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Bipolar Disorders Dec 2021The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic... (Review)
Review
Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations.
OBJECTIVES
The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided-a critical gap which the current update aims to address.
METHOD
Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion.
RESULTS
No agents met threshold for first-line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second-line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second-line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first-line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second-line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first-line, and lithium and olanzapine identified as second-line options.
CONCLUSION
The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.
Topics: Antipsychotic Agents; Anxiety; Aripiprazole; Bipolar Disorder; Canada; Humans; Olanzapine; Valproic Acid
PubMed: 34599629
DOI: 10.1111/bdi.13135 -
Current Psychiatry Reports Jul 2022Identifying medications that may be used as therapeutic agents for eating disorders is a longstanding focus of research, with varying degrees of success. The present... (Review)
Review
PURPOSE OF REVIEW
Identifying medications that may be used as therapeutic agents for eating disorders is a longstanding focus of research, with varying degrees of success. The present review consolidates the most recent findings on pharmacological treatment of three eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED).
RECENT FINDINGS
Recent research suggests that olanzapine demonstrates positive effects on weight gain among outpatients with AN. There are fewer recent advances in psychopharmacological treatment for BN and BED, likely due to the relative success of prior medication trials. Olanzapine is the first medication to safely promote weight gain among individuals with AN. Fluoxetine is FDA-approved for BN treatment, and lisdexamfetamine is FDA-approved for BED treatment. BN and BED also generally respond well to SSRIs prescribed off-label. Research on psychopharmacological treatments for other eating disorders, such as avoidant-restrictive food intake disorder and other specified feeding and eating disorders, are sorely needed.
Topics: Anorexia Nervosa; Binge-Eating Disorder; Bulimia Nervosa; Feeding and Eating Disorders; Humans; Olanzapine; Weight Gain
PubMed: 35576089
DOI: 10.1007/s11920-022-01340-5 -
Journal of Clinical Oncology : Official... May 2023Anorexia occurs in 30%-80% of patients with advanced malignancies, which may be worsened with chemotherapy. This trial assessed the efficacy of olanzapine in stimulating... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer.
PURPOSE
Anorexia occurs in 30%-80% of patients with advanced malignancies, which may be worsened with chemotherapy. This trial assessed the efficacy of olanzapine in stimulating appetite and improving weight gain in patients receiving chemotherapy.
METHODS
Adults (≥18 years) with untreated, locally advanced, or metastatic gastric, hepatopancreaticobiliary (HPB), and lung cancers were randomly assigned (double-blind) to receive olanzapine (2.5 mg once a day for 12 weeks) or placebo along with chemotherapy. Both groups received standard nutritional assessment and dietary advice. The primary outcomes were the proportion of patients with weight gain > 5% and the improvement in appetite (assessed by the visual analog scale [VAS] and the Functional Assessment of Chronic Illness Therapy system of Quality-of-Life questionnaires Anorexia Cachexia subscale [FAACT ACS]). Secondary end points were change in nutritional status, quality of life (QOL), and chemotherapy toxicity.
RESULTS
We enrolled 124 patients (olanzapine, 63 and placebo, 61) with a median age of 55 years (18-78 years), of whom 112 (olanzapine, 58 and placebo, 54) were analyzable. The majority (n = 99, 80%) had metastatic cancer (gastric [n = 68, 55%] > lung [n = 43, 35%] > HPB [n = 13, 10%]). The olanzapine arm had a greater proportion of patients with a weight gain of > 5% (35 of 58 [60%] 5 of 54 [9%], < .001) and improvement in appetite by VAS (25 of 58 [43%] 7 of 54 [13%], < .001) and by FAACT ACS (scores ≥37:13 of 58 [22%] 2 of 54 [4%], = .004). Patients on olanzapine had better QOL, nutritional status, and lesser chemotoxicity. Side effects attributable to olanzapine were minimal.
CONCLUSION
Low-dose, daily olanzapine is a simple, inexpensive, well-tolerated intervention that significantly improves appetite and weight gain in newly diagnosed patients on chemotherapy.
