Lumateperone: A Novel Antipsychotic for Schizophrenia

2020 ◽  
Vol 55 (1) ◽  
pp. 98-104
Author(s):  
Jessica Greenwood ◽  
Rucha B. Acharya ◽  
Valerie Marcellus ◽  
Jose A. Rey
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
English Language ◽  
Partial Agonist ◽  
Data Extraction ◽  
Double Blind ◽  
Study Selection ◽  
Syndrome Scale ◽  
Negative Syndrome ◽  
Key Terms

Objective: To provide a concise review of the new Food and Drug Administration (FDA)-approved antipsychotic, lumateperone, for use in schizophrenia. Data Sources: A literature search of PubMed was performed (January 2000 to May 2020) using the following key terms: lumateperone, Caplyta, and ITI-007. Abstracts from conferences, review articles, clinical trials, and drug monographs were reviewed. Study Selection and Data Extraction: Relevant English-language monographs and studies conducted in humans were considered. Data Synthesis: Lumateperone was FDA approved for the treatment of schizophrenia in December 2019 based on 2 published randomized, double-blind, placebo-controlled trials. Lumateperone’s pharmacology is consistent with that of other second-generation antipsychotics in that it has a higher affinity for the serotonin (5-HT2A) receptors compared with dopamine (D2) receptors but with lower affinities for α-1 and histaminergic receptors. In addition, it serves as a presynaptic dopamine partial agonist, serotonin reuptake inhibitor, and an indirect modulator of glutamatergic systems. Based on the 4-week clinical trials, lumateperone was well tolerated. Most common treatment-emergent adverse events were headache, somnolence, and dizziness. Relevance to Patient Care and Clinical Practice: At this time, lumateperone had a statistically significant reduction in Positive and Negative Syndrome Scale when compared with placebo and was not significantly associated with the extrapyramidal symptoms (EPS) and metabolic adverse effects commonly seen with other antipsychotics. Conclusions: Lumateperone has the potential to benefit individuals with schizophrenia who are intolerant to the EPSs or metabolic adverse effects of other antipsychotics. However, further head-to-head trials with commercially available antipsychotics are still required to assist in establishing its role in treatment.

Flibanserin

2016 ◽  
Vol 30 (2) ◽  
pp. 256-260 ◽  
Author(s):  
Ximena Vallejos ◽  
Christine Wu
Keyword(s):  
Clinical Trials ◽  
Sexual Desire ◽  
English Language ◽  
Human Subjects ◽  
Data Extraction ◽  
Premenopausal Women ◽  
Relevant Information ◽  
Time Frame ◽  
Double Blind ◽  
Study Selection

Objective: To review pivotal clinical trials, pharmacology, contraindications, precautions, and key patient education points of flibanserin for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. Data Sources: A literature search of PubMed using the key words flibanserin and HSDD was conducted in September 2015. There was no time frame to exclude relevant clinical trials. All trials referenced were published between March 2012 and June 2014. Other relevant information was obtained from the Food and Drug Administration (FDA) Web site, press releases, prescribing information from the manufacturer, and ClinicalTrials.gov . Study Selection/Data Extraction: All articles in the English language and involving human subjects were reviewed. Data Synthesis: There are three 24-week, multicenter, randomized, double-blind, placebo-controlled trials that evaluated the efficacy of flibanserin in North American premenopausal women with HSDD. There was 1 trial that studied the effects of flibanserin in postmenopausal women. In all of the trials, the investigators found statistical significant improvements in Female Sexual Function Index (FSFI) desire domain score and satisfying sexual events (SSEs). The most frequently reported adverse events in all flibanserin arms of treatment were somnolence, dizziness, and nausea. Conclusion: Flibanserin, a novel, nonhormonal agent that modulates excitatory and inhibitory neurotransmitters was studied in premenopausal women and has shown efficacy in improving sexual desire and SSEs.

