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Effects of betahistine on weight and BMI. Values (mean + s.e.m.) are least square estimated mean from mixed model analysis. Significance of difference of values for betahistine or placebo subjects at indicated time point from their own baseline values in the individual graphs: * P < .05, **P < .01. Significance of difference between betahistine and placebo subjects’ values at indicated time point: A = P < .05
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Rationale
Weight gain during treatment with antipsychotics is a prominent side-effect, especially with some second-generation antipsychotics, such as olanzapine and clozapine, and pharmacological treatments which ameliorate this side-effect are important to investigate. Decreases in histaminergic transmission in the brain induced by antipsychotics...
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Betahistine dihydrochloride is widely used to reduce the severity and frequency of vertigo attacks associated with Ménière’s disease. Betahistine is an analogue of histamine, and is a weak histamine H1 receptor agonist and potent histamine H3 receptor antagonist. The recommended therapeutic dose for adults ranges from 24 to 48 mg given in doses div...
Citations
... Only telmisartan was ineffective (Fan et al. 2019). Exenatide, liraglutide, metformin, orlistat, fluvoxamine (Lu et al. 2018), aripiprazole (Fan et al. 2013), and betahistine (Smith et al. 2018) all significantly reduced weight (Table 3). Liraglutide showed no additional effect on the bone turnover markers CTX and P1NP (Maagensen (Li et al., 2013) et al. 2021). ...
... Number of studies Percentage Citation 1-2 7 10.9 % (Every-Palmer et al., 2019), , (Kim et al., 2013), (Curto et al., 2015) (Rostagno et al., 2012), (Bruno et al., 2020), (Veerman et al., 2017) 3-4 33 51.6% (Zhao et al., 2021), (Diaz et al., 2018), (Zai et al., 2015), (Sun et al., 2016), (Brandl et al., 2016), (Glue et al., 2012), (Sanz-Fuentenebro et al., 2013), (Kluge et al., 2014), (Feng and Melkersson, 2012), (Schnell et al., 2014), (Segev et al., 2019), (Mubaslat and Lambert, 2020), (Takeuchi et al., 2017), (Wehring et al., 2018), (Veerman et al., 2016), (Wehring et (Fan et al., 2017), (Elgazzar et al., 2021), (Krivoy et al., 2017), (Møller et al., 2022) 5-6 24 37.5% (Constantine et al., 2018), (Bogers et al., 2015), (Krakowski et al., 2021), (Mishra et al., 2022), (Kahn et al., 2018), (Shakir et al., 2022), (Schooler et al., 2016), (Schooler et al., 2016), (Lin, Chao-Cheng et al., 2013), (Machielsen et al., 2014), (Nakajima et al., 2015), (Li et al., 2013), (Kreinin et al., 2016), (Lin, C. H. et al., 2018), (Maagensen et al., 2021), (Behdani et al., 2018), (Smith et al., 2018), (Chukhin et al., 2013), (Chiu et al., 2016), (Chen, P. et al., 2015), , (Lu et al., 2018), , (Morrison et al., 2018), (Wu and Lan, 2017) ...
Clozapine has been considered the “gold standard” in the treatment of schizophrenia for many years. Clozapine has a superior effect, particularly in the treatment of negative symptoms and suicidal behaviour. However, due to its numerous adverse reactions, clozapine is mainly used for treatment-resistant schizophrenia. The aim of this paper is to analyze the results of clinical studies on clozapine from 2012-2022. PubMed was used as the database. Sixty-four studies were included and categorised by topic. The pharmacokinetic properties of clozapine tablets and a clozapine suspension solution did not differ markedly. Clozapine was superior to olanzapine and risperidone in reducing aggression and depression. A long-term study showed that metabolic parameters changed comparably with olanzapine and clozapine after 8 years. Risperidone and ziprasidone can be used as an alternative to clozapine. Scopolamine, atropine drops, and metoclopramide are effective in the treatment of clozapine-induced hypersalivation. Eight drugs, including liraglutide, exenatide, metformin, and orlistat, are potentially effective in the treatment of clozapine-induced weight gain. Ziprasidone, haloperidol, and aripiprazole showed a positive effect on symptoms when added to clozapine. No investigated drug was superior to clozapine for the treatment of schizophrenia. Ziprasidone and risperidone can also be used well for the treatment of schizophrenia. In the treatment of clozapine-induced hypersalivation and weight gain, some drugs proved to be effective.
