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Few studies have evaluated the efficacy of ketamine-assisted psychotherapy (KAP) in the treatment of treatment-resistant depression (TRD) and substance use disorders (SUD).A systematic review of clinical trials reporting on the efficacy of KAP and discussing mechanisms of action, identified on PubMed and PsycInfo.Five randomized-controlled trials reported on the efficacy of KAP treatment and discussed active mechanisms. Four of the studies treated adults with SUD and a single study treated adults with TRD. Overall, KAP had a significant positive effect on primary outcome measures compared to controls, however, the data is mixed. The study examining KAP for TRD found no benefit.Lack of large, replicated clinical trials. No studies actively examining mechanisms of action.Evidence suggests that temporary neural changes caused by ketamine such as n-methyl-d-aspartate receptor (NMDAR) inhibition and increase of synaptic neuroplasticity affect treatment outcomes of KAP. Based on reports of preliminary findings, we speculate that adjunct psychotherapy, changes in perspective, and spirituality may also play a role.

Hallucinogen persisting perception disorder (HPPD) affects a subset of persons who use hallucinogens and is defined as the repeated experience of hallucinations and other perceptual disturbances as a result of prior intoxications. As select hallucinogens are under development for the treatment of selectmental disorders, there is a need to better characterize this disorder.A scoping review of the literature on HPPD was completed from inception to July 2021. Topics covered in the review herein include treatments for HPPD, prevalence or incidence data on HPPD among different classes of hallucinogens, risk factors for HPPD, and data pertaining to the pathophysiology of HPPD.Hallucinogen persisting perception disorder appears to be an uncommon yet serious event associated with prior hallucinogen exposure. The renewed interest in psychedelics as potential treatment options for select mental disorders, especially agents with hallucinogenic potential, provides the impetus to characterize HPPD in its frequency, risk and protective factors, key characteristics, as well as other clinical and treatment-related factors.

Anhedonia is a common, persistent, and disabling condition. However, available therapeutics primarily focus on the reduction of depressive and negative symptoms rather than amelioration of deficits in positive affect. As such, extant drug treatments remain largely ineffective in treating symptoms of anhedonia. Ketamine is a rapid-acting and novel therapeutic treatment for treatment-resistant depression, which has also been demonstrated to attenuate symptoms of anhedonia. However, the literature on the anti-anhedonic effects of ketamine is limited-especially within independent dimensions of this symptom domain. Herein, this review examined the impact of ketamine treatment on anhedonia and its dimensions on anticipatory, consummatory, and motivation-related reward deficits. Overall, the findings have shown a trend towards symptom reduction and/or improvements in anhedonia and their respective subdomains, in both human and preclinical studies, as well as its potential to provide additional benefit in reducing suicidality and improving quality-of-life. Although further research is required in understanding the long-term efficacy and mechanism, ketamine may provide an effective and rapid-acting therapeutic in an otherwise unmet domain.

The Coronavirus Disease 2019 (COVID-19) pandemic is a syndemic of viral infection and mental health adversity. The pandemic has exacerbated inequalities of access to care in vulnerable populations within the Canadian mental healthcare system. Primary care services are first-line health services in Canada, and are necessary to access specialized services. However, as a result of the limited availability of primary health services, and subsequently, specialized providers (eg, psychiatrists), the demand for these services outweigh the supply. Hitherto, timely access to appropriate services has been cited as a common challenge in Canada as a result of limitations as it relates to resources and in-person activities and support services. While there has been an increase in virtual care opportunities, concerns have been raised with respect to the digital divide. Moreover, while individuals with serious mental illness (SMI) and psychosis are at an increased risk for hospitalization and death from COVID-19, testing and vaccination services have not been prioritized for this population. Taken together, increased funding for mental health service delivery should be emphasized especially for individuals with SMI. There should also be a focus on increased collaboration among individuals with lived experience and health care providers to ensure future policies are developed specifically for this population. Addressing the social determinants of health and prioritizing a continuum of care across various stakeholders may lead to strong integration of care both during and after the pandemic.