Topics: Adult; Humans; Middle Aged; Olanzapine; Anorexia; Quality of Life; Lung Neoplasms; Double-Blind Method; Weight Gain
PubMed: 36977285
DOI: 10.1200/JCO.22.01997 -
Pharmacogenomics Sep 2021Genetic polymorphism in olanzapine-metabolizing enzymes, transporters and drug targets is associated with alterations in safety and efficacy. The aim of this systematic...
Genetic polymorphism in olanzapine-metabolizing enzymes, transporters and drug targets is associated with alterations in safety and efficacy. The aim of this systematic review is to describe all clinically relevant pharmacogenetic information on olanzapine and to propose clinically actionable variants. Two hundred and eighty-four studies were screened; 76 complied with the inclusion criteria and presented significant associations. Taq1A (rs1800497) *A1, -2548 (rs7799039) G and *1F alleles were related to olanzapine effectiveness and safety variability in several studies, with a high level of evidence. -141 (rs1799732) Ins, A-241G (rs1799978) G, Ser9Gly (rs6280) Gly, rs7997012 A, C3435T (rs1045642) T and G2677T/A (rs2032582) T and *3 alleles were related to safety, effectiveness and/or pharmacokinetic variability with moderated level of evidence.
Topics: Antipsychotic Agents; Humans; Olanzapine; Pharmacogenetics; Polymorphism, Genetic; Schizophrenia; Treatment Outcome
PubMed: 34528455
DOI: 10.2217/pgs-2021-0051 -
Brain and Behavior Feb 2022Anorexia nervosa (AN) is a severe psychiatric disorder characterized by starvation and malnutrition, a high incidence of coexisting psychiatric conditions, and treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by starvation and malnutrition, a high incidence of coexisting psychiatric conditions, and treatment resistance. The effect of pharmacotherapy has been controversial.
METHOD
A systematic review was conducted for evidence of an effect of olanzapine versus placebo in adults or its effect as adjuvant treatment of AN in adolescents.
RESULTS
A total of seven articles (304 patients with AN) were identified. There were four double-blind, randomized studies examining the effect of olanzapine in the treatment of AN. The mean difference in body mass index (BMI) at the end of treatment between olanzapine and placebo was 0.67 kg/m (95% confidence interval (CI) 0.15-1.18 kg/m ; p = 0.01; I = 0%, p for heterogeneity < 0.79). The olanzapine groups showed a significant increase in BMI of 0.68 kg/m (95% CI 0.22-1.13 kg/m ; p < 0.001; I = 0%, p for heterogeneity = 0.74) compared to the placebo groups. Only two studies examined the effect of olanzapine as adjuvant treatment in adolescents and showed an increase in BMI of 0.66 kg/m (95% CI -0.36 to 1.67 kg/m ; p = 0.21; I = 11%, p for heterogeneity = 0.32).
DISCUSSION
Olanzapine showed efficacy in the treatment of AN with an increased BMI at the end of treatment in adults. The effect of olanzapine as adjuvant treatment in adolescents remains unclear.
Topics: Adolescent; Adult; Anorexia Nervosa; Benzodiazepines; Body Mass Index; Double-Blind Method; Humans; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35020271
DOI: 10.1002/brb3.2498 -
Clinics in Perinatology Mar 2022Delirium is likely present in the neonatal intensive care unit and has been largely unrecognized. There are several risk factors for delirium including illness severity,... (Review)
Review
Delirium is likely present in the neonatal intensive care unit and has been largely unrecognized. There are several risk factors for delirium including illness severity, neurosedative exposure, and environmental disruptions that put infants at risk for delirium. Regular use of scoring systems should be considered to improve delirium detection. When identified, initial steps in management should include resolving underlying causes and implementation of standard nonpharmacologic measures. Mounting pediatric evidence suggests that the atypical antipsychotics, as well as the α-2 agonists, may be additionally beneficial in treating delirium as well as improving the ability to wean off other neurosedative medications.
Topics: Antipsychotic Agents; Benzodiazepines; Child; Delirium; Humans; Infant; Infant, Newborn; Olanzapine; Risperidone
PubMed: 35209993
DOI: 10.1016/j.clp.2021.11.001 -
Current Psychiatry Reports Nov 2021Over the last ten years, the treatment of psychosis has seen a near explosion of creative development in both novel agents and new delivery modalities. The current... (Review)
Review
PURPOSE OF REVIEW
Over the last ten years, the treatment of psychosis has seen a near explosion of creative development in both novel agents and new delivery modalities. The current review summarizes these developments over the past decade (2011-2020). We performed a systematic review utilizing PubMed and PsychInfo with the aim of identifying all the RCT and related analyses in adults with psychosis (schizophrenia and mania).
