Search Results (25)

Background: Schizophrenia with comorbid substance use disorder (SUD) is associated with greater clinical severity, poorer adherence, and worse functional outcomes. Third-generation antipsychotics, through partial dopamine agonism, may represent a useful strategy in this complex population. This study compared the long-term efficacy of brexpiprazole and aripiprazole in patients with schizophrenia, with or without comorbid SUD. Methods: Patients (N = 243) with DSM-5/DSM-5-TR schizophrenia orally received 4 mg/day brexpiprazole or 30 mg/day aripiprazole for 12 months in a real-world clinical setting. Psychopathology was assessed at baseline and after 1, 3, 6, and 12 months using the Brief Psychiatric Rating Scale (BPRS) and the Positive And Negative Syndrome Scale (PANSS). Analyses were performed on 217 completers, excluding 26 drop-outs. Outcomes were compared according to drug and presence/absence of comorbid SUD. Results: Both brexpiprazole and aripiprazole were associated with psychotic symptom and global psychopathology improvement over 12 months (p < 0.01). In patients without SUD, the two treatments showed comparable efficacy. Among patients with comorbid SUD, brexpiprazole showed greater improvement in BPRS and PANSS outcomes than aripiprazole (p < 0.01). Treatment response to aripiprazole, but not to brexpiprazole, was diminished by substance use. Brexpiprazole was associated with better tolerability and lower rates of subjective agitation-related discontinuation. Conclusions: Both dopamine partial agonists were effective in treating schizophrenia; however, brexpiprazole was superior in patients with comorbid SUD. Findings suggest that brexpiprazole may represent a promising therapeutic option in dual-disorder patients. Full article

Background/Objectives: Obsessive–compulsive disorder (OCD) is a chronic psychiatric illness with intrusive obsessions and compulsive behaviors severely impacting daily functioning and quality of life. The purpose of this narrative review is to present an updated summary of available evidence on third-generation antipsychotics (TGAs) as augmentation strategies for SRI-refractory OCD. Methods: The literature was reviewed using the PubMed database to recognize studies on the use of TGAs in treatment-resistant OCD. Only articles in the English language and on human participants were included. Results: We included nine reports in our review. More numerous (five reports) and higher evidence-level reports were retrieved for aripiprazole, which consistently shows high response rates compared to placebo and other antipsychotics. Two cohort studies were included on brexpiprazole, with no active or placebo comparator. These showed varying but high response rates. One cohort study reported a response rate of 61.5% to cariprazine. Only one paper reported on the efficacy of lumateperone in OCD. This was a single-case report on an adolescent patient with refractory OCD responding to lumateperone monotherapy. Conclusions: The current state of evidence supports the clinical utility of TGAs, particularly aripiprazole, in augmenting SRI treatment in patients with refractory OCD. Evidence regarding cariprazine and lumateperone is scarce, but still contributes to the discussion on the use of TGAs in OCD. Full article

Adolescent-onset schizophrenia (AOS; onset between ages 13 and 18) represents a rare but severe subtype of schizophrenia that disrupts crucial neurodevelopmental and psychosocial milestones. Marked by prominent cognitive deficits, negative symptoms, and poor long-term outcomes, AOS poses unique diagnostic and therapeutic challenges distinct from adult-onset cases. A comprehensive search of PubMed/MEDLINE (January 2003–February 2025) and reference lists of prior reviews identified twenty-four primary studies addressing pharmacological, psychosocial, and neurobiological aspects of AOS. Synthesis of this evidence highlights atypical antipsychotics such as aripiprazole and brexpiprazole as well-tolerated first-line options for positive symptom reduction, while clozapine remains the most effective treatment for resistant AOS. High-dose olanzapine offers comparable efficacy but carries greater metabolic risk. Psychosocial approaches—including cognitive behavioral therapy (CBT) and motivational enhancement therapy (MET)—enhance adherence, insight, and functional recovery when integrated with pharmacotherapy. Converging neuroimaging and biomarker data reveal persistent neuroinflammatory and glutamatergic dysregulation, characterized by elevated interleukin-6 (IL-6), C-C motif chemokine ligand 11 (CCL11), and dorsomedial prefrontal hypoglutamatergia, suggesting immune-mediated and developmental mechanisms underlying symptom persistence. Emerging research on neuromodulation and N-methyl-D-aspartate (NMDA)-targeted strategies further broadens the therapeutic landscape. Collectively, these findings highlight the importance of early, developmentally informed, and multidisciplinary interventions tailored to adolescents. Strengthening longitudinal, biomarker-guided, and neuromodulation-inclusive studies will be critical for refining precision treatment models and informing future clinical and policy frameworks for adolescent psychosis care. Full article

