Combination Of Olanzapine Research Articles

A Sustainable Chromatographic Method for Simultaneous Analysis of Fluoxetine and Olanzapine Antidepressants: Assessment of Greenness with Green Metric Tools .

The combination of Fluoxetine HCL and Olanzapine treats depression in bipolar disorder and patients unresponsive to other antidepressants. The research aims to optimize a sensitive, simple, rapid, reliable, eco-friendly liquid chromatographic method by minimizing feedstock’s, reagents, energy, and waste to protect the environment and conserve resources, additionally assessed the environmental impact of a method using various green metric tools, and applied the method to pharmaceuticals. The separation was conducted using isocratic RP-HPLC with a DAD at 227nm. The mobile phase used was a 40:40:20 (v/v/v) ratios of buffer, acetonitrile, and ethanol. An L1 column (150 x 4.6mm, 5µm) was utilized with a flow rate of 1.5mL/min and injection volume of 5µL. The column oven and auto-sampler were both maintained at 45°C and 25°C respectively. The optimized method was validated as per ICH guidelines and found to be specific, precise, and robust to slight changes in mobile phase flow, column temperature, and buffer pH. Linearity was demonstrated from 0.1-150µg/mL for olanzapine and 0.4-610µg/mL for fluoxetine HCL. The accuracy was tested with recovery ranges of 0.1–157 µg/mL for olanzapine and 0.4–606 µg/mL for fluoxetine HCl in tablet placebo, and 0.1–150 µg/mL for olanzapine and 0.4–605 µg/mL for fluoxetine HCl in capsule placebo, indicating that the method is suitable for both tablet and capsule dosage forms. The method’s greenness was evaluated using AES, NEMI, GAPI, and AGREE tools. The optimized method was successfully applied to pharmaceutical analysis. The newly optimized method found simple, sensitive, rapid, eco-friendly, incorporating green analytical concepts, has been successfully achieved for the identification and quantification of Fluoxetine HCL and Olanzapine present in pharmaceuticals.

Developing a community-based model of care for venipuncture in children and young adults with an intellectual disability: a retrospective study

BackgroundRegular blood tests for monitoring metabolic side effects are often unable to be collected for people with an intellectual/developmental disability (ID/DD) and challenging behaviours (CBs) using usual pathways. We aimed...

Treatment of bipolar depression: clinical practice vs. adherence to guidelines-data from a Bavarian drug surveillance project.

Pharmacotherapy of bipolar depression (BPD) is confronted with major clinical challenges, like limited evidence-based treatment options, regular cases of treatment resistance, and risk of treatment-emergent affective switches. Medical guidelines can support practitioners to make decisions based on current scientific evidence. The objective of this study is to evaluate to what extent recommendations of the 2019 German S3 guidelines "Diagnosis and Treatment of Bipolar Disorders" are reflected in clinical practice in inpatient treatment. We conducted a descriptive analysis of prescription numbers in 2,627 patients with BPD in a naturalistic inpatient setting analyzing data from the ongoing Bavarian multicenter drug safety project Pharmaco-Epidemiology and Vigilance (Pharmako-EpiVig) from the years 2014-2022. Of the patients, 38% were not administered any drug explicitly recommended for treatment of BPD, that is, quetiapine, lamotrigine, carbamazepine, or olanzapine. Only 6% of the patients received monotherapy with one of those drugs. Of the patients, 34% were administered ≥4 psychotropic drugs simultaneously. Patients received 912 different therapy regimens of mono or combination therapy with mood stabilizers (MS), atypical antipsychotics (AAP), and antidepressants. Of the patients, 72% received an antidepressant and 6% without concomitant prescription of an AAP or MS. Prescription rates of venlafaxine (21% to 14%) and tricyclic antidepressants (9% to 6%) decreased significantly from the first (2014-2016) to the last (2020-2022) observed time period. Of the patients, 60% received an MS. Prescription rate of valproate (22% to 14%) decreased significantly, while lithium prescription increased significantly (29% to 35%). Of the patients, 71% were administered an AAP. Quetiapine was the most prescribed drug overall (43%). Only two patients were administered a combination of olanzapine and fluoxetine. Our results demonstrate a substantial gap between guideline recommendations and current clinical practice. The remarkable heterogeneity in treatment regimens, with no discernible dominant treatment approach, is in part a reflection of the complexity of bipolar disorder but also substantiates the need of comprehensive recommendations regarding combination therapies. Increase in lithium prescription is an encouraging development due to its unique efficacy in maintenance treatment. To improve the quality of clinical practice guideline implementation, more randomized controlled trials shouldbeconducted in the future to prospectively investigate different implementation strategies.

