Depression · Tel Aviv · Evidence-Informed Treatment

Ketamine Therapy for Depression in Tel Aviv

When antidepressants haven’t worked well enough, ketamine offers a different mechanism. Not a first-line treatment, not a miracle — but one option within a comprehensive plan, with psychotherapy at the center.

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When Antidepressants Aren’t Enough

Major depressive disorder is one of the most common psychiatric conditions, and for many patients, first-line treatments — psychotherapy and antidepressant medications (SSRIs, SNRIs) — produce meaningful improvement. However, approximately 30% of people with major depression do not achieve remission with standard antidepressants, even after adequate trials. This is sometimes called treatment-resistant depression (TRD).

Ketamine is not a first-line treatment for depression. First-line treatments have a stronger evidence base and work well for many patients. KAP is considered when these treatments have not produced adequate response — typically after two or more medications have been tried at therapeutic dose for a sufficient duration. It is one option within a broader treatment plan, not a replacement for standard care.

What “Treatment-Resistant” Means

“Treatment-resistant” does not mean treatment has failed or that nothing else can help. It means that standard first-line treatments have not produced sufficient improvement. It is a clinical signal that a different approach may be worth considering — whether that is a different medication class, augmentation strategies, brain-stimulation treatments like TMS, or ketamine-assisted psychotherapy.

Signs that may indicate treatment-resistant depression include:

•Persistent depressive symptoms despite two or more adequate antidepressant trials
•Partial response to medication without achieving remission
•Significant functional impairment despite ongoing treatment
•Recurrent depressive episodes that have not fully resolved

For a deeper discussion of treatment-resistant depression as a clinical concept, see our dedicated treatment-resistant depression guide.

Why Ketamine May Help When SSRIs Don’t

Most antidepressants work on the monoamine system — primarily serotonin and norepinephrine. Ketamine acts on a different system: glutamate, the brain’s primary excitatory neurotransmitter. This difference in mechanism may partly explain why ketamine can produce improvement in patients who have not responded to serotonin-targeting medications.

BDNF and Synaptogenesis

Preclinical studies suggest ketamine may influence brain-derived neurotrophic factor (BDNF) signaling and promote changes in synaptic density (synaptogenesis) in animal models. However, the direct relevance of these findings to clinical depression treatment in humans has not been established. The translation from animal research to human therapeutic outcomes is an ongoing area of investigation.

Default Mode Network

Some neuroimaging research suggests ketamine may modulate default mode network activity, which is often altered in depression — particularly the rumination and negative self-referential thinking that characterize the condition. The clinical significance of these observations is still being investigated, and the interpretation of neuroimaging findings in the context of therapeutic outcomes remains an open question.

Prediction Error

Some researchers have proposed that ketamine’s effects may relate to “prediction error” — the brain’s process of updating expectations when reality differs from prediction. This is a theoretical framework, not an established mechanism, and its relevance to clinical improvement in depression is speculative at this stage.

Honest framing: The mechanisms described here are hypothesized, not proven. What we know is that clinical studies have observed improvement in depressive symptoms in some patients receiving ketamine. Why this happens — and which patients will respond — is still being investigated. No mechanism described above should be understood as established fact.

What the Evidence Shows

The evidence base for ketamine in depression is more developed than for PTSD, but important questions remain.

Key Findings

•Meta-analyses — including Cochrane reviews such as Caddy et al., have generally found that ketamine is associated with rapid short-term improvement in depressive symptoms compared to placebo, with effects often observable within hours to days.
•Response rates — in clinical trials typically range from approximately 50–70% for initial response. However, response is not universal — a meaningful proportion of patients do not improve.
•Durability — is the key open question. The duration of benefit beyond the acute treatment period is less clear. Without maintenance treatment or ongoing psychotherapy, effects may diminish over days to weeks.

What We Do Not Yet Know

•The optimal number of sessions, dosing strategy, and maintenance protocol have not been established.
•Most controlled studies have examined ketamine infusion alone, not ketamine-assisted psychotherapy. The added benefit of combining ketamine with structured psychotherapy is an active area of research.
•Long-term safety data, particularly for repeated use, is still being collected.

For a detailed review of the research, see our ketamine research and evidence. For a comparison with other depression treatments, see ketamine vs TMS and antidepressants.

Summary: Evidence suggests ketamine can produce rapid short-term improvement in depression for some patients. What remains uncertain is how to sustain that improvement, which patients are most likely to benefit, and how KAP compares to ketamine alone. Treatment should be guided by clinical evaluation, not by the promise of rapid results alone.

