Circadian Reinforcement Therapy in Combination With Electronic Self-Monitoring to Facilitate a Safe Postdischarge Period for Patients With Major Depression: Randomized Controlled Trial.

BACKGROUND: Patients with major depression exhibit circadian disturbance of sleep and mood, and when they are discharged from inpatient wards, this disturbance poses a risk of relapse. We developed a circadian reinforcement therapy (CRT) intervention to facilitate the transition from the inpatient ward to the home for these patients. CRT focuses on increasing the zeitgeber strength for the circadian clock through social contact, physical activity, diet, daylight exposure, and sleep timing. OBJECTIVE: In this study, we aimed to prevent the worsening of depression after discharge by using CRT, supported by an electronic self-monitoring system, to advance and stabilize sleep and improve mood. The primary outcome, which was assessed by a blinded rater, was the change in the Hamilton Depression Rating Scale scores from baseline to the end point. METHODS: Participants were contacted while in the inpatient ward and randomized 1:1 to the CRT or the treatment-as-usual (TAU) group. For 4 weeks, participants in both groups electronically self-monitored their daily mood, physical activity, sleep, and medication using the Monsenso Daybuilder (MDB) system. The MDB allowed investigators and participants to simultaneously view a graphical display of registrations. An investigator phoned all participants weekly to coinspect data entry. In the CRT group, participants were additionally phoned between the scheduled calls if specific predefined trigger points for mood and sleep were observed during the daily inspection. Participants in the CRT group were provided with specialized CRT psychoeducation sessions immediately after inclusion, focusing on increasing the zeitgeber input to the circadian system; a PowerPoint presentation was presented; paper-based informative materials and leaflets were reviewed with the participants; and the CRT principles were used during all telephone consultations. In the TAU group, phone calls focused on data entry in the MDB system. When discharged, all patients were treated at a specialized affective disorders service. RESULTS: Overall, 103 participants were included. Participants in the CRT group had a significantly larger reduction in Hamilton Depression Scale score (P=.04) than those in the TAU group. The self-monitored MDB data showed significantly improved evening mood (P=.02) and sleep quality (P=.04), earlier sleep onset (P=.009), and longer sleep duration (P=.005) in the CRT group than in the TAU group. The day-to-day variability of the daily and evening mood, sleep offset, sleep onset, and sleep quality were significantly lower in the CRT group (all P<.001) than in the TAU group. The user evaluation was positive for the CRT method and the MDB system. CONCLUSIONS: We found significantly lower depression levels and improved sleep quality in the CRT group than in the TAU group. We also found significantly lower day-to-day variability in daily sleep, mood parameters, and activity parameters in the CRT group than in the TAU group. The delivery of the CRT intervention should be further refined and tested. TRIAL REGISTRATION: ClinicalTrials.gov NCT02679768; https://clinicaltrials.gov/study/NCT02679768. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12888-019-2101-z.

In situ fNIRS measurements during cognitive behavioral emotion regulation training in rumination-focused therapy: A randomized-controlled trial.

Repetitive negative thinking (RNT), including rumination, plays a key role in various psychopathologies. Although several psychotherapeutic treatments have been developed to reduce RNT, the neural correlates of those specific treatments and of psychotherapy in general are largely unknown. Functional near-infrared spectroscopy (fNIRS) offers the potential to investigate the neural correlates of psychotherapeutic techniques in situ. Therefore, in this study we investigated the efficacy and neural correlates of a fNIRS adapted Mindfulness-based Emotion Regulation Training (MBERT) for the treatment of depressive rumination in 42 subjects with major depressive disorder (MDD) in a cross-over designed randomized controlled trial. Using psychometric measures, subjective ratings and fNIRS, we analyzed in situ changes in depressive symptom severity, ruminative thoughts and cortical activity in the Cognitive Control Network (CCN). Our results show that MBERT is effective in treating depressive symptoms and rumination. On a neural level, we found consistently higher cortical activation during emotion regulation training compared to control trials in the bilateral inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC). Furthermore, cortical oxygenation decreased from session to session in the bilateral DLPFC. The relevance of the results for the psychotherapeutic treatment of MDD as well as further necessary investigations are discussed.

Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviours.

Early flow cytometry studies revealed T cell activation in major depressive disorder (MDD). MDD is characterised by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS), including deficits in T regulatory (Treg) cells. This study examines the number of cannabinoid type 1 (CB1) and type 2 (CB2) receptor-bearing T/B lymphocytes in MDD, and the effects of in vitro cannabidiol (CBD) administration on CB1/CB2-bearing immunocytes. Using flow cytometry, we determined the percentage of CD20+CB2+, CD3+CB2+, CD4+CB2+, CD8+CB2+ and FoxP3+CB1+ cells in 19 healthy controls and 29 MDD patients in 5 conditions: baseline, stimulation with anti-CD3/CD28 with or without 0.1 µg/mL, 1.0 µg/mL, or 10.0 µg/mL CBD. CB2+ was significantly higher in CD20+ than CD3+ and CD4+ and CD 8+ cells. Stimulation with anti-CD3/CD8 increases the number of CB2-bearing CD3+, CD4+ and CD8+ cells, as well as CB1-bearing FoxP3+ cells. There was an inverse association between the number of reduced CD4+ CB2+ and IRS profiles, including M1 macrophage, T helper-(Th)-1 and Th-17 phenotypes. MDD is characterised by lowered basal FoxP3+ CB1+% and higher CD20+ CB2+%. 33.2% of the variance in the depression phenome (including severity of depression, anxiety and current suicidal behaviours) is explained by CD20+ CB2+ % (positively) and CD3+ CB2+% (inversely). All five immune cell populations were significantly increased by 10 µg/mL of CBD administration. Reductions in FoxP3+ CB1+% and CD3+ /CD4+ CB2+% contribute to deficits in immune homoeostasis in MDD, while increased CD20+CB2+% may contribute to the pathophysiology of MDD by activating T-independent humoral immunity.

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder.

The pharmacological treatment of depression consists of taking antidepressant drugs for prolonged periods; its modest therapeutic effect can often be associated with significant adverse effects, while its discontinuation can lead to relapses. Psilocybin is today a novel and breakthrough therapy for major depression. It is a natural alkaloid in Psilocybe mushrooms, which are endemic to Mexico. Research on a larger scale is lacking in various populations, including the Mexican people. This proposal contemplates the experimental design of a preclinical (toxicity and pharmacological evaluation of an extract in mice) and clinical study by including the chemical analysis of a species of Psilocybe cubensis mushroom to characterize its main constituents. The clinical study will consider the safety evaluation by exploring tolerated doses of Psilocybe cubensis by measuring pharmacokinetic parameters after oral administration in healthy adults and an open trial on a sample of patients with major depressive disorder to assess the safety and efficacy of fully characterized Psilocybe cubensis in a two-single doses treatment, (with assisted psychotherapy), compared with the traditional care model at the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz in Mexico City. This report presents the design of a research project with preclinical and clinical experimental components.

Light Therapy for Adolescent Depression: A Scoping Review.

PURPOSE: Depressive disorders in adolescents are a major health concern associated with developmental, social, and educational impairment. Bright Light Therapy (BLT) is a feasible and effective treatment for depressive disorders in adults, but few controlled trials have been conducted with children or adolescents. This scoping review focuses on the current state of knowledge for BLT in the treatment of adolescent depression. We reviewed the literature for novel data and methodologic approaches using BLT and pediatric and young adult populations. RECENT FINDINGS: BLT is a tolerable treatment with few side effects. However, there is a marked lack of well-powered studies to support BLT as a treatment for depressive disorders in adolescent populations. Given evidence of tolerability and positive treatment effect on depression in the adult literature, research is needed to establish the efficacy, feasibility, and acceptability of BLT in adolescents.

Factors that contribute to trait mindfulness level among hospitalized patients with major depressive disorder.

