Topiramate: A New Antiepileptic Drug

1997 ◽  
Vol 31 (10) ◽  
pp. 1164-1173 ◽  
Author(s):  
Michael D Privitera
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Antiepileptic Drug ◽  
Development Program ◽  
Clinical Effects ◽  
Controlled Clinical Trials ◽  
Psychomotor Slowing ◽  
Open Label ◽  
Double Blind ◽  
Label Data

OBJECTIVE: To review proposed mechanisms of action, clinical pharmacology, efficacy, safety, and tolerability of the antiepileptic drug (AED) topiramate. METHODS: All available data from the clinical development program — Published and unpublished data (provided by investigators or the RW Johnson Pharmaceutical Research Institute) — Were analyzed, with emphasis on the results of double-blind, placebo-controlled trials. Data from open-label studies provided information about long-term efficacy and tolerability. FINDINGS: Topiramate is highly effective in the control of previously therapy-resistant partial seizures, with or without secondary generalization. In the refractory adult patient population enrolled in controlled clinical trials, seizures were reduced by 50% or more in 27–47% of patients compared with 0–18% in placebo-treated patients and by 75% or more in 9–36% of the patients compared with 0–9% of those receiving placebo. The most common adverse effects involve the central nervous system and are mild to moderate in nature. Adverse effects include somnolence, fatigue, psychomotor slowing, and concentration problems. The currently recommended dosing is lower and titration slower than schedules used in the clinical trials; this may improve the tolerability of topiramate. Topiramate has few interactions with currently available AEDs, but phenytoin concentrations increased in some patients. Topiramate can be used initially as adjunctive therapy. Plasma topiramate concentrations are reduced substantially when used with enzyme-inducing AEDs. Open-label data and a single double-blind trial suggest that topiramate monotherapy may be effective. Open-label data also indicate that topiramate may be effective in generalized seizures of nonfocal origin, including those associated with Lennox-Gastaut syndrome. CONCLUSIONS: The robust clinical effects of topiramate expand the therapeutic options for patients with epilepsy. Controlled clinical trials are needed to verify initial observations that topiramate may be effective against a broad spectrum of seizure types and to directly compare efficacy and tolerability with other new and standard AEDs.

Modafinil Augmentation for Residual Symptoms of Fatigue in Patients with a Partial Response to Antidepressants

2007 ◽  
Vol 41 (6) ◽  
pp. 1005-1012 ◽  
Author(s):  
Jenny Y Lam ◽  
Maisha Kelly Freeman ◽  
Marshall E Cates
Keyword(s):  
Clinical Trials ◽  
Data Extraction ◽  
Controlled Clinical Trials ◽  
Open Label ◽  
Double Blind ◽  
Residual Symptoms ◽  
Randomized Controlled ◽  
Manual Search ◽  
Number Of Patients ◽  
Residual Fatigue

OBJECTIVE: To evaluate the literature discussing the use of modafinil in the treatment of residual symptoms of fatigue in patients with depression. DATA SOURCES: PubMed (1966–March 2007) and International Pharmaceutical Abstracts(1970–March 2007) were searched using the key words modafinil and depression. A manual search of the reference section of the articles retrieved was conducted to identify articles not indexed in either of these sources. STUDY SELECTION AND DATA EXTRACTION: All articles published in English were evaluated. Studies were included if modafinil was used to treat patients with residual fatigue from depression and the effects were measured with validated fatigue subscales. DATA SYNTHESIS: One retrospective study, 5 open-label trials, and 2 randomized controlled clinical trials met the inclusion criteria for assessment of residual symptoms of fatigue as assessed by commonly used fatigue subscales after modafinil administration. Although improvement with fatigue has occurred with modafinil therapy, literature regarding the topic is limited by the lack of well-controlled clinical trials. Modafinil does appear to improve residual fatigue with depression as evidenced by open-label trials; however, the efficacy of this agent has not been duplicated in randomized controlled trials. The open-label trials that have been conducted often had no comparator and a small number of patients. In addition, outcome measures used in the studies were not consistent between trials. Modafinil appears to be well tolerated, with the main adverse effects being headache and nausea. CONCLUSIONS: Open-label trials indicate that modafinil may be effective in ameliorating fatigue associated with depression; however, this effect has not been reproduced in randomized, double-blind, placebo-controlled clinical trials. Therefore, the use of modafinil for the treatment of residual fatigue is not recommended due to the lack of reproducible data of its efficacy. Long-term, adequately powered clinical trials should be conducted to determine its place in therapy.

