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Drugs for anxiety are a billion-dollar business in the United States. Yet in 1955, when the prescription tranquilizer Miltown became available, pharmaceutical executives worried that there was no market. InThe Age of Anxiety, historian Andrea Tone provides a comprehensive account of the rise of America's prescription drug culture through the lens of our complicated relationship with tranquilizers.

Few data are available on the efficacy and safety of antipsychotics with different dopamine D2 receptor (D2-R)-binding properties in drug-naïve and non-drug-naïve schizophrenia. Thus, we aimed to assess whether antipsychotic medication history influences efficacy and tolerability in schizophrenia, based on a randomized controlled study of antipsychotics with mechanisms involving either full antagonism or partial agonism of D2-R. Patients with schizophrenia were recruited and given perospirone or aripiprazole in a 12-week, flexible-dose, open-label, randomized controlled study. Data were analyzed after dividing the patients into antipsychotic-naïve and antipsychotic-treated group according to antipsychotic medication histories. Efficacy and safety were evaluated using the Positive and Negative Syndrome Scale (PANSS), the Drug-Induced Extrapyramidal Symptoms Scale, and the Barnes Akathisia Rating Scale. In patients receiving perospirone, the antipsychotic-naïve group ( n  = 22) showed greater symptom improvement than that shown by the antipsychotic-treated group ( n  = 29), as assessed by efficacy evaluation scales such as the PANSS total, positive, and excited component score ( p  = .006, p  < .001, p  = .003, respectively). In patients receiving aripiprazole, however, there was no significant difference in efficacy between the antipsychotic-naïve ( n  = 18) and antipsychotic-treated ( n  = 31) groups. No significant intra-group or inter-group difference was noted with respect to any of the tolerability-related parameters assessed. The present study data support the hypothesis that antipsychotic medication history may influence efficacy in patients who receive a D2-R full antagonist but not a D2-R partial agonist.

Background Given that antipsychotic medication is a cornerstone for treating and preventing relapse in people with schizophrenia, non-adherence has been indicated as a big challenge. This study aimed to assess antipsychotic medication non-adherence and factors associated among patients with schizophrenia in eastern Ethiopia. Methods We conducted an institution-based cross-sectional study in two public hospitals in Eastern Ethiopia from December 1, 2022, to January 31, 2023. Antipsychotic medication adherence was assessed using MOrisky medication adherence rating scale questionnaire, and insight was measured using the self-report insight scale for Psychosis (ISP). Multiple stepwise logistic regression models with Adjusted Odds Ratio (AOR) and 95% confidence interval (CI) were applied to identify the factors. Statistical significance was considered at p-value  ≤  0.05. Results We found that 44.57% of patients with schizophrenia experienced non-adherence to their antipsychotic medication. Being single (AOR = 2.48, 95% confidence interval [CI]:1.71, 3.58), alcohol users (AOR = 2.00, 95% confidence interval [CI]:1.46, 2.72), Khat chewers (AOR = 2.84, 95% confidence interval [CI]; 2.06, 3.90) and having no insight to their illness (AOR = 2.1, 95% confidence interval [CI]:1.52, 2.90) were more likely to be non-adherent to their antipsychotic medications. Conclusions Our study revealed that antipsychotic medication non-adherence was high among individuals suffering from schizophrenia and that it was influenced by various factors such as single marital status, alcohol usage, Khat chewing, and having no understanding of their condition. As a result, comprehensive intervention methods should be developed to address the factors associated with psychotropic medication non-adherence among patients. Healthcare professionals should pay attention to these aspects and consider developing specific strategies to promote adherence to medications while treating individuals with schizophrenia.

Schizophrenia is a disease syndrome with major public health implications. The primary advance in pharmacotherapeutics was in 1952 with the introduction of antipsychotic medications (ie, chlorpromazine, dopamine D2 antagonism). Barriers to progress have been substantial, but many will be subject to rapid change based on current knowledge. There are attractive psychopathology indications for drug discovery (eg, impaired cognition and negative symptoms), and drugs with efficacy in these domains may have application across a number of disease classes. These pathologies are observed prior to psychosis raising the possibility of very early intervention and secondary prevention. Success in drug discovery for cognition and negative symptom pathologies may bring forth issues in ethics as the potential for enhancing normal function is explored.

