1. In this study, individual patient and study-level analyzes revealed a negative correlation between placebo response and treatment effect, as measured with the Positive and Negative Syndrome Scale (PANSS) to assess the severity of symptoms in schizophrenic patients.
2. In addition, heterogeneity of treatment effects showed variation in antipsychotic-specific effects in people with schizophrenia.
Level of evidence assessment: 1 (Excellent)
People with schizophrenia have a wide range of symptomatic responses to antipsychotic treatment, as is commonly observed by practicing psychiatrists. Given the possible benefits of tailored treatment optimized for patients, it is essential to quantify the heterogeneity of treatment effects (defined as variations in drug-specific effects) in schizophrenia. Specifically, it is important to further elucidate the relationship between treatment effect and placebo response. Without this feature, a growing body of literature cannot be interpreted accurately.
The present study estimated this correlation using individual patient data and study-level treatment effects from clinical trials, which were applied to a variability meta-analysis to formally estimate the heterogeneity of antipsychotic effects in schizophrenic patients. Individual data from adult patients aged 18-65 receiving antipsychotic treatment (n=384) or placebo (n=88) were included from the Yale University Open Data Access database. Study-level data from schizophrenic patients aged 18-65 years were included in a meta-analysis of 66 clinical trials (n=17,202). The results of the study analyzed the severity of symptoms in schizophrenic patients using the PANSS.
The study results demonstrated that both in the individual patient analysis and at the study level, there was a negative correlation between placebo response and treatment effect. Additionally, a meta-analysis of treatment effect heterogeneity using the most conservative of these estimates found variation in antipsychotic-specific effects among people with schizophrenia. Notably, the top quartile of individuals experienced healthy treatment effects of 17.7 points or better on the PANSS total score, while the bottom quartile had a worse treatment effect than placebo. However, this study was limited by correlation detected in study-level searches that may not reflect person-level correlation, known as aggregation bias. Nevertheless, this study was significant in supporting the notion that in schizophrenia there is significant interindividual variation in terms of symptomatic response to antipsychotic treatment.
1. AKL-T03 is a digital therapy that works by activating the frontoparietal networks of the brain to increase attention and related attentional control processes.
2. In this study, treatment with AKL-T03 led to a significant improvement in sustained attention compared to control, in patients with depression.
Level of evidence assessment: 2 (good)
Concentration, decision-making, slow thinking, and forgetfulness are all reported challenges for people with major depressive disorder. Several studies have shown that patients with depression perform worse on neuropsychological tests of memory, attention, and executive function. Patients with significant depression and cognitive abnormalities have a limited number of treatment options. The aim of the study was to see if AKL-T03, an experimental digital therapeutic device that triggers the brain’s frontoparietal networks, could improve cognitive function in adults with depression and documented cognitive impairment.
In this double-blind randomized controlled trial, patients aged 22 to 55 years with mild to moderate residual depression and cognitive impairment while taking stable antidepressants were included. Patients with comorbid psychiatric illnesses and active suicide risk or ideation were excluded. Patients were randomized to either the AKL-T03 intervention (n=37) or an educational-style digital control (n=37). The primary outcome of the study assessed the change in sustained attention from baseline as measured by reaction time for performance using the Test of Variables of Attention (TOVA).
The results demonstrated that AKL-T03 significantly improved performance on the primary outcome of sustained attention in adults compared to the control condition. However, this study was limited because it used particular clinical research centers and inclusion and exclusion criteria, which could have limited the generalizability of the results. Anyway, the intervention was well supported. The digital aspect of the intervention makes it more accessible to patients who would otherwise be unable to find a solution to their depression-related cognitive impairments.
1. In most situations, CUD in probands and families started before the mood disorder subtypes.
2. An increased risk of cannabis use disorder (CUD) in family members of probands with bipolar-II disorder suggests that CUD and BP-II may have a similar underlying illness.
Level of evidence assessment: 2 (good)
The most widely used illegal substance in the United States is cannabis. It is the most common substance use disorder, affecting 4.8 million people in the United States in 2019. Previous literature has identified a link between CUD and other psychiatric comorbidities, such as depression and the bipolar. disorder. However, the stability of these conclusions has been called into question by the inconsistency found across different studies. As such, this study aimed to further elucidate the potential mechanisms underlying the relationship between CUD and mood disorders.
In this controlled cross-sectional family study conducted in Washington, DC, USA, semi-structured diagnostic interviews and family history records were used to assess lifetime DSM-IV disorders in parents and probands. With additional factors taken into account, mixed-effects measures were used to assess familial aggregation and coaggregation of CUDs with mood disorders. 586 adult probands (55 with CUD, 186 with bipolar disorder) and 698 first-degree relatives (68 with CUD, 91 with bipolar disorder) who were proficient in English were included in the study. The primary outcome assessed for lifetime CUD in first-degree relatives.
The results of the study supported family reunification of CUD. CUD among probands was associated with CUD among parents. Additionally, bipolar II (BP-II) disorder in probands was associated with an increased risk of CUD in relatives. Interestingly, bipolar I disorder and major depressive disorder in probands were not associated with CUD in parents. Finally, among parents, CUD was associated with middle age, major depressive disorder, and BP-II. However, this study was limited by not having the ability to investigate potential links between mood disorders and CUD due to cross-sectional data. Also, a limited percentage of applicants and their families meet the CUD criteria, despite the large overall sample size. Nevertheless, these results indicate a possible role of BP-II treatments in the prevention of CUD.
1. Excitatory noninvasive brain stimulation (NIBS) intervention protocols on the left dorsolateral prefrontal cortex were associated with significant improvements in the severity of negative symptoms.
2. None of the NIBS approaches studied were associated with significantly different changes in the severity of positive symptoms compared to control groups.
Level of evidence assessment: 2 (good)
According to the 2019 Global Burden of Disease Study, schizophrenia represents a significant burden worldwide. The negative symptoms of schizophrenia have a significant impact on patients’ quality of life and unfortunately respond poorly to antipsychotics. As an alternative, noninvasive brain stimulation therapies (NIBS) may be successful in relieving these symptoms, but their effectiveness has not yet been studied. Accordingly, the aim of the present study was to assess the effectiveness of NIBS interventions in alleviating the negative symptoms of schizophrenia.
Of 4867 records identified, this study included 48 randomized clinical trials (n=211, 30.6% female) from database inception to December 2021. Studies were included if they included patients with schizophrenia who have undergone NIBS interventions. Studies were excluded if they did not examine negative symptoms and included patients other than schizophrenia/schizoaffective disorder. PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses) were followed. Pairwise meta-analytic procedures were conducted using a random-effects model. The results demonstrated that NIBS treatments on the left dorsolateral prefrontal cortex were linked to a significant reduction in the severity of negative symptoms. Moreover, none of the NIBS approaches studied were associated with significantly different changes in the severity of positive symptoms.
Despite these findings, the study was limited by participant heterogeneity which may have underpowered the study. However, the present study demonstrated the potential of NIBS to alleviate the negative symptoms of schizophrenia.
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