Homeopathic aggravations: a systematic review of randomised, placebo-controlled clinical trials

Homeopathy ◽  
2003 ◽  
Vol 92 (02) ◽  
pp. 92-98
Author(s):  
S Grabia ◽  
E Ernst
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Effects ◽  
Randomised Clinical Trials ◽  
Controlled Clinical Trials ◽  
Double Blind ◽  
Literature Searches

AbstractHomeopathic aggravations have often been described anecdotally. However, few attempts have been made to scientifically verify their existence. This systematic review aimed at comparing the frequency of homeopathic aggravations in the placebo and verum groups of double-blind, randomised clinical trials. Eight independent literature searches were carried out to identify all such trials mentioning either adverse effects or aggravations. All studies thus found were validated and data were extracted by both authors. Twenty-four trials could be included. The average number of aggravations was low. In total, 50 aggravations were attributed to patients treated with placebo and 63 to patients treated with homoeopathically diluted remedies. We conclude that this systematic review does not provide clear evidence that the phenomenon of homeopathic aggravations exists.

The Use of Methotrexate in Rheumatoid Arthritis

1985 ◽  
Vol 19 (5) ◽  
pp. 349-358 ◽  
Author(s):  
Peter W. Letendre ◽  
Douglas J. DeJong ◽  
Donald R. Miller
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Folic Acid ◽  
Side Effects ◽  
Adverse Effects ◽  
Systemic Administration ◽  
Refractory Disease ◽  
Controlled Clinical Trials ◽  
Folic Acid Antagonist ◽  
Acid Antagonist

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5–15 mg/wk in a “pulse” fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.

Oral Terbinafine: A New Antifungal Agent

1997 ◽  
Vol 31 (4) ◽  
pp. 445-456 ◽  
Author(s):  
Susan M Abdel-Rahman ◽  
Milap C Nahata
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Fungal Infections ◽  
Case Reports ◽  
Current Standard ◽  
Open Label ◽  
Double Blind ◽  
Pathogenic Yeast

Objective To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of terbinafine. Available comparative data of terbinafine and other antimycotic agents are described for understanding the potential role of terbinafine in patient care. Data Sources A MEDLINE search restricted to English language during 1966–1996 and extensive review of journals was conducted to prepare this article. MeSH headings included allylamines, terbinafine, SF 86–327, dermatophytosis, dermatomycosis. Data Extraction The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open-label and controlled studies and case reports. Controlled single- or double-blind studies were evaluated to describe the efficacy of terbinafine in the treatment of various fungal infections. Data Synthesis Terbinafine is the first oral antimycotic in the allylamines class: a fungicidal agent that inhibits ergosterol synthesis at the stage of squalene epoxidation. Terbinafine demonstrates excellent in vitro activity against the majority of dermatophyte species including Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum; less activity is seen against Dematiaceae and the filamentous fungi. It is least active against the pathogenic yeast and this correlates with the relatively poor efficacy against these organisms in vivo. High concentrations of terbinafine are achieved in keratinous tissues, the site of superficial infections, and these concentrations are maintained for up to 3 months. The clinical efficacy of terbinafine against a number of dermatophyte infections exceeds that of the current standard of therapy, griseofulvin. The efficacy of terbinafine may be as good or better than that of the azole antifungals. Additional studies are required to confirm these observations. Terbinafine demonstrates a good safety profile, and relatively few drug interactions have been identified. Conclusions Terbinafine is more effective than the gold standard, griseofulvin, in the treatment of tinea pedis and tinea unguinum, with considerably shorter treatment duration in the latter. It has been proven as effective as griseofulvin in the treatment of tinea capitis, tinea corporis, and tinea cruris. Terbinafine does not appear to offer any advantage in the treatment of nondermatophyte infections; its utility in the treatment of systemic infections has yet to be established. Depending on individual institutional costs, terbinafine may be a front-line drug for some superficial infections responding poorly to the current standard of therapy.

scholarly journals S44. LUMATEPERONE (ITI-007) FOR THE TREATMENT OF SCHIZOPHRENIA: PLACEBO-CONTROLLED CLINICAL TRIALS AND AN OPEN-LABEL SAFETY SWITCHING STUDY

2018 ◽  
Vol 44 (suppl_1) ◽  
pp. S341-S341 ◽  
Author(s):  
Kimberly Vanover ◽  
Alex Dmitrienko ◽  
Steven Glass ◽  
Susan Kozauer ◽  
Jelena Saillard ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Controlled Clinical Trials ◽  
Open Label