Background: Schizophrenia is a chronic disorder requiring long-term pharmacological treatment. Many patients experience inadequate response and adverse effects, often leading to poor adherence and need for antipsychotic switch or polypharmacotherapy. In this context, brexpiprazole, an atypical antipsychotic with favorable tolerability profile, may offer clinical benefits following previous treatment failure or intolerance. However, real-world evidence after treatment switch remains limited. Methods: This retrospective, observational study included 50 outpatients with schizophrenia switched to brexpiprazole (2–4 mg/day) via cross-titration and evaluated over 12 weeks. Primary outcomes were changes in Patient Life Engagement, assessed through a 14-item subset of the Positive and Negative Syndrome Scale (PANSS), along with response/remission rates. Secondary outcomes included changes in subjective well-being, quality of life, sexual functioning (based on Subjective Well-being under Neuroleptics—Short Form [SWN-S], WHO-5 Well-Being Index [WHO-5], and Arizona Sexual Experience Scale [ASEX] scores, respectively), metabolic parameters, and prolactin levels. Results: Life engagement improved significantly (p < 0.001) across all domains, and clinical response was achieved in 40% of patients. Significant improvements were observed in SWN-S and WHO-5 scores (both p < 0.001). Weight and BMI significantly decreased (–2.64 kg, p = 0.013, and –0.91 kg/m², p = 0.006, respectively). Numerical non-significant reductions were found in ASEX (p = 0.067) and prolactin levels (–30.7 ng/mL, p = 0.077). Overall, treatment was well-tolerated. Conclusions: Switching to brexpiprazole was associated with improvements in psychopathological, functional, and physical health domains. These findings support its potential role in real-world, personalized therapeutic strategies for patients with schizophrenia following suboptimal outcomes with prior antipsychotic treatments. Full article

Recent years have provided numerous reports on the mechanisms of action of psychiatric medications (antidepressants, antipsychotics, mood stabilizers, and antidementia drugs) that directly inhibit the growth of cancer cells, as well as on their indirect effects on the psyche and immune system, and their supportive effects on chemotherapeutic agents. The mechanisms of the anticancer activity of psychiatric drugs include inhibition of dopamine and N-methyl-D-aspartate receptors that work via signaling pathways (PI3K/AKT/mTOR/NF-κB, ERK, Wnt/ß-catenin, and bcl2), metabolic pathways (ornithine decarboxylase, intracellular cholesterol transport, lysosomal enzymes, and glycolysis), autophagy, Ca²⁺-dependent signaling cascades, and various other proteins (actin-related protein complex, sirtuin 1, p21, p53, etc.). The anticancer potential of psychiatric drugs seems to be extremely broad, and the most extensive anticancer literature has been reported on antidepressants (fluoxetine, amitriptyline, imipramine, mirtazapine, and St John’s Wort) and antipsychotics (chlorpromazine, pimozide, thioridazine, and trifluoperazine). Among mood stabilizers, lithium and valproates have the largest body of literature. Among antidementia drugs, memantine has documented anticancer effects, while there is limited evidence for galantamine. Of the new psychiatric substances, the antipsychotic drug brexpiprazole and the antidepressant vortioxetine have a very interesting body of literature regarding glioblastoma, based on in vitro and in vivo animal survival studies. Their use in brain tumors and metastases is particularly compelling, as these substances readily cross the blood–brain barrier (BBB). Moreover, the synergistic effect of psychiatric drugs with traditional cancer treatment seems to be extremely important in the fight against chemo- and radio-resistance of tumors. Although there are some studies describing the possible carcinogenic effects of psychiatric drugs in animals, the anticancer effect seems to be extremely significant, especially in combination treatment with radio/chemotherapy. The emerging evidence supporting the anticancer properties of psychiatric drugs presents an exciting frontier in oncology. The anticancer properties of psychiatric drugs may prove particularly useful in the period between chemotherapy and radiotherapy sessions to maintain the tumor-inhibitory effect. While further research is necessary to elucidate the mechanisms, clinical implications, dose-dependence of the effect, and clear guidelines for the use of psychiatric medications in cancer therapy, the potential for these commonly prescribed medications to contribute to cancer treatment enhances their value in the management of patients facing the dual challenges of mental health and cancer. Full article

