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Frontiers in Oncology 2022Although immune checkpoint inhibitors (ICIs) have revolutionized the current anticancer therapies, a considerable proportion of patients are found to hardly benefit from...
An Up-To-Date Investigation Into the Correlation Between Proton Pump Inhibitor Use and the Clinical Efficacy of Immune Checkpoint Inhibitors in Advanced Solid Cancers: A Systematic Review and Meta-Analysis.
BACKGROUND
Although immune checkpoint inhibitors (ICIs) have revolutionized the current anticancer therapies, a considerable proportion of patients are found to hardly benefit from these drugs. Accumulating studies have demonstrated that concomitant proton pump inhibitor (PPI) use may affect the clinical efficacy of ICIs; however, their results are inconsistent. In this study, based on updated evidence, we aimed to perform a meta-analysis to clarify the prognostic significance of PPI use in advanced solid cancer patients receiving ICI therapy.
METHODS
Eligible literature was searched using PubMed, Cochrane Library, Web of Science, EMBASE, and other network resources before July 2021. Clinical outcome was evaluated using overall survival (OS) and progression-free survival (PFS). The correlation of PPI use with OS or PFS was determined based on hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS
A total of 17 studies enrolling 9,978 ICI-treated cancer patients were included in our meta-analysis. The global analysis demonstrated that PPI use was significantly correlated with worse OS [HR = 1.29 (1.10-1.50)] instead of PFS [HR = 1.19 (0.98-1.44)] in solid cancer patients receiving ICI therapy. In a subgroup analysis, the negative correlation of PPI use with ICI efficacy was significant in patients with non-small cell lung cancer [PFS, HR = 1.27 (1.10-1.47)] and urothelial carcinoma [OS, HR = 1.55 (1.31-1.84), PFS, HR = 1.52 (1.13-2.06)] and mixed cohorts containing multiple cancer types [OS, HR = 1.40 (1.16-1.69)], while an opposite result was observed in the PFS of patients with melanoma [HR = 0.48 (0.25-0.90)]. Moreover, the unfavorable prognostic impact of PPI use was also significant in patients over 65 years old [OS, HR = 1.28 (1.05-1.55), PFS, HR = 1.32 (1.12-1.56)] or those receiving anti-PD-1 [OS, HR = 1.37 (1.04-1.79)] or anti-PD-L1 therapies (OS, HR = 1.49 (1.30-1.69), PFS, HR = 1.34 (1.20-1.50). Finally, PPI use was significantly correlated with a worse prognosis in patients receiving PPIs 30 days before and/or after ICI initiation (OS, HR = 1.38 (1.18-1.62), PFS, HR = 1.23 (1.06-1.43)).
CONCLUSION
Although our global analysis revealed PPI use was not correlated with the PFS of ICI-treated patients, considering the results of our subgroup analysis, PPIs should be still cautiously used shortly before or during ICI therapy. Furthermore, more clinical validations and related mechanism investigations are of great necessity to clarify the clinical correlation of PPI use with ICI efficacy.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], PROSPERO [No. CRD42021243707].
PubMed: 35280736
DOI: 10.3389/fonc.2022.753234 -
World Journal of Surgical Oncology Jul 2020The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer.
METHODS
The meta-analysis searched the PubMed, Web of Science, EBSCO, and Cochrane libraries from inception to February 2020 to identify relevant studies. And the main results of this study were long-term prognosis and treatment-related adverse events.
RESULTS
The results showed that the addition of PARP inhibitors could significantly prolong progression-free survival (PFS) and overall survival (OS) for patients with ovarian cancer (HR 0.44, 95% CI 0.34-0.53, p < 0.001; HR, 0.79, 95% CI 0.65-0.94, p < 0.001, respectively). In the BRCA 1/2 mutation patients, the HR of PFS was 0.29 (p < 0.001), and the HR was 0.51 (p < 0.001) in the no BRCA 1/2 mutation patients. The HR of PFS was 0.40 (p < 0.001) in the homologous recombination deficiency (HRD) mutation patients, while the HR was 0.80 (p < 0.001) in the no HRD mutation patients. Moreover, the analysis found that the use of PARP inhibitors did not significantly increase the risk of all grade adverse events (AEs) (RR = 1.04, p = 0.16). But the incidence of grade 3 or higher AEs was increased (RR = 1.87, p = 0.002). In general, the AEs were mainly manifested in the blood system.
