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The article presents the results of a study on how to interpret findings concerning newly approved antipsychotic agents in 2012. According to the authors, the Program to Evaluate the Antipsychotic Response to Lurasidone (PEARL 2) trial was deemed relevant for discussion since it was a well-designed registration study that included an active control. The study concluded that clinicians should focus on safety issue in selecting the most appropriate antipsychotic for a specific patient.

The article presents a meta-analysis of antidepressant or antipsychotic monotherapy compared with combination antidepressant-antipsychotic treatment for psychotic depression. Data such as study-defined inefficacy, all-cause discontinuation, and side effects are cited to have been extracted from trials. Combination antidepressant-antipsychotic treatment is showed to have lesser study-defined inefficacy than monotherapy.

The article examines the prevalence of prediabetes in patients receiving antipsychotics and to compare the psychiatric and metabolic characteristics of prediabetic patients with normal glucose patients and patients with diabetes mellitus. Adult psychiatric inpatients with no history of diabetes and taking antipsychotics are cited to have been measured of criteria such as body mass index and fasting insulin. Prediates is presented to be highly prevalent in patients treated with antipsychotics.

The article examines the desirable characteristics that clinicians look for when deciding on antipsychotic agents to be used for treating schizophrenia. Characteristics of an ideal antipsychotic drug include comparable efficacy for positive systems, agitations, and aggression, better efficacy for negative and cognitive symptoms, relapse prevention, treatment-resistant illness, and related comorbid problems, subjective well-being, quality of life, and survival.

The article discusses a research study on examining differences in the efficacy of long-term and mid-term use of antipsychotic medications for the treatment of schizophrenia. Selected studies were used for the data-driven study in a clinical approach where Phase 1 Clinical Antipsychotic Trials of Intervention Effectiveness results are similar to European First-Episode Schizophrenia Trial short-term efficacy studies. Conclusions indicated the importance of second-generation antipsychotics.

The article assesses the incidence of palpitations, syncope and other symptoms and electrocardiographic signs of increased QT duration and dispersion of an increased risk of torsades de pointes in youth treated with ziprasidone. A cohort study of youth who were administered antipathetic treatment was conducted, with all patients having normal electrocardiograms (ECGs) at baseline. The study showed that ziprasidone was associated with a dose- and level-independent, significant prolongation of corrected QT (QTc) duration in one-fourth of youth subjects.

The article highlights developments in pediatric psychopharmacology, focusing on stimulants, antidepressants and anti-psychotics, as of May 2011. It examines the debate over psychotropic medication use in young patients, and the findings that psychotropic medications may have developmentally dependent effects that differ from those observe in adult patients. The study also evaluated the extent to which pediatric psychopharmacology has developed, and the gaps that still need to be addressed.

The article discusses a research study on the poor oral health of patients with schizophrenia and the risk for fatal infections and social stigmatization. Conducted was a historical and prospective study of dental visits of 21,417 patients diagnosed with schizophrenia using the database of the Danish National Patient Registry from 2004 to 2006. Results indicated that patients with schizophrenia visit dentists at the rate of 43% within 12 months in comparison to dental visits of Danish adult population who visit the dentist at the rate of 68% per year.

The article presents a historical review of the pharmacologic developments in the treatment of schizophrenia since 1960. A review of new advances in maximizing the treatment and outcomes in patients with schizophrenia as of September 2010 is presented. It highlights the methodological challenges, possible answers and areas of specific need for further research. Also discussed is the efficacy and safety of first- and second-generation antipsychotics like clozapine.

The article discusses the use of the aripiprazole adjunctive to quetiapine or risperidone monotherapy in the treatment of schizophrenia or schizoaffective disorder. In the conducted multicenter, randomized, double-blind placebo-controlled study, it was found out that the addition of aripiprazole to the antipsychotics did not have an effect on psychiatric symptoms, but was generally safe and allowed.