RECENT FINDINGS
We identified 11 significant developments: the introduction of new antipsychotics cariprazine, brexpiprazole, lumateperone, and pimavanserin; introduction of new delivery methods: subcutaneous long-acting risperidone, aripiprazole lauroxil, transdermal asenapine, and inhaled loxapine; and the introduction of new approaches such as olanzapine/samidorphan for olanzapine-associated weight gain, examination of the TAAR1 agonist SEP 363,856 as a test of concept, and the combination of Xanomeline/Trospium, an M and M muscarinic receptor agonist in conjunction with a peripheral anticholinergic. Last decade has seen a tremendous development in second-generation antipsychotics which provides unprecedented treatment options for clinicians in treating psychosis.
Topics: Adult; Antipsychotic Agents; Humans; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia
PubMed: 34843030
DOI: 10.1007/s11920-021-01298-w -
Journal of Affective Disorders May 2020We investigated the comparative efficacy and tolerability of pharmacological treatment strategies for the treatment of acute bipolar depression. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We investigated the comparative efficacy and tolerability of pharmacological treatment strategies for the treatment of acute bipolar depression.
DATA SOURCES
A systematic review and network meta-analysis was conducted by searching eight registries for published and unpublished, double-blind, randomized controlled trials of pharmacotherapies for the acute treatment of bipolar depression.
DATA EXTRACTION AND SYNTHESIS
PRISMA guidelines were used for abstracting data, while the Cochrane Risk of Bias Tool was used to assess data quality. Data extraction was done independently by two reviewers, with discrepancies resolved by consensus. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
Primary outcomes were efficacy (response and remission rate) and acceptability (completion of treatment and dropouts due to adverse events). Summary odds ratios (ORs) were estimated using pairwise and network meta-analysis with random effects.
RESULTS
Identified citations (4,404) included 50 trials comprising 11,448 participants. Escitalopram, phenelzine, moclobemide, carbamazepine, sertraline, lithium, paroxetine, aripiprazole, gabapentin and ziprasidone appear to be ineffective as compared to placebo in treatment of bipolar depression. Divalproex, olanzapine/fluoxetine, olanzapine, quetiapine, cariprazine, and lamotrigine, appear to be effective as compared to placebo in treatment of bipolar depression according to the network meta-analysis. Aripiprazole showed higher discontinuation rates versus placebo due to the appearance of any adverse event. Quetiapine was better than placebo at reducing treatment-emergent affective switches. For Bipolar I Disorder, cariprazine, fluoxetine, imipramine, lamotrigine, lurasidone, olanzapine-fluoxetine, and olanzapine were significantly better than placebo at response, while fluoxetine, imipramine, cariprazine, lurasidone, olanzapine-fluoxetine, and olanzapine were significantly better than placebo at remission.
CONCLUSIONS AND RELEVANCE
These results could serve evidence-based practice and inform patients, physicians, guideline developers, and policymakers on the relative benefits of the different antidepressants, antipsychotics, and mood-stabilizing agents for the treatment of bipolar depression.
REGISTRATION
PROSPERO (CRD42019122172).
Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Lurasidone Hydrochloride; Network Meta-Analysis; Olanzapine
PubMed: 32339131
DOI: 10.1016/j.jad.2020.03.030 -
The Lancet. Oncology Feb 2020Olanzapine 10 mg added to standard antiemetic therapy including aprepitant, palonosetron, and dexamethasone has been recommended for the prevention of... (Randomized Controlled Trial)
Randomized Controlled Trial
Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
BACKGROUND
Olanzapine 10 mg added to standard antiemetic therapy including aprepitant, palonosetron, and dexamethasone has been recommended for the prevention of chemotherapy-induced nausea and vomiting. Guidelines suggest that a dose reduction to 5 mg should be considered to prevent sedation. In several phase 2 studies, olanzapine 5 mg has shown equivalent activity to olanzapine 10 mg and a favourable safety profile in relation to somnolence. We evaluated the efficacy of olanzapine 5 mg combined with standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting caused by cisplatin-based chemotherapy.
