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Journal of Clinical Neurophysiology :... Jan 1990Narcolepsy is a neurological condition with a prevalence of up to 1 per 1,000 that is characterized by irresistible bouts of sleep. Associated features include the...
Narcolepsy is a neurological condition with a prevalence of up to 1 per 1,000 that is characterized by irresistible bouts of sleep. Associated features include the pathological manifestations of rapid-eye-movement (REM) sleep: cataplexy, sleep paralysis, hypnagogic hallucinations, and abnormal sleep-onset REM periods and disturbed nocturnal sleep. The condition is strongly associated with the HLA-DR2 and DQw1 phenotype. The phenomenology of narcolepsy is discussed, and diagnostic procedures are reviewed. Treatment modalities involving central nervous system stimulants for somnolence and tricyclic drugs for REM-sleep abnormalities are discussed. Sleep laboratory studies on the treatment efficacy of methylphenidate, pemoline, dextroamphetamine, protriptyline, and viloxazine are presented. Data suggest that: (1) methylphenidate and dextroamphetamine objectively improve somnolence; (2) pemoline, at doses up to 112.5 mg, is less effective in controlling somnolence but may improve certain aspects of performance; and (3) protriptyline and viloxazine are effective anticataplectic agents that produce little improvement in somnolence.
Topics: Adult; Antidepressive Agents; Central Nervous System Stimulants; Circadian Rhythm; Electroencephalography; Female; Humans; Male; Middle Aged; Narcolepsy; Pedigree; Sleep Stages
PubMed: 1968069
DOI: 10.1097/00004691-199001000-00008 -
The Turkish Journal of Gastroenterology... Oct 2011Certain drugs including oxyphenisatin, methyldopa, nitrofurantoin, diclofenac, interferon, infliximab, pemoline, minocycline, atorvastatin, and rosuvastatin can induce...
BACKGROUND/AIMS
Certain drugs including oxyphenisatin, methyldopa, nitrofurantoin, diclofenac, interferon, infliximab, pemoline, minocycline, atorvastatin, and rosuvastatin can induce hepatocellular injury that mimics autoimmune hepatitis. Whether drugs and herbs unmask or induce autoimmune hepatitis or simply cause a drug-induced hepatitis with accompanying autoimmune features is unclear. We describe the clinicopathologic details of eight cases with ornidazole-induced hepatitis with autoimmune features.
MATERIAL AND METHODS
Patients who presented with acute hepatitis between February 2001 and March 2009 were reevaluated for the etiology of liver disease. Patients with acute viral hepatitis, metabolic liver disease, vascular liver disease such as Budd-Chiari syndrome, biliary obstruction, or alcohol consumption were excluded. The autoimmune hepatitis scores, which were calculated at the time of diagnosis according to the criteria of the International Autoimmune Hepatitis Group, were recorded. In addition, the simplified criteria of the same group were applied retrospectively to each patient. Patients with ornidazole-induced toxic hepatitis with autoimmune hepatitis were included to constitute the study group of this report. All patients underwent initial liver biopsy, and one patient underwent liver biopsy three years later. All biopsies were scored according to the hepatitis scoring system by Ishak et al. (10).
RESULTS
Overall, eight patients (all female) were diagnosed as drug-induced autoimmune hepatitis. With the exception of one patient, all were treated with prednisolone 30 mg/day + azathioprine 50 mg/day. The prednisolone dose was tapered according to the decrease in the level of transaminases. A two-year treatment program was planned for all patients.
CONCLUSIONS
Ornidazole may cause drug-induced autoimmune hepatitis. Withdrawal of the drug may not provide the recovery despite a rather long wait. Thus, immunosuppressive therapy may be suggested in these cases.
Topics: Adult; Azathioprine; Biopsy; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Female; Glucocorticoids; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Middle Aged; Ornidazole; Prednisolone; Retrospective Studies
PubMed: 22234756
DOI: 10.4318/tjg.2011.0245 -
The Cochrane Database of Systematic... May 2015This review updates the original review, 'Pharmacological treatments for fatigue associated with palliative care' and also incorporates the review 'Drug therapy for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review updates the original review, 'Pharmacological treatments for fatigue associated with palliative care' and also incorporates the review 'Drug therapy for the management of cancer-related fatigue'.In healthy individuals, fatigue is a protective response to physical or mental stress, often relieved by rest. By contrast, in palliative care patients' fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Fatigue frequently occurs in patients with advanced disease (e.g. cancer-related fatigue) and modalities used to treat cancer can often contribute. Further complicating issues are the multidimensionality, subjective nature and lack of a consensus definition of fatigue. The pathophysiology is not fully understood and evidence-based treatment approaches are needed.