The article discusses a study which examined appropriateness in pediatric psychiatric emergency room service (PPERS) visits. A retrospective cohort study was conducted in which youngsters at less than 18 years of age were assessed in relation to the characteristics of PPERS visits. Findings on the percentages of PPERS patient visits which led to hospitalization and emergency room admission are presented. The study concludes inappropriateness in more than one third of PPERS visits.

The author discusses a study which examined the origins of increased cardiovascular risk in children with bipolar disorder, published within the issue. He provides an overview of the study, including its findings on the link between overweight and bipolar disorder and the limitations of the study. He argues that despite its limitations, the study provides a guide to design further studies. The author adds that such study is relevant to guide the clinical management of obesity in children with bipolar disorder.

The article examines the association between second-generation antipsychotic medications and diabetes. It discusses five aripiprazole-associated cases of severe glucose dysregulation. It suggests that clinicians should strictly follow the guidelines for medical monitoring until reliable and very sensitive predictors for the development of diabetes and diabetic ketoacidosis (DKA) are available.

Abstract ., Objective: To conduct a targeted literature review to examine the impact of cognitive impairment and negative symptoms among patients with schizophrenia treated in the United States across a range of outcomes pertinent to the US health care system decision-makers, such as payers and policy-makers., Data Sources: The authors searched EMBASE and PubMed from January 2012 to January 2024. Search terms included schizophrenia, cognitive impairment and negative symptoms, and direct medical and nonmedical, indirect, and societal outcomes., Study Selection: Considered for inclusion were US-based studies reporting on the relationship between cognitive impairment or negative symptoms and direct medical and nonmedical, indirect, and societal outcomes in patients with schizophrenia. A total of 4,212 articles were initially identified for screening., Data Extraction: One reviewer extracted data and another reviewer ensured studies met Population, Intervention, Comparison, Outcomes, Study Design-Time Period (PICOS-T) criteria for inclusion and exclusion., Results: Eight studies (n = 262,683) were included that reported specifically on associations between cognitive impairment or negative symptoms and targeted outcomes. Patients with schizophrenia and moderate/severe cognitive impairment had a 100% increase in relapse-related hospitalizations (0.6 vs 0.3, adjusted incidence rate ratio = 1.85, P < .05) and ER visits (0.4 vs 0.2, adjusted odds ratio = 1.77, P < .05) vs patients with no/mild cognitive impairment. Additionally, there was an almost 50% increase in outpatient visits (8.4 vs 5.5, P < .001) and inpatient admissions (6.8 vs 4.5, P < .001) over the study period (2014 Q1-2017 Q4) for patients with negative symptoms vs without negative symptoms. Direct nonmedical, indirect, and societal outcomes are described., Conclusions: This review highlights the economic burden of cognitive impairment and negative symptoms by focusing on outcomes relevant to health care decision-makers in the United States., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Objective: Current clinician-rated tardive dyskinesia (TD) symptom scales have not addressed the expanding clinical signs and functional impact of TD. The study objective was to develop and test the reliability of a new integrated instrument., Methods: A movement disorder neurologist devised the outline of the rating scale. A Steering Committee (5 neurologists and 2 psychiatrists) provided revisions until consensus was reached. The Clinician's Tardive Inventory (CTI) assesses abnormal movements of the eye/eyelid/face, tongue/mouth, jaw, and limb/trunk; complex movements defined as complicated movements different from simple patterned movements or postures; and vocalizations. The CTI rates frequency of symptoms from 0 to 3 (ranging from absent to constant). Functional impairments, including activities of daily living (ADL), social impairment, symptom distress, and physical harm, are rated 0-3 (ranging from unawareness to severe impact). The CTI underwent interrater and test-retest reliability testing between February and June 2022 based on videos and accompanying vignettes, which were reviewed by 2 movement disorder specialists to determine adequacy. Four clinicians rated each video/vignette. Interrater agreement was analyzed via 2-way random-effects intraclass correlation (ICC), and test-retest agreement was assessed utilizing the Kendall tau-b., Results: Forty-five video/vignettes were assessed for interrater reliability and 16 for test-retest reliability. The most prevalent movements were those of the tongue and mouth (77.8%) and jaw (55.6%). ICCs for movement frequency for anatomic symptoms were as follows: anatomic symptom summary score 0.92, abnormal eye movement 0.89, abnormal tongue/mouth movement 0.91, abnormal jaw movement 0.89, abnormal limb movement 0.76, complex movement 0.87, and abnormal vocalization 