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You've tried two, maybe three antidepressants. Each time, you waited weeks hoping this one would finally work. Now you're researching ketamine-based treatments and running into confusing terminology: Spravato, esketamine, IV ketamine, sublingual ketamine. Which one actually makes sense for your situation?

About one-third of people with major depression don't respond to standard medications. If you're among them, understanding the differences between these options matters.

Your choice comes down to three factors: insurance coverage, time commitment, and how quickly you need relief. Spravato requires clinic visits but is often covered by insurance. IV ketamine works faster but costs $400–800 per session out-of-pocket. At-home sublingual ketamine through providers like Innerwell offers convenience with integrated therapeutic support, starting at $54 per session with insurance.

Spravato is the brand name for esketamine, an FDA-approved nasal spray for treatment-resistant depression. The FDA approved it on March 5, 2019. It was the first NMDA receptor antagonist authorized specifically for depression treatment.

Spravato has two approved uses: treatment-resistant depression in adults (typically defined as not responding to at least two adequate antidepressant trials) who may take it as monotherapy or with an oral antidepressant, and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior, in conjunction with an oral antidepressant.

Because of its potential for misuse, Spravato carries Schedule III classification. You can only receive it at certified healthcare facilities enrolled in the federal REMS program. You cannot take it at home.

Ketamine is an FDA-approved anesthetic that doctors prescribe off-label for depression. Research shows response rates of 50–70% in treatment-resistant depression following a single low-dose IV infusion, with symptom relief occurring as early as two hours.

Intravenous (IV) infusion delivers ketamine directly into your bloodstream. The standard protocol involves 0.5 mg/kg infusion over 40 minutes, typically six infusions over two to three weeks. IV infusion has the most extensive research support.

Sublingual/oral administration involves dissolving ketamine under your tongue. Your liver metabolizes much of the medication before it reaches your bloodstream, so higher doses are needed compared to IV administration. Sublingual ketamine is used primarily for maintenance or home-based protocols through telehealth providers.

Both Spravato and ketamine target NMDA receptors and glutamate signaling in the brain. Traditional antidepressants work on serotonin, norepinephrine, or dopamine and typically take four to six weeks to show effects. Ketamine-based treatments work through a fundamentally different mechanism.

The chemical distinction matters. Spravato contains only esketamine (the S-enantiomer), while IV ketamine is racemic, containing equal parts of both S-ketamine and R-ketamine molecules. Preclinical research suggests the R-ketamine component may contribute to longer-lasting effects with fewer dissociative side effects, though human evidence is still emerging.

Both medications promote neuroplasticity, your brain's ability to form new neural connections. The neuroplasticity window creates an opportunity where your brain becomes more capable of breaking entrenched patterns that depression reinforces. The medication opens a door; therapy helps you walk through it.

Why does speed matter? According to the McLean study, the first head-to-head comparison, IV ketamine showed improvement immediately after the first treatment, while Spravato showed significant improvement after the second treatment. When you've been experiencing symptoms for months or years, even a few days matters.

Spravato requires the highest ongoing commitment: eight clinic visits during the first month, each lasting 1.5–3 hours including mandatory observation. In one long-term continuation study, about 76% of patients who responded to esketamine remained in maintenance treatment for two years or longer, with depressive symptoms generally staying improved.

IV ketamine involves fewer initial sessions (typically six infusions over two to three weeks) with maintenance frequency varying based on individual response, often monthly.

At-home ketamine eliminates travel time entirely. Treatment happens in your own space. Unlike Spravato's two-hour observation requirement, at-home protocols involve telehealth check-ins rather than in-person monitoring.

Both Spravato and ketamine share similar side effects because they work through the same mechanism:

Dissociation (feeling temporarily detached from your surroundings) occurs during treatment and typically resolves within the observation period, though experiences can vary. Your blood pressure will be checked before and after each session, as both treatments cause temporary increases.

