The prevalence and impact of polypharmacy in rheumatology.

Polypharmacy is increasingly common in rheumatology due to the complex nature of managing chronic autoimmune diseases. To date there has been limited research into the impact of polypharmacy on rheumatology patients. In this article we reviewed the literature to characterize the prevalence of polypharmacy and its effect on patients. In addition, we have highlighted some key drug-drug interactions to consider involving DMARDs as well as complementary and alternative medicines. There is emerging evidence demonstrating that polypharmacy contributes to adverse outcomes and alters treatment response. This association is best described in RA and is less clear in other patient cohorts. It is also unclear whether polypharmacy is directly harmful or just a surrogate marker for other factors affecting outcomes. Rheumatologists should be aware of the risk of polypharmacy as well as specific drug-drug interactions that can occur in managing chronic autoimmune disease.

Efficacy analysis and research progress of complementary and alternative medicines in the adjuvant treatment of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has impacted human lifestyles around the world, causing huge distress in terms of public health systems, emergency response capacity and economic development. The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with respiratory involvement, cardiovascular-related diseases, and ultimately causes multiple organ failure and death in severely affected individuals. Thus, effective prevention or early treatment of COVID-19 is critical. An effective vaccine offers a way out of the pandemic for governments, the scientific community and people worldwide, but we still lack effective drug therapies, including treatments for the prevention and treatment of COVID-19. This had led to a high global demand for many complementary and alternative medicines (CAMs). Moreover, many healthcare providers are now requesting information about CAMs that prevent, relieve, or treat the symptoms of COVID-19 and even alleviate vaccine-related side effects. Experts and scholars must therefore become familiar with the use of CAMs in COVID-19, current research directions and effectiveness of CAMs for COVID-19. This narrative review updates the current status and research worldwide on the use of CAMs for COVID-19. The review provides reliable evidence on theoretical viewpoints and therapeutic efficacies of CAM combinations, and evidence in support of the therapeutic strategy of Taiwan Chingguan Erhau (NRICM102) against moderate-to-severe novel coronavirus infectious disease in Taiwan.

Quality of life in terminally ill cancer patients: what is the role of using complementary and alternative medicines?

BACKGROUND AND PURPOSE: Cancer is the world's second greatest cause of mortality and a leading cause of death in both developed and developing countries. Patients employ a number of complementary and alternative medicine (CAM) methods to deal with the problems and difficulties of cancer, which can have an impact on their quality of life (QOL). The aim of the present study was to assess the correlation between QOL and the use of different CAM methods in terminally ill cancer patients. METHODS: This was a cross-sectional study. In southern Iran, 238 individuals with advanced cancer were studied in oncology centers and doctors' offices. During the months of January to August 2021, patients were selected using convenience sampling. A demographic information questionnaire, the EORTC core quality of life questionnaire, and the CAM questionnaire were used to collect data. RESULTS: The results showed that terminally ill cancer patients had a good quality of life. Last year, 85.7% of participants used at least one kind of CAM. Furthermore, 45.4% of participants used only one form of CAM, 30.3% used two types of CAM, 6.7% used three types of CAM, and 3.4% used four to five types of CAM. When all CAM users were compared to non-CAM users, CAM users had significantly higher social QOL and overall quality of life. Two subscales of QOL symptoms and function were correlated with cancer history, income, and use of CAMs, and the scores of QOL symptoms and function were greater in CAM users compared to non-CAM users. Among all the study variables, only the usage of CAM was correlated to overall QOL among terminally ill cancer patients. CONCLUSION: The current study found that using CAM could affect different aspects of QOL in terminally ill cancer patients. As a result, it is feasible that using CAM could help these people enhance their health and QOL.

Meditation-Based Therapy for Chronic Low Back Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Chronic low back pain (CLBP) is among the most common types of pain in adults. Currently, injections and analgesic and nonsteroidal anti-inflammatory drugs are often provided for patients with CLBP. However, their effectiveness remains questionable, and the safest approach to CLBP remains debated. Meditation-based therapies constitute an alternative treatment with high potential for widespread availability. We evaluated the applicability of meditation-based therapies for CLBP management. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy of meditation-based therapies for CLBP management. The primary outcomes were pain intensity, quality of life, and pain-related disability; the secondary outcomes were the experienced distress or anxiety and pain bothersomeness in the patients. The PubMed, Embase, and Cochrane databases were searched for studies published from the databases' inception dates until July 2021, without language restrictions. RESULTS: We reviewed 12 randomized controlled trials with 1,153 patients. In 10 trials, meditation-based therapies significantly reduced the CLBP pain intensity compared with nonmeditation therapies (standardized mean difference [SMD] -0.27, 95% confidence interval [CI] = -0.43 to -0.12, P = 0.0006). In seven trials, meditation-based therapies also significantly reduced CLBP bothersomeness compared with nonmeditation therapies (SMD -0.21, 95% CI = -0.34 to -0.08, P = 0.002). In three trials, meditation-based therapies significantly improved patient quality of life compared with nonmeditation therapies (SMD 0.27, 95% CI = 0.17 to 0.37, P < 0.00001). CONCLUSIONS: In conclusion, meditation-based therapies constitute a safe and effective alternative approach to CLBP management.