The research evidence base for homeopathy: a fresh assessment of the literature

Homeopathy ◽  
2003 ◽  
Vol 92 (02) ◽  
pp. 84-91
Author(s):  
RT Mathie
Keyword(s):  
Clinical Trials ◽  
Research Evidence ◽  
Controlled Trial ◽  
Relative Number ◽  
Evidence Base ◽  
Weight Of Evidence ◽  
Clinical Effects ◽  
Upper Respiratory Tract ◽  
Medical Conditions ◽  
Double Blind

Abstract Background. The claims made for the clinical effects of homeopathy are controversial. The results of several meta-analyses of clinical trials are positive, but they fail in general to highlight specific medical conditions that respond well to homeopathy. Aims. This review examines the cumulative research from randomised and/or double-blind clinical trials (RCTs) in homeopathy for individual medical conditions reported since 1975, and asks the question: What is the weight of the original evidence from published RCTs that homeopathy has an effect that is statistically significantly different from that in a comparative group? Method. Analysis of the 93 substantive RCTs that compare homeopathy either with placebo or another treatment. Results. 50 papers report a significant benefit of homeopathy in at least one clinical outcome measure, 41 that fail to discern any inter-group differences, and two that describe an inferior response with homeopathy. Considering the relative number of research articles on the 35 different medical conditions in which such research has been carried out, the weight of evidence currently favours a positive treatment effect in eight: childhood diarrhoea, fibrositis, hayfever, influenza, pain (miscellaneous), side-effects of radio- or chemotherapy, sprains and upper respiratory tract infection. Based on published research to date, it seems unlikely that homeopathy is efficacious for headache, stroke or warts. Insufficient research prevents conclusions from being drawn about any other medical conditions. Conclusions. The available research evidence emphasises the need for much more and better-directed research in homeopathy. A fresh agenda of enquiry should consider beyond (but include) the placebo-controlled trial. Each study should adopt research methods and outcome measurements linked to a question addressing the clinical significance of homeopathy's effects.

scholarly journals M42. INDEPENDENT REVIEW & MONITORING IMPROVES QUALITY OF PANSS DATA IN GLOBAL CLINICAL TRIALS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S150-S150
Author(s):  
Barbara Echevarria ◽  
Cong Liu ◽  
Selam Negash ◽  
Mark Opler ◽  
Patricio Molero ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Data Quality ◽  
Working Group ◽  
Double Blind Study ◽  
Open Label ◽  
Rater Training ◽  
Double Blind ◽  
Open Label Extension ◽  
Expert Working Group ◽  
Independent Review

Abstract Background The Positive and Negative Syndrome Scale (PANSS) (1) is the most widely used endpoint for measuring change in schizophrenia clinical trials. A set of flags have been developed by ISCTM expert working group to identify potential scoring errors in PANSS assessments (2). Measures have been taken by sponsors (pharmaceutical industry) with the goal of increasing scoring reliability and data quality, such as the use of Independent Review (IRev). We evaluated changes in data quality when site raters stop being recorded and monitored via IRev by comparing two studies with the same cohort of raters, one with independent review and one without. Methods Data from PANSS assessments in two global multisite schizophrenia clinical trials were analyzed. We selected data from raters participating in both studies (which run concurrently for a significant period of time). Raters were rigorously trained on administration and scoring conventions and certified prior to the study through demonstration of adequate interrater reliability. In addition to these steps, raters in study A were required to audio record all PANSS assessments with a selected subset of visits being subject to IRev. PANSS assessments in study B were neither recorded nor monitored via IRev. Data quality after study completion was examined by calculating the frequency of anomalous data patterns identified as “high” (very probable or definite error) by the ISCTM Working Group in both studies. Additionally, we examined the percentage of assessments with lower than expected PANSS interview duration as captured via an eCOA platform. Results There were 9441 eCOA PANSS assessments in study A and 6178 in study B included in this analysis. The proportions of flags that represented highly probable/definite error differed significantly between the studies (9% vs 18% for Study A and B, respectively, p<.01). The most significant differences in ISCTM flags were related to overly consistent scoring patterns (27 or more items scored identically to the prior visit) occurring with higher frequency in study B. Additionally, study B also had a significantly higher frequency of assessments flagged for low interview duration (< 15 minutes) (1% vs 4% for Study A and B, respectively, p<.01). Discussion Initial rater training is necessary but not sufficient to ensure adequate data quality in schizophrenia trials. Implementation of additional in-study oversight through Independent Review or similar methods reduces the probability of data error in PANSS assessments, including the appearance of improbable rating patterns and decreased time spent interviewing study subjects. One potential limitation is that study A is a double-blind study whereas study B is an open label extension of study A.

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