Efficacy of Low-dose Olanzapine in Combination with Sertraline on Negative Symptoms and Psychosocial Functioning in Schizophrenia: A Randomized Controlled Trial.

Evidence for the efficacy of a low dose of olanzapine (OLA) in combination with antidepressants has been limited and without positive trials in first-episode (FE) patients with schizophrenia (SCH). This study aimed to compare the efficacy in treating negative and depressive symptoms between those FE patients with SCH treated with a combination of OLA plus sertraline and those treated with OLA monotherapy. One hundred and ninety-six first-episode and drug naïve patients with SCH were randomized to receive low-dose OLA (7.5-10 mg/day) combined with sertraline (50-100 mg/day) (OS group) or normal-dose OLA monotherapy (12.5-20 mg/day) (NO group). Clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS), and the depressive symptoms were evaluated by the Hamilton Depression Scale (HAMD). Psychosocial functioning was assessed by the Personal and Social Performance Scale (PSP). In the intent-to-treat efficacy analysis, the OS group had greater decreases in negative and depressive symptoms (pall < 0.01) and a greater increase in PSP total score compared with the NO group (p < 0.01). Moreover, reductions in HAMD total score and PANSS negative subscore and sex were associated with the improvements in psychosocial functioning from baseline to week 24, after controlling for baseline psychosocial function, age, and onset age. This study demonstrates that low-dose OLA in combination with sertraline had clinically meaningful improvements not only in the negative and depressive symptoms but also in psychosocial functioning in patients with FE-SCH, while not affecting positive symptoms.

Development and Characterization of Lipid Nanoparticles Loaded with Antipsychotic Drugs using Central Composite Design

Background: Fluoxetine and olanzapine combination tablets are available in the market for oral administration in the treatment of depression, but fluoxetine has been shown to have a dose-related side effect due to its high oral dose and ability to undergo excessive first-pass metabolism. Olanzapine has low solubility and low bioavailability. Objective: The objective of this study was to prepare lipid nanoparticles containing fluoxetine and olanzapine to enhance the solubility and dissolution profile of the drugs. Methods: Lipid nanoparticles (LNs) were prepared by high-speed homogenization using the ultrasonication method. Different lipids and surfactants were used to screen out the best lipids, surfactants, and their ratio in the preparation of lipid nanoparticles. Drug and polymer compatibil-ity was examined using FTIR and DSC studies. The formulation was optimized using the central composite design to establish functional relationship between independent variables and respons-es. Optimized batch was characterized using particle size, PDI, zeta potential, % EE, % CDR, and stability. Results: Phase solubility study revealed FLX to have highest solubility in stearic acid and oleic acid, whereas OLZ showed highest solubility in Precirol ATO 5 and oleic acid. Poloxamer 188 was selected on the basis of high entrapment efficiency of the drug. In LNs, no significant interaction between drug and polymer was confirmed by DSC and FTIR. The particle size of optimized batch was found to be 411.5 nm with 0.532 PDI and - 9.24 mV zeta potential. For FLX and OLZ, the %EE and %CDR after 8h were found to be more than 90%. No significant change in %EE and %CDR of the formulation was observed after 4 weeks of storage. Conclusion: Experimental results demonstrated excellent drug entrapment as well as controlled release behavior from optimized LNs of FLX and OLZ at reduced dosage frequency.