Mindfulness training among patients with major depressive disorder (MDD) reduces symptoms, prevents relapse, improves prognosis, and is more efficient for those with a high level of trait mindfulness. Upon hospital admission, 126 MDD patients completed the Beck Depression Inventory (BDI), World Health Organization Quality of Life Brief, Five-Factor Mindfulness Questionnaire (FFMQ), and the Rumination Response Scale (RRS). The 65 patients that scored less than the median of all subjects on the FFMQ were placed into the low mindfulness level (LML) group. The other 61 patients were placed in the high mindfulness level (HML) group. All facet scores were statistically different between the mental health assessment scores of the HML and LML groups except for RRS brooding and FFMQ nonjudgement. Trait mindfulness level exhibited a negative and bidirectional association with MDD severity primarily through the facets of description and aware actions. Trait mindfulness was also related positively with age primarily through the facets of nonreactivity and nonjudgement. Being married is positively associated with trait mindfulness levels primarily through the facet of observation and by an associated increase in perceived quality of life. Mindfulness training prior to MDD diagnosis also associates positively with trait mindfulness level. Hospitalized MDD patients should have their trait mindfulness levels characterized to predict treatment efficiency, help establish a prognosis, and identify mindfulness-related therapeutic targets.

Arketamine for bipolar depression: Open-label, dose-escalation, pilot study.

There are significantly fewer options for the treatment of bipolar depression than major depressive disorder, with an urgent need for alternative therapies. In this pilot study, we treated six subjects with bipolar disorder types I and II (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria) who had been in a current depressive episode for at least four weeks. Four subjects were female (66.66%), and the mean age was 45.33 (±12.32). Subjects received adjunct treatment with two arketamine intravenous infusions one week apart-0.5 mg/kg first and then 1 mg/kg. The mean baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score was 36.66, which decreased to 27.83 24h after the first infusion of 0.5 mg/kg of arketamine (p = 0.036). In respect of the 1 mg/kg dose, the mean MADRS total score before the second infusion was 32.0, which dropped to 17.66 after 24h (p < 0.001). Arketamine appears to have rapid-acting antidepressant properties, consistent with previous animal studies on major depression. All individuals tolerated both doses, exhibiting nearly absent dissociation, and no manic symptoms. To the best of our knowledge, this pilot trial is the first to test the feasibility and safety of the (R)-enantiomer of ketamine (arketamine) for bipolar depression.

Clinical efficacy and immune effects of acupuncture in patients with comorbid chronic pain and major depression disorder: A double-blinded, randomized controlled crossover study.

BACKGROUND: Depression and pain are highly comorbid and share biological mechanisms. Acupuncture is commonly used to manage both pain and depression, but the choice of acupoints for specific disorders differs. This study aimed to investigate whether specific acupuncture intervention on pain- and depression-acupoints would have specific efficacy and immune effects in patients with comorbid chronic pain and major depressive disorder (MDD). METHODS: We performed a subject- and assessor-blinded, crossover, and randomized controlled clinical trial of depression- and pain-specific acupuncture intervention and measured clinical responses and proinflammatory cytokines in patients with comorbid chronic pain and MDD. Specific acupoints for pain and depression were used in random order with a washout interval. Forty-seven patients were enrolled and randomly assigned to two groups: (1) the depression-pain group (23 patients who were treated with depression-specific acupoints and then the pain-specific acupoints after the washout) and (2) pain-depression group (24 patients with the reverse order). RESULTS: The pain-specific acupoints for pain did not reduce Brief Pain Inventory scores to a significantly greater degree (-0.97 ± 1.69) than the depression-specific acupoints (-0.28 ± 1.88); likewise, the depression-specific acupoints did not significantly ameliorate Hamilton Depression Rating Scale (-4.59 ± 6.02) than the pain-specific acupoints (-6.69 ± 6.61). The pain-specific acupoints improved Beck Depression Inventory-Second Edition (-6.74 ± 9.76) even better than the depression-specific acupoints (-1.92 ± 10.74). The depression-specific acupoints did not significantly decrease the depression-related interleukin (IL)-6 level (-1.24 ± 6.67) than the pain-specific acupoints (-0.60 ± 4.36). The changed levels of IL-1ß, tumor necrosis factor (TNF)-α between the depression-specific acupoints (-37.41 ± 194.49; -12.53 ± 54.68) and the pain-specific acupoints (-15.46 ± 87.56; -7.28 ± 27.86) could not reach significantly different, too. CONCLUSION: This study rejected our hypothesis that the pain-specific acupoints might produce superior analgesic effects than the depression-specific acupoints and vice versa. The cytokine results might imply that pain and depression share common biological mechanisms. (trial registration: https://www. CLINICALTRIALS: gov: NCT03328819).

