Rapid antidepressant effect of S-ketamine in schizophrenia

Post-psychotic depression (ICD-10: F20.4) is described as a common but often neglected complication of schizophrenia, affecting up to 36% of patients and carrying substantial clinical need for new treatment options. Earlier research has repeatedly documented rapid antidepressant and anti‑suicidal effects of ketamine in unipolar and bipolar depression, and some studies reported benefit in depressed patients with a history of psychotic symptoms. Despite this, ketamine has been largely avoided in primary psychotic disorders because of a theoretical risk of provoking dissociative or psychotic symptoms, leaving its clinical effects in schizophrenia poorly characterised. This paper reports a single case intended to document the feasibility, tolerability and clinical outcome of intravenous S‑ketamine augmentation in a patient with schizophrenia who developed a severe post‑psychotic depression with suicidal ideation. The authors aim to show whether S‑ketamine can produce rapid antidepressant and anti‑suicidal effects in this diagnostic context without provoking meaningful psychotic or dissociative phenomena, and to prompt further research on ketamine use in psychotic disorders.

This report is a single‑patient clinical case of a 30‑year‑old female inpatient (weight 114 kg) with chronic schizophrenia (ICD‑10 F20.0; DSM‑5 295.90) who developed severe post‑psychotic depression (ICD‑10 F20.4) after remission of positive symptoms. The patient presented with concrete suicidal ideation and a Montgomery‑Åsberg Depression Rating Scale (MADRS) score of 48; positive symptoms were measured using the Positive and Negative Syndrome Scale — Positive symptoms subscale (PANSS‑P). Prior to S‑ketamine, the patient was receiving multiple psychotropic agents: venlafaxine 300 mg, pregabalin 600 mg, valproate 1000 mg, clozapine 400 mg and risperidone 8 mg daily. Intravenous S‑ketamine augmentation was initiated after non‑response to this regimen. The initial dose was 25 mg given as a 30‑minute infusion (calculated at 0.22 mg/kg). After an initial response and acceptable tolerability, the dose was increased to 37.5 mg (0.33 mg/kg) and administered as 30‑minute infusions three times weekly for three weeks in total. Clinical measurements included MADRS for depressive severity, PANSS‑P for positive psychotic symptoms, and the Clinician‑Administered Dissociative States Scale (CADSS) to assess dissociation during infusions. Vital signs were monitored during and after infusions. As a single‑case descriptive report, no inferential statistical analyses were performed; outcomes are presented as observed clinical changes over the treatment course. The extracted text does not report details on consent procedures, ethics approval, or longer‑term follow‑up beyond the described treatment period.

Immediately after the first 30‑minute infusion of 25 mg S‑ketamine (0.22 mg/kg), a rapid and marked antidepressant and anti‑suicidal response was observed. MADRS score fell from 48 at baseline to 6 after the first treatment, indicating a large reduction in depressive symptoms. Positive psychotic symptoms did not meaningfully worsen; PANSS‑P was reported as 7 at baseline and 8 after the first infusion. The CADSS indicated discrete dissociative phenomena during the infusion (score 16), but these effects resolved within minutes of completing the infusion. No relevant changes in vital parameters were recorded during or after treatment. Because the initial infusion was well tolerated and effective, the dose was increased to 37.5 mg (0.33 mg/kg) and given as 30‑minute infusions three times per week for three weeks. Over this treatment course the patient achieved sustained remission of depressive symptoms and suicidality, with MADRS reported as 4 at the end of treatment. PANSS‑P remained stable (reported as 7) and no meaningful induction of positive psychotic symptoms was observed during or after the S‑ketamine treatment series. The extracted text does not provide formal safety tables, specific numerical vital‑sign data, or longer‑term outcome data beyond the sustained remission during the described treatment period.

Bartova and colleagues describe what they state is the first report of antidepressant augmentation with S‑ketamine in a patient with schizophrenia, producing rapid anti‑suicidal and antidepressant effects without accompanying meaningful psychotic or persistent dissociative phenomena. The authors emphasise that these clinical benefits occurred at doses lower than the commonly recommended intravenous antidepressant dose of 0.5 mg/kg; their patient achieved full remission at approximately 0.3 mg/kg. They note that discrete dissociation was observed during infusions but resolved within minutes and that no substantial changes in positive psychotic symptoms or vital signs were detected. In positioning their findings relative to earlier work, the authors underline that ketamine has established rapid antidepressant efficacy in mood disorders and in some depressed patients with a history of psychosis, yet its use in primary psychotic disorders has been limited by safety concerns. They argue that this single‑case experience suggests S‑ketamine can be safe and effective in at least some patients with schizophrenia and post‑psychotic depression, but they stop short of making broad clinical claims. The authors call for further research to clarify ketamine’s effects in psychotic disorders, explicitly recommending examination of higher doses and alternative routes of administration to improve understanding. The extracted text does not present a formal limitations section, but by urging further study the authors acknowledge the preliminary nature of a single‑case report and the need for larger, systematic investigations.