Adjunctive Aripiprazole Research Articles

A specialized unit for women with schizophrenia: Results from the healthcare model Observatories-Monitoring Stations and Interventions.

IntroductionThere are many theoretical reasons to implement gender-specific care for schizophrenia. For all these reasons, the Mutua Terrassa-Functional Unit for Women with Schizophrenia was inaugurated in January 2023 in the context of a community mental health service.ObjectivesOur aim today is to describe the health care model applied in this newly initiated unit.MethodsWe created a healthcare model in our new unit consisting of A)Five observatories of Health (somatic morbi-mortality, hyperprolactinemia-HPRL, substance use disorders, social exclusion/discrimination, and drug safety); B)Monitoring stations or vigilance teams (reflecting the 5 observatories); and C)resulting actions (specific interventions). The observatory teams each meet monthly. In this presentation, according to the healthcare model we implemented, we first describe data about the original patient recruitment and then focus on the observatories of somatic morbi-mortality and hyperprolactinemia.ResultsFrom 265 potentially eligible women, 42 were included in the 5 observatories. (A) of the 11 women in the observatory of somatic morbi-mortality, 10 women had died within the last 24 months. Causes of Death: (1)respiratory tract disease (n=5,45.4%), (2)cancer (n=3;27.3%): lung cancer (n=1), pancreatic cancer (n=1), kidney cancer (n=1), (3)ischemic colitis (n=1;9%), (4)Alzheimer disease (n=1;9%). 2) Morbidity. One woman had an ongoing glioblastoma. (B)Observatory of HPRL. Eight women with moderate/severe HPRL were included. Strategies for lowering prolactin levels were discussed with neuroendocrinologists. Interventions:adjunctive aripiprazole (n=3), switch to aripiprazole (n=2), lowering antipsychotic doses (n=2), and adjunctive cabergoline (n=1).ConclusionsDesignating special teams to focus on specific problems of women with schizophrenia will reduce morbidity and improve outcomes in this vulnerable population.Disclosure of InterestNone Declared

Assessing remission in major depressive disorder using a functional-structural data fusion pipeline: A CAN-BIND-1 study

Neural network-level changes underlying symptom remission in major depressive disorder (MDD) are often studied from a single perspective. Multimodal approaches to assess neuropsychiatric disorders are evolving, as they offer richer information about brain networks. A FATCAT-awFC pipeline was developed to integrate a computationally intense data fusion method with a toolbox, to produce a faster and more intuitive pipeline for combining functional connectivity with structural connectivity (denoted as anatomically weighted functional connectivity (awFC)). Ninety-three participants from the Canadian Biomarker Integration Network for Depression study (CAN-BIND-1) were included. Patients with MDD were treated with 8 weeks of escitalopram and adjunctive aripiprazole for another 8 weeks. Between-group connectivity (SC, FC, awFC) comparisons contrasted remitters (REM) with non-remitters (NREM) at baseline and 8 weeks. Additionally, a longitudinal study analysis was performed to compare connectivity changes across time for REM, from baseline to week-8. Association between cognitive variables and connectivity were also assessed. REM were distinguished from NREM by lower awFC within the default mode, frontoparietal, and ventral attention networks. Compared to REM at baseline, REM at week-8 revealed increased awFC within the dorsal attention network and decreased awFC within the frontoparietal network. A medium effect size was observed for most results. AwFC in the frontoparietal network was associated with neurocognitive index and cognitive flexibility for the NREM group at week-8. In conclusion, the FATCAT-awFC pipeline has the benefit of providing insight on the ‘full picture’ of connectivity changes for REMs and NREMs while making for an easy intuitive approach.

Pro-inflammatory markers are associated with response to sequential pharmacotherapy in major depressive disorder: a CAN-BIND-1 report.

There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD). In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10-20mg daily for 8weeks. Responders continued escitalopram while non-responders received adjunctive aripiprazole 2-10mg daily for 8weeks. Plasma levels of pro-inflammatory markers-C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C-C motif ligand-2 (CCL-2)-measured at baseline, and after 2, 8 and 16weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16. Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.

