Intranasal ketamine in the management of Treatment-Resistant Depression – a small cohort study from Unidade Local de Saúde de Coimbra

Introduction

Although there is a lack of consensus on the exact definition of Treatment-Resistant Depression (TDR), current epidemiological studies show that up to 55% of patients who are treated for Major Depressive Disorder with “typical” antidepressant medication - serotonin, dopamine and norepinephrine pathways - do not improve significantly, even after different therapeutic trials. With this in mind, new ways of improving depressive symptoms have arisen recently, with one of them being the glutamate pathway, spearheaded by ketamine. The manipulation of glutamate pathways, the nervous system most prevalent excitatory neurotransmitter, through ketamine would allow the medical field to tap into its synaptic plasticity potential, in a different manner than the typical antidepressants, due to its long-term potentiation. In 2019, one of ketamine’s enantiomers – esketamine – was approved by the U.S. Food and Drug Administration, marking a possible turning point in the management of TDR. Six years later, our hospital (Unidade Local de Saúde de Coimbra in Portugal) started offering this treatment to patients that fit the criteria for TDR.

Aims

Our aim with this work is to present the early findings of the administration of intranasal esketamine in patients with TDR in our local hospital. A search of relevant bibliography was also carried out using Pubmed.

Methods and results: We present six patients, aged 30 to 62 years of age, diagnosed with TDR due to multiple prior therapeutic failures. They were all treated with bi-weekly intranasal esketamine for 4 weeks (induction with 56 mg followed by 84 mg at subsequent visits) as and adjuvant to the regular antidepressive medication already in effect. Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), the EQ-5D-5L and the Patient Health Questionnaire-9 (PHQ 9). A significant decrease in depressive symptoms was observed: mean MADRS score was 33.8 points at baseline and 17.8 points after 4 weeks of treatment, with an absolute mean reduction of 16.0 points (relative mean reduction ≈47.3%); remission, defined as score of MADRS≤10, occurred in 2/6 (33%). There was an improvement in patients’ quality of life, with the reported mean increasing from 33.3 to 54.2 points (+20.8). Global functioning also improved: mean PHQ 9 score decreased from 18.5 to 10.2 (mean reduction 8.3 points, ≈45%). Three patients showed marked clinical improvement (final MADRS scores of 5, 5, and 12). Reported side effects were mild and transient

Conclusions

In this cohort, during 4 weeks of treatment with intranasal esketamine, clinical improvement in depressive symptoms and quality of life was observed, with remission in a third of the patients. These early results show the promise that esketamine, and therefore the glutamate pathway, presents in the treatment of TDR in our population, with longer form studies needed to attest to its validity in the long run.

References

No references