Rapid infusion of esketamine for unipolar and bipolar depression: a retrospective chart review

Abstract

BackgroundThis study evaluated efficacy and safety of intravenous subanesthetic doses of esketamine using an administration time of 10 minutes in patients with treatment-resistant depression and bipolar depression.MethodsA retrospective chart review was conducted to identify patients who met the inclusion criteria for treatment-resistant depression and bipolar depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, and these patients received rapid infusion of esketamine between June 2012 and December 2015. The Montgomery–Åsberg Depression Rating Scale (MADRS) was administered to measure and score depressive symptom severity before infusion and at 24 hours, 72 hours, and 7 days after infusion. In addition, Clinical Global Impression scale was administered before and 7 days after esketamine infusion.ResultsEsketamine was administered to 30 patients. A total of 27 patients met the inclusion criteria and had MADRS evaluation data, which showed that 23 had unipolar and 4 had bipolar depression. Thirteen patients (48.1%) showed therapeutic response (MADRS reduction ≥50%) within 1 week (7 days) of intervention. Remission (MADRS <7) was observed in 10 patients (37.0%) in the same period. Therapeutic response and remission frequencies were seen in 16 (59.3%) and 11 (40.7%) patients, respectively, within 24 hours following drug infusion. The most relevant side effect observed during the esketamine infusion was dissociative symptoms ranging from mild to severe, which was reported by 11.1% of patients as a very disturbing experience.LimitationsThis study was done retrospectively, had a small sample size, and there was no comparative group.ConclusionThe present study demonstrates that rapid infusion of esketamine is possibly not the optimal choice to administer this drug for treatment-resistant depression due to tolerability reasons. Further controlled studies are required to investigate efficacy, safety, and tolerability profiles among the different types of ketamines and methods of using this drug in depressed patients.

Safety and Tolerability of Ketamine Use in Treatment-Resistant Bipolar Depression Patients with Regard to Central Nervous System Symptomatology: Literature Review and Analysis

“…Some researchers showed that the presence of dissociative symptoms is a marker of antidepressant effectiveness [3]. The BPRS and BPRS+ scales indicated the absence of psychosis during the time of assessment [4,25]. Table 2.…”

“…The current psychopharmacological treatment approaches in depression mainly focus on mood stabilizers, second-generation antipsychotics, and monoaminergic interventions, but a significant proportion of patient do not respond to them adequately. Treatment-resistant bipolar depression (TRBD) patients who do not achieve remission are up to 33% of the depressive patients global count [2][3][4]. Delayed onset of the clinical action of the antidepressants, tolerability of the drugs, comorbidities, and low drug efficacy in some patients are the key unmet challenges of contemporary psychiatry [5].…”

Functional connectivity changes with rapid remission from moderate-to-severe major depressive disorder

“…Electroconvulsive therapy (ECT) has greater efficacy and more rapid onset of action than antidepressant medications; however, mean onset is still >2 weeks (9), open-label remission rates occur in only 50-65% of patients (5), and there are numerous significant off-target effects, including cognitive disturbances (10) and effects on the motor system (11), making it difficult to determine which network changes are specific to remission from depression. Ketamine induces brief remission rapidly but only in a third of patients (12,13) and with significant off-target effects (14,15). Incipient investigations of potent 5-HT2a agonists demonstrate high rates of rapid remission (16,17); yet, the off-target effects are profound (18).…”

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)

“…Ketamine/sketamine has recently been FDA-approved for treatment-resistant depression; however, ketamine has several limitations. Approximately 11% of patients report the dissociative symptoms as very disturbing 64 , remission rates for ketamine/s-ketamine are lower than the remission rate we observed for SAINT 33,35,65 , very few studies have investigated the antidepressant efficacy of ketamine beyond a single infusion 66,67 and the opioid mechanism of action poses a potential risk 68 . The other available rapid-acting treatment is ECT, for which less than 2% of eligible patients receive due to concerns regarding cognitive side-effects and stigma 69,70 .…”