Early-Onset Effectiveness of Adjunctive Aripiprazole in Patients With Depression With Inadequate Response to First-Line Antidepressants

The aim of this study was to investigate the early effectiveness of adjunctive aripiprazole treatment on the clinical symptoms and quality of life in patients with major depressive disorder. In this 8-week study, subjects were randomly assigned to the early treatment group ( n = 26) or the delayed treatment group ( n = 20), which started adjunctive aripiprazole treatment from the first and third weeks of the study, respectively. Clinical symptoms and quality of life were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the World Health Organization Quality of Life Scale Abbreviated Version. The mean MADRS score and three MADRS items (apparent sadness, reported sadness, and reduced appetite) were significantly improved in the early treatment group than in the delayed treatment group only at week 2. In the total treatment group, depression significantly improved from week 2. The quality of life related to psychological health, physical health, and environment was significantly improved at week 4. Adjunctive aripiprazole treatment did not increase the severity of adverse events. Our results suggest the early effects of adjunctive aripiprazole treatment on depression and quality of life, especially for core mood symptoms and appetite. Hence, adjunctive aripiprazole treatment may be a clinically meaningful therapeutic alternative for patients with depression. [ Psychiatr Ann. 2022;52(12):518–526.]

Pain severity and pain interference during major depressive episodes treated with escitalopram and aripiprazole adjunctive therapy: a CAN-BIND-1 report

Escitalopram may have pain-alleviating effects for patients with comorbid pain and depression. This study aimed to quantify improvements in pain for patients on escitalopram and adjunctive aripiprazole. A secondary analysis of the CAN-BIND-1 trial was conducted which only included participants with a current depressive episode and pain. Participants received escitalopram (10-20mg) for eight weeks and treatment response was defined as a reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) of at least 50% from baseline. Non-responders at week 8 received adjunctive aripiprazole (2-10mg) for another eight weeks. The Brief Pain Inventory's pain severity (PSC) and pain interference (PIC) composite scores were measured at baseline, week 8, and week 16. Linear regression was used to determine how PSC and PIC differed between treatment responders and non-responders. Eighty-two participants with pain and depression received escitalopram. PSC and PIC decreased significantly regardless of treatment response at week 8, although responders had significantly lower PSC and PIC than non-responders. For the group receiving aripiprazole after week 8, neither PSC nor PIC improved further. Further research is needed to identify interventions that might treat both pain and depression symptoms.

Pretreatment anxious depression as a predictor of side effect frequency and severity in escitalopram and aripiprazole adjunctive therapy.

ObjectiveTo report side effect frequency and severity in patients with major depressive disorder (MDD) receiving escitalopram and aripiprazole adjunctive therapy and to examine whether pretreatment anxious depression is associated with the number and presence of specific side effects.Methods188 of the 211 trial participants provided information on side effects during treatment with escitalopram (10–20 mg) for 8 weeks, and nonresponders received further augmentation on aripiprazole (2–10 mg) adjunctive therapy for another 8 weeks, whereas responders remained on escitalopram. Participants completed the Toronto Side Effects Scale at weeks 2, 4, 10, and 12. Covariate‐adjusted negative binomial regression and Wilcoxon tests examined the association between anxious depression (GAD‐7 ≥ 10) and number of side effects. Covariate‐adjusted logistic regression and chi‐square tests explored the association between anxious depression and specific side effects.ResultsFor both therapies, the most frequent side effects were also the most severe. They mostly related to the central nervous system (CNS) (i.e., drowsiness and nervousness). Between baseline and week 2, the number of side effects participants experienced (incidence rate ratio [IRR] = 1.38, p = .010) or had trouble with (IRR = 1.34, p = .026) was significantly higher among those with anxious depression for escitalopram but not adjunctive aripiprazole. Further, odds of experiencing and having trouble with nervousness and agitation were also significantly higher in anxious depression for escitalopram only (p < .05).ConclusionPatients on escitalopram and aripiprazole adjunctive therapy may experience and have trouble with CNS side effects. Pretreatment anxious depression may predispose escitalopram recipients with MDD to developing side effects, especially those related to anxiety.

The impact of adjunctive aripiprazole on QT interval: a 12-week open-label trial in users on atypical antipsychotics

The impact of adjunctive aripiprazole on QT interval: a 12-week open-label trial in users on atypical antipsychotics

Efficacy and Safety of Adjunctive Aripiprazole, Metformin, and Paeoniae-Glycyrrhiza Decoction for Antipsychotic-Induced Hyperprolactinemia: A Network Meta-Analysis of Randomized Controlled Trials.

Aripiprazole, metformin, and paeoniae–glycyrrhiza decoction (PGD) have been widely used as adjunctive treatments to reduce antipsychotic (AP)-induced hyperprolactinemia in patients with schizophrenia. However, the comparative efficacy and safety of these medications have not been previously studied. A network meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety between aripiprazole, metformin, and PGD as adjunctive medications in reducing AP-induced hyperprolactinemia in schizophrenia. Both international (PubMed, PsycINFO, EMBASE, and Cochrane Library databases) and Chinese (WanFang, Chinese Biomedical, and Chinese National Knowledge infrastructure) databases were searched from their inception until January 3, 2019. Data were analyzed using the Bayesian Markov Chain Monte Carlo simulations with the WinBUGS software. A total of 62 RCTs with 5,550 participants were included in the meta-analysis. Of the nine groups of treatments included, adjunctive aripiprazole (<5 mg/day) was associated with the most significant reduction in prolactin levels compared to placebo (posterior MD = −65.52, 95% CI = −104.91, −24.08) and the other eight treatment groups. Moreover, adjunctive PGD (>1:1) was associated with the lowest rate of all-cause discontinuation compared to placebo (posterior odds ratio = 0.45, 95% CI = 0.10, 3.13) and adjunctive aripiprazole (>10 mg/day) was associated with fewer total adverse drug events than placebo (posterior OR = 0.93, 95% CI = 0.65, 1.77) and other eight treatment groups. In addition, when risperidone, amisulpride, and olanzapine were the primary AP medications, adjunctive paeoniae/glycyrrhiza = 1:1, aripiprazole <5 mg/day, and aripiprazole >10 mg/day were the most effective treatments in reducing the prolactin levels, respectively. Adjunctive aripiprazole, metformin, and PGD showed beneficial effects in reducing AP-induced hyperprolactinemia in schizophrenia, with aripiprazole (<5 mg/day) being the most effective one.

Long-term Efficacy and Tolerability of Adjunctive Aripiprazole for Major Depressive Disorder: Systematic Review and Meta-analysis.

Objective: To assess the long-term efficacy and safety of aripiprazole as an augmentation strategy for major depressive disorder (MDD).Data Sources: Ovid MEDLINE, PsycInfo, and Embase databases were systematically searched for clinical studies of adult patients with MDD on long-term aripiprazole augmentation.Study Selection and Data Extraction: Long-term follow-up was defined as ≥ 6 months. Primary outcome was remission from depression. Secondary outcome was incidence of adverse effects.Results: Four open-label studies were included in this review. Random effects meta-analysis of 3 studies (n = 2,117) revealed a weighted average remission proportion of 0.33 (0.16-0.51), showing trend of improved response with duration of treatment. Three studies (n = 2,231) provided adverse effects data. Medically significant weight gain (25%-28% participants) was higher in studies with patients receiving doses ≥ 5 mg and lower (3.5%) in a study using doses < 5 mg. Akathisia (15%-16%), insomnia (12%-17%), somnolence (14%), and fatigue (18%) were common adverse effects. Tardive dyskinesia risk was low (< 1%) at 1-year follow-up. All included studies were open-label, noncontrolled studies, with longest follow-up of 52 weeks, limiting efficacy and safety conclusions.Conclusions: Aripiprazole augmentation may be an effective long-term strategy for treatment of refractory MDD. Lower maintenance doses (2-5 mg) of aripiprazole may be effective and have fewer side effects compared to larger doses (> 5 mg-10 mg).

Metabolic profiles differences of overweight patients on olanzapine, clozapine and risperidone

AimsWe set out to examine the differences in metabolic profiles of at risk (overweight) patients across commonly used atypical antipsychotics (Olanzapine, Risperidone, Clozapine). We hypothesized that Olanzapine and Clozapine group will have more metabolic abnormalities compared to Risperidone.BackgroundCardiovascular diseases remain the leading cause of morbidity and mortality among people with schizophrenia. Since the introduction of atypical antipsychotics, there is cumulative evidence of their association with metabolic abnormalities. Clozapine and Olanzapine are known to constitute the highest metabolic risks amongst atypical antipsychotics.MethodThis study is based on the data of 67 subjects recruited into a 12-week open-labelled trial looking at the effects of adjunctive Aripiprazole in atypical antipsychotics for weight reduction and improvement in metabolic profile. Metabolic profiles including weight, waist circumference, fasting blood glucose, HbA1c, serum total, HDL and LDL cholesterol levels and triglycerides were measured at baseline. The measurements were then compared across the different subgroups of atypical antipsychotics. The definition of metabolic syndrome proposed by the Third Report of the National Cholesterol Education Program Expert Panel (Adults Treatment Panel III) was used.ResultThe atypical antipsychotics were grouped into Olanzapine (n = 27), Risperidone (n = 24) and Clozapine (n = 16). More than 50% of clozapine-treated and Olanzapine-treated overweight patients were demonstrated to have metabolic syndrome at baseline. There was a statistically significant difference in serum triglycerides (p = 0.012), LDL (p = 0.046) and HbA1c (p = 0.045) across the three groups as demonstrated by one-way ANOVA. A Tukey post hoc test showed that both the Olanzapine (p = 0.032) and Risperidone (p = 0.013) groups demonstrated statistically significant lower serum triglycerides when compared to Clozapine. Interestingly, the mean serum HbA1c was significantly lower in Clozapine when compared to Olanzapine group (p = 0.045), perhaps reflecting the closer monitoring of fasting blood sugar in clozapine patients. When controlled for age and BMI, the significant differences in serum triglycerides remain between Clozapine and Risperidone groups [but not for serum HbA1c]. There were no statistically significant differences across the groups with respect to other metabolic parameters.ConclusionAt baseline, metabolic dysregulation was demonstrated in all subgroups of overweight patients. As hypothesized, patients on Olanzapine and Clozapine groups fared worse than Risperidone. Further studies examining long term effects of atypical antipsychotics in a larger sample of patients are warranted to confirm these findings. These findings have clinical significance in terms of choosing the first antipsychotic for drug naïve patients or where there is no clinically significant difference in efficacy.

Metabolic profiles differences of overweight patients on olanzapine, clozapine and risperidone

AimsWe set out to examine the differences in metabolic profiles of at risk (overweight) patients across commonly used atypical antipsychotics (Olanzapine, Risperidone, Clozapine). We hypothesized that Olanzapine and Clozapine group will have more metabolic abnormalities compared to Risperidone.BackgroundCardiovascular diseases remain the leading cause of morbidity and mortality among people with schizophrenia. Since the introduction of atypical antipsychotics, there is cumulative evidence of their association with metabolic abnormalities. Clozapine and Olanzapine are known to constitute the highest metabolic risks amongst atypical antipsychotics.MethodThis study is based on the data of 67 subjects recruited into a 12-week open-labelled trial looking at the effects of adjunctive Aripiprazole in atypical antipsychotics for weight reduction and improvement in metabolic profile. Metabolic profiles including weight, waist circumference, fasting blood glucose, HbA1c, serum total, HDL and LDL cholesterol levels and triglycerides were measured at baseline. The measurements were then compared across the different subgroups of atypical antipsychotics. The definition of metabolic syndrome proposed by the Third Report of the National Cholesterol Education Program Expert Panel (Adults Treatment Panel III) was used.ResultThe atypical antipsychotics were grouped into Olanzapine (n = 27), Risperidone (n = 24) and Clozapine (n = 16). More than 50% of clozapine-treated and Olanzapine-treated overweight patients were demonstrated to have metabolic syndrome at baseline. There was a statistically significant difference in serum triglycerides (p = 0.012), LDL (p = 0.046) and HbA1c (p = 0.045) across the three groups as demonstrated by one-way ANOVA. A Tukey post hoc test showed that both the Olanzapine (p = 0.032) and Risperidone (p = 0.013) groups demonstrated statistically significant lower serum triglycerides when compared to Clozapine. Interestingly, the mean serum HbA1c was significantly lower in Clozapine when compared to Olanzapine group (p = 0.045), perhaps reflecting the closer monitoring of fasting blood sugar in clozapine patients. When controlled for age and BMI, the significant differences in serum triglycerides remain between Clozapine and Risperidone groups [but not for serum HbA1c]. There were no statistically significant differences across the groups with respect to other metabolic parameters.ConclusionAt baseline, metabolic dysregulation was demonstrated in all subgroups of overweight patients. As hypothesized, patients on Olanzapine and Clozapine groups fared worse than Risperidone. Further studies examining long term effects of atypical antipsychotics in a larger sample of patients are warranted to confirm these findings. These findings have clinical significance in terms of choosing the first antipsychotic for drug naïve patients or where there is no clinically significant difference in efficacy.

