ABSTRACT
Anhedonia, a complex symptom rooted in deficits across reward processes, is primarily linked to depression and schizophrenia but transcends diagnostic boundaries across various mental disorders. Its presence correlates with poorer clinical outcomes, including an increased risk of suicide and diminished response to treatment. The neurobiological underpinnings of anhedonia remain incompletely understood despite advancements in biomarkers and imaging that contribute to deeper insights. Ketamine, known for its rapid-acting antidepressant properties, appears to possess antianhedonic effects through a mechanism of action not fully elucidated. This effect appears to be independent of its antidepressant properties. Explorations into alternative antianhedonic treatments have been underway, yet lingering questions persist, underscoring the imperative need for ongoing research to advance the field.
Subject(s)
Depressive Disorder, Treatment-Resistant , Ketamine , Tachyphylaxis , Female , Humans , Middle Aged , Administration, Intravenous , Antidepressive Agents/administration & dosage , Antidepressive Agents/pharmacology , Depressive Disorder, Treatment-Resistant/drug therapy , Ketamine/administration & dosage , Ketamine/pharmacologySubject(s)
Depressive Disorder, Major , Drug-Related Side Effects and Adverse Reactions , Electroconvulsive Therapy , Ketamine , Humans , Depressive Disorder, Major/therapy , Depressive Disorder, Major/chemically induced , Ketamine/adverse effects , Electroconvulsive Therapy/adverse effects , Iatrogenic DiseaseABSTRACT
BACKGROUND: ECT is considered the fastest and most effective treatment for TRD. Ketamine seems to be an attractive alternative due to its rapid-onset antidepressant effects and impact on suicidal thoughts. This study aimed to compare efficacy and tolerability of ECT and ketamine for different depression outcomes (PROSPERO/CRD42022349220). METHODS: We searched MEDLINE, Web of Science, Embase, PsycINFO, Google Scholar, Cochrane Library and trial registries, which were the ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform, without restrictions on publication date. SELECTION CRITERIA: randomized controlled trials or cohorts comparing ketamine versus ECT in patients with TRD. RESULTS: Eight studies met the inclusion criteria (of 2875 retrieved). Random-effects models comparing ketamine and ECT regarding the following outcomes were conducted: a) reduction of depressive symptoms severity through scales, g = -0.12, p = 0.68; b) response to therapy, RR = 0.89, p = 0.51; c) reported side-effects: dissociative symptoms, RR = 5.41, p = 0.06; nausea, RR = 0.73, p = 0.47; muscle pain, RR = 0.25, p = 0.02; and headache, RR = 0.39, p = 0.08. Influential & subgroup analyses were performed. LIMITATIONS: Methodological issues with high risk of bias in some of the source material, reduced number of eligible studies with high in-between heterogeneity and small sample sizes. CONCLUSION: Our study showed no evidence to support the superiority of ketamine over ECT for severity of depressive symptoms and response to therapy. Regarding side effects, there was a statistically significant decreased risk of muscle pain in patients treated with ketamine compared to ECT.
