Antipsychotic Monotherapy Research Articles

Estimation of cardiac QTc intervals in people prescribed antipsychotics: a comparison of correction factors.

Background:A prolonged electrocardiogram (ECG) QT interval is associated with cardiac events and increased mortality. Antipsychotics can prolong the QT interval. The QT interval requires correction (QTc) for heart rate using a formula or QT-nomogram. The QT and QTc can be calculated automatically by the ECG machine or manually; however, machine-measured QT(c) intervals may be inaccurate.Objective:We aimed to investigate the mean QTc and proportion of prolonged QTc intervals in people taking antipsychotic medicines.Methods:We conducted an observational retrospective chart review and data analysis of all consecutive patients taking antipsychotics, with an ECG record, admitted to the psychiatric unit of a large tertiary hospital in Brisbane, Australia, between 1 January 2017 and 30 January 2019. We investigated the mean QTc of people taking antipsychotics to determine differences using (a) machine versus manual QT interval measurement and (b) QTc correction formulae (Bazett, Fridericia, Framingham, Hodges and Rautaharju) and the QT-nomogram. We also determined the number of people with a prolonged QTc using different methods and compared rates of prolonged QTc with antipsychotic monotherapy and polypharmacy.Results:Of 920 included people, the mean (±SD) machine-measured, Bazett-corrected QT interval (recorded from the ECG) was 435 ms (±27), significantly longer (p < 0.001) than the mean manually measured corrected QT intervals with Fridericia 394 ms (±24), Framingham 395 ms (±22), Hodges 398 ms (±22) and Rautaharju 400 ms (±24) formulae. There were significantly more people with a prolonged QTc using machine-measured QT and the Bazett formula (12.0%, 110/920) when compared with manually measured QT and the Fridericia formula (2.2%, 20/920) or QT-nomogram (0.7%, 6/920). Rates of QTc prolongation did not differ between people taking antipsychotic polypharmacy compared with monotherapy.Conclusion:Machine-measured QTc using the Bazett formula overestimates the QTc interval length and number of people with a prolonged QTc, compared with other formulae and the QT-nomogram. We recommend manually measuring the QT and correcting with the Fridericia formula or QT-nomogram prior to modifying antipsychotic therapies.

Safety of antipsychotic polypharmacy versus monotherapy in specific dose categories in a nation-wide cohort of 61,889 patients with schizophrenia

Safety of antipsychotic polypharmacy versus monotherapy in specific dose categories in a nation-wide cohort of 61,889 patients with schizophrenia

Metabolic and clinical effect of alpha-lipoic acid administration in schizophrenic subjects stabilized with atypical antipsychotics: A 12-week, open-label, uncontrolled study

BackgroundMany of the atypical antipsychotics induce metabolic side effects, limiting their use in clinical practice. Alpha-lipoic acid (ALA) was proposed as a new approach in schizophrenia to improve metabolic effects of atypical antipsychotics. The aim of the study is to evaluate the effect of ALA on metabolic and clinical parameters among schizophrenic subjects. Methods15 schizophrenic subjects, in stable atypical antipsychotic monotherapy were included in the study. ALA was administrated at the oral daily dose of 600 ​mg/d in addition to antipsychotic therapy. Metabolic, clinical, and psychopathological parameters were measured at typical antipsychotics. e initial screening, and after 12 weeks. ResultsALA produced a statistically significant reduction in QTc (p ​= ​0.012), blood glucose (p ​= 0.005), AST (p ​= ​0.021), γGT (p ​= ​0.035), CPK (p ​= ​0.005) and prolactinaemia (p ​= ​0.026). In contrast, there was a significant increase in HbA1c (p ​= ​0.026). No effects on body weight and blood lipid levels (triglycerides, total cholesterol, HDL, LDL) emerged. ConclusionsALA treatment appeared to be effective for reducing diabetes risk, liver functionality parameters, hyperprolactinaemia and QTC interval. ALA appears to be safe as adjunctive components in schizophrenia.