The prevalence of complementary and alternative medicines (CAM) usage among allergic rhinitis patients in Malaysia.

PURPOSE: We conducted this study to estimate the prevalence of complementary and alternative medicines (CAM) usage among allergic rhinitis (AR) patients in Malaysia and understand the practice of CAM usage among them. We also included a literature review on the commonly used CAM for AR. METHODS: A cross-sectional study which included a questionnaire-based study and information of allergic rhinitis from patient's clinic records. Patients with AR who attended the ORL-HNS department in Hospital Universiti Sains Malaysia and Hospital Sultanah Aminah, Malaysia were enrolled after consented, on a first-come first-serve basis as convenience sampling from July 2020 until February 2021. A pre-tested self-administered, 16-item questionnaire in Malay language was distributed to the participants. The questionnaire consists of a set of 16 questions with subsets to enquire about the sociodemographic data and pattern of usage of CAM and its effectiveness. RESULTS: 372 patients were enrolled in this study consisting of 217 (58.3%) female and 155 (41.7%) male patients. 231 (62.1%) participants had used CAM for AR in the past 10 years. A higher proportion of females (p = 0.015) and those with higher income (p = 0.004) had used CAM. Among the users, 87.9% found CAM to be effective. No differences were found in terms of age (p = 0.888) and education level (p = 0.057) for CAM usage. CONCLUSION: CAM is widely used in Malaysia to alleviate AR symptoms, with a large proportion of users think it is effective. Therefore, more researches should be conducted to provide evidence and guidance to integrate CAM into AR management.

Bacosides from Bacopa monnieri extract: An overview of the effects on neurological disorders.

From ancient history, complementary and alternative medicines have played a significant role as holistic therapeutic treatments of various human diseases including cancer, diabetes, neurological diseases, and skin problems. One Indian medicinal plant (herb), Bacopa monnieri has been used in many parts of the world as such medicine, particularly for the treatment of various neurological disorders. It is well known as a potent "tonic for the human brain," which serves as a memory enhancer. Multiple studies proved that this herb contains a plethora of potential bioactive, phytochemical compounds with synergistic properties. The main purpose of the present review is to shed light on the use of Bacopa monnieri and its active principles (bacosides) in the management of neurological disorders. Furthermore, the signaling pathways modulated by bacosides have been critically discussed in this review. Moreover, we have critically summarized the present knowledge of this perennial creeping herb based upon the literature mining from different scientific engines.

The Impact of an Evidence-Based Education on Complementary and Alternative Medicine Usage in People with Cancer: Pilot Study.

Complementary and alternative medicine (CAM) usage amongst cancer patients is high globally and in Australia. CAM use in cancer care has the ability to increase chemotherapy toxicity or cause sub-therapy due to altered metabolism as well as increase a patient's bleeding risk. Furthering these risks, people with cancer are largely obtaining their CAM use information from non-evidence-based sources. This study aimed to determine whether the implementation of a CAM education influenced decision-making with regard to CAM usage amongst cancer patients. Twenty people with cancer were recruited for participation in this study. The aims of this study were achieved by surveying patients via questionnaire, both prior to and following receiving an evidence-based CAM education, in either or both written or audiovisual format. This exploratory study found, consistent with the literature, that the majority of participants were obtaining their CAM use information from non-evidenced-based sources. Additionally, it found that the participants wanted more CAM use information and that they demonstrated some altered decision-making after receiving evidenced-based information. On the post-educational questionnaire, the number of participants that stated that they would use CAMs decreased by almost 14%, and some participants made CAM use decisions in accordance with the information provided in the resources. Furthermore, a small increase in CAM knowledge was demonstrated, and it was reported that the resource had prompted them to look further into CAM information. Lastly, the participants in this study found the resource to be mostly useful and helpful and preferred the animated video to the written information.

