An Attempt to Estimate the Noises in Homeopathic Pathogenetic Trials by Employing the Jaccard Similarity Index and Noise Index.

BACKGROUND: The critical task of researchers conducting double-blinded, randomized, placebo-controlled homeopathic pathogenetic trials is to segregate the signals from the noises. The noises are signs and symptoms due to factors other than the trial drug; signals are signs and symptoms due to the trial drug. Unfortunately, the existing tools (criteria for a causal association of symptoms only with the tested medicine, qualitative pathogenetic index, quantitative pathogenetic index, pathogenic index) have limitations in analyzing the symptoms of the placebo group as a comparator, resulting in inadequate segregation of the noises. Hence, the Jaccard similarity index and the Noise index are proposed for analyzing the symptoms of the placebo group as a comparator. METHODS: The Jaccard similarity index is the ratio of the number of common elements among the placebo and intervention groups to the aggregated number of elements in these groups. The Noise index is the ratio of common elements among the placebo and intervention group to the total elements of the intervention group. Homeopathic pathogenetic trials of Plumbum metallicum, Piper methysticum and Hepatitis C nosode were selected for experimenting with the computation of the Jaccard similarity index and the Noise index. RESULTS: Jaccard similarity index calculations show that 8% of Plumbum metallicum's elements, 10.7% of Piper methysticum's elements, and 19.3% of Hepatitis C nosode's elements were similar to the placebo group when elements of both the groups (intervention and placebo) were aggregated. Noise index calculations show that 10.7% of Plumbum metallicum's elements, 13.9% of Piper methysticum's elements and 25.7% of Hepatitis C nosode's elements were similar to those of the placebo group. CONCLUSION: The Jaccard similarity index and the Noise index might be considered an additional approach for analyzing the symptoms of the placebo group as a comparator, resulting in better noise segregation in homeopathic pathogenetic trials.

Emerging trends from COVID-19 research registered in the Clinical Trials Registry - India.

Since the beginning of the year, the deadly coronavirus pandemic, better known as coronavirus disease 2019 (COVID-19), brought the entire world to an unprecedented halt. In tandem with the global scenario, researchers in India are actively engaged in the conduct of clinical research to counter the pandemic. This review attempts to provide a comprehensive overview of the COVID-19 research in India including design aspects, through the clinical trials registered in the Clinical Trials Registry - India (CTRI) till June 5, 2020. One hundred and twenty two registered trials on COVID-19 were extracted from the CTRI database. These trials were categorized into modern medicine (n=42), traditional medicine (n=67) and miscellaneous (n=13). Of the 42 modern medicine trials, 28 were on repurposed drugs, used singly (n=24) or in combination (n=4). Of these 28 trials, 23 were to evaluate their therapeutic efficacy in different severities of the disease. There were nine registered trials on cell- and plasma-based therapies, two phytopharmaceutical trials and three vaccine trials. The traditional medicine trials category majorly comprised Ayurveda (n=45), followed by homeopathy (n=14) and others (n=8) from Yoga, Siddha and Unani. Among the traditional medicine category, 31 trials were prophylactic and 36 were therapeutic, mostly conducted on asymptomatic or mild-to-moderate COVID-19 patients. This review would showcase the research being conducted on COVID-19 in the country and highlight the research gaps to steer further studies.

CORE-Hom: a powerful and exhaustive database of clinical trials in homeopathy.

The CORE-Hom database was created to answer the need for a reliable and publicly available source of information in the field of clinical research in homeopathy. As of May 2014 it held 1048 entries of clinical trials, observational studies and surveys in the field of homeopathy, including second publications and re-analyses. 352 of the trials referenced in the database were published in peer reviewed journals, 198 of which were randomised controlled trials. The most often used remedies were Arnica montana (n = 103) and Traumeel(®) (n = 40). The most studied medical conditions were respiratory tract infections (n = 126) and traumatic injuries (n = 110). The aim of this article is to introduce the database to the public, describing and explaining the interface, features and content of the CORE-Hom database.

A quantum-like model of homeopathy clinical trials: importance of in situ randomization and unblinding.