Background/Objectives: Dopamine partial agonists are drugs initially developed to treat schizophrenia, seeking a double effect of increased dopaminergic transmission in the prefrontal cortex and decrease in the accumbens/striatum. Of these drugs, aripiprazole, brexpiprazole, and cariprazine are currently marketed and used in schizophrenia spectrum and mood disorders. It is debated whether patients with psychiatric disorders becoming pregnant should discontinue or continue their antipsychotic treatment despite some risks for the fetus, i.e., whether it is worse to have an untreated disorder or treating it with drugs. The safety of drugs for mother and baby extend from pregnancy to the postpartum, when breastfeeding assumes great importance. We set to investigate the use of dopamine partial agonists in pregnancy and lactation. Methods: On 23 June 2025, we used suitable strategies for identifying cases and studies of cariprazine, aripiprazole, brexpiprazole, dopamine partial agonists in pregnancy, perinatal period, and/or lactation on PubMed, CINAHL, PsycInfo/PsycArticles, Scopus, and ClinicalTrials.gov. We used the PRISMA Statement in developing our review. We included case reports and clinical studies. We excluded reports without pregnancy or focused on other drugs than the above. We reached consensus on eligibility with Delphi rounds among all authors. Results: Our searches produced 386 results on the above databases. We included 24 case reports/series and 15 studies. Most studies showed no negative pregnancy outcomes. There were serious concerns about the use of dopamine D₂/D₃ partial agonists during lactation. Conclusions: The use of dopamine partial agonists during pregnancy appears to be safe, but during breastfeeding they should be better avoided. Full article

Schizophrenia is a chronic and severe psychiatric disorder affecting approximately 1% of the global population, characterized by disrupted synaptic plasticity and brain connectivity. While substantial evidence supports its classification as a neurodevelopmental disorder, non-canonical neurodegenerative features have also been reported, with increasing attention given to astrocytic dysfunction. Overall, in this study, we explore the role of astrocytes as a structural and functional link between neurodevelopment and neurodegeneration in schizophrenia. Specifically, we examine how astrocytes contribute to forming an aberrant substrate during early neurodevelopment, potentially predisposing individuals to later neurodegeneration. Astrocytes regulate neurotransmitter homeostasis and synaptic plasticity, influencing early vulnerability and disease progression through their involvement in Ca²⁺ signaling and dopamine–glutamate interaction—key pathways implicated in schizophrenia pathophysiology. Astrocytes differentiate via nuclear factor I-A, Sox9, and Notch pathways, occurring within a neuronal environment that may already be compromised in the early stages due to the genetic factors associated with the ‘two-hits’ model of schizophrenia. As a result, astrocytes may contribute to the development of an altered neural matrix, disrupting neuronal signaling, exacerbating the dopamine–glutamate imbalance, and causing excessive synaptic pruning and demyelination. These processes may underlie both the core symptoms of schizophrenia and the increased susceptibility to cognitive decline—clinically resembling neurodegeneration but driven by a distinct, poorly understood molecular substrate. Finally, astrocytes are emerging as potential pharmacological targets for antipsychotics such as clozapine, which may modulate their function by regulating glutamate clearance, redox balance, and synaptic remodeling. Full article

Antipsychotic drugs (APs) have profoundly changed the treatment landscape for psychiatric disorders, yet their impact on neuroplasticity and neurotrophism remains only partially understood. While second-generation antipsychotics (SGAs) are associated with a better side effect profile than their predecessors, the emergence of third-generation antipsychotics (TGAs)—such as brexpiprazole, cariprazine, lurasidone, iloperidone, lumateperone, pimavanserin, and roluperidone—has prompted renewed interest in their potential neuroprotective and pro-cognitive effects. This review attempts to carefully examine the evidence on the neurotrophic properties of TGAs and their role in modulating brain plasticity by analyzing studies published between 2010 and 2024. Although data remain limited and focused primarily on earlier SGAs, emerging findings suggest that some TGAs may exert positive effects on neuroplastic processes, including the modulation of brain-derived neurotrophic factors (BDNFs) and synaptic architecture. However, robust clinical data on their long-term effects and comparative efficacy are lacking; therefore, further research is necessary to validate their role in preventing neurodegenerative changes and improving cognitive outcomes in patients with psychiatric conditions. Full article