A longitudinal study of alterations of circulating DJ-1 and miR203a-3p in association to olanzapine medication in a sample of first episode patients with schizophrenia

Among different proposed pathophysiological mechanisms, redox imbalance has been suggested to be a potential contributor in the pathogenesis of schizophrenia.DJ-1 is a redox-sensitive protein that has been shown to have neuroprotective function in the brain in Parkinson's disease and other neurodegenerative diseases. However, a role for DJ-1 in schizophrenia is unknown. Bioinformatic analysis suggested that microRNA (miR)-203a-3p could target the 3′ untranslated region (UTR) of DJ-1. In whole blood and blood-derived exosomes of 11 first episode antipsychotic naïve schizophrenia patients, DJ-1 protein and mRNA demonstrated decreased DJ-1 mRNA and protein and increased miR203a-3p levels compared to healthy controls. In whole blood, antipsychotic monotherapy with olanzapine for 6 weeks increased DJ-1 and attenuated miR203a-3p levels, whereas in blood derived exosomes, olanzapine returned DJ-1 and miR203a-3p to levels seen healthy controls. Consistent with this finding, we showed that human umbilical vein endothelial cells (HUVACs) transfected with a DJ-1–3′ UTR luciferase reporter construct displayed reduced gene expression when subjected to the oxidative stressor H2O2. Transfection of a miR203a-3p mimic into HUVACs reduced DJ-1–3 ‘UTR reporter gene expression, while transfection of an anti miR-203a-3p prevented the H2O2-induced downregulation of the reporter gene. We conclude that miR-203a-3p is an essential mediator of oxidative stress in schizophrenia via its ability to target the 3’ UTR of DJ-1 and antipsychotic monotherapy restores DJ-1 antioxidant levels by regulating miR203a-3p expression. miR-203a-3p and DJ-1 might represent attractive targets for the treatment of pathologies such as schizophrenia that has underlying oxidative stress.

Subjective Medication Satisfaction With Antipsychotic Polypharmacy in a Naturalistic Inpatient and Outpatient Sample.

Objective: The aim of this study was to examine satisfaction with pharmacologic treatment in patients who received antipsychotic polypharmacy compared to antipsychotic monotherapy. Methods: This longitudinal cohort study was conducted in two mental health care institutes in Amsterdam, the Netherlands, among a randomly selected sample of in- and outpatients with a severe mental illness. Analyses were performed on data collected in 2011 for 185 patients who were diagnosed with schizophrenia or unspecified psychosis according to DSM-IV criteria. The outcome measure was the Treatment Satisfaction Questionnaire for Medication, version II. One-way analyses of covariance were performed to examine differences in treatment satisfaction between patients who received antipsychotic polypharmacy compared to antipsychotic monotherapy while controlling for the effects of clozapine, antipsychotic dose, and use of long-acting injectable antipsychotics. Results: Twenty percent of patients in this sample received 2 antipsychotic agents; in half of those patients, this involved a combination with clozapine. Polypharmacy resulted in less satisfaction with side effects compared to monotherapy (P = .002). No difference was found in perceived effectiveness (P = .168) or overall medication satisfaction (P = .379). Conclusions: These results confirm that antipsychotic polypharmacy is common in a random in- and outpatient sample. Patients who receive 2 antipsychotic agents are just as positive about the effectiveness and ease of use of and overall satisfaction with their medication compared to those who receive antipsychotic monotherapy. They are, however, less satisfied with perceived side effects of their medication, which may indicate that side effect profiles of antipsychotic combinations are less favorable.

Pharmacological treatment for psychotic depression.

Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an antipsychotic, another treatment (e.g. mifepristone), or combination of an antidepressant plus an antipsychotic. This is an update of a review first published in 2005 and last updated in 2015. 1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, mifepristone monotherapy,and the combination of an antidepressant plus an antipsychotic versus placeboand/oreach other. 2. To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment. A search of the CochraneCentral Register of Controlled Trials(CENTRAL),in the Cochrane Library; the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR);Ovid MEDLINE (1950-);Embase (1974-); and PsycINFO (1960-)wasconducted on21 February 2020.Reference lists of allincludedstudies and related reviews were screened and key study authors contacted. All randomised controlled trials (RCTs) that included participants with acute major depression with psychotic features, as well as RCTs consisting of participants with acute major depression with or without psychotic features, that reported separately on the subgroup of participants with psychotic features. Two review authors independently extracted data and assessed risk of bias in the included studies, according to criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used intention-to-treat data. Primary outcomes were clinical response for efficacy and overall dropout rate for harm/tolerance. Secondary outcome were remission of depression, change from baseline severity score, quality of life, and dropout rate due to adverse effects. For dichotomous efficacy outcomes (i.e. response and overall dropout), risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Regarding the primary outcome of harm, only overall dropout rates were available for all studies. If the study did not report any of the response criteria as defined above, remission as defined here could be used as an alternative. For continuously distributed outcomes, it was not possible to extract data from the RCTs. MAIN RESULTS: The search identified 3947 abstracts, but only 12 RCTs with a total of 929 participants could be included in the review. Because of clinical heterogeneity, few meta-analyses were possible. The main outcome was reduction in severity (response) of depression, not of psychosis. For depression response, we found no evidence of a difference between antidepressant and placebo (RR 8.40, 95% CI 0.50 to 142.27; participants = 27, studies = 1; very low-certainty evidence) or between antipsychotic and placebo (RR 1.13, 95% CI 0.74 to 1.73; participants = 201, studies = 2; very low-certainty evidence). Furthermore, we found no evidence of a difference in overall dropouts with antidepressant (RR 1.24, 95% CI 0.34 to 4.51; participants = 27, studies = 1; very low-certainty evidence) or antipsychotic monotherapy (RR 0.79, 95% CI 0.57 to 1.08; participants = 201, studies = 2; very low-certainty evidence). No evidence suggests a difference in depression response (RR 2.09, 95% CI 0.64 to 6.82; participants = 36, studies = 1; very low-certainty evidence) or overall dropouts (RR 1.79, 95% CI 0.18 to 18.02; participants = 36, studies = 1; very low-certainty evidence) between antidepressant and antipsychotic. For depression response, low- to very low-certainty evidence suggests that the combination of an antidepressant plus an antipsychotic may be more effective than antipsychotic monotherapy (RR 1.83, 95% CI 1.40 to 2.38; participants = 447, studies = 4), more effective than antidepressant monotherapy (RR 1.42, 95% CI 1.11 to 1.80; participants = 245, studies = 5), and more effective than placebo (RR 1.86, 95% CI 1.23 to 2.82; participants = 148, studies = 2). Very low-certainty evidence suggests no difference in overall dropouts between the combination of an antidepressant plus an antipsychotic versus antipsychotic monotherapy (RR 0.79, 95% CI 0.63 to 1.01; participants = 447, studies = 4), antidepressant monotherapy (RR 0.91, 95% CI 0.55 to 1.50; participants = 245, studies = 5), or placebo alone (RR 0.75, 95% CI 0.48 to 1.18; participants = 148, studies = 2). No study measured change in depression severity from baseline, quality of life, or dropouts due to adverse events. We found no RCTs with mifepristone that fulfilled our inclusion criteria. Risk of bias is considerable: we noted differences between studies with regards to diagnosis, uncertainties around randomisation and allocation concealment, treatment interventions (pharmacological differences between various antidepressants and antipsychotics), and outcome criteria. Psychotic depression is heavily under-studied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone. Evidence for efficacy of mifepristone is lacking.

Exploring Hidden Issues in the Use of Antipsychotic Polypharmacy in the Treatment of Schizophrenia.

The mainstay of schizophrenia treatment is pharmacological therapy using various antipsychotics including first- and second-generation antipsychotics which have different pharmacokinetic and pharmacodynamic property leading to differential presentation of adverse events (AEs) and treatment effects such as negative symptoms, cognitive symptoms and cormorbid symptoms. Major treatment guidelines suggest the use of antipsychotic monotherapy (APM) as a gold standard in the treatment of schizophrenia. However, the effects of APM is inadequate and less potent to achieve symptom remission as well as functional recovery in real practice which has been consistently reported in numerous controlled clinical trials, large practical trials, independent small studies and systematic reviews till today. Therefore antipsychotic polypharmacy (APP) regardless of the class of antipsychotics has been also commonly utilized for many reasons in real world practice. However, APP has also crucial pitfalls including increase of total psychotics including antipsychotics, high-doses of antipsychotics used, poor compliance, drug-drug interaction and risks for developing AEs, all of which are paradoxically related to poor clinical outcomes, whereas APP has also substantial advantages in reduction of re-hospitalization, severe psychopathology and targeted control of concurrent symptoms. Given currently limited therapeutic options, it is also important to properly utilize APP in order to maximize its clinical utility and minimize its risk for better treatment outcomes for patients with schizophrenia, based on risk/benefit with full understanding of pharmacological and clinical issues on APP. The present paper intends to address intriguing and important issues in the use of APP in real world practice.