OBJECTIVES
To evaluate the efficacy of pharmacological treatments for fatigue in palliative care, with a focus on patients at an advanced stage of disease, including patients with cancer and other chronic diseases.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO and EMBASE, and a selection of cancer journals up to 28 April 2014. We searched the references of identified articles and contacted authors to obtain unreported data. To validate the search strategy we selected sentinel references.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) concerning adult palliative care with a focus on pharmacological treatment of fatigue compared to placebo, application of two drugs, usual care or a non-pharmacological intervention. The primary outcome had to be non-specific fatigue (or related terms such as asthenia). We did not include studies on fatigue related to antineoplastic treatment (e.g. chemotherapy, radiotherapy, surgical intervention). We also included secondary outcomes that were assessed in fatigue-related studies (e.g. exhaustion, tiredness).
DATA COLLECTION AND ANALYSIS
Two review authors (MM and MC) independently assessed trial quality and extracted data. We screened the search results and included studies if they met the selection criteria. If we identified two or more studies that investigated a specific drug with the same dose in a population with the same disease and using the same assessment instrument or scale, we conducted meta-analysis. In addition, we compared the type of drug investigated in specific populations, as well as the frequent adverse effects of fatigue treatment, by creating overview tables.
MAIN RESULTS
For this update, we screened 1645 publications of which 45 met the inclusion criteria (20 additional studies to the previous reviews). In total, we analysed data from 18 drugs and 4696 participants. There was a very high degree of statistical and clinical heterogeneity in the trials and we discuss the reasons for this in the review. There were some sources of potential bias in the included studies, including a lack of description of the methods of blinding and allocation concealment, and the small size of the study populations. We included studies investigating pemoline and modafinil in participants with multiple sclerosis (MS)-associated fatigue and methylphenidate in patients suffering from advanced cancer and fatigue in meta-analysis. Treatment results pointed to weak and inconclusive evidence for the efficacy of amantadine, pemoline and modafinil in multiple sclerosis and for carnitine and donepezil in cancer-related fatigue. Methylphenidate and pemoline seem to be effective in patients with HIV, but this is based only on one study per intervention, with only a moderate number of participants in each study. Meta-analysis shows an estimated superior effect for methylphenidate in cancer-related fatigue (standardised mean difference (SMD) 0.49, 95% confidence interval (CI) 0.15 to 0.83). Therapeutic effects could not be described for dexamphetamine, paroxetine or testosterone. There were a variety of results for the secondary outcomes in some studies. Most studies had low participant numbers and were heterogeneous. In general, adverse reactions were mild and had little or no impact.
AUTHORS' CONCLUSIONS
Based on limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Fatigue research in palliative care seems to focus on modafinil and methylphenidate, which may be beneficial for the treatment of fatigue associated with palliative care although further research about their efficacy is needed. Dexamethasone, methylprednisolone, acetylsalicylic acid, armodafinil, amantadine and L-carnitine should be further examined. Consensus is needed regarding fatigue outcome parameters for clinical trials.
Topics: Adult; Amantadine; Benzhydryl Compounds; Carnitine; Central Nervous System Stimulants; Chronic Disease; Fatigue; Humans; Kidney Failure, Chronic; Methylphenidate; Modafinil; Multiple Sclerosis; Neoplasms; Palliative Care; Pemoline; Randomized Controlled Trials as Topic
PubMed: 26026155
DOI: 10.1002/14651858.CD006788.pub3 -
The Cochrane Database of Systematic... Mar 2018Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. This review, one in a series examining the treatment of TD, covers miscellaneous treatments not covered elsewhere.
OBJECTIVES
To determine whether drugs, hormone-, dietary-, or herb-supplements not covered in other Cochrane reviews on TD treatments, surgical interventions, electroconvulsive therapy, and mind-body therapies were effective and safe for people with antipsychotic-induced TD.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers (16 July 2015 and 26 April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA
We included reports if they were randomised controlled trials (RCTs) dealing with people with antipsychotic-induced TD and schizophrenia or other chronic mental illnesses who remained on their antipsychotic medication and had been randomly allocated to the interventions listed above versus placebo, no intervention, or any other intervention.