... KIDS-KD is available to the public and health care professionals (including doctors, nurses, and pharmacists), and any ADE reports submitted to the KIDS-KD are further verified by multiple health care professionals appointed by the Korea Institute of Drug Safety & Risk Management (Ministry of Food and Drug Safety) based on patient's medical charts, interviews with patient or health care professional, and scientific pharmacovigilance data from manufacturers to minimise biases [20,21]. We evaluated any ADE reports caused by anti-obesity medications commonly prescribed for obesity treatment in South Korea: amfepramone (diethylpropion) [22], betahistine [23], bupropion and naltrexone [9], liraglutide [9], lorcaserin [24], mazindol [25], orlistat [9], phentermine [9], sibutramine [26], and topiramate [9,23,27,28]. Any cases reported as ADEs induced by "other obesity agents" or "centrally acting anti-obesity agents" were excluded from the analysis to ensure the validity of medication-specific ADE analysis. ...
... KIDS-KD is available to the public and health care professionals (including doctors, nurses, and pharmacists), and any ADE reports submitted to the KIDS-KD are further verified by multiple health care professionals appointed by the Korea Institute of Drug Safety & Risk Management (Ministry of Food and Drug Safety) based on patient's medical charts, interviews with patient or health care professional, and scientific pharmacovigilance data from manufacturers to minimise biases [20,21]. We evaluated any ADE reports caused by anti-obesity medications commonly prescribed for obesity treatment in South Korea: amfepramone (diethylpropion) [22], betahistine [23], bupropion and naltrexone [9], liraglutide [9], lorcaserin [24], mazindol [25], orlistat [9], phentermine [9], sibutramine [26], and topiramate [9,23,27,28]. Any cases reported as ADEs induced by "other obesity agents" or "centrally acting anti-obesity agents" were excluded from the analysis to ensure the validity of medication-specific ADE analysis. ...
Introduction:
Despite rising concerns regarding the safety of anti-obesity medications, there is a lack of comprehensive pharmacovigilance investigations utilising real-world data. We aimed to characterise the prevalence and seriousness of adverse drug events (ADEs) related to anti-obesity medications and to identify predictors associated with increased risk of serious adverse events (SAE), thereby conveying evidence on drug safety.
Methods:
We conducted a cross-sectional analysis on ADE cases spontaneously reported to the Korea Adverse Event Reporting System Database (KIDS-KD). ADE reports pertaining to anti-obesity medications prescribed for overweight, obesity (International Classification of Disease, 10th revision (ICD-10) code E66) and abnormal weight gain (ICD-10 code E63.5) were included in the analysis. We performed a disproportionality to detect the association of the system organ class-based ADEs with their seriousness an individual's sex by estimating reporting odds ratios (RORs) and their 95% confidence intervals (CIs). We performed logistic regression to investigate factors that are substantially associated with increased SAE risks by estimating odds ratio (OR) and their 95% CIs.
Results:
The most common causative anti-obesity medication was phentermine, followed by liraglutide. ADEs associated with psychiatric disorders (ROR = 1.734; 95% CI = 1.111-2.707), liver and biliary system disorders (ROR = 22.948; 95% CI = 6.613-70.635), cardiovascular disorders (ROR = 5.707; 95% CI = 1.965-16.574), and respiratory disorders (ROR = 4.567; 95% CI = 1.774-11.762) were more likely to be serious events. Additionally, men are more likely to experience ADEs related gastrointestinal disorders (ROR = 1.411) and less likely to have heart and rhythm disorders (ROR = 0.507). The risk of SAE incidences was positively correlated with being male (OR = 2.196; 95% CI = 1.296-3.721), dual or triple combination of anti-obesity medications (OR = 3.258; 95% CI = 1.633-6.501 and OR = 8.226; 95% CI = 3.046-22.218, respectively), and concomitant administration of fluoxetine (OR = 5.236; 95% CI = 2.218-12.365).