BACKGROUND: The randomized controlled trial (RCT) is the 'gold standard' of modern clinical pharmacology. However, for many practitioners of homeopathy, blind RCTs are an inadequate research tool for testing complex therapies such as homeopathy. METHODS: Classical probabilities used in biological sciences and in medicine are only a special case of the generalized theory of probability used in quantum physics. I describe homeopathy trials using a quantum-like statistical model, a model inspired by quantum physics and taking into consideration superposition of states, non-commuting observables, probability interferences, contextuality, etc. RESULTS: The negative effect of blinding on success of homeopathy trials and the 'smearing effect' ('specific' effects of homeopathy medicine occurring in the placebo group) are described by quantum-like probabilities without supplementary ad hoc hypotheses. The difference of positive outcome rates between placebo and homeopathy groups frequently vanish in centralized blind trials. The model proposed here suggests a way to circumvent such problems in masked homeopathy trials by incorporating in situ randomization/unblinding. CONCLUSION: In this quantum-like model of homeopathy clinical trials, success in open-label setting and failure with centralized blind RCTs emerge logically from the formalism. This model suggests that significant differences between placebo and homeopathy in blind RCTs would be found more frequently if in situ randomization/unblinding was used.

Homeopathy for eczema: a systematic review of controlled clinical trials.

BACKGROUND: Homeopathy is often advocated for patients with eczema. OBJECTIVES: This article systematically reviews the evidence from controlled clinical trials of any type of homeopathic treatment for any type of eczema. METHODS: Electronic searches were conducted in Medline, Embase and the Cochrane Library with no restrictions on time or language. In addition, the bibliographies of the retrieved articles and our departmental files were hand searched. All controlled trials of homeopathy in patients with eczema were considered. Their methodological quality was estimated using the Jadad score. RESULTS: One randomized and two nonrandomized clinical trials met the inclusion criteria. All were methodologically weak. None demonstrated the efficacy of homeopathy. CONCLUSIONS: The evidence from controlled clinical trials therefore fails to show that homeopathy is an efficacious treatment for eczema.

Development of botanical principles for clinical use in cancer: where are we lacking?

Development of drugs from plant sources (botanicals) for the treatment of cancer has not been successful in India, despite a plethora of medicinal plants and an equal number of experiments demonstrating anti-cancer activity of plant principles in vitro. There are several pitfalls in our approach to botanical drug development. Foremost is the lack of industry-academia collaborations in this field. Research goals in Indian academic institutions are generally short-term and mostly aimed at fulfilling the minimum requirements of a doctoral/MD or MPharm thesis. Secondly, quality assurance of herbal formulations is difficult to achieve and good manufacturing practices are expensive to implement. This could introduce bias during the biological evaluation of botanicals. A systematic approach covering a wide range of investigations including but not limited to mechanistic studies, potential herb-drug interactions, pharmacokinetics and bioavailability could help in the optimization of herbal formulations in the preclinical stage of development before they can be considered for clinical trials. Government initiatives such as Ayurveda, Unani, Siddha and Homeopathic have encouraged research in these areas, but are insufficient to promote focused and aggressive evaluation of potential herbs. Particular emphasis should be given to clinical pharmacokinetics, drug interactions and clinical trials in specific cancers for the evaluation of dosage, safety, efficacy and concomitant use with chemotherapy. Only such policies can result in meaningful evaluation of botanicals for cancer therapy.

Monitoring improvement in health during homeopathic intervention. Development of an assessment tool based on Hering's Law of Cure: the Hering's Law Assessment Tool (HELAT).

INTRODUCTION: Hering's 'Law of Cure' is considered important in homeopathy and thought to predict a positive outcome to treatment. No formal outcome measures are currently available to monitor response to homeopathic treatment on the basis of these assumptions. We describe a simple assessment tool, the Hering's Law Assessment Tool (HELAT) to identify and differentiate patient responses to homeopathic treatment as corresponding to Hering's Law from other symptomatic responses. We describe the development of the tool and assess its face, content and predictive validity. METHOD: The HELAT was initially developed through literature review, discussion between homeopaths and clinical experience. In phase one, the tool was reviewed by three experienced homeopaths to assess face and content validity. In phase two, we tested its predictive validity by hypothesizing that the HELAT total score may predict changes in a clinical response (using standard validated rheumatological outcome, the American College of Rheumatology (ACR)20%) in 32 patients with rheumatoid arthritis receiving homeopathic intervention over 24 weeks as part of a clinical trial. RESULTS: The HELAT was piloted and changed to improve face and content validity and the final version was then employed for phase two as a predictor of outcome. HELAT total score predicted patient's clinical response (ACR20) [B = 1.142, SE = 0.462, P = 0.013] which was independent of practitioner assessing the patients treatment response [B = 1.04, SE = 1.01, P = 0.302]. CONCLUSION: The initial data suggests that the HELAT may hold promise for a potential clinical and research outcome measure in homeopathy. Further work is now needed to formally assess its reliability and validity for potential use in clinical practice and trials.

