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Neuroscience Jun 2024Major depressive disorder is one of the most prevalent psychiatric diseases, and up to 30-40% of patients remain symptomatic despite treatment. Novel therapies are... (Review)
Review
Major depressive disorder is one of the most prevalent psychiatric diseases, and up to 30-40% of patients remain symptomatic despite treatment. Novel therapies are sorely needed, and animal models may be used to elucidate fundamental neurobiological processes that contribute to human disease states. We conducted a systematic review of current preclinical approaches to investigating treatment resistance with the goal of describing a path forward for improving our understanding of treatment resistant depression. We conducted a broad literature search to identify studies relevant to the preclinical investigation of treatment resistant depression. We followed PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) guidelines and included all relevant studies. We identified 467 studies in our initial search. Of these studies, we included 69 in our systematic review after applying our inclusion/exclusion criteria. We identified 10 broad strategies for investigating treatment resistance in animal models. Stress hormone administration was the most commonly used model, and the most common behavioral test was the forced swim test. We systematically identified and reviewed current approaches for gaining insight into the neurobiology underlying treatment resistant depression using animal models. Each approach has its advantages and disadvantages, but all require careful consideration of their potential limitations regarding therapeutic translation. An enhanced understanding of treatment resistant depression is sorely needed given the burden of disease and lack of effective therapies.
Topics: Animals; Disease Models, Animal; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Humans; Depressive Disorder, Major
PubMed: 38697464
DOI: 10.1016/j.neuroscience.2024.04.013 -
Trends in Psychiatry and Psychotherapy Apr 2024Recent guidelines on depressive disorders suggest a combination of antidepressants and psychotherapy in case of moderate to severe symptomatology. While cognitive...
INTRODUCTION
Recent guidelines on depressive disorders suggest a combination of antidepressants and psychotherapy in case of moderate to severe symptomatology. While cognitive behavioral therapy and interpersonal therapy are the most investigated interventions, psychodynamic psychotherapies have been less explored.
OBJECTIVE
The aim of this paper is to systematically review literature data on the efficacy of shortterm psychodynamic psychotherapy (STPP) in combination with antidepressants in the treatment of depressive disorders, focusing both on short and on long-term results and on potential moderators that could influence its effectiveness.
METHODS
The systematic review was conducted using the PRISMA guidelines. Databases searched were PubMed, Ovid, Scopus, and Cochrane Library, from inception to August 2023.
RESULTS
Adding STPP to medications in the first six months of treatment didn't influence remission rates, but improved acceptability, work adjustment, interpersonal relationships, social role functioning, hospitalization rates and cost-effectiveness. After 12 months, a significant difference in remission rates arised, favouring combined therapy. In a long-term perspective, adding STPP to pharmacotherapy reduced the recurrence rate by almost 50%. STPP has proven to be more effective in longer depressive episodes, in more severe depressions and in patients with a childhood abuse history. Instead, STPP had no impact on major depressive disorder with comorbid Obsessive-Compulsive Disorder (OCD).
CONCLUSIONS
Combining STPP with antidepressants appeared to be helpful both in a short-term and in a long-term perspective. Still, there are few rigorous studies with large samples and further research is needed to identify which subgroups of patients may benefit more from STPP.
