Safety and Tolerability of Ketamine Use in Treatment-Resistant Bipolar Depression Patients with Regard to Central Nervous System Symptomatology: Literature Review and Analysis
Abstract
:1. Introduction
2. Ketamine in Major Depressive Disorder (MDD) and Bipolar Depressive Disorder
2.1. Special Populations
2.2. Central Nervous System Safety of Ketamine in Depression Treatment
2.3. Central Nervous System Symptomatology with Add-on Ketamine in TRBD Patients
2.4. Clinical Relevance
2.5. Indications for Best Practice
3. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Group | Examples |
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Psychiatric | Dissociative symptoms (distortion of reality, feeling of bodily changes, acting as if dreaming, feeling of unreality or identity confusion), |
Affective | Irritability, nightmares, agitation, anxiety, lethargy, |
Cognitive | Global cognitive deterioration, sleepiness, |
Neurologic | Transitory lack of motor coordination (duration <1 h), dizziness, headache, blurred vision |
Title | ||||
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‘Adverse events associated only with ketamine (≥10% of subjects) included dissociation, feeling strange, weird, or bizarre’ | Diazgranados et al., 2010 | Ketamine hydrochloride 0.5 mg/kg, 40 min infusion (single dose) | double-blind, randomized, placebo controlled, add-on | 18 TRBD patients |
‘Typical effects occurring at subanesthetic doses of ketamine were dissociation/perceptual disturbances, confusion (…); in no case did (…) dissociation persist beyond 60 min.’ | Sos et al., 2013 | Ketamine hydrochloride 0.54 mg/kg, 30 min (0.27 mg/kg for the first 10 min, followed by a maintenance infusion of 0.27 mg/kg within 20 min) | double-blind, randomized, placebo controlled | 27 TRD-MDD patients, recurrent and single episodes |
‘Eight of the 47 patients receiving ketamine (17%) had significant dissociative symptoms (i.e., feeling outside of one’s body or perceiving that time is moving more slowly or more quickly than normal) immediately after ketamine infusion; symptoms resolved by 2 h post-infusion. No severe psychotic symptoms (paranoia, hallucinations, delusions, or thought disorder) occurred in any patient.’ ‘There was no trend toward increasing dissociative or psychotomimetic effects over the course of the trial.’ | Murrough et al., 2013 | Ketamine hydrochloride 0.5 mg/kg, 40 min infusion | double-blind, randomized, with midazolam (active placebo) | 24 TRD–MDD patients |
‘Ketamine resulted in a mild increase in dissociative symptoms as measured by the Clinician-Administered Dissociative States Scale (increase from a mean of 0 before infusion to 8.60 ± 6.49 at the end of the infusion (t0 + 40 min); p = 0.0001), which returned to baseline by 120 min after infusion ends.’ | Shiroma et al., 2014 | Ketamine hydrochloride 0.5 mg/kg, 40 min infusion (up to 6 infusions, three times per week over a 12-day period) | Open-label | 14 TRD-MDD patients |
‘Intranasal ketamine was associated with small increases of measures of psychosis and dissociation. No relationship between ketamine-associated changes in dissociative or psychotomimetic symptoms and antidepressant response was found (p < 0.05 for CADSS and Brief Psychiatric Rating Scale).’ | Lapidus et al., 2014 | Ketamine hydrochloride 50 mg intranasal administration | Five intranasal applications of solution separated by 5 min each of five ketamine applications provided 10 mg of study drug. | 20 TRD-MDD patients |
‘Adverse events occurring during the infusion in 10% or more of the subjects receiving ketamine or placebo included feeling woozy or loopy, feeling lethargic or drowsy, cognitive impairment, fear or anxiety, nausea, dizziness, odd sensations, blurred vision, and headache. No adverse event was significantly different from placebo at 80 min or thereafter. Headaches, drowsiness, or sedation, early morning awakening, and difficulty falling asleep were reported in 10% of the sample in both the ketamine and the placebo phases. Dry mouth, dizziness or faintness, difficulty falling asleep, and flatulence were reported for ketamine only; irritability and muscle, bone, or joint pain were reported for placebo only. No significant changes occurred in electrocardiogram, respiratory, or laboratory values during the study.’ | Zarate et al., 2012 | Ketamine hydrochloride 0.5 mg/kg, 40 min. infusion | double-blind, randomized, placebo controlled, add-on | 15 TRBD patients |
Educate Your Colleagues about Ketamine Safety and Efficacy |
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Consider ketamine for TRBD patients (or TRBD ‘special populations’ and/or patients with suicidal thoughts) |
Monitor TRBD patients, despite adverse events’ resolution is mostly spontaneous and uncomplicated |
Treat adverse events only if necessary (f. ex. lorazepam 1 mg, orally) |
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Włodarczyk, A.; Cubała, W.J. Safety and Tolerability of Ketamine Use in Treatment-Resistant Bipolar Depression Patients with Regard to Central Nervous System Symptomatology: Literature Review and Analysis. Medicina 2020, 56, 67. https://doi.org/10.3390/medicina56020067
Włodarczyk A, Cubała WJ. Safety and Tolerability of Ketamine Use in Treatment-Resistant Bipolar Depression Patients with Regard to Central Nervous System Symptomatology: Literature Review and Analysis. Medicina. 2020; 56(2):67. https://doi.org/10.3390/medicina56020067
Chicago/Turabian StyleWłodarczyk, Adam, and Wiesław Jerzy Cubała. 2020. "Safety and Tolerability of Ketamine Use in Treatment-Resistant Bipolar Depression Patients with Regard to Central Nervous System Symptomatology: Literature Review and Analysis" Medicina 56, no. 2: 67. https://doi.org/10.3390/medicina56020067