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Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD's clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the need for precise biomarkers to guide treatment choices in TRD, herein we introduce the SelecTool Project. This initiative focuses on developing (WorkPlane 1/WP1) and conducting preliminary validation (WorkPlane 2/WP2) of a computational tool (SelecTool) that integrates clinical data, neurophysiological (EEG) and peripheral (blood sample) biomarkers through a machine-learning framework designed to optimize TRD treatment protocols. The SelecTool project aims to enhance clinical decision-making by enabling the selection of personalized interventions. It leverages multi-modal data analysis to navigate treatment choices towards two validated therapeutic options for TRD: esketamine nasal spray (ESK-NS) and accelerated repetitive Transcranial Magnetic Stimulation (arTMS). In WP1, 100 subjects with TRD will be randomized to receive either ESK-NS or arTMS, with comprehensive evaluations encompassing neurophysiological (EEG), clinical (psychometric scales), and peripheral (blood samples) assessments both at baseline (T0) and one month post-treatment initiation (T1). WP2 will utilize the data collected in WP1 to train the SelecTool algorithm, followed by its application in a second, out-of-sample cohort of 20 TRD subjects, assigning treatments based on the tool's recommendations. Ultimately, this research seeks to revolutionize the treatment of TRD by employing advanced machine learning strategies and thorough data analysis, aimed at unraveling the complex neurobiological landscape of depression. This effort is expected to provide pivotal insights that will promote the development of more effective and individually tailored treatment strategies, thus addressing a significant void in current TRD management and potentially reducing its profound societal and economic burdens.
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The article presents a systematic literature review on the use and the psychiatric implications of over-the-counter drugs (OTC), prescription-only-medications (POM), and new psychoactive substances (NPS) within custodial settings. The searches wer carried out on 2 November 2022 on PubMed, Scopus, and Web of Science in line with PRISMA guidelines. A total of 538 records were identified, of which 37 met the inclusion criteria. Findings showed the most prevalent NPS and OTC and POM classes reported in prisons were synthetic cannabinoids receptor agonists (SCRAs) and opioids, respectively. NPS markets were shown to be in constant evolution following the pace of legislations aimed to reduce their spread. The use of such substances heavily impacts the conditions and rehabilitation of persons in custody, with consequent physical and mental health risks. It is important to raise awareness of the use and misuse of such substances in prisons (i) from an early warning perspective for law enforcement and policy makers (ii) to prompt doctors to cautiously prescribe substances that may be misused (iii) to improve and increase access to treatment provided (iv) to add such substances to routine toxicological screening procedures (v) to improve harm reduction programmes.
Subject(s)
Nonprescription Drugs , Psychotropic Drugs , Substance-Related Disorders , Humans , Substance-Related Disorders/epidemiology , Prisons , Prescription Drugs , PrisonersABSTRACT
BACKGROUND: This systematic review aims to comprehensively explore the impact of psychostimulant substances on neurotrophic and inflammatory pathways, including brain-derived neurotrophic factor (BDNF), pro-BDNF, cortisol, dehydroepiandrosterone sulfate (DHEAS), thiobarbituric acid reactive substances (TBARS), interleukins, and the role of genetic factors. The study seeks to address existing gaps in the literature by providing a thorough evaluation of neurotrophic and inflammatory system alterations associated with different stages of psychostimulant dependence for a more nuanced understanding of substance use disorder (SUD) neurobiology. METHODS: A systematic review was conducted in PubMed, Scopus, and Web of Science databases following the PRISMA guidelines. The research encompasses 50 studies with a participant pool totaling 6792 individuals using psychostimulant substances. RESULTS: Key findings include diverse impacts of cocaine on BDNF levels, mainly consisting of their significant increase during withdrawal. In contrast, NGF showed an opposite behavior, reducing during withdrawal. Cortisol and DHEAS levels exhibited relevant increases after psychostimulant use, while TBARS showed conflicting results. Genetic investigations predominantly focused on the Val66Met polymorphism of the BDNF gene, revealing associations with susceptibility to stimulant addiction. CONCLUSIONS: Neurotrophins and inflammatory molecules play a significant role in the pathophysiological mechanisms following psychostimulant use. A better understanding of their complex interplay could aid clinicians in identifying biomarkers of different disease stages. Moreover, clinical interventions designed to interfere with neurotrophic and inflammatory pathways could possibly lead to craving-modulatory strategies and reduce pathological neuronal and systemic consequences of psychostimulant use.
Subject(s)
Biomarkers , Central Nervous System Stimulants , Nerve Growth Factors , Oxidative Stress , Substance-Related Disorders , Humans , Biomarkers/metabolism , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Central Nervous System Stimulants/pharmacology , Hydrocortisone/metabolism , Nerve Growth Factors/genetics , Nerve Growth Factors/metabolism , Oxidative Stress/drug effects , Oxidative Stress/physiology , Substance-Related Disorders/geneticsABSTRACT
Background: Dual disorders (DD) entail the coexistence of a substance use disorder (SUD) and another mental health condition, often within psychotic and affective disorders. This study aims to evaluate lurasidone, an innovative atypical antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder and concurrent comorbidities of alcohol use disorder/substance use disorder (AUD/SUD). Methods: A cohort of 23 subjects diagnosed with schizophrenia spectrum disorder and comorbid AUD/SUD underwent psychometric assessments at baseline (T0) and one-month (T1) post-lurasidone initiation. Results: Lurasidone exhibited significant reductions in psychopathological burden, evidenced by decreased total PANSS scores (Z = 2.574, p = 0.011). Positive symptoms, substance craving (VAS Craving; Z = 3.202, p = 0.001), and aggressivity (MOAS scale; Z = 2.000, p = 0.050) were notably reduced. Clinical Global Impression (CGI) scores significantly improved (Z = 2.934, p = 0.003). Quality of life enhancements were observed in SF-36 subscales (energy, emotional well-being, and social functioning) (p < 0.05) and Q-LES-Q-SF scale (Z = -2.341, p = 0.021). A safety analysis indicated lurasidone's good tolerability, with only 8.7% reporting discontinuation due to side effects. Conclusions: This study offers initial evidence supporting lurasidone's efficacy and safety in dual diagnoses, highlighting positive effects on psychopathology, substance craving, and quality of life. These findings emphasize the need for tailored, comprehensive treatment strategies in managing the complexities of this patient population.