PubMed: 38687843
DOI: 10.47626/2237-6089-2023-0764 -
CNS Spectrums Apr 2024Obsessive-compulsive disorder (OCD) is a prevalent condition with multifactorial etiology involving genetic and environmental factors. The present study aims to... (Review)
Review
Obsessive-compulsive disorder (OCD) is a prevalent condition with multifactorial etiology involving genetic and environmental factors. The present study aims to summarize the correlates of stressful life events (SLEs) in OCD by reviewing studies comparing OCD associated or not with SLEs before its onset. To do so, a systematic review was performed by searching PubMed, Web of Science, Scopus, and PsycINFO databases for studies published between the database's inception and November 27, 2023. Studies including individuals whose OCD was precipitated or not by SLEs (SLEs OCD and NSLEs OCD, respectively) were assessed. Effect sizes or odds ratios were then calculated to identify the strength of association between SLEs and clinical characteristics, such as gender, age of onset, family history of OCD, severity of OCD symptoms, depressive symptoms, and mood comorbidities among patients with OCD. Out of the 4083 records initially identified, 5 studies met the inclusion criteria and 3 were comparable through a meta-analysis. Notably, the analyses were limited by the small number of studies available in the literature. The meta-analysis demonstrated SLEs OCD to be associated with female gender, later OCD onset, and increased comorbidity rates with mood disorders. Despite the cross-sectional nature of the reviewed studies, women may be more vulnerable to develop a later onset of OCD following SLEs, which may also lead to mood disorders. Caution is needed to avoid prematurely classifying this presentation as a distinct subtype of OCD.
PubMed: 38685590
DOI: 10.1017/S1092852924000269 -
Human Psychopharmacology Apr 2024Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential... (Review)
Review
BACKGROUND
Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential therapeutic option for managing manic episodes associated with bipolar disorder (BD). This review aims to assess the existing evidence base for endoxifen in BD treatment and evaluate the strengths and limitations of current research findings.
METHODS
A systematic search was conducted on Medline, Embase, and Web of Science databases. We included studies published in English that used endoxifen in BD, alongside any relevant studies identified through manual searching and conference papers with full-text availability. Information pertaining to dose, duration, clinical effects, and safety profiles was extracted from the included studies. The Cochrane Risk of Bias 2 tool was used to assess the risk of bias in clinical trials.
RESULTS
The final review included seven case reports (including two conference presentations), two clinical trials, and one prospective study. Most studies administered endoxifen 8 mg and reported an improvement in manic symptoms. Several case reports included patients with comorbid substance use, and most patients received mood stabilizers concurrently. Few reports lacked any structured outcome measures. The clinical trials used divalproex 1000 mg as an active comparator, which was deemed sub-therapeutic. Despite being multicentric, the first trial lacked data on center-wise recruitment, and certain methodological concerns were observed across the included trials. There were no serious adverse effects noted, except for a significant elevation in lipid profile within a 3-week period. Limited data were available regarding endoxifen efficacy and safety in mixed episodes, depressive episodes, and maintenance treatment.
CONCLUSION
There is a paucity of research on the efficacy and safety of endoxifen in BD. While existing evidence suggests short-term efficacy in manic episodes, significant limitations were identified in most of the included studies. Further research is imperative to establish the efficacy and safety of endoxifen in BD before considering its recommendation as a viable treatment option.
PubMed: 38683854
DOI: 10.1002/hup.2899 -
Focus (American Psychiatric Publishing) Apr 2024Individuals with autism spectrum disorder often present somatic and/or psychiatric co-morbid disorders. The DSM-5 allows for consideration of additional diagnoses...
OBJECTIVE
Individuals with autism spectrum disorder often present somatic and/or psychiatric co-morbid disorders. The DSM-5 allows for consideration of additional diagnoses besides ASD and may have impacted the prevalence of co-morbidities as well as being limited in capturing the true differences in prevalence observed between males and females. We describe the prevalence of ASD and frequently observed co-morbidities in children and adolescents (<18 years) in the United States and five European countries.
METHODS
Two systematic literature reviews were conducted in PubMed and Embase for the period 2014-2019 and focusing on the prevalence of ASD and nine co-morbidities of interest based on their frequency and/or severity: Attention Deficit Hyperactivity Disorder (ADHD), anxiety, depressive disorders, epilepsy, intellectual disability (ID), sleep disorders, sight/hearing impairment/loss, and gastro-intestinal syndromes (GI).