METHODS
This was a randomised, double-blind, placebo-controlled, phase 3 study to evaluate the efficacy of olanzapine 5 mg with triplet-combination antiemetic therapy done in 26 hospitals in Japan. Key inclusion criteria were patients with a malignant tumour (excluding those with a haemopoietic malignancy) who were scheduled to be treated with cisplatin (≥50 mg/m) for the first time, age between 20 and 75 years, and with Eastern Cooperative Oncology Group performance status of 0-2. Eligible patients were randomly assigned (1:1) to receive either oral olanzapine 5 mg or placebo once daily on days 1-4 combined with aprepitant, palonosetron, and dexamethasone (dosage based on the standard antiemetic therapy against highly emetogenic chemotherapy). Patients were randomly assigned to interventions by use of a web entry system and the minimisation method with a random component, with sex, dose of cisplatin, and age as factors of allocation adjustment. Patients, medical staff, investigators, and individuals handling data were all masked to treatment assignment. The primary endpoint was the proportion of patients who achieved a complete response, defined as absence of vomiting and no use of rescue medications in the delayed phase (24-120 h). All randomly assigned patients who satisfied eligibility criteria received a dose of cisplatin 50 mg/m or more, and at least one study treatment, were included in efficacy analysis. All patients who received any treatment in this study were assessed for safety. This study is registered at UMIN Clinical Trials Registry, number UMIN000024676.
FINDINGS
Between Feb 9, 2017, and July 13, 2018, 710 patients were enrolled; 356 were randomly assigned to receive olanzapine and 354 were assigned to receive placebo. All eligible patients were observed 120 h after cisplatin initiation. One patient in the olanzapine group and three in the placebo group did not receive treatment and were excluded from all analyses. One patient in the olanzapine group discontinued treatment on day 1 and was excluded from the efficacy analysis. In the delayed phase, the proportion of patients who achieved a complete response was 280 (79% [95% CI 75-83] of 354 patients in the olanzapine group and 231 (66% [61-71] of 351 patients in the placebo group (p<0·0001). One patient had grade 3 constipation and one patient had grade 3 somnolence related to treatment in the olanzapine group.
INTERPRETATION
Olanzapine 5 mg combined with aprepitant, palonosetron, and dexamethasone could be a new standard antiemetic therapy for patients undergoing cisplatin-based chemotherapy.
FUNDING
Japan Agency for Medical Research and Development.
Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Female; Humans; Japan; Male; Middle Aged; Olanzapine; Palonosetron; Postoperative Nausea and Vomiting; Time Factors; Treatment Outcome; Young Adult
PubMed: 31838011
DOI: 10.1016/S1470-2045(19)30678-3 -
Journal of Affective Disorders Aug 2022Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the... (Review)
Review
OBJECTIVES
Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the clinician. The aim of this paper is to give an overview of the evidence-based treatment options for rapid cycling.
METHODS
A systematic search on Pubmed, Embase and Cochrane databases from inception until December 2021 was conducted according to the PRISMA guidelines. An additional search on clinicaltrials.gov was done. References of retrieved papers and key reviews were hand-searched. Randomized controlled trials including at least 10 patients with bipolar disorder, rapid cycling, reporting an objective outcome measure were selected.
RESULTS
Our search, initially revealing 1330 articles, resulted in 16 papers about treatment of an acute mood episode, relapse prevention or both. Lithium, anticonvulsants, second generation antipsychotics, antidepressants and thyroid hormone were assessed as treatment options in the presented data. Evidence supporting the use of aripiprazole, olanzapine, quetiapine, valproate and lamotrigine for treatment of rapid cycling bipolar disorder was found.
LIMITATIONS
Small sample sizes, different index episodes and variety of outcome measures.
CONCLUSION
Evidence regarding treatment of rapid cycling remains scarce. Evidence supports the use of aripiprazole, olanzapine, and valproate for acute manic or mixed episodes, quetiapine for acute depressive episodes and aripiprazole and lamotrigine for relapse prevention. Given the paucity of available evidence, and the burden that accompanies rapid cycling, future research is warranted.
Topics: Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Valproic Acid
PubMed: 35545157
DOI: 10.1016/j.jad.2022.05.017