Reaching the limits of antipsychotic treatment: the upper end of severe schizophrenia in forensic institutions - a case report

IntroductionSevere schizophrenia is often closely related to delinquency resulting in relative overrepresentation of these manifestations of disease in forensic institutions.ObjectivesThe aim of the present work is to report the therapeutic challenges in a case of severe schizophrenia in a forensic institution from a clinical viewpoint as a basis for discussion.MethodsThe case report is based on the available clinical documentation, exploratory interviews as well as a structured clinical interview (PANSS).ResultsPresenting a case of a 41-year-old, male Caucasian inpatient suffering from a catatonic schizophrenia, we report the challenges in treatment of chronic, major schizophrenic disease resistant to antipsychotic medication. Without any previous criminal convictions, he has been instutionalized in a forensic psychiatry after a bodily harm to a random stranger about three years ago. Regarding medical history, information is limited to a few inpatient admissions prior to detention documenting intravenous opioid and cocaine abuse. Initially, the patient presented sexual disinhibition and ongoing endangerment of others with frequent assaults to other patients and prison guards. From a psychopathological viewpoint several phenomenona such as delusional intuition, acoustic, tactile and coenaesthetic hallucinations, echolalia, mannerisms and thought diffusions reflect the severe course of the disease (PANSS: P 34/49, N 38/49, G 73/112; total 145/210). Therapeutic attempts with an antipsychotic combination of risperidone, olanzapine and quetiapine as well as valproic acid resulted in insufficient recovery with persistent physical assaults and florid psychosis. In reaction to that zuclopenthixol for impulse control was added. As from the beginning of this year a switch of medication by gradually replacing risperidone and zuclopenthixol with haloperidol and clozapine showed modest success. Under the current medication and therapeutic drug levels the patient does not pose endangerment to others. However, regular tonic-eye fits require supplementary treatment with biperiden, and the patient still presents frequent periods of self-harm punching himself, verbal lack of impulse control and the psychopathological phenomenona described before. In addition to pharmacological treatment the patient receives psychotherapeutic one-on-one conversations. Despite approaching all limits of the available antipsychotic repertoire, psychopathology is only insufficiently controlled leading considerations to electroconvulsive therapy as a treatment of last resort.ConclusionsCertainly, the present case is exemplary for a severely ill population of patients reaching – after a long and untreated course of disease - a chronic stage that does not sufficiently respond to a multitude of treatment attempts despite proper compliance raising the urgent need for further treatment options.Disclosure of InterestNone Declared

Case Series: The use of Lithium in Bipolar Affective Disorder and End-Stage Renal Disease

IntroductionLithium is a highly effective treatment in the management of Bipolar Affective Disorder (BPAD) however it is associated with increased risk of developing chronic kidney disease. There is a lack of clear guidance on alternative approaches to managing those individuals that require cessation of lithium due to progression to end stage renal disease (ESRD).ObjectivesWe discuss two patients with BPAD on lithium therapy who have developed ESRD. In both cases, lithium was discontinued due to ESRD, with alternatives trialled. In one case, the patient continues to be managed without lithium, whereas in the second, a decision was made to recommence lithium at a low dose. We reviewed the literature to provide meaningful context to the cases.MethodsCase 1 This patient with a long history of BPAD and multiple medical co-morbidities experienced progressive decline in renal function. A decision was made to cease lithium therapy with close monitoring for signs of affective relapse. The patient was stabilised using a combination of sodium valproate and quetiapine. Since cessation of lithium, the patient has required a significant increase in support from the CMHT and more frequent admissions to manage mood and anxiety symptoms that cause significant subjective distress.Results Case 2 This patient had a long history of stable BPAD, with no episodes of illness for over 30 years. Unfortunately they developed CKD and despite a significant reduction in lithium over time, they developed ESRD requiring haemodialysis. Lithium was discontinued leading to a manic relapse of BPAD requiring a prolonged admission and a combination of carbamezapine, olanzapine, escitalopram and clonazepam to stabilise their mental state. Following discharge home, their mental state failed to reach baseline and they reported significant anxiety symptoms and memory impairment. Following protracted assessment and support they were deemed unfit for renal transplant and a decision was then made by the patient, their family, nephrology and psychiatry to recommence lithium therapy whilst on haemodialysis. Their anxiety and functioning improved significantly following the reintroduction of low dose lithium, allowing the withdrawal of other neuroleptics.ConclusionsBoth cases required an individual approach to balance physical and mental health considerations. There are no clear markers to predict if a patient will respond to alternative mood stabilisers, nor is there a guarantee that kidney function will improve or stop declining when lithium is discontinued. Decisions should reflect patient preference and balance risks associated with relapse and of declining ESRD.Disclosure of InterestNone Declared

A combination of fluoxetine and olanzapine for the treatment of an adolescent with severe misophonia

A combination of fluoxetine and olanzapine for the treatment of an adolescent with severe misophonia

Navigating the intersection of Post-COVID olfactory dysfunction and mental Health: A biopsychosocial case study

Background: Olfactory Dysfunction (OD) post-SARS-CoV-2 infection can manifest in various forms, including qualitative impairments such as parosmia. We describe a 26-year-old woman's trajectory from anosmia following COVID-19 infection to parosmia, which evolved into severe depression. This young woman from North India began perceiving a "garbage-like" odor from food items several months after recovering from COVID-19. Her distress from this condition, exacerbated by her family's lack of understanding, led to significant dietary restrictions, weight loss, and subsequent development of an episode of severe depression linked to the distress from her persistent olfactory dysfunction. A combination of escitalopram, olanzapine, and carbamazepine was initiated alongside psychoeducation sessions for the family. Over the following months, her depressive and olfactory symptoms showed significant improvement. This case illuminates the complex relationship between sensory dysfunction and mental health post-COVID-19, emphasizing the need for an integrated biopsychosocial treatment approach and the crucial role of familial understanding and support.

Evaluation of palonosetron, fosaprepitant, and olanzapine as antiemetic prophylaxis for fludarabine and melphalan-based conditioning regimens prior to allogeneic hematopoietic stem cell transplants

BackgroundLimited data are available regarding efficacious antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). In patients aged 60 years or older, allogeneic HSCT is associated with improved survival, but tolerability of the transplant is a significant barrier. Fludarabine and melphalan (Flu–Mel) is a frequently utilized multi-day reduced intensity conditioning regimen for allogeneic HSCT. However, the optimal CINV prevention regimen is unknown. ObjectiveThe purpose of this study was to evaluate the efficacy of a novel CINV prophylaxis regimen prior to allogeneic HSCT with Flu–Mel compared to a historical control group. Study designThis was a retrospective, single-center, cohort review of 123 patients who received a Flu–Mel preparative regimen prior to allogeneic HSCT from January 1, 2019, to September 30, 2022. Fifty-nine patients received high dose ondansetron (HDO) for CINV prevention, while sixty-four patients received a combination of palonosetron, fosaprepitant, and olanzapine (PFO). The primary outcome was average number of rescue antiemetic doses administered per day. A key secondary outcome was time to first rescue antiemetic. ResultsThe median number of antiemetic doses used per day was significantly lower in patients who received PFO compared to HDO (1.94 doses [0.31–3.60] vs 3.31 doses [1.61–4.92]; p = 0.002). In addition, use of PFO significantly prolonged the median time to first rescue antiemetic compared to HDO (41.3 h [24.3–122.7] vs 26.2 h [14.7–48.1]; p = 0.016). ConclusionThe combination of palonosetron, fosaprepitant, and olanzapine is an effective antiemetic regimen for patients receiving a Flu–Mel-based preparative regimen.

Treatment of Depression With Psychotic Features in Maltreated Adolescents: Evidence-Based Case Report

Introductions: Depressive disorders are expected consequences of experiencing child maltreatment. Many depressive disorders can occur with or without psychosis, which has different implications for treatment and prognosis. This condition raises the challenge of treating depression in maltreated adolescents because the patient has inadequate family and social support. Consequently, it is difficult for the patient to undergo psychotherapy that involves family. Case: A 17-year-old female was diagnosed with psychotic depression. The patient had symptoms of depression, accompanied by hallucinations, since five years ago. The patient was hospitalized for suicidal ideation and food refusal for days. Patient had a history of child maltreatment by family and experienced bullying since elementary school. Patient believes that her family, especially her mother, had hated her from the beginning. Discussions: After stabilization of the patient’s general condition, psychopathology exploration was done together with selection of appropriate treatment. Combined Cognitive Behavioral Therapy (CBT), Selective Serotonin Reuptake Inhibitor (SSRI) and atypical antipsychotic treatment are the evidence-based treatments for psychotic depression in maltreated adolescents. Studies involving patients with psychotic depression which were treated by combination of sertraline and olanzapine showed significant improvement of depression and psychotic symptoms and reduced the risk of relapse over 36 weeks, compared to sertraline plus placebo. Conclusion: Combination of SSRI, atypical antipsychotic and CBT with a trauma-informed approach should be considered as treatment for psychotic depression in maltreated adolescents.

Effects of Combined Therapy of Olanzapine and Samidorphan on Safety and Metabolic Parameters in Schizophrenia Patients: A Meta-Analysis.

This meta-analysis intended to evaluate the safety and metabolic effects of the combination of olanzapine (OLZ) and samidorphan (SAM) in the treatment of schizophrenia (SCZ) patients. We searched for the English and Chinese databases for randomized controlled trials (RCTs) on the OLZ combined with SAM for SCZ. The English databases included PubMed, Web of Science, EMbase, and Cochrane Library, however, Chinese databases included Chinese Biology Medicine (CBM), VIP, Wanfang, and China National Knowledge Infrastructure (CNKI). All database searches were due by May 31, 2023. Using Review Manager 5.4 software, a meta-analysis was conducted following a literature review and data extraction. This study included five RCTs involving 1781 patients. Regarding safety, the meta-analysis revealed that the probability of weight gain was reduced in the OLZ and SAM group than in the OLZ group (RR = 0.83, 95% CI (0.69, 0.99), P < 0.05). Statistically, the incidence of severe adverse safety events, dry mouth, headache, drowsiness, death, and suicidal perception events was insignificant (P > 0.05); in terms of metabolism, compared with the OLZ group, the OLZ plus SAM group reduced total cholesterol (TC) levels (MD = -3.58, 95% CI (-6.81, -0.34), P < 0.05). However, it had no significant effect on metabolic indices, including low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, and insulin index (P > 0.05). In patients with SCZ, treatment with the combination of OLZ and SAM decreased the incidence of weight gain adverse events and TC levels; nevertheless, it did not affect other adverse events or metabolic parameters. These findings provide clinicians with evidence-based guidance and support for drug selection. However, it is crucial to confirm these findings through further high-quality research.

Effects of low-dose combined olanzapine and sertraline on negative and depressive symptoms in treatment-resistant outpatients with acute exacerbated schizophrenia.

Background: Treatment-resistant schizophrenia (TRS) is a major clinical challenge. Current antipsychotic medications do not adequately address negative and depressive symptoms in patients with TRS, and novel treatments are thus needed. This study examines the efficacy of low-dose combined olanzapine (OLA) and sertraline on depressive and negative symptoms in patients with TRS. Methods: A total of 34 TRS outpatients with acutely exacerbated schizophrenia were randomly assigned to OLA monotherapy (12.5-20mg/day) (control group) or low-dose combined OLA (7.5-10mg/day) and sertraline (50-100mg/day) (OS group). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of treatment in weeks 4, 8, 12, and 24. Depressive symptoms and social functioning were also assessed. Results: Compared to the control group, the OS group showed significant improvements in depressive and negative symptoms over time. In addition, the low-dose combination of OLA and sertraline significantly improved social functioning compared with OLA monotherapy. There were no significant between-group differences in psychotic symptom improvement. However, the reduction in Hamilton Depression Rating Scale total score and PANSS negative subscore were not associated with improvements in social functioning, suggesting that these effects of combined treatment are independent. Conclusion: Low-dose combined OLA and sertraline may be effective in the treatment of negative and depressive symptoms compared with standard OLA monotherapy in patients with TRS who are experiencing an acute exacerbation of schizophrenia. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04076371].