Risk evaluation of the use of complementary and alternative medicines in cancer.

INTRODUCTION: Cancer patients use complementary and alternative medicines (CAM) to improve their well-being. Little is known about real risks. OBJECTIVE: To highlight 3 different types of axes: 1/cancer patients' perceptions concerning CAM; 2/misinformation/miscommunication about CAM; 3/CAM toxicity (direct toxicity, CAM-anticancer drugs, CAM-cancer interactions). METHOD: A questionnaire was proposed to cancer patients for 2 months. The CAM toxicity was analyzed if patients documented their drugs and CAM. RESULTS: Eighty-five patients responded: 72/85 were taking≥1CAM. In total, 95% patients were satisfied. There was an increasing CAM intake after cancer diagnosis. One hundred and seventeen different CAM were identified (63 herbs, 24 essential oils, 28 food supplements, 2 homeopathic specialities). Only 30/85 were aware CAM could interact with anticancer drugs. No other type of risk was perceived. INFORMATION SOURCES: 43/85 Internet, 38/85 general practitioner, 38/85 community pharmacist, 32/85 entourage, 25/85 other patients, 22/85 oncologist. In total, 81.3% questioned healthcare professionals (HCP) about CAM. Twelve patients noticed HCP lacked knowledge regarding CAM. The toxicity analysis was carried out for 24 patients who consumed 1 to 24CAM. In total, 133CAM were reported, including 87 different CAM. For only 43CAM/87, studies were found. All patients presented≥1risk: 14 at risk of CAM-cancer interactions, 15 of CAM-anticancer drug interactions, 21 of CAM direct toxicities. CONCLUSION: Many CAM are used by patients. The diagnosis of cancer favors their use. The risks are manifold: low perception of risk that can be induced by CAM, diverse and insecure sources of information and many potential toxicities that are not scientifically documented.

EFFICACY OF HERBAL AND NATURALLY-DERIVED DIETARY SUPPLEMENTS FOR THE MANAGEMENT OF KNEE OSTEOARTHRITIS: A MINI-REVIEW.

Knee osteoarthritis (OA) accounts for approximately 85% of the burden of OA worldwide. Knee OA is a whole joint disorder involving structural alterations in the hyaline articular cartilage, subchondral bone, ligaments, capsule, synovium, and periarticular muscles. The complex knee OA pathogenesis includes mechanical, inflammatory, and metabolic factors, eventually leading to the synovial joint's structural destruction and failure. This review aims to present an overview of current knowledge on dietary supplements, such as glucosamine, chondroitin, methylsulfonylmethane, diacerein, avocado-soybean unsaponifiables, curcuminoids, as well as boswellic acids. Results originating from several small studies with natural products in managing knee OA are encouraging. However, additional well-designed placebo-controlled clinical trials are required.

The use of CAM products, practices, and practitioners by long-term endometrial cancer survivors in Australia.

BACKGROUND: The use of complementary and alternative medicines (CAM) has been reported to be frequent and increasing in the general population and among cancer survivors. Very few studies have investigated the use of CAM among long-term endometrial cancer survivors. To address this gap in evidence, this qualitative study aimed to understand the use of CAM and factors motivating the use among long-term survivors of endometrial cancer. METHODS: Semi-structured qualitative interviews were conducted with 17 women diagnosed with endometrial cancer 7-10 years previously, to understand their CAM use and its impact on their wellbeing. Thematic analysis was performed by two researchers to extract the most relevant quotes related to CAM products, practices, and practitioners. RESULTS: All 17 women interviewed used some type of CAM practices, practitioners, or products, specifically 94% concentrated on their diet, 88% focused on their exercise, 59% used a CAM product, 53% visited a CAM practitioner, and 18% used a CAM psychological approach. The main motivators for CAM use included to reduce physical and psychological symptoms, and to stop or reduce medications. Women reported a lack of lifestyle advice from their traditional medical healthcare team which they therefore tried to obtain from other sources. CONCLUSIONS: Our findings suggest CAM practices, practitioners, or products form an important part of women's healthcare options and are commonly used by long-term endometrial cancer survivors. Our data can be of importance to health care professionals and hospitals, as it reflects an unfulfilled need among cancer survivors that does not currently appear to be met by their traditional healthcare team.

Health care professionals' personal and professional views of herbal medicines in the United Kingdom.

