Research and Clinical Trials on Clonazepam (Klonopin, Rivotril)
This list of current clinical research trials on Clonazepam (Klonopin, Rivotril) is followed by a short set of abstracts from the most recent research articles published on the drug.
Clonazepam (Klonopin, Rivotril) Clinical Research Trials
From our searchable database at ClinicalTrialsFeeds.org, this list includes all the latest information about clinical trials involving Clonazepam (Klonopin, Rivotril).
- Study of Antiepileptic Drug in Generalised Convulsive Status Epilepticus
Status: Recruiting, Condition Summary: Status; Epilepticus, Tonic-clonic
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Clonazepam: 
Current Research Literature on Clonazepam (Klonopin, Rivotril)
Here are abstracts for some of the latest research articles to have appeared on Clonazepam (Klonopin, Rivotril):
Sleep in patients with epilepsy.
Acta Neurol Taiwan. 2011 Dec; 20(4): 229-131
Kwan SY
Sleep disorder is common in all societies, so are in the patients with epilepsy (PWE). In the International Classification of Sleep Disorders (ICSD) published 2001, it is categorized into four main subsidiaries, which are (1) dyssomnias, (2) parasomnias, (3) sleep disorders associated with mental, neurologic, or other medical disorders and (4) proposed sleep disorders (1). No matter what the final diagnosis is, the results usually are poor quality of sleep and excessive daytime sleepiness. There are complex pathophysiologic mechanisms that underlie the interaction of sleep and epilepsy. These include (1) epilepsy seizure per se, (2) psychotic and psychiatric impact from epilepsy and (3) side effects from antiepileptic drugs (AEDs). In PWE, poor sleep quality causes sleep deprivation, which in turn exaggerates the attacks of seizures and falls into vicious cycles. Thus, it is worth paying attention to this field. Sleep is an extremely valuable physiological activating technique in epilepsy and is used routinely in the electroencephalographic (EEG) recording. The importance in the activation of epileptiform discharges (EDs) during sleep was first demonstrated by Gibbs and Gibbs in 1947 (2). It is proposed that non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep have contrasting effects on ictal and interictal EDs. EDs are likely to propagate during NREM sleep, including its synchronized EEG transients, such as K-complexes and sleep spindles. In contrast, REM sleep, with its asynchronous cellular discharge patterns and skeletal motor paralysis, is resistant to propagation of EDs and to clinical motor accompaniment. In addition, the preserved skeletal muscle tone in NREM permits seizure-related movement, whereas the lower motor neuron inhibition in REM prevents seizure-related movement (3). These can explain why clinical seizures and interictal EDs tend to occur in NREM rather than REM sleep. Seizures markedly activated by sleep including the seizures of frontal lobe origin and the generalized tonic seizures of Lenox-Gastaut syndrome. The epilepsies that having interictal EDs markedly activated during NREM sleep include benign rolandic epilepsy, temporal lobe epilepsy and infantile spasm. While the Landau-Kleffner syndrome and the atypical benign rolandic epilepsy possess the most striking increase of EDs with continuous spike-and-wave complexes during slow wave sleep (CSWS) or electrical status epilepticus during sleep (ESES) in EEG (Figure 1) and absence of normal sleep activities. On days after nocturnal seizures, patients had more severe excessive daytime sleepiness as compared with days after seizure free nights. As compared with seizurefree nights, nights with seizures were characterized by a reduction of REM and stage 3 sleep, prolonged REM latency and reduced sleep efficiency(4). These findings held true even on seizure-free nights. Nocturnal generalized seizures would decrease sleep time and REM sleep percentage, prolong REM latency, and fragment sleep(5). Multiple focal seizures in a night also significantly reduced REM sleep. In addition, not only seizures occurring at night but also those occurring during the day can affect sleep architecture, with proved significant reduction of REM sleep and prolongation REM latency in the following nights(6). Psychological or psychiatric problems, having a high incidence in PWE, may also play a role in disturbing normal sleep. It was reported that 40% of respondents with insomnia and 46.5% of respondents with hypersomnia had a psychiatric disorder. Anxiety disorders were found to be the most common mental disorders (7). Another study found that 93% of depressed inpatients complained of insomnia (8). In PWE, depression is the most frequent comorbid psychiatric disorder, with a prevalence of 10% to 20% among patients with controlled seizures and 20% to 60% among those with refractory epilepsy(9,10). The prevalence of anxiety disorder, panic disorder, obsessive-compulsive disorder and phobias is also high in PWE, with estimates of 3% to 66% (10). Psychosis consisting of visual or auditory illusions and hallucinations, paranoia, depersonalization, derealization, autoscopy, or delusion is reported in 0.6% to 7% of PWE in the community, and in 19% to 27% of hospital-derived populations (11). The overall frequency of psychosis among PWE is approximately 7% to 14%. Reports suggest that up to 69% of patients with temporal lobe epilepsy and 72% of patients with generalized epilepsy suffer from personality disorders (12). Even as benign as juvenile myoclonic epilepsy, 14% was reported to have personality disorders (13). Sleep disturbance in PWE may be secondary to AEDs they are treated with. Most old AEDs were reported to result in a normalization of the sleep architecture and sleep efficiency (14). Studies suggest that phenytoin (PHT), phenobarbital (PB), carbmazepine (CBZ) and clonazepam (CZP) can decrease sleep latency. PB and ethosuximide (ESM) can decrease awakening and arousal. CBZ and CZP can decrease wake time after sleep onset. PHT, PB and ESM can increased stage 1 and stage 2 sleep. CZP can increase stage 2 sleep. PHT, CBZ and valproic acid (VPA) can increased slow wave sleep. PB, VPA and CZP can decrease REM sleep. In newer AEDs, gabapentin (GBP) can decrease awakening and arousal but increased slow wave sleep (14). However, AEDs can also have negative effect on sleep architecture. VPA and ESM can increase awakening and arousal. VPA can increase wake time after sleep onset. PHT, CZP and ESM can decrease slow wave sleep. ESM will increase REM sleep. In newer AEDs, GBP can increase REM sleep, lamotrigine produced somnolence in 14% and insomnia in 6% of patients. Topiramate produced somnolence in approximately 30% of patients treated. Somnolence and insomnia occurred in 18 and 6%, respectively of patients receiving tiagabine(15). The mechanisms of sleep disorders related to AEDs are complex, some related to their direct sedative effect on central nervous system, and can be ameliorated by gradual escalating the dosages when initiation of treatment. Some are more complicated, for example, the slow wave sleep-enhancing effects were thought to reflect the effect of CBZ on 5-hydroxytryptamine (5-HT) levels or its effect on adenosine receptors that modulate the release of 5-HT and catecholamines (16). Therefore, it is not difficult to expect that sleep disorders are more prevalent in patients with polytherapy than in those with monotherapy and improved after reducing the number of AEDs. Under the invention of modern diagnostic tools especially video monitoring with polysomnography, the types and causes of sleep disorders are much easier to be clarified than before. In the paper "Sleep Quality and Daytime Sleepiness in Patients with Epilepsy" by Chen NC et al (Acta Neurologica Taiwanica Vol 21 No 2 June 2011), they adopted self-rated questionales of Epworth Sleepiness Scale (ESS) and the Pittsburg Sleep Quality Index (PSQI) as tools to estimate excessive daytime sleepiness and sleep quality. They had three main findings: (1) Twenty percent of PWE (23/117) in contrast to 7% of healthy controls (2/30) had excessive daytime sleepiness. (2) There is a significantly higher prevalence of poor sleep quality in the partial seizure, non-seizurefree, and polytherapy groups. (3) The poor seizure control was the strongest independent risk factor for poor sleep quality. Their findings are consistent with the studies in the past decades and worth paying appreciation for it has been the first large scale study in Taiwanese PWE (117 cases) ever since. Indeed, the complex relationship between epilepsy and sleep disorder must be addressed in order to provide the best management of sleep disturbance in PWE.
J Neural Transm. 2012 Feb 7;
Nieoczym D, Socała K, Luszczki JJ, Czuczwar SJ, Wlaź P
The aim of the present study was to investigate the effect of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on threshold for clonic seizures in mice. In addition, the effects of sildenafil on the anticonvulsant activity of selected antiepileptic drugs (AEDs), i.e., clonazepam (CZP), valproate (VPA), phenobarbital (PB), ethosuximide (ETS) and tiagabine (TGB), were also evaluated. The subcutaneous pentylenetetrazole (PTZ) test was used to determine the effects of sildenafil on convulsive susceptibility and the anticonvulsant activity of the studied AEDs in mice, while the acute side effects of sildenafil and its combinations with the studied AEDs were evaluated in the chimney test, step-through passive-avoidance task and grip-strength test in mice. Total brain concentrations of AEDs were also determined. Sildenafil (5-40 mg/kg) did not influence the threshold for PTZ-induced clonic seizures in mice, but increased the anticonvulsant activity of ETS in this test without any significant changes in the total brain concentration. The activity of the remaining AEDs was not significantly changed by sildenafil. Neither sildenafil alone nor its combinations with the studied AEDs produced any changes in the motor coordination, long-term memory and muscular strength in mice. Co-administration of sildenafil with ETS in male epileptic patients with co-existing erectile dysfunctions might lead to the pharmacodynamic interactions that may be beneficial for the patients. Combinations of sildenafil with CZP, VPA, PB and TGB appear to be neutral in terms of their influence on seizures.
Psychopathological dimensions of tinnitus and psychopharmacologic approaches in its treatment.
Gen Hosp Psychiatry. 2012 Jan 26;
Belli H, Belli S, Oktay MF, Ural C
BACKGROUND: The aim of this review to investigate presence of psychopathological states and efficacy of psychopharmacological drugs in the treatment of tinnitus. MATERIALS AND METHODS: An extensive Internet search has been performed for this aim through PubMed by using related key words in English. RESULTS: Higher anxiety and depression levels and somatoform disorder clusters are defined in patients with tinnitus. Additionally, impulsivity, hostility, demanding, physical discomfort, anxiety for health, emotionality and suicidal tendency are also defined in these people. Personality characteristics in these patients are depression, hysteria and hypochondriac features. Besides these symptom clusters, more severe psychopathologies like personality disorders may be encountered in these patients. Sertraline, paroxetine and nortriptyline can be considered as the first-line antidepressants in the psychopharmacological treatment of tinnitus. There are studies which have reported the efficacy of sulpiride. Carbamazepine, valproate and gabapentin can be effective as mood stabilizers. Short-acting benzodiazepines like alprazolam and midazolam are effective in signs of anxiety. Clonazepam and diazepam can be evaluated as other options. However, some glutamate receptor antagonists also can be used in the treatment of tinnitus. Disturbed sleep is frequently associated with tinnitus. Sleep disturbance can disrupt the quality of life in the patients with tinnitus. These patients might benefit from cognitive-behavioral therapy, which offers the promise of relief from tinnitus-related distress and insomnia. CONCLUSION: When pathophysiologic reasons are excluded, it should be at least considered that tinnitus is exaggerated by psychopathological symptoms. Life quality of patients can be increased by treating these symptoms.
Muscle relaxants for pain management in rheumatoid arthritis.
Cochrane Database Syst Rev. 2012; 1: CD008922
Richards BL, Whittle SL, Buchbinder R
Pain management is a high priority for patients with rheumatoid arthritis (RA). Muscle relaxants include drugs that reduce muscle spasm (for example benzodiazepines such as diazepam (Valium), alprazolam (Xanax), lorazepam (Ativan) and non-benzodiazepines such as metaxalone (Skelaxin) or a combination of paracetamol and orphenadrine (Muscol)) and drugs that prevent increased muscle tone (baclofen and dantrolene). Despite a paucity of evidence supporting their use, antispasmodic and antispasticity muscle relaxants have gained widespread clinical acceptance as adjuvants in the management of patients with chronic musculoskeletal pain.The aim of this review was to determine the efficacy and safety of muscle relaxants in pain management in patients with RA. The muscle relaxants that were included in this review are the antispasmodic benzodiazepines (alprazolam, bromazepam, chlordiazepoxide,cinolazepam, clonazepam, cloxazolam, clorazepate, diazepam, estazolam, flunitrazepam, flurazepam, flutoprazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, midazolam, nimetazepam, nitrazepam, nordazepam, oxazepam, pinazepam, prazepam, quazepam, temazepam, tetrazepam, triazolam), antispasmodic non-benzodiazepines (cyclobenzaprine, carisoprodol, chlorzoxazone, meprobamate, methocarbamol, metaxalone, orphenadrine, tizanidine and zopiclone), and antispasticity drugs (baclofen and dantrolene sodium).We performed a search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 4th quarter 2010), MEDLINE (1950 to week 1 November 2010), EMBASE (Week 44 2010), and PsycINFO (1806 to week 2 November 2010). We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of reference lists of relevant articles.We included randomised controlled trials which compared a muscle relaxant to another therapy (active, including non-pharmacological therapies, or placebo) in adult patients with RA and that reported at least one clinically relevant outcome.Two blinded review authors independently extracted data and assessed the risk of bias in the trials. Meta-analyses were used to examine the efficacy of muscle relaxants on pain, depression, sleep and function, as well as their safety.Six trials (126 participants) were included in this review. All trials were rated at high risk of bias. Five cross-over trials evaluated a benzodiazepine, four assessed diazepam (n = 71) and one assessed triazolam (n = 15). The sixth trial assessed zopiclone (a non-benzodiazepine) (n = 40) and was a parallel group study. No trial duration was longer than two weeks while three single dose trials assessed outcomes at 24 hours only. Overall the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo, alone (at 24 hrs, 1 or 2 weeks) or in addition to non-steroidal anti-inflammatory drugs (NSAIDs) (at 24 hrs), on pain intensity, function, or quality of life. Data from two trials of longer than 24 hours duration (n = 74) (diazepam and zopiclone) found that participants who received a muscle relaxant had significantly more adverse events compared with those who received placebo (number needed to harm (NNTH) 3, 95% CI 2 to 7). These were predominantly central nervous system side effects, including dizziness and drowsiness (NNTH 3, 95% CI 2 to 11). Based upon the currently available evidence in patients with RA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or one week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over two weeks. However, even short term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.
Anal Bioanal Chem. 2012 Jan 12;
Lu M, Wolff C, Cui W, Chen H
Recently we have shown that, as a versatile ionization technique, desorption electrospray ionization (DESI) can serve as a useful interface to combine electrochemistry (EC) with mass spectrometry (MS). In this study, the EC/DESI-MS method has been further applied to investigate some aqueous phase redox reactions of biological significance, including the reduction of peptide disulfide bonds and nitroaromatics as well as the oxidation of phenothiazines. It was found that knotted/enclosed disulfide bonds in the peptides apamin and endothelin could be electrochemically cleaved. Subsequent tandem MS analysis of the resulting reduced peptide ions using collision-induced dissociation (CID) and electron-capture dissociation (ECD) gave rise to extensive fragment ions, providing a fast protocol for sequencing peptides with complicated disulfide bond linkages. Flunitrazepam and clonazepam, a class of nitroaromatic drugs, are known to undergo reduction into amines which was proposed to involve nitroso and N-hydroxyl intermediates. Now in this study, these corresponding intermediate ions were successfully intercepted and their structures were confirmed by CID. This provides mass spectrometric evidence for the mechanism of the nitro to amine conversion process during nitroreduction, an important redox reaction involved in carcinogenesis. In addition, the well-known oxidation reaction of chlorpromazine was also examined. The putative transient one-electron transfer product, the chlorpromazine radical cation (m/z 318), was captured by MS, for the first time, and its structure was also verified by CID. In addition to these observations, some features of the DESI-interfaced electrochemical mass spectrometry were discussed, such as simple instrumentation and the lack of background signal. These results further demonstrate the feasibility of EC/DESI-MS for the study of the biology-relevant redox chemistry and would find applications in proteomics and drug development research.