Interactions between neuroticism and stressful life events predict response to pharmacotherapy for major depression: A CAN-BIND 1 report.

Exposure to stressful life events and individual differences in the personality trait neuroticism are important risk factors that interact to predict major depressive disorder (MDD). Less is known about their effect on treatment response in depression. Here, we examine whether stressful life events experienced prior to and during treatment interact with neuroticism to predict response to 16-week pharmacotherapy for MDD. Participants included 159 outpatients with MDD who were initially treated with 8weeks of escitalopram. Those who responded to the initial treatment continued on escitalopram monotherapy, whereas non-responders received 8weeks of adjunctive aripiprazole. Personality was assessed using the NEO-Five Factor Inventory, and stressful life events were assessed using the Life Events and Difficulties Schedule, a rigorous contextual interview that includes independent ratings of threatening life events. High baseline neuroticism was associated with a lower likelihood of response when patients experienced one or more negative life events before treatment. Secondary analyses indicated that this effect was specific to neuroticism, and not better accounted for by its self-criticism or negative affect facets. Our results suggest that assessing personality and stressful life events at baseline can help clinicians assess which patients will respond to antidepressant therapy and which may need treatment augmentation.

Predictors of Quality of Life Improvement with Escitalopram and Adjunctive Aripiprazole in Patients with Major Depressive Disorder: A CAN-BIND Study Report.

Non-response to first-line treatment for major depressive disorder (MDD) is common; for such individuals, quality of life (QoL) impairments can be severe. Identifying predictors of QoL changes may support the management of cases with persistent depressive symptoms despite adequate initial pharmacological/psychological treatment. The present study aimed to explore predictors of domain-specific QoL improvement following adjunctive aripiprazole treatment for inadequate response to initial antidepressant therapy. We evaluated secondary QoL outcomes from a CAN-BIND (Canadian Biomarker Integration Network in Depression) study in patients with MDD who did not respond to an initial 8 weeks of escitalopram and received a further 8 weeks of adjunctive aripiprazole (n = 96). Physical, psychological, social, and environmental QoL domains were assessed using the World Health Organization QoL Scale Brief Version (WHOQOL-BREF). Clinician-rated depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Functioning was measured with the Sheehan Disability Scale (SDS). Satisfaction with medication was assessed with a single item from the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Exploratory t-tests were used to describe domain score changes. A hierarchical linear regression was used to explore demographic, clinical, and treatment-related predictors of improvement. Across domains, QoL improved with adjunctive aripiprazole treatment. Satisfaction with medication and MADRS and SDS scores similarly improved. Symptom reduction was a predictor for positive change to physical and psychological QoL; functioning improvements were predictive of increases to all QoL domains. Satisfaction with medication predicted improvements to physical and psychological domains, whereas number of medication trials was a predictor of worsening QoL in the physical domain. The final model explained the most variance in psychological (68%) and physical (67%) QoL. Less variance was explained for environmental (43%) and social QoL (33%), highlighting a need for further exploration of predictors in these domains. Strategies such as functional remediation may have potential to support QoL for individuals with persistent depressive symptoms. ClinicalTrials.gov identifier: NCT016557.

Impacts on Quality of Life with Escitalopram Monotherapy and Aripiprazole Augmentation in Patients with Major Depressive Disorder: A CAN-BIND Report

Many individuals with major depressive disorder (MDD) do not respond to initial antidepressant monotherapy. Adjunctive aripiprazole is recommended for treatment non-response; however, the impacts on quality of life (QoL) for individuals who receive this second-line treatment strategy have not been described. We evaluated secondary QoL outcomes in patients with MDD (n=179). After 8 weeks of escitalopram, non-responders (<50% decrease in clinician-rated depression) were treated with adjunctive aripiprazole for 8 weeks (n=97); responders continued escitalopram (n=82). A repeated-measures ANOVA evaluated change in Quality of Life Enjoyment and Satisfaction Short Form scores. QoL was described relative to normative benchmarks. Escitalopram responders experienced the most QoL improvements in the first treatment phase. For non-responders, QoL improved with a large effect during adjunctive aripiprazole treatment. At the endpoint, 47% of patients achieving symptomatic remission still had impaired QoL. Individuals who were treated with adjunctive aripiprazole after non-response to escitalopram experienced improved QoL, but a substantial degree of QoL impairment persisted. Since QoL deficits may predict MDD recurrence, attention to ways to support this outcome is required.

Guidance on the treatment of antipsychotic-induced hyperprolactinemia when switching the antipsychotic is not an option.

DisclaimerIn an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.PurposeThis article aims to evaluate management options for antipsychotic-induced hyperprolactinemia and associated treatment considerations such as efficacy, tolerability, drug interactions, contraindications, and dosing regimens.SummaryHyperprolactinemia is a common adverse effect of antipsychotics. First-line management includes reducing the dose of the offending antipsychotic, discontinuing the antipsychotic, or switching to another antipsychotic associated with a lower risk of hyperprolactinemia. However, these options are not always practical and are associated with a risk of relapse of the psychiatric illness. Other management options include adjunctive aripiprazole, dopamine agonists (cabergoline and bromocriptine), metformin, and herbal supplements. A search of Embase, PubMed, and Google Scholar using key terms such as hyperprolactinemia, prolactin, antipsychotic, treatment guidelines, aripiprazole, dopamine agonist, cabergoline, bromocriptine, metformin, herbals, supplements, and medications was conducted for literature retrieval. Upon evaluation of the available literature we found the following: (1) aripiprazole is safe and effective in lowering prolactin levels within normal limits; (2) adjunctive cabergoline and bromocriptine decrease elevated prolactin levels, while cabergoline may be more effective in reducing prolactin but can also be associated with a more serious adverse effect of cardiac valvular abnormalities; (3) metformin causes a mild reduction of prolactin levels; and (4) there are limited data to support use of herbal medications (chamomile, Peony-Glycyrrhiza decoction, and shakuyaku-kanzo-to) in antipsychotic-induced hyperprolactinemiaConclusionThere are treatments available for antipsychotic-induced hyperprolactinemia in patients who are unable to alter their current antipsychotic regimen. However, there remains a need for additional short- and long-term studies to determine the efficacy and safety of these treatment strategies, given that patients taking antipsychotics typically require chronic, life-long treatment for their illnesses.

Accelerated brain aging in major depressive disorder and antidepressant treatment response: A CAN-BIND report

