Clonazepam

Abstract: Benzodiazepines (BZDs) remain important agents in the management of epilepsy. They are drugs of first choice for status epilepticus and seizures associated with post-anoxic insult and are also frequently used in the treatment of febrile, acute repetitive and alcohol withdrawal seizures. Clinical advantages of these drugs include rapid onset of action, high efficacy rates and minimal toxicity. Benzodiazepines are used in a variety of clinical situations because they have a broad spectrum of clinical activity and can be administered via several routes. Potential shortcomings of BZDs include tolerance, withdrawal symptoms, adverse events, such as cognitive impairment and sedation, and drug interactions. Benzodiazepines differ in their pharmacologic effects and pharmacokinetic profiles, which dictate how the drugs are used. Among the approximately 35 BZDs available, a select few are used for the management of seizures and epilepsy: clobazam, clonazepam, clorazepate, diazepam, lorazepam and midazolam. Among these BZDs, clorazepate has a unique profile that includes a long half-life of its active metabolite and slow onset of tolerance. Additionally, the pharmacokinetic characteristics of clorazepate (particularly the sustained-release formulation) could theoretically help minimize adverse events. However, larger, controlled studies of clorazepate are needed to further examine its role in the treatment of patients with epilepsy.

Abstract: A simple model system for the behavioral actions of benzodiazepines is analyzed for its dose-response predictiveness, using several benzodiazepines, and for its pharmacological specificity, using other non-anxiolytic classes of psychoactive drugs The model demonstrates an increase in mouse exploratory activity between a brighty-lit open field and a small, dark compartment by clonazepam, diazepam, flurazepam, chlordiazepoxide and meprobamate, but not by the peripheral benzodiazepine R05-4864, nor by clorgyline, butriptyline, or chlorpromazine

Abstract: The main actions of benzodiazepines (hypnotic, anxiolytic, anticonvulsant, myorelaxant and amnesic) confer a therapeutic value in a wide range of conditions. Rational use requires consideration of the large differences in potency and elimination rates between different benzodiazepines, as well as the requirements of individual patients. As hypnotics, benzodiazepines are mainly indicated for transient or short term insomnia, for which prescriptions should if possible be limited to a few days, occasional or intermittent use, or courses not exceeding 2 weeks. Temazepam, loprazolam and lormetazepam, which have a medium duration of action are suitable. Diazepam is also effective in single or intermittent dosage. Potent, short-acting benzodiazepines such as triazolam appear to carry greater risks of adverse effects. As anxiolytics, benzodiazepines should generally be used in conjunction with other measures (psychological treatments, antidepressants, other drugs) although such measures have a slower onset of action. Indications for benzodiazepines include acute stress reactions, episodic anxiety, fluctuations in generalised anxiety, and as initial treatment for severe panic and agoraphobia. Diazepam is usually the drug of choice, given in single doses, very short (1 to 7 days) or short (2 to 4 weeks) courses, and only rarely for longer term treatment. Alprazolam has been widely used, particularly in the US, but is not recommended in the UK, especially for long term use. Benzodiazepines also have uses in epilepsy (diazepam, clonazepam, clobazam), anaesthesia (midazolam), some motor disorders and occasionally in acute psychoses. The major clinical advantages of benzodiazepines are high efficacy, rapid onset of action and low toxicity. Adverse effects include psychomotor impairment, especially in the elderly, and occasionally paradoxical excitement. With long term use, tolerance, dependence and withdrawal effects can become major disadvantages. Unwanted effects can largely be prevented by keeping dosages minimal and courses short (ideally 4 weeks maximum), and by careful patient selection. Long term prescription is occasionally required for certain patients.

Abstract: Summary of Recommendations: Modifying the sleep environment is recommended for the treatment of patients with RBD who have sleep-related injury. Level A Clonazepam is suggested for the treatment of RBD but should be used with caution in patients with dementia, gait disorders, or concomitant OSA. Its use should be monitored carefully over time as RBD appears to be a precursor to neurodegenerative disorders with dementia in some patients. Level B Clonazepam is suggested to decrease the occurrence of sleep-related injury caused by RBD in patients for whom pharmacologic therapy is deemed necessary. It should be used in caution in patients with dementia, gait disorders, or concomitant OSA, and its use should be monitored carefully over time. Level B Melatonin is suggested for the treatment of RBD with the advantage that there are few side effects. Level B Pramipexole may be considered to treat RBD, but efficacy studies have shown contradictory results. There is little evidence to support the use of paroxetine or L-DOPA to treat RBD, and some studies have suggested that these drugs may actually induce or exacerbate RBD. There are limited data regarding the efficacy of acetylcholinesterase inhibitors, but they may be considered to treat RBD in patients with a concomitant synucleinopathy. Level C The following medications may be considered for treatment of RBD, but evidence is very limited with only a few subjects having been studied for each medication: zopiclone, benzodiazepines other than clonazepam, Yi-Gan San, desipramine, clozapine, carbamazepine, and sodium oxybate. Level C