Methylation of melatonin receptors in patients with unipolar and bipolar depression.

Disturbances of melatonin secretion alter the circadian rhythm and sleep-wake cycle, which is observed among patients with depression. Melatonin acts via melatonin receptors MT1 and MT2, which are present in many tissues, including peripheral blood mononuclear cells (PBMC). We assume that disturbances of the melatonin pathway in the brain may be reflected by molecular changes in peripheral organs. The study objective was to evaluate the methylation profile of CpG island in the promoter region of melatonin receptor genes MTNR1A and MTNR1B in PBMC of patients with depression and compare it with healthy volunteers. The study group comprised 85 patients with unipolar (UP) and bipolar disorders (BP) and 83 controls. The methylation pattern of CpG island in the promoter region was analyzed using the quantitative methylation-specific real-time PCR (qMSP-PCR) method. We found that the methylation profile of the patients with depression varied in comparison to the control group. The methylation level of MTNR1A was significantly lower among depressed patients compared to controls. Additionally, melatonin concentration was negatively correlated with MTNR1B methylation level among the UP patients. The study may suggest that the methylation profile of melatonin receptors in PBMC may be used as a complementary molecular marker in depression diagnosis.

Research and Diagnostic Algorithmic Rules (RADAR) for mood disorders, recurrence of illness, suicidal behaviours, and the patient's lifetime trajectory.

The top-down Diagnostic and Statistical Manual/International Statistical Classification of Diseases categories of mood disorders are inaccurate, and their dogmatic nature precludes both deductive (as indisputable) and inductive (as top-down) remodelling of case definitions. In trials, psychiatric rating scale scores employed as outcome variables are invalid and rely on folk psychology-like narratives. Using machine learning techniques, we developed a new precision nomothetic model of mood disorders with a recurrence of illness (ROI) index, a new endophenotype class, namely Major Dysmood Disorder (MDMD), characterised by increased ROI, a more severe phenome, and more disabilities. Nonetheless, our previous studies did not compute Research and Diagnostic Algorithmic Rules (RADAR) to diagnose MDMD and score ROI, lifetime (LT), and current suicidal behaviours, as well as the phenome of mood disorders. Here, we provide rules to compute bottom-up RADAR scores for MDMD, ROI, LT and current suicidal ideation and attempts, the phenome of mood disorders, and the lifetime trajectory of mood disorder patients from a family history of mood disorders and substance abuse to adverse childhood experiences, ROI, and the phenome. We also demonstrate how to plot the 12 major scores in a single RADAR graph, which displays all features in a two-dimensional plot. These graphs allow the characteristics of a patient to be displayed as an idiomatic fingerprint, allowing one to estimate the key traits and severity of the illness at a glance. Consequently, biomarker research into mood disorders should use our RADAR scores to examine pan-omics data, which should be used to enlarge our precision models and RADAR graph.

YY1 (Yin-Yang 1), a transcription factor regulating systemic inflammation, is involved in cognitive impairment of depression.

