Successful Use of Ketamine for the Treatment of Psychotic Depression in a Teenager

Zarrinnegar, Paria; Kothari, Jay S.; Cheng, Keith

doi:10.1089/cap.2019.0028

Cited by 33 publications

(28 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, it is possible that ( R,S )-ketamine effects are more rapid in females than in males, similarly to what has been shown by a previous study ( Franceschelli et al, 2015 ). Additional studies in humans have shown that ( R,S )-ketamine has a rapid antidepressant effect in adolescents ( Dwyer et al, 2017 ; Cullen et al, 2018 ; Zarrinnegar et al, 2019 ), but sex was not considered as biological variable. Previous works have also shown that testing mice of different genetic backgrounds in the same behavioral assays can lead to opposing conclusions, suggesting that a variety of mouse strains should be tested to determine ( R,S )-ketamine efficacy ( Sittig et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…Despite the prevalence of ( R,S )-ketamine among children as an anesthetic ( Dolansky et al, 2008 ; Dwyer et al, 2017 ), few studies have examined whether ( R,S )-ketamine is effective in treating adolescent mood disorders ( Papolos et al, 2013 ; Dwyer et al, 2017 ; Cullen et al, 2018 ; Zarrinnegar et al, 2019 ). Similarly, ( R,S )-ketamine is used as an anesthetic in older adults ( Wickström et al, 1982 ; Maneglia and Cousin, 1988 ), often combined with other drugs ( Willman and Andolfatto, 2007 ; Andolfatto et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acute (R,S)-Ketamine Administration Induces Sex-Specific Behavioral Effects in Adolescent but Not Aged Mice

et al. 2022

View full text Add to dashboard Cite

(R,S)-ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that was originally developed as an anesthetic. Most recently, (R,S)-ketamine has been used as a rapid-acting antidepressant, and we have reported that (R,S)-ketamine can also be a prophylactic against stress in adult mice. However, most pre-clinical studies have been performed in adult mice. It is still unknown how an acute (R,S)-ketamine injection influences behavior across the lifespan (e.g., to adolescent or aged populations). Here, we administered saline or (R,S)-ketamine at varying doses to adolescent (5-week-old) and aged (24-month-old) 129S6/SvEv mice of both sexes. One hour later, behavioral despair, avoidance, locomotion, perseverative behavior, or contextual fear discrimination (CFD) was assessed. A separate cohort of mice was sacrificed 1 h following saline or (R,S)-ketamine administration. Brains were processed to quantify the marker of inflammation Cyclooxygenase 2 (Cox-2) expression to determine whether the acute effects of (R,S)-ketamine were partially mediated by changes in brain inflammation. Our findings show that (R,S)-ketamine reduced behavioral despair and perseverative behavior in adolescent female, but not male, mice and facilitated CFD in both sexes at specific doses. (R,S)-ketamine reduced Cox-2 expression specifically in ventral CA3 (vCA3) of male mice. Notably, (R,S)-ketamine was not effective in aged mice. These results underscore the need for sex- and age-specific approaches to test (R,S)-ketamine efficacy across the lifespan.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acute (R,S)-Ketamine Administration Induces Sex-Specific Behavioral Effects in Adolescent but Not Aged Mice

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Repeated ketamine i.v. infusion was also proved to be efficacious in a 15-year-old adolescent female with TRD, generalized anxiety disorder and PTSD secondary to sexual trauma (Zarrinnegar et al, 2019); even in this case, ketamine (0.5 mg/kg; six i.v. infusion in 2 weeks) reduced significantly depressive symptoms, and suicidal ideation and the girl could be dismissed with a pharmacotherapy support because a resolution of depressive and psychotic symptoms was achieved and maintained for several months.…”

Section: Current Use and Potential For Ketamine Use In Resistant Depression In Adolescence And Childhoodmentioning

confidence: 91%

“…Nonetheless, a consistent number of adolescent patients that do not respond even after two medications treatments with CBT, can be categorized as TRD; they require diagnostic careful evaluation, clinical attention and innovative therapies (Dwyer et al, 2020). Among new therapies, several studies investigated the efficacy of ketamine in children and adolescent with TRD (Papolos et al, 2013;Dwyer et al, 2017;Cullen et al, 2018;Zarrinnegar et al, 2019). In particular Cullen et al (2018) administered ketamine (0.5 mg/kg; six i.v.…”

Section: Current Use and Potential For Ketamine Use In Resistant Depression In Adolescence And Childhoodmentioning

confidence: 99%

Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success?