Postpartum depression (PPD) is a severe, debilitating mood disorder with consequences for both mothers and children, highlighting the need for rapid-acting and effective treatments for PPD. The aim of this narrative review is to synthesize the available literature on the administration of ketamine for PPD and propose ketamine as a viable and advantageous treatment.A search was conducted on MEDLINE/PubMed, PsycInfo, and Embase databases from inception to October 10, 2021 for preclinical studies, interventional studies (ie, open-label and randomized controlled trials), as well as systematic reviews and meta-analyses evaluating the use of ketamine in postpartum populations. Completed and ongoing clinical trials were identified on ClinicalTrials.gov.Four clinical trials were identified. Results from this review support additional investigation into ketamine as a potential treatment for PPD.Ketamine may be a favorable option for treating PPD due to its antidepressive and analgesic effects, short infusion time, and rapid clearance from the maternal bloodstream. However, there is insufficient evidence to support its use in this population, underscoring the importance of additional clinical research investigating ketamine for PPD.

A considerable proportion of individuals report persistent, debilitating and disparate symptoms despite resolution of acute COVID-19 infection (i.e. long COVID). Numerous registered clinical trials investigating treatment of long COVID are expected to be completed in 2021-2022. The aim of this review is to provide a scope of the candidate treatments for long COVID. A synthesis of ongoing long COVID clinical trials can inform methodologic approaches for future studies and identify key research vistas.Scoping searches were conducted on multiple national and international clinical trial registries. Interventional trials testing treatments for long COVID were selected. The search timeline was from database inception to 28 July 2021.This scoping review included 59 clinical trial registration records from 22 countries with a total projected enrolment of 6718. Considerable heterogeneity was exhibited amongst component records with respect to the characterization of long COVID (i.e. name, symptoms- including frequency, intensity, trajectory and duration- mode of ascertainment, and definition of acute phase). In addition, the majority of proposed interventions were non-pharmacological and either targeted multiple long COVID symptoms simultaneously, or focussed on treatment of respiratory/pulmonary sequelae. Multiple interventions targeted inflammation, as well as tissue oxygenation and cellular recovery, and several interventions were repurposed from analogous conditions.The results of this scoping review investigating ongoing clinical trials testing candidate treatments for long COVID suggest that a greater degree of definitional stringency and homogeneity is needed insofar as the characterization of long COVID and inclusion/exclusion criteria.

Objectives: The association between chronic diseases and depression has received increasing attention, and are both considered to increase the risk of functional impairment. However, previous research evidence is controversial. Our study aimed to investigate the association between depression, three types of vascular disease (i.e., hypertension, myocardial infarction, stroke), diabetes mellitus, and functional impairment in middle-aged and elderly Chinese people. Methods: We designed a cross sectional study. Data were collected from the China Health and Retirement Longitudinal Study (CHARLS) in 2018. Logistic regression models were used to explore the association between independent variables and functional status. Results: Lower functional status was significantly associated with comorbid depression and vascular disease/diabetes mellitus (Activity of Daily Living/Instrumental Activity of Daily Living: Adjusted OR of Hypertension, Diabetes mellitus, Myocardial infarction, Stroke is 3.86/4.30, 3.80/4.38, 3.60/4.14, 6.62/7.72, respectively; all p < 0.001). Conclusions: Depression is associated with functional decline in middle-aged and elderly Chinese individuals with vascular disease/diabetes mellitus. Identifying mediational factors and preventative strategies to reduce concurrent depression in persons with vascular diseases should be a priority therapeutic vista.

The emerging roles of ketamine and esketamine as effective rapid-acting antidepressants hold promise for patients suffering from treatment-resistant depression and/or major depressive disorder with suicidality. Practitioner familiarity with common tolerability/safety concerns along with pragmatic prevention and management strategies are needed to reduce patient burden and improve the acceptability and accessibility of these treatments. The most common treatment-emergent adverse events associated with ketamine/esketamine are dissociation, anxiety, nausea, increased blood pressure, and headache. The majority of side effects are mild, transient, dose dependent, and attenuate with subsequent treatments. Patient selection, baseline physical and psychiatric assessments, and an appropriate setting are critical first steps in the prevention and mitigation of adverse events. Patient education and supportive interventions play central roles in the prevention and management of select adverse events. Severe and/or clinically significant adverse effects may necessitate the judicious use of adjunctive medications. Moreover, practitioners must remain vigilant to the potential for abuse liability and long-term adverse events, for which there are insufficient data. This article succinctly reviews common treatment-emergent adverse events of ketamine and esketamine within the context of mood disorders, and provides practical suggestions for prevention and management at point-of-care.