Comparison of Efficacy and Safety between Long-Acting Injectable Antipsychotic Monotherapy and Combination of Long-Acting Injectable and Oral Antipsychotics in Patients with Schizophrenia

Background Long-acting injectable (LAI) antipsychotics are used as a monotherapy in patients with schizophrenia. However, the combination of LAI and oral antipsychotics is commonly used in clinical practice, despite there being very limited studies investigating the efficacy and safety of this combination compared with LAI antipsychotic monotherapy. Objective To study the efficacy and safety of LAI antipsychotic monotherapy compared with the combination of LAI and oral antipsychotics in patients with schizophrenia. Methods This study was a retrospective cohort study, which classified eligible patients into two groups: the LAI antipsychotic monotherapy group and the combination of LAI and oral antipsychotic group. The primary outcome was hospitalization between groups. The duration of the study was 2 years. Results In total, 86 patients completed the study and were analysed (LAI antipsychotic monotherapy group: n = 25; combination of LAI and oral antipsychotic group: n = 61). There was no significant difference in hospitalization between the two groups (P = 1.000). For other outcomes, there were also no significant differences in both all-cause discontinuation (P = 0.667) and adverse drug reactions (P = 0.732) between the two groups. Conclusion The efficacy and safety of LAI antipsychotic monotherapy appeared similar to the combination of LAI and oral antipsychotics in patients with schizophrenia. Therefore, the combination of LAI and oral antipsychotics, which is commonly used in clinical practice, may not be necessary.

Antipsychotic medication-mediated cognitive change in schizophrenia and polygenic score for cognitive ability

Cognitive symptoms of schizophrenia are reported to be minimally responsive to treatment with antipsychotic medications, though variability exists and many prior studies have significant confounds. Here, we examined the response of cognitive symptoms to antipsychotic medications in 71 inpatients with schizophrenia on and off antipsychotic medications in a blinded, placebo-controlled, cross-over study design. Patients received either antipsychotic medication monotherapy or placebo for 4–6 weeks before switching conditions. Neuropsychological testing, including working memory, intelligence, episodic memory, and verbal fluency tests, was administered during each condition. Additionally, we assessed whether polygenic scores for cognitive ability (PGScog) related to variability in antipsychotic medication-induced changes in cognitive performance. Overall, significant changes in cognition were not observed in response to medications (p's > 0.05) except for in episodic memory (p = 0.01), which showed a medication-related improvement. Some antipsychotic medication-related cognitive changes were associated with genetic predisposition to cognitive ability: PGScog showed positive correlations with medication-induced improvements in verbal list learning (p = 0.02) and category fluency (p = 0.03). Our primary results reinforce the notion that in general, cognitive measures are minimally responsive to antipsychotic medication. However, PGScog results suggest that genetic variation may influence the ability of current treatments to affect cognitive change within this patient population. This study underscores the need for development of novel treatment options specifically targeting cognitive symptoms as well as the importance of genetic variability in treatment response for patients with schizophrenia.

Comparison of Clinical Features of Bipolar Disorder Patients with and without Psychiatric Comorbidity.

Bipolar disorder (BPD) is a psychiatric condition that often manifests together with Axis-I comorbidity. Comorbidity of psychiatric disorders influences the recognition, prognosis, and treatment of the disorder, posing difficulties for the patient and physician. This study aims at identifying Axis-I comorbidities and their characteristics in patients with BPD. This retrospective study included 255 patients diagnosed with BPD according to the DSM-IV. Comorbidities were determined using the SCID-I, a semistructured sociodemographic data form developed by the authors, and a mood chart assessing clinical aspects. The patients were divided into 2 groups, those with and without comorbidity, and compared. Out of these 255 patients, 35% was found to have a current and 84.3% a lifelong comorbid psychiatric disorder. About 33.1% of these patients had 1, 11.3% had 2, and 8.8% had more than 2 comorbid disorders. At least one comorbid anxiety disorder was found in 38.7% of the patients. Obsessive and compulsive disorder (OCD) being the most common comorbid psychiatric disorder, followed by social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Comparing the clinical parameters between the 2 groups due to the presence of psychiatric comorbidity in the BD patients, there were statistically significant differences in terms of the number of depressive episodes (P = .041) and mania/hypomania (P = .048), and the need for antipsychotic monotherapy (P = .007) and antidepressants (P = .001) for prophylaxis between the 2 groups. Axis-I psychiatric disorders and particularly OCD and anxiety disorders accompanying BPD prevail at a high rate. The presence of comorbid psychiatric disorder in BPD may negatively affect the clinical prognosis of the condition; therefore, this area requires more study and careful investigation.

