Combination of intravenous S-ketamine and oral tranylcypromine in treatment-resistant depression: A report of two cases

Bartova, Lucie; Vogl, Sonja; Stamenkovic, M.; Praschak-Rieder, Nicole; Naderi-Heiden, Angela; Kasper, Siegfried; Willeit, Matthäus

doi:10.1016/j.euroneuro.2015.07.021

Cited by 26 publications

(18 citation statements)

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“…The phenotypical correlate of the, at most discrete, SERT binding we show at low doses is not entirely clear, though a recent publication on co-medication of ketamine and the irreversible MOA-inhibitor tranylcypromine promotes skepticism ( Bartova et al, 2015 ). However, this report is a set of case studies, and ketamine metabolism and plasma levels have been shown to vary after administration of a constant dose ( Zarate et al, 2012 ; Zhao et al, 2012 ).…”

Section: Discussionmentioning

confidence: 88%

Assessment of Ketamine Binding of the Serotonin Transporter in Humans with Positron Emission Tomography

Spies¹,

James²,

Berroterán-Infante³

et al. 2017

International Journal of Neuropsychopharmacology

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BackgroundComprehensive description of ketamine’s molecular binding profile becomes increasingly pressing as use in real-life patient cohorts widens. Animal studies attribute a significant role in the substance’s antidepressant effects to the serotonergic system. The serotonin transporter is a highly relevant target in this context, because it is central to depressive pathophysiology and treatment. This is, to our knowledge, the first study investigating ketamine’s serotonin transporter binding in vivo in humans.MethodsTwelve healthy subjects were assessed twice using [11C]DASB positron emission tomography. A total of 0.50 mg/kg bodyweight ketamine was administered once i.v. prior to the second positron emission tomography scan. Ketamine plasma levels were determined during positron emission tomography. Serotonin transporter nondisplaceable binding potential was computed using a reference region model, and occupancy was calculated for 4 serotonin transporter-rich regions (caudate, putamen, thalamus, midbrain) and a whole-brain region of interest.ResultsAfter administration of the routine antidepressant dose, ketamine showed <10% occupancy of the serotonin transporter, which is within the test-retest variability of [11C]DASB. A positive correlation between ketamine plasma levels and occupancy was shown.ConclusionsMeasurable occupancy of the serotonin transporter was not detectable after administration of an antidepressant dose of ketamine. This might suggest that ketamine binding of the serotonin transporter is unlikely to be a primary antidepressant mechanism at routine antidepressant doses, as substances that facilitate antidepressant effects via serotonin transporter binding (e.g., selective serotonin reuptake inhibitors) show 70% to 80% occupancy. Administration of high-dose ketamine is widening. Based on the positive relationship we find between ketamine plasma levels and occupancy, there is a need for investigation of ketamine’s serotonin transporter binding at higher doses.

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Section: Discussionmentioning

confidence: 88%

Assessment of Ketamine Binding of the Serotonin Transporter in Humans with Positron Emission Tomography

Spies¹,

James²,

Berroterán-Infante³

et al. 2017

International Journal of Neuropsychopharmacology

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“…No reports were found that confirmed the hypothesized risk of hypertensive crisis or serotonergic syndrome caused by the combination of MAOIs and ketamine. We retrieved 2 case reports about patients with depression receiving tranylcypromine in dosages ranging from 10 to 80 mg daily in combination with S-ketamine ( Bartova et al, 2015 ; Dunner et al, 2019 ). Two patients were administered IV S-ketamine (dosages 12.5–75 mg) while the other patient received intranasal (IN) S-ketamine (dosages 28–56 mg).…”

Section: Resultsmentioning

confidence: 99%

Pharmacodynamic Interactions Between Ketamine and Psychiatric Medications Used in the Treatment of Depression: A Systematic Review

Veraart

Smith-Apeldoorn

Bakker

et al. 2021

International Journal of Neuropsychopharmacology

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Background The use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine oxidase-inhibitors (MAOIs), antipsychotics and psychostimulants. Methods MEDLINE and Web of Science were searched. Results Twenty-four studies were included. For lithium, no significant interactions with ketamine were reported. Two out of five studies on lamotrigine indicated that the effects of ketamine were attenuated. Benzodiazepines were repeatedly shown to reduce the duration of ketamine’s antidepressant effect. For the MAO-inhibitor tranylcypromine, case reports showed no relevant changes in vital signs during concurrent S-ketamine use. One paper indicated an interaction between ketamine and haloperidol, two other studies did not. Four papers investigated risperidone, including three neuroimaging studies showing an attenuating effect of risperidone on ketamine-induced brain perfusion changes. Clozapine significantly blunted ketamine-induced positive symptoms in patients with schizophrenia, but not in healthy subjects. One paper reported no effect of olanzapine on ketamine’s acute psychotomimetic effects. Conclusion Current literature shows that benzodiazepines and probably lamotrigine reduce ketamine’s treatment outcome, which should be taken into account when considering ketamine treatment. There is evidence for an interaction between ketamine and clozapine, haloperidol and risperidone. Due to small sample sizes, different subject groups and various outcome parameters, the evidence is of low quality. More studies are needed to provide insight into pharmacodynamic interactions with ketamine.

