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Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression.

ABSTRACT: Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions. Thirty-seven participants with treatment-resistant depression (TRD) and baseline SI first received a single ketamine infusion during a randomized, double-blind crossover with midazolam. Following relapse of depressive symptoms, participants received six open-label ketamine infusions administered thrice-weekly over 2 weeks. Antidepressant responders (?50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) received four further open-label infusions administered once-weekly. Changes in SI were assessed with the suicide items on the MADRS (item 10, MADRS-SI) and the Quick Inventory of Depressive Symptomatology-Self Report (item 12, QIDS-SI). Linear mixed models revealed that compared with midazolam, a single ketamine infusion elicited larger reduction in SI (P?=?0.01), with maximal effects measured at 7 days postinfusion (P?

SUBMITTER: Phillips JL

PROVIDER: S-EPMC7021716 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression.

Phillips Jennifer L JL Norris Sandhaya S Talbot Jeanne J Hatchard Taylor T Ortiz Abigail A Birmingham Meagan M Owoeye Olabisi O Batten Lisa A LA Blier Pierre P

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20191123 4

Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions. Thirty-seven participants with treatment-resistant depression (TRD) and baseline SI first received a single ketamine infusion during a randomi ...[more]

PMID: 31759333

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Project description:ObjectiveIt is recognised that ketamine treatment can reduce suicidal ideation (SI) in people with depression, at least in the short term. However, information is lacking on patients' perspectives on such effects. Studying these can contribute to greater understanding of the mechanisms underlying impact of ketamine treatment on SI. The aim of this study was to investigate patients' reports of the impact of treatment on their SI, the duration of effects and possible mechanisms.Design and settingThis qualitative study consisted of semi-structured interviews with patients who had received ketamine treatment for depression. Interview data were analysed thematically.ParticipantsFourteen patients (8 females, 6 males, aged 24-64 years) who had received treatment with ketamine for treatment-resistant depression, and had SI at the initiation of treatment. Two participants also had a diagnosis of bipolar type 1 and two of emotionally unstable personality disorder. Eight had a history of self-harm.ResultsSI reduced following ketamine treatment in 12 out of 14 participants for periods of a few hours following a single treatment to up to three years with ongoing treatment. Reduction of SI was variable in terms of extent and duration, and re-emergence of suicidal thoughts often occurred when treatment ceased. Participants' accounts indicated that reduced SI was associated with improved mood and reduced anxiety, as were clarity of thought, focus and concentration, and ability to function. Participants reported experiencing some or all of these effects in various orders of occurrence.ConclusionGenerally, ketamine treatment was experienced as effective in reducing SI, although duration of effects varied considerably. Patients' perspectives indicated similarities in the mechanisms of reduction in SI, but some differences in their manifestation, particularly in relation to chronology. Experiences of this cohort suggest that reduced anxiety and improvement in ability to think and function were important mechanisms alongside, or in some cases independently of, improvement in mood. Further studies of patients' experiences are required to gain enhanced understanding of the variability of effects of ketamine on SI and functionality.

Project description:Therapeutic seizures may work for treatment-resistant depression (TRD) by producing neuroplasticity. We evaluated whether magnetic seizure therapy (MST) produces changes in suicidal ideation and neuroplasticity as indexed through transcranial magnetic stimulation and electroencephalography (TMS-EEG) of the dorsolateral prefrontal cortex (DLPFC). Twenty-three patients with TRD were treated with MST. Changes in suicidal ideation was assessed through the Scale for Suicidal Ideation (SSI). Before and after the treatment course, neuroplasticity in excitatory and inhibitory circuits was assessed with TMS-EEG measures of cortical-evoked activity (CEA) and long-interval cortical inhibition (LICI) from the left DLPFC, and the left motor cortex as a control condition. As in our previous report, the relationship between TMS-EEG measures and suicidal ideation was examined with the SSI. Results show that 44.4% of patients experienced resolution of suicidal ideation. Based on DLPFC assessment, MST produced significant CEA increase over the frontal central electrodes (cluster p?<?0.05), but did not change LICI on a group level. MST also reduced the SSI scores (p?<?0.005) and the amount of reduction correlated with the decrease in LICI over the right frontal central electrodes (cluster p?<?0.05; rho?=?0.73 for Cz). LICI change identified patients who were resolved of suicidal ideation with 90% sensitivity and 88% specificity (AUC?=?0.9, p?=?0.004). There was no significant finding with motor cortex assessment. Overall, MST produced significant rates of resolution of suicidal ideation. MST also produced neuroplasticity in the frontal cortex, likely through long-term potentiation (LTP)-like mechanisms. The largest reduction in suicidal ideation was demonstrated in patients showing concomitant decreases in cortical inhibition-a mechanism linked to enhanced LTP-like plasticity. These findings provide insights into the mechanisms through which patients experience resolution of suicidal ideation following seizure treatments in depression.

Project description:In this review, we will discuss the safety of repeated treatments with ketamine for patients with treatment-resistant depression (TRD), a condition in which patients with major depression do not show any clinical improvements following treatments with at least two antidepressant drugs. We will discuss the effects of these treatments in both sexes at different developmental periods. Numerous small clinical studies have shown that a single, low-dose ketamine infusion can rapidly alleviate depressive symptoms and thoughts of suicidality in patients with TRD, and these effects can last for about one week. Interestingly, the antidepressant effects of ketamine can be prolonged with intermittent, repeated infusion regimens and produce more robust therapeutic effects when compared to a single infusion. The safety of such repeated treatments with ketamine has not been thoroughly investigated. Although more studies are needed, some clinical and preclinical reports indicated that repeated infusions of low doses of ketamine may have addictive properties, and suggested that adolescent and adult female subjects may be more sensitive to ketamine's addictive effects. Additionally, during ketamine infusions, many TRD patients report hallucinations and feelings of dissociation and depersonalization, and therefore the effects of repeated treatments of ketamine on cognition must be further examined. Some clinical reports indicated that, compared to women, men are more sensitive to the psychomimetic effects of ketamine. Preclinical studies extended these findings to both adolescent and adult male rodents and showed that male rodents at both developmental periods are more sensitive to ketamine's cognitive-altering effects. Accordingly, in this review we shall focus our discussion on the potential addictive and cognitive-impairing effects of repeated ketamine infusions in both sexes at two important developmental periods: adolescence and adulthood. Although more work about the safety of ketamine is warranted, we hope this review will bring some answers about the safety of treating TRD with repeated ketamine infusions.

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Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression.

Publications

Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression.

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