BACKGROUND Depression is associated with significant morbidity and human capital costs globally. Early screening for depressive symptoms and timely depressive disorder case identification and intervention may improve health outcomes and cost-effectiveness among affected individuals. China’s public and academic communities have reached a consensus on the need to improve access to early screening, diagnosis, and treatment of depression. OBJECTIVE This study aims to estimate the screening prevalence and associated factors of subthreshold depressive symptoms among Chinese residents enrolled in the cohort study using a mobile app–based integrated mental health care model and investigate the 12-month incidence rate and related factors of major depressive disorder (MDD) among those with subthreshold depressive symptoms. METHODS Data were drawn from the Depression Cohort in China (DCC) study. A total of 4243 community residents aged 18 to 64 years living in Nanshan district, Shenzhen city, in Guangdong province, China, were encouraged to participate in the DCC study when visiting the participating primary health care centers, and 4066 (95.83%) residents who met the DCC study criteria were screened for subthreshold depressive symptoms using the Patient Health Questionnaire-9 at baseline. Of the 4066 screened residents, 3168 (77.91%) with subthreshold depressive symptoms were referred to hospitals to receive a psychiatric diagnosis of MDD within 12 months. Sleep duration, anxiety symptoms, well-being, insomnia symptoms, and resilience were also investigated. The diagnosis of MDD was provided by trained psychiatrists using the Mini-International Neuropsychiatric Interview. Univariate and multivariate logistic regression models were performed to explore the potential factors related to subthreshold depressive symptoms at baseline, and Cox proportional hazards models were performed to explore the potential factors related to incident MDD. RESULTS Anxiety symptoms (adjusted odds ratio [AOR] 1.63, 95% CI 1.42-1.87) and insomnia symptoms (AOR 1.13, 95% CI 1.05-1.22) were associated with an increased risk of subthreshold depressive symptoms, whereas well-being (AOR 0.93, 95% CI 0.87-0.99) was negatively associated with depressive symptoms. During the follow-up period, the 12-month incidence rate of MDD among participants with subthreshold depressive symptoms was 5.97% (189/3168). After incorporating all significant variables from the univariate analyses, the multivariate Cox proportional hazards model reported that a history of comorbidities (adjusted hazard ratio [AHR] 1.49, 95% CI 1.04-2.14) and anxiety symptoms (AHR 1.13, 95% CI 1.09-1.17) were independently associated with an increased risk of incident MDD. The 5-item World Health Organization Well-Being Index was associated with a decreased risk of incident MDD (AHR 0.90, 95% CI 0.86-0.94). CONCLUSIONS Elevated anxiety symptoms and unfavorable general well-being were significantly associated with subthreshold depressive symptoms and incident MDD among Chinese residents in Shenzhen. Early screening for subthreshold depressive symptoms and related factors may be helpful for identifying populations at high risk of incident MDD.

Replicated clinical trials have demonstrated rapid and robust antidepressant effects with ketamine in treatment resistant mood disorders. Sex (biological) and gender differences in therapeutic effects for any new intervention is an important consideration, however, the differential efficacy, safety and tolerability of ketamine in males versus females remains underexplored. The objective of the present systematic review is to identify and qualitatively synthesize all published clinical studies relevant to the sex differential effects of ketamine for mood disorders. A systematic search of PubMed, Medline, and PsycInfo from inception until January 20, 2021, yielded 27 reports including 1715 patients (742 males and 973 females) that met inclusion criteria. Results from the vast majority of studies (88.8%) do not support significant sex differences in antidepressant response, tolerability or safety of ketamine. Nine (33.3%) of the reports included a bioanalytical component in the analysis and only one reported on sex differences. Evidence from the present review does not support clinically or statistically significant sex differences in therapeutic effects with ketamine. Nevertheless, future studies should continue to consider sex and biological sex differences in study design and data analytic plans.