[Placebo and the relationship between doctors and patients. Overview]. / Placeboaspekte der Arzt-Patienten-Beziehung. Übersicht.

In medicine, placebos are used both in scientific studies and for practical therapeutic purposes. In evidence-based medicine, the efficacy of treatment may be determined as the difference between the effects of the verum (the active study drug) and the placebo, the latter being a substance lacking specific action on the disease under consideration. However, the improvements in patients' conditions under placebo treatment may be substantial and comparable to those with verum. Genuine placebos predominate in clinical studies, while pseudoplacebos prevail in practical therapy. The term pseudoplacebo can also be applied to many procedures in complementary medicine, including homeopathic medicine (Büchel et al., Placebo in der Medizin, 2011). The comprehensive definition of placebo, as used in a report by the German Medical Association (Büchel et al., Placebo in der Medizin, 2011), states that a placebo effect may occur even when treating with verum. The placebo effect is modulated by the context of the treatment, by the expectations of the patients and the doctors, and by the success of the relationship between doctors and patients. A number of unspecific effects, e.g., spontaneous alleviation, statistical effects, variance with time, methodological errors, in addition to the placebo effect make up the total response that is called"placebo reaction." A complete list of the effectiveness of placebo for all important diseases is still lacking. Further, it is not possible to predict which patients will respond to placebo. Which characteristics of doctors are important (competence, empathy, communicative ability and partnership, trust) in order to achieve a placebo effect, particularly in addition to the verum effect measures of evidence-based medicine? Are there doctors who are better in this than others? Could the nocebo effect weaken the efficacy of treatment in evidence-based medicine? Since a placebo effect may occur in almost any standard therapy, information about placebos should be provided during medical education and continuing medical education (CME). The use of placebo in clinical studies is ethically justified and lawful in consenting patients if there is no other effective treatment available with which the test substance could be compared. For daily practical therapeutic purposes, placebos may be ethically acceptable and lawful if there is no effective therapy available, if the complaints are minor, if the patient expressly wishes treatment, and if there is a reasonable likelihood of success. However, an explanation of the expected benefits and risks must be provided to the patients. At present, there are two explanatory theories for the mechanism of action of placebo, namely, the associative and the mentalistic explanation (Büchel et al., Placebo in der Medizin, 2011). Interestingly, effects of placebo and of verum can be localized in the brain by physiological and anatomical techniques. With many open questions remaining, research on placebo is currently very active. These aspect and neurobiological findings in particular may facilitate for "scientifically" educated doctors to accept that ineffective materials, i.e., placebos, are in fact effective.

A discussion: the future role of homeopathy in the National Health Service (NHS).

Homeopathy has been provided by the National Health Service in the UK for over 60 years, funded largely by taxpayer's money. However, in recent years, its provision has come under much criticism questioning its true value. Taking a neutral stance, arguments both for and against the provision of homeopathy on the NHS is presented. It includes issues such as the evidence and safety profile of homeopathy, but also takes into account costs and benefits of homeopathy in a wider perspective. Overall, the provision of homeopathy is justified as long as there is a need within the population, occupying a complementary role alongside conventional medicine.

Systematic Review on the Use of Homeopathy in Dentistry: Critical Analysis of Clinical Trials.

Objectives: The objective of this research was to systematically map the literature on homeopathy and dentistry studies and to evaluate the effectiveness of using homeopathy in dental practice through the critical analysis of clinical studies. Design: The search for scientific articles in any language, year, and place of publication was made in the databases of Public Medline (PUBMED), Web of Science, Cochrane, and Virtual Health Library; the articles selected were later classified according to the type of study. Gray literature was accessed through Google Scholar. Clinical trials were analyzed for methodological quality. Two previously trained reviewers accomplished the entire process independently. Results: Of the 281 studies retrieved by means of the search, 44 met the eligibility criteria, with prevalence of literature reviews (56.8%), followed by clinical trials (34.1%), cross-sectional studies (6.8%), laboratory research (6.8%), and longitudinal observational studies (4.5%). The clinical trials identified were published from 1965 to 2019, using homeopathy in several dental specialties: in Endodontics, Periodontics, Orofacial Pain, Surgery, Pediatric Dentistry, and Stomatology, as well as in cases of dental anxiety. Qualitative failures, in all criteria investigated, and positive influences of the individual prescriptions on the results of treatments reported were observed. Conclusions: There is still a scarcity of studies about homeopathy and dentistry. The clinical trials selected showed positive effects on oral health; however, when they were critically evaluated, it was possible to recognize qualitative failures, mainly relative to double-blinding. It is necessary to encourage research on the subject, using standardized methodological procedures, to obtain better evaluation of the clinical applicability.

