Possible Affective Switch Associated With Intravenous Ketamine Treatment in a Patient With Bipolar I Disorder

McInnes, L. Alison; James-Myers, Molly B.; Turner, Mason S.

doi:10.1016/j.biopsych.2015.07.003

Cited by 17 publications

(4 citation statements)

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“…In this case, mania emerged in the absence of concomitant medications (12). The second BP I patient after single infusion of 0.5 mg/kg ketamine, developed elevated mood, hypersexuality, and excessive spending despite a therapeutic lithium level (13). The next case describes a patient with active substance use disorder who underwent surgical intervention (14).…”

Section: Discussionmentioning

confidence: 92%

Affective Switch Associated With Oral, Low Dose Ketamine Treatment in a Patient With Treatment Resistant Bipolar I Depression. Case Report and Literature Review

et al. 2020

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There is a growing evidence for the rapid and robust antidepressive effect of ketamine in unipolar and bipolar treatment resistant depression although evidence for the risk of affective switch is still limited. This case presents bipolar I disorder patient with treatment resistant depressive episode experiencing a switch to manic episode with mixed features shortly after receiving eight subanaesthetic doses of oral ketamine as an add-on treatment preceded by 2-day period of manic symptoms.

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Section: Discussionmentioning

confidence: 92%

Affective Switch Associated With Oral, Low Dose Ketamine Treatment in a Patient With Treatment Resistant Bipolar I Depression. Case Report and Literature Review

et al. 2020

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“…Clinical reports have also found that ketamine administration can alleviate depressive symptoms of major depressive disorder (MDD) and BD within minutes but may cause manic symptoms in non-psychiatric patients. These findings indicate that the affective switch is associated with ketamine use ( McInnes et al, 2016 ).…”

Section: Introductionmentioning

confidence: 77%

Chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway

Ni¹,

Gao²,

Wang³

et al. 2022

Zoological Research

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Ketamine, a rapid-acting antidepressant drug, has been used to treat major depressive disorder and bipolar disorder (BD). Recent studies have shown that ketamine may increase the potential risk of treatment-induced mania in patients. Ketamine has also been applied to establish animal models of mania. At present, however, the underlying mechanism is still unclear. In the current study, we found that chronic lithium exposure attenuated ketamine-induced mania-like behavior and c-Fos expression in the medial prefrontal cortex (mPFC) of adult male mice. Transcriptome sequencing was performed to determine the effect of lithium administration on the transcriptome of the PFC in ketamine-treated mice, showing inactivation of the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. Pharmacological inhibition of AKT signaling by MK2206 (40 mg/kg), a selective AKT inhibitor, reversed ketamine-induced mania. Furthermore, selective knockdown of AKT via AAV-AKT-shRNA-EGFP in the mPFC also reversed ketamine-induced mania-like behavior. Importantly, pharmacological activation of AKT signaling by SC79 (40 mg/kg), an AKT activator, contributed to mania in low-dose ketamine-treated mice. Inhibition of PI3K signaling by LY294002 (25 mg/kg), a specific PI3K inhibitor, reversed the mania-like behavior in ketamine-treated mice. However, pharmacological inhibition of mammalian target of rapamycin (mTOR) signaling with rapamycin (10 mg/kg), a specific mTOR inhibitor, had no effect on ketamine-induced mania-like behavior. These results suggest that chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway, which may be a novel target for the development of BD treatment.

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“…Although ketamine has seen an increase in clinical usage and research, caution is still warranted with using ketamine in certain scenarios. For instance, certain side effects, such as affective switch,48 have been reported as well as decompensation in mood symptoms and an increase in suicidality in patients with obsessive-compulsive disorder and no current depressive symptoms 32. Access to providers who are experienced in evaluation of patients with SIB and administration of ketamine in a controlled environment may also be challenging for patients seeking care.…”

Section: Discussionmentioning

confidence: 99%

The effects of ketamine on suicidality across various formulations and study settings

Dadiomov¹,

Lee²

2019

Mental Health Clinician

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IntroductionSuicidality and self-injurious behavior afflict patients with a wide variety of psychiatric illnesses. Currently, there are few pharmacologic treatments for suicidality and self-injurious behavior and none that treat these conditions emergently. Recently, ketamine has demonstrated efficacy in treating both depression and acute suicidal ideation. An increasing usage of ketamine, of a variety of formulations, has been studied for these indications. This article reviews the evidence for use of ketamine in self-injurious behavior and suicidality.MethodsA review of the MEDLINE database for articles relating to ketamine, self-injurious behavior, suicidality, and self-harm was conducted. Additional articles were assessed via cross-reference.ResultsA total of 24 articles that included clinical trials, meta-analyses, case series, and case reports were analyzed. The majority of studies of ketamine for suicidal ideation include the intravenous route using a dose of 0.5 mg/kg over 40 minutes. These studies suggest that intravenous ketamine may be effective at reducing suicidal ideation acutely. Data on use of ketamine in the intramuscular, intranasal, and oral forms are limited and of poorer quality. Studies on these formulations contain greater variability of positive and negative results of ketamine for reducing suicidality and self-injurious behavior. The durability of the antisuicidal effects across all formulations is limited.DiscussionKetamine may be an effective option for the treatment of suicidal ideation in patients across inpatient, outpatient, or emergent settings. At this time, more research is needed on the efficacy of ketamine across all formulations being used in clinical practice.

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Possible Affective Switch Associated With Intravenous Ketamine Treatment in a Patient With Bipolar I Disorder

Cited by 17 publications

References 0 publications

Affective Switch Associated With Oral, Low Dose Ketamine Treatment in a Patient With Treatment Resistant Bipolar I Depression. Case Report and Literature Review

Affective Switch Associated With Oral, Low Dose Ketamine Treatment in a Patient With Treatment Resistant Bipolar I Depression. Case Report and Literature Review

Chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway

The effects of ketamine on suicidality across various formulations and study settings

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