RESULTS
Thirteen studies on prevalence of ASD and 33 on prevalence of co-morbidities were included. Prevalence of ASD was 1.70 and 1.85% in U.S children aged 4 and 8 years respectively, while prevalence in Europe ranged between 0.38 and 1.55%. Additionally, current evidence is supportive of a global increase in ASD prevalence over the past years. Substantial heterogeneity in prevalence of co-morbidities was observed: ADHD (0.00-86.00%), anxiety (0.00-82.20%), depressive disorders (0.00-74.80%), epilepsy (2.80-77.50%), ID (0.00-91.70%), sleep disorders (2.08-72.50%), sight/hearing impairment/loss (0.00-14.90%/0.00-4.90%), and GI syndromes (0.00-67.80%). Studies were heterogeneous in terms of design and method to estimate prevalence. Gender appears to represent a risk factor for co-morbid ADHD (higher in males) and epilepsy/seizure (higher in females) while age is also associated with ADHD and anxiety (increasing until adolescence).
CONCLUSION
Our results provide a descriptive review of the prevalence of ASD and its co-morbidities in children and adolescents. These insights can be valuable for clinicians and parents/guardians of autistic children. Prevalence of ASD has increased over time while co-morbidities bring additional heterogeneity to the clinical presentation, which further advocates for personalized approaches to treatment and support. Having a clear understanding of the prevalence of ASD and its co-morbidities is important to raise awareness among stakeholders.Appeared originally in 2021; 12:744709.
PubMed: 38680973
DOI: 10.1176/appi.focus.24022005 -
Campbell Systematic Reviews Jun 2024Among youth, symptoms of depression, anxiety, and alcohol use are associated with considerable illness and disability. Youth face many personal and health system... (Review)
Review
BACKGROUND
Among youth, symptoms of depression, anxiety, and alcohol use are associated with considerable illness and disability. Youth face many personal and health system barriers in accessing mental health care. Mobile applications (apps) offer youth potentially accessible, scalable, and anonymous therapy and other support. Recent systematic reviews on apps to reduce mental health symptoms among youth have reported uncertain effectiveness, but analyses based on the type of app-delivered therapy are limited.
OBJECTIVES
We conducted this systematic review with youth co-researchers to ensure that this review addressed the questions that were most important to them. The objective of this review is to synthesize the best available evidence on the effectiveness of mobile apps for the reduction of depressive symptoms (depression, generalized anxiety, psychological distress) and alcohol use among youth.
SEARCH METHODS
We conducted electronic searches of the following bibliographic databases for studies published between January 1, 2008, and July 1, 2022: MEDLINE (via Ovid), Embase (via Ovid), PsycINFO (via Ovid), CINAHL (via EBSCOHost), and CENTRAL (via the Cochrane Library). The search used a combination of indexed terms, free text words, and MeSH headings. We manually screened the references of relevant systematic reviews and included randomized controlled trials (RCTs) for additional eligible studies, and contacted authors for full reports of identified trial registries or protocols.
SELECTION CRITERIA
We included RCTs conducted among youth aged 15-24 years from any setting. We did not exclude populations on the basis of gender, socioeconomic status, geographic location or other personal characteristics. We included studies which assessed the effectiveness of app-delivered mental health support or therapy interventions that targeted the management of depressive disorders and/or alcohol use disorders. We excluded apps that targeted general wellness, apps which focused on prevention of psychological disorders and apps that targeted bipolar disorder, psychosis, post-traumatic stress disorder, attention-deficit hyperactivity disorder, substance use disorders (aside from alcohol), and sleep disorders. Eligible comparisons included usual care, no intervention, wait-list control, alternative or controlled mobile applications. We included studies which reported outcomes on depressive symptoms, anxiety symptoms, alcohol use and psychological distress over any follow-up period.
DATA COLLECTION AND ANALYSIS
We standardized the PICO definitions (population, intervention, comparison, and outcome) of each included study and grouped studies by the type of therapy or support offered by the app. Whenever app design and clinical homogeneity allowed, we meta-analyzed outcomes using a random-effects model. Outcome data measured using categorical scales were synthesized using odds ratios. Outcome data measured using continuous scales were synthesized as the standardized mean difference. We assessed the methodological quality of each included study using the Cochrane Risk of Bias 2.0 tool and we assessed certainty of the evidence using the GRADE approach.
