Extended Release Quetiapine Research Articles

Discontinuation Rate of Lurasidone and Quetiapine Extended Release in Bipolar Depression.

Lurasidone (LUR) was compared with quetiapine extended release (QUE-ER) regarding 1-year discontinuation in patients with bipolar depression (n=317). This is a retrospective cohort study. Although the time to all-cause discontinuation was estimated using the Kaplan-Meier survival curve with log-rank tests to compare treatment groups, no difference was found (p=0.317). The Cox proportional hazard model revealed that only the presence of adverse events (AEs) is associated with increased treatment discontinuation (p<0.0001). The most common AEs were akathisia for LUR (17.7%) and somnolence for QUE-ER (34.7%). In other Cox models divided by LUR or QUE-ER, the presence of akathisia or somnolence was associated with increased LUR (p=0.0205) or QUE-ER (p<0.0001) discontinuation, respectively. The acceptability of both antipsychotics to bipolar depression in clinical practice may be similar. However, specific AEs for each antipsychotic (LUR: akathisia and QUE-ER: somnolence) were associated with high treatment discontinuation.

Weight changes in esketamine nasal spray and quetiapine extended-release treated patients with treatment resistant depression: Results from ESCAPE-TRD study

IntroductionIn ESCAPE-TRD, esketamine nasal spray (ESK-NS) significantly increased the probability of remission at Week (Wk)8 and being relapse‑free through Wk32 after remission at Wk8 versus (vs) quetiapine extended-release (QTP-XR), in patients (pts) with treatment resistant depression (TRD). Safety data were consistent with established profiles of each treatment, with no new safety signals identified (Reif et al. DGPPN 2022; P-01-04).ObjectivesTo explore weight changes and their impact on treatment discontinuation in ESCAPE-TRD.MethodsESCAPE‑TRD (NCT04338321) was a randomised, open-label, rater-blinded, phase IIIb trial comparing efficacy and safety of ESK-NS vs QTP-XR in pts with TRD. Safety analyses were conducted on pts who received ≥1 dose of study treatment. Treatment-emergent adverse events (TEAEs) were defined as occurring at or after the first dose of study treatment and within 14 days/30 days (non-serious/serious) of the last dose. A ≥7% increase/decrease in weight from screening was considered for evaluation as a TEAE. Weights were measured and are reported as observed, with no missing data imputation.Results336 and 340 pts were randomised to ESK-NS and QTP-XR; 334 and 336 were included in the safety population. Over the 32-week study, a TEAE of weight increase was reported in fewer pts treated with ESK-NS than QTP-XR (9 [2.7%] vs 42 [12.5%]), leading to treatment discontinuation in 0 vs 6 (1.8%) pts, respectively. Incidences of weight increase TEAEs were balanced across pts categorised as normal, overweight or obsese by baseline body mass index (BMI; Figure). A weight decrease TEAE was reported in 7 pts (2.1%) in the ESK-NS arm vs 0 pts in the QTP-XR arm. Mean (standard deviation [SD]) weight at baseline was 76.4 (16.2) kg (ESK-NS; n=334) vs 79.1 (16.9) kg (QTP-XR; n=336). At Wk32, mean weight was maintained (76.5 [16.3] kg) in ESK-NS treated pts (n=249; mean [SD] change from baseline: 0.1 [4.0] kg) and increased (80.7 [15.6] kg) in QTP-XR treated pts (n=203; mean [SD] change from baseline: 2.5 [5.1] kg).Image:ConclusionsIncrease in weight was uncommon with ESK-NS; weight increases were more common with QTP-XR and resulted in more treatment discontinuations. Weight increase was independent from baseline BMI.AcknowledgementsWe thank the patients who participated. Funding: Janssen, medical writing: Costello Medical, UKDisclosure of InterestNone Declared

Diagnosis &amp; Treatment Options in Depression with comorbid Dementia

AbstractDepression and Dementia Professor Allan H Young, Head of Academic Psychiatry, Maudsley Hospital and King’s College London UK. allan.young@kcl.ac.uk Mood Disorders are common, encompass cognitive impairments and occur in later life including first onset after the age of 50 years of age. There is a considerable overlap between depression and dementia. The relationship between depression and dementia will be reviewed and the implications for diagnosis and treatment will be discussed. Novel agents targeting alternative neurotransmitter pathways and inflammatory processes are promising potential treatment options. Neurostimulation treatments play a role with ECT at present having the best utility for late onset depression. Key words: depression, dementia, antidepressants; pharmacotherapyDisclosure of Interest A. Young Grant / Research support from: Principal Investigator in the Restore-Life VNS registry study funded by LivaNova. Principal Investigator on ESKETINTRD3004: “An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression.” Principal Investigator on “The Effects of Psilocybin on Cognitive Function in Healthy Participants” Principal Investigator on “The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)” Principal Investigator on “A Double-Blind, Randomized, Parallel-Group Study with Quetiapine Extended Release as Comparator to Evaluate the Efficacy and Safety of Seltorexant 20 mg as Adjunctive Therapy to Antidepressants in Adult and Elderly Patients with Major Depressive Disorder with Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy.” (Janssen) Principal Investigator on “ An Open-label, Long-term, Safety and Efficacy Study of Aticaprant as Adjunctive Therapy in Adult and Elderly Participants with Major Depressive Disorder (MDD).” (Janssen) Principal Investigator on “A Randomized, Double-blind, Multicentre, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants with Major Depressive Disorder (MDD) with Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy.” Principal Investigator on “ A Study of Disease Characteristics and Real-life Standard of Care Effectiveness in Patients with Major Depressive Disorder (MDD) With Anhedonia and Inadequate Response to Current Antidepressant Therapy Including an SSRI or SNR.” (Janssen) UK Chief Investigator for Compass; COMP006 &amp; COMP007 studies UK Chief Investigator for Novartis MDD study MIJ821A12201, Consultant of: Paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Flow Neuroscience, Novartis, Roche, Janssen, Takeda, Noema pharma, Compass, Astrazenaca, Boehringer Ingelheim, Eli Lilly, LivaNova, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, Sage, Neurocentrx

Schizoaffective Disorder and Parkinson’s Disease: a case report

IntroductionWe present the case of a patient with schizoaffective disorder and Parkinson’s disease (PD), requiring treatment adjustment, with the use of high doses of quetiapine for the treatment of psychotic symptomatology.ObjectivesThe aim is to briefly review the treatment of dopaminergic psychosis in the elderly.Methods Patient aged 86 years, institutionalised, presenting severe episodes of behavioural alteration, high anxiety and delusions of harm, together with auditory and visual hallucinations. As relevant physical history, the patient has AHT, aortic insufficiency, and bladder cancer operated on in 2012. As psychiatric history of interest, the patient has been diagnosed since his 30s with schizoaffective disorder, Parkinson’s disease and moderate-severe cognitive impairment secondary to the previous two.As usual treatment, in addition to anticoagulation and antihypertensive therapy, the patient has been receiving L-dopa for his PD for years, antidepressant treatment with escitalopram 10mg, haloperidol 80 drops a day, divided into three doses, and lormetazepam 2mg as a hypnotic.In addition to the symptoms described above, the patient had episodes of confusional features, as well as marked stiffness in the cogwheel and significant gait disturbance, having suffered several falls without serious repercussions.Results Due to the comorbid neurological pathology, it was decided to progressively modify the treatment, withdrawing the benzodiazepine due to the risk of confusional disorder and replacing it with trazodone. Antipsychotic treatment was gradually replaced by extended-release quetiapine, reaching a maximum dose of 800mg. Likewise, escitalopram treatment is replaced by sertraline.With this adjustment, there was an improvement in the psychotic symptoms, as well as in the anxious symptoms. Episodes of distress are NOT observed, and the patient’s functionality improves, allowing him/her to participate in daily activities, both cognitive stimulation and physiotherapy.ConclusionsThe Spanish Society of Psychogeriatrics recommends that before using antipsychotics, it is advisable to first treat the underlying potentially treatable causes (pain, infections, toxic effects of drugs…), assess non-pharmacological interventions and always, if the use of antipsychotics is required, assess the risk-benefit ratio.In relation to the above, it is not surprising that in the elderly, the use of second-generation antipsychotics is recommended in the first place, as opposed to the classical ones. The latter are only recommended in emergency situations where an almost immediate effect is required.For dopaminergic psychosis, there are only controlled trials with clozapine. However, due to prescribing difficulties, aripiprazole or quetiapine is recommended in the first instance.Disclosure of InterestNone Declared

Major depressive episode in the elderly. Use of maintenance ECT: a case report.

IntroductionWe present the case of an elderly patient with a severe depressive episode who, in order to maintain psychopathological stabilisation, receives ECT on an outpatient basis.ObjectivesThe objective is to briefly review the use of ECT as a maintenance treatment for severe depression in the elderly.MethodsPatient aged 76 years, multipathological, with a history of hypertension, DM and LBP. Femoral head fracture, myelodysplastic syndrome, severe osteoporosis with vertebral crushing, requiring rescue treatment with tramadol, and renal failure.She came for consultation, reporting depressive symptoms of months’ duration, together with delusions of ruin and nihilism. Despite antidepressant and stabilising treatment with duloxetine at daily doses of 120mg, extended-release quetiapine 600mg, lorazepam 2.5mg and mirtazapine 45mg, the patient began to show negative behaviour towards accepting food, clinophilic behaviour and abandonment, which led to her being admitted to the short-term hospitalisation unit.ResultsDue to the severity of the depressive symptomatology, it was decided to start ECT, administering a total of 12 sessions, which were effective, and outpatient follow-up was resumed. However, after a week, the patient again began to show marked apathy and abulia, as well as complete anorexia lasting more than 24 hours, which led to a new admission. It was then that it was decided to maintain the ECT treatment, on an outpatient basis, as maintenance treatment, together with pharmacological treatment.ConclusionsECT is indicated in severe depression, with or without psychotic symptoms, with malnutrition and organic pathology. According to studies, it has a beneficial response of more than 60%. However, the rate of receiving depressive symptomatology in a severe episode is high, despite ECT, so studies and clinical practice recommend maintenance ECT. It is usual to start with weekly sessions, and progressively space them out to maintain the minimum that guarantees stability.Disclosure of InterestNone Declared

Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression

BackgroundIn treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin–norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown.MethodsIn an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery–Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures.ResultsOverall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] vs. 60 of 340 patients [17.6%]; P=0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments.ConclusionsIn patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.)

Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape.

One in three adults with major depressive disorder (MDD) do not experience clinically significant improvement after multiple sequential courses of antidepressants and have treatment-resistant depression (TRD). The presence of TRD contributes to the morbidity and excess mortality associated with MDD and has been linked to significantly increased health care expenses. In the absence of a consensus definition of TRD, this report takes a broad approach by considering inadequate response to one or more courses of antidepressants and focuses on atypical antipsychotics that are approved by the U.S. Food and Drug Administration for treatment of depression (aripiprazole, brexpiprazole, cariprazine, extended-release quetiapine, and olanzapine-fluoxetine combination). While multiple acute-phase studies have demonstrated the efficacy of these medications in improving depressive symptoms, clinically meaningful improvement (i.e., remission) remains limited, with significant concerns about side effects (including weight gain, metabolic dysfunction, extrapyramidal symptoms, and tardive dyskinesia), especially with long-term use. With the rapidly evolving landscape of antidepressant treatments over the past few years, which has witnessed approval of rapid-acting antidepressants (e.g., esketamine nasal spray and dextromethorphan-bupropion combination) and several more in the late-stage pipeline (e.g., zuranolone and psilocybin), it remains to be seen whether the use of atypical antipsychotics will go the way of the older and rarely prescribed antidepressants (such as tricyclics and monoamine oxidase inhibitors). Pragmatic clinical trials are needed to compare the effectiveness of atypical antipsychotics with TRD-specific pharmacotherapies and neuromodulation treatments and to identify the optimal sequencing of these varied approaches for patients with MDD. When using atypical antipsychotics, clinicians and patients are encouraged to use a shared decision-making approach by personalizing treatment selection based on anticipated side effects, tolerability, cost, and feasibility.

Early Antipsychotic Nonresponse as a Predictor of Nonresponse and Nonremission in Adolescents With Psychosis Treated With Aripiprazole or Quetiapine: Results From the TEA Trial.

To evaluate 1) whether early nonresponse to antipsychotics predicts nonresponse and nonremission, 2) patient and illness characteristics as outcome predictors, and 3) response prediction of 30-item Positive and Negative Syndrome Scale (PANSS-30) compared with 6-item PANSS (PANSS-6) and Clinical Global Impressions-Improvement Scale (CGI-I) in youths with first-episode psychosis. Post hoc analysis from a 12-week, double-blinded, randomized trial of aripiprazole vs extended-release quetiapine in adolescents (age 12-17 years) with first-episode psychosis was performed. Early nonresponse (week 2 or week 4) was defined as<20% symptom reduction (PANSS-30) (or<20% symptom reduction [PANSS-6] or CGI-I score 4-7 [less than "minimally improved"]). Nonresponse (week 12) was defined as<50% symptom reduction (PANSS-30). Nonremission (week 12) was defined as a score of >3 on 8 selected PANSS-items. Positive/negative predictive values (PPV/NPV) and receiver operating characteristics, binary logistic regression models, and PPV/NPV using PANSS-6 and CGI-I were analyzed. Of 113 randomized patients, 84 were included in post hoc analysis (mean [SD] age= 15.7 [1.3] years; 28.6% male). The 12-week symptom decrease was 31.9% [27.9%], most pronounced within the first 2 weeks (61.1% of total PANSS reduction). Response (27.4%) and remission (22.6%) rates were low. Results indicated that early nonresponse reliably predicted 12-week nonresponse (PPV: week 2, 82.2%; week 4, 90.0%) and nonremission (PPV: week 2, 80.0%; week 4, 90.0%); early nonresponse at week 4 was a statistically significant baseline predictor for 12-week nonresponse; and PANSS-6 had similar predictive significance as PANSS-30. However, outcomes were heterogeneous using CGI-I. In youths with first-episode psychosis showing early nonresponse to aripiprazole or extended-release quetiapine, switching antipsychotic drug should be considered. PANSS-6 is a feasible and clinically relevant alternative to PANSS-30 to predict 12-week nonresponse/nonremission. Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis; https://www. gov/; NCT01119014.

Randomized, Placebo-Controlled Effectiveness Study of Quetiapine XR in Comorbid Depressive and Anxiety Disorders.

Objective: Quetiapine is approved as an adjunctive treatment for major depressive disorder (MDD) and as monotherapy for bipolar depression. It is often used off-label for treating anxiety conditions and as an augmentation agent for treatment-resistant depression. However, its benefit in depression with comorbid anxiety disorders has not been systematically evaluated. The current study evaluated the benefit and tolerability of quetiapine as augmentation to first-line antidepressants for MDD comorbid with anxiety disorders.Methods: In this multicenter trial (June 2008-June 2013), 76 adults (aged 18-65 years) with a primary diagnosis of unipolar depression comorbid with at least 1 anxiety disorder (per DSM-IV-TR criteria) received flexible-dose quetiapine extended-release (XR) 50-300 mg/d or placebo as add-on for 12 weeks in a 2:1 ratio. Depression, anxiety, life satisfaction, and adverse events were assessed.Results: Depression, anxiety, and function improved significantly in both groups. On primary outcome measures, quetiapine was superior to placebo in improving depression (17-item Hamilton Depression Rating Scale score: mean difference = -3.64; 95% CI, -7.01 to -0.27) and anxiety symptoms (Hamilton Anxiety Rating Scale score: mean difference = -4.02; 95% CI, -7.41 to -0.64), as well as Clinical Global Impressions-Severity of Illness scale score (mean difference = -0.64; 95% CI, -1.13 to -0.15). On secondary measures including the Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, Penn State Worry Questionnaire, and Quality of Life Satisfaction and Enjoyment Questionnaire, quetiapine produced a greater degree of improvement compared to placebo, but group differences were not statistically significant. Quetiapine was well tolerated, with mostly minor and no serious adverse effects.Conclusions: Quetiapine augmentation may be a useful intervention for MDD with comorbid anxiety.Trial Registration: ClinicalTrials.gov Identifier: NCT00688818.

CYP2D6 Genotyping and Antipsychotic-Associated Extrapyramidal Adverse Effects in a Randomized Trial of Aripiprazole Versus Quetiapine Extended Release in Children and Adolescents, Aged 12-17 Years, With First Episode Psychosis.

The aim of this study was to examine the association between genetically predicted CYP2D6 phenotypes and extrapyramidal symptoms (EPSs). Data from the Tolerability and Efficacy of Antipsychotics trial of adolescents with first-episode psychosis randomized to aripiprazole versus quetiapine extended release were studied. Extrapyramidal symptom assessments included the Simpson-Angus Scale and the Barnes Akathisia Rating Scale. Patients were CYP2D6 genotyped. Plasma concentrations of antipsychotics and antidepressants were analyzed. One hundred thirteen youths (age, 12-17 years; males, 30%; antipsychotic naive, 51%) were enrolled. Poor metabolizers had a significantly higher dose-adjusted aripiprazole plasma concentration (±SD) compared with normal metabolizers at week 4 (24.30 ± 6.40 ng/mL per milligram vs 14.85 ± 6.15 ng/mL per milligram; P = 0.019), but not at week 12 (22.15 ± 11.04 ng/mL per milligram vs 14.32 ± 4.52 ng/mL per milligram; P = 0.067). This association was not found in the quetiapine extended release group. No association between CYP2D6 genotype groups and global Barnes Akathisia Rating Scale score or Simpson-Angus Scale score was found in any of the treatment arms. Our results do not support routine use of CYP2D6 testing as a predictor of drug-induced parkinsonism or akathisia risk in clinical settings. Further studies with larger samples of CYP2D6 poor metabolizers are needed.

Assessing the genetic diversity of twenty one Colombo limon L. genotypes through multivariate and covariance matrix analysis

Assessing the genetic diversity of twenty one Colombo limon L. genotypes through multivariate and covariance matrix analysis

Efficacy and Safety Considerations With Second-Generation Antipsychotics as Adjunctive Analgesics: A Review of Literature.

Objective: To determine the efficacy and safety of second-generation antipsychotics (SGAs) as adjunctive analgesics. Data Sources: A comprehensive literature review was conducted between August 2020 and January 2021 on PubMed, Scopus, and ProQuest Central. Study Selection and Data Extraction: Keyword and Boolean phrase searches using the following terminology were conducted: "Quetiapine" OR "Risperidone" OR "Olanzapine" OR "Ziprasidone" AND "Analgesia" NOT "Psychosis" NOT "Psych." Articles that involved human adult patients who received any of the SGAs mentioned in the searching filter with an opioid were included. Articles that described pediatrics, pregnant women, patients who received any of these agents for treatment of psychosis and articles that were not in English, or readily translatable to English, were excluded. Data Synthesis: Three articles were selected for inclusion in this review, with 2 articles detailing reports with olanzapine and 1 article describing a randomized, controlled trial with extended-release quetiapine. Both olanzapine and quetiapine were able to decrease pain scores on the numeric rating scale, indicating a reduction pain experienced, and additionally reduced opioid craving behavior in patients. Depression scores and quality-of-life indicators improved with quetiapine, though those metrics were not studied with olanzapine. Conclusions: Select SGAs, specifically extended-release quetiapine and olanzapine, may serve as an appropriate adjunctive analgesic choice in select patients. Further research is required in a clinical setting to determine the exact role of this drug class in pain management.

Lurasidone, olanzapine, and quetiapine extended‐release for bipolar depression: A systematic review and network meta‐analysis of phase 3 trials in Japan

AimThis systematic review and random‐effect model, network meta‐analysis of the phase 3 trials in Japan assessed the efficacy and safety profile of lurasidone compared with olanzapine and quetiapine extended‐release (QUE‐XR) for the treatment of bipolar depression.MethodsThe study included double‐blind, randomized, placebo‐controlled, phase 3 trials in Japan that included patients with bipolar depression. Outcomes included response rate (primary), remission rate (secondary), improvement of Montgomery‐Åsberg Depression Rating Scale (MADRS) total score, discontinuation rates, and incidence of individual adverse events.ResultsThree studies were included (n = 1223). Lurasidone and olanzapine but not QUE‐XR were superior to placebo in response rate [risk ratio (95% credible interval): lurasidone = 0.78 (0.66, 0.92); olanzapine = 0.84 (0.71, 0.99); QUE‐XR = 0.87 (0.73, 1.03)]. Lurasidone, olanzapine and QUE‐XR were superior to placebo in remission rate [lurasidone = 0.90 (0.83, 0.98); olanzapine = 0.87 (0.77, 0.99); QUE‐XR = 0.84 (0.73, 0.98)] and the improvement of MADRS total score. There were not differences in discontinuation rates between each antipsychotic and placebo. Compared with placebo, lurasidone was higher incidence of akathisia, and increased body weight and blood prolactin level; olanzapine was higher incidence of somnolence and ≥7% weight gain, and increased body weight, blood total cholesterol level, blood LDL cholesterol level, and blood triglyceride levels; QUE‐XR was higher incidence of extrapyramidal symptoms, akathisia, somnolence, dry mouth, constipation and ≥7% weight gain, and increased body weight, blood total cholesterol level, blood LDL cholesterol level, and blood triglyceride levels.ConclusionsOur results suggested although the efficacy of three SGAs was similar, there were the differences in the safety profile among the SGAs.

Melancholic depression and response to quetiapine: A pooled analysis of four randomized placebo-controlled trials

BackgroundMelancholic depression may preferentially respond to certain treatments. This study examined the efficacy of extended-release quetiapine monotherapy in patients with melancholic and nonmelancholic major depressive disorder. MethodsData from four randomized placebo-controlled trials was pooled. Melancholic features were assessed with baseline depression scale items according to DSM criteria. The outcome measure was response on the Montgomery–Åsberg Depression Rating Scale. Cox regression models predicting response over time with interactions between treatment condition and melancholic status were used to test for treatment effect heterogeneity. ResultsThe 6-week response rate difference between quetiapine and placebo was roughly 10% greater in the melancholic subgroup, primarily due to a lower placebo response, although the subgroup-treatment interactions did not reach statistical significance. The main effect of quetiapine was significant in every model. LimitationsThe main limitations were the retrospective analysis and the post-hoc designation of melancholic depression based on scale items not designed for that purpose. Results should be considered preliminary and exploratory until replicated. ConclusionsThe lower placebo response rate in the melancholic subgroup is consistent with past research and reinforces the benefit of pharmacotherapy for these patients.

Population Pharmacokinetics Analysis of Quetiapine Extended-release Formulation in Japanese Patients with Bipolar Depression

PurposeThe objectives of this study were to explore covariates of plasma quetiapine concentrations after oral administration of quetiapine extended-release formulation (XR), and to examine the exposure–response relationship in Japanese patients with bipolar depression, using population pharmacokinetics (PopPK) modeling. MethodsIn a multicenter, randomized, double-blind, placebo-controlled study of quetiapine XR in patients with bipolar depression, plasma for the measurement of quetiapine concentration was collected at weeks 2, 4, 8, 12, 20, 28, and 52 during oral administration of 150 or 300 mg once daily of quetiapine XR before bedtime. A PopPK model of quetiapine XR was developed using nonlinear mixed-effects modeling with first-order conditional estimation with interactions. The exposure–response relationship was examined using post-hoc exposures. The post-hoc AUC estimate was plotted against the change in the Montgomery-Åsberg Depression Rating Scale (ΔMADRS) total score from baseline to 8 weeks following once-daily doses at 300 mg. FindingsThe final PopPK analysis dataset contained 322 patients and 1162 observations (cutoff data at week 28; cutoff date, February 2016). The plasma quetiapine concentration–time profile in patients with bipolar depression after oral administration of quetiapine XR was represented well using a 1-compartment with first-order absorption model. Covariate analysis led to the selection of γ-glutamyl transpeptidase on apparent oral clearance and body weight on apparent volume of distribution as covariates. The final population mean values of apparent oral clearance and apparent volume of distribution were 87.7 L/h and 277 L, respectively, and the interindividual %CVs were 32.6% and 75.0%, respectively. ImplicationsThe effects of covariates on PK parameters were not large compared with the interindividual variability. In addition, there was no clear relationship between the AUC and ΔMADRS. ClinicalTrials.gov identifier: NCT01725308.

Real-World Economic Outcomes of Brexpiprazole and Extended-Release Quetiapine Adjunctive Use in Major Depressive Disorder.

PurposeMajor depressive disorder (MDD) is a chronic mental disorder with a substantial clinical and economic burden. Despite the efficacy of adjunctive atypical antipsychotics (AAP) for augmentation in patients with major depressive disorder (MDD) who failed first-line antidepressant therapy (ADT), little is known of the impact of AAP choices on healthcare resource use and costs in real-world practice. Therefore, this study compared real-world healthcare utilization and costs in patients with MDD treated with brexpiprazole or extended-release (XR) quetiapine as adjunctive treatment to ADT.Patients and methodsAdults with MDD starting adjunctive treatment with brexpiprazole (n=844) or extended-release (XR) quetiapine (n=688) were identified in the adjudicated health plan claims data (07/2014 – 09/2016). Resource use and healthcare costs in the 6 months following treatment initiation were compared between non-matched populations, and between propensity score-matched groups, and by multivariable regression analyses.ResultsDuring follow-up, unadjusted all-cause hospitalization (6.6% vs 12.5%) and ED visits (17.0% vs 27.5%) were lower with brexpiprazole compared to quetiapine XR (both p<0.001). Brexpiprazole-treated patients had significantly lower mean medical costs (US$6,421 vs US$8,545, p=0.0123) but higher mean pharmacy costs (US$7,401 vs US$4,691, p<0.0001) than quetiapine XR-treated patients did. Total healthcare costs were not significantly different between the two cohorts. Propensity score-matched comparisons of 397 patients in each cohort showed no statistically significant difference in all-cause hospitalization, ED visits, and total healthcare costs; and significantly lower medical costs (US$5,719 vs US$8,602, p=0.0092) but higher pharmacy costs (US$7,091 vs US$5,091, p=0.0007) in brexpiprazole compared to quetiapine XR. In multivariable regressions, brexpiprazole was associated with 16.1% lower medical costs (p=0.0186) and 9.4% higher total healthcare costs (p=0.0463) as compared to quetiapine XR.ConclusionSignificantly lower medical costs were observed in patients with MDD treated with brexpiprazole vs quetiapine XR.

Efficacy and Tolerability of Quetiapine Extended Release (XR) as Monotherapy in the Treatment of Major Depressive Disorder

Efficacy and Tolerability of Quetiapine Extended Release (XR) as Monotherapy in the Treatment of Major Depressive Disorder

Quetiapine extended-release vs olanzapine for Japanese patients with bipolar depression: A Bayesian analysis.