Background Schizophrenia (SCZ) shares high clinical relevance with the immune system, and the potential interactions of psychopharmacological drugs with the immune system are still an overlooked area. Here, we aimed to identify whether the second-generation antipsychotics (SGA) monotherapy or combined therapy of SGA with other psychiatric medications influence the routine blood immunity biomarkers of patients with SCZ. Methods Medical records of inpatients with SCZ from January 2019 to June 2023 were retrospectively screened from June 2023 to August 2023. The demographic data and peripheral levels of cytokines (IL-2, IL-4, IL-6, TNF-α, INF-γ, and IL-17 A), lymphocyte subtype proportions (CD3+, CD4+, CD8 + T-cell, and natural killer (NK) cells), and thyroid autoimmune antibodies (thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb)) were collected and analyzed. Results 30 drug-naïve patients, 64 SGA monotherapy (20 for first-episode SCZ, 44 for recurrent SCZ) for at least one week, 39 combined therapies for recurrent SCZ (18 with antidepressant, 10 with benzodiazepine, and 11 with mood stabilizer) for at least two weeks, and 23 used to receive SGA monotherapy (had withdrawn for at least two weeks) were included despite specific medication. No difference in cytokines was found between the SGA monotherapy sub-groups ( p  > 0.05). Of note, SGA monotherapy appeared to induce a down-regulation of IFN-γ in both first (mean [95% confidence interval]: 1.08 [0.14–2.01] vs. 4.60 [2.11–7.08], p  = 0.020) and recurrent (1.88 [0.71–3.05] vs. 4.60 [2.11–7.08], p  = 0.027) episodes compared to drug-naïve patients. However, the lymphocyte proportions and thyroid autoimmune antibodies remained unchanged after at least two weeks of SGA monotherapy ( p  > 0.05). In combined therapy groups, results mainly resembled the SGA monotherapy for recurrent SCZ ( p  > 0.05). Conclusion The study demonstrated that SGA monotherapy possibly achieved its comfort role via modulating IFN-γ, and SGA combined therapy showed an overall resemblance to monotherapy.

AbstractBipolar disorders (BDs) are recurrent and sometimes chronic disorders of mood that affect around 2% of the world’s population and encompass a spectrum between severe elevated and excitable mood states (mania) to the dysphoria, low energy, and despondency of depressive episodes. The illness commonly starts in young adults and is a leading cause of disability and premature mortality. The clinical manifestations of bipolar disorder can be markedly varied between and within individuals across their lifespan. Early diagnosis is challenging and misdiagnoses are frequent, potentially resulting in missed early intervention and increasing the risk of iatrogenic harm. Over 15 approved treatments exist for the various phases of bipolar disorder, but outcomes are often suboptimal owing to insufficient efficacy, side effects, or lack of availability. Lithium, the first approved treatment for bipolar disorder, continues to be the most effective drug overall, although full remission is only seen in a subset of patients. Newer atypical antipsychotics are increasingly being found to be effective in the treatment of bipolar depression; however, their long term tolerability and safety are uncertain. For many with bipolar disorder, combination therapy and adjunctive psychotherapy might be necessary to treat symptoms across different phases of illness. Several classes of medications exist for treating bipolar disorder but predicting which medication is likely to be most effective or tolerable is not yet possible. As pathophysiological insights into the causes of bipolar disorders are revealed, a new era of targeted treatments aimed at causal mechanisms, be they pharmacological or psychosocial, will hopefully be developed. For the time being, however, clinical judgment, shared decision making, and empirical follow-up remain essential elements of clinical care. This review provides an overview of the clinical features, diagnostic subtypes, and major treatment modalities available to treat people with bipolar disorder, highlighting recent advances and ongoing therapeutic challenges.

Background To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. Methods We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. Results The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P  < 0.001), while the number of hospitalizations decreased (1 (1,3) vs. 1 (1,2), Z = 5.625, P  < 0.001). The inpatient costs in the direct medical expenses of patients after 12 months of treatment decreased compared to before (5000(2000,12000) vs. 3000 (1000,8050), P  < 0.05), while there was no significant change in outpatient expenses and direct non-medical expenses (transportation, accommodation, meal, and family accompanying expenses, etc.) ( P  > 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P  < 0.05). Conclusion Palmatine palmitate reduces the number of hospitalizations for patients, as well as their direct and indirect economic burdens, and has good economic benefits.

A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-induced weight gain. Two multicenter, open-label, parallel-cohort studies were performed to evaluate the effect of moderate hepatic impairment (Child-Pugh score 7-9 [class B]; study 1) and severe renal impairment (estimated glomerular filtration rate: 15-29 mL/min/1.73 m ; study 2) on the pharmacokinetics, safety, and tolerability of a single dose of OLZ/SAM 5/10 mg. There was a 1.67-fold increase in area under the plasma concentration-time curve from time 0 to infinity (AUC ) and a 2.17-fold increase in maximum plasma concentration (C ) of olanzapine, and a 1.52-fold increase in AUC and a 1.63-fold increase in C of samidorphan, in subjects with moderate hepatic impairment compared with healthy control subjects. Compared with healthy control subjects, subjects with severe renal impairment had a 33% and 56% reduction in clearance, a 1.51- and 2.31-fold increase in AUC , and a 1.32- and 1.37-fold increase in C of olanzapine and samidorphan, respectively. OLZ/SAM 5/10 mg was generally well tolerated under the conditions of the studies, with a safety profile consistent with that observed in other clinical studies of OLZ/SAM.

Schizophrenia today: three views of the future Three Perspectives in this issue cover different aspects of the current state of our knowledge about schizophrenia. Thomas Insel, director of the US National Institute of Mental Health in Bethesda, Maryland, outlines a new approach to schizophrenia that could in time lead to new treatments. He calls for schizophrenia to be emphasized as a neurodevelopmental disorder in which psychosis is a late — and potentially curable — stage. Andreas Meyer-Lindenberg, director of the Central Institute of Mental Health in Mannheim, Germany, explains how neuroimaging and other systems-level techniques can help develop future treatment. And Jim van Os, Gunter Kenis and Bart Rutten review our knowledge of the environmental factors that influence schizophrenia risk, and the major challenges that will be involved in teasing them out. How will we view schizophrenia in 2030? Schizophrenia today is a chronic, frequently disabling mental disorder that affects about one per cent of the world’s population. After a century of studying schizophrenia, the cause of the disorder remains unknown. Treatments, especially pharmacological treatments, have been in wide use for nearly half a century, yet there is little evidence that these treatments have substantially improved outcomes for most people with schizophrenia. These current unsatisfactory outcomes may change as we approach schizophrenia as a neurodevelopmental disorder with psychosis as a late, potentially preventable stage of the illness. This ‘rethinking’ of schizophrenia as a neurodevelopmental disorder, which is profoundly different from the way we have seen this illness for the past century, yields new hope for prevention and cure over the next two decades.

Dynamic treatment regimes (DTRs) operationalize the clinical decision process as a sequence of functions, one for each clinical decision, where each function maps up‐to‐date patient information to a single recommended treatment. Current methods for estimating optimal DTRs, for example Q‐learning, require the specification of a single outcome by which the “goodness” of competing dynamic treatment regimes is measured. However, this is an over‐simplification of the goal of clinical decision making, which aims to balance several potentially competing outcomes, for example, symptom relief and side‐effect burden. When there are competing outcomes and patients do not know or cannot communicate their preferences, formation of a single composite outcome that correctly balances the competing outcomes is not possible. This problem also occurs when patient preferences evolve over time. We propose a method for constructing DTRs that accommodates competing outcomes by recommending sets of treatments at each decision point. Formally, we construct a sequence of set‐valued functions that take as input up‐to‐date patient information and give as output a recommended subset of the possible treatments. For a given patient history, the recommended set of treatments contains all treatments that produce non‐inferior outcome vectors. Constructing these set‐valued functions requires solving a non‐trivial enumeration problem. We offer an exact enumeration algorithm by recasting the problem as a linear mixed integer program. The proposed methods are illustrated using data from the CATIE schizophrenia study.