Health care professionals (HCPs) have a pivotal role in optimizing patient care and should be familiar with complementary and alternative medicines. The aim of the study was to explore UK-based HCP personal and professional opinions and experiences of herbal medicines (HMs). An online questionnaire was distributed via social media to recruit (n = 112) a range of HCPs from across the United Kingdom. HCPs from primary and secondary care, the private sector, and academia took part. A large proportion of participants (62%) said they did not personally use any HMs, and 38% did use HMs. HCPs who had personally used HMs had a positive impression of HMs and were more likely to recommend HMs to patients than those who had not used HMs themselves. Participants were given the opportunity to share their perceptions on the safety and efficacy of HMs and their experiences with patients reporting adverse drug reactions to HMs and herb-drug interactions. HCPs identified their lack of knowledge on HMs and insufficient training, which made them unable to advise patients on the safe use of HMs. More education on HMs would help improve HCP knowledge of HMs and help them make better informed decisions when considering patient pharmaceutical care plans.

The regulation of acupuncture in France and the UK: Shifts and fragmentation in contrasting healthcare systems.

This article explores the regulation of acupuncture in the UK and France. It focuses on the dilemmas such regulation has raised, and the effects of two contrasting approaches to the regulatory organisation of acupuncture within healthcare systems on practices and care. Although the question of how acupuncture, like other complementary, alternative or traditional therapies, should be regulated has often been reduced to a question of scientific knowledge, it is also dependent on the intricacies of national health system governance, state rationales and professional identities. France and the UK provide exemplary instances of contrasting systems, in which each of these factors has come to shape the regulation of the highly heterodox practice that is acupuncture. Overall, exploring the challenges of regulating acupuncture provides useful perspectives on how the make-up of legitimate therapies is constituted in particular healthcare contexts.

Complementary and alternative medicines use among pediatric patients with epilepsy in a multiethnic community.

OBJECTIVE: Prior studies highlighted that patients on chronic medications who used complementary and alternative medicines (CAMs) did not share this information with their healthcare providers. Furthermore, there might be potential adverse interactions between CAMs and antiepileptic drug (AED) therapy. However, there are no studies that investigate the effect of religion or race on CAM use in a multiethnic community. Therefore, we aimed to investigate CAM usage among pediatric patients with epilepsy (PPE) and identify predictors of CAM usage in our multiethnic setting. METHODS: This was a cross-sectional study where caregivers of recruited at an outpatient epilepsy clinic between September 2013 and July 2014 completed a self-administered survey. Those who declined participation, lacked understanding of English or Mandarin, or missed the clinic appointments were excluded. Those caring for more than one patient participated only once. RESULTS: Of the 195 surveys collected, 178 were used for analysis. The PPE used an average of 1.50 AEDs (range: 0-4). Forty-nine (27.5%) caregivers reported giving CAMs to their PPE. Commonly used CAMs were multivitamins (44.4%), traditional herbs (42.2%), and acupuncture (17.4%). Multivitamins were mostly given by Christian/Catholic caregivers while Buddhist caregivers mostly gave traditional herbs or acupuncture. The majority of the CAM users were Chinese. Univariate analysis showed that caregivers with secondary school (high school) education were 3.52 times more likely to use CAMs compared to those with primary school (elementary school) education. CONCLUSIONS: While some caregivers gave CAMs to their PPE, they had various misconceptions and did not discuss the usage with their healthcare providers. We propose that the predictors identified in this study can help to identify potential CAM users. Healthcare providers should routinely probe about the usage of CAMs by PPE, and thereafter, the suitability of CAM use could be evaluated. The caregivers will benefit from open discussion with healthcare professionals on the safe use of AEDs with or without CAMs.

Anti-infective potential of Citrus bergamia Risso et Poiteau (bergamot) derivatives: a systematic review.

Infectious diseases remain among the leading causes of morbidity and mortality worldwide, mainly because of the increase of resistance to chemotherapeutic drugs. Nature is the major source of anti-infective drugs and could represent a font of medicines that may help overcome antibiotic resistance. Recently, the potential antimicrobial effect of certain plant extracts has attracted attention within the scientific community as alternatives to synthetic drugs. Here, we present a systematic review on the anti-infective properties of bergamot derivatives that highlight the activity of bergamot essential oil against bacteria, mycetes and larvae, as well as the anti-Helicobacter pylori effect of bergamot juice and the antimicrobial properties of extracts from bergamot peel. Findings presented herein could be used to develop novel and alternative preventive and therapeutic strategies aimed to overcome antibiotic resistance. Copyright © 2016 John Wiley & Sons, Ltd.