Depression persists as one of the illnesses described relentlessly through the centuries because it affects a large group of people. Background/Objectives: The treatment of depression consists of various therapeutic agents, among which selective serotonin reuptake inhibitors (SSRIs) are elective. As polypharmacy tends to become the norm in modern days, the study of the real-life occurrence of drug–drug interactions is imperative. The aim of this study was the evaluation of drug–drug interactions (DDIs) between antidepressant medicines, namely SSRIs (each representative) versus eleven representatives from other antidepressant classes. Methods: Based on the spontaneous safety reports (ICSRs) uploaded to EudraVigilance until the end of July 2024, the descriptive and the disproportionality analyses were performed, and results were interpreted in the context of pharmacologic variability. Results: SSRIs were the focus of 137,369 ICSRs while for the other antidepressants, namely amitriptyline, clomipramine, duloxetine, venlafaxine, mirtazapine, bupropion, trazodone, tianeptine, agomelatine, brexpiprazole, and esketamine, a total of 155,458 reports were registered. The most notable differences appeared in psychiatric adverse drug reactions. Except fluvoxamine (n = 463), the remaining SSRIs had a higher number of DDIs reported (n = 1049 for escitalopram and n = 1549 for sertraline) compared to other antidepressants. However, similar numbers of DDIs were reported for duloxetine (n = 1252) and venlafaxine (n = 1513). Sertraline unspecified DDIs were reported with a higher probability compared to all other drugs (e.g., esketamine ROR: 9.37, 95% CI: 5.17–16.96, tianeptine ROR: 4.08, 95% CI: 2.49–6.69, etc.). Conclusions: SSRIs, although known to influence various cytochrome P450 isoenzymes, have not shown higher inhibitory interactions compared to any of the drugs selected as reference. Sertraline appears in more reports concerning DDIs than the other antidepressants. Still, further real world studies related to the DDIs of SSRIs are needed to complete the relevant knowledge level. Full article

In the military, combat wound infections can progress rapidly to life-threatening sepsis. The discovery of effective small-molecule drugs to prevent and/or treat sepsis is a priority. To identify potential sepsis drug candidates, we used an optimized larval zebrafish model of endotoxicity/sepsis to screen commercial libraries of drugs approved by the U.S. Food and Drug Administration (FDA) and other active pharmaceutical ingredients (APIs) known to affect pathways implicated in the initiation and progression of sepsis in humans (i.e., inflammation, mitochondrial dysfunction, coagulation, and apoptosis). We induced endotoxicity in 3- and 5-day post fertilization larval zebrafish (characterized by mortality and tail fin edema (vascular leakage)) by immersion exposure to 60 µg/mL Pseudomonas aeruginosa lipopolysaccharide (LPS) for 24 h, then screened for the rescue potential of 644 selected drugs at 10 µM through simultaneous exposure to LPS. After LPS exposure, we used a neurobehavioral assay (light-dark test) to further evaluate rescue from endotoxicity and to determine possible off-target drug side effects. We identified 29 drugs with > 60% rescue of tail edema and mortality. Three drugs (Ketanserin, Tegaserod, and Brexpiprazole) produced 100% rescue and did not differ from the controls in the light-dark test, suggesting a lack of off-target neurobehavioral effects. Further testing of these three drugs at a nearly 100% lethal concentration of Klebsiella pneumoniae LPS (45 µg/mL) showed 100% rescue from mortality and 88–100% mitigation against tail edema. The success of the three identified drugs in a zebrafish endotoxicity/sepsis model warrants further evaluation in mammalian sepsis models. Full article

Background: According to scientific literature, some 99% of patients affected by Alzheimer’s disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances. To date, there are no specific solutions for treating agitation. The only authorized drug is risperidone (as well as brexpiprazole, approved by the FDA on 11 May 2023), which can be used for no longer than 6–12 weeks because it increases the risk of death—owing to cardiocerebrovascular accidents—by 1.6–1.7 times. Methods: In order to address the latter noteworthy unmet medical need, NanoBEO was produced. The aim of the present work is to generate the health technology assessment (HTA) of this nanotechnological device. The latter consists of a controlled release system, based on solid lipid nanoparticles loaded with bergamot essential oil (BEO). Results: The results of the present research assessed the current evidence in the field of non-pharmacological treatments for this condition, including relevant primary preclinical and clinical data studies supporting the use of this device and the production of the operative plan for its launch on the market. The findings offer recommendations for decision-making on its implementation in dementia. Conclusions: NanoBEO represents a public-worth innovation in this neglected area, marking a significant advancement in the history of dementia, moving from academic research to product development. Full article