AIM: Clinical and preclinical studies suggest that alterations in the peripheral and brain immune system are associated with the pathophysiology of depression, also leading to changes in local glucose metabolism in the brain. Here, the authors identified Yin-Yang 1 (YY1), a transcription factor closely associated with central and peripheral inflammation. METHODS: Plasma levels of YY1, interleukin (IL) 6, and IL-1ß in major depressive disorder (MDD) were collected before and after treatment with vortioxetine, and correlation with clinical and cognitive scores was studied. Chronic unpredictable mild stress was treated with vortioxetine. Micropositron emission tomography (microPET) was used to analyze glucose metabolism and mRNA, and the protein level of the YY1-nuclear factor κB (NF-κB)-IL-1ß inflammatory pathway were measured in related brain regions. RESULTS: Plasma levels of YY1 and IL-1ß were significantly increased in MDD and decreased after treatment with vortioxetine. Meanwhile, the level of YY1 in plasma was negatively correlated with cognitive functions in patients with MDD and positively correlated with the level of IL-1ß in plasma. Compared with the control group, in chronic unpredictable mild stress rats, (microPET) analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum, and medial prefrontal cortex was reversed after treatment. mRNA and protein level of related molecular in YY1-NF-κB-IL-1ß inflammatory pathway decreased in the hippocampus and was reversed by vortioxetine. CONCLUSION: The current study suggests that the YY1-NF-κB-IL-1ß inflammatory pathway may play an essential role in both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in emotion regulation and cognition. These findings provide new evidence for the inflammatory mechanisms of depression.

Is the mainstream construction of mood disorders resistant to systemic thinking?

Introduction: In this study we explore how the diagnostic category of mood disorders is constructed in two handbooks of Psychopathology as an example of the mainstream construction of psychopathology. Despite the increasing criticism and lack of evidence, the debunked chemical imbalance theory of the etiology of depression still dominates the professional and pop/folk understanding and interventions. Methods: We analysed the breadth of the inference field and the type of etiopathogenetic contents of the explanations of mood disorders using the "1to3" Coding System. Results: Our findings show that the dominant explanations draw almost exclusively onto monadic explanations, followed by limited dyadic ones. Intrapersonal etiopathogenetic contents prevailed, and biomedical explanations were dominant in both textbooks. Discussion: We critically discuss the underpinnings of these results and address the clinical implications of these biased representations, as well as potential alternative approaches to psychopathology.

The Effects of Yoga on Bipolar Disorder: A Systematic Review.

Bipolar disorder (BD) is a mood disorder characterized by severe mood swings and or periods of depression. This study examined the role that practicing yoga has on the symptoms of BD. One of the main goals was to identify if patients with BD believe that yoga is a viable treatment option. Six research databases were searched using the keywords "yoga" AND "therapy" AND "BD" AND "bipolar depression." Articles published in 2005 and later were included in the search. After duplicates were removed, and inclusion and exclusion criteria were applied, five articles were analyzed and included in this literature review. Results of this review indicate that yoga has been shown to be associated with both benefits and risks for the treatment of BD. Studies have shown that yoga might relieve some symptoms of BD and depression. However, due to the lack of research on the impact of yoga on BD and the small number of studies included in this review, results should be approached with caution. Overall, yoga was well-tolerated in the studies reviewed in this article. Yoga may relieve the symptoms of depression. Future research should analyze the long-term impact of yoga on bipolar depression. Yoga instructional standards should also be considered.

An observational study of acupuncture and complementary treatments for major depression: Case series from a preliminary study of proposed collaborative care model.

Background: Major depressive disorder is identified as a mood disorder characterized by episodically recurring and potentially life-threatening negative symptoms. It is currently important for study, as it involves high morbidity, mortality and prevalence, as well as unsatisfactory treatment results. Aim: Establish an outpatient model from an integrative approach promoting the diversified development of traditional Chinese and Western medicine cooperation, leading to a holistic intervention for patients with depression. Experimental procedure: Fifteen participants with moderate to severe depression were followed up for eight weeks in the Acupuncture Department of the China Medical University Hospital in Taichung, Taiwan, under a collaborative outpatient model that combined Western psychiatry and traditional Chinese medicine (TCM). Interdisciplinary Intervention included manual acupuncture twice a week (16 sessions), tai chi, yoga meditation, and nutritional assessment. Symptomatology was measured with primary outcomes (self-reporting via questionnaires) and secondary outcomes (heart rate variability [HRV] and blood samples to measure inflammation via high-sensitivity C-reactive protein [hs-CRP]). Results: The response rate was 80% (12/15 participants), with a statistically and clinically significant decrease in depression severity according to the 21-question Hamilton depression rating scale (HDRS21) (p < 0.001), the Beck Depression Inventory (BDI) (p < 0.003), and quality of life (QoL) questionnaires (p < 0.002). We found body constitution heterogeneity in the participants with major depressive disorder (MDD), predominantly blood stagnation and Qi stagnation (in 70% of participants). Conclusion: An interdisciplinary outpatient treatment method of complementary therapies can be applied successfully with pharmacological treatment in clinical practice to reduce depression symptomatology. Section: Physical/Mental practices. Taxonomy: Major Depressive Disorder, Collaborative healthcare Treatment, Observational study.

The relationships between use of alcohol, tobacco and coffee in adolescence and mood disorders in adulthood.

INTRODUCTION: Alcohol, tobacco and coffee are commonly used substances and use in adolescence has previously been linked to mood disorders. However, few large prospective studies have investigated adolescent use in relation to mental health outcomes in adulthood. The main aim of this study was to examine the prospective associations between alcohol use, cigarette smoking and coffee consumption at age 16 and subsequent mood disorders up to 33 years of age. METHODS: Data from The Northern Finland Birth Cohort 1986 Study were used and a total of 7660 participants (49.9% male) were included. Associations between alcohol use, cigarette smoking and coffee consumption at age 16 and later diagnoses of major depression and bipolar disorder were examined using multinomial logistic regression analyses. RESULTS: Mean number of cigarettes/day (OR, 1.23 [95% CI 1.01-1.50]) and mean volume of alcohol consumption (OR, 1.22 [95% CI 1.01-1.47]), but not frequency of excessive drinking, in adolescence were associated with increased risk for subsequent bipolar disorder after adjustment for sex, parental psychiatric disorders, family structure, illicit substance use, and emotional and behavioral problems at age 16. An association between cigarette smoking and major depression attenuated to statistically non-significant when adjusted for emotional and behavioral problems. No associations were observed between adolescent coffee consumption and subsequent mood disorders. CONCLUSIONS: This is the first study to report an association of adolescent cigarette smoking and subsequent bipolar disorder diagnosis providing grounds for further research and pointing to a place for preventive measures among adolescents.

A systematic review and meta-ethnographic synthesis of Mindfulness-based Cognitive Therapy for people with major depression.

BACKGROUND: Mindfulness-based Cognitive Therapy (MBCT) is a relapse-prevention intervention for people experiencing major depression. Three qualitative meta-syntheses investigating experiences of taking part in MBCT and/or Mindfulness-based Stress Reduction (MBSR) across different diagnostic populations reported themes including control, choice, group processes, relationships and struggles. As multiple studies have been published since, we aimed to update, systematically review and synthesize the experiences of participants with depression taking part in MBCT. METHODS: Four databases were searched systematically (PsycInfo, Web of Science, Medline and CINAHL) up to and including 12 November 2021. Twenty-one qualitative studies met the review criteria. All papers were rated as fair using a quality appraisal tool. Meta-ethnography was applied. RESULTS: Across 21 studies of participants with current or previous depression who had participated in MBCT, three overarching themes were developed: 'Becoming skilled and taking action', 'Acceptance' and 'Ambivalence and Variability'. Participants became skilled through engagement in mindfulness practices, reporting increased awareness, perspective and agency over their experiences. Participants developed acceptance towards their experiences, self and others. There was variability and ambivalence regarding participants' expectations and difficulties within mindfulness practices. LIMITATIONS: Many studies were conducted in MBCT-research centres that may hold conflicts of interest. Many studies did not address the impact of the participant-researcher relationship thus potentially affecting their interpretations. Studies were skewed towards the experiences of female participants. CONCLUSIONS: Our findings help to enhance participant confidence in MBCT, alongside understanding the processes of change and the potential for difficulties. MBCT is beneficial and provides meaningful change for many but remains challenging for some.

CME: Light Therapy: Why, What, for Whom, How, and When (And a Postscript about Darkness).

Light therapy has become established as an evidence-based treatment for Seasonal Affective Disorder. Light impacts the timing and stability of circadian rhythms as expressed in sleep, mood, alertness, and cognition. Forty years of clinical trials and open treatment have led to guidelines for patient selection, using light alone or in combination with antidepressants (or lithium for bipolar depression). Mood and sleep disturbances can also respond to adjunct light therapy in a broader set of psychiatric, neurologic and medical illnesses. We specify criteria for choice of treatment devices: optimum dose (10,000 lux), spectrum (white light), exposure duration (30-60 minutes) and timing (early morning). Protocol adjustment requires continual monitoring with attention to rate of improvement and management of potential side effects.

Investigating the effect of magnesium supplement in patients with major depressive disorder under selective serotonin reuptake inhibitor treatment.

Background: Major depression disorder (MDD) is a mental disorder that affects millions of people worldwide. This disease has negative impacts on quality of life and psychological-related functions. This is a multifactorial disorder; both genetic background and environmental factors have their role. Antidepressants are prescribed as the first line of treatment for patients with depressive disorders. Selective serotonin reuptake inhibitor (SSRI) antidepressants are used to treat MDD and anxiety; however, some patients do not respond to them. Regarding that, magnesium plays a major role in mood regulation; therefore, this study aimed to investigate the role of magnesium supplement in patients with MDD and under an SSRI treatment regimen. Methods: In this randomized, double-blind controlled trial, 60 patients with major depressive disorders based on the DSM-V diagnosis referred to Golestan Hospital in Ahvaz, Iran, were included. The eligible patients were categorized randomly into two thirty-people groups receiving magnesium (intervention) and placebo (control) along with SSRI for 6 weeks. To evaluate the depression status, the Beck II test was applied. Subjects were examined before and after the intervention. Results: There was no statistically significant difference between the two groups in terms of demographic characteristics (P > 0.05). The mean Beck scores at the beginning of the study and the second week after the intervention were not different between the two groups (P = 0.97, P = 0.56), whereas the mean Beck scores were lower in the intervention group than in the control group in the fourth and sixth weeks after the intervention (P = 0.02 and P = 0.001, respectively). Conclusion: Administration of Mg supplement for at least 6 weeks might improve depression symptoms. It can also be considered as a potential adjunct treatment option for MDD patients who are under SSRI treatment.

Association between Traditional Chinese medicine and a lower risk of dementia in patients with major depression: A case-control study.

ETHNOPHARMACOLOGICAL RELEVANCE: Major depression is an important risk factor for dementia. Traditional Chinese medicine (TCM) can alleviate the symptoms of major depression. However, it is unclear whether TCM decreases the risk of dementia in patients with major depression. Therefore, in this nationwide case-control study, we aimed to evaluate the association between TCM and the risk of dementia. MATERIALS AND METHODS: We included 31,981 major depression patients with dementia from the National Dementia Database as the case group, and 4391 major depression patients without dementia from a one-million random sample database as the control group. We matched age (plus or minus two years), sex, and year of depression diagnosis based on a 1:4 ratio. RESULT: There were 11,724 and 2931 patients in the case and control groups, respectively. Based on a conditional logistic regression analysis, the TCM groups exhibited significantly lower odds ratios with a 95% confidence interval of 0.83 (0.74-0.91). TCM treatment for more than 90 days, dispersing Qi, and activating blood circulation resulted in lower dementia risk with the following odds ratios and 95% confidence intervals: 0.60 (0.56-0.68), 0.87 (0.74-1.08), and 0.66 (0.49-0.81). CONCLUSION: The results suggest that TCM is associated with lower dementia risk in major depression patients.