Psychotic Depression (MDD with Psychotic Features)

Tovani does not treat this with ketamine

This page is here for honesty and completeness. Ketamine is not an appropriate treatment for Psychotic Depression, and in some cases it is contraindicated. Below is what the condition is and the treatments that genuinely help — and where, if at all, ketamine has any narrow role (usually only for a separate co-occurring depression). If you’re in crisis, call or text 988.

The short version

●Psychotic depression is a major depressive episode that includes psychotic features — delusions or hallucinations, often with guilt, worthlessness, illness, or punishment themes.
●It is more severe and higher-risk than non-psychotic depression, with a substantially elevated suicide risk, and it is frequently under-recognized.
●It is treated as a serious condition: the combination of an antidepressant plus an antipsychotic, or ECT, which is highly effective for psychotic depression.¹ ²
●Ketamine is not appropriate here: active psychosis is a standard contraindication to therapeutic ketamine, whose mechanism can worsen psychotic symptoms.³
●This needs prompt, often urgent, specialist psychiatric care — not an at-home program.
●Tovani does not treat psychotic depression. This page is here for honesty and to point you toward the right, effective care.

Clinical definition

Psychotic depression is a major depressive episode with psychotic features — delusions and/or hallucinations occurring during the episode. The psychotic content is often mood-congruent (themes of guilt, worthlessness, deserved punishment, nihilism, illness, or poverty), though it can be mood-incongruent. It represents a more severe form of depression, with greater functional impairment, higher relapse rates, and notably elevated suicide risk. It is frequently underdiagnosed because patients may not disclose psychotic symptoms. Accurate recognition matters because treatment differs from non-psychotic depression: it specifically requires targeting the psychosis as well as the mood.

How it differs from related conditions

vs. Major depressive disorder

Non-psychotic MDD lacks delusions or hallucinations; the presence of psychotic features marks a more severe subtype with different, more intensive treatment.

vs. Schizoaffective disorder

There, psychosis also occurs outside of mood episodes; in psychotic depression the psychosis is confined to the depressive episode.

vs. Postpartum psychosis

A separate peripartum psychotic emergency; both involve psychosis that makes ketamine inappropriate and requires urgent specialist care.

First-line treatments

Antidepressant + antipsychotic

The combination is first-line pharmacotherapy and more effective than either alone for psychotic depression.

ECT

Highly effective and often rapid for psychotic depression, particularly in severe or high-risk cases.

Urgent risk assessment

Given the elevated suicide risk, prompt safety assessment and often a higher level of care are essential.

Specialist psychiatric management

Diagnosis and treatment belong with psychiatry, with close follow-up and relapse prevention.

Evidence-based therapy guides

All therapy guides

When standard treatments fail

When psychotic depression does not respond to an optimized antidepressant-antipsychotic combination, ECT is a mainstay and is highly effective. Care remains within specialist psychiatry, with attention to safety, adherence, and relapse prevention. Rapid-acting glutamatergic agents such as ketamine are not part of this pathway — the psychotic component contraindicates them.

Where ketamine fits

Ketamine is not appropriate for psychotic depression. Active psychosis is a standard contraindication to therapeutic ketamine because its NMDA-antagonist mechanism can induce or worsen psychotic symptoms, and expert consensus specifically excludes active psychosis.³ Even though the underlying problem is depression, the presence of delusions or hallucinations rules ketamine out while psychotic features are present. The effective treatments — an antidepressant-antipsychotic combination and ECT — are well established, and ECT in particular works rapidly for this severe presentation. Care belongs with specialist psychiatry, not an at-home model.

Where this fits with Tovani

Tovani does not treat psychotic depression, and eligibility screening excludes active psychosis for safety. This is a severe, higher-risk condition that needs prompt specialist psychiatric care, where the combination of medication or ECT is genuinely effective. If you or someone you love has depression with delusions or hallucinations — or any thoughts of suicide — seek help promptly; in the US call or text 988, or go to an emergency room. This page exists to make the answer clear and point toward care that works.

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Frequently asked

Can ketamine treat psychotic depression?

No — it's not appropriate. Active psychosis is a standard contraindication to therapeutic ketamine because its mechanism can worsen delusions or hallucinations. Even though the core problem is depression, the psychotic features rule ketamine out. The effective treatments are an antidepressant-plus-antipsychotic combination and ECT.

What's the best treatment for psychotic depression?

The combination of an antidepressant and an antipsychotic is first-line and more effective than either alone, and ECT is highly effective — often rapidly — especially in severe or high-risk cases. Because suicide risk is elevated, prompt specialist care and safety assessment are essential.

Is psychotic depression an emergency?

It can be. It carries a substantially elevated suicide risk and is a severe condition needing prompt, often urgent, psychiatric care. If there are thoughts of suicide, get help immediately — in the US call or text 988 or go to an emergency room.

Does Tovani treat psychotic depression?

No. Active psychosis is screened out for safety, and psychotic depression needs specialist psychiatric care with medication or ECT — treatments that genuinely work. We say so plainly and point you toward that care rather than offer something inappropriate.

References

Rothschild AJ 2013, Schizophrenia Bulletin — Reviews the challenges and treatment of major depressive disorder with psychotic features. (PMID 23599251)
Mowafi W & Millard J 2021, BJPsych Bulletin — ECT is highly effective for severe depression and psychotic depression. (PMID 32513333)
Sanacora G et al. 2017, JAMA Psychiatry — Consensus statement identifying active psychosis as a contraindication to therapeutic ketamine. (PMID 28249076)

Last reviewed by Dr. Ben Soffer, DO on June 2, 2026. This page is educational and not a substitute for clinical evaluation. A physician determines whether ketamine therapy is appropriate for your specific situation.