Post-clozapine in a clinical setting: A retrospective case note review in Kumamoto, Japan (2009-2019).

Clozapine is commonly prescribed in dopamine supersensitivity psychosis (DSP) cases in Japan. However, limited knowledge on treatment post-clozapine discontinuation use exists. We investigated antipsychotic medications, patient status, and DSP episodes before, during, and after clozapine treatment using medical records of 30 schizophrenia patients (mean age, 51 years; mean illness duration before clozapine treatment, 24 years; mean clozapine treatment duration, 1.6 years), who discontinued clozapine between 2009 and 2019. In our region, long-acting injectable antipsychotic monotherapy and polypharmacy (half with aripiprazole) accounted for 17% and 50% post-clozapine use, respectively. Furthermore, patient status rarely improved with subsequent DSP treatment, including clozapine re-initiation.

Characteristics of the corpus callosum in chronic schizophrenia treated with clozapine or risperidone and those never-treated

BackgroundThe corpus callosum (CC) deficits have been well documented in chronic schizophrenia. However, the long-term impacts of antipsychotic monotherapies on callosal anatomy remain unclear. This cross-sectional study sought to explore micro- and macro-structural characteristics of the CC in never-treated patients and those with long-term mono-antipsychotic treatment.MethodsThe study included 23 clozapine-treated schizophrenia patients (CT-SCZ), 19 risperidone-treated schizophrenia patients (RT-SCZ), 23 never-treated schizophrenia patients (NT-SCZ), and 35 healthy controls (HCs). High resolution structural images and diffusion tensor imaging (DTI) data for each participant were obtained via a 3.0 T MR scanner. FreeSurfer was used to examine the volumes and fractional anisotropy (FA) values of the CC for each participant.ResultsThere were significant deficits in the total and sub-regional CC volume and white matter integrity in NT-SCZ in comparison with healthy subjects. Compared with NT-SCZ, both CT-SCZ and RT-SCZ showed significantly increased FA values in the anterior CC region, while only RT-SCZ showed significantly increased volume in the mid-anterior CC region. Moreover, the volume of the mid-anterior CC region was significantly smaller in CT-SCZ compared to HCs. No correlations of clinical symptoms with callosal metrics were observed in schizophrenia patients.ConclusionsOur findings provide insight into micro- and macro-structural characteristics of the CC in chronic schizophrenia patients with or without antipsychotics. These results suggest that the pathology itself is responsible for cerebral abnormalities in schizophrenia and that chronic exposure to antipsychotics may have an impact on white matter structure of schizophrenia patients, especially in those with risperidone treatment.

A systematic review and meta‐analysis of maintenance treatment for psychotic depression

Purpose To perform a systematic review on the use of maintenance treatment to prevent relapse and recurrence in patients with psychotic unipolar or bipolar depression. Methods We conducted an electronic search in December 2019 (and an updated search in July 2021) of four databases (PubMed, Embase, PsycINFO, and Cochrane) to identify controlled studies comparing the relapse rates of patients receiving maintenance treatment for psychotic unipolar depression and psychotic bipolar depression. A meta-analysis was made that included three studies comparing antidepressant (AD) and antipsychotic (AP) combination therapy with AD monotherapy. We used the GRADE tool to assess the quality of evidence. Results We included five randomized controlled trials fulfilling the inclusion criteria, making three comparisons: (a) AD + AP versus AD monotherapy; (b) AD + AP versus AP monotherapy; (c) AD + electroconvulsive therapy versus AD monotherapy. The included studies only examined patients with psychotic unipolar depression. The largest included study reported a statistically significant advantage of AD + AP compared with AD monotherapy. We made a meta-analysis of the three studies comparing AD + AP combination therapy with AD monotherapy, which included 195 patients and 56 events. The meta-analysis did not show a statistically significant difference between these treatments. Conclusions Contrary to the finding of the largest study, we did not find a statistically significant difference between AD + AP combination therapy and AD monotherapy in the meta-analysis. There is insufficient evidence to support the superiority of any treatment modality as maintenance treatment for psychotic depression. Further studies are required.