Rifaximin: A New Treatment for Travelers' Diarrhea

2005 ◽  
Vol 39 (2) ◽  
pp. 284-289 ◽  
Author(s):  
Amy L Pakyz
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
English Language ◽  
Data Extraction ◽  
Cross Resistance ◽  
Double Blind ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
New Treatment

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions and precautions, and dosing recommendations of rifaximin, a new nonabsorbed antimicrobial agent for travelers' diarrhea. DATA SOURCES: A MEDLINE search (1966–July 2004) was conducted to extract human and animal research data in the English language on rifaximin. STUDY SELECTION AND DATA EXTRACTION: Randomized, double-blind, placebo-controlled trials were reviewed and included to evaluate the efficacy of rifaximin in the treatment of travelers' diarrhea. DATA SYNTHESIS: Rifaximin is approved for the treatment of travelers' diarrhea in patients ≥12 years of age with diarrhea caused by noninvasive strains of Escherichia coli. Rifaximin was superior to placebo and trimethoprim/sulfamethoxazole and equivalent to ciprofloxacin in the primary clinical endpoint of the time to the last unformed stool passed. CONCLUSIONS: Rifaximin is a viable alternative to ciprofloxacin for the treatment of travelers' diarrhea. As rifaximin is not systemically absorbed, it offers the advantage of leading to the development of less resistance compared with systemically absorbed antibiotics, in addition to fewer systemic adverse effects and drug interactions. However, the potential for cross-resistance between rifaximin and rifampin, as well as with other classes of antibiotics, is of concern and needs to be elucidated.

Zolpidem: Distinct from Triazolam?

1997 ◽  
Vol 31 (5) ◽  
pp. 625-632 ◽  
Author(s):  
Bob L Lobo ◽  
William L Greene
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Memory Impairment ◽  
English Language ◽  
Data Extraction ◽  
Residual Effects ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
Pertinent Information

OBJECTIVE: TO review the literature that compares Zolpidem with triazolam, with an emphasis on efficacy and safety in humans. DATA SOURCES: Information was retrieved from a MEDLINE search (1983–1996) of the English-language literature using the terms triazolam and zolpidem. STUDY SELECTION: Reports of clinical trials comparing the safety and efficacy of zolpidem and triazolam were included in this review. DATA EXTRACTION: Data were evaluated according to study design, efficacy, and adverse effects. Pertinent information was selected and the data synthesized into a review format. DATA SYNTHESIS: Zolpidem and triazolam have similar pharmacokinetic and pharmacodynamic effects in humans. Clinical trials have shown that usually recommended, equipotent dosages of zolpidem and triazolam do not differ with respect to pharmacokinetics, efficacy, tolerability, residual effects, memory impairment, rebound insomnia, abuse potential, or other adverse effects. CONCLUSIONS: Zolpidem offers no distinct therapeutic advantage over triazolam for the treatment of insomnia.

Transdermal Fentanyl

1992 ◽  
Vol 26 (11) ◽  
pp. 1393-1399 ◽  
Author(s):  
Lisa Y. Yee ◽  
Julio R. Lopez
Keyword(s):  
Chronic Pain ◽  
Clinical Trials ◽  
Placebo Group ◽  
Adverse Effects ◽  
English Language ◽  
Data Extraction ◽  
Opioid Analgesia ◽  
Transdermal Fentanyl ◽  
Study Selection ◽  
The Cost

OBJECTIVE: To review the use of transdermal fentanyl for the treatment of moderate to severe chronic pain. The article provides background on the pharmacology and pharmacokinetics of the drug, as well as the properties of the transdermal system. In addition, clinical trials, adverse effects, and therapeutic considerations and recommendations are presented. DATA SOURCES: Clinical trials, review articles, and reference texts. STUDY SELECTION: Comparative clinical trials involving the use of transdermal fentanyl on postoperative and chronic pain patients. DATA EXTRACTION: Data from clinical human trials published in the English language were reviewed. Trials were assessed by sample size, opioid dosage regimen, and therapeutic outcome. DATA SYNTHESIS: Transdermal fentanyl was found to be effective in the control of chronic and postoperative pain. In one trial the overall patient satisfaction with pain control was 79 percent for the transdermal fentanyl group and 44 percent for the placebo group. In another trial, the amount of additional parenteral morphine was significantly lower for the group receiving transdermal fentanyl than for the placebo group (49.9 ± 4.9 vs. 77.0 ± 6.3 mg, respectively, p<0.01). The most common adverse effects recorded were nausea (45–85 percent), pruritus (14–60 percent), and sedation (40–59 percent). The cost of analgesic therapy with this delivery system is higher than that of parenteral opioid analgesia, but less than patient-controlled analgesia. CONCLUSIONS: The transdermal fentanyl formulation offers some minor advantages over other forms of conventional pain management. Results of early clinical trials are promising, but more studies are needed to evaluate its long-term effectiveness and adverse effects. Specifically, comparisons with standard parenteral and patient-controlled opioid analgesia in chronic malignant and nonmalignant pain are necessary for adequate evaluation of transdermal fentanyl.