CONCLUSIONS
PARP inhibitors can improve the prognosis of ovarian cancer patients with and without genetic mutations (BRCA 1/2 or HRD). Furthermore, PARP inhibitors were tolerable to patients when added to their current therapy, although it inevitably adds the grade 3 and higher AEs.
Topics: Adenosine Diphosphate Ribose; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Prognosis
PubMed: 32622363
DOI: 10.1186/s12957-020-01931-7 -
PloS One 2016We aimed to compare the safety of antidepressants for the treatment of persistent depressive disorder (PDD) with each other and with placebo. We conducted a systematic... (Comparative Study)
Comparative Study Meta-Analysis Review
We aimed to compare the safety of antidepressants for the treatment of persistent depressive disorder (PDD) with each other and with placebo. We conducted a systematic electronic search and included randomized controlled trials that investigated antidepressants for the treatment of PDD in adults. Outcomes were the incidence of experiencing any adverse event, specific adverse events and related treatment discontinuations. We analyzed the data using traditional and network meta-analyses. Thirty-four studies that comprised 4,769 patients and examined 20 individual agents in nine substance classes were included. Almost all analyzed substance classes were associated with higher discontinuation rates than placebo including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), antipsychotics, and the serotonin antagonist and reuptake inhibitor (SARI) trazodone. The odds of experiencing any adverse event were significantly higher for TCAs and serotonin noradrenaline reuptake inhibitors (SNRIs) compared to placebo. Pairwise comparisons among the substance classes revealed that more patients receiving TCAs or SNRIs experienced any adverse event and that more patients receiving TCAs or the SARI trazodone discontinued treatment. The complementary treatment with acetyl-l-carnitine showed lower rates of experiencing any adverse event and related discontinuations than all other comparators. TCAs were primarily associated with (anti-)cholinergic and sedating adverse events. SSRIs primarily showed gastrointestinal adverse events. Patients treated with the antipsychotic amisulpride were more likely to manifest weight gain and endocrine adverse events. The comparative evidence for further agents was insufficient or lacking. The identified safety differences may be used to inform the selection among the antidepressants.
Topics: Antidepressive Agents; Depression; Humans
PubMed: 27187783
DOI: 10.1371/journal.pone.0153380 -
Medicine Sep 2023To evaluate through meta-analysis whether long-term use of proton pump inhibitor (PPI) increases the risk of precancerous lesions in the stomach. (Meta-Analysis)
Meta-Analysis
Whether long-term use of proton pump inhibitor increases the risk of precancerous lesions in the stomach: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
To evaluate through meta-analysis whether long-term use of proton pump inhibitor (PPI) increases the risk of precancerous lesions in the stomach.
METHODS
Randomized controlled trials that compared the occurrence and progression of precancerous lesions in patients receiving PPI treatment versus non-PPI treatment were retrieved from CNKI, VIP, Wanfang, CBM, Pubmed, Embase, Web of Science, and Cochrane Library databases (from database inception to May 1, 2023). The Revman 5.3 and STATA 17.0 software were used for analysis, and subgroup analysis was conducted based on follow-up time (≤12 months and > 12 months) and lesion type (atrophic gastritis, intestinal metaplasia, and epithelial dysplasia).
RESULTS
Six randomized controlled trials with a total of 1623 cases were included, including 1015 cases in the experimental group and 608 cases in the control group. The meta-analysis results showed that the overall abnormal lesion rate combined with statistical relative risk (RR) = 1.31 (0.85-2.02), P = .23. Subgroup analysis showed that the follow-up time > 12 months combined result was RR = 2.21 (1.47-3.33), P = .0001, the intestinal metaplasia group combined result was RR = 1.96 (0.91-2.47), P = .04.
CONCLUSION SUBSECTIONS
During long-term follow-up, patients using PPI exhibited a significantly higher incidence of overall abnormal lesions compared to the control group, particularly with a higher risk observed for intestinal metaplasia. However, there were no statistically significant differences between the 2 groups in terms of short-term follow-up and other types of lesions. It is important to exercise caution when interpreting these findings due to the limited number of nominated investigations included in the meta-analysis.