Journal Digest: CBT With Cardiac Rehab, PMDD Neurochemistry, and More

Journal Digest: CBT With Cardiac Rehab, PMDD Neurochemistry, and More

A Review of Current Strategies in Treatment-Resistant Schizophrenia: Considering Paliperidone Palmitate LAI With and Without Olanzapine as an Alternative to Clozapine

AbstractBackgroundSchizophrenia is a debilitating mental illness that affects patient’s function and quality of life. Estimates indicate a lifetime prevalence of 0.48%, causing up to 13.4 million years of life burdened by disability. 30% of these patients are deemed as having treatment-resident schizophrenia (TRS), a subset of which do not respond to clozapine, the medication designated for TRS. Those that do not respond to clozapine are deemed to have clozapine-resistant schizophrenia (CRS), requiring further augmentation or multiple antipsychotics.Current limitationsClozapine only has limited formulations available (oral [PO] and dissolving [ODT]) and has a substantial side effect burden. Most serious among these side effects includes agranulocytosis, which in some cases can cause severe infections such as septicemia. Regular blood draws monitoring for this are vital to prevent this dangerous consequence, but place further burden on patients, requiring weekly to monthly lab work and visits. Other common and burdensome side effects include tachycardia, hypotension, sialorrhea, weight gain, and metabolic syndrome, to name a few. However, treatment for TRS is still needed, and further alternatives must be explored.Proposed alternativesAmong studies done on clozapine, few compare second-generation antipsychotics head-to-head, and those that do find similar improvement in overall symptom burden among multiple antipsychotics, especially olanzapine and paliperidone (in particular, paliperidone palmitate). Due in part to the improved receptor profile of these medications (especially 5-HT2A, 6, and 7) compared to clozapine, they can have similar or superior effect in patients with TRS without substantial patient side effect and functional burden. Paliperidone palmitate formulations are developing that can be spaced further and further apart, allowing for minimal impact on patient’s livelihood, while demonstrating similar overall effect with improved side effect profile. However, onset of action is slow, and an effective adjunct strategy may be to initially administer olanzapine for the first 6 months until peak effect is expected from paliperidone palmitate, at which point monotherapy with paliperidone is preferred.ConclusionsAlternative therapies for patients with TRS may be more functional with fewer side effects, and this work indicates a particularly effective strategy may be to pursue paliperidone palmitate monotherapy long-term while utilizing the unique combination of paliperidone and olanzapine in the short-term (first 6 months) while awaiting peak efficacy.FundingNo Funding

Amisulpride Augmentation in Schizophrenia Patients with Poor Response to Olanzapine: A 4-week, Randomized, Rater-Blind, Controlled, Pilot Study

