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Objective Electroconvulsive therapy (ECT) is a well-established therapeutic intervention for major depressive disorder. Recent literature has shown that the anesthetic agent ketamine has some antidepressant properties at low doses and may be an alternative therapy for treatment-resistant major depressive disorder. We hypothesized that the use of low-dose ketamine as an anesthetic adjunct in ECT would more rapidly improve depression while maintaining hemodynamic stability than ECT with propofol alone. Methods Institutional ethics approval was obtained, and the use of ketamine in this study was approved by Health Canada. This is a randomized, double-blinded, placebo-controlled trial that involved ketamine administration at 0.5 mg/kg IV in addition to propofol anesthesia for ECT. The primary outcome was the number of ECT treatments required to achieve a 50% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included the number of ECT treatments required to achieve a 25% reduction in MADRS score, as well as any differences in the Clinical Global Impression Scale for Severity, hemodynamic variables, and seizure duration. Adverse events were recorded for safety assessment. Results A total of 45 patients completed the study. No difference was found between groups with respect to the primary or secondary outcomes. The ketamine group showed a trend towards a decreased dose of propofol required to achieve adequate anesthesia. No adverse events were reported. Conclusion Low-dose ketamine does not improve psychiatric outcomes in the setting of propofol-based anesthesia for ECT. Specifically, ketamine did not reduce the number of ECT sessions necessary to achieve a 50 or 25% reduction in MADRS scores. Reassuringly, the fact that no differences in hemodynamic variables or unexpected adverse events occurred suggests that low-dose ketamine may be safely used in this setting should clinical indications warrant its use. Clinical trial registration ClinicalTrials.gov, NCT02579642.

This case report describes successful maintenance treatment with oral S-ketamine in a patient with severe depression, who previously was resistant to electroconvulsive therapy and deep brain stimulation, and who also had comorbid psychotic and obsessive compulsive symptoms.

Three types of hyperalgesia can occur during the postoperative period: primary hyperalgesia, which disappears with wound healing, secondary or central hyperalgesia, which can lead to chronic pain, and opiate-induced hyperalgesia. Different drugs, most of which are NMDA receptors antagonists, are used to decrease or prevent the risk of central or opiate-induced hyperalgesia. However, it is difficult to determine whether they are really effective and at which dosage: the results of most published studies are difficult to interpret because of methodological problems. The two most frequent of those are: absence of objective measurement of secondary hyperalgesia and difficulties targeting an at risk population.

Recent evidence suggests that critical molecules in neurotrophic signaling cascades are long-term targets for currently available monoaminergic antidepressants. As chronic and severe mood disorders are characterized by impairments in neuronal resilience, pharmacological strategies that subserve a neuroprotective function might alter disorder pathophysiology and modify disease progression. Several promising approaches involve modulation of the glutamate neurotransmitter system, via post-synaptic receptor blockade or potentiation and presynaptic vesicular release inhibition. A focused review of the extant scientific literature was conducted, with a discussion of 3 compounds or classes of drugs currently undergoing clinical investigation: ketamine, riluzole, and AMPA receptor potentiators. Recent investigations in mood disordered patients suggest that the NMDA receptor antagonist ketamine might demonstrate rapid antidepressant properties. Riluzole has been shown to reverse glutamate-mediated impairments in neuronal plasticity and to stimulate the synthesis of brain derived neurotrophic factor. Open-label trials in treatment-resistant depression have yielded promising results. Likewise, AMPA receptor potentiators favorably impact neurotrophic factors as well as enhance cognition. CONCLUSIONS: Pharmacological approaches that modulate components of the glutamate system offer novel targets for severe, recurrent mood disorders. Controlled studies are necessary. Recentes evidências sugerem que as moléculas críticas nas cascatas de sinalização neurotrófica são alvos de longo prazo dos antidepressivos monoaminérgicos disponíveis atualmente. Na medida em que transtornos graves e crônicos são caracterizados por deficiências na resiliência neuronal, estratégias farmacológicas que sejam úteis para uma função neuroprotetora talvez possam alterar a fisiopatologia e modificar a progressão da doença. Vários enfoques promissores envolvem a modulação do sistema neurotransmissor do glutamato, via bloqueio ou potencialização do receptor pós-sináptico e inibição da liberação vesicular pré-sináptica. Foi realizada uma revisão focada da literatura científica existente, com a discussão de três compostos ou classes de drogas que estão atualmente sob investigação clínica: a ketamina, o riluzol e os potencializadores de receptores de AMPA. DISCUSSÃO: Estudos recentes com pacientes com transtornos de humor sugerem que a ketamina, um antagonista do receptor NMDA, poderia ter demonstrado propriedades antidepressivas rápidas. O riluzol demonstrou reverter deficiências mediadas pelo glutamato na plasticidade neuronal e estimular a síntese de fatores neurotróficos derivados do cérebro. Ensaios abertos com depressão resistente ao tratamento produziram resultados promissores. Da mesma forma, os potencializadores de receptores de AMPA impactam favoravelmente os fatores neurotróficos, assim como melhoram a cognição. CONCLUSÕES: Enfoques farmacológicos que modulam os componentes do sistema de glutamato oferecem novos alvos para transtornos de humor recorrentes e graves. São necessários estudos controlados.