Single bolus low-dose of ketamine does not prevent postpartum depression: a randomized, double-blind, placebo-controlled, prospective clinical trial

Yang, Xu; Li, Yuantao; Huang, Xiaolei; Chen, Daili; She, Bao-Zuan; Ma, Ding

doi:10.1007/s00404-017-4334-8

Cited by 63 publications

(59 citation statements)

References 29 publications

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“…Fluoxetine, a traditional antidepressant targeting serotonin reuptake inhibition, is used as treatment for depression including that of women with PPD ( 24 – 26 ) and requires at least 3 weeks to take effect ( 27 ). Other antidepressants like ketamine may have limited preventative benefits in PPD ( 28 ). On postnatal day 28 after fluoxetine administration for 3 weeks, behavioral tests confirmed the reversal of depressive-like behaviors.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Autophagy in Microglia Alters Depressive-Like Behavior via BDNF Pathway in Postpartum Depression

Tan

Jiang

et al. 2018

Front. Psychiatry

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Postpartum depression (PPD) is associated with mood disorders and elevated inflammation. Studies have evidenced the activation/inhibition of autophagy and excessive activation of microglia to have a close relationship with depression. C57 and microglia-specific autophagy-deficient mice (Cx3Cr1Cre/+ATG5loxp/loxp) were employed to establish the chronic unpredicted mild stress depression mice model from embryonic day 7 (E7) to embryonic day 16 (E16). Fluoxetine was administered for 3 weeks (commencing from 1 week after birth). Behavioral tests (open field, forced swimming, and sucrose preference tests) were implemented. Western blot and immunofluorescence staining were employed to assess the brain-derived neurotrophic factor (BDNF) expression level, autophagy-associated proteins, and inflammatory factors. Depressive behavior was reversed following fluoxetine treatment; this was evidenced via open field, sucrose preference, and forced swimming tests. Both BDNF and autophagy-associated proteins (ATG5, Beclin-1, and LC3II) were upregulated following fluoxetine treatment. Inflammatory factors including nuclear factor kappa B and inducible nitric oxide synthase were reduced while anti-inflammatory factor interleukin-10 (IL-10) was increased after fluoxetine treatment. Microglia-specific autophagy-deficient mice (Cx3Cr1Cre/+ATG5loxp/loxp) showed a curtailed autophagy level, higher inflammatory level, and reduced BDNF expression when compared with C57 mice. Autophagy inhibition in microglia contributes to inflammation, which further instigates PPD. Fluoxetine might mediate its antidepressant effect in PPD through the autophagic pathway while upregulating BDNF expression. In view of this, regulating BDNF in microglia is a potential novel therapy target for PPD.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Autophagy in Microglia Alters Depressive-Like Behavior via BDNF Pathway in Postpartum Depression

Tan

Jiang

et al. 2018

Front. Psychiatry

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“…Systematic reviews evaluating efficacy of postpartum use of selective serotonin reuptake inhibitors (SSRIs) suggest that these drugs are no more effective than placebo in mothers by 3-6 months postpartum (Yonkers et al, 2008;De Crescenzo et al, 2014). Other antidepressants like ketamine (Xu et al, 2017) may have limited preventative benefits in the postpartum. Nonetheless, approximately 6% of mothers use antidepressants after childbirth (Smolina et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Voluntary running influences the efficacy of fluoxetine in a model of postpartum depression

et al. 2018

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“…9 Not all studies of ketamine and postoperative depressive symptoms have revealed therapeutic benefit. Intraoperative administration of subanaesthetic ketamine did not prevent postpartum depression in a randomised controlled trial of parturients undergoing Caesarean section (n¼330), 14 although the pathophysiology of this condition is likely distinct as compared with that of a major depressive disorder or depressive symptoms after non-obstetric surgery. Ketamine has also been explored as an adjunct to electroconvulsive therapy that could possibly mitigate adverse cognitive outcomes and improve therapeutic efficacy, but a multicentre trial testing this possibility did not find strong evidence of benefit.…”

mentioning

confidence: 99%

Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial

Mashour

Abdallah

Pryor

et al. 2018

British Journal of Anaesthesia

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Background: Ketamine is a general anaesthetic with anti-depressant effects at subanaesthetic doses. We hypothesised that intraoperative administration of ketamine would prevent or mitigate postoperative depressive symptoms in surgical patients. Methods: We conducted an international, randomised clinical trial testing the effects of intraoperative administration of ketamine [0.5 mg kg À1 (Lo-K) or 1.0 mg kg À1 (Hi-K)] vs control [saline placebo (P)] in patients !60 yr old undergoing major surgery with general anaesthesia. We administered the Patient Health Questionnaire-8 before the operation, on postoperative day (POD) 3 (primary outcome), and on POD30 to assess depressive symptoms, a secondary outcome of the original trial.

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Single bolus low-dose of ketamine does not prevent postpartum depression: a randomized, double-blind, placebo-controlled, prospective clinical trial

Abstract: Intra-operative low-dose ketamine (0.25 mg/kg) does not have a preventive effect on postpartum depression.

Cited by 63 publications

References 29 publications

Inhibition of Autophagy in Microglia Alters Depressive-Like Behavior via BDNF Pathway in Postpartum Depression

Inhibition of Autophagy in Microglia Alters Depressive-Like Behavior via BDNF Pathway in Postpartum Depression

Voluntary running influences the efficacy of fluoxetine in a model of postpartum depression

Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial

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