The Impact of Antipsychotic Dose Reduction on Clinical Outcomes and Health Care Resource Use Among Medicare Patients with Schizophrenia.

BackgroundAntipsychotic medications are used to treat schizophrenia and may be associated with adverse effects, including tardive dyskinesia (TD), following prolonged use or upon changes in dosing regimen.ObjectiveThis retrospective analysis evaluated the burden of antipsychotic dose reduction in Medicare patients with schizophrenia.MethodsThis matched cohort study used Medicare claims data (2006–2017) analyzed for patients with schizophrenia and two or more claims for antipsychotics, with one or more antipsychotic monotherapy period ≥ 90 days. Cohorts were defined for patients with antipsychotic dose reductions ≥ 10% and stable doses. A separate analysis was conducted using patients with dose reductions ≥ 30%. Outcomes included all-cause emergency room (ER) visits, all-cause inpatient visits, schizophrenia relapse, other psychiatric relapse, and TD diagnosis. Covariates included age, disease duration, comorbidities, and medication use.ResultsThe analysis included 276,030 patients with ≥ 10% dose reductions and 211,575 patients with ≥ 30% dose reductions. Patient characteristics were balanced between cohorts. Patients with ≥ 10% or ≥ 30% dose reductions had a shorter time to ER visit, inpatient visit, schizophrenia relapse, other psychiatric relapse, and TD diagnosis versus those receiving stable doses (all p < 0.001). Significance was maintained when unmatched baseline characteristics were adjusted.ConclusionsPatients with antipsychotic dose reductions may be at risk for increased ER visits, increased hospitalizations, and significant unfavorable mental health-related clinical outcomes, suggesting that dose reduction may increase overall health care burden in some patients with schizophrenia. This work highlights the need for alternative strategies in the management of patients with TD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40261-021-01060-3.

Selective Serotonin Reuptake Inhibitors and Clozapine: Clinically Relevant Interactions and Considerations.

The monoamine hypothesis of depression attributes the symptoms of major depressive disorders to imbalances of serotonin, noradrenaline, and dopamine in the limbic areas of the brain. The preferential targeting of serotonin receptor (SERT) by selective serotonin reuptake inhibitors (SSRIs) has offered an opportunity to reduce the range of these side effects and improve patient adherence to pharmacotherapy. Clozapine remains an effective drug against treatment-resistant schizophrenia, defined as failing treatment with at least two different antipsychotic medications. Patients with schizophrenia who display a constellation of negative symptoms respond poorly to antipsychotic monotherapy. Negative symptoms include the diminution of motivation, interest, or expression. Conversely to the depressive symptomology of interest presently, supplementation of antipsychotics with SSRIs in schizophrenic patients with negative symptoms lead to synergistic improvements in the function of these patients. Fluvoxamine is one of the most potent inhibitors of CYP1A2 and can lead to an increase in clozapine levels. Similar increases in serum clozapine were detected in two patients taking sertraline. However, studies have been contradictory as well, showing no such increases, which are worrying. Clinicians should be aware that clozapine levels should be monitored with any coadministration with SSRIs.

Consideration of Long-Acting Injectable Antipsychotics for Polypharmacy Regimen in the Treatment of Schizophrenia: Put It on the Table or Not?