0.77; ICCs for functional impairments were as follows: total impairment score 0.92, physical harm 0.82, social embarrassment 0.88, ADLs 0.83, and symptom bother 0.92; Retests were conducted a mean (SD) of 15 (3) days later with correlation coefficients ranging from 0.66 to 0.87., Conclusions: The CTI is a new integrated instrument with proven reliability in assessing TD signs and functional impacts. Future validation study is warranted., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Objective: To identify outcome predictors in hospitalized youth with mental disorders., Methods: This retrospective analysis of systematically recorded clinical parameters in youth hospitalized for psychiatric treatment in 2004-2015 assessed magnitude and correlates of symptom response (SR), global illness response (GIR), social functioning (SF), out-of-home placement (OOHP), and length of stay (LOS). Backward elimination regression analyses were performed to identify independent baseline correlates of each of the 5 outcomes, with R 2 representing the variance explained by the independent correlates retained in the final model., Results: Across 1,189 youth (median age = 14.4 years; interquartile range = 11.6,16.1 years; range, 5-19 years; females = 61.5%), frequencies of coprimary outcomes were as follows: SR = 57.5% (statistically significant correlates = 13, R 2  = 0.154), GIR = 30.0% (correlates = 5, R 2  = 0.078), SF = 19.0% (correlates = 8, R 2  = 0.207), OOHP recommendation = 35.2% (correlates = 13, R 2  = 0.275), and mean ± SD LOS = 65.0 ± 37.5 days (correlates = 11, R 2  = 0.219). In multivariable analyses, 11 factors were statistically significantly ( P  < .05) associated with > 1 poor outcome: 4 with 4 outcomes (disturbed social interaction, substance abuse/dependence symptoms; sole exception for both = LOS; disturbed drive/attention/impulse control, sole exception = OOHP; higher admission BMI percentile [but shorter LOS], sole exception = GIR), 3 with 3 outcomes (higher admission age [but good SF and shorter LOS], more abnormal psychosocial circumstances, more mental health diagnoses), and 4 with 2 outcomes (intelligence level [IQ] < 85, obsessive-compulsive disorder symptoms, disturbed social behavior, somatic findings). Additionally, 17 correlates were statistically significantly ( P  < .05) associated with 1 outcome, ie, SR = 6, OOHP = 5, LOS = 5, SF = 1., Conclusions: Higher admission BMI percentile, disturbed social interaction, disturbed drive/attention/impulse control, and substance abuse/dependence symptoms were independently associated with multiple poor outcomes in mentally ill youth requiring inpatient care. Knowledge of global and specific correlates of poor inpatient treatment outcomes may help inform treatment decisions., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Objective: Patients with early-phase schizophrenia or bipolar I disorder (BD-I) are at greater risk for antipsychotic-associated weight gain. This 12-week, randomized, double-blind study conducted between June 2017 and December 2021 evaluated weight effects of combination olanzapine and samidorphan (OLZ/SAM) versus olanzapine in early-phase illness., Methods: Young adults (16-39 years) with DSM-5 schizophrenia, schizophreniform disorder, or BD-I, < 4 years since symptom onset, body mass index < 30 kg/m 2 , and < 24 weeks' cumulative antipsychotic exposure were randomized to OLZ/SAM (5-20/10 mg/d) or olanzapine (5-20 mg/d). Primary endpoint was percent change from baseline body weight at week 12. Secondary endpoints, tested hierarchically, were proportions of patients with ≥ 10% or ≥ 7% weight gain, waist circumference change, and Clinical Global Impressions-Severity (CGI-S) change., Results: Of 428 patients (OLZ/SAM, n = 213; olanzapine, n = 215), 408 had ≥ 1 postbaseline weight assessment and were analyzed. Percent weight change was significantly lower with OLZ/SAM versus olanzapine (4.91% vs 6.77%; least-squares mean [LSM] [SE] difference, -1.87% [0.75]; P  = .012). Although fewer patients treated with OLZ/SAM had ≥ 10% weight gain, the difference was not statistically significant versus olanzapine (21.9% vs 30.4%, respectively; OR = 0.64; 95% CI  =  0.39 to 1.05); hierarchical testing precluded further statistical evaluation of secondary endpoints. Proportions of patients with ≥ 7% weight gain (33.1% vs 44.8%; OR = 0.61, 95% CI = 0.39 to 0.94) and waist circumference change (2.99 vs 3.90 cm; LSM [SE] difference, -0.92 cm [0.58]; 95% CI = -2.06 to 0.22) favored OLZ/SAM. LSM (SE) CGI-S change with OLZ/SAM was -0.82 (0.06). OLZ/SAM and olanzapine had similar safety profiles, including small, similar metabolic parameter changes., Conclusions: In patients with early-phase schizophrenia, schizophreniform disorder, or BD-I, OLZ/SAM treatment resulted in less weight gain versus olanzapine., Trial Registration: ClinicalTrials.gov identifier: NCT03187769., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Outcome measures in major depressive disorder have traditionally focused on characteristic symptoms included in the DSM-5 definition of major depressive disorder (MDD): depressed mood, lack of interest or pleasure in activities, fatigue, guilt, and change in weight/appetite. Addressing these symptoms is clearly a treatment priority, especially in the