Rational use of Ashwagandha in Ayurveda (Traditional Indian Medicine) for health and healing.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal (Physalis somnifera L.) is a fairly known perennial shrub of Solanaceae family, and is used in Ayurveda- Traditional Indian Medicine (TIM), since ancient times. It is well known as Ashwagandha in Sanskrit language in Ayurvedic classics. Its Mula (root) is recommended for health and healing, and the number of single and compound formulation is prescribed rationally. It is believed that the species name-somnifera is coined based on popular use to "induce sleep" in Ayurveda. AIM OF THE STUDY: The present study was aimed to bring out the experience-based traditional uses of Ashwagandha for health and healing with an emphasis on the pharmacological and biochemical scientific evidences to corroborate them. The scientific evidences have been explored from the national and international publications. MATERIALS AND METHOD: A comprehensive literary search of Ayurvedic classics was carried out systematically regarding Ashwagandha for its rationality behind the traditional uses. To excavate the subject matter, the original Ayurvedic scriptures and several standard Ayurvedic texts of different period was studied insightfully for meaningful contribution. It is to be noted that the primary source of knowledge was considered in writing this manuscript without any biased attitude. The available literature on Ashwagandha was also searched to ascertain the basis of scientific Latin name and correct identity. The Ayurvedic Pharmacopoeia and other relevant scientific works were also taken into consideration to make the subject matter more clearly to the scientific world. For the scientific evidence of the uses, the international and national Journals and other published material were also searched to make it inquisitiveness to the scholars interested in Ayurvedic medicinal plants. RESULTS: The present paper throws ancient luminosity behind the therapeutic uses of one of the promising plant drug i.e., Ashwagandha of ancient India even to the present time. The scientific evidences corroborate the rationality ascribed in available Ayurvedic classics of various period of India has been gained. CONCLUSION: The study explores that the first reference of Ashwagandha with its significant nomenclature, useful part, properties, action, and eloquent uses has its footprint in the original texts of Ayurveda. In later works enhanced knowledge with traditional uses continued even today. Several single and compound formulations have been found to maintain the health and to alleviate the disorders rationally. It is worthy to note here that the scientific evidences corroborate the uses practiced in Ayurveda.

A review of homeopathic research in the treatment of respiratory allergies.

There are conceptual and historical links between homeopathic medicine and modern allergy desensitization treatment. Conventional allergy desensitization and homeopathic treatment both utilize small doses of substances that might cause symptoms in order to prevent or treat a hypersensitive state. Homeopathy has historically been associated with allergy treatment. This article reviews evidence from controlled trials for the use of homeopathy in respiratory allergies. Several clinical trials, many of which were published in "high impact" conventional medical journals, describe significant effects of homeopathic treatment in allergic patients. Most of these clinical studies have been deemed to be high quality trials, according to the three most commonly referenced meta-analyses of homeopathic research. Basic in vitro experimental studies also provide evidence that the effects of homeopathy differ from placebo.

Non-pharmacological approach to migraine prophylaxis: part II.

Acupuncture has been used to both prevent and treat diseases for over 3,000 years. Recently, a Cochrane review on its use in migraine concluded that acupuncture is effective and should be considered as a prophylactic measure for patients with frequent or insufficiently controlled migraine attacks. In contrast, there is no clear evidence to support or refute the use of homeopathy in the management of migraine. Among vitamins and other supplements, riboflavin and coenzyme Q10 significantly decreased the frequency of migraine attacks. Alpha lipoic acid also reduced migraine frequency, albeit not significantly as compared to placebo. The prophylactic efficacy of magnesium, particularly for children and menstrually related migraine, has recently been substantiated. Among the herbal remedies, butterbur significantly decreases attack frequency, whereas the efficacy of feverfew was not confirmed in a Cochrane review, probably because of the 400% variations in the dosage of its active principle. Finally, ginkgolide B has proved significantly effective in controlling migraine with aura and pediatric migraine in uncontrolled studies that need a confirmation.