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. Full article

Background: Borderline personality disorder (BPD) is a heterogeneous and highly comorbid disorder. Suicidality, aggression and substance abuse are common presentations of BPD. Our case series is the first to highlight the role of brexpiprazole in improving these symptoms in patients with BPD. Case presentation: We describe three cases demonstrating the role of brexpiprazole in improving BPD’s prominent features and comorbidities. All cases improved when brexpiprazole was added to their treatment regime. Case 1: A 26-year-old woman who was diagnosed with BPD and cyclothymia, presented to the psychiatric emergency unit with impulsive suicidal behaviour. Case 2: A 43-year-old woman suffering from BPD sought help due to her violent behaviour and emotional dysregulation. Case 3: A 22-year-old woman with underlying attention deficit and hyperactivity disorder, polysubstance use disorder and BPD presented with dysregulated emotions. Conclusions: Our case series provides anecdotal evidence of the potential role of brexpiprazole in attenuating suicidality, aggression and substance abuse in patients with BPD. We postulate that brexpiprazole’s high affinity for the 5HT1A/5HT2A receptors, coupled with its low intrinsic effect on the D2/D3 receptor system, is fundamental in its actions to stabilise the aberrant dopaminergic and serotonergic signalling in BPD. Future research should focus on well-designed clinical trials investigating the efficacy of brexpiprazole in patients with BPD. Full article

This narrative review explores the efficacy and tolerability of third-generation antipsychotics (TGAs)—aripiprazole, cariprazine, brexpiprazole, and lurasidone—for the management of substance-induced psychosis (SIP). SIP is a psychiatric condition triggered by substance misuse or withdrawal, characterized by unique features distinct from those of primary psychotic disorders. These distinctive features include a heightened prevalence of positive symptoms, such as hallucinations and delusions, in addition to a spectrum of mood and cognitive disturbances. This review comprehensively investigates various substances, such as cannabinoids, cocaine, amphetamines, and LSD, which exhibit a greater propensity for inducing psychosis. TGAs exhibit substantial promise in addressing both psychotic symptoms and issues related to substance misuse. This review elucidates the distinctive pharmacological properties of each TGA, their intricate interactions with neurotransmitters, and their potential utility in the treatment of SIP. We advocate for further research to delineate the long-term effects of TGAs in this context and underscore the necessity for adopting an integrated approach that combines pharmacological and psychological interventions. Our findings underscore the intricate and multifaceted nature of treating SIP, highlighting the potential role of TGAs within therapeutic strategies. Full article

Aggressive behaviors of people with dementia pose a significant challenge to employees in nursing homes and aged care facilities. Aggressive behavior is a result of psychomotor agitation in dementia (BPSD). Globally, psychotropic interventions are the preferred treatment for BPSD. However, it is still unclear which psychotropic should be prescribed. The purpose of this systematic review is to compare pharmacological interventions for psychomotor agitation and psychosis symptoms. Method: The studies were extracted from databases, such as PubMed, OVID, and Cochrane, with a date restriction from 2000 to present, and in English. PRISMA steps were used to refine the extracted data. The RCTs extracted for this systematic review compared active ingredient medications to one another or to a placebo. Results: PRISMA was used to assess all selected trials comprehensively. Four trials are being conducted on quetiapine, two on haloperidol, one on olanzapine, three on risperidone, one on brexpiprazole, one on pimavanserin, and two on aripiprazole. Compared to typical antipsychotics, quetiapine showed tolerable adverse effects and did not worsen parkinsonism. Psychosis symptoms and behavioral improvements can be improved with haloperidol. Among elderly patients with psychosis, risperidone reduces angriness, paranoia, and aggression, as well as improves global functioning. As compared with other antipsychotics, aripiprazole provides a lower risk of adverse effects and demonstrated improvement in agitation, anxiety, and depression associated with psychosis. While olanzapine improves hostile suspiciousness, hallucinations, aggression, mistrust, and uncooperativeness, it worsens depression symptoms. Psychosis was treated effectively with pimavanserin without adverse effects on motor functions. Psychosis symptoms are well tolerated by brexpiprazole, but insomnia, headache, and urinary tract infections are common side effects. Conclusions: In this systematic review, we provide an overview of how to choose the correct antipsychotics and dosages for the management of BPSD and emphasize the importance of safe and conservative use of these drugs. Full article