Pharmacotherapeutic Options for the Treatment of Patients with Obesity

2012 ◽  
Vol 28 (5) ◽  
pp. 211-218
Author(s):  
Lindsay R Debellis ◽  
Mark J Wrobel
Keyword(s):  
Weight Loss ◽  
Adverse Effects ◽  
English Language ◽  
Data Extraction ◽  
Double Blind ◽  
Obesity Epidemic ◽  
Safety Risks ◽  
Study Selection ◽  
Study Results ◽  
Antiobesity Agents

Objective: To assess the safety and efficacy of FDA-approved and in-development antiobesity agents. Data Sources: Literature was accessed through MEDLINE (1950-current) and EMBASE using the terms antiobesity agent, diethylpropion, phentermine, orlistat, topiramate, lorcaserin, bupropion, and naltrexone. In addition, reference citations from publications identified were reviewed. Files related to FDA expert panel hearings were retrieved from the FDA website. Study Selection and Data Extraction: Randomized double-blind trials assessing the efficacy and safety of antiobesity agents compared with placebo in the treatment of overweight and obese adults were reviewed. Only English-language or English-translated literature was reviewed. Medications were selected based on FDA approval status. Data Synthesis: Ten double-blind clinical trials were reviewed. There are currently 5 FDA-approved antiobesity agents and 1 agent recently rejected by the FDA. Study results for all agents showed statistically significant weight loss compared with placebo, but with varying adverse effects. The combination of phentermine and topiramate is the most efficacious antiobesity agent approved by the FDA. However, this combination has various neurologic, cardiovascular, and teratogenic safety risks that may limit its use. Based on its safety profile, orlistat is the preferred antiobesity medication, despite the lesser extent to which it induces weight loss versus newer agents. The incidence of unwanted gastrointestinal adverse effects limits its use. Conclusions: Despite a glaring medical need for options to treat obesity, available medications are limited. No current drug option is ideal; each has either safety risks or efficacy concerns. Safe agents that meet FDA efficacy standards are needed to help treat the obesity epidemic.

Lactulose in the Management of Constipation: A Current Review

1992 ◽  
Vol 26 (10) ◽  
pp. 1277-1282 ◽  
Author(s):  
Theresa V. Kot ◽  
Ngaire A. Pettit-Young
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Clinical Studies ◽  
Data Extraction ◽  
Point Of View ◽  
Data Synthesis ◽  
Study Selection ◽  
Beneficial Response ◽  
A Current

OBJECTIVE: To review the current published clinical studies evaluating the clinical efficacy and safety of lactulose compared with other laxatives or placebo. Adverse effects associated with lactulose are also reported. DATA SOURCES: Information was retrieved by searching the MEDLINE and EMBASE databases for clinical trials, abstracts, conference proceedings, and review articles dealing with lactulose. STUDY SELECTION: Emphasis was placed on clinical trials where lactulose was compared with other laxatives or placebo in patient populations where the diagnosis of constipation was reasonably established. DATA EXTRACTION: The methodology and results from clinical studies were evaluated. Assessment of the studies was made based on diagnosis of constipation, prior management of patients, follow-up of patients, dosage, and adverse effects. DATA SYNTHESIS: Clinical trials in geriatric patients, terminally ill patients, children, and normal and constipated subjects were reviewed. In most instances, lactulose was compared with a placebo, without incorporating the current education on dietary techniques for improving defecation. CONCLUSIONS: Generally, clinical trials have demonstrated a beneficial response compared with placebo, although sometimes that response has been only marginally better, from a clinical point of view.