Contraindications include aneurysmal vascular disease, history of intracerebral hemorrhage, and hypersensitivity to ketamine or esketamine. Pregnancy carries a major warning due to embryo-fetal toxicity risk, with recommendations to avoid use. Review the full prescribing information with your provider before starting treatment.

Depression distorts your sense of what's possible. So what should you watch for once treatment begins?

People often notice changes before their mood fully lifts. The first shift is frequently described as the "heavy blanket" sensation easing: that crushing weight that makes getting out of bed feel impossible. Many report being able to imagine a positive future for the first time in months, even if they don't feel happy yet.

Energy and motivation often improve before emotional symptoms resolve. You might find yourself doing small tasks you'd been avoiding, not because you feel better, but because the paralysis has loosened. Sleep improvements frequently occur early in treatment, and better sleep creates a foundation for other gains.

The dissociation you experience during treatment is temporary and distinct from improvement; it's part of the process, not the result. Most people see meaningful improvement within four to six sessions, though some notice changes after their very first treatment.

Your insurance covers it and you can commit to eight clinic visits over the first month, then ongoing visits potentially for two or more years

You value FDA approval and standardized safety protocols

You're willing to continue taking an oral antidepressant alongside Spravato

The time commitment is substantial. If eight clinic visits in the first month feels unsustainable, completion rates may suffer.

You need immediate symptom relief after your first treatment

You're paying out-of-pocket regardless of treatment choice

Your area has established ketamine infusion clinics

Costs add up quickly. Six initial infusions at $400–800 each means $2,400–$4,800 before maintenance begins.

Clinic visits create significant barriers (work schedules, childcare, distance)

You want therapeutic support integrated into treatment

You value the privacy and comfort of your own space

Watch for: Any program that skips mental health follow-up, promises permanent cures, or lacks proper supervision isn't prioritizing your safety.

What does treatment actually look like? And can you access it without rearranging your life around clinic visits?

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

Phase 1: Evaluation. A virtual psychiatric assessment by licensed providers (Master's or Doctoral level) determines whether ketamine is right for you, reviews your medical history and current medications, and creates a personalized protocol.

Phase 2: Delivery. Sublingual ketamine tablets ship securely to your door with dosing instructions and direct clinician access through secure messaging.

Phase 3: Preparation and integration. Before your first session, you'll work with a licensed psychotherapist who helps you prepare, set intentions, and understand what to expect. After each session, integration therapy helps you process insights and apply them to lasting change.

Phase 4: Ongoing monitoring. Your care team tracks progress continuously, adjusting protocols based on your response. Regular check-ins and secure messaging keep you connected to clinical support.

Evidence suggests ketamine therapy produces better outcomes when combined with psychotherapy. The medication creates a window of neuroplasticity: a period when your brain is more receptive to change. Without therapeutic guidance, that window may close before meaningful patterns shift.

In Innerwell's internal outcomes tracking, people report a 69% reduction in depression symptoms and 60% reduction in anxiety symptoms after 10 weeks. 87% see improvement within four weeks. Average satisfaction ratings reach 4.7 out of 5.

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

Spravato offers FDA approval and insurance coverage but demands significant clinic time: eight visits in the first month alone. IV ketamine may work faster but costs $400–800 per session out-of-pocket. At-home ketamine through Innerwell combines convenience with integrated therapeutic support that clinic-based treatments often lack.

There's no universally "best" option. The right treatment is the one you can actually access, afford, and sustain long enough to see results. If you've been stuck in the antidepressant trial-and-error cycle, ketamine-based treatments offer a fundamentally different approach.

Ready to find out if you're a candidate? Take the free assessment to connect with Innerwell's clinical team.

What does dissociation during ketamine treatment feel like?

Dissociation involves temporary feelings of detachment from your body or surroundings. Things may look or sound different; time may seem to move faster or slower. Effects typically peak within 40 minutes and resolve within 1.5–3 hours. Most people describe the experience as tolerable, especially knowing it's temporary. Learn more about what ketamine feels like.