IntroductionOlanzapine (OLA) is a common first-prescribed antipsychotic and has shown favorable efficacy in acutely exacerbated patients with schizophrenia. The mixed receptor activity of OLA and its greater affinity for serotonin 5-HT2A rather than dopamine D2 receptors are similar to those of clozapine. Pharmacokinetically, OLA is metabolized mainly by hepatic cytochrome enzyme P450 1A2 (CYP1A2). Because risks of antipsychotic polypharmacy include increased drug-drug interactions, pharmacokinetic considerations are important for selection of antipsychotics to be combined. Due to its pharmacological characteristics, amisulpride (AMI), another atypical antipsychotic with proven efficacy, is a promising adjuvant agent of special interest. AMI is unlikely to interact with other drugs due to the low plasma protein binding and metabolism and does not affect the activity of the CYP system. Furthermore, AMI is highly selective for dopamine D2/D3 receptors; has minimal or no affinity for D1, D4, or D5 receptors. Despite the potential benefits of the combination of OLA and AMI, only a few open-label studies have been conducted, and no randomized clinical trial has been performed to date to examine the efficacy and tolerability of the combination. Hence, the goals of this study were to test the hypothesis that AMI augmentation would improve psychotic symptoms and be well tolerated in schizophrenic patients who showed poor response to OLA monotherapy.ObjectivesThe purpose of this study was to compare the efficacy and tolerability of continued olanzapine (OLA) versus amisulpride (AMI) augmentation in schizophrenic patients with poor response to OLA monotherapy.MethodsThe present 4-week, randomized, rater-blinded study included 25 patients with schizophrenia who were partially or completely unresponsive to treatment with OLA monotherapy. Eligible subjects were randomly assigned at a 1:1 ratio to continuation of OLA monotherapy (OLA group) or OLA with AMI augmentation (AMI group). Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at 1, 2, and 4 weeks.ResultsThe changes in PANSS total score and PANSS-positive subscale score were significantly different (p &lt; 0.05) between the OLA and AMI groups. The differences between the two groups in PANSS-negative subscale, PANSS-general subscale, Brief Psychiatric Rating Scale, and Clinical Global Impression-Severity (CGI-S) scale scores were not statistically significant.ConclusionsAMI augmentation could be an effective strategy for patients with schizophrenia who show inadequate early response to OLA monotherapy.Disclosure of InterestW.-M. Bahk Grant / Research support from: Handok Pharmaceuticals, Seoul, Korea, Y. S. Woo: None Declared, S.-Y. Park: None Declared, B.-H. Yoon: None Declared, S.-M. Wang: None Declared, M.-D. Kim: None Declared

Evolution of patients with bipolar disorder according to pharmacological treatment Pediatric Hospital "Juan Manuel Márquez" 2009-2011

To know the evolution, according to the pharmacological treatment received, of the patients admitted to the Psychiatric Ward of the "Juan Manuel Márquez" Paediatric Hospital, with Bipolar Disorder (TB) in the period from January 2009 to December 2011, the present study. The objective is to identify the evolution of the patients three, six and twelve months after hospital discharge according to the pharmacological treatment used. A retrospective longitudinal descriptive study was carried out between May 2012 and May 2013. 81 hospitalized patients with TB were studied. The source of information was their medical records and a semi-structured interview. The data was processed in SPSS version 15 and the results are presented in statistical tables. Three months after hospital discharge, the highest percentage of patients with satisfactory clinical status had treatment with Haloperidol alone, in second place Risperdal and Carbamazepine and in third place the combination of Haloperidol and Magnesium Valproate (Mg), while Six months was Haloperidol alone, followed by the combination of Olanzapine and Lithium Carbonate, Risperdal and Mg Valproate, one year after hospital discharge the combination of Olanzapine and Lithium Carbonate was found first, followed by Risperdal with Carbamazepine and of quetiapine alone. The treatments most associated with satisfactory clinical status were: Haloperidol alone, Quetiapine alone, as well as the combinations of Risperdal and Carbamazepine, Risperdal and Mg Valproate, Olanzapine and Lithium Carbonate, and Haloperidol with Mg Valproate.

Combining samidorphan with olanzapine to mitigate weight gain as a side effect in schizophrenia treatment.

