Pharmacodynamic effects of buspirone and clobazam.

Alford, Chris; Bhatti, J. Z.; Curran, Stephen; McKay, G.; Hindmarch, Ian

doi:10.1111/j.1365-2125.1991.tb05618.x

Cited by 15 publications

(7 citation statements)

References 22 publications

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“…Data from both acute and repeated dosing regimen studies (22–70) of drugs with a documented use in the treatment of SAD, which matched the inclusion criteria, were included in the analysis (Table 1). Although phenelzine, selegeline and tranylcypromine are documented for potential use in SAD, no suitable psychometric/pharmacodynamic data were found and these substances are discussed no further.…”

Section: Resultsmentioning

confidence: 99%

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Cognitive toxicity of pharmacotherapeutic agents used in social anxiety disorder

Hindmarch

2009

International Journal of Clinical Practice

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Summary Objective: To compare cognitive impairment of medications used in social anxiety disorder (SAD). Methods: Data from peer‐reviewed publications (1975–2007) of controlled, crossover design, pharmacodynamic studies on SAD medications in healthy volunteers were analysed. The number of objective psychometrics for each drug/dose level at all time points after dosing, and of instances of statistically significant impairment of cognitive function, enabled calculation of drug‐induced cognitive impairment. The magnitude of impairment between drugs was compared using proportional impairment ratios (PIRs). Results: Olanzapine, oxazepam, lorazepam and mianserin had twice the average cognitive toxicity of other treatments. Selective serotonin reuptake inhibitors (SSRIs) impaired cognition to a lesser extent than other pharmacological groupings. There was extensive intra‐class variation: fluvoxamine (PIR = 0.08) possessed little detrimental cognitive activity, whereas sertraline (PIR = 5.33) caused impairment over five times the SSRI group average. Benzodiazepines caused noticeable cognitive impairment. Conclusions: Substantial differences exist, both between and within therapeutic classes, in the behavioural toxicity of medications used for SAD.

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Section: Resultsmentioning

confidence: 99%

“…Propanolol (26,27,30,36) Bupropion (44,54) Azapirones Mianserin (3,28,29,42,44,56) Buspirone (22,25,47,50) Mirtazapine (48,57,68) Miscellaneous Moclobemide (34,45,56,64) Atypical antipsychotics Nefazodone (53) Olanzapine (24,69) Venlafaxine (51,53) SAD, social anxiety disorder.…”

Section: Other Antidepressantsmentioning

confidence: 99%

Cognitive toxicity of pharmacotherapeutic agents used in social anxiety disorder

Hindmarch

2009

International Journal of Clinical Practice

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“…Previous reports of other 5HT 1 agonists, like buspirone and umespirone, have shown mixtures of sedative and stimulant effects (37–41). Buspirone showed a subjective sedative effect on analogue rating scales, impaired memory and increased reaction times for cognitive tests.…”

Section: Discussionmentioning

confidence: 95%

“…Umespirone also increased reaction times. Stimulant effects such as an increase in subjective alertness and a decrease in reaction times were observed for buspirone (39) and improvements in word recognition and mood were observed for umespirone (37). Our observations on the 5HT 1B/D agonist‐triptans are partly compatible with these findings.…”

Section: Discussionmentioning

confidence: 99%

Cns Effects of Sumatriptan and Rizatriptan in Healthy Female Volunteers

et al. 2002

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This study investigates the CNS effects of sumatriptan and rizatriptan, with temazepam as an active comparator, in healthy female volunteers. Sixteen volunteers completed a randomized, double-blind, crossover study and on four separate occasions received either 100 mg sumatriptan, 20 mg rizatriptan or 20 mg temazepam. The main parameters were eye movements, EEG, body sway, visual analogue scales and a cognitive test battery. Rizatriptan and sumatriptan decreased saccadic peak velocity by 18.3 (95% CI: 5.7, 30.8) and 15.0 (2.2, 27.9) degrees/sec, respectively, about half the decrease induced by temazepam (35.0 (22.1, 47.8) degrees/sec). Body sway increased (30% for rizatriptan (16%, 45%) and 14% for sumatriptan (1%, 27%), respectively). Temazepam caused larger, similar effects. In contrast to temazepam, sumatriptan and rizatriptan decreased reaction times of recognition tasks and increased EEG alpha power (significant for sumatriptan, 0.477 (0.02, 0.935). Therapeutic doses of sumatriptan and rizatriptan caused CNS effects indicative of mild sedation. For EEG and recognition reaction times the effects were opposite to temazepam, indicating central stimulation.

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“…71–77 However, in anxiety RCTs that used repeated clobazam dosing and allowed for N-desmethylclobazam accumulation, it was not clear that clobazam was better than other benzodiazepines regarding drowsiness. 78 …”

Section: Literature Reviewmentioning

confidence: 99%

Clobazam Therapeutic Drug Monitoring

Leon

Spina

Díaz

2013

Therapeutic Drug Monitoring

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Background Clobazam was recently approved for Lennox-Gastaut syndrome in the US. There is no published review article focused on clobazam therapeutic drug monitoring (TDM) in English. Methods More than two hundred clobazam articles identified by a PubMed search were carefully reviewed for information on clobazam pharmacokinetics. Clobazam is mainly metabolized by a cytochrome P450 (CYP) isoenzyme, CYP3A4, to its active metabolite, N-desmethylclobazam. Then, N-desmethylclobazam is mainly metabolized by CYP2C19 unless the individual has no CYP2C19 activity (poor metabolizer, PM). Results Using a mechanistic approach to reinterpret the published findings of steady-state TDM and single-dosing pharmacokinetic studies, four different serum clobazam concentration ratios were studied. The available limited steady-state TDM data suggest that the serum N-desmethylclobazam/clobazam ratio can be useful for clinicians, including identifying CYP2C19 PMs (ratio >25 in the absence of inhibitors). There are three possible concentration/dose (C/D) ratios. The clobazam C/D ratio has the potential to measure the contribution of CYP3A4 activity to the clearance of clobazam from the body. The N-desmethylclobazam C/D ratio does not appear to be a good measure of clobazam clearance and should be substituted with the total (clobazam+N-desmethylclobazam) C/D ratio. Conclusions Future clobazam TDM studies need to use trough concentrations after steady-state has been reached (>3 weeks in normal individuals and several months in CYP2C19 PMs). These future studies need to explore the potential of clobazam and total C/D ratios. Better studies on the relative potency of N-desmethylclobazam compared to the parent compound are needed to provide weighted total serum concentrations that correct for the possible lower N-desmethylclobazam pharmacodynamic activity. Standardization and more studies of C/D ratios from clobazam and other drugs can be helpful to move TDM forward.

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Pharmacodynamic effects of buspirone and clobazam.

Cited by 15 publications

References 22 publications

Cognitive toxicity of pharmacotherapeutic agents used in social anxiety disorder

Cognitive toxicity of pharmacotherapeutic agents used in social anxiety disorder

Cns Effects of Sumatriptan and Rizatriptan in Healthy Female Volunteers

Clobazam Therapeutic Drug Monitoring

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