ObjectivesPrevious studies suggest that major depressive disorder (MDD) may be associated with volumetric indications of accelerated brain aging. This study investigated neuroanatomical signs of accelerated aging in MDD and evaluated whether a brain age gap is associated with antidepressant response. MethodsIndividuals in a major depressive episode received escitalopram treatment (10–20 mg/d) for 8 weeks. Depression severity was assessed at baseline and at weeks 8 and 16 using the Montgomery-Asberg Depression Rating Scale (MADRS). Response to treatment was characterized by a significant reduction in the MADRS (≥50%). Nonresponders received adjunctive aripiprazole treatment (2–10 mg/d) for a further 8 weeks. The brain-predicted age difference (brain-PAD) at baseline was determined using machine learning methods trained on 3377 healthy individuals from seven publicly available datasets. The model used features from all brain regions extracted from structural magnetic resonance imaging data. ResultsBrain-PAD was significantly higher in older MDD participants compared to younger MDD participants [t(147.35) = -2.35, p < 0.03]. BMI was significantly associated with brain-PAD in the MDD group [r(155) = 0.19, p < 0.03]. Response to treatment was not significantly associated with brain-PAD. ConclusionWe found an elevated brain age gap in older individuals with MDD. Brain-PAD was not associated with overall treatment response to escitalopram monotherapy or escitalopram plus adjunctive aripiprazole.

S3. DOES SWITCHING OR AUGMENTING HELP WITH ANTIPSYCHOTIC-RELATED SEXUAL DYSFUNCTION: SYSTEMATIC REVIEW

BackgroundSexual dysfunction is one of the most frequently occurring side-effects of antipsychotic medication, impacting both quality of life and adherence to treatment. Despite this, limited evidence-based guidance on treatment options is available. The aim of this systematic review was to synthesize and analyze the evidence on the management of antipsychotic-related sexual dysfunction, specifically taking note of the more recently developed antipsychotics that have been incorporatedMethodsEMBASE, Medline, and PsychINFO databases were searched using search terms related to sexual or erectile dysfunction, treatments, and antipsychotics. 2 reviewers independently assessed papers for the inclusion criteria for randomized controlled trials (RCTs) of treatments for antipsychotic-related sexual dysfunction, including adjunctive medications and a switch of antipsychotic. Studies were excluded if participants did not have recorded sexual dysfunction at baseline.ResultsThe primary outcome measure was any change in sexual function. Results 6 RCTs were identified, all of which investigated different interventions; hence, it was not possible to synthesize the data quantitatively. Results were overall limited by small sample size, brief treatment duration, and the potential for bias. 2 studies, one assessing adjunctive sildenafil and the other adjunctive aripiprazole, reported a reduction in antipsychotic-related sexual dysfunction.DiscussionDue to the lack of high-quality data, no clinical recommendations can be made. Our findings highlight the paucity of high-quality research in this area, and conjecture that it may be difficult to recruit participants with antipsychotic-related sexual dysfunction. Future research may be necessary to unlock and address these difficulties. Furthermore, fully powered future studies should focus on the management of sexual dysfunction rather than the surrogate marker of hyperprolactinemia.

An investigation of cortical thickness and antidepressant response in major depressive disorder: A CAN-BIND study report

Major depressive disorder (MDD) is considered a highly heterogeneous clinical and neurobiological mental disorder. We employed a novel layered treatment design to investigate whether cortical thickness features at baseline differentiated treatment responders from non-responders after 8 and 16 weeks of a standardized sequential antidepressant treatment. Secondary analyses examined baseline differences between MDD and controls as a replication analysis and longitudinal changes in thickness after 8 weeks of escitalopram treatment. 181 MDD and 95 healthy comparison (HC) participants were studied. After 8 weeks of escitalopram treatment (10-20mg/d, flexible dosage), responders (>50% decrease in Montgomery-Åsberg Depression Scale score) were continued on escitalopram; non-responders received adjunctive aripiprazole (2-10mg/d, flexible dosage). MDD participants were classified into subgroups according to their response profiles at weeks 8 and 16. Baseline group differences in cortical thickness were analyzed with FreeSurfer between HC and MDD groups as well as between response groups. Two-stage longitudinal processing was used to investigate 8-week escitalopram treatment-related changes in cortical thickness. Compared to HC, the MDD group exhibited thinner cortex in the left rostral middle frontal cortex [MNI(X,Y,Z=-29,9,54.5,-7.7); CWP=0.0002]. No baseline differences in cortical thickness were observed between responders and non-responders based on week-8 or week-16 response profile. No changes in cortical thickness was observed after 8 weeks of escitalopram monotherapy. In a two-step 16-week sequential clinical trial we found that baseline cortical thickness does not appear to be associated to clinical response to pharmacotherapy at 8 or 16 weeks.

