Effectiveness of Xiaoyao capsule on sleep disorders and mood disturbance in patients in recovery from coronavirus disease 2019: a randomized controlled trial.

OBJECTIVE: To study the efficacy of Xiaoyao capsule in improving the clinical symptoms of sleep and mood disorders during recovery from coronavirus disease 2019 (COVID-19). METHODS: The study cohort comprised 200 patients with sleep and mood disorders during recovery from COVID-19. Patients were randomized into the control group and the experimental group in a 1:1 ratio by blocked randomization. The patients received either Xiaoyao capsule (experimental group) or a placebo Xiaoyao capsule (control group) for 2 weeks. The improvements in the Traditional Chinese Medicine (TCM) syndrome scales, total effective rates, and disappearance rates of irritability, anxiety, and poor sleep were compared between the two groups. RESULTS: The TCM syndrome pattern scales, total effective rates, and disappearance rates of irritability, anxiety, and poor sleep did not significantly differ between the experimental group versus the control group in the full analysis set and the per protocol set after 1 and 2 weeks of treatment ( > 0.05). CONCLUSIONS: Xiaoyao capsule do not significantly improve the clinical symptoms of sleep and mood disorders in patients in recovery from COVID-19.

Nutraceuticals in mood disorders: current knowledge and future directions.

PURPOSE OF REVIEW: There is a large evidence base of clinical trials that have investigated the efficacy of a range of nutraceuticals on mood disorders. The aim of the current review is to provide an update regarding the efficacy and safety of nutraceutical agents in mood disorders and to highlight considerations for future research. RECENT FINDINGS: Nutraceuticals such as omega-3, probiotics, zinc, saffron and curcumin have been recommended as adjunctive interventions to standard treatments for people with depression, while St John's wort has been recommended as a monotherapy. In contrast, less research has been devoted to investigating the effect of nutraceuticals in bipolar disorder, with omega-3 being weakly recommended as an adjunctive to standard treatments. Although the safety profile of most nutraceuticals appears acceptable, more insight into the long-term effects within a range of cohorts is recommended. SUMMARY: There are a number of nutraceuticals that have clinical trial support for their use as either adjunctive interventions for depression; however, there is mostly limited support for their use in bipolar disorder. Further randomized controlled trials that take into consideration a number of emerging mechanisms, potential nutraceutical combinations and factors that may predict treatment response are required to inform clinical use.

Combined action of SAMe, Folate, and Vitamin B12 in the treatment of mood disorders: a review.

Mood disorders affect more than 500 million people around the world. In the last decade, their prevalence has increased, and many people suffer from nervousness, anxiety, and stress at least once in their lives. The incidence of mood disorders and anxiety increases during perimenopause or under stressful conditions. The social restrictions introduced during the COVID-19 pandemic have significantly increased the normal burden of psychological and psychic disorders. In moderate to severe cases, pharmacological treatment is currently recommended, while in mild disorders, especially in the initial phase, psychological therapy is preferable. It is known that several nutrients are crucial for brain function. Among them, folate (vitamin B9), cyanocobalamin (vitamin B12), and S-adenosyl-L-methionine (SAMe) have been shown to influence various neurobiological processes. Overall, the available evidence suggests that dietary supplementation with folic acid, vitamin B12, and SAMe can be beneficial for people with mild mood disorders.

Guidelines for diagnosis and treatment of depression in older adults: A report from the Japanese Society of mood disorders.

The Committee for Treatment Guidelines of Mood Disorders, Japanese Society of Mood Disorders, published a Japanese guideline for the treatment of late-life depression in 2020. Based on that guideline, the present guideline was developed and revised to incorporate the suggestions of global experts and the latest published evidence. In the diagnosis of late-life depression, it is important to carefully differentiate it from bipolar disorders, depressive states caused by physical and organic brain disease, drug effects, and dementia, and to determine the comorbidity between late-life depression and dementia. It is necessary to fully understand the clinical characteristics and psychosocial background of late-life depression, evaluate the patient's condition, and provide basic interventions based on these factors. Problem-solving therapy, reminiscence therapy/life review therapy, and behavioral activation therapy, and other forms of psychotherapy can reduce depressive symptoms. In terms of pharmacotherapy, newer antidepressants or non-tricyclic antidepressants are recommended for late-life depression, and it is recommended that the efficacy of least the minimal effective dosage should first be determined. Switching antidepressants and aripiprazole augmentation can be used to treatment-resistant therapy. Electroconvulsive therapy and repetitive transcranial magnetic stimulation have demonstrated usefulness for late-life depression. Exercise therapy, high-intensity light therapy, and diet therapy also show some effectiveness and are useful for late-life depression. Continuation therapy should be maintained for at least 1 year after remission.