Topics: Humans; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Stomach; Precancerous Conditions; Carcinoma in Situ
PubMed: 37747015
DOI: 10.1097/MD.0000000000035062 -
PloS One 2023The triple combination of hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus tyrosine kinase inhibitor (TKI) and... (Meta-Analysis)
Meta-Analysis
Triple combination of HAIC-FO plus tyrosine kinase inhibitors and immune checkpoint inhibitors for advanced hepatocellular carcinoma: A systematic review and meta-analysis.
BACKGROUND
The triple combination of hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitors (ICIs) is expected to have a synergistic anticancer effect in HCC. We conducted this meta-analysis to evaluate the efficacy and safety of the triple combination treatment in advanced HCC patients.
METHODS
PubMed, Embase, Cochrane Library, Web of Science databases were systematically searched for relevant studies from the inception of each database to May 10, 2023. All articles focusing the triple combination treatment of HAIC-FO plus TKI and ICIs for advanced HCC were eligible. The meta-analysis was conducted following the PRISMA guidelines. The risk of bias was assessed using the Joanna Briggs Institute (JBI) for case series and Newcastle-Ottawa Scale (NOS) for cohort studies. The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). The secondary results were adverse events. Further meta-analysis of control studies demonstrated the superiority of the triple combination modality to TKI plus ICIs, and TKI alone.
RESULTS
Nine articles (four cohort studies and five one-arm studies) involving 777 advanced HCC patients were included in this meta-analysis. In terms of survival analysis, the pooled median PFS was 11 months (95% CI: 10.1-12.0 months) with low heterogeneity (I2 = 0%, p = 0.97). With regard to tumor response, the pooled ORR and DCR was 61.6% (I2=0%, p = 0.71) and 87.9% (I2 = 13%, p = 0.33) with low heterogeneity, respectively. As compared with TKIs plus ICIs, and TKIs alone, the triple combination thrapy was associated with improved median OS (HR=0.51, 95%CI 0.41-0.62) with low heterogeneity across studies (I2 = 0%, p = 0.47), median PFS (HR=0.51, 95%CI 0.41-0.64) with low heterogeneity across studies (I2 = 0%, p = 0.41), ORR (RR = 0.56, 95% CI: 0.42-0.74) with high heterogeneity across studies (I2 = 69%, p = 0.02), and DCR (RR = 0.38, 95%CI 0.27-0.54) with low heterogeneity across studies (I2 = 14%, p = 0.32). The most common 3/4 AEs were elevated ALT and AST, thrombocytopenia, hypertension, nausea and vomiting in this meta-analysis.
CONCLUSIONS
The triple combination therapy of HAIC-FO plus TKI and ICIs showed promising efficacy and safety in patients with advanced HCC.
REGISTRATION
The protocol was registered with PROSPERO (ID:CRD42023424281).
Topics: Humans; Carcinoma, Hepatocellular; Antineoplastic Agents; Immune Checkpoint Inhibitors; Tyrosine Kinase Inhibitors; Liver Neoplasms; Protein Kinase Inhibitors
PubMed: 37844117
DOI: 10.1371/journal.pone.0290644 -
The Cochrane Database of Systematic... Apr 2018Panic disorder is characterised by repeated, unexpected panic attacks, which represent a discrete period of fear or anxiety that has a rapid onset, reaches a peak within... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Panic disorder is characterised by repeated, unexpected panic attacks, which represent a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes, and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. It is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, the National Institute for Health and Care Excellence (NICE) and the British Association for Psychopharmacology consider antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Several classes of antidepressants have been studied and compared, but it is still unclear which antidepressants have a more or less favourable profile in terms of effectiveness and acceptability in the treatment of this condition.
OBJECTIVES
To assess the effects of antidepressants for panic disorder in adults, specifically:1. to determine the efficacy of antidepressants in alleviating symptoms of panic disorder, with or without agoraphobia, in comparison to placebo;2. to review the acceptability of antidepressants in panic disorder, with or without agoraphobia, in comparison with placebo; and3. to investigate the adverse effects of antidepressants in panic disorder, with or without agoraphobia, including the general prevalence of adverse effects, compared to placebo.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders' (CCMD) Specialised Register, and CENTRAL, MEDLINE, EMBASE and PsycINFO up to May 2017. We handsearched reference lists of relevant papers and previous systematic reviews.