How Fast Does Ketamine Work for Depression?

One of the most notable differences between ketamine and standard antidepressants is the potential speed of onset. While SSRIs and SNRIs typically require 4–6 weeks to reach full effect, ketamine’s effects — when they occur — can be observed within hours to days.

However, it is important to distinguish between rapid onset and sustained response. A rapid improvement in symptoms does not automatically mean a lasting one. The initial response may diminish over time without further treatment. This is why ongoing psychotherapy and, when clinically appropriate, follow-up sessions are part of the treatment approach — not as upselling, but because the evidence suggests that rapid ketamine effects alone are not reliably durable.

For a dedicated discussion of the speed question, see how fast does ketamine work?

The KAP Depression Protocol

When KAP is appropriate for depression, it follows a structured process. The integration sessions — not just the ketamine administration — are where much of the therapeutic work happens. Preparation and integration are not optional add-ons; they are the framework that gives the ketamine experience clinical meaning.

Psychiatric Evaluation

Comprehensive review of medical history, symptoms, prior treatment trials, and clinical suitability.

Preparation

Sessions to set therapeutic intentions, expectations, and prepare for the altered-state experience.

In-Home KAP Sessions

IM ketamine administered at home with full medical monitoring.

Integration

Integration sessions within 24–72 hours of each session — processing the experience.

Follow-up

Ongoing psychiatric follow-up and assessment of response over time.

How KAP Differs from Infusion-Only Clinics

Some clinics offer ketamine infusions as a medical procedure — you receive the medication and go home. There is no structured psychotherapy before or after. KAP, by contrast, is an integrated model: ketamine is used within a psychotherapy framework, with preparation and integration sessions that are as central to the treatment as the dosing itself. The question is not just “did the medication work?” but “what did the experience make available, and how can it be integrated into lasting change?”

For what each session involves, see what happens during a ketamine session.

The Role of Psychotherapy in KAP for Depression

In KAP for depression, psychotherapy is not an adjunct to ketamine — it is the framework that gives the experience clinical meaning. The question is not simply whether ketamine reduces symptoms temporarily, but whether the altered-state experience can be integrated into lasting change in the patterns of thinking, feeling, and relating that constitute depression.

What Integration Actually Involves

Integration sessions — typically within 24–72 hours after each KAP session — are where the therapeutic work is done. They involve:

Processing the experience — what emerged during the session: emotions, memories, insights, body sensations, or simply the felt sense of the experience.
Identifying themes — patterns that recur across sessions, which may point to underlying dynamics.
Connecting insights to daily life — how what emerged in the session relates to relationships, work, self-perception, and the structure of everyday life.
Building new patterns — using the period following a session, when some patients report feeling more open or flexible, to practice new ways of relating to oneself and others.

The “Neuroplastic Window” Hypothesis

Some researchers have proposed that ketamine may create a period of enhanced neural flexibility — sometimes called a “neuroplastic window” — during which the brain may be more receptive to new patterns of thought and behavior. The idea is that psychotherapy during this window may help consolidate changes that ketamine alone would not produce. This is a hypothesis, not an established fact. The clinical value of KAP may lie in this combination — but the mechanism by which it works, if it does, is still being investigated.

For more on the neuroplasticity concept, see our ketamine and neuroplasticity page.

Relapse Prevention and Maintenance

One of the most important — and honest — things to say about ketamine for depression is this: there is no universally accepted maintenance protocol. The field is still determining how best to sustain improvement after an initial response. What follows is a discussion of the approaches clinicians consider, not a prescription.

Approaches to Sustaining Response

Ongoing psychotherapy — continuing the therapeutic work that gives the ketamine experience meaning. Integration is not a one-time event; it continues as you process what emerges.
Continued psychiatric care — medication management, monitoring, and assessment of whether the current plan remains appropriate.
Follow-up sessions — some patients benefit from periodic KAP sessions, though the optimal frequency and total number is not established.
Lifestyle and social factors — sleep, movement, relationships, stress management, and meaning all affect long-term outcomes.

When Someone Responds but Later Loses Response

This is not uncommon, and it is not a failure. If an initial response diminishes, the clinical approach involves reassessment: Was the initial response complete or partial? Have life circumstances changed? Is there an ongoing stressor? Is the current treatment plan still optimal? Based on that reassessment, options may include adjusting the treatment plan, exploring whether additional KAP sessions are appropriate, or considering alternative approaches. The key is that losing an initial response is information — not a dead end.