Anti-Inflammatory Activity of Citrus bergamia Derivatives: Where Do We Stand?

Inflammatory diseases affect a large portion of the worldwide population, and chronic inflammation is a major risk factor for several dangerous pathologies. To limit the side effects of both synthetic and biological anti-inflammatory drugs, the use of herbal medicines, nutraceuticals and food supplements has increased tremendously as alternative and/or complementary medicine to treat several pathologies, including inflammation. During the last decades, the biological properties of Citrus bergamia (bergamot) derivatives have obtained important scientific achievements, and it has been suggested their use in a context of a multitarget pharmacological strategy. Here, we present an overview of the anti-inflammatory properties of bergamot extracts that could represent the scientific basis for develop novel and alternative strategies to improve health status and attenuate inflammatory conditions.

The Anticonvulsant Activity of a Flavonoid-Rich Extract from Orange Juice Involves both NMDA and GABA-Benzodiazepine Receptor Complexes.

The usage of dietary supplements and other natural products to treat neurological diseases has been growing over time, and accumulating evidence suggests that flavonoids possess anticonvulsant properties. The aim of this study was to examine the effects of a flavonoid-rich extract from orange juice (OJe) in some rodent models of epilepsy and to explore its possible mechanism of action. The genetically audiogenic seizures (AGS)-susceptible DBA/2 mouse, the pentylenetetrazole (PTZ)-induced seizures in ICR-CD1 mice and the WAG/Rij rat as a genetic model of absence epilepsy with comorbidity of depression were used. Our results demonstrate that OJe was able to exert anticonvulsant effects on AGS-sensible DBA/2 mice and to inhibit PTZ-induced tonic seizures, increasing their latency. Conversely, it did not have anti-absence effects on WAG/Rij rats. Our experimental findings suggest that the anti-convulsant effects of OJe are likely mediated by both an inhibition of NMDA receptors at the glycine-binding site and an agonistic activity on benzodiazepine-binding site at GABAA receptors. This study provides evidences for the antiepileptic activity of OJe, and its results could be used as scientific basis for further researches aimed to develop novel complementary therapy for the treatment of epilepsy in a context of a multitarget pharmacological strategy.

Community pharmacists' knowledge, attitudes, and practices regarding counselling on vitamins and dietary supplements in Malaysia: A study on complementary medicines.

Background: The utilization of vitamins and dietary supplements (DSs) among consumers in Malaysia has seen a notable increase. However, there is limited research available on how pharmacists in Eastern countries manage the provision of these products. Objective: This study aims to assess the knowledge, attitudes, and practices of community pharmacists in Malaysia regarding the provision of counselling services on vitamins and DSs. The findings will inform education strategies in this area. Methods: A cross-sectional quantitative study was conducted from February to April 2022 using a validated online-based questionnaire. The survey was distributed to community pharmacists across Malaysia through social media channels. t-test and ANOVA test were used for data analysis. Results: Among the 260 participants, 73.5% were categorized as having average product knowledge. Key concerns included a lack of knowledge about the indications of new products and when to discontinue their use. Regarding dosing in specific patient groups, 33.5% of pharmacists only occasionally consulted references and primarily relied on product labels. Furthermore, 29% of pharmacists believed it was unnecessary to refer patients to doctors when they experienced ongoing symptoms while taking vitamins or DSs. Interestingly, 44.6% of pharmacists believed there was a correlation between the efficacy of vitamins and their price, often recommending more expensive brands despite similar content. Conclusion: There is an opportunity to enhance the knowledge of pharmacists in Malaysia regarding vitamins and DSs. Education interventions should focus on areas such as dosing for specific patient groups, when to discontinue products, understanding new products, evidence-based efficacy of products for specific conditions, and providing a framework for appropriate referral to support pharmacists in their practice.

Pachydermoperiostosis Presenting With End-Stage Kidney Disease.

Pachydermoperiostosis, also known as Touraine-Solente-Golé syndrome, is an uncommon hereditary condition. This condition includes skin thickening (pachydermia), abnormalities of the bones (periostosis), and digital clubbing (acropachy). We present a case of complete pachydermoperiostosis who presented with end-stage kidney disease. Chronic tubulointerstitial disease secondary to long-term analgesics and complementary and alternative medications was considered the likely etiology for renal dysfunction. The patient underwent serial hemodialysis followed by arteriovenous fistula surgery. In view of significant synovial inflammation, he was also given a selective COX-2 inhibitor. Pachydermoperiostosis is a rare condition, and although there is no therapy for the condition itself, medicinal or surgical interventions can effectively control its secondary effects.