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BACKGROUND: Dual disorders (DDs) involve the coexistence of a substance use disorder (SUD) with another mental illness, often from the psychotic and affective categories. They are quite common in clinical practice and present significant challenges for both diagnosis and treatment. This study explores the effectiveness of brexpiprazole, a third-generation antipsychotic, in an Italian sample of individuals diagnosed with schizophrenia spectrum disorder and a comorbid SUD. METHODS: Twenty-four patients, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and enrolled in several Italian hospitals, underwent a psychometric assessment at baseline (T0) and one month (T1) after starting brexpiprazole treatment administered at a mean dosage of 2 mg/day. RESULTS: Brexpiprazole demonstrated significant reductions in psychopathological burden (Positive and Negative Syndrome Scale/PANSS total score: p < 0.001). Positive (p = 0.003) and negative (p = 0.028) symptoms, substance cravings (VAS craving: p = 0.039), and aggression (MOAS scale: p = 0.003) were notably reduced. Quality of life improved according to the 36-item Short Form Health Survey (SF-36) subscales (p < 0.005). CONCLUSIONS: This study provides initial evidence supporting brexpiprazole's efficacy and safety in this complex patient population, with positive effects not only on psychopathology and quality of life, but also on cravings. Further studies involving larger cohorts of subjects and extended follow-up periods are needed.
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OBJECTIVE: Peripartum depression is defined as the onset of depressive symptoms during pregnancy or within 12 months postpartum and affects 11.9% of women. Currently, its treatment often involves psychotherapy and antidepressants, though only one medication has been specifically approved to treat it. In this context, novel, safe non-pharmacological treatment options have gained growing interest. The present review aims to assess current literature on possible side effects on the developing fetus/newborn of Transcranial Magnetic Stimulation (TMS) use in women with peripartum depression. METHOD: A systematic search was performed using the PubMed, Scopus and Web of Science databases. PRISMA and PROSPERO guidelines were applied. The risk of bias assessment was performed using the Cochrane risk of bias tool version 2.0. RESULTS: Twenty-three studies were included in our systematic review, two were randomized controlled trials. Eleven studies reported mothers experienced mild side effects; none of the included studies reported major side effects for newborns. CONCLUSION: The present systematic review demonstrated that TMS use in women with peripartum depression is safe, feasible and well-tolerated by the developing fetus/newborn, with a good safety and tolerability profile even during breastfeeding.
Subject(s)
Depression , Transcranial Magnetic Stimulation , Pregnancy , Humans , Female , Infant, Newborn , Transcranial Magnetic Stimulation/adverse effects , Depression/therapy , Peripartum Period , Antidepressive Agents/therapeutic use , PsychotherapyABSTRACT
BACKGROUND: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD. OBJECTIVES: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch. METHODS: Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up. RESULTS: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch. CONCLUSIONS: Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.
Subject(s)
Bipolar Disorder , Depressive Disorder, Treatment-Resistant , Ketamine , Humans , Antidepressive Agents/therapeutic use , Bipolar Disorder/drug therapy , Bipolar Disorder/chemically induced , Ketamine/therapeutic use , Depression , Depressive Disorder, Treatment-Resistant/drug therapyABSTRACT
BACKGROUND: Women represent an increasing number of individuals with alcohol and substance use disorders (ASUDs), and sex-differences might affect results of interventional clinical trials (CTs). We aim at assessing the proportion of women and the reporting of sex-stratified and female-specific data in CTs for ASUDs. METHODS: We extracted data from ClinicalTrials.gov on Phase 1-3 CTs of investigational drugs for ASUDs conducted from 2000 to 2021 and identified articles related to these trials. We determined the average proportions of women enrolled per trial overall, over time, and by disease area and trial phase. Next, we calculated the proportion of articles reporting sex-stratified and female-specific data. RESULTS: In the 234 CTs identified, the overall proportion of women was 33.4% [95% CI: 32.7%-33.9%]), with an increasing temporal trend. Women's participation was higher in CTs of investigational drugs for tobacco (43.5% [95% CI: 42.4% -44.5%]) and alcohol use disorder (35.9% [95% CI: 34.54%-37.21%]), and closely mirrored their representation in the disease populations (46% and 37%). Conversely, women were underrepresented in clinical trials of drugs for cocaine and stimulant use disorders (25.8% [95% CI: 24.6%-27.1%]) and opioid use disorders (25.9% [95% CI:24.2%-27.7%]). Nine publications reported sex-stratified data in the method and/or result section, whereas none documented female-specific data. CONCLUSIONS: Enrollment of women in ASUDs CTs has increased over time but remains low in several disease areas. This, together with the low rates of reporting of sex-stratified data, calls for an adequate inclusion of sex in the design and analysis of CTs for ASUDs.