EEG and Sleep Effects of Tramadol Suggest Potential Antidepressant Effects with Different Mechanisms of Action

Koncz, Szabolcs; Papp, Noémi; Menczelesz, Noémi; Pothorszki, Dóra; Bagdy, György

doi:10.3390/ph14050431

Cited by 8 publications

(6 citation statements)

References 66 publications

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“…The sleep-wake stages were classified using SleepSign for Animal sleep analysis software (Kissei Comtec America Inc., Fort Lee, NJ, USA), using conventional criteria ( Kantor et al, 2004 ; Koncz et al, 2021 ). We used the automatic scoring feature of the software to score the vigilance stages at first; after that, visual supervision was conducted by researchers who were unaware of the treatment of the rats.…”

Section: Methodsmentioning

confidence: 99%

(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats

Koncz

Papp

Pothorszki

et al. 2023

International Journal of Neuropsychopharmacology

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Background Racemic ketamine consists of two enantiomers, namely (R)ketamine and (S)ketamine, with distinguishable pharmacological properties. Both enantiomers have been reported to show rapid antidepressant effects in rodents. Currently, the (S)enantiomer has been approved for the treatment of major depression, while (R)ketamine failed to show antidepressant effect in recent clinical studies. Major depressive disorder is frequently characterized by disinhibition of rapid eye movement (REM) sleep and disruption of nonREM (NREM) sleep. Racemic ketamine and most conventional antidepressants affect these parameters. However, it remains largely unknown which enantiomer is responsible for these effects. Methods Here, we compared acute effects of the two ketamine enantiomers (15 mg/kg i.p.) on different sleepwake stages in freely moving, EEGequipped rats. We also evaluated the antidepressant-like activity of the enantiomers in a chronic restraint stress model of depression. Results (S)ketamine, but not (R)ketamine increased REM sleep latency and decreased REM sleep time at 2h and 3h, and increased EEG delta power during NREM sleep. In addition, only (S)-ketamine increased wakefulness and decreased NREM sleep in the first 2 hours. In the forced swimming test only (S)-ketamine decreased the immobility time of chronically stressed rats. Conclusion Effects of the two ketamine enantiomers on rat sleepwake architecture and behavior are markedly different when administered in the same dose. (S)ketamine remarkably affects sleepwake cycle and very likely sleeprelated neuroplasticity, which may be relevant for its antidepressant efficacy. Our results regarding (R)-ketamine’s lack of effect on vigilance and behavior are in line with the recent clinical studies.

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Section: Methodsmentioning

confidence: 99%

(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats

Koncz

Papp

Pothorszki

et al. 2023

International Journal of Neuropsychopharmacology

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“…44 Recent animal studies have also found that tramadol dose-dependently reduces sleep time during rapid eye movement sleep and increases the attack latency of rapid eye movement sleep. 45 In this study, we found that compared with the control group, tramadol can directly improve the sleep score of patients on the first to third day after surgery. One study has indicated that opioids can affect the quality of sleep, and both acute (for sedation or postoperative analgesia) or chronic (long-term for chronic pain) can disrupt sleep patterns.…”

mentioning

confidence: 68%

Effects of Intravenous Analgesia Using Tramadol on Postoperative Depression State and Sleep Quality in Women Undergoing Abdominal Endoscopic Surgery: A Randomized Controlled Trial

Fu¹,

Chen²,

Xu³

et al. 2022

DDDT

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This study aimed to explore the effects of intravenous analgesia using tramadol on postoperative depression, anxiety, and sleep in women undergoing abdominal endoscopic surgery. Patients and Methods: Two hundred female patients (100 in each group) who underwent abdominal endoscopic surgery were recruited to randomly receive intravenous analgesia with sufentanil combined with tramadol (tramadol group) or sufentanil (control group). The primary outcome was the incidence of postoperative depression, which was assessed at 1, 2, and 3 days after surgery using the 13-item Beck Depression Inventory. The secondary outcomes were the incidence of anxiety and sleep quality, which were assessed using the 20-item Self-Rating Anxiety Scale and Richards-Campbell Sleep Questionnaire. Results: The incidence of depression (Beck depression scale≥4) during the 3-day follow-up in the control group was 51%, which was significantly higher than that in the tramadol group of 28% (relative risk [RR]=0.55; 95% confidence interval [CI], 0.38-0.79; P=0.001). No difference was found in the incidence of anxiety state (Self-Rating Anxiety Scale≥40) between the tramadol and control groups (7%vs 5%; RR=1.40; 95% CI, 0.46-4.25; P=0.552). All of the Richards-Campbell sleep scales of patients in the tramadol group at 1 (77.4±15.2 vs 64.2±20.1, P<0.001), 2 (84.1±14.9 vs 71.8±18.8, P<0.001), and 3 days (87.0±12.2 vs 70.3±21.0, P<0.001) after surgery were higher than those in the control group. Conclusion: Intravenous analgesia using tramadol can effectively improve the postoperative depression and sleep status of women undergoing abdominal endoscopic surgery. Tramadol is recommended for use in postoperative analgesia when improving postoperative mood, and sleep is needed in clinical practice.

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“…Rats (9 weeks old), weighing between 290–325 g at surgery, were implanted with EEG and electromyographic (EMG) electrodes under 2% isoflurane anesthesia, using a Kopf stereotaxic instrument, as described earlier [ 6 , 27 , 28 , 29 ]. Briefly, for frontoparietal EEG recordings, stainless steel screw electrodes were placed epidurally over the left frontal cortex (1.5 mm lateral and 2.0 mm anterior to bregma) and over the left parietal cortex (1.5 mm lateral and 2.0 mm anterior to lambda), and a ground electrode was equipped over the cerebellum.…”

Section: Methodsmentioning

confidence: 99%

Unique Effects of (R)-Ketamine Compared to (S)-Ketamine on EEG Theta Power in Rats

Pothorszki,

Koncz,

Török

et al. 2024

Pharmaceuticals

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Differences in the pharmacological effects of (S)-ketamine and (R)-ketamine are at the focus of research. Clinical data and our rat studies confirmed the antidepressant effect of (S)- but not (R)-ketamine, with similar differences in quantitative electroencephalogram (EEG) and sleep effects. In contrast, studies mainly on mice showed some stronger, preferable effects of (R)-ketamine. EEG theta (5–9 Hz) rhythm originates from the hippocampus, and its power is associated with cognitive functions, attention, and decreased anxiety. To find a brain parameter that is not associated with the antidepressant effect of drugs and may confirm potent in vivo effects of (R)-ketamine in rats, theta EEG power-inducing effects of the two enantiomers were measured and compared for 23 h. EEG-equipped Wistar rats were treated with (R)-ketamine (7.5, 15, 30 mg/kg i.p.), (S)-ketamine (7.5 and 15 mg/kg i.p.), or vehicle at the beginning of the passive phase. Frontoparietal EEG, electromyogram, and motor activity were recorded. (R)-ketamine but not (S)-ketamine dose-dependently increased EEG theta power during wakefulness and rapid eye movement (REM) sleep for 23 h. These results suggest that (R)-ketamine has an effect on a hippocampal function that was not affected by (S)-ketamine and may be associated with neural plasticity and memory encoding.

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EEG and Sleep Effects of Tramadol Suggest Potential Antidepressant Effects with Different Mechanisms of Action

Cited by 8 publications

References 66 publications

(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats

(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats

Effects of Intravenous Analgesia Using Tramadol on Postoperative Depression State and Sleep Quality in Women Undergoing Abdominal Endoscopic Surgery: A Randomized Controlled Trial

Unique Effects of (R)-Ketamine Compared to (S)-Ketamine on EEG Theta Power in Rats

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