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“…Two studies describe BP increases that range between 15.8 mmHg systolic and 9.4 mmHg diastolic [ 20 ], and 23 mmHg systolic and 12 mmHg diastolic [ 21 ]. Another study reported no ‘relevant hemodynamic changes’ [ 18 ] but failed to provide exact data. Lastly, a recent study analyzed 22 ketamine infusions in three patients and did not find statistically significant differences in BP or HR after ketamine infusions [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…This deviates slightly from reports in previous studies. Again, these slight differences might be explained by mode of administration, because all other studies report intravenous [17][18][19][20]22] or nasal [21] application of (es)ketamine, which might lead to bigger hemodynamic changes, or by differences in setting between baseline and esketamine BP readings. Generally, it is important to note that these factors might slightly limit the comparability of our BP change measurements to previous study results of BP change.…”

Section: Comparison With Other Studiesmentioning

confidence: 99%

“…Later on, case studies reported data on psychiatric patients who received (es)ketamine in subanesthetic doses for TRD while simultaneously taking MAOIs. Two case reports on a total of five patients concomitantly receiving an MAOI (tranylcypromine or phenelzine) and intravenous (es)ketamine for TRD observed no relevant hemodynamic changes [ 18 , 19 ]. In contrast, three other case studies described significant increases in BP after the administration of (es)ketamine (intravenous and nasal) in subjects treated with MAOIs (tranylcypromine, phenelzine, selegiline) in a total of nine patients [ 20 – 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Cardiovascular Effects of Combining Subcutaneous or Intravenous Esketamine and the MAO Inhibitor Tranylcypromine for the Treatment of Depression: A Retrospective Cohort Study

et al. 2021

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Background (Es)ketamine and monoamine oxidase inhibitors (MAOIs), e.g., tranylcypromine, are therapeutic options for treatment-resistant major depression. Simultaneous administration is currently not recommended because of concern about hypertensive crises. Objective Our objective was to evaluate whether changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) during esketamine administration differed between patients who concomitantly received tranylcypromine and those who did not. Methods This was a retrospective cohort study utilizing cardiovascular monitoring data from inpatients treated for severe depression in unipolar, bipolar, and schizoaffective disorder. Primary outcomes were change in mean BP and HR during the first hour after intravenous or subcutaneous esketamine administration compared with baseline, controlled for confounders. Secondary analyses quantify differences in absolute BP during esketamine treatment and comparisons of BP peaks, temporal effects, and intraindividual comparisons before and after tranylcypromine initiation. Results Our analysis included 509 esketamine administrations in 43 patients, 14 of whom concomitantly received tranylcypromine. Controlling for creatinine and age, mean ± standard deviation (SD) BP changes were significantly increased by concomitant tranylcypromine treatment (ΔSBP: F[1,503] = 86.73, p < 0.001; ΔDBP: F[1,503] = 55.71, p < 0.001), but HR remained unaffected. Mean SBP change during esketamine administration was 2.96 ± 18.11 mmHg in patients receiving tranylcypromine (TCP+) and −8.84 ± 11.31 mmHg in those who did not (TCP−). Changes in DBP were −2.81 ± 11.20 mmHg for TCP+ and −10.77 ± 9.13 mmHg for TCP−. Moreover, we found a significant dose-response relationship between tranylcypromine dose and BP (SBP: B = 0.35, standard error [SE] = 0.12, 95% confidence interval [CI] 0.12-0.60, p = 0.004; adjusted R 2 = 0.11, p = 0.008; DBP: B = 0.21, SE = 0.08, 95% CI 0.06-0.36, p = 0.007; adjusted R 2 = 0.08; p = 0.023). Conclusions Although statistically significant changes in BP were identified in patients receiving tranylcypromine and esketamine, these changes were clinically insignificant. Thus, combining esketamine and this MAOI appears to be safe at standard doses. The dose-response relationship calls for caution with higher doses of tranylcypromine.

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Combination of intravenous S-ketamine and oral tranylcypromine in treatment-resistant depression: A report of two cases

Cited by 26 publications

References 5 publications

Assessment of Ketamine Binding of the Serotonin Transporter in Humans with Positron Emission Tomography

Assessment of Ketamine Binding of the Serotonin Transporter in Humans with Positron Emission Tomography

Pharmacodynamic Interactions Between Ketamine and Psychiatric Medications Used in the Treatment of Depression: A Systematic Review

Cardiovascular Effects of Combining Subcutaneous or Intravenous Esketamine and the MAO Inhibitor Tranylcypromine for the Treatment of Depression: A Retrospective Cohort Study

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