How long will I need to continue ketamine treatment?

Treatment duration varies significantly. After a single ketamine infusion, effects typically last 3–7 days; repeated infusions extend benefit to 18–19 days. Most people need ongoing maintenance, though frequency decreases over time. Your care team will help determine the right schedule based on your symptom patterns. Read more about treatment duration.

Is at-home ketamine as effective as clinic-based treatment?

At-home sublingual ketamine has less peer-reviewed research than IV ketamine or Spravato. However, the therapeutic support integrated into at-home programs may improve outcomes; several studies suggest ketamine works best when combined with psychotherapy. The convenience also improves adherence: you're more likely to complete treatment you can fit into your life.

Will my employer or insurance company find out I'm using ketamine?

Spravato treatment appears on insurance claims. IV ketamine paid out-of-pocket creates no insurance record. HIPAA generally prevents health plans and providers from sharing your protected health information with employers without your authorization, except in limited, legally defined situations. If privacy concerns you, discuss payment options with your provider before starting treatment. Check state regulations for specific rules.

Compare Spravato vs ketamine for depression: efficacy, cost, access, and which option fits your life. At-home ketamine starts at $54/session.

Spravato vs Ketamine: Comparing Depression Treatments

Introduction

What Is Spravato?

What Is Ketamine for Depression?

How Do They Work Differently?

Comparing Your Options

How Do Access, Cost, and Risks Compare?

What Improvement Actually Looks Like

Which Is Right for You?

How Innerwell's Approach Works

Making Your Decision

Spravato vs Ketamine: Choosing the Best Depression Relief

The suspicious thoughts won't stop. Your loved one refuses to leave the house, convinced people are watching. Or maybe you're the one struggling to trust anyone, to feel safe in your own home. If you've tried standard treatments without relief, you're probably searching for alternatives.

Ketamine can help depression when nothing else works, and for good reason. Research shows it provides rapid relief when standard medications fail. But this doesn't apply to paranoia. The drug's mechanism actually worsens psychotic symptoms rather than helping them.

Here's what you need to know upfront: Ketamine therapy is not recommended for people experiencing paranoia or psychotic symptoms.

This guide explains why ketamine is inappropriate for paranoia, documents the specific safety risks from clinical research, and identifies evidence-based treatments that actually work. If you're caring for someone with paranoia, this article also addresses how Innerwell can support your own mental health as a caregiver.

Paranoia involves persistent, unfounded beliefs that others intend harm. It exists on a spectrum, from mild suspicious thoughts to severe delusional beliefs that disconnect a person from reality.

A substantial minority of the general public report experiencing some paranoid thoughts. The lifetime prevalence of persecutory delusions is estimated at around 5%. Paranoia ranges from common everyday suspiciousness to clinical conditions requiring psychiatric care.

Belief that people are plotting or conspiring

Difficulty confiding in others due to fear of betrayal

Reading threatening meanings into benign events

In severe cases, fixed delusional beliefs

Paranoia appears across multiple conditions. Recent research suggests paranoia is common among people with schizophrenia, though precise prevalence varies. Paranoid symptoms also occur in dementia, with delusions reported in around 10–12% of Alzheimer's patients.

Depression and anxiety frequently co-occur with paranoia. A 2023 meta-analysis found 60% combined prevalence of anxiety and mood disorders in people at clinical high risk for psychosis. The high rate of comorbid mood symptoms creates a clinical challenge we'll address later.

Why Is Ketamine NOT Recommended for Paranoia?

Ketamine poses genuine risks for people with paranoid symptoms. The concern isn't theoretical. It's based on how ketamine affects the brain and documented adverse outcomes.

Ketamine is classified as a dissociative anesthetic because it induces altered states of consciousness. At therapeutic doses, it can cause hallucinations, perceptual disturbances, and breaks from reality.