Antipsychotic monotherapy (APM) is considered best-acceptable treatment option regardless of antipsychotic class and formulation types for treating schizophrenia. However, antipsychotic polypharmacy (APP) has been also widely utilized in routine clinical practice. Despite APP has some clinical benefits it has also numerous pitfalls in relation with increased total number and doses of APs leading to adverse events as well as decrease of treatment adherence and persistence resulting in poor clinical outcomes. Recent introduction of long-acting injectable antipsychotics (LAIs) to the market has offered a chance for better medication adherence/persistence and also provided a simplification of treatment regime leading to more stabilized treatment for schizophrenia patients. When we cannot stay away from APP in the treatment of schizophrenia, clinicians need to find more proper APP regimens and thereby utilization of APP in efficient way should be a practical strategy to benefit schizophrenia patient in a real world treatment setting. With this regard, LAIs can be one of available APP regimen for treatment of schizophrenia in routine practice since their clinical utility and pharmacokinetic stability over oral APs have been well-elaborated today. However, when we have to commence LAIs as a part of APP with oral APs or other LAIs, every effort should be made before doing so whether or not validated and available treatment options or other clinical factors were not done or evaluated yet. Any treatment guidelines do not support APP regardless of the formulation of APP regimen or address two or more LAIs for treatment of schizophrenia till today.

Antipsychotic polypharmacy in adult patients diagnosed with schizophrenia: A retrospective study.

Antipsychotic polypharmacy (APP) is a common practice in the treatment of schizophrenia. In this study, we aimed to identify the prevalence of APP in our department, as well as the trends associated with co-prescribing antipsychotics. We collected data from the medical records of all 193 inpatients diagnosed with schizophrenia who were admitted to Prof. Dr. Alexandru Obregia Clinical Psychiatry Hospital (Bucharest, Romania), Department 9, during January 2019-December 2019. Demographic characteristics of the patients, clinical diagnosis, psychiatric admission type and duration of hospitalization were examined. Data regarding the antipsychotic regimen at discharge and other psychotropic drugs used were collected. A total of 69 (35.75%) patients received more than 2 antipsychotics upon discharge. Patients treated with APP did not differ in regards to sex, age, education level, employment status, marital status, living situation, type of admission from those receiving antipsychotic monotherapy (APM). Prolonged hospitalization was found to be an independent predictor of APP (P=0.014). Most of the combinations used in our unit included clozapine (47.8%), and the most frequently used treatment in the APP group was the combination of paliperidone and clozapine (14.5%). In the APP group, 30 (43.5%) patients included in their regimen was a long-acting intramuscular antipsychotic. There was no significant difference in terms of the use of mood stabilizers, antiparkinsonian drugs or anxiolytics between the APP and the APM group; yet, a higher prevalence of antidepressant use, although not statistically significant (P=0.067), in the APP group compared to the APM group, was observed. The use of APP as a long-term regimen is a common practice in our department, as it is worldwide. There is a great need for randomized-control trials and evidence-based studies in order to define the safest and most effective combinations of antipsychotics and also the characteristics of patients that may benefit from these combinations.

Real-World Functioning in Patients With Schizophrenia: Beyond Negative and Cognitive Symptoms.

Introduction: Interest in the idea of recovery for certain patients with schizophrenia has been growing over the last decade. Improving symptomatology and functioning is crucial for achieving this. Our study aims to identify those factors that substantially contribute to real-world functioning in these patients.Methods: We carried out a cross-sectional study in stable outpatients with schizophrenia on maintenance antipsychotic monotherapy. Patients: We studied 144 outpatients with schizophrenia (DSM-IV-TR criteria) meeting the following criteria: (1) 18–65 years of age; (2) being clinically stable for at least the previous three months; (3) on maintenance antipsychotic monotherapy (prescriptions ≤ 10 mg olanzapine, ≤200 mg quetiapine, or ≤100 mg levomepromazine as hypnotics were also allowed); and (4) written informed consent. Assessment: We collected information on demographic and clinical variables by using an ad hoc questionnaire. For psychopathology, we employed the Spanish versions of the following psychometric instruments: the Positive and Negative Syndrome Scale (PANSS), the Brief Negative Symptom Scale (BNSS-Sp), and the Calgary Depression Scale (CDS). In addition, cognitive domains were assessed using the Verbal Fluency Test (VFT), the Digit Symbol Substitution Test (DSST), and the Trail Making Test, parts A and B (TMT-A and TMT-B). Finally, we employed the Spanish versions of the University of California San Diego Performance-based Skills Assessment (Sp-UPSA) and the Personal and Social Performance (PSP) for assessing functional capacity and real-world functioning, respectively. Statistical analysis: A forward stepwise regression was conducted by entering those variables significantly associated with PSP total score into the univariate analyses (Student's t-test, ANOVA with Duncan's post-hoc test, or bivariate Pearson correlation).Results: A total of 144 patients; mean age 40 years, 64% males, mean length of illness 12.4 years, PSP total score 54.3. The final model was a significant predictor of real-world functioning [F(7, 131) = 36.371, p < 0.001] and explained 66.0% of the variance. Variables retained in the model: BNSS-Sp abulia, asociality, and blunted affect, PANSS general psychopathology, Sp-UPSA transportation, TMT-B, and heart rate.Conclusion: Our model will contribute to a more efficient and personalized daily clinical practice by assigning specific interventions to each patient based on specific impaired factors in order to improve functioning.