Shumian capsule improves symptoms of sleep mood disorder in convalescent patients of Corona Virus Disease 2019.

OBJECTIVE: To evaluate the clinical effectiveness of Shumian capsule in improving the symptoms of insomnia, anxiety, depression, and other symptoms of convalescent patients of COVID-19. METHODS: Totally 200 patients were collected and randomly divided into experiment group (n = 100) and control group (n = 100). The control group was treated with Shumian capsule simulator, and the experiment group was treated with Shumian capsule. The improvement of TCM symptom score, the total effective rate and symptom disappearance rate of TCM symptoms in the two groups before and after treatment were observed, and the clinical effect was evaluated. RESULTS: One week after treatment, the scores of anxiety symptoms in the experiment group were significantly different from those in the control group (P < 0.05), but there was no significant difference in the scores of insomnia and depression between the experiment group and the control group (P > 0.05). There was no significant difference in the total effective rate and disappearance rate of TCM symptoms of insomnia, anxiety and depression between the experiment group and the control group (P > 0.05). After 2 weeks of treatment, the scores of insomnia, anxiety, depression and the total effective rate of TCM symptoms in the experiment group were significantly different from those in the control group (P < 0.05). There was no significant difference in the disappearance rate of insomnia, anxiety and depression between the experiment group and the control group (P > 0.05). There were no significant differences in heart rate, respiration, systolic blood pressure and diastolic blood pressure between the experiment group and the control group (P > 0.05). CONCLUSION: Shumian capsule can significantly improve the symptoms of insomnia, anxiety and depression in COVID-19's convalescent patients with sleep and mood disorders.

Therapeutic Effect and Mechanisms of Essential Oils in Mood Disorders: Interaction between the Nervous and Respiratory Systems.

Essential oils (EOs) are extracted from plants and contain active components with therapeutic effects. Evidence shows that various types of EOs have a wide range of health benefits. In our previous studies, the potential of lavender EO for prevention and even treatment of depression and anxiety symptoms was demonstrated. The favourable outcomes may be due to multiple mechanisms, including the regulation of monoamine level, the induction of neurotrophic factor expression, the regulation of the endocrine system and the promotion of neurogenesis. The molecules of EOs may reach the brain and exert an effect through two distinctive pathways, namely, the olfactory system and the respiratory system. After inhalation, the molecules of the EOs would either act directly on the olfactory mucosa or pass into the respiratory tract. These two delivery pathways suggest different underlying mechanisms of action. Different sets of responses would be triggered, such as increased neurogenesis, regulation of hormonal levels, activation of different brain regions, and alteration in blood biochemistry, which would ultimately affect both mood and emotion. In this review, we will discuss the clinical effects of EOs on mood regulation and emotional disturbances as well as the cellular and molecular mechanisms of action. Emphasis will be put on the interaction between the respiratory and central nervous system and the involved potential mechanisms. Further evidence is needed to support the use of EOs in the clinical treatment of mood disturbances. Exploration of the underlying mechanisms may provide insight into the future therapeutic use of EO components treatment of psychiatric and physical symptoms.

Allopregnanolone in mood disorders: Mechanism and therapeutic development.

The neuroactive steroid allopregnanolone (ALLO) is an endogenous positive allosteric modulator of GABA type A receptor (GABAAR), and the down-regulation of its biosynthesis have been attributed to the development of mood disorders, such as depression, anxiety and post-traumatic stress disorder (PTSD). ALLO mediated depression/anxiety involves GABAergic mechanisms and appears to be related to brain-derived neurotrophic factor (BDNF), dopamine receptor, glutamate neurotransmission, and Ca2+ channel. In the clinical, brexanolone, as a newly developed intravenous ALLO preparation, has been approved for the treatment of postpartum depression (PPD). In addition, traditional antidepressants such as selective serotonin reuptake inhibitor (SSRI) could reverse ALLO decline. Recently, the translocation protein (TSPO, 18 kDa), which involves in the speed-limiting step of ALLO synthesis, and ALLO derivatization have been identified as new directions for antidepressant therapy. This review provides an overview of ALLO researches in animal model and patients, discusses its role in the development and treatment of depression/anxiety, and directs its therapeutic potential in future.