For someone already experiencing paranoid thoughts, introducing ketamine creates unacceptable risk. 1997 research found ketamine caused "exacerbation of core psychotic and cognitive symptoms in schizophrenia." The drug worsened both hallucinations and delusions. No clinical trials have studied ketamine for paranoia treatment, and patients with paranoid features are excluded from existing studies due to safety concerns.

Ketamine works by blocking NMDA receptors, brain switches that control learning and memory. In depression, this process may help repair damaged connections through neuroplasticity. But in people with paranoia, the same mechanism destabilizes circuits that help process reality.

Here's the problem: The "glutamate hypothesis of schizophrenia" proposes that NMDA receptor dysfunction causes psychotic symptoms. 2016 research confirms NMDA receptor hypofunction is believed to underlie schizophrenic psychosis. Ketamine blocks these same receptors. While this mechanism may help reset circuits involved in depression, it paradoxically destabilizes circuits that generate paranoia and other psychotic symptoms.

A 2020 review found ketamine induces schizophrenia-like symptoms with large effect sizes in healthy participants. Scientists use ketamine as a research model to understand how psychotic states develop. They use it to study psychosis, not treat it.

Published case reports reveal what happens when ketamine reaches vulnerable patients. A 2024 case report documented a 55-year-old with treatment-resistant depression on antipsychotic medication who developed acute psychotic symptoms 48 hours after esketamine administration. Another case documented prolonged psychosis with delusions and hallucinations following ketamine for pain control.

Major safety concern: Psychotic symptoms can emerge after ketamine treatment, sometimes 48 hours later despite concurrent antipsychotic medication. These symptoms can be prolonged and severe, requiring emergency psychiatric intervention.

What Treatments Actually Work for Paranoia?

For schizophrenia-related paranoia, standard antipsychotic medications help approximately two-thirds of patients. Treatment effectiveness varies by underlying condition.

Antipsychotic medications remain first-line treatment. Both first-generation (like haloperidol) and second-generation (like risperidone) antipsychotics are recommended by the American Psychiatric Association. However, approximately one-third of patients with schizophrenia are classified as treatment-resistant, characterized by persistent symptoms despite two or more medication trials at adequate doses.

While paranoid symptoms may improve with medication, negative and cognitive symptoms often show limited response. Individual response varies considerably.

For those who don't respond to initial treatments, several evidence-based alternatives exist:

Clozapine is specifically recommended by the APA for treatment-resistant schizophrenia. Research finds that 30–40% of treatment-resistant patients respond to clozapine. It requires regular blood monitoring but helps many who haven't responded to other medications.

Long-acting injectable antipsychotics improve medication consistency and significantly reduce relapse risk compared to daily pills.

Cognitive behavioral therapy for psychosis (CBTp) is strongly recommended by WHO and NICE guidelines for all adults with psychotic disorders. It helps patients examine beliefs, develop coping strategies, and reduce symptom-related distress.

Even when medications don't fully eliminate paranoid delusions, they often reduce intensity and distress.

Additional resources include NAMI (National Alliance on Mental Illness) at nami.org and the SAMHSA National Helpline at 1-800-662-4357.

What Conditions Can Ketamine Therapy Help With?

While ketamine isn't appropriate for paranoia, it works remarkably well for other treatment-resistant mental health conditions.

Ketamine therapy has shown strong results for:

Treatment-resistant depression: Response rates exceed 50%, with effects beginning within hours rather than weeks

Anxiety disorders: Ketamine targets different brain pathways than traditional medications

PTSD: Helps process traumatic memories when other treatments haven't worked

Borderline personality disorder: Supports emotional regulation and stability

If you have one of these conditions without paranoid symptoms and haven't found relief through standard care, ketamine therapy might offer the breakthrough you've been searching for.

Learn more about whether ketamine is right for you.

How Can Innerwell Support Your Mental Health Journey?