MAIN RESULTS
From 5280 unique citations, we included 36 RCTs published in 37 reports and conducted in 15 different countries (7984 participants). Among the 36 included trials, we assessed two with an overall low risk of bias, 8 trials with some concern regarding risk of bias, and 26 trials with a high risk of bias. Interventions varied in the type of therapy or supports offered. The most common intervention designs employed mindfulness training, cognitive behavioral therapy (CBT), or a combination of the two (mindfulness + CBT). However, other interventions also included self-monitoring, medication reminders, cognitive bias modification or positive stimulation, dialectical behavioral therapy, gamified health promotion, or social skill building. Mindfulness apps led to short term improvements in depressive symptoms when compared to a withheld control (SMD = -0.36; 95% CI [-0.63, -0.10]; = 0.007, = 3 RCTs, GRADE: very low certainty) and when compared to an active control (SMD = -0.27; 95% CI [-0.53, -0.01]; = 0.04, = 2 RCTs, GRADE: very low). Apps delivering this type of support also significantly improved symptoms of anxiety when compared to a withheld control (SMD = -0.35; 95% CI [-0.60, -0.09]; = 0.008, = 3 RCTs, GRADE: very low) but not when compared to an active control (SMD = -0.24; 95% CI [-0.50, 0.02]; = 0.07, = 2 RCTs, GRADE: very low). Mindfulness apps showed improvements in psychological stress that approached statistical significance among participants receiving the mindfulness mobile apps compared to those in the withheld control (SMD = -0.27; 95% CI [-0.56, 0.03]; = .07, = 4 RCTs, GRADE: very low). CBT apps also led to short-term improvements in depressive symptoms when compared to a withheld control (SMD = -0.40; 95% CI [-0.80, 0.01]; = 0.05, = 2 RCTs, GRADE: very low) and when compared to an active control (SMD = -0.59; 95% CI [-0.98, -0.19]; = 0.003, = 2 RCTs, GRADE: very low). CBT-based apps also improved symptoms of anxiety compared to a withheld control (SMD = -0.51; 95% CI [-0.94, -0.09]; = 0.02, = 3 RCTs, GRADE: very low) but not when compared to an active control (SMD = -0.26; 95% CI [-1.11, 0.59]; = 0.55, = 3 RCTs, GRADE: very low). Apps which combined mindfulness and CBT did not significantly improve symptoms of depression (SMD = -0.20; 95% CI [-0.42, 0.02]; = 0.07, = 2 RCTs, GRADE: very low) or anxiety (SMD = -0.21; 95% CI [-0.49, 0.07]; = 0.14, = 2 RCTs, GRADE: very low). However, these apps did improve psychological distress (SMD = -0.43; 95% CI [-0.74, -0.12]; = 0.006, = 2 RCTs, GRADE: very low). The results of trials on apps to reduce alcohol use were inconsistent. We did not identify any harms associated with the use of apps to manage mental health concerns. All effectiveness results had a very low certainty of evidence rating using the GRADE approach, meaning that apps which deliver therapy or other mental health support may reduce symptoms of depression, anxiety and psychological distress but the evidence is very uncertain.
AUTHORS' CONCLUSIONS
We reviewed evidence from 36 trials conducted among youth. According to our meta-analyses, the evidence is very uncertain about the effect of apps on depression, anxiety, psychological distress, and alcohol use. Very few effects were interpreted to be of clinical importance. Most of the RCTs were small studies focusing on efficacy for youth at risk for depressive symptoms. Larger trials are needed to evaluate effectiveness and allow for further analysis of subgroup differences. Longer trials are also needed to better estimate the clinical importance of these apps over the long term.
PubMed: 38680950
DOI: 10.1002/cl2.1398 -
Reviews in the Neurosciences Apr 2024Cognitive disorders such as major depressive disorder and bipolar disorder severely compromise brain function and neuronal activity. Treatments to restore cognitive... (Review)
Review
Cognitive disorders such as major depressive disorder and bipolar disorder severely compromise brain function and neuronal activity. Treatments to restore cognitive abilities can have severe side effects due to their intense and excitatory nature, in addition to the fact that they are expensive and invasive. Low-field magnetic stimulation (LFMS) is a novel non-invasive proposed treatment for cognitive disorders. It repairs issues in the brain by altering deep cortical areas with treatments of low-intensity magnetic stimulation. This paper aims to summarize the current literature on the effects and results of LFMS in cognitive disorders. We developed a search strategy to identify relevant studies utilizing LFMS and systematically searched eight scientific databases. Our review suggests that LFMS could be a viable and effective treatment for multiple cognitive disorders, especially major depressive disorder. Additionally, longer, more frequent, and more personalized LFMS treatments tend to be more efficacious.
PubMed: 38671560
DOI: 10.1515/revneuro-2024-0023 -
BMC Psychology Apr 2024Covid-19 has disrupted the lives of many and resulted in high prevalence rates of mental disorders. Despite a vast amount of research into the social determinants of...
A systematic review on the relationship between socioeconomic conditions and emotional disorder symptoms during Covid-19: unearthing the potential role of economic concerns and financial strain.
BACKGROUND
Covid-19 has disrupted the lives of many and resulted in high prevalence rates of mental disorders. Despite a vast amount of research into the social determinants of mental health during Covid-19, little is known about whether the results are consistent with the social gradient in mental health. Here we report a systematic review of studies that investigated how socioeconomic condition (SEC)-a multifaceted construct that measures a person's socioeconomic standing in society, using indicators such as education and income, predicts emotional health (depression and anxiety) risk during the pandemic. Furthermore, we examined which classes of SEC indicators would best predict symptoms of emotional disorders.
METHODS
Following PRISMA guidelines, we conducted search over six databases, including Scopus, PubMed, etc., between November 4, 2021 and November 11, 2021 for studies that investigated how SEC indicators predict emotional health risks during Covid-19, after obtaining approval from PROSPERO (ID: CRD42021288508). Using Covidence as the platform, 362 articles (324 cross-sectional/repeated cross-sectional and 38 longitudinal) were included in this review according to the eligibility criteria. We categorized SEC indicators into 'actual versus perceived' and 'static versus fluid' classes to explore their differential effects on emotional health.
RESULTS
Out of the 1479 SEC indicators used in these 362 studies, our results showed that 43.68% of the SEC indicators showed 'expected' results (i.e., higher SEC predicting better emotional health outcomes); 51.86% reported non-significant results and 4.46% reported the reverse. Economic concerns (67.16% expected results) and financial strains (64.16%) emerged as the best predictors while education (26.85%) and living conditions (30.14%) were the worst.
CONCLUSIONS
This review summarizes how different SEC indicators influenced emotional health risks across 98 countries, with a total of 5,677,007 participants, ranging from high to low-income countries. Our findings showed that not all SEC indicators were strongly predictive of emotional health risks. In fact, over half of the SEC indicators studied showed a null effect. We found that perceived and fluid SEC indicators, particularly economic concerns and financial strain could best predict depressive and anxiety symptoms. These findings have implications for policymakers to further understand how different SEC classes affect mental health during a pandemic in order to tackle associated social issues effectively.
Topics: Humans; COVID-19; Financial Stress; Socioeconomic Factors; Depression; Anxiety; Mental Health; SARS-CoV-2
PubMed: 38671542
DOI: 10.1186/s40359-024-01715-8 -
Bipolar Disorders Apr 2024Clinicians are often hesitant to prescribe psychostimulants in bipolar disorder (BD) due to concerns of inducing (hypo)mania, despite limited published evidence on... (Review)
Review
OBJECTIVES
Clinicians are often hesitant to prescribe psychostimulants in bipolar disorder (BD) due to concerns of inducing (hypo)mania, despite limited published evidence on associations between prescribed psychostimulant use and recurrence of mood episodes in BD. The current systematic review and meta-analysis evaluated the emergence of (hypo)manic symptoms in patients with BD receiving prescribed psychostimulants or other pro-cognitive medications in euthymic or depressive states.
METHODS
A systematic search was performed of MEDLINE, Embase, and PsychINFO from inception to April 5, 2023 and search of Clinicaltrials.gov and Clinicaltrialsregister.eu for unpublished data. References of included studies were hand-searched. Randomized trials and prospective longitudinal studies that evaluated psychostimulants and non-stimulant medications recommended for the treatment of ADHD by the Canadian ADHD practice guidelines were included. The review was reported in line with PRISMA guidelines and was preregistered on PROSPERO (CRD42022358588).
RESULTS
After screening 414 unique records, we included 27 studies, of which five reported data that was quantitatively synthesized (n = 1653). The use of psychostimulants in BD was not associated with increased scores on the Young Mania Rating Scale in patients who were in a euthymic or depressed state (SMD IV -0.17; 95% CI, -0.40 to 0.06) compared to placebo. There was a high degree of study-level heterogeneity (I = 80%). A qualitative synthesis of studies revealed a limited risk of medication-induced manic symptoms.
CONCLUSIONS
Our review provides preliminary evidence to suggest psychostimulants and non-stimulant ADHD medications have a limited risk of precipitating (hypo)mania symptoms. More extensive studies evaluating the safety and efficacy of these medications are warranted.
PubMed: 38670627
DOI: 10.1111/bdi.13440 -
PloS One 2024To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy and safety of aripiprazole or... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression or major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.
OBJECTIVES
To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression (TRD) or major depressive disorder(MDD).
METHODS
We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April 2023 for RCT, which evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching for patients with TRD or MDD. Outcomes measured were changes in the Montgomery-Asberg Depression Rating Scale (MADRS), response and remission rate, and serious adverse events.
RESULTS
Five RCTs, including 4480 patients, were included for meta-analysis. Among them, two RCTs were rated as "high risk" in three aspects (allocation concealment, blinding of participants and personnel and blinding of outcome assessment) because of the non-blind method, and the quality evaluation of the remaining works of literature was "low risk". Augmentation treatment with Aripiprazole (A-ARI) was associated with a significant higher response rate compared with augmentation treatment with bupropion (A-BUP) (RR: 1.15; 95% CI: 1.05, 1.25; P = 0.0007; I2 = 23%). Besides, A-ARI had a significant higher remission rate compared with switching to bupropion (S-BUP) (RR: 1.22; 95% CI: 1.00, 1.49; P = 0.05; I2 = 59%) and A-BUP had a significant higher remission rate compared with S-BUP (RR: 1.20; 95% CI: 1.06, 1.36; P = 0.0004; I2 = 0%). In addition, there was no significant difference in remission rate(RR: 1.05; 95% CI: 0.94, 1.17; P = 0.42; I2 = 33%), improvement of MADRS(WMD: -2.07; 95% CI: -5.84, 1.70; P = 0.28; I2 = 70%) between A-ARI and A-BUP. No significant difference was observed in adverse events and serious adverse events among the three treatment strategies.
CONCLUSIONS
A-ARI may be a better comprehensive antidepressant treatment strategy than A-BUP or S-BUP for patients with TRD or MDD. More large-scale, multi-center, double-blind RCTs are needed to further evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching treatment strategies.
Topics: Aripiprazole; Bupropion; Humans; Depressive Disorder, Major; Randomized Controlled Trials as Topic; Depressive Disorder, Treatment-Resistant; Treatment Outcome; Drug Therapy, Combination
PubMed: 38669232
DOI: 10.1371/journal.pone.0299020