Repetitions of fundamental research models for homeopathically prepared dilutions beyond 10(-23): a bibliometric study.

INTRODUCTION: Repeatability of experiments is an important criterion of modern research and a major challenge for homeopathic basic research. There is no recent overview about basic research studies in high homeopathic potencies that have been subjected to laboratory-internal, multicenter or independent repetition trials. METHODS: We considered biochemical, immunological, botanical, cell biological and zoological studies on high potencies, i.e. beyond a dilution of 10(-23). Main sources of information were reviews, personal contact with members of the homeopathic basic research community, and the MEDLINE and HOMBREX databases. Studies were extracted from the publications and grouped into models. Studies were further sorted according to repetition type (laboratory-internal, multicenter, or independent) and results achieved. RESULTS: A total of 107 studies were found. Of these, 30 were initial studies. In the attempt to reproduce one of these initial studies, 53 follow-up studies yielded comparable effects (35 laboratory-internal, 8 multicenter, 10 independent repetitions), eight studies showed a consistent, yet different result from the initial study (2 laboratory-internal, 2 multicenter, 4 independent repetitions), and 16 studies yielded no effects (5 laboratory-internal, 2 multicenter, 9 independent repetitions). When all repetitive studies are considered, 69% reported effects comparable to that of the initial study, 10% different effects, and 21% no effects. Independently performed repetition studies reported 44% comparable effects, 17% different effects, and 39% no effects. CONCLUSIONS: We identified 24 experimental models in basic research on high homeopathic potencies, which were repeatedly investigated. 22 models were reproduced with comparable results, 6 models with different results, and repetition showed no results for 15 models. Independent reproductions with either comparable or different results were found for seven models. We encourage further repetition trials of published studies, in order to learn more about the model systems used and in order to test their repeatability.

The placebo effect and homeopathy.

BACKGROUND: Like other forms of medicine, including Complementary and Alternative Medicine (CAM), homeopathy elicits expectations in patients. The physician-patient relationship, personal and comprehensive treatment and lack of adverse effects are elements in creating positive expectations. Other elements may be associated with negative expectations. METHODS: We conducted a systematic literature review on placebo and nocebo effects in acupuncture and homeopathy using Medline. RESULTS: Findings on the psychophysiological and neuromediating mechanisms of the placebo-nocebo phenomenon are reviewed. Studies of these effects reveal how expectations and unconscious conditioning can be measured by imaging and EEG methods. They result in significant, non-specific therapeutic effects, which may confuse the evaluation of the specific therapeutic effects treatment, hampering selection of the simillimum. CONCLUSIONS: Directions for future research on non-specific therapeutic effects of homeopathy to improve clinical practice and clinical research are discussed.

Clinical trials of homeopathy in urological disorders: a systematic review.

OBJECTIVES: Homeopathy remains one of the most sought after therapies for urological disorders. The aim of this paper was to systematically review the available clinical researches of homeopathy in the said conditions. CONTENT: Relevant trials published between Jan 1, 1981 and Dec 31, 2016 (with further extension up to Dec 31, 2017) was identified through a comprehensive search. Internal validity of the randomized trials and observational studies was assessed by The Cochrane Collaboration's tool and methodological index for non-randomized studies (MINORS) criteria respectively, homeopathic model validity by Mathie's six judgmental domains, and quality of homeopathic individualization by Saha's criteria. SUMMARY: Four controlled (three randomized and one sequentially allocated controlled trial) trials were reviewed and 14 observational studies alongside - all demonstrated positive effect of homeopathy. Major focus areas were benign prostatic hypertrophy and renal stones. One of the four controlled trials had 'adequate' model validity, but suffered from 'high' risk of bias. None of the non-randomized studies was tagged as 'ideal' as all of those underperformed in the MINORS rating. Nine observational studies had 'adequate' model validity and quality criteria of individualization. Proof supporting individualized homeopathy from the controlled trials remained promising, still inconclusive. OUTLOOK: Although observational studies appeared to produce encouraging effects, lack of adequate quality data from randomized trials hindered to arrive at any conclusion regarding the efficacy or effectiveness of homeopathy in urological disorders. The findings from the RCTs remained scarce, underpowered and heterogeneous, had low reliability overall due to high or uncertain risk of bias and sub-standard model validity. Well-designed trials are warranted with improved methodological robustness. FUNDING: None; Registration web-link: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018081624&ID=CRD42018081624.

