Alternatives to Spravato If You Can't Fill Your Prescription

Spravato (esketamine) is a groundbreaking treatment for treatment-resistant depression (TRD) — but for many patients, accessing it is a serious challenge. The REMS program restrictions, high cost, limited certified treatment centers, and insurance hurdles mean that some patients simply cannot get it. If that's your situation, you're not out of options.

Here's a comprehensive look at the most evidence-based alternatives to Spravato for adults with treatment-resistant depression in 2026, including what each option costs, how effective it is, and how to access it.

What Is Treatment-Resistant Depression?

Treatment-resistant depression (TRD) is defined as depression that has not adequately responded to at least two different antidepressant medications taken at adequate doses for adequate durations (typically 6–8 weeks each). TRD affects approximately 30% of people diagnosed with major depressive disorder, representing millions of patients in the U.S. who need more than a standard SSRI or SNRI.

Alternative 1: IV Ketamine Infusions (Off-Label)

Best for: Patients who need rapid symptom relief and can pay out-of-pocket

Intravenous (IV) ketamine is the racemic form of ketamine — meaning it contains both the S- and R-enantiomers of the molecule — and has been used off-label for depression since the early 2000s. Like esketamine (Spravato), IV ketamine works by blocking NMDA receptors and producing rapid antidepressant effects, often within hours.

IV ketamine is NOT FDA-approved for depression, so insurance rarely covers it. Costs typically run $400–$800 per infusion, with a standard course of 6 infusions over 2–3 weeks costing $2,400–$4,800 out of pocket. However, access is often easier than Spravato because IV ketamine clinics are widespread and do not require REMS enrollment.

Alternative 2: Transcranial Magnetic Stimulation (TMS)

Best for: Patients who want an insurance-covered, non-drug option with minimal systemic side effects

Transcranial Magnetic Stimulation (TMS) is an FDA-cleared, non-invasive treatment for major depressive disorder. It uses magnetic pulses to stimulate nerve cells in the part of the brain associated with mood control. Unlike Spravato, TMS does not involve any medication, dissociation, or sedation, and patients can drive themselves home after sessions.

A typical TMS course involves 30 to 36 sessions over 6 to 8 weeks (5 days/week). Most major insurers — including Medicare — cover TMS for MDD. Out-of-pocket costs vary widely, but patients with coverage typically pay copays only. Full courses without insurance can cost $6,000–$15,000. Newer accelerated TMS protocols (such as Stanford's SAINT) can deliver a full course in just 5 days.

Alternative 3: Auvelity (Dextromethorphan/Bupropion)

Best for: Patients who want an oral at-home alternative to Spravato with a rapid-onset mechanism

Auvelity (dextromethorphan/bupropion) was FDA-approved in August 2022 for major depressive disorder in adults. Like Spravato, it works in part through NMDA receptor antagonism, but it can be taken at home as an oral tablet — no in-clinic monitoring required. It begins working faster than most antidepressants, with some patients seeing improvements within 1–2 weeks.

Cash price for Auvelity runs approximately $900/month, but manufacturer savings programs and insurance coverage can significantly reduce costs. It is approved for MDD broadly, not specifically for TRD, but physicians may prescribe it for TRD patients who cannot access Spravato.

Alternative 4: Electroconvulsive Therapy (ECT)

Best for: Patients with severe, life-threatening TRD who have not responded to other treatments

Electroconvulsive Therapy (ECT) has the longest track record of any biological treatment for severe depression, with decades of evidence showing it is the single most effective treatment for severe TRD. Despite its dated reputation, modern ECT is performed under brief general anesthesia and is very different from its historical portrayal.

ECT is covered by most major insurance plans including Medicare and Medicaid. A typical course involves 6–12 sessions over 2–4 weeks. Side effects can include short-term memory impairment. ECT is generally reserved for severe, refractory depression or situations with imminent suicidal risk.

Alternative 5: Medication Augmentation Strategies

Best for: Patients who want to try additional medication combinations before pursuing procedural treatments

Before trying Spravato or other procedural treatments, psychiatrists often try adding augmenting agents to existing antidepressants. Common options include:

Atypical antipsychotics: Aripiprazole (Abilify), quetiapine (Seroquel), olanzapine — FDA-approved as adjuncts for MDD

Lithium augmentation: Adding lithium to existing antidepressants has decades of evidence in TRD

Symbyax (olanzapine/fluoxetine): FDA-approved for TRD; oral combination pill taken at home

Thyroid hormone augmentation: Adding T3 (liothyronine) to antidepressant therapy — low-cost, well-tolerated option

Comparing Spravato Alternatives at a Glance

Here's a quick overview to help you discuss options with your doctor:

IV Ketamine: Rapid (hours); off-label; usually self-pay $400-800/infusion; widely available

TMS: Non-drug; 6-8 week course; insurance-covered for MDD; no sedation; can drive after

Auvelity: Oral at-home pill; faster than SSRIs; FDA-approved for MDD; ~$900/month cash

ECT: Highest efficacy in severe TRD; requires anesthesia; insurance-covered; short-term memory side effects

Augmentation strategies: Oral medications; most insurance-covered; slower onset but lower-risk entry point

Talk to Your Doctor About Your Options

No single treatment works for every patient with TRD. The right choice depends on your medical history, the severity of your depression, insurance coverage, geographic access, and personal preference about side effects and treatment format. Always work with your psychiatrist to evaluate all options.

If you're pursuing any of these alternatives and struggling to fill other prescriptions, medfinder can help you locate pharmacies that have your other medications in stock near you.

If cost is the barrier to Spravato, check out our guide: How to Save Money on Spravato in 2026.