SELECTION CRITERIA
All double-blind, randomised, controlled trials (RCTs) allocating adults with panic disorder to antidepressants or placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently checked eligibility and extracted data using a standard form. We entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details and settings. Primary outcomes included failure to respond, measured by a range of response scales, and treatment acceptability, measured by total number of dropouts for any reason. Secondary outcomes included failure to remit, panic symptom scales, frequency of panic attacks, agoraphobia, general anxiety, depression, social functioning, quality of life and patient satisfaction, measured by various scales as defined in individual studies. We used GRADE to assess the quality of the evidence for each outcome MAIN RESULTS: Forty-one unique RCTs including 9377 participants overall, of whom we included 8252 in the 49 placebo-controlled arms of interest (antidepressant as monotherapy and placebo alone) in this review. The majority of studies were of moderate to low quality due to inconsistency, imprecision and unclear risk of selection and performance bias.We found low-quality evidence that revealed a benefit for antidepressants as a group in comparison with placebo in terms of efficacy measured as failure to respond (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.66 to 0.79; participants = 6500; studies = 30). The magnitude of effect corresponds to a number needed to treat for an additional beneficial outcome (NNTB) of 7 (95% CI 6 to 9): that means seven people would need to be treated with antidepressants in order for one to benefit. We observed the same finding when classes of antidepressants were compared with placebo.Moderate-quality evidence suggested a benefit for antidepressants compared to placebo when looking at number of dropouts due to any cause (RR 0.88, 95% CI 0.81 to 0.97; participants = 7850; studies = 30). The magnitude of effect corresponds to a NNTB of 27 (95% CI 17 to 105); treating 27 people will result in one person fewer dropping out. Considering antidepressant classes, TCAs showed a benefit over placebo, while for SSRIs and serotonin-norepinephrine reuptake inhibitor (SNRIs) we observed no difference.When looking at dropouts due to adverse effects, which can be considered as a measure of tolerability, we found moderate-quality evidence showing that antidepressants as a whole are less well tolerated than placebo. In particular, TCAs and SSRIs produced more dropouts due to adverse effects in comparison with placebo, while the confidence interval for SNRI, noradrenergic reuptake inhibitors (NRI) and other antidepressants were wide and included the possibility of no difference.
AUTHORS' CONCLUSIONS
The identified studies comprehensively address the objectives of the present review.Based on these results, antidepressants may be more effective than placebo in treating panic disorder. Efficacy can be quantified as a NNTB of 7, implying that seven people need to be treated with antidepressants in order for one to benefit. Antidepressants may also have benefit in comparison with placebo in terms of number of dropouts, but a less favourable profile in terms of dropout due to adverse effects. However, the tolerability profile varied between different classes of antidepressants.The choice of whether antidepressants should be prescribed in clinical practice cannot be made on the basis of this review.Limitations in results include funding of some studies by pharmaceutical companies, and only assessing short-term outcomes.Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.
Topics: Adult; Agoraphobia; Antidepressive Agents; Humans; Numbers Needed To Treat; Panic Disorder; Patient Dropouts; Placebos; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 29620793
DOI: 10.1002/14651858.CD010676.pub2 -
The Cochrane Database of Systematic... Sep 2016A panic attack is a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes and in which at least four of 13 characteristic symptoms... (Review)
Review
BACKGROUND
A panic attack is a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. Panic disorder is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, antidepressants and benzodiazepines are the mainstay of treatment for panic disorder. Different classes of antidepressants have been compared; and the British Association for Psychopharmacology, and National Institute for Health and Care Excellence (NICE) consider antidepressants (mainly selective serotonin reuptake inhibitors (SSRIs)) as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). In addition to antidepressants, benzodiazepines are widely prescribed for the treatment of panic disorder.
OBJECTIVES
To assess the evidence for the effects of antidepressants and benzodiazepines for panic disorder in adults.