A retrospective naturalistic study on the psychopharmacological treatment of schizoaffective disorder.

Evidence on the effectiveness of psychopharmacological treatment of schizoaffective disorder is scarce and mostly comes from indirect, nonspecific sources. We carried out a large retrospective study (n = 770) of every other consecutively numbered clinical record with a recorded ICD-10 diagnosis of schizoaffective disorder in the Andalusian Health Service record system. We gathered sociodemographic, drug treatment and clinical outcomes such as improvement, relapses and change over time on DSM-5 psychotic dimensions. We analyzed data to explore associations between drug use and clinical improvement. Antipsychotics were the most commonly used drugs (77%). 22.4% of patients experienced at least a mild improvement. Clozapine (odds ratio [OR] = 2.4) and aripiprazole (OR = 2.3) for global improvement, and quetiapine (OR = 3.5) for depression were the most effective drugs. Antidepressants, mood stabilizers and benzodiazepines were also associated with a better outcome in some DSM-5 dimensions such as delusions, hallucinations and language, respectively. Antipsychotic monotherapy was not associated with a better outcome. Our findings corroborate the role of antipsychotics as the essential psychopharmacological treatment for different symptoms of schizoaffective disorder. However, the role of mood stabilizers, antidepressants or BZD is controversial and should be individually considered.

Antipsychotic Polypharmacy for the Management of Schizophrenia: Evidence and Recommendations.

Schizophrenia is a debilitating illness with a lifetime prevalence estimate of 0.6% and consists of symptoms from the positive, negative, and cognitive domains. Social support, therapy, psychoeducation, and overall case management are very important aspects of the treatment of schizophrenia. However, as abnormalities in neurotransmission are one of the key findings of schizophrenia pathology, pharmacotherapies are cornerstones of the management of schizophrenia. Antipsychotics have been used as the primary pharmacological treatment of schizophrenia. These agents often have a good effect on reducing positive symptoms, but may not markedly improve negative symptoms or cognitive defects. However, at least 20% of individuals with schizophrenia do not experience a substantial response from monotherapy with antipsychotics. Further, despite evolving treatment protocols and advances in early recognition of the disorder, 70% of patients with schizophrenia require long-term, even lifetime, medication to control their symptoms and do not achieve complete recovery. To address these shortcomings, clinicians and research scientists have explored different combinations of treatments, polypharmacy, to improve the treatment of patients. Antipsychotic polypharmacy has been shown to cause more side effects than monotherapy, which is the main reason why most treatment guidelines caution against it. Antipsychotic monotherapy should be strived for and clozapine should be tried at the latest if two monotherapy trials with other antipsychotics have failed and no absolute contraindications exist. If residual symptoms exist despite trials of adequate dose and duration, other reasons that may reduce treatment effect should be ruled out. Long-acting injectables or blood concentration measurements should be considered to affirm compliance and proper serum levels. Antipsychotic polypharmacy should be considered and discussed with patients from whom the aforementioned procedures do not produce a satisfactory treatment result. In some cases, antipsychotic polypharmacy may produce better results than other forms of treatment augmentation, such as benzodiazepines. In particular, combining aripiprazole with clozapine may be effective in reducing treatment side effects or residual symptoms, and this is likely to hold true for combining other partial dopamine D2 agonists with clozapine as well, although currently scant data exist. More research is needed, both in controlled but also real-world settings, to define optimal antipsychotic polypharmacy and/or other psychotropic treatment augmentation strategies for specific patient groups and situations.