acute stages of the treatment process. However, patients express that, beyond symptom relief, they have additional goals: restoration of functioning and of the feeling that one can participate in, and engage with, their own life. Life engagement encompasses aspects of life experience relating to cognition (including cognition colored by emotion), vitality, motivation and reward, and the ability to feel pleasure. In a recent roundtable meeting, a panel of 5 experts discussed life engagement and its relationship to symptoms and functioning in patients with major depressive disorder and schizophrenia. This Academic Highlights, part 3 in a series, summarizes the experts' discussion of how life engagement can be integrated into patient-centered discussions of treatment goals, as well as how it can inform treatment selection in for those with MDD., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Objective: Switching of antipsychotic medications, which are used for many psychiatric conditions, is common. However, reasons and clinical documentation of such switches have scarcely been studied., Methods: A systematic, retrospective review of prescription records and prescriber notes was conducted to characterize reasons for and types of antipsychotic switches at one hospital during inpatient or outpatient care, starting August 1, 2017, until 270 antipsychotic switches with type and reasons were collected, as required by power analysis., Results: After removing 7 cases in which quetiapine was switched to a non-antipsychotic agent, 263 antipsychotic switches involving 195 unique subjects (median age = 31 [interquartile range, 24-47] years; schizophrenia = 36.9%, bipolar disorder = 27.7%, schizoaffective disorder = 18.5%) were analyzed. Frequent reasons for antipsychotic switch were intolerability (45.7%) and inefficacy/clinical worsening (17.6%). Reasons did not differ by race ( P  = .2644), age ( P  = .0621), or insurance type ( P  = .2970), but differed heterogeneously regarding different reasons by sex ( P  = .004). The most common reported switches were from second-generation oral antipsychotics (SGA-OAPs) to other SGA-OAPs (N = 155, 58.9%), mostly due to tolerability or inefficacy; second-generation long-acting injectable antipsychotics (SGA-LAIs) to SGA-OAPs (11%), mostly due to intolerability, patient preference, or insurance coverage problems; and SGA-OAPs to SGA-LAIs (10.7%) due to nonadherence. Reasons for antipsychotic switch were properly documented in 208 (79.1%) of the prescriber notes., Conclusions: In this retrospective chart review, switching varied by sex regarding reasons and occurred almost in half of the cases due to intolerability. Different reasons predominated in switches from SGA-OAP to SGA-OAP, SGA-LAI to SGA-OAP, and SGA-OAP to SGA-LAI. One in 5 switches were not properly documented, requiring attention., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Unmet needs in the treatment of schizophrenia include nonadherence to treatment, symptom relapse, incomplete functional recovery, and poor quality of life. Incorporating the patient's perspective into the treatment plan and measuring treatment outcomes that are meaningful to patients is an important part of addressing these issues. Goal setting is associated with greater improvements in motivation and role functioning, but clinicians should keep in mind that their goals for treatment may not align with those of their patients. Patients tend to think about their lives more holistically than clinicians, with equal weight given to social and clinical needs, and improved functioning and engagement with life are likely to emerge as priorities, beyond the need for symptom control. In a recent roundtable meeting, a panel of 5 experts discussed life engagement and its relationship to symptoms and functioning in patients with major depressive disorder (MDD) and schizophrenia. This Academic Highlights, part 2 in a series, summarizes the experts' discussion of how life engagement can inform goal-setting and treatment selection in patients with schizophrenia., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Definitions of treatment success used in clinical trials of medications for serious mental illness have generally focused on reduction in symptoms assessed via observer-rated instruments such as the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale in MDD and the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale in schizophrenia. In recent years, there has been a shift toward incorporating outcomes into clinical research that are patient-reported and reflect outcomes and goals that are meaningful to the patient. These outcomes include aspects of functioning (eg, activities of daily living and role fulfillment), as well as life engagement, which interacts with symptomatic and functional outcomes and encompasses aspects such as motivation and vitality. In a recent roundtable meeting, a panel of 5 experts discussed life engagement and its relationship to symptoms and functioning in patients with major depressive disorder (MDD) and schizophrenia. This Academic Highlights summarizes their discussion., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Objective: To evaluate the short- and long-term effects of brexpiprazole on patient functioning in