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management

2021 ◽  
pp. 106002802110538
Author(s):  
Courtney L. Bradley ◽  
Sara M. McMillin ◽  
Andrew Y. Hwang ◽  
Christina H. Sherrill
Keyword(s):  
Weight Loss ◽  
Adverse Effects ◽  
Data Extraction ◽  
High Dose ◽  
Lifestyle Interventions ◽  
Double Blind ◽  
Study Selection ◽  
Patients With Diabetes ◽  
Glycemic Indices ◽  
Overweight Or Obesity

Objective To review the pharmacology, efficacy, and safety of high-dose once-weekly semaglutide for chronic weight management. Data Sources PubMed/MEDLINE and ClinicalTrials.gov were searched (inception to September 8, 2021) using keywords “semaglutide” and “obesity,” “weight,” “high dose,” “high-dose,” or “2.4.” Study Selection and Data Extraction Clinical trials with published results were included. Publications studying the oral or <2.4 mg formulation of semaglutide were excluded. Data Synthesis Four phase 3, multicenter, randomized, double-blind trials demonstrated efficacy of high-dose once-weekly semaglutide compared with placebo for weight loss. Study populations included patients with overweight or obesity (STEP 1, STEP 3, and STEP 4) or patients with diabetes and with overweight or obesity (STEP 2). Lifestyle interventions for diet and exercise were included for all participants. Weight loss from baseline was significant for all studies, and secondary outcomes demonstrated cardiometabolic improvements including waist circumference, systolic blood pressure, and lipid profiles. Gastrointestinal adverse effects were common, but the medication was otherwise well tolerated. Relevance to Patient Care and Clinical Practice High-dose semaglutide offers significant weight-lowering potential and favorable effects on cardiometabolic risk factors and glycemic indices. Clinicians and patients should consider the route and frequency of administration, adverse effect profile, and cost when choosing an antiobesity medication. The importance of concomitant lifestyle interventions should be emphasized. Conclusions High-dose once-weekly semaglutide can significantly reduce weight, and although gastrointestinal adverse effects were common, it is generally well tolerated.

Nelarabine: A Nucleoside Analog with Efficacy in T-Cell and other Leukemias

2005 ◽  
Vol 39 (6) ◽  
pp. 1056-1063 ◽  
Author(s):  
David F Kisor
Keyword(s):  
T Cell ◽  
English Language ◽  
Data Extraction ◽  
Safety Information ◽  
Hematologic Malignancies ◽  
Water Soluble ◽  
Significant Activity ◽  
Study Selection ◽  
Important Addition ◽  
Key Terms

OBJECTIVE: To present the pharmacology and pharmacokinetics of nelarabine, 9-β-D-arabinofuranosylguanine (ara-G) and intraleukemic cellular pharmacokinetics of 9-β-D-arabinofuranosylguanine triphosphate (ara-GTP) generated from the administration of nelarabine, and clinical and safety information relative to nelarabine use in the treatment of hematologic malignancies. DATA SOURCES: MEDLINE (1966—December 2004) was searched using the English-language key terms 2-amino-6-methoxypurine arabinoside, 506U78, and nelarabine. Data were also obtained from published abstracts. STUDY SELECTION AND DATA EXTRACTION: Clinical studies evaluating the pharmacokinetics of nelarabine, ara-G, and cellular ara-GTP and use of nelarabine, alone or in combination with other agents for the treatment of hematologic malignancies, were included in this review. DATA SYNTHESIS: Nelarabine is the water-soluble, 6-methoxy analog of 9-β-D-ara-G. Nelarabine is readily converted to ara-G by endogenous adenosine deaminase. The half-life of nelarabine is approximately 15 minutes compared with 2–4 hours for ara-G. The clearance of ara-G is higher in children than in adults (0.312 vs 0.213 L × h−1 × kg−1). Intracellular ara-GTP elimination is slow relative to nelarabine and ara-G. In pediatric and adult patients, neurologic toxicity is dose limiting. Severe myelosuppression was not consistently observed. Major responses were seen in patients with T-cell malignancies. Patients who responded had significantly higher intracellular ara-GTP concentrations compared with those who did not respond. CONCLUSIONS: Nelarabine is an effective ara-G prodrug. Nelarabine has significant activity against malignant T-cells and appears to be an important addition to treatments of various leukemias.