Intravenous (IV) ketamine has been shown to have rapid and robust antidepressant effects in adults with treatment-resistant depression (TRD). Urological toxicity has been observed in chronic ketamine abusers as evidenced by dysuria, urgency, and hematuria. The foregoing observation provides the basis for evaluating whether ketamine-induced urological toxicity (KIUT) is associated with sub-anesthetic doses of ketamine (0.5-1.0 mg/kg) in adults with mood disorders. The overarching objective of this article is to identify potential mechanisms of KIUT which appears to be dose and frequency dependent. Available research indicates that high-frequency ketamine is associated with disruption of the urothelial barrier as well as direct ketamine toxicity (i.e., decreased expression of junction proteins) in KIUT of the bladder. Chronic and high-frequency ketamine use is also associated with bladder inflammation mediated via neurogenic and IgE inflammation. Other non-mutually exclusive causes are nerve hyperplasia, hypersensitivity, cell apoptosis, microvascular damage, and overexpression of carcinogenic genes. Notwithstanding the evidence of KIUT in ketamine abusers, there is no evidence that ketamine and/or esketamine treatment in adults with mood disorders is associated with KIUT. However, all patients receiving ketamine/esketamine for mood disorder treatment should be queried about genitourinary symptoms during acute and, where applicable, maintenance dosing.

Antidepressants are associated with symptomatic worsening in a subgroup of patients. Replicated evidence has demonstrated rapid and robust antidepressant effects with intravenous (IV) ketamine in treatment resistant depression (TRD); however, the risk of ketamine worsening depressive symptoms in a subgroup of patients remains unknown. Herein we report a retrospective analysis on the rates of symptomatic worsening during an acute course of IV ketamine in individuals with unipolar (n = 142) and bipolar (n = 22) TRD. Adults (N = 164; mean age = 45.97) with TRD underwent four sub-anesthetic infusions (0.5-0.75 mg/kg over 40 min) of IV ketamine over two weeks, and were assessed with the Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SR