P.161 Factors affecting the efficacy of adjunctive aripiprazole in risperidone- or paliperidone-induced hyperprolactinemia

The optimal cutoff for systolic blood pressure (SBP) level to define high-risk pulmonary embolism (PE) remains to be defined.To evaluate the relationship between SBP levels on admission and mortality in patients with acute symptomatic PE, the current study included 39,257 consecutive patients with acute symptomatic PE from the RIETE registry between 2001 and 2018. Primary outcomes included all-cause and PE-specific 30-day mortality. Secondary outcomes included major bleeding and recurrent venous thromboembolism (VTE).There was a linear inverse relationship between admission SBP and 30-day all-cause and PE-related mortality that persisted after multivariable adjustment. Patients in the lower SBP strata had higher rates of all-cause death (reference: SBP 110–129 mmHg) (adjusted odds ratio [OR] 2.9; 95% confidence interval [CI], 2.0–4.2 for SBP <70 mmHg; and OR 1.7; 95% CI, 1.4–2.1 for SBP 70–89 mmHg). The findings for 30-day PE-related mortality were similar (adjusted OR 4.4; 95% CI, 2.7–7.2 for SBP <70 mmHg; and OR 2.6; 95% CI, 1.9–3.4 for SBP 70–89 mmHg). Patients in the higher strata of SBP had significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR 0.7; 95% CI, 0.5–0.9 for SBP 170–190 mmHg; and OR 0.6; 95% CI, 0.4–0.9 for SBP >190 mmHg). Consistent findings were also observed for 30-day PE-related death.In patients with acute symptomatic PE, a low SBP portends an increased risk of all-cause and PE-related mortality. The highest mortality was observed in patients with SBP <70 mmHg.

Management of Antipsychotic-Related Sexual Dysfunction: Systematic Review

IntroductionSexual dysfunction is one of the most frequently occurring side-effects of antipsychotic medication, impacting both quality of life and adherence to treatment. Despite this, limited evidence-based guidance on treatment options is available. AimTo synthesize and analyze the evidence on management of antipsychotic-related sexual dysfunction, specifically taking note of the more recently developed antipsychotics that have been incorporated in studies over the past decade. MethodsEMBASE, Medline, and PsychINFO databases were searched using search terms related to sexual or erectile dysfunction, treatments, and antipsychotics. 2 reviewers independently assessed papers for the inclusion criteria for randomized controlled trials (RCTs) of treatments for antipsychotic-related sexual dysfunction, including adjunctive medications and a switch of antipsychotic. Studies were excluded if participants did not have recorded sexual dysfunction at baseline. Main Outcome MeasureThe primary outcome measure was any change in sexual function. Results6 RCTs were identified, all of which investigated different interventions; hence, it was not possible to synthesize the data quantitatively. Results were overall limited by small sample size, brief treatment duration, and the potential for bias. 2 studies, one assessing adjunctive sildenafil and the other adjunctive aripiprazole, reported a reduction in antipsychotic-related sexual dysfunction. Clinical ImplicationsDue to the lack of high-quality data, no clinical recommendations can be made. Strengths & LimitationsA comprehensive search strategy was used with an extensive number of relevant search terms including “erectile dysfunction” and newer antipsychotics such as aripiprazole. In light of evidence that prolactin is not a reliable marker for sexual dysfunction, this review focused its inclusion criteria on participants presenting with sexual dysfunction rather than with hyperprolactinemia, which should give its recommendations more validity. However, only 6 RCTs were identified, and results were overall limited by small sample size, brief treatment duration, and the potential for bias. ConclusionOur findings highlight the paucity of high-quality research in this area, and conjecture that it may be difficult to recruit participants with antipsychotic-related sexual dysfunction. Future research may be necessary to unlock and address these difficulties. Furthermore, fully powered future studies should focus on the management of sexual dysfunction rather than the surrogate marker of hyperprolactinemia.Allen K, Baban A, Munjiza J, et al. Management of Antipsychotic-Related Sexual Dysfunction: Systematic Review. J Sex Med 2019;16:1978–1987.