SEARCH METHODS
The Specialised Register of the Cochrane Common Mental Disorders Group (CCMDCTR) to 11 September 2015. This register includes relevant randomised controlled trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-) and PsycINFO (1967-). Reference lists of relevant papers and previous systematic reviews were handsearched. We contacted experts in this field for supplemental data.
SELECTION CRITERIA
All double-blind randomised controlled trials allocating adult patients with panic disorder to antidepressants or benzodiazepines versus any other active treatment with antidepressants or benzodiazepines.
DATA COLLECTION AND ANALYSIS
Two review authors independently checked eligibility and extracted data using a standard form. Data were entered in RevMan 5.3 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings and outcome measures in terms of efficacy, acceptability and tolerability.
MAIN RESULTS
Thirty-five studies, including 6785 participants overall (of which 5365 in the arms of interest (antidepressant and benzodiazepines as monotherapy)) were included in this review; however, since studies addressed many different comparisons, only a few trials provided data for primary outcomes. We found low-quality evidence suggesting no difference between antidepressants and benzodiazepines in terms of response rate (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.67 to 1.47; participants = 215; studies = 2). Very low-quality evidence suggested a benefit for benzodiazepines compared to antidepressants in terms of dropouts due to any cause, even if confidence interval (CI) ranges from almost no difference to benefit with benzodiazepines (RR 1.64, 95% CI 1.03 to 2.63; participants = 1449; studies = 7). We found some evidence suggesting that serotonin reuptake inhibitors (SSRIs) are better tolerated than TCAs (when looking at the number of patients experiencing adverse effects). We failed to find clinically significant differences between individual benzodiazepines. The majority of studies did not report details on random sequence generation and allocation concealment; similarly, no details were provided about strategies to ensure blinding. The study protocol was not available for almost all studies so it is difficult to make a judgment on the possibility of outcome reporting bias. Information on adverse effects was very limited.
AUTHORS' CONCLUSIONS
The identified studies are not sufficient to comprehensively address the objectives of the present review. The majority of studies enrolled a small number of participants and did not provide data for all the outcomes specified in the protocol. For these reasons most of the analyses were underpowered and this limits the overall completeness of evidence. In general, based on the results of the current review, the possible role of antidepressants and benzodiazepines should be assessed by the clinician on an individual basis. The choice of which antidepressant and/or benzodiazepine is prescribed can not be made on the basis of this review only, and should be based on evidence of antidepressants and benzodiazepines efficacy and tolerability, including data from placebo-controlled studies, as a whole. Data on long-term tolerability issues associated with antidepressants and benzodiazepines exposure should also be carefully considered.The present review highlights the need for further higher-quality studies comparing antidepressants with benzodiazepines, which should be conducted with high-methodological standards and including pragmatic outcome measures to provide clinicians with useful and practical data. Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.
PubMed: 27618521
DOI: 10.1002/14651858.CD011567.pub2 -
International Journal of Molecular... Jun 2022Most ovarian cancer cases are diagnosed at an advanced stage (III or IV), in which a primary debulking surgery combined with adjuvant systemic chemotherapy is the... (Review)
Review
Most ovarian cancer cases are diagnosed at an advanced stage (III or IV), in which a primary debulking surgery combined with adjuvant systemic chemotherapy is the standard management. Since targeted therapy is less toxic to human cells than systemic chemotherapy, it has drawn much attention and become more popular. Angiogenesis is a critical process during the proliferation of ovarian cancer cells. Currently, many studies have put emphases on anti-angiogenetic medication, such as bevacizumab, the first and most investigated angiogenesis inhibitor that can exert anti-neoplastic effects. Bevacizumab is a recombinant humanized monoclonal antibody that has been approved for first-line maintenance treatment of advanced ovarian cancer. This review is a summary of current literature about the molecular mechanisms of actions, safety, and effects of bevacizumab for use in advanced epithelial ovarian cancer. Some common side effects of bevacizumab will be also discussed. As an inhibitor of angiogenesis, bevacizumab binds to circulating vascular endothelial growth factor (VEGF) and thereby inhibits the binding of VEGF to its receptors on the surface of endothelial cells. Neutralization of VEGF prevents neovascularization and leads to apoptosis of tumor endothelial cells and a decrease in interstitial fluid pressure within the tumors, which allows greater capacity for chemotherapeutic drugs to reach specific targeted sites. Grossly, bevacizumab has demonstrated some significant therapeutic benefits in many randomized trials in combination with the standard chemotherapy for advanced epithelial ovarian cancer. Based on the available evidence, a higher dosage and a longer duration of bevacizumab appear to achieve better therapeutic effects and progression-free survival. On the other hand, patients with more severe diseases or at a higher risk of progression seem to benefit more from bevacizumab use. However, many unknown aspects of bevacizumab, including detailed mechanisms of actions, effectiveness, and safety for the treatment of ovarian cancer, warrant further investigation.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Ovarian Epithelial; Endothelial Cells; Female; Humans; Neovascularization, Pathologic; Ovarian Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 35805914
DOI: 10.3390/ijms23136911 -
Pharmaceutical Biology Dec 2020Research interest in monoamine oxidase (MAO) as a promising drug target for neurodegenerative diseases has a long history. However, efforts to develop MAO inhibitors...