Ketamine is not a miracle treatment. It does not work for everyone. When it does work, the improvement may be partial rather than complete. The duration of benefit is not yet well-established. And the field is still learning how best to use this tool. Honest treatment planning means holding both the genuine potential and the real limitations.

Medication Management During KAP

A common question is what happens to existing medications during KAP. The short answer: in most cases, current medications are continued, and KAP is integrated with — not substituted for — ongoing medication management.

What to Expect

Comprehensive medication review — the psychiatric evaluation includes all current medications, not just psychiatric ones. This is important because some medications and supplements can interact with ketamine.
Continuation in most cases — existing antidepressants are typically continued during KAP. Stopping medications abruptly is not recommended and is not part of the KAP process.
Adjustments, if needed — in some cases, the evaluation may suggest medication adjustments. These are made collaboratively, gradually, and based on your full clinical picture — not unilaterally.
Coordination with prescribers — if another physician prescribes your medications, care is coordinated to ensure consistency.

Do not stop or change medications on your own. Abruptly discontinuing antidepressants can cause withdrawal symptoms and destabilize your condition. Any medication changes are made under medical supervision, as part of a coordinated treatment plan.

For safety considerations including medication interactions, see our ketamine safety guide.

Who Is Typically Considered

Candidacy is assessed individually. Factors typically considered include:

Major depression that has not responded adequately to two or more antidepressant trials at therapeutic dose for sufficient duration
Chronic depressive symptoms with significant functional impairment
Trauma-related depression (in which case, stabilization considerations also apply — see our PTSD page)
Suicidal ideation in an appropriate clinical context (KAP may be considered, but acute crisis management takes priority)
Absence of contraindications — see safety considerations

For a broader candidacy discussion, including conditions that require careful evaluation, see our full candidacy guide. Treatment costs are described on our pricing page.

Frequently Asked Questions

Is ketamine addictive?⌄

Ketamine has a potential for misuse and is classified as a controlled substance in many jurisdictions. When used in a structured clinical setting — at therapeutic doses, with medical supervision, and within a treatment plan — the risk of misuse is different from recreational use. However, this is why treatment is medically supervised, and why a history of substance use is assessed during evaluation.

How long do the effects last?⌄

The duration of benefit is not well-established. Some patients experience improvement lasting days to weeks after a session; for others, effects diminish sooner. Sustaining improvement typically involves ongoing psychotherapy and, when clinically appropriate, follow-up sessions. There is no standard answer — it is assessed individually.

Do I still need my antidepressants?⌄

This is determined individually during the psychiatric evaluation. Some patients continue their current medications; in some cases, adjustments are made. Do not stop or change medications on your own. Medication decisions are made collaboratively, based on your full clinical picture.

What about TMS or other options?⌄

Ketamine is one of several options for treatment-resistant depression. Transcranial magnetic stimulation (TMS), medication augmentation, and psychotherapy are also options. Each has its own evidence base, benefits, and limitations. For a comparison, see our ketamine vs TMS page. The choice depends on your individual circumstances and should be discussed with a clinician.

What if I don’t respond?⌄

Not everyone responds to ketamine, and this is not a failure — it is clinical information. If KAP does not produce meaningful improvement, other options will be discussed, including alternative treatments or revisiting the diagnosis. A non-response helps clarify which direction may be more appropriate.

What happens during a KAP session for depression?⌄

A KAP session involves receiving ketamine (IM, administered by the physician) in a safe, comfortable setting — typically at home for appropriate patients. You are monitored throughout. The experience varies: some patients report altered perception, emotional shifts, or a sense of distance from usual thought patterns; others have a quieter experience. The session lasts approximately 1.5–2 hours, with the physician present. For a detailed walkthrough, see our what happens during a ketamine session guide.

Can I continue working during KAP treatment?⌄

KAP sessions require the rest of the day — you should not work, drive, or make important decisions on the day of a session. Between sessions, most patients continue their normal activities, though some find that the integration process benefits from some additional space and self-care. This is discussed during treatment planning based on your individual circumstances.

About Dr. Rosenbach

Dr. (Andrew) Dror Rosenbach completed his medical training in the United States and holds board certification in psychiatry. He practices in Tel Aviv and serves both English- and Hebrew-speaking patients, with over 20 years of clinical experience.