The Science Behind Ketamine Therapy: How It Works, How Fast, and What Research Shows

You've heard ketamine works differently than antidepressants. You've seen claims about rapid results. You’re curious about neuroplasticity. But what's actually happening in the brain—and why would that matter for someone who hasn't found relief from traditional medications?

The short answer: Ketamine targets a completely different system than SSRIs. Instead of adjusting serotonin levels, it blocks NMDA receptors and triggers a cascade involving glutamate and brain-derived neurotrophic factor (BDNF) that can promote new neural connections within hours. For people with treatment-resistant depression, this distinct mechanism explains why ketamine sometimes works when nothing else has.

Why Traditional Antidepressants Don't Work for Everyone

SSRIs and SNRIs work primarily by increasing serotonin and other monoamines in the brain. For many people, this approach helps. But roughly 20–30% of people with major depressive disorder remain significantly symptomatic despite multiple adequate antidepressant trials.

This is treatment-resistant depression. Because ketamine targets NMDA receptors and downstream glutamate/BDNF pathways rather than monoamines, some people who haven't responded to SSRIs may still benefit from ketamine therapy.

How Fast Does Ketamine Work for Depression?

Ketamine's most notable difference from SSRIs is speed. Randomized trials show that a single low-dose infusion can reduce depressive symptoms within about 2–4 hours in many participants. Compare that to the 2–6 weeks SSRIs typically require.

Why does rapid onset matter? For someone experiencing suicidal ideation, severe functional impairment, or years of failed SSRI trials, waiting another month to know if a treatment works isn't just inconvenient. Faster relief can mean the difference between maintaining a job, staying connected to family, or holding on through a crisis.

The benefits of a single ketamine dose often last several days to about a week, with repeated treatments generally associated with higher and more sustained response rates:

• One study of people with treatment-resistant depression found that 44% met response criteria after 24 hours compared with 6% in the placebo group. Effects persisted 48 hours post-treatment.
• In internal outcome tracking at Innerwell, approximately 87% of patients report improvements in depression and anxiety symptoms within the first 4 weeks. These are preliminary data based on patient-reported outcomes and have not yet undergone external peer review.

How Ketamine Works in the Brain

Traditional antidepressants modulate serotonin and other monoamines. Ketamine takes a different approach: it blocks NMDA receptors, which triggers a cascade of effects that ultimately promote neuroplasticity—your brain's ability to form new neural connections and break out of entrenched patterns.

Here's how that process unfolds:

Stage 1: Releasing the brake. Ketamine blocks NMDA receptors on inhibitory brain cells, removing the "brake" that depression puts on neural activity.

Stage 2: Glutamate surge. With the brake removed, your brain releases glutamate—the primary neurotransmitter that gets neurons communicating and activating.

Stage 3: Growth factor release. The glutamate surge triggers production of Brain-Derived Neurotrophic Factor (BDNF). Think of BDNF as fertilizer for brain cells; it supports the growth and survival of neurons.

Stage 4: New connections form. Preclinical rodent studies and early human neuroimaging suggest that new synaptic connections can begin forming within hours. The exact timelines in humans are still being clarified, but the rapid clinical improvements people experience are consistent with fast-acting neuroplastic changes.

Neuroimaging research shows ketamine is associated with changes in connectivity within brain networks disrupted by depression, including the salience network (which helps you identify what matters) and reward-related circuits. Some preclinical studies suggest ketamine might also influence myelination, though evidence for meaningful effects in humans remains preliminary.

Ketamine vs SSRIs: Key Differences

How Ketamine Compares to ECT

Electroconvulsive therapy (ECT) has long been considered the gold standard for treatment-resistant depression. How does ketamine compare?

Recent meta-analyses generally find that ECT remains at least as effective—and in some analyses more effective—than ketamine in reducing depressive symptoms in the acute phase. However, ketamine may have faster onset, and the practical differences matter:

• Efficacy: ECT may have a slight edge in acute symptom reduction; long-term comparative data are still limited
• Onset: Ketamine often works faster (hours vs. days to weeks for ECT's full effect)
• Side effects: Ketamine causes transient dissociation and perceptual changes; ECT more commonly causes muscle soreness and cognitive effects
• Logistics: ECT requires clinic visits, anesthesia, and recovery time; ketamine can be administered at home

When ECT may still be preferred: Severe psychotic depression, certain inpatient situations, or when ketamine is contraindicated. Treatment choice should weigh efficacy, side effects, patient preference, and access.

