers faster oral relief: As an FDA-approved oral medication, Auvelity can show symptom improvement in as little as one week, a significant reduction from the 4-6 weeks required by most standard antidepressants.
Administrative differences are significant: Esketamine requires administration in a clinical setting under supervision due to potential side effects, while Auvelity is an oral tablet for at-home use.
Individual circumstances dictate the best option: Factors like depression severity, treatment history, and tolerance for side effects determine which rapid-acting treatment is most appropriate, requiring a personalized medical consultation.
Faster is not always better: While speed is a factor, potential side effects, abuse risk, and need for ongoing treatment must be weighed against the quicker onset of action.

The shift from slow-acting to rapid-acting treatments

Traditional antidepressants, which primarily target monoamine neurotransmitters, typically require weeks or months to show noticeable effects. This delay is problematic for those with severe or treatment-resistant depression (TRD) and those requiring urgent relief. Newer rapid-acting treatments, which often target the glutamate system, have emerged to address this need.

Ketamine and esketamine (Spravato): The quickest responders

Ketamine, administered intravenously (IV) in a clinical setting, can provide rapid relief for severe or TRD, sometimes within hours. Its effects are temporary, usually lasting about a week. Esketamine (Spravato), an FDA-approved nasal spray, is a form of ketamine used for adults with TRD or major depressive disorder (MDD) with suicidal ideation. Spravato can work within 24 to 72 hours, particularly when combined with an oral antidepressant. It must be administered under medical supervision due to potential side effects and risk of abuse.

Auvelity: A fast-acting oral option

Auvelity is an FDA-approved oral medication combining dextromethorphan and bupropion. Bupropion enhances the effects of dextromethorphan, which acts on the glutamate system. Clinical trials showed symptom relief in some patients in as little as one week, significantly faster than traditional antidepressants. Auvelity can be taken at home, offering a convenient option for those needing a quicker response without requiring clinic visits.

Comparison of rapid-acting treatments


Factor	Esketamine (Spravato)	Auvelity (dextromethorphan/bupropion)	Traditional Oral Antidepressants (SSRIs/SNRIs)
Speed of Relief	Can be as fast as 24-72 hours	As early as 1 week	4-6 weeks for noticeable effects
Administration	Nasal spray, administered in a clinic under medical supervision	Oral tablet, taken at home	Oral tablet, taken at home
Approval for Use	Treatment-resistant depression & MDD with suicidal ideation	Major depressive disorder (MDD)	General depression, anxiety, OCD, PTSD
Primary Mechanism	Targets the glutamate (NMDA) system	Targets the glutamate (NMDA) system	Modulates serotonin and norepinephrine levels
Treatment Setting	Requires a certified doctor's office or clinic due to potential side effects and risk of misuse	Can be used at home like other oral medications	Used at home with regular medical follow-ups
Common Side Effects	Temporary dissociation, dizziness, nausea, blood pressure changes	Dizziness, dry mouth, sleepiness, headache	Weight gain, sexual dysfunction, fatigue, emotional blunting

Other quick-acting treatments and considerations

Electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) are non-medication options that can also provide faster relief than standard oral antidepressants, especially ECT for severe cases. Deciding on the fastest treatment requires consulting a healthcare provider to consider symptom severity, treatment history, side effect tolerance, and lifestyle. A personalized treatment plan is essential.

Conclusion: Tailoring speed to need

While traditional antidepressants are foundational, rapid-acting options like esketamine and Auvelity provide quicker relief for those who need it. Esketamine is for severe or TRD and requires clinical oversight. Auvelity offers a faster oral route for a broader patient group. Selecting the right treatment involves balancing speed with benefits, limitations, and individual needs.

For more information on brain stimulation therapies, consult trusted medical resources such as the Mayo Clinic.

Frequently Asked Questions

For emergency situations involving severe depression or suicidal ideation, treatments like intravenous (IV) ketamine or the nasal spray esketamine (Spravato) are the fastest options, with effects potentially seen within hours.

Spravato (esketamine) is one of the fastest FDA-approved treatments for depression, offering potential relief in 24 to 72 hours for patients with treatment-resistant depression or MDD with suicidal ideation.

No. Due to its potential for serious side effects and abuse, ketamine is typically administered intravenously in a controlled clinical setting under strict medical supervision.

Auvelity is designed to act much faster than traditional oral antidepressants like SSRIs, with some patients experiencing symptom relief in as little as one week, compared to the 4-6 weeks for standard medications.

Yes, fast-acting medications like esketamine and Auvelity primarily modulate the glutamate system in the brain, whereas traditional antidepressants like SSRIs and SNRIs affect serotonin and norepinephrine levels.

Side effects vary by medication. Esketamine can cause temporary dissociation, dizziness, and nausea. Auvelity's side effects can include dizziness, dry mouth, and headache. All require discussion with a doctor.

Eligibility depends on the specific medication. Esketamine is typically for severe or treatment-resistant cases, while Auvelity is for adults with MDD. A full medical evaluation is necessary to determine suitability for any rapid-acting treatment.