This article analyzes clinical trials that provide evidence for the positive effects of using samidorphan to mitigate undesirable weight gain in patients diagnosed with schizophrenia who are undergoing treatment with olanzapine. Weight gain is a prevalent and problematic side effect of antipsychotic drug therapy, particularly in patients with schizophrenia. To address this issue, extensive research is being conducted to explore new drug therapies that can effectively counteract psychotic symptoms while minimizing the occurrence of unwanted side effects. One promising approach involves the addition of weight-loss substances to existing medications. Studies have indicated that opioid receptor antagonists, such as samidorphan, have the potential to facilitate weight loss. Consequently, a novel therapy combining samidorphan and olanzapine has been developed and is discussed in detail in this article. The combination of samidorphan and olanzapine has demonstrated its ability to effectively reduce weight gain in patients with schizophrenia, without compromising the drug's primary function of alleviating psychotic symptoms. Moreover, the inclusion of samidorphan in the treatment regimen may contribute to a lower risk of cardiovascular events, though it is worth noting that it could also lead to an increase in digestive side effects. Despite this potential drawback, the introduction of this innovative therapy represents a significant advancement in the management of obesity among individuals with schizophrenia.

In vivo Characterization of the Opioid Receptor-Binding Profiles of Samidorphan and Naltrexone in Rats: Comparisons at Clinically Relevant Concentrations.

The atypical antipsychotic olanzapine is approved for the treatment of schizophrenia and bipolar I disorder; however, weight gain and metabolic dysregulation associated with olanzapine therapy have limited its clinical utility. In clinical studies, treatment with the combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) mitigated olanzapine-associated weight gain while providing antipsychotic efficacy similar to that of olanzapine. Although samidorphan is structurally similar to the opioid receptor antagonist naltrexone, the two differ in their pharmacokinetics and in vitro binding affinities to mu, delta, and kappa opioid receptors (MOR, DOR, and KOR, respectively). The objective of this series of nonclinical studies was to compare the in vivo binding profiles of samidorphan and naltrexone and their receptor occupancies at MOR, DOR, and KOR in rat brains. Male rats were injected with samidorphan or naltrexone to obtain total and unbound plasma and brain concentrations representing levels observed in humans at clinically relevant oral doses. Subsequently, samidorphan and naltrexone brain receptor occupancy at MOR, DOR, and KOR was measured using ultra-performance liquid chromatography and high-resolution accurate-mass mass spectrometry. A dose-dependent increase in samidorphan occupancy was observed at MOR, DOR, and KOR (EC50: 5.1, 54.7, and 42.9 nM, respectively). Occupancy of naltrexone at MOR (EC50: 15.5 nM) and KOR was dose dependent; minimal DOR occupancy was detected. At the clinically relevant unbound brain concentration of 23.1nM, samidorphan bound to MOR, DOR, and KOR with 93.2%, 36.1%, and 41.9% occupancy, respectively. At 33.5 nM, naltrexone bound to MOR and KOR with 79.4% and 9.4% occupancy, respectively, with no binding at DOR. At clinically relevant concentrations, samidorphan occupied MOR, DOR, and KOR, whereas naltrexone occupied only MOR and KOR. The binding profile of samidorphan differs from that of naltrexone, with potential clinical implications.

Olanzapine add-on treatment promotes neuronal differentiation of neural stem cells compared with fluoxetine alone.

The addition of olanzapine to fluoxetine produces an antidepressant effect on fluoxetine nonresponders. Promoting hippocampal neurogenesis is associated with the successful treatment of depression. The present study aimed to investigate the interaction of olanzapine and fluoxetine in regulating neurogenesis. We found that fluoxetine alone does not affect cell proliferation and inhibits the neuronal differentiation of cultured neural stem cells (NSCs), but promotes NSCs proliferation and exerts no effect on neuronal fate when NSCs are cocultured with neurons. In addition, fluoxetine alone also does not alter the neuronal fate of newborn hippocampal cells in vivo. Although fluoxetine treatment elicits different results, our data consistently show that olanzapine alone does not affect the proliferation and neuronal differentiation of NSCs. The combination of olanzapine and fluoxetine has no profound effect on NSCs proliferation compared with fluoxetine alone, but olanzapine add-on treatment produces a greater number and percentage of differentiated neurons from NSCs. Further investigations are needed to explore the underlying mechanisms of the increased neurogenesis caused by the combination of olanzapine with fluoxetine.