schizophrenia., Methods: Data were included from three 6-week, randomized, double-blind, placebo-controlled studies (hospitalized patients); a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study (terminated early by the study sponsor based on the positive result of an interim analysis); and two 52-week, open-label extension studies-all in patients with schizophrenia ( DSM-IV-TR criteria) and conducted from July 2011-February 2016. Patients allocated to oral brexpiprazole received 2-4 mg/d (short-term studies) or 1-4 mg/d (long-term studies). Functioning was measured using the Personal and Social Performance (PSP) and Global Assessment of Functioning (GAF) scales, with response defined as a PSP/GAF increase of ≥ 10 points and remission as PSP score ≥ 71 or GAF score ≥ 61., Results: Patients receiving brexpiprazole (n = 831) showed greater improvement than those receiving placebo (n = 490) from baseline to week 6 in PSP score (least squares mean difference, 3.20; 95% confidence interval, 1.82-4.58; P  < .0001; Cohen d  = 0.31) and in all 4 PSP domains. At week 52 of the maintenance study (which had a low completion rate primarily due to the early termination), GAF functional remission was achieved by 65.3% (62/95) of stabilized patients randomized to brexpiprazole and 47.1% (48/102) of stabilized patients randomized to placebo, with a number needed to treat of 6 (95% confidence interval, 4-22; P  = .0076). At week 52 of the open-label studies (n = 177), PSP functional response and remission were achieved by 84.2% and 41.8% of patients receiving brexpiprazole, respectively., Conclusions: Although limited by the lack of an active comparator, analyses of this large dataset demonstrate that brexpiprazole treatment is associated with clinically relevant improvement in functioning among patients with schizophrenia, in the short term and long term., Trial Registration: Data used in this post hoc analysis were from studies with ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380, NCT01668797, NCT01397786, and NCT01810783., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Although antipsychotics have been available for almost 70 years and greatly improved outcomes for individuals with schizophrenia, all currently available options derive their efficacy from blockade of dopaminergic receptors. However, this mechanism of action leaves many symptoms unresolved and is associated with a significant side effect burden. The mechanisms underlying schizophrenia, which were initially thought to be related to excessive presynaptic dopamine in specific areas of the brain, are now understood to be much more complex and involve structural and molecular changes throughout brain circuits. Consequently, drug discovery efforts have sought new targets in the search for safer and more effective medications that can improve symptoms of schizophrenia and psychosis, including trace amine-associated receptors (TAARs), muscarinic receptors, and serotonergic receptors. Positive phase 2 trial results indicating efficacy and safety of the TAAR1 agonist ulotaront (SEP-363856) and of the muscarinic M1/M4 agonist KarXT (xanomeline plus trospium) for total, positive, and negative symptoms in patients with acute exacerbation of schizophrenia, and of the serotonin 5-HT2A agonist/antagonist pimavanserin in patients with schizophrenia and predominant negative symptoms for negative symptom control are encouraging. Taken together, these data indicate in the context of ongoing phase 3 trial programs that patients with schizophrenia may soon have access to the first non-D2 blocking medication, which could drastically change the treatment landscape and improve outcomes for many of the individuals with schizophrenia who do not fully respond to or cannot tolerate currently available antipsychotic agents that currently all act via postsynaptic dopamine D2 receptor blockade., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Tardive dyskinesia (TD) consists of involuntary movements of the tongue, lips, face, trunk, and extremities that occur in patients treated long-term with dopamine antagonist medications. TD can be associated with significant functional impairment and be socially stigmatizing. TD, once established, has proved to be often irreversible and remains a significant treatment issue. An accurate and early diagnosis of TD is crucial because the risk of permanence increases over time. Clinicians should be educated on which patients are most at risk for TD and conduct assessments through clinical examination or through the use of a structured evaluative tool such as the Abnormal Involuntary Movement Scale (AIMS). Patients and caregivers need to be educated about the risks of and alternatives to antipsychotic medication and early signs of TD. New treatment approaches to persistent TD are available and approved by the US Food and Drug Administration: the vesicular monoamine transporter-2 (VMAT2) inhibitors, deutetrabenazine and valbenazine. When treatment is initiated, a baseline assessment should be obtained by clinicians using the AIMS and follow-up assessments should be done on a regular basis. In this educational activity, Drs Correll and Citrome offer a review of the diagnostic and treatment fundamentals for TD., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