Innerwell provides at-home ketamine therapy for conditions where it's proven safe and effective, including treatment-resistant depression, anxiety disorders, and borderline personality disorder. Every potential patient undergoes comprehensive psychiatric evaluation to ensure safety and appropriateness.

Innerwell's eligibility criteria explicitly exclude patients with psychosis or psychotic disorders from ketamine treatment. This isn't a limitation; it's a commitment to your safety.

If you have a psychotic disorder, Innerwell still offers traditional psychiatry and therapy services that include:

Medication management with qualified psychiatric providers

Individual psychotherapy using evidence-based approaches

Ongoing clinical support through a secure patient portal

For caregivers: If you're caring for someone with paranoia and experiencing treatment-resistant depression or anxiety yourself (without psychotic symptoms), Innerwell's at-home therapy program may help you maintain the resilience you need. Treatment delivered to your home fits around caregiving responsibilities.

Take our free assessment to connect with Innerwell's clinical team about the right treatment path for your situation.

Frequently Asked Questions About Ketamine and Paranoia

Why isn't ketamine recommended for paranoia?

Ketamine blocks NMDA receptors, creating a brain state that mirrors the glutamate hypothesis of schizophrenia. Research shows it causes "exacerbation of core psychotic and cognitive symptoms" rather than improvement. No clinical trial evidence supports its use for paranoid conditions.

Why does ketamine help depression but worsen paranoia?

Depression and psychotic disorders involve different brain chemistry. Ketamine's NMDA blocking mechanism helps depression by promoting new neural connections. However, psychotic disorders involve dysregulated NMDA function where blocking these receptors worsens rather than improves symptoms.

What if my paranoia is mild or only occasional?

Even a history of paranoid thoughts should be disclosed to Innerwell's clinical team before considering ketamine. Full disclosure of any psychiatric history is essential for determining eligibility and ensuring your safety.

What should I try if standard treatments aren't working for paranoia?

Evidence-based alternatives include clozapine for treatment-resistant schizophrenia, CBTp, long-acting injectable antipsychotics, and comprehensive psychosocial services including family therapy and case management. Innerwell's psychiatric team can help you explore which options fit your situation.

Does Innerwell screen for paranoia before treatment?

Yes. All patients undergo comprehensive psychiatric evaluation. Patients with active psychosis or psychotic disorders are explicitly excluded from ketamine treatment eligibility.

 Ketamine therapy isn't suitable for paranoia. Learn why, what the risks are, and which evidence-based treatments actually work.

Ketamine Therapy for Paranoia: What You Need to Know

What Is Paranoia?

It's 3am again. You've tried Ambien, then Lunesta, then trazodone. You've done the sleep hygiene, the CBT-I, the meditation apps. Your doctor says you've "tried everything."

You're not alone. About 60% of people who try CBT-I don't achieve complete remission, and roughly 11-58% of patients have persistent symptoms despite available treatments. So you lie awake scrolling through Reddit threads about ketamine for insomnia, wondering if this could finally help.

Here's what the research actually shows: No clinical trials have tested ketamine as a primary treatment for insomnia. The Reddit threads reflect a growing disconnect between online marketing and medical evidence.

Ketamine has shown promise for sleep symptoms among people with treatment-resistant depression. For those whose insomnia stems from underlying mood disorders, ketamine may offer relief by treating the root cause. All documented sleep improvements occurred in patients being treated for depression—not insomnia alone.

Ketamine isn't a sleep medication, but it may help insomnia driven by depression or anxiety. Learn about the research, risks, and Innerwell's approach.

Therapy

Spravato vs Ketamine: Choosing the Best Depression Relief

Ketamine Therapy for Paranoia: What You Need to Know

Ketamine Therapy for Insomnia: Complete Guide

Ketamine Therapy Dosage Guide

How Ketamine Affects the Brain: Understanding the Science

Ketamine Therapy for Grief: Science, Safety & Hope

Ketamine Therapy for OCD: Complete Guide