To evaluate the development and implementation of clinical practice guidelines for the management of depression globally.We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries.We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence.Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes.Évaluer le développement et la mise en œuvre des directives de pratique clinique pour la gestion de la dépression dans le monde.Nous avons effectué une revue systématique des directives existantes en matière de gestion de la dépression chez les adultes souffrant de troubles dépressifs majeurs ou de troubles bipolaires. Pour chaque directive identifiée, nous avons vérifié le degré de conformité vis-à-vis des mesures de qualité du développement des directives (transparence des processus d'élaboration des directives et de leur financement, composition multidisciplinaire du groupe d'auteurs, revue systématique des études d'efficacité comparative) ainsi que de la mise en œuvre (indicateurs de qualité). Nous avons confronté les directives des pays à faible et moyen revenu avec celles des pays à haut revenu.Nous avons identifié 82 directives de pratique clinique nationales et 13 directives de pratique clinique internationales dans 83 pays et en 27 langues. Les processus d'élaboration des directives et les sources de financement étaient explicitement indiquées dans une moindre proportion chez les pays à faible et moyen revenu (8/29; 28%) par rapport aux pays à haut revenu (35/58; 60%). Le nombre de directives rédigées par un groupe d'auteurs multidisciplinaire était moins élevé dans les pays à faible et moyen revenu (2/29; 7%) que dans les pays à haut revenu (22/58; 38%). Une revue systématique de l'efficacité comparative a été menée pour 31% (9/29) des directives dans les pays à faible et moyen revenu, contre 71% (41/58) des directives dans les pays à haut revenu. Seulement 10% (3/29) des directives émises par les pays à faible et moyen revenu et 19% (11/58) de celles émises par les pays à haut revenu comprenaient un programme d'évaluation des indicateurs de qualité ou de l'adhérence aux recommandations.La mise en œuvre des directives est mal planifiée, mal analysée et mal mesurée. Réduire les disparités de développement et de mise en œuvre des directives dans les pays à faible et moyen revenu est une priorité. À l'avenir, ces directives devraient prévoir des stratégies d'exécution des recommandations, mais aussi d'évaluation de la faisabilité, de la rentabilité et de l'impact sur l'état de santé.Evaluar la elaboración e implementación de las directrices de práctica clínica para el tratamiento de la depresión a nivel mundial.Se realizó una revisión sistemática de las directrices existentes para el tratamiento de la depresión en adultos con trastorno depresivo mayor o bipolar. Por cada directriz identificada, se evaluó el cumplimiento de las medidas de calidad de elaboración de directrices (como la transparencia en los procesos de elaboración de directrices y su financiamiento, la composición del grupo multidisciplinario de autores, la revisión sistemática del estudio de eficacia comparativo) y la implementación (como los indicadores de calidad). En este contexto, se compararon las directrices de los países de ingresos bajos y medios con las de los países de ingresos altos.Se identificaron las directrices de práctica clínica a nivel nacional (82) y a nivel internacional (13) de 83 países en 27 idiomas. Los procesos de elaboración de directrices y las fuentes de financiamiento se especificaron de manera explícita en un porcentaje menor de directrices de los países de ingresos bajos y medios (8/29; 28 %) en relación con las de los países de ingresos altos (35/58; 60 %). Un grupo de desarrollo multidisciplinario elaboró menos directrices (2/29; 7 %) para los países de ingresos bajos y medios, en relación con las de los países de ingresos altos (22/58; 38 %). Además, se realizó una revisión sistemática sobre la efectividad comparativa en el 31 % (9/29) de las directrices de los países de ingresos bajos y medios, frente al 71 % (41/58) de las directrices de los países de ingresos altos. Solo el 10 % (3/29) de las directrices de los países de ingresos bajos y medios y el 19 % (11/58) de las directrices de los países de ingresos altos describieron planes para evaluar los indicadores de calidad o el cumplimiento de las recomendaciones.La implementación de las directrices no se planifica, notifica ni evalúa de manera adecuada a nivel mundial. Es prioritario reducir las desigualdades en la elaboración y la implementación de las directrices en los países de ingresos bajos y medios. Las directrices que se elaboren en el futuro deberán presentar estrategias para implementar las recomendaciones y evaluar la viabilidad, la rentabilidad y el impacto en los resultados sanitarios.