Conclusions:
Seriousness of anti-obesity medication-related ADEs differs among system-organ class, while sex-related differences in ADE profiles are also present. The predictors substantially increasing risk of SAE incidences include being male, having a higher number of concomitant medications (including multiple combination of anti-obesity medications), and concurrent use of fluoxetine. Nonetheless, further pharmacovigilance investigation and monitoring are needed to enhance awareness on ADEs induced by anti-obesity medications.
... Current management of overweight and obese patients treated with antipsychotics includes pharmacological interventions, dietary advice, and behavioral strategies [8]. Drug intervention in the SGAs has a significant reduction in weight gain such as reboxetine combined with olanzapine, olanzapine combined with statin group, and olanzapine combined with the new drug samidorphan [71][72][73]. The mechanism by which combination intervention drugs inhibit SGAS-induced weight gain is unknown. ...
Background:
Accumulating evidence have shown that diet and nutrition play significant roles in mental illness, such as depression, anxiety and bipolar disorder. However, comprehensive evaluation of the relationship between nutrition and schizophrenia is lacking.
Objective:
The present review aims to synthetic elaborate the associations between nutrition and schizophrenia. Relevant studies on dietary patterns, macronutrients, micronutrients were performed through a literature search to synthesize the extracted data.
Summary:
Dietary interventions may help prevent the occurrence of schizophrenia, or delay symptoms: Healthy diets like nutritious plant-based foods and high-quality protein, have been linked to reducing the risk or symptoms of schizophrenia. Moreover, diet high in saturated fat and sugar is linked to more serious outcomes of schizophrenia. Additionally, when N-acetylcysteine acts as an adjuvant therapy, the overall symptoms of schizophrenia are significantly reduced. Also nascent evidence showed mental disorders may be related to intestinal microbiota dysfunction. Our study offered important insights into the dietary habits of patients with schizophrenia and the potential impact of nutritional factors on the disease. We also emphasized the need for further research, particularly in the form of large randomized double-blind controlled trials, to better understand the effects of nutrients on schizophrenia symptoms in different populations and disease types.
... Betahistine acts as a modulator of the histaminergic system and has both H1 receptor agonistic and H3 receptor antagonistic properties in the brain [8,9]. Although the preclinical results remain to be completely replicated by clinical studies, recent evidence has demonstrated that olanzapine-induced weight gain and metabolic side effects were significantly alleviated by co-treatment with betahistine in both preclinical animal models and clinical trials [4,[10][11][12][13][14]. However, the underlying mechanisms have still not been well investigated. ...
... The drug dosages were translated from human dosages to rats based on the body surface area and followed the FDA guidelines [51,52]. In consideration of the shorter half-lives of these drugs in rats than in humans, 1 mg/kg olanzapine and 9.6 mg/kg betahistine in rats are equivalent to~10 mg olanzapine clinical dosage and~48 mg betahistine used in clinical trials, respectively [10,14,16]. ...
As a partial histamine H1 receptor agonist and H3 antagonist, betahistine has been reported to partially prevent olanzapine-induced dyslipidemia and obesity through a combination therapy, although the underlying epigenetic mechanisms are still not known. Recent studies have revealed that histone regulation of key genes for lipogenesis and adipogenesis in the liver is one of the crucial mechanisms for olanzapine-induced metabolic disorders. This study investigated the role of epigenetic histone regulation in betahistine co-treatment preventing dyslipidemia and fatty liver caused by chronic olanzapine treatment in a rat model. In addition to abnormal lipid metabolism, