Is Ketamine Therapy Safe? Common Concerns Answered

You've done the research on antidepressants, tried therapy, maybe explored multiple medications without finding relief. Now you're reading about ketamine, and the questions are piling up. Is it actually safe? Will you lose control during treatment? Could you become dependent?

These concerns make sense. You've probably been burned before by treatments that promised more than they delivered. The idea of "psychedelic therapy" might feel like a leap into the unknown.

In clinical trials of low-dose ketamine for treatment-resistant depression, 50–70% of people respond, achieving at least a 50% reduction in symptoms. For people who haven't found relief through conventional treatments, those numbers represent real hope.

The bottom line: Ketamine therapy has a favorable safety profile when administered with proper medical oversight. Side effects are temporary, usually resolving within 90 minutes to a few hours. Safety depends on both the medication's properties and the quality of screening, supervision, and therapeutic support.

What Is Ketamine Therapy?

Ketamine therapy uses sub-anesthetic doses of ketamine to treat depression, anxiety, and other mental health conditions. These doses are far lower than surgical applications.

Originally developed as an anesthetic, ketamine gained psychiatric interest after researchers discovered its rapid antidepressant effects. Improvements can appear within hours rather than the 4–6 weeks traditional antidepressants require.

Clinicians prescribe ketamine for depression and anxiety off-label. The FDA has approved ketamine as an anesthetic and esketamine (Spravato) for treatment-resistant depression in adults, but racemic ketamine for psychiatric conditions is prescribed off-label.

Ketamine therapy takes several forms: FDA-approved esketamine nasal spray administered in certified clinics, off-label IV ketamine at specialized facilities, and sublingual tablets with telehealth supervision.

Professional medical guidelines position ketamine as an option for people with treatment-resistant depression, not a first-line approach. VA and DoD guidelines recommend ketamine or esketamine as an augmentation option for adults whose depression hasn't responded to adequate medication trials.

How Does Ketamine Work for Depression?

Ketamine operates through a fundamentally different mechanism than traditional antidepressants. While SSRIs and SNRIs adjust serotonin levels gradually over weeks, ketamine works much faster.

Animal and human studies indicate ketamine's effects stem from a cascade of brain changes. Researchers continue mapping the exact pathways, but here's what the current science shows:

Stage 1: Releasing the brake. Ketamine blocks NMDA receptors on certain inhibitory brain cells, removing the "brake" that depression appears to place on neurons.

Stage 2: The glutamate surge. With the brake lifted, your brain releases glutamate, the primary chemical signal that activates neurons and promotes communication between brain cells.

Stage 3: Growth factor release. The glutamate surge triggers a cascade of cellular events. Brain cells begin forming new connections, a process called synaptogenesis. Ketamine also activates BDNF (brain-derived neurotrophic factor), which acts like fertilizer for brain cells. BDNF helps neurons grow, survive, and form connections that support improved mood.

Stage 4: New connections form. These new neural pathways can help bypass the damaged circuits that depression has created. Markers of neuroplasticity appear to remain elevated for several days after a single ketamine dose in many studies.

The rapid synaptic remodeling explains why ketamine can provide relief when months of SSRIs haven't. New connections form within hours.

What Are the Short-Term Side Effects?

Understanding ketamine's side effects helps you know what to expect. Most are temporary and resolve quickly.

Common Side Effects

Dissociation, the feeling disconnected from your body, occurs in about 28% of people and typically resolves within two hours. Many find it therapeutically valuable because it creates distance from entrenched thought patterns.

Physical symptoms like headache, dizziness, and nausea affect roughly one in four people. These usually resolve within 24 hours.

Blood pressure elevation occurs temporarily during treatment. Providers monitor vital signs throughout, and levels return to baseline within hours. Cardiovascular screening before treatment matters for this reason.

What Does Improvement Actually Look Like?

Clinical trials measure symptom reduction on standardized scales. But what does a 50–70% response rate feel like in daily life?