DATA COLLECTION AND ANALYSIS
We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included 31 RCTs of 24 interventions with 1278 participants; 22 of these trials were newly included in this 2017 update. Five trials are awaiting classification and seven trials are ongoing. All participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. Studies were primarily of short (three to six6 weeks) duration with small samples size (10 to 157 participants), and most (61%) were published more than 20 years ago. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment, generation of the sequence, and blinding.Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found moderate-quality evidence of a benefit of the intervention compared with placebo: valbenazine (RR 0.63, 95% CI 0.46 to 0.86, 1 RCT, n = 92) and extract of Ginkgo biloba (RR 0.88, 95% CI 0.81 to 0.96, 1 RCT, n = 157), respectively. However, due to small sample sizes we cannot be certain of these effects.We consider the results for the remaining interventions to be inconclusive: Low- to very low-quality evidence of a benefit was found for buspirone (RR 0.53, 95% CI 0.33 to 0.84, 1 RCT, n = 42), dihydrogenated ergot alkaloids (RR 0.45, 95% CI 0.21 to 0.97, 1 RCT, n = 28), hypnosis or relaxation, (RR 0.45, 95% CI 0.21 to 0.94, 1 study, n = 15), pemoline (RR 0.48, 95% CI 0.29 to 0.77, 1 RCT, n = 46), promethazine (RR 0.24, 95% CI 0.11 to 0.55, 1 RCT, n = 34), insulin (RR 0.52, 95% CI 0.29 to 0.96, 1 RCT, n = 20), branched chain amino acids (RR 0.79, 95% CI 0.63 to 1.00, 1 RCT, n = 52), and isocarboxazid (RR 0.24, 95% CI 0.08 to 0.71, 1 RCT, n = 20). There was low- to very low-certainty evidence of no difference between intervention and placebo or no treatment for the following interventions: melatonin (RR 0.89, 95% CI 0.71 to 1.12, 2 RCTs, n = 32), lithium (RR 1.59, 95% CI 0.79 to 3.23, 1 RCT, n = 11), ritanserin (RR 1.00, 95% CI 0.70 to 1.43, 1 RCT, n = 10), selegiline (RR 1.37, 95% CI 0.96 to 1.94, 1 RCT, n = 33), oestrogen (RR 1.18, 95% CI 0.76 to 1.83, 1 RCT, n = 12), and gamma-linolenic acid (RR 1.00, 95% CI 0.69 to 1.45, 1 RCT, n = 16).None of the included studies reported on the other primary outcome, 'no clinically significant extrapyramidal adverse effects'.
AUTHORS' CONCLUSIONS
This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia. However, since only one RCT has investigated each one of these compounds, we are awaiting results from ongoing trials to confirm these results. Results for the remaining interventions covered in this review must be considered inconclusive and these compounds probably should only be used within the context of a well-designed evaluative study.
Topics: Adrenergic Uptake Inhibitors; Adult; Anti-Anxiety Agents; Antipsychotic Agents; Dihydroergotoxine; Dyskinesia, Drug-Induced; Ginkgo biloba; Humans; Hypnosis; Plant Extracts; Randomized Controlled Trials as Topic; Relaxation Therapy; Tetrabenazine; Valine
PubMed: 29552749
DOI: 10.1002/14651858.CD000208.pub2 -
British Journal of Clinical Pharmacology Nov 19801 Effects of prolintane (15 and 30 mg) and pemoline (60 and 100 mg) on sleep were studied in six healthy adult males. Sleep was assessed by electroencephalography and by... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
1 Effects of prolintane (15 and 30 mg) and pemoline (60 and 100 mg) on sleep were studied in six healthy adult males. Sleep was assessed by electroencephalography and by analogue scales. 2 Prolintane (15 and 30 mg) reduced rapid eye movement (REM) sleep both by delaying the first period (P < 0.05 and < 0.001 respectively) and by reducing total REM sleep (P < 0.05 and < 0.001 respectively). In some subjects there were increased awakenings during the early part of the night, and in two subjects long periods of wakefulness occurred. 3 With pemoline (60 and 100 mg) sleep duration was marked reduced (P < 0.001). There was evidence in some subjects of delay to the first REM period, and reduced percentage REM sleep (P < 0.01). Shortened and fragmented sleep with 60 and 100 mg were associated with reduced sleep efficiency indices (P < 0.001), and shorter sleep period times led to reduced REM/NREM ratios. Absence of an effect on REM latency for the subjects as a group may be related to relatively slow absorption. 4 The heterocyclic amphetamine derivatives have variable effects on sleep. The differences may be dose related, and wakefulness and reduced REM sleep may be seen together or separately. Alterations in sleep occur with doses of pemoline and prolintane which also modify performance.
