Effects of repeated dosing with mirtazapine, trazodone, or placebo on driving performance and cognitive function in healthy volunteers

Sasada, Kazumi; Iwamoto, Kunihiro; Kawano, Naoki; Kohmura, Kunihiro; Yamamoto, Maeri; Aleksić, Branko; Ebe, Koji; Noda, Yukihiro; Ozaki, Norio

doi:10.1002/hup.2321

Cited by 27 publications

(34 citation statements)

References 35 publications

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“…Mirtazapine treatment also significantly improved depressive symptoms; however, the absence of placebo and/or an a priori subgroup analysis, as well as the absence of other method approaches to determine direct effect, disallows any firm conclusions about mirtazapine's putative, direct, and beneficial effects [45]. Moreover, any assertions of mirtazapine's beneficial effects on cognition would need to be considered in light of the replicated evidence of clinically significant rates of sedation, somnolence, and possible interference with psychomotor performance associated with this agent [46].…”

Section: Antidepressantsmentioning

confidence: 94%

The Prevalence, Measurement, and Treatment of the Cognitive Dimension/Domain in Major Depressive Disorder

et al. 2015

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Insufficient outcomes amongst adults with major depressive disorder (MDD) provide the impetus to identify and refine therapeutic targets that are most critical to outcome from patient, provider, and societal perspectives. Towards this aim, a pivotal shift towards the transnosological domain, cognition, is occurring in the study of MDD and other brain disorders. This paper aims to provide a framework for conceptualizing and prioritizing cognitive function amongst adults with MDD with a particular view to provide a conceptual framework for research and clinical priorities. We also summarize extant data pertaining to psychotropic effects, notably antidepressants, on the cognitive dimension/domain. This narrative review was based on articles identified through a PubMed/MEDLINE search of all English-language articles published between January 1966 and October 2014. The search words were major depressive disorder, depression, unipolar depression, cognition, cognitive dysfunction, cognitive deficit, and cognitive function. The search was supplemented with a manual review of relevant references. The selection of articles for inclusion in this review was based on overall methodological quality as well as on their pertinence to informing the framework described herein. Cognitive dysfunction in MDD is a discrete domain subserved by discrete yet overlapping substrates. There is a need to provide a glossary of terms commonly employed in the cognition literature for consensus as to the appropriate screening, measurement, and monitoring tools. The guiding principle of measurement-based care should include systematic assessment and measurement of cognition in subpopulations with MDD, as a tactic to improve outcome. Relatively few treatment strategies have demonstrated efficacy specifically for the cognitive domain in MDD. The antidepressant vortioxetine has replicated evidence of specific pro-cognitive effects in adults with MDD across multiple subdomains of cognitive function. Vortioxetine is a novel antidepressant that is hypothesized to act through a combination of direct effects on receptor activity and serotonin receptor inhibition, as well as other systems. Pro-cognitive effects for other US FDA-approved agents are suggested, but pseudospecificity has not been excluded as a possible explanation of their beneficial effects on cognitive function. A disparate assortment of other agents are currently under investigation for possible benefit in mitigating cognitive deficits and improving cognitive performance (e.g., intranasal insulin, erythropoietin, anti-inflammatory agents). Non-pharmacological approaches including, but not limited to, cognitive remediation (CR), aerobic exercise, and neuromodulation are promising.

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Section: Antidepressantsmentioning

confidence: 94%

The Prevalence, Measurement, and Treatment of the Cognitive Dimension/Domain in Major Depressive Disorder

et al. 2015

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“…Trailmaking B, a task commonly used to evaluate executive functions in various clinical situations, is a well-studied predictor of unsafe driving [139][140][141] and participant performance is significantly altered by ketamine administration. Moreover, the Wisconsin Card Sorting Test, [143][144][145].…”

Section: Att Entionmentioning

confidence: 99%

Effects of ketamine on psychomotor, sensory and cognitive functions relevant for driving ability

Giorgetti¹,

Marcotulli²,

Tagliabracci³

et al. 2015

Forensic Science International

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“…19 This finding may point to the fact that the sedative effect of MIR at doses of 30 mg/kg or higher gradually decreases. Our statistical analyses revealed no difference between the different doses of MIR tested herein.…”

Section: Experiments 2: Effect Of Chronic Mir Dosing On Sedationmentioning

confidence: 99%

“…42 This suggests that the adverse effects of different daily dosing regimens of MIR disappear within minutes of administration, which is consistent with its sleep-promoting effects. 19,29 This pharmacological property of MIR increases its treatment adherence and substantially improves the symptoms of depression.…”

Section: Experiments 2: Effect Of Chronic Mir Dosing On Sedationmentioning

confidence: 99%

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Chronic dosing with mirtazapine does not produce sedation in rats

Salazar-Juárez

Barbosa-Méndez

Merino-Reyes

et al. 2017

Rev. Bras. Psiquiatr.

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Objective: Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used. The purpose of this study was to explore the effects of acute and chronic administration of different doses of MIR on sedation in the rat. Methods: Assessment of sedation was carried out behaviorally using the rotarod, spontaneous locomotor activity, and fixed-bar tests. Results: A 15-mg/kg dose of MIR induced sedative effects for up to 60 minutes, whereas 30 mg/kg or more produced sedation within minutes and only in the first few days of administration. Conclusion: These results suggest that 30 mg/kg is a safe, well-tolerated dose of MIR which generates only temporary sedative effects.

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Effects of repeated dosing with mirtazapine, trazodone, or placebo on driving performance and cognitive function in healthy volunteers

Cited by 27 publications

References 35 publications

The Prevalence, Measurement, and Treatment of the Cognitive Dimension/Domain in Major Depressive Disorder

The Prevalence, Measurement, and Treatment of the Cognitive Dimension/Domain in Major Depressive Disorder

Effects of ketamine on psychomotor, sensory and cognitive functions relevant for driving ability

Chronic dosing with mirtazapine does not produce sedation in rats

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