[Alternative agents used in ADHD]. / Substanzgebundene Alternativen in der Therapie von ADHS.

Attention-deficit/hyperactivity disorder (ADHD) is, with a prevalence of 2% to 6%, one of the most common neurobehavioral disorder affecting children and adolescents, persisting into adulthood. Comorbidity and psychosocial circumstances enter into the choice of intervention strategies. Several agents have been demonstrated effective in treating individuals with ADHD. Direct or indirect attenuation of dopamine and norepinephrine neurotransmission appears closely related to both the stimulant and nonstimulant medications efficacious in ADHD. However, important differences concerning efficacy and side effects exist both between and with the specific classes of agents like neuroleptics, antidepressants, antiepileptics, alpha-agonists, beta-blockers, buspiron, l-dopa, melatonin, pycnogenol, zinc, magnesium, polyunsaturated fatty acids, and homeopathy. Elucidating the various mechanisms of action of ADHD medications may lead to better choices in matching potential responses to the characteristics of individuals. We review the purported mechanism of action and available evidence for selected complementary and alternative medicine therapies for ADHD in childhood and adolescence.

Effectiveness of a homeopathic complex medicine in infantile colic: A randomized multicenter study.

OBJECTIVES: Infantile colic is a common benign disease occurring in early infancy that may have a great impact on family life. In the present study, the effectiveness and safety of the complex homeopathic medicine Enterokind was compared with Simethicone for treating infantile colic. DESIGN AND SETTING: Current data were drawn from a prospective, multicenter, randomized, open-label, controlled clinical trial that was conducted in 2009 in 3 Russian outpatient clinics. Children received either Enterokind (Chamomilla D6, Cina D6, Colocynthis D6, Lac defloratum D6 and Magnesium chloratum D6) or Simethicone. Data from infants ≤ 6 months with infantile colic are presented here. MAIN OUTCOME MEASURES: The main outcomes assessments were the change of total complaints score (maximum 17 points) and total objective symptoms score (maximum 22 points) after 10 days of treatment. RESULTS: Data from 125 infants ≤ 6 months with infantile colic were analyzed. The differences in total complaints and objective symptoms scores between baseline and day 10, estimated from the ANCOVA model, were found to be highly significant (p < 0.0001; ITT) in favor of Enterokind, both for complaints (Δ=-2.38; 95% confidence interval (CI): [-2.87; -1.89]) and for objective symptoms (Δ=-2.07; 95% CI: [-2.65; -1.49]). 1 adverse event (AE), vomiting, occurred under Enterokind and was rated to be unlikely related to it; 4 AEs occurred under Simethicone. All AEs were non-serious. CONCLUSIONS: The current study indicates that Enterokind is an effective and safe homeopathic treatment for functional intestinal colic in infants ≤ 6 months.

Traditional, complementary and alternative medicine in children constipation: a systematic review.

OBJECTIVES: This review aims to evaluate the efficacy and safety of complementary and alternative medicine methods for constipation in the pediatric population. EVIDENCE ACQUISITION: Medical literature search was performed in several databases for a variety of Traditional, Complementary and Alternative Medicine in childhood constipation. Databases included Web of Science, Scopus, Embase, Cochrane Library, PubMed, ScienceDirect, Google scholar and a number of Persian databases including IranDoc, Magiran and SID. No time limitation was determined. Clinical trials or case series that had evaluated the effectiveness of CAM therapies in functional constipation of 1-18 year old children were included. Papers not in English or Persian language were excluded. Related articles were screened independently by two reviewers according to their titles and abstracts. A data extraction form was filled in for each eligible paper. Quality assessment of eligible documents was also performed. RESULTS: 30 studies were included, comprising 27 clinical trials and 3 case series. Ten documents were on herbal medicine, nine on traditional medicine, ten on manual therapies and one on homeopathy. Except for two herbal and one reflexology interventions, all studies reported positive effects on childhood constipation, with the majority being statistically significant. As the number of studies in each method was limited, we could not perform a meta-analysis. CONCLUSION: The scarcity of research on the efficacy and safety of different types of complementary and alternative medicine methods in children with constipation necessitates conducting more studies in each field. Graphical abstract.