Beyond Depression: Ketamine for Anxiety and PTSD

Depression commonly co-occurs with anxiety disorders, with some clinical samples reporting high comorbidity rates. Early research suggests ketamine can reduce anxiety symptoms in certain people, though this evidence is less extensive than for depression.

Emerging research also suggests potential benefits for PTSD and stress-related conditions. These applications remain under active investigation.

Why Therapeutic Support Matters

Current clinical practice and early studies support combining ketamine with psychotherapy. Ketamine opens a window of neuroplasticity when your brain is more capable of forming new patterns. Therapy helps you use that window intentionally.

Without therapeutic support, ketamine's effects tend to fade within days to a week. With preparation and integration sessions, you can work through the insights that emerge during treatment and translate them into lasting changes: new ways of responding to triggers, different thought patterns, healthier coping strategies.

The medication opens a door. Therapy helps you walk through it.

The Innerwell Approach

So what does this science look like in practice? And can you access it without rearranging your life around clinic visits?

Innerwell delivers at-home sublingual ketamine therapy paired with licensed psychotherapist support. This isn't ketamine dropped off with minimal supervision. It's a comprehensive program built around the understanding that the therapeutic relationship matters as much as the medicine.

Innerwell is different in a few key ways:

• Licensed clinicians, not unlicensed guides. Sessions are overseen by Master's or Doctoral-level licensed therapists with specialized training through partners such as Fluence Training.
• Structured protocols with symptom tracking. Your clinical team monitors your progress and adjusts your protocol based on how you're responding.
• Preparation and integration built in. Before each session, you'll set intentions with your therapist. Afterward, you'll process what came up and work on translating insights into daily life.
• At-home comfort. Treatment happens in your own space, reducing barriers for people who've struggled to access care.
• Insurance partnerships. For eligible patients with participating plans in California and New York, cost-sharing may start around $54 per session; exact costs depend on plan details.

People report a 69% reduction in depression symptoms and 60% reduction in anxiety symptoms after 10 weeks in internal tracking using standardized self-report scales. Approximately 87% see improvement within four weeks. These are preliminary program data and haven't been independently validated, but they're consistent with what published research suggests about ketamine's potential.

For many, those numbers translate to tangible changes: more energy to get through the day, better sleep, renewed ability to engage with work and relationships, and a quieter version of the constant background noise that depression creates.

Take our free assessment to see if ketamine therapy might be right for you.

Frequently Asked Questions

How long do ketamine's effects last?

Effects from a single session often last several days to about a week. Most protocols involve multiple sessions to build and sustain relief. With repeated treatments and therapeutic integration, many people maintain improvement for months, though durability varies. Learn more about how long effects last.

Is ketamine safe for long-term use?

Ketamine has a well-characterized short-term safety profile under medical supervision. Long-term safety with repeated psychiatric use is still being studied. Innerwell's approach includes ongoing monitoring and individualized maintenance plans. Contraindications include uncontrolled hypertension and history of psychosis. Learn what to expect.

What does ketamine therapy feel like?

Most people describe the experience as dreamlike or floating, with altered perceptions of time and space. Dissociative effects are typically transient and resolve within one to two hours, though intensity varies. Read more about the ketamine experience.

Is ketamine FDA-approved for depression?

Ketamine itself is FDA-approved as an anesthetic, not for depression specifically. Psychiatric use is off-label. Esketamine (Spravato), a related compound, has FDA approval for treatment-resistant depression when used with an oral antidepressant.

Is at-home ketamine as effective as IV infusions?

Direct head-to-head data comparing at-home sublingual ketamine to in-clinic IV infusions are limited. Early findings and Innerwell's internal outcomes suggest sublingual protocols can offer comparable symptom improvements for some people, especially when paired with robust therapeutic support. Compare the options.