Within hours or days, many people notice shifts that feel almost unfamiliar after months or years of depression. The intrusive thoughts quiet down. Tasks that felt insurmountable start feeling possible again: answering an email, taking a shower, calling a friend.

For some, the change is dramatic. For others, it's subtle at first. You realize you laughed at something, or you didn't dread waking up this morning.

Many people describe it as finally having access to parts of themselves that depression had locked away. The motivation that used to come naturally starts returning. Planning for the future feels possible instead of pointless. Small pleasures register again: a good meal, a conversation with a friend.

Mayo Clinic reports symptom relief can last weeks after treatment.

What Are the Long-Term Risks?

Ketamine therapy is not right for everyone, and long-term data are still emerging. Here's what we know and what remains uncertain.

What the Evidence Shows

In pooled clinical trial data, fewer than 5% of people discontinue due to adverse effects. Some reviews cite rates below 1%. In therapeutic settings at sub-anesthetic doses, serious complications remain uncommon.

In long-term studies of intranasal esketamine for treatment-resistant depression, follow-up extending to about 4.5 years has not revealed new major safety signals under monitored clinical use.

What Remains Under Study

Most long-term safety data come from intranasal esketamine programs in monitored clinic settings. Caution is still warranted when generalizing to all ketamine protocols.

Bladder and urinary concerns have been documented in chronic, high-dose recreational ketamine users, not in therapeutic protocols. Medical dosing is far lower and less frequent than patterns associated with these complications.

Cognitive effects have not been consistently observed in therapeutic use. Some studies suggest ketamine may actually improve cognitive function as depression lifts.

Is Ketamine Addictive?

In properly supervised medical settings, addiction risk is low. A systematic review found no documented cases of ketamine dependence originating in clinical treatment programs, though long-term data remain limited.

The key protective factors: sub-anesthetic dosing, spaced treatments (not daily use), medical oversight, limited medication supply, and integration with therapy. The therapeutic approach differs fundamentally from recreational use patterns.

Who Should Not Receive Ketamine?

Ketamine therapy requires careful screening. Not everyone is a candidate.

Do not use ketamine if you have:

• Cardiovascular conditions with weakened blood vessels (aneurysms, brain hemorrhage)
• Active psychotic disorders with current hallucinations or delusions
• Pregnancy
• Current use of MAO inhibitors

Relative contraindications require careful evaluation:

• Uncontrolled high blood pressure (must be managed first)
• Severe heart disease (requires cardiovascular evaluation)
• Active substance use disorder
• History of psychosis (even if not currently active)

Before starting treatment, you'll receive comprehensive screening that assesses cardiovascular health, psychiatric history, medication interactions, and contraindications.

How Does Ketamine Compare to Other Treatments for Safety?

Ketamine vs. SSRIs

Ketamine's common side effects are typically short-lived around each dosing session. SSRIs often cause side effects (such as sexual dysfunction or weight changes) that can persist for as long as treatment continues.

Ketamine has not been associated with the chronic sexual dysfunction, weight gain, or emotional blunting commonly seen with many SSRIs. Unlike SSRIs, ketamine doesn't cause a classic antidepressant discontinuation syndrome between supervised treatments, though you can still experience symptom return between doses.

SSRIs have decades of long-term safety data, while ketamine data extends to about 4.5 years. Available clinical data and expert reviews indicate that ketamine is generally safe to use alongside many SSRIs under medical supervision, though careful monitoring is still recommended.

Ketamine vs. ECT

In a large randomized trial comparing ketamine with ECT for treatment-resistant depression, ketamine showed comparable response rates (55% vs. 41%) with a different side-effect profile. ECT requires anesthesia and can cause memory effects. Ketamine's effects are typically temporary and don't require general anesthesia.

Is At-Home Ketamine Therapy Safe?

The FDA has raised concerns about compounded ketamine products used without adequate medical supervision. These warnings target services with minimal oversight, not all at-home treatment.

Supervision quality matters more than location.

A large prospective study found telehealth-supported sublingual ketamine to be safe and effective, with low adverse event rates. Response and remission rates were consistent with clinic-administered ketamine. Safety depends critically on telehealth supervision quality, emergency protocols, proper screening, and trained support person presence. Direct head-to-head safety comparisons between settings are still limited.

Why Does the Therapeutic Approach Matter?

Expert consensus and early data suggest ketamine therapy works best when embedded in a comprehensive care plan that includes psychotherapy and follow-up support. The medication opens a door. Therapy helps you walk through it.

Integration sessions help you process the experiences and insights that emerge during treatment. A skilled mental health professional helps you connect what you felt during ketamine sessions to patterns in your daily life.

The combination matters because ketamine creates a window of neuroplasticity. During this window, your brain becomes more adaptable. Old thought patterns become easier to interrupt. New responses to stress, new ways of relating to yourself and others, become possible in ways they weren't before. Therapy helps direct that adaptability toward meaningful growth.

At-Home Ketamine Therapy with Innerwell

What does treatment actually look like? And can you access effective care 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. The program operates with real-time telehealth supervision and comprehensive clinical oversight, addressing the concerns the FDA has raised about inadequately supervised at-home treatment.

Innerwell's safety protocols include:

• Comprehensive screening before treatment begins: cardiovascular evaluation, psychiatric history review, medication interaction check, and contraindication assessment.
• Licensed clinicians overseeing every session. Master's or Doctoral-level therapists with specialized training through partnerships like Fluence Training.
• Real-time telehealth monitoring. Clinicians are present via video during your session, monitoring for adverse reactions and providing support.
• Required support person. A trusted adult must be present during and after treatment.
• Therapeutic support built in. Preparation and integration sessions help translate insights into lasting improvement.
• Accessible pricing. Treatment costs as low as $54/session with insurance.

In Innerwell's program data, people report a 69% reduction in depression symptoms and a 60% reduction in anxiety symptoms after 10 weeks, with 87% reporting improvement within four weeks and an average satisfaction rating of 4.7/5 stars.

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

The Bottom Line

Ketamine therapy has accumulated substantial safety evidence over more than a decade of clinical research. Side effects are typically temporary, serious complications are rare with proper oversight, and long-term data show no new major safety signals.

Treatment safety depends on both ketamine's pharmacology and the quality of screening, dosing, and supervision. Proper medical oversight and therapeutic integration determine outcomes.

Frequently Asked Questions

Will I feel out of control during ketamine treatment?

No. While about 28% of people experience dissociation—feeling temporarily disconnected from your body—you remain aware throughout and effects resolve within two hours. Clinicians can adjust dosing to manage intensity. Most describe the experience as unusual but manageable, not frightening.

Can I drive after ketamine therapy?

No. You should not drive or operate heavy machinery for at least 24 hours after treatment. Arrange transportation in advance and have your support person available to help if needed.

Can I drink alcohol or take benzodiazepines with ketamine?

You should avoid alcohol for 24 hours before and after treatment. Benzodiazepines can affect the ketamine experience and may reduce therapeutic benefit. Discuss all medications with your clinician during screening.

How often is ketamine treatment safe?

Initial treatment typically involves sessions 2–3 times per week for several weeks, then transitions to maintenance as needed. The spaced, limited dosing in therapeutic protocols differs significantly from patterns associated with recreational misuse.

What happens if I have an adverse reaction during treatment?

With Innerwell, a licensed clinician monitors your session via telehealth and can intervene immediately. You'll also have a trained support person physically present. Emergency protocols are in place, and your clinician can adjust dosing or discontinue treatment if needed.

How does ketamine compare to traditional antidepressants for safety?

Ketamine's common side effects are typically short-lived around each dosing session, while SSRI side effects can persist throughout treatment. SSRIs have longer safety track records (decades vs. about 4.5 years for ketamine), but available ketamine data shows no major safety signals under medical supervision.