et al. 2021

View full text Add to dashboard Cite

Repurposing ketamine in the therapy of depression could well represent a breakthrough in understanding the etiology of depression. Ketamine was originally used as an anesthetic drug and later its use was extended to other therapeutic applications such as analgesia and the treatment of addiction. At the same time, the abuse of ketamine as a recreational drug has generated a concern for its psychotropic and potential long-term effects; nevertheless, its use as a fast acting antidepressant in treatment-resistant patients has boosted the interest in the mechanism of action both in psychiatry and in the wider area of neuroscience. This article provides a comprehensive overview of the actions of ketamine and intends to cover: (i) the evaluation of its clinical use in the treatment of depression and suicidal behavior; (ii) the potential use of ketamine in pediatrics; (iii) a description of its mechanism of action; (iv) the involvement of specific brain areas in producing antidepressant effects; (v) the potential interaction of ketamine with the hypothalamic-pituitary-adrenal axis; (vi) the effect of ketamine on neuronal transmission in the bed nucleus of stria terminalis and on its output; (vii) the evaluation of any gender-dependent effects of ketamine; (viii) the interaction of ketamine with the inflammatory processes involved in depression; (ix) the evaluation of the effects observed with single or repeated administration; (x) a description of any adverse or cognitive effects and its abuse potential. Finally, this review attempts to assess whether ketamine’s use in depression can improve our knowledge of the etiopathology of depression and whether its therapeutic effect can be considered an actual cure for depression rather than a therapy merely aimed to control the symptoms of depression.

show abstract

“…( R,S )-ketamine is used for short-term procedural sedation in the emergency department setting in a wide age range, starting at 3 months of age ( Rosenbaum et al, 2021 ). Yet, even with a high prevalence of ( R,S )-ketamine being administered as an anesthetic in children ( Green et al, 2004 ; Dolansky et al, 2008 ), few studies have systematically evaluated the behavioral effects of ( R,S )-ketamine administration in children ( Papolos et al, 2013 ; Dwyer et al, 2017 ; Cullen et al, 2018 ; Zarrinnegar et al, 2019 ). Moreover, the long-term effects of adolescent ( R,S )-ketamine administration later in life, or in males vs females, have not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

Prophylactic (R,S)-Ketamine Is Effective Against Stress-Induced Behaviors in Adolescent but Not Aged Mice

Mastrodonato

Pavlova

Kee

et al. 2022

International Journal of Neuropsychopharmacology

View full text Add to dashboard Cite

Background (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is frequently used as an anesthetic and as a rapid-acting antidepressant. We and others have reported that (R,S)-ketamine is prophylactic against stress in adult mice, but have yet to test its efficacy in adolescent or aged populations. Methods Here, we administered saline or (R,S)-ketamine as a prophylactic at varying doses to adolescent (5-week-old) and aged (24-month-old) 129S6/SvEv mice of both sexes 1 week before a 3-shock contextual fear conditioning (CFC) stressor. Following CFC, we assessed behavioral despair, avoidance, perseverative behavior, locomotion, and contextual fear discrimination (CFD). To assess whether the prophylactic effect could persist into adulthood, adolescent mice were injected with saline or varying doses of (R,S)-ketamine, and administered a 3-shock contextual fear conditioning (CFC) as a stressor 1 month later. Mice were then re-exposed to the aversive context 5 days later and administered behavioral tests as aforementioned. Brains were also processed to quantify Cyclooxygenase 2 (Cox-2) expression as a proxy for inflammation to determine whether the prophylactic effects of (R,S)-ketamine were partially due to changes in brain inflammation. Results Our data indicate that (R,S)-ketamine is prophylactic at sex-specific doses in adolescent, but not aged mice. (R,S)-ketamine attenuated learned fear and perseverative behavior in females and reduced behavioral despair in males, and facilitated CFD in both sexes. (R,S)-ketamine reduced Cox-2 expression specifically in ventral CA3 (vCA3) of male mice. Conclusions These findings demonstrate that prophylactic (R,S)-ketamine efficacy is sex-, dose-, and age-dependent and will inform future studies investigating (R,S)-ketamine efficacy across the lifespan.

show abstract

Successful Use of Ketamine for the Treatment of Psychotic Depression in a Teenager

Cited by 33 publications

References 2 publications

Acute (R,S)-Ketamine Administration Induces Sex-Specific Behavioral Effects in Adolescent but Not Aged Mice

Acute (R,S)-Ketamine Administration Induces Sex-Specific Behavioral Effects in Adolescent but Not Aged Mice

Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success?

Prophylactic (R,S)-Ketamine Is Effective Against Stress-Induced Behaviors in Adolescent but Not Aged Mice

Contact Info

Product

Resources

About