CONTEXT
Research interest in monoamine oxidase (MAO) as a promising drug target for neurodegenerative diseases has a long history. However, efforts to develop MAO inhibitors (MAOIs) from marine sources have been limited, despite the increasing number of interesting marine natural products.
OBJECTIVE
To review the potential of marine natural products as MAOIs source, including their activities and selectivity on MAO.
METHODS
Public databases such as SciFinder, MarinLit and PubMed were systematically searched from 1991 until Dec 2019. MAO and MAOI were the key terms searched combined with marine natural products and marine.
RESULTS
Six classes of marine natural products with good selectivity between the two MAO subtypes were organized with their selectivity and sources.
CONCLUSIONS
This is the first review to investigate the potential of marine natural products as MAOIs source. Despite the small number of known MAOIs from marine sources, marine natural products are potential leads for the further development of MAOI drugs with novel chemical frames and good selectivity.
Topics: Animals; Aquatic Organisms; Biological Products; Drug Development; Humans; Monoamine Oxidase Inhibitors; Neurodegenerative Diseases
PubMed: 32697127
DOI: 10.1080/13880209.2020.1790618 -
British Journal of Clinical Pharmacology Sep 2018To the best of our knowledge, there are no systematic reviews or meta-analyses that compare rasagiline, selegiline and safinamide. Therefore, we aimed to perform a drug... (Comparative Study)
Comparative Study Meta-Analysis
AIMS
To the best of our knowledge, there are no systematic reviews or meta-analyses that compare rasagiline, selegiline and safinamide. Therefore, we aimed to perform a drug class review comparing all available monoamine oxidase type B (MAO-B) inhibitors in a multiple treatment comparison.
METHODS
We performed a systematic literature search to identify randomized controlled trials assessing the efficacy of MAO-B inhibitors in patients with Parkinson's disease. MAO-B inhibitors were evaluated either as monotherapy or in combination with levodopa or dopamine agonists. Endpoints of interest were change in the Unified Parkinson's Disease Rating Scale (UPDRS) score and serious adverse events. We estimated the relative effect of each MAO-B inhibitor versus the comparator drug by creating three networks of direct and indirect comparisons. For each of the networks, we considered a joint model.
RESULTS
The systematic literature search and study selection process identified 27 publications eligible for our three network analyses. We found the relative effects of rasagiline, safinamide and selegiline treatment given alone and compared to placebo in a model without explanatory variables to be 1.560 (1.409, 1.734), 1.449 (0.873, 2.413) and 1.532 (1.337, 1.757) respectively. We also found all MAO-B inhibitors to be efficient when given together with levodopa. When ranking the MAO-B inhibitors given in combination with levodopa, selegiline was the most effective and rasagiline was the second best.
CONCLUSIONS
All of the included MAO-B inhibitors were effective compared to placebo when given as monotherapy. Combination therapy with MAO-B inhibitors and levodopa showed that all three MAO-B inhibitors were effective compared to placebo, but selegiline was the most effective drug.
Topics: Antiparkinson Agents; Drug Therapy, Combination; Humans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease; Randomized Controlled Trials as Topic; Selegiline; Treatment Outcome
PubMed: 29847694
DOI: 10.1111/bcp.13651