Granisetron: The Second Serotonin-Receptor Antagonist

1995 ◽  
Vol 29 (12) ◽  
pp. 1240-1251 ◽  
Author(s):  
Val R Adams ◽  
Amy W Valley
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Receptor Antagonist ◽  
Serotonin Receptor ◽  
English Language ◽  
Data Extraction ◽  
Optimal Dose ◽  
Nausea And Vomiting ◽  
Cost Comparison ◽  
Antiemetic Agents

Objective: To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of granisetron, focusing on critical analysis of published clinical trials and comparison with other antiemetic agents, including ondansetron. Data Sources: MEDLINE (1966–1995) and CANCERLIT (1991–1995) searches of English-language literature using the terms “granisetron” and “granisetron (m)” were performed. Study Selection And Data Extraction: All articles were considered for possible inclusion in this review. Abstracts of clinical trials were included only when they were judged to add critical information not otherwise available in the medical literature. For studies published more than once, the most recent publication was cited. Data Synthesis: Nausea and vomiting are rated by patients as the most distressing chemotherapy-related adverse effects and may produce potentially life-threatening complications. The discovery of the role of serotonin in nausea and vomiting and the development of selective serotonin3-receptor (5-HT3) antagonists has significantly diminished the incidence and consequences of chemotherapy-related nausea and vomiting. Granisetron is the second 5-HT3-receptor antagonist to be marketed in the US. Granisetron has been compared with other antiemetic agents, including ondansetron, against highly and moderately emetogenic chemotherapy. The results of these trials have shown granisetron to be superior to conventional antiemetics and as effective as ondansetron in the prevention of chemotherapy-induced nausea and vomiting. The optimal dose of granisetron has yet to be determined. Formulary decisions should be based on a cost comparison among the 5-HT3-receptor antagonists at individual institutions. Conclusions: Granisetron is a safe, effective antiemetic agent for the management of nausea and vomiting caused by cancer chemotherapy.

scholarly journals Asenapine for the Treatment of Psychotic Disorders

2016 ◽  
Vol 62 (2) ◽  
pp. 123-137 ◽  
Author(s):  
Catherine Orr ◽  
Santosh Deshpande ◽  
Sonja Sawh ◽  
Philip M. Jones ◽  
Kamini Vasudev
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Psychotic Disorders ◽  
Randomized Clinical Trials ◽  
Current Evidence ◽  
Metabolic Outcomes ◽  
Syndrome Scale ◽  
Efficacy Measures ◽  
Clinically Significant ◽  
Negative Syndrome

Objective: A systematic review was conducted to examine the efficacy, tolerability, and acceptability of asenapine compared with other antipsychotics in the treatment of psychotic disorders. Methods: Four databases, 8 trial registries, and conference presentations were searched for randomized clinical trials of asenapine versus any comparator for the treatment of any psychotic illness. Primary outcome measures were changes in the Positive and Negative Syndrome Scale (PANSS) total score and the incidence of withdrawal due to adverse effects. Results: Eight randomized clinical trials, encompassing 3765 patients, that compared asenapine with placebo ( n = 5) and olanzapine ( n = 3) were included. No differences were found between asenapine and olanzapine in terms of changes to PANSS total or PANSS negative subscale scores. Patients taking asenapine were more likely to experience worsening schizophrenia and/or psychosis than were those taking olanzapine. No differences were found between asenapine and olanzapine in rates of discontinuation due to adverse drug reactions or lack of efficacy, but those taking asenapine had higher rates of withdrawal for any reason than those taking olanzapine. Asenapine caused less clinically significant weight gain or increases in triglycerides than olanzapine and was more likely to cause extrapyramidal symptoms than olanzapine. In comparison to placebo, either no difference or superiority was demonstrated in favour of asenapine on all efficacy measures. Conclusion: The current evidence is limited, as asenapine has been compared only with placebo or olanzapine. In the randomized clinical trials analysed, asenapine was similar or superior to placebo and similar or inferior to olanzapine on most efficacy outcomes. While asenapine demonstrated fewer adverse metabolic outcomes than olanzapine, rates of extrapyramidal symptom–related adverse effects were higher.

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