Alternative Treatments to Pharmacological Therapy in Pediatric Populations With Attention-Deficit/Hyperactivity Disorder (ADHD): A Scoping Review.

In recent years, there has been an increase in the prevalence of the diagnosis of attention-deficit/hyperactivity disorder (ADHD), a cognitive and behavioral disorder in which individuals present with inattention and impulsivity, in the pediatric population. With an increase in diagnoses, there is also increasing concern regarding overdiagnosis and overtreatment with medications for ADHD. The objective of this study was to map out and compile the recent literature pertaining to alternative therapies (e.g., physical activity, diet, mindfulness, and computer-based interventions) for children and adolescents diagnosed with ADHD in an attempt to reduce or replace the use of pharmacological therapy. This scoping review searched articles from multiple databases (PubMed, ScienceDirect, Web of Science, Directory of Open Access Journals, Scopus, and CINAHL). Using search terms "children with ADHD," "alternative treatment," and "cognitive behavioral therapy," articles were identified that were specific to the research question. The inclusion criteria were patients under the age of 18 with a previous diagnosis of ADHD, no other comorbid illnesses, alternative treatments, and was limited to studies published between 2012 and 2022. After removing duplicates, screening for eligibility criteria, and conducting a critical appraisal of the articles, 16 articles were retained for the final review. The main alternative therapeutic domains that emerged were (1) physical activity, (2) diet, (3) mindfulness, (4) computer-based interventions, and (5) miscellaneous interventions. Seven articles assessed the effect of physical activity on executive and cognitive function in children and adolescents with ADHD. Most findings showed improvement with increased physical activity. Two articles explored the effect of diet on the improvement of ADHD symptoms and reported a positive impact. The two articles that evaluated the effects of mindfulness on ADHD symptoms reported a reduction in ADHD symptoms. Two studies evaluated the use of computer-based interventions as an adjunct treatment in children and adolescents with ADHD; improvements in symptoms were reported. One study each evaluated interventions based on music and nerve stimulation. These showed an improvement in attention, memory, and executive function. With the increasing prevalence of ADHD diagnosis in children and adolescents, alternative and/or adjunctive treatments may be a viable and valuable alternative to pharmaceutical interventions. The findings from this review suggest that multiple non-pharmacological interventions effectively reduce symptoms of ADHD in children and adolescents, including diet, exercise, mindfulness, computer-based interventions, music, and nerve stimulation. While there are implications for alternatives to be used in the future, more research is warranted using larger samples with controlled trials.

Development and validation of a LC-MS/MS method for the in vitro analysis of 1-hydroxymidazolam in human liver microsomes: application for determining CYP3A4 inhibition in complex matrix mixtures.

Complementary and alternative medicines (CAM) can affect the pharmacokinetics of anticancer drugs by interacting with the metabolizing enzyme cytochrome P450 (CYP) 3A4. To evaluate changes in the activity of CYP3A4 in patients, levels of 1-hydroxymidazolam in plasma are often determined with liquid chromatography-quadrupole mass spectrometry (LC-MS/MS). However, validated LC-MS/MS methods to determine in vitro CYP3A4 inhibition in human liver microsomes are scarce and not optimized for evaluating CYP3A4 inhibition by CAM. The latter is necessary because CAM are often complex mixtures of numerous compounds that can interfere with the selective measurement of 1-hydroxymidazolam. Therefore, the aim was to validate and optimize an LC-MS/MS method for the adequate determination of CYP3A4 inhibition by CAM in human liver microsomes. After incubation of human liver microsomes with midazolam, liquid-liquid extraction with tert-butyl methyl ether was applied and dried samples were reconstituted in 50% methanol. These samples were injected onto a reversed-phase chromatography consisting of a Zorbax Extend-C18 column (2.1 × 150 mm, 5.0 µm particle size), connected to a triple quadrupole mass spectrometer with electrospray ionization. The described LC-MS/MS method was validated over linear range of 1.0-500 nm for 1-hydroxymidazolam. The results revealed good inter-assay accuracy (≥85% and ≤115%) and within-day and between-day precisions (coefficient of variation ≤ 4.43%). Furthermore, the applicability of this assay for the determination of CYP3A4 inhibition in complex matrix mixtures was successfully demonstrated in an in vitro experiment in which CYP3A4 inhibition by known CAM (ß-carotene, green tea, milk thistle and St. John's wort) was determined.