تقييم عملية وضع المبادئ التوجيهية للممارسة السريرية للتعامل مع الاكتئاب وتنفيذها على مستوى العالم.لقد أجرينا مراجعة منهجية للمبادئ التوجيهية الحالية الخاصة بالتعامل مع الاكتئاب لدى البالغين المصابين بحالات الاضطراب الاكتئابي أو الاضطراب ثنائي القطب. وفيما يتعلق بكل مبدأ توجيهي محدد، قمنا بتقييم الامتثال لمقاييس جودة وضع المبدأ التوجيهي (كالشفافية في عمليات وضع المبدأ التوجيهي والتمويل، وتكوين مجموعة من المؤلفين متعددي التخصصات، وكذلك المراجعة المنهجية لأبحاث الفعالية النسبية)، وتنفيذها (مثل مؤشرات الجودة). كما قمنا بمقارنة المبادئ التوجيهية الموجودة في البلدان منخفضة الدخل ومتوسطة الدخل، مع مثيلاتها الموجودة في البلدان مرتفعة الدخل.لقد حددنا 82 مبدأً توجيهيًا وطنيًا، و13 مبدأً توجيهيًا دوليًا من المبادئ التوجيهية الخاصة بالممارسات السريرية، من 83 بلدًا بـ 27 لغة. ولقد تم تحديد عمليات وضع المبدأ التوجيهي، ومصادر التمويل بشكل واضح في نسبة أصغر من المبادئ التوجيهية، الواردة من البلدان منخفضة الدخل ومتوسطة الدخل (8/29؛ 28%)، مقارنة بالبلدان مرتفعة الدخل (35/58؛ 60%). وتم وضع عدد أقل من المبادئ التوجيهية (2/29؛ 7%) الواردة من البلدان منخفضة الدخل ومتوسطة الدخل، بواسطة إحدى مجموعات التطوير متعددة التخصصات، مقارنة بالبلدان مرتفعة الدخل (22/58؛ 38%). وقد تم إجراء مراجعة منهجية للفعالية النسبية في 31% (9/29) من المبادئ التوجيهية للبلدان منخفضة الدخل ومتوسطة الدخل، مقابل 71% (41/58) من المبادئ التوجيهية للبلدان ذات الدخل المرتفع. ولم يتم وصف خطط لتقييم مؤشرات الجودة أو الالتزام بالتوصيات إلا في 10% من المبادئ التوجيهية فقط (3/29) الواردة من البلدان منخفضة الدخل ومتوسطة الدخل، و19% فقط (11/58) من المبادئ التوجيهية للبلدان عالية الدخل.لم يتم التخطيط لعملية تنفيذ المبدأ التوجيهي، والإبلاغ عنها وتقييمها، بشكل مناسب على الصعيد العالمي. إذ يعد تضييق الفوارق في عملية وضع المبادئ التوجيهية وتنفيذها في البلدان منخفضة الدخل ومتوسطة الدخل، إحدى الأولويات. ويجب أن تقدم المبادئ التوجيهية المستقبلية إستراتيجيات لتنفيذ التوصيات، وقياس الجدوى، وفعالية التكلفة، والتأثير على النتائج الصحية.评估全球抑郁症治疗临床实践指南的制定和实施情况。.我们系统评价了现有的成人重度抑郁或双相情感障碍的抑郁治疗指南。针对每份符合纳入标准的指南，我们评估其是否达到指南制定的质量标准（如制定过程和资金的透明度、多学科编著成员、比较疗效研究的系统评价），实施（如质量指标）是否合规。我们对比了中低收入国家和高收入国家的治疗指南。.我们最终确定了 82 份国家级和 13 份国际级的临床实践指南，涉及 83 个国家 27 种语言。与高收入国家相比，中低收入国家指南中明确说明其制定过程和资金来源的比例略低，29 份中仅 8 份给予明确说明，占比 28%，而高收入国家则达 60%，58 份中有 35 份。中低收入国家由多学科编撰成员编著的指南（29 份中仅有 2 份，占比 7%）相较于高收入国家也较少（58 份中有 22 份，占比 38%）。中低收入国家的指南中，有 31% (9/29) 对比较疗效展开系统审查，而高收入国家则达 71% (41/58)。中低收入国家仅有 10% (3/29) 的指南论述了评估质量指标的计划或随附了相关建议，而高收入国家则达 19% (11/58)。.全球范围内，指南的实施均缺乏充分的计划、报道和衡量。缩小中低收入国家在指南制定和实施方面的差距是当务之急。未来制定指南时，应提出实施策略建议，并衡量其可行性、成本效益及对健康结果的影响。.Оценить разработку и внедрениепрактических клинических рекомендаций по лечению депрессии во всем мире.Авторы выполнили систематический обзор существующих клинических рекомендаций по лечению депрессии у взрослых с клинической депрессией или биполярным расстройством. Всем идентифицированным клиническим рекомендациям была дана оценка по соответствию критериям качества разработки клинических рекомендаций (таким как прозрачность процессов разработки клинических рекомендаций и финансирования, мультидисциплинарный состав группы авторов, систематический обзор сравнительных исследований эффективности) и реализации (например, показатели качества). Авторы сравнили клинические рекомендации из стран с низким и средним уровнем доходов и из стран с высоким уровнем доходов.Было выявлено 82 национальных и 13 международных клинических рекомендации из 83 стран на 27 языках. Процессы разработки клинических рекомендаций и источники финансирования были четко указаны в меньшем количестве клинических рекомендаций из стран с низким и средним уровнем доходов (8/29; 28%) по сравнению со странами с высоким уровнем доходов (35/58; 60%). Меньшее количество клинических рекомендаций (2/29; 7%) из стран с низким и средним уровнем доходов по сравнению со странами с высоким уровнем доходов (22/58; 38%) было разработано мультидисциплинарной группой авторов. Систематический обзор сравнительной эффективности был выполнен в 31% (9/29) клинических рекомендаций из стран с низким и средним уровнем доходов по сравнению с 71% (41/58) клинических рекомендаций из стран с высоким уровнем доходов. Только в 10% (3/29) клинических рекомендаций из стран с низким и средним уровнем доходов и в 19% (11/58) клинических рекомендаций из стран с высоким уровнем доходов описаны планы по оценке показателей качества или приверженности соблюдению рекомендаций.В глобальном масштабе при внедрении клинических рекомендаций вопросы планирования, отчетности и измерения показателей внедрения решаются неадекватно. Приоритетной задачей является приближение стандартов разработки и внедрения клинических рекомендаций в странах с низким и средним уровнем доходов к таковым в странах с высоким уровнем доходов. В будущих клинических рекомендациях должны быть представлены стратегии по внедрению рекомендаций и оценке их осуществимости, экономической эффективности и воздействию на результаты в отношении здоровья.