Topics: Adult; Humans; Male; Pemoline; Pyrrolidines; Sleep, REM; Time Factors; Wakefulness
PubMed: 7437258
DOI: 10.1111/j.1365-2125.1980.tb01790.x -
Journal of Cachexia, Sarcopenia and... Mar 2016In palliative care patients, fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Further... (Review)
Review
BACKGROUND
In palliative care patients, fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Further complicating issues are the multidimensionality, subjective nature and lack of a consensus definition of fatigue. The review aimed to evaluate the efficacy of pharmacological treatments for fatigue in palliative care, with a focus on patients at an advanced stage of disease, including patients with cancer and other chronic diseases.
METHODS
We considered randomized controlled trials concerning adult palliative care with a focus on pharmacological treatment of fatigue compared with placebo, application of two drugs, usual care or a non-pharmacological intervention. The primary outcome had to be non-specific fatigue (or related terms such as asthenia). We searched the CENTRAL, MEDLINE, PsycINFO and EMBASE, and a selection of cancer journals up to 28 April 2014. Two review authors independently assessed trial quality and extracted the data.
RESULTS
We screened 1645 publications of which 45 met the inclusion criteria. In total, we analysed data from 18 drugs and 4696 participants. There was a very high degree of statistical and clinical heterogeneity in the trials. Meta-analysis of data was possible for modafinil, pemoline, and methylphenidate.
CONCLUSIONS
Due to the limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Some drugs, which may be beneficial for the treatment of fatigue associated with palliative care such as amantadine, methylphenidate, and modafinil, should be further researched.
PubMed: 27066315
DOI: 10.1002/jcsm.12101 -
The American Journal of Managed Care Jul 2004A brief review of the efficacy and common side effects of pharmacological treatments for attention-deficit/hyperactivity disorder (ADHD) is presented. Methylphenidate... (Review)
Review
A brief review of the efficacy and common side effects of pharmacological treatments for attention-deficit/hyperactivity disorder (ADHD) is presented. Methylphenidate and amphetamine continue to have the strongest base of empiric support. They are both available in extended- and immediate-release preparations. Although most children with ADHD respond favorably to either medication, many children who do not respond to one medication will respond to the other. Additional pharmacological options include the nonstimulant atomoxetine, the stimulant pemoline, the antidepressants bupropion and desipramine, and the antihypertensives clonidine and guanfacine. In selecting the appropriate pharmacological regimen, consideration should be given to the child's daily school and after-school schedule, the presence of aggressive symptoms, and the risk of diversion. Careful selection of an appropriate medication regimen and active engagement of the child, parents, and teacher in daily management may help to ensure long-term adherence.
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Mental Disorders; Propylamines; United States
PubMed: 15352538
DOI: No ID Found -
Irish Veterinary Journal Aug 2010Pemoline is a central nervous system stimulant that has been used to treat attention-deficit hyperactivity disorder and narcolepsy in humans; its identification in...
Pemoline is a central nervous system stimulant that has been used to treat attention-deficit hyperactivity disorder and narcolepsy in humans; its identification in horses could be considered evidence of attempts to influence performance. Two recent pemoline 'positives' in English racehorses led us to review the chemical relationships between tetramisole, levamisole, aminorex and pemoline. Pemoline is a simple oxidation product of aminorex, which has been shown in the United States and elsewhere to be an equine metabolite of levamisole. Based on the clear structural relationships between aminorex and pemoline, we conclude that levamisole can metabolise to pemoline in horses and that pemoline identifications in horses post levamisole administration are likely to be associated with levamisole administration. Levamisole should not be administered to horses about to compete because of its ability to metabolise to two central nervous system stimulants, aminorex and pemoline.
