Repeated subcutaneous racemic ketamine in treatment-resistant depression: case series

Abstract

Interest in the use of parenteral ketamine has been increasing over the last 2 decades for the management of treatment-resistant depression (TRD). While intravenous (IV) ketamine has been the most common parenteral route of administration, subcutaneous (SC) and intramuscular options have been described. We developed a clinical treatment protocol for the use of repeated SC racemic ketamine (maximum six treatments, twice per week) in an inpatient psychiatric care setting with inclusion/exclusion criteria, dosing schedule, and description of treatment, assessment, and monitoring procedures. Results from the first 10 consecutive patients demonstrated the effectiveness of SC racemic ketamine in relieving symptoms of TRD as measured by the Montgomery–Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16). Response (≥50% reduction in scores from baseline to endpoint) was achieved in 8/10 cases on the MADRS and 6/10 on the QIDS-SR16. Remission was achieved in 8/10 (based on MADRS ≤10) and 5/10 (based on QIDS-SR16 ≤6). Patients tolerated the treatments well with only transient blood pressure changes and dissociative side effects. Repeated SC ketamine treatments could be a safe, feasible, and effective alternative to IV ketamine infusions for patients with TRD.

A Critical View on New and Future Antidepressants

“…Interest in glutamatergic modulators began more than 15 years ago with ketamine [ 34 ], suggesting for the first time a new antidepressant mechanism that showed efficacy within hours rather than weeks. In the years that followed, many studies confirmed the initial findings and we now have ketamine in clinical practice plus the more convenient nasal esketamine [ 35 - 38 ]. Research then expanded to include similar psychoactive drugs such as the serotonergic psychedelics, especially psilocybin.…”

Anhedonia and Depressive Disorders

“…Ketamine is reaching a wide clinical use due to the rapid antidepressant effects [ 87 - 89 ], the preliminary evidence available suggest that it has a relevant anti-anhedonic effect with a rapid onset of action [ 50 , 90 ], thus suggesting its use in specific clinical contexts where rapid effect is needed. Within a similar drug class, much interest is now focusing on psilocybin, which has the further benefit of one point administration [ 91 ].…”

Innovation in psychopharmacology

“…There is now strong support for its rapid benefit in resistant depression (Bahji et al ., 2021; Alnefeesi et al ., 2022), with evidence of being second in efficacy only to electroconvulsive therapy (Rhee et al ., 2022). Ketamine is a valuable option also in emergency situations (Pompili et al ., 2022), and recently convenient subcutaneous administration methods have been suggested (Rocha et al ., 2021; Tham et al ., 2022). However, ketamine benefits may extend to other less common clinical conditions that are quite challenging to manage.…”