ObjectiveIt is unknown whether there are differences in efficacy and safety between quetiapine extended‐release, 300 mg/d (QUEXR300), and olanzapine, 5‐20 mg/d (OLA), for Japanese patients with bipolar depression.MethodsWe conducted a Bayesian analysis of data from phase 3 studies in Japan of QUEXR300 and OLA. Outcomes were remission rate (primary), response rate, improvement on the Montgomery‐Åsberg Depression Rating Scale and 17‐item Hamilton Depression Rating Scale scores, discontinuation rate, and incidence of individual adverse events. We calculated the standardized mean difference (SMD) and the risk ratio (RR) and 95% credible interval (95% CrI) for continuous and dichotomous data, respectively.ResultsThere were no significant differences between QUEXR300 and OLA for any of the efficacy outcomes. QUEXR300 was associated with a higher incidence of somnolence than OLA (RR = 5.517; 95% CrI = 1.563, 19.787), while OLA was associated with greater increase body weight (SMD = −0.488; 95% CrI = −0.881, −0.089) and blood prolactin levels (SMD = −0.642; 95% CrI = −1.073, −0.213) than QUEXR300, and a greater decrease in high‐density lipoprotein cholesterol levels (SMD = −0.408; 95% CrI = −0.785, −0.030) than QUEXR300.ConclusionAlthough the two drugs’ efficacy did not differ, OLA increased the risk of metabolic syndrome and QUEXR300 the risk of somnolence. A large scale, long‐term, head‐to‐head comparison study of QUEXR300 vs OLA for Japanese patients with bipolar depression is needed to confirm the results of the current study.

Results from a drug utilization study of extended release quetiapine fumarate prescribed by psychiatrists as treatment for major depressive disorder in selected countries in the European Union

This multicenter, observational drug utilization (DU) study (NCT01594996) investigated the profile of patients and specialist providers who prescribed extended release quetiapine fumarate (quetiapine XR) for treatment of major depressive disorder (MDD) across five European countries (Germany, Italy, Romania, Spain, and Sweden). A DU data abstraction form captured information on the characteristics of physicians, patients, and drugs utilized in the medical management of depressive episodes in MDD, where the therapeutic regimen included quetiapine XR. Data were reported descriptively. This analysis included 811 patients. Psychiatric histories indicated a burden of severe MDD in these patients. Patient demographics were similar across countries; however, those in Sweden had a younger mean age. Physicians’ ratings of the therapeutic effect of prior treatment with antidepressants suggested the need for an add-on treatment for most patients. Overall, 15.7% of patients initiated quetiapine XR treatment as monotherapy. Presence of psychotic symptoms during depressive episodes predicted treatment with higher than recommended doses of quetiapine XR (odds ratio=3.11; 95% confidence interval: 1.6–6.0). This analysis demonstrated similarities in DU across the countries analyzed, largely in accordance with the recommended dose of quetiapine XR as an adjunctive therapy to antidepressants in MDD (50–300 mg/day).

Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment of major depressive disorder: a randomized, active-referenced, placebo-controlled study

Objective: To assess the efficacy, safety, and tolerability of brexpiprazole as adjunctive treatment in adults with major depressive disorder (MDD) and an inadequate response to prior antidepressant treatment (ADT).Methods: Patients with a current major depressive episode after prior treatment with 1−3 ADTs entered an 8- or 10-week prospective treatment phase in which they received double-blind placebo adjunct to open-label ADT. Inadequate responders were randomized (2:2:1) to brexpiprazole 2−3 mg/day, placebo, or quetiapine extended-release (XR) 150−300 mg/day, adjunct to the same ADT, for 6 weeks. The primary efficacy endpoint was the change from baseline (randomization) to week 6 in Montgomery−Åsberg Depression Rating Scale (MADRS) total score. The key secondary efficacy endpoint was the change in Sheehan Disability Scale (SDS) mean score.Results: Adjunctive brexpiprazole showed a greater improvement in MADRS total score than adjunctive placebo (least squares mean difference [95% confidence interval] = −1.48 [−2.56, −0.39]; p = .0078), whereas adjunctive quetiapine XR did not separate from placebo (−0.30 [−1.63, 1.04]; p = .66). Adjunctive brexpiprazole failed to separate from placebo on the SDS mean score (−0.23 [−0.52, 0.07]; p = .13), but did improve functioning on two of the three SDS items (family life and social life). The most frequent treatment-emergent adverse events in patients receiving brexpiprazole were akathisia (6.1%), somnolence (5.6%), and headache (5.6%).Conclusions: Adjunctive brexpiprazole 2−3 mg/day improved symptoms of depression compared with adjunctive placebo in patients with MDD and an inadequate response to ADTs, and was well tolerated with no unexpected side effects.