PubMed: 21777496
DOI: 10.1186/2046-0481-63-8-498 -
Journal of Rehabilitation Research and... 2002Fatigue is a very common symptom of multiple sclerosis (MS). Theoretically, fatigue may be related to neuromodulation by soluble products of the autoimmune process or by... (Review)
Review
Fatigue is a very common symptom of multiple sclerosis (MS). Theoretically, fatigue may be related to neuromodulation by soluble products of the autoimmune process or by disruption of central nervous system pathways necessary for sustained activity, but little empirical evidence supports these possibilities. Amantadine, pemoline, and modafanil improved fatigue in placebo-controlled clinical trials, but these studies all had significant limitations. Difficulty measuring fatigue has impeded studies of its characteristics, mechanisms, and therapeutics. Most studies have relied on self-report questionnaires. These may be inappropriate, however, because they can be easily confounded by other symptoms of MS, they are entirely subjective, and they require patients to make difficult retrospective assessments. Studies of fatigue would be improved by including measures of more rigorously defined, quantifiable components of fatigue. For example, motor fatigue can be measured as the decline in strength during sustained muscle contractions. Cognitive fatigue can be measured as the analogous decline in cognitive performance during tasks requiring sustained attention. Lassitude is defined as a subjective sense of reduced energy, and it can be measured with the use of a visual analog diary. These measures provide reproducible results and demonstrate significant differences between MS patients and healthy controls. Dividing fatigue into these components can provide objective assessments that are less likely to be confounded by other symptoms of MS, such as weakness, spasticity, cognitive impairment, and depressed mood.
Topics: Evidence-Based Medicine; Fatigue; Female; Humans; Male; Multiple Sclerosis; Muscle Fatigue; Prognosis; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome
PubMed: 12051465
DOI: No ID Found -
Journal of Intellectual Disability... May 2012Self-injurious behaviour (SIB) is prevalent in neurodevelopmental disorders, but its expression is highly variable within, and between diagnostic categories. This raises...
BACKGROUND
Self-injurious behaviour (SIB) is prevalent in neurodevelopmental disorders, but its expression is highly variable within, and between diagnostic categories. This raises questions about the factors that contribute to aetiology and expression of SIB. Expression of SIB is generally described in relation to social reinforcement. However, variables that predispose vulnerability have not been as clearly characterised. This study reports the aetiology and expression of self-injury in an animal model of pemoline-induced SIB. It describes changes in gross neuronal activity in selected brain regions after chronic treatment with pemoline, and it describes the impact that a history of social defeat stress has on the subsequent expression of SIB during pemoline treatment.
METHODS
Experiment 1--Male Long-Evans rats were injected on each of five consecutive days with pemoline or vehicle, and the expression of SIB was evaluated using a rating scale. The brains were harvested on the morning of the sixth day, and were assayed for expression of cytochrome oxidase, an index of sustained neuronal metabolic activity. Experiment 2--Male Long-Evans rats were exposed to a regimen of 12 daily sessions of social defeat stress or 12 daily sessions of handling (i.e. controls). Starting on the day after completion of the social defeat or handling regimen, each rat was given five daily injections of pemoline. The durations of self-injurious oral contact and other stereotyped behaviours were monitored, and the areas of tissue injury were quantified.
RESULTS
Experiment 1--Neuronal metabolic activity was significantly lower in a variety of limbic and limbic-associated brain structures in the pemoline-treated rats, when compared with activity in the same regions of vehicle-treated controls. In addition, neuronal activity was low in the caudate-putamen, and in subfields of the hypothalamus, but did not differ between groups for a variety of other brain regions, including nucleus accumbens, substantia nigra, ventral tegmentum, thalamus, amygdala, and cortical regions. Experiment 2--All the pemoline-treated rats exhibited SIB, and whereas the social defeat regimen did not alter the total amount of self-injurious oral contact or other stereotyped behaviours, it significantly increased the severity of tissue injury.
CONCLUSIONS
A broad sampling of regional metabolic activity indicates that the pemoline regimen produces enduring changes that are localised to specific limbic, hypothalamic and striatal structures. The potential role of limbic function in aetiology of SIB is further supported by the finding that pemoline-induced self-injury is exacerbated by prior exposure to social defeat stress. Overall, the results suggest brain targets that should be investigated further, and increase our understanding of the putative role that stress plays in the pathophysiology of SIB.
Topics: Animals; Central Nervous System Stimulants; Corpus Striatum; Disease Models, Animal; Electron Transport Complex IV; Hypothalamus; Lesch-Nyhan Syndrome; Limbic System; Male; Pemoline; Rats; Rats, Long-Evans; Self-Injurious Behavior; Social Dominance; Stress, Psychological
PubMed: 21988194
DOI: 10.1111/j.1365-2788.2011.01485.x