Cannabidiol as a Potential Treatment for Anxiety and Mood Disorders: Molecular Targets and Epigenetic Insights from Preclinical Research.

Cannabidiol (CBD) is the most abundant non-psychoactive component of cannabis; it displays a very low affinity for cannabinoid receptors, facilitates endocannabinoid signaling by inhibiting the hydrolysis of anandamide, and stimulates both transient receptor potential vanilloid 1 and 2 and serotonin type 1A receptors. Since CBD interacts with a wide variety of molecular targets in the brain, its therapeutic potential has been investigated in a number of neuropsychiatric diseases, including anxiety and mood disorders. Specifically, CBD has received growing attention due to its anxiolytic and antidepressant properties. As a consequence, and given its safety profile, CBD is considered a promising new agent in the treatment of anxiety and mood disorders. However, the exact molecular mechanism of action of CBD still remains unknown. In the present preclinical review, we provide a summary of animal-based studies that support the use of CBD as an anxiolytic- and antidepressant-like compound. Next, we describe neuropharmacological evidence that links the molecular pharmacology of CBD to its behavioral effects. Finally, by taking into consideration the effects of CBD on DNA methylation, histone modifications, and microRNAs, we elaborate on the putative role of epigenetic mechanisms in mediating CBD's therapeutic outcomes.

Factors associated with initiation of community-based therapy for emerging adults with mood and anxiety disorders.

AIM: The First Episode Mood and Anxiety Program (FEMAP) is a community-based early intervention program that has been shown to improve health outcomes for emerging adults (EAs) with mood and anxiety disorders. However, not all EAs who are admitted to the program initiate treatment. Our aim was to identify factors that distinguish those who initiated treatment from those who did not. METHODS: FEMAP administered questionnaires to EAs upon first contact with the program, collecting information on a range of socioeconomic, patient and condition-related factors. We compared EAs who initiated treatment in the program (n = 318, 87.4%) to those who did not (n = 46, 12.6%). To examine factors associated with treatment initiation, we specified a parsimonious logistic regression model, using the method of purposeful selection to choose from a range of candidate variables. RESULTS: Anxiety Sensitivity Index - Revised (ASI-R), binge drinking and cannabis use were included in the final logistic regression model. Each one-point increment in the ASI-R score was associated with a 1% increase in the odds of treatment initiation (OR = 1.014; 95% CI [1.003, 1.026]). No other variable was significantly associated with treatment initiation. CONCLUSIONS: Our study provides insight on the differences between EAs with mood and anxiety disorders who initiated targeted treatment services and those who did not. Anxiety sensitivity was significantly associated with treatment initiation at FEMAP. Our findings suggest that it may be anxiety sensitivity, rather than depression or functional impairment per se that drive treatment initiation among EAs.

Lithium treatment in the era of personalized medicine.

In 1949, an Australian psychiatrist, John Cade, reported on the antimanic efficacy of lithium carbonate, which is regarded as an introduction of lithium into contemporary psychiatry. Since the 1960s, lithium has been a precursor of mood stabilizers and has become first-choice drug for the prevention of affective episodes in mood disorders. For nearly four decades, lithium has also been used for the augmentation of antidepressant drugs in treatment-resistant depression. The knowledge of clinical and biological factors connected with the capability of long-term lithium treatment to prevent manic and depressive recurrences makes an important element of the personalized medicine of mood disorders. Excellent prophylactic lithium responders can be characterized by distinct mood episodes, with full remissions between them, the absence of other psychiatric morbidity, and the family history of bipolar illness. In recent years, many other clinical and biological factors connected with such a response have been identified, helping to select the best candidates for lithium prophylaxis. The antisuicidal effect of lithium during its long-term administration has been demonstrated and should also be taken into account as the element of personalized medicine for the pharmacological prophylaxis of patients with mood disorders. Several studies pertaining to personalized medicine were also dedicated to lithium treatment of acute mood episodes. Lithium still has a value in the treatment of mania and bipolar depression. However, it seems that the more important indication would be the augmentation of antidepressant drugs in treatment-resistant depression. The factors connected with the efficacy of lithium in these conditions are reviewed.

Innovative therapies for mood disorders: A case report.

BACKGROUND: Mood disorders, including depression and anxiety, are complex and multifactorial, impacting the quality of life for those suffering and making them difficult to manage for their providing health care providers. Diet, stress, medication, genetics, and the microbiome have been attributed to playing a role. Currently, prescription drugs are the first course of treatment despite the World Health Organization calling for a need to develop lifestyle interventions to manage these disorders. The use of single amino acids to impact selected neurotransmitters has demonstrated positive outcomes in the literature, however, the use of multiple amino acids, alongside personalized nutritional therapies is not well documented for mood disorders. This case report demonstrates the effective use of amino acids as an innovative therapy for the management of mood disorders. CASE DESCRIPTION: A 26-year-old Caucasian female presented with anxiety, depression, sleep disturbances, carbohydrate cravings, and low energy. She had been diagnosed with Post Traumatic Stress Disorder (PTSD), bipolar depression II and generalized anxiety. The patient was under the care of a counselor and physician and was prescribed Lamictal (200 mg/day). With only moderate success with other therapies, the patient sought nutritional counseling. A personalized nutrition intervention was created to include targeted amino acid therapy (tryptophan, glycine, L-glutamine, D-phenylalanine, L-theanine, and L-tyrosine), select nutrients (multi vitamin/mineral, zinc, vitamin C, GLA and magnesium) and a low-glycemic diet to be followed for 12 weeks. CONCLUSION: This case report demonstrated the use of targeted micronutrient and amino acid therapy, along with a low glycemic diet, resulted in marked improvement in all mood disorder symptoms this patient experienced. It also highlights that a comprehensive integrative approach may be a beneficial option for individuals with mood disorders.

KiwiC for Vitality: Results of a Randomized Placebo-Controlled Trial Testing the Effects of Kiwifruit or Vitamin C Tablets on Vitality in Adults with Low Vitamin C Levels.

Consumption of vitamin C-rich fruits and vegetables has been associated with greater feelings of vitality. However, these associations have rarely been tested in experimental trials. The aim of the current study was to test the effects of eating a vitamin C-rich food (kiwifruit) on subjective vitality and whether effects are driven by vitamin C. Young adults (n = 167, 61.1% female, aged 18­35 years) with plasma vitamin C < 40 µmol/L were allocated to three intervention conditions: kiwifruit (2 SunGold™ kiwifruit/day), vitamin C (250 mg tablet/day), placebo (1 tablet/day). The trial consisted of a two-week lead-in, four-week intervention, and two-week washout. Plasma vitamin C and vitality questionnaires (total mood disturbance, fatigue, and well-being) were measured fortnightly. Self-reported sleep quality and physical activity were measured every second day through smartphone surveys. Nutritional confounds were assessed using a three-day food diary during each study phase. Plasma vitamin C reached saturation levels within two weeks for the kiwifruit and vitamin C groups. Participants consuming kiwifruit showed a trend of improvement in mood disturbance, significantly decreased fatigue, and significantly improved well-being after two weeks of the intervention. Improvements in well-being remained elevated through washout. Consumption of vitamin C tablets alone was associated with improved well-being after two weeks, and additionally improved mood and fatigue for participants with consistently low vitamin C levels during lead-in. Diet records showed that participants consuming kiwifruit reduced their fat intake during the intervention period. Intervention effects remained significant when adjusting for condition allocation groupings, age, and ethnicity, and were not explained by sleep quality, physical activity, BMI, or other dietary patterns, including fat intake. There were no changes in plasma vitamin C status or vitality in the placebo group. Whole-food consumption of kiwifruit was associated with improved subjective vitality in adults with low vitamin C status. Similar, but not identical changes were found for vitamin C tablets, suggesting that additional properties of kiwifruit may contribute to improved vitality.

Design, Synthesis, and Preclinical Evaluation of 3-Methyl-6-(5-thiophenyl)-1,3-dihydro-imidazo[4,5-b]pyridin-2-ones as Selective GluN2B Negative Allosteric Modulators for the Treatment of Mood Disorders.

Selective inhibitors of the GluN2B subunit of N-methyl-d-aspartate receptors in the ionotropic glutamate receptor superfamily have been targeted for the treatment of mood disorders. We sought to identify structurally novel, brain penetrant, GluN2B-selective inhibitors suitable for evaluation in a clinical setting in patients with major depressive disorder. We identified a new class of negative allosteric modulators of GluN2B that contain a 1,3-dihydro-imidazo[4,5-b]pyridin-2-one core. This series of compounds had poor solubility properties and poor permeability, which was addressed utilizing two approaches. First, a series of structural modifications was conducted which included replacing hydrogen bond donor groups. Second, enabling formulation development was undertaken in which a stable nanosuspension was identified for lead compound 12. Compound 12 was found to have robust target engagement in rat with an ED70 of 1.4 mg/kg. The nanosuspension enabled sufficient margins in preclinical toleration studies to nominate 12 for progression into advanced good laboratory practice studies.

Novel Therapeutic Approach for the Management of Mood Disorders: In Vivo and In Vitro Effect of a Combination of L-Theanine, Melissa officinalis L. and Magnolia officinalis Rehder & E.H. Wilson.

Mood disorders represent one of the most prevalent and costly psychiatric diseases worldwide. The current therapies are generally characterized by several well-known side effects which limit their prolonged use. The use of herbal medicine for the management of several psychiatric conditions is becoming more established, as it is considered a safer support to conventional pharmacotherapy. The aim of this study was to investigate the possible anxiolytic and antidepressant activity of a fixed combination of L-theanine, Magnolia officinalis, and Melissa officinalis (TMM) in an attempt to evaluate how the multiple modulations of different physiological systems may contribute to reducing mood disorders. TMM showed an anxiolytic-like and antidepressant-like activity in vivo, which was related to a neuroprotective effect in an in vitro model of excitotoxicity. The effect of TMM was not altered by the presence of flumazenil, thus suggesting a non-benzodiazepine-like mechanism of action. On the contrary, a significant reduction in the effect was observed in animals and neuronal cells co-treated with AM251, a cannabinoid receptor type 1 (CB1) antagonist, suggesting that the endocannabinoid system may be involved in the TMM mechanism of action. In conclusion, TMM may represent a useful and safe candidate for the management of mood disorders with an innovative mechanism of action, particularly as an adjuvant to conventional therapies.

Waddling Gait: A complication of valproate therapy and a thought beyond vitamin D deficiency.

Proximal muscle weakness is a common presentation in paediatric-orthopaedic clinics and is frequently paired with a vitamin D deficiency diagnosis. Recently, side effects of the extensive use of antiepileptic and antipsychotic drugs such as sodium valproate in childhood disorders are being documented. Sodium valproate causes a time-dependent, drug-induced proximal myopathy. We report a 13-year-old female patient who presented at the Orthopaedic Outpatient Department at Lady Hardinge Medical College, New Delhi, India, in 2019 with an abnormal gait. The patient was taking a combination therapy of sodium valproate, risperidone and trihexyphenidyl for absence seizures and a mood disorder. Following clinical investigations, the patient was diagnosed with proximal myopathy. As a result of elevated serum alkaline phosphatase and creatine kinase myocardial band levels, sodium valproate was replaced with ethosuximide and a carnitine supplementation was prescribed. The patient fully recovered and regained full mobility. Proximal myopathy had been incorrectly managed and assumed to be caused by a vitamin D deficiency.

Calcium-Involved Action of Phytochemicals: Carotenoids and Monoterpenes in the Brain.

BACKGROUND: Neurodegenerative and mood disorders represent growing medical and social problems, many of which are provoked by oxidative stress, disruption in the metabolism of various neurotransmitters, and disturbances in calcium homeostasis. Biologically active plant compounds have been shown to exert a positive impact on the function of calcium in the central nervous system. METHODS: The present paper reviews studies of naturally occurring terpenes and derivatives and the calcium-based aspects of their mechanisms of action, as these are known to act upon a number of targets linked to neurological prophylaxis and therapy. RESULTS: Most of the studied phytochemicals possess anticancer, antioxidative, anti-inflammatory, and neuroprotective properties, and these have been used to reduce the risk of or treat neurological diseases. CONCLUSION: The neuroprotective actions of some phytochemicals may employ mechanisms based on regulation of calcium homeostasis and should be considered as therapeutic agents.

The "Entourage Effect": Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders.

Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders. Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa was suggested for their treatment. The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, 'cannabis' is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes. Thus, the "entourage effect" is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here, we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids. Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.

Perspectives in affective disorders: Clocks and sleep.

Mood disorders are often characterised by alterations in circadian rhythms, sleep disturbances and seasonal exacerbation. Conversely, chronobiological treatments utilise zeitgebers for circadian rhythms such as light to improve mood and stabilise sleep, and manipulations of sleep timing and duration as rapid antidepressant modalities. Although sleep deprivation ("wake therapy") can act within hours, and its mood-elevating effects be maintained by regular morning light administration/medication/earlier sleep, it has not entered the regular guidelines for treating affective disorders as a first-line treatment. The hindrances to using chronotherapeutics may lie in their lack of patentability, few sponsors to carry out large multi-centre trials, non-reimbursement by medical insurance and their perceived difficulty or exotic "alternative" nature. Future use can be promoted by new technology (single-sample phase measurements, phone apps, movement and sleep trackers) that provides ambulatory documentation over long periods and feedback to therapist and patient. Light combinations with cognitive behavioural therapy and sleep hygiene practice may speed up and also maintain response. The urgent need for new antidepressants should hopefully lead to reconsideration and implementation of these non-pharmacological methods, as well as further clinical trials. We review the putative neurochemical mechanisms underlying the antidepressant effect of sleep deprivation and light therapy, and current knowledge linking clocks and sleep with affective disorders: neurotransmitter switching, stress and cortico-limbic reactivity, clock genes, cortical neuroplasticity, connectomics and neuroinflammation. Despite the complexity of multi-system mechanisms, more insight will lead to fine tuning and better application of circadian and sleep-related treatments of depression.

Cannabis and Cannabinoids in Mood and Anxiety Disorders: Impact on Illness Onset and Course, and Assessment of Therapeutic Potential.

BACKGROUND AND OBJECTIVES: Cannabis use is common in people with and mood and anxiety disorders (ADs), and rates of problematic use are higher than in the general population. Given recent policy changes in favor of cannabis legalization, it is important to understand how cannabis and cannabinoids may impact people with these disorders. We aimed to assess the effects of cannabis on the onset and course of depression, bipolar disorder, ADs, and post-traumatic stress disorder (PTSD), and also to explore the therapeutic potential of cannabis and cannabinoids for these disorders. METHODS: A systematic review of the literature was completed. The PubMed® database from January 1990 to May 2018 was searched. We included longitudinal cohort studies, and also all studies using cannabis or a cannabinoid as an active intervention, regardless of the study design. RESULTS: Forty-seven studies were included: 32 reported on illness onset, nine on illness course, and six on cannabinoid therapeutics. Cohort studies varied significantly in design and quality. The literature suggests that cannabis use is linked to the onset and poorer clinical course in bipolar disorder and PTSD, but this finding is not as clear in depression and anxiety disorders (ADs). There have been few high-quality studies of cannabinoid pharmaceuticals in clinical settings. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These conclusions are limited by a lack of well-controlled longitudinal studies. We suggest that future research be directed toward high-quality, prospective studies of cannabis in clinical populations with mood and ADs, in addition to controlled studies of cannabinoid constituents and pharmaceuticals in these populations. (Am J Addict 2019;00:00-00).

The Management of Stroke Rehabilitation: A Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

Description: In June 2019, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved an update of the joint clinical practice guideline for rehabilitation after stroke. This synopsis summarizes the key recommendations from this guideline. Methods: In February 2018, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and stroke survivors and conformed to the National Academy of Medicine (formerly the Institute of Medicine) tenets for trustworthy clinical practice guidelines. The guideline panel identified key questions, systematically searched and evaluated the literature, and developed 2 algorithms and 42 key recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Stroke survivors and their family members were invited to share their perspectives to further inform guideline development. Recommendations: The guideline recommendations provide evidence-based guidance for the rehabilitation care of patients after stroke. The recommendations are applicable to health care providers in both primary care and rehabilitation. Key features of the guideline are recommendations in 6 areas: timing and approach; motor therapy; dysphagia; cognitive, speech, and sensory therapy; mental health therapy; and other functions, such as returning to work and driving.