Use of repeated intravenous ketamine therapy in treatment-resistant bipolar depression with suicidal behaviour: a case report from Spain

Ketamine is a non-competitive NMDA receptor antagonist and a dissociative anaesthetic that has long been used in anaesthesiology, particularly in paediatrics. Its use in adults has been controversial because of dissociative and psychotomimetic adverse effects and potential for misuse. Since the first report of antidepressant effects about 15 years prior to this paper, systematic reviews and meta-analyses have described rapid and robust antidepressant and anti‑suicidal effects of ketamine, while also noting that these benefits are typically transient and that double‑blind trials face methodological challenges. This case report presents an additional clinical observation intended to inform how ketamine might be used in treatment‑refractory depression (TRD). Specifically, the authors describe the use of repeated intravenous ketamine infusions in a patient with refractory bipolar depression and chronic suicidal behaviour, documenting the treatment rationale, clinical course, tolerability and the durability of response. The report aims to contribute to the limited Spanish literature on off‑label ketamine use in severe mood disorders and to highlight the unresolved issue of how best to sustain benefit after initial response.

The paper describes a single clinical case. A 45‑year‑old female with treatment‑resistant bipolar depression and persistent suicidal ideation was admitted after an aborted suicide attempt. On admission she showed marked hopelessness, high anxiety and ongoing suicidal behaviour. Multiple trials of antidepressants, mood stabilisers and antipsychotics, together with intensive psychotherapy, failed to produce clinical improvement. A pharmacogenetic test was performed without yielding a profile favouring specific psychotropics. A 4‑week course of antidepressant treatment at recommended doses was judged ineffective. Electroconvulsive therapy (ECT) was offered but the patient declined because of concerns about stigma and side effects. After approximately 6 months of hospitalisation and with limited remaining options, the clinical team proposed off‑label intravenous ketamine. Institutional approvals were obtained from the hospital ethics committee, the pharmacy department and the medical director; informed consent was provided by the patient and her relatives. Oral psychotropic medications that the patient had been taking were continued at the same doses during ketamine treatment. The chosen regimen followed prior evidence favouring repeated dosing: ketamine 0.5 mg/kg diluted in normal saline, administered intravenously over 40 minutes, on Mondays, Wednesdays and Fridays for 2 weeks (six infusions in total). Clinical assessment used the Montgomery‑Åsberg Depression Rating Scale (MADRS) and the InterSePT Scale for Suicidal Thinking (ISST). Vital signs (blood pressure and heart rate) and adverse effects were monitored periodically up to 4 hours after each infusion.

Clinical improvement began rapidly: an ‘‘impressive’’ response was observed within hours of the first infusion and was consolidated across the subsequent five sessions. By 2 weeks from treatment initiation the patient had improved sufficiently for discharge and was referred to outpatient psychiatric follow‑up. Euthymia and functional recovery were maintained for 4 weeks after discharge. In the 5th week depressive symptoms recurred abruptly, culminating in a suicide attempt and readmission to hospital. Adverse effects were limited and transient. During infusions the patient experienced mainly sedative effects that resolved within about 2 hours. No psychotomimetic or dissociative symptoms were recorded and vital signs remained stable throughout monitoring. The report notes that the patient remained on alprazolam during treatment; the authors remark that some recent studies suggest benzodiazepines can attenuate ketamine’s effectiveness in non‑responders, but in this case remission occurred despite concurrent benzodiazepine use.

The authors outline current mechanistic hypotheses for ketamine’s antidepressant action, emphasising that the effect is complex and not fully understood. At sub‑anaesthetic doses ketamine may rapidly increase synaptic glutamate release, upregulate AMPA receptor expression and relieve inhibition of brain‑derived neurotrophic factor (BDNF) synthesis. Preclinical work also implicates activation of the mTOR signalling pathway and stimulation of synaptogenesis in neural circuits that have been damaged by chronic stress and depression. These mechanisms differ from those of conventional antidepressants and therefore position ketamine as a potential catalyst for new interventions in TRD. Despite the positive clinical response observed in this case, the authors urge caution. Risks of misuse and the occurrence of dissociative or psychotomimetic adverse effects during administration remain important concerns, although this patient experienced no notable side effects beyond transient sedation. Rojas and colleagues suggest that intravenous ketamine infusion can be considered in hospital settings for patients with TRD and recurrent suicidal ideation, but they highlight the key unresolved problem of sustaining benefit after initial response, as relapse is common and was illustrated by the patient’s recurrence in week 5.