Oral Ketamine-Assisted Psychotherapy in DNSD: Case Report and Clinical Implications

Case Report: Oral Ketamine-Assisted Psychotherapy Achieves Remission in DNSD

A recent case report published on October 12, 2026 (OpenAlex W7221633366) describes a 56-year-old woman with dissociative neurological symptom disorder (DNSD)—also known as functional neurological symptom disorder (FNSD) in DSM-5-TR—who experienced prolonged remission of mutism following a course of oral ketamine-assisted psychotherapy. DNSD is characterized by neurological symptoms, such as paralysis or mutism, that lack an identifiable structural or medical cause. The patient had previously failed to respond to standard treatments, including selective serotonin reuptake inhibitors (SSRIs), intravenous ketamine without psychotherapy, and intensive inpatient therapy. Notably, speech returned during the fourth session of oral ketamine-assisted psychotherapy, and remission was sustained for over a year after discontinuing all psychotropic medications.

Mechanism and Therapeutic Context: Integrating Pharmacology and Psychotherapy

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is increasingly studied for its rapid-acting antidepressant and dissociative properties. In this case, the patient underwent six alternate-day sessions of oral ketamine (50–150 mg), administered within a psychodynamically informed therapeutic frame alongside ongoing family therapy and venlafaxine. The patient began to speak during the third session and was able to articulate previously unspoken psychological conflicts by the fourth. This sequence suggests that ketamine's dissociative effects may facilitate access to repressed emotions or conflicts, potentially overcoming barriers that had stalled traditional psychotherapy.

Unlike previous attempts with intravenous ketamine administered without psychotherapy, the integration of a structured therapeutic environment appears critical. The report specifically contrasts the outcome with a lorazepam-assisted interview, which produced only sedation and no improvement in speech, suggesting that ketamine's unique pharmacological profile, when combined with psychotherapy, may offer distinct advantages for selected patients with treatment-resistant DNSD.

Policy and Research Implications: A Hypothesis-Generating Signal

This case report highlights a potential new indication for ketamine-assisted psychotherapy—treatment-resistant DNSD with mutism—but its anecdotal nature limits generalizability. DNSD is a challenging and often refractory condition, with limited evidence-based pharmacological options. The report underscores the need for controlled studies comparing ketamine-assisted psychotherapy to existing approaches, such as benzodiazepine-assisted interviews or intensive inpatient therapy. Policymakers and research funders may consider supporting pilot trials to systematically evaluate efficacy, safety, and the role of the therapeutic frame in such interventions.

Importantly, the case also raises regulatory and ethical questions regarding off-label use of ketamine for functional neurological disorders. While ketamine is approved by the U.S. Food and Drug Administration (FDA) for anesthesia and, in intranasal form, for treatment-resistant depression, its use in DNSD remains investigational. Clinicians contemplating similar interventions should be aware of local regulations, informed consent requirements, and the necessity of robust monitoring for adverse effects.

Risks, Unknowns, and the Importance of Controlled Evidence

The efficacy and safety of oral ketamine-assisted psychotherapy for DNSD remain unknown outside of this single case. Ketamine carries risks of dissociation, abuse potential, and cognitive side effects, particularly with repeated use. The optimal dosing, frequency, and therapeutic context are not established, and it is unclear which patient subgroups may benefit or be at heightened risk. The report also highlights a real-world failure mode: intravenous ketamine without psychotherapy did not yield benefit, emphasizing that the therapeutic setting and integration may be as important as the drug itself.

Further, the durability of remission and long-term safety profile require systematic study. The case's success may reflect unique individual factors, such as psychological readiness, family dynamics, or prior treatment experiences, that may not generalize. Controlled trials with standardized protocols and long-term follow-up are essential before broader adoption or policy recommendations can be made.

Looking Forward: Directions for Research and Clinical Practice

The report of sustained remission of mutism in DNSD after oral ketamine-assisted psychotherapy offers a hypothesis-generating signal for future research. Investigators designing trials should consider head-to-head comparisons with established interventions, careful patient selection criteria, and standardized outcome measures. For clinicians and health systems, this case illustrates both the promise and the complexity of integrating novel pharmacological agents with psychotherapy for functional neurological disorders.

As interest in psychedelic-assisted psychotherapy grows, this example underscores the importance of rigorous evaluation, multidisciplinary collaboration, and ethical stewardship. The field must balance innovation with caution, ensuring that new interventions are supported by evidence and delivered within safe, supportive therapeutic frameworks.

By Dr. Alex R. Mendel, MD, MSc. Reviewed by Dr. Jamie Chen, MD, FRCP(C), on 2026-10-13. Research based on first-party clinical case report (OpenAlex W7221633366).