T reatment-resistant schizophrenia (TRS) represents a major clinical challenge. The broad definition of TRS requires nonresponse to at least 2 sequential antipsychotic trials of sufficient dose, duration, and adherence. Several demographic, clinical, and neurologic predictors are associated with TRS. Primary (or early) TRS is present from the beginning of therapy, while patients with secondary (or later-onset) TRS initially respond to antipsychotics but become resistant over time, often after relapses. Guidelines worldwide recognize clozapine as the most effective treatment option for TRS, but clozapine is underused due to various barriers. Importantly, studies indicate that response rates are higher when clozapine is initiated earlier in the treatment course. Side effects are common with clozapine, particularly in the first few weeks, but can mostly be managed without discontinuation; they do require proactive assessment, intervention, and reassurance for patients. Furthermore, plasma leucocyte and granulocyte levels must be monitored weekly during the first 18-26 weeks of treatment, and regularly thereafter, according to country regulations. Therapeutic drug monitoring of clozapine trough plasma levels is helpful to guide dosing, with greatest efficacy at plasma clozapine levels ≥350 µg/L, although this level is not universal. Notably, plasma clozapine levels are generally greater at lower doses in nonsmokers, patients with heavy caffeine consumption, in women, in obese people, in those with inflammation (including COVID-19 infection), and in older individuals. Earlier and broader use of clozapine in patients with TRS is an important measure to improve outcomes of patients with this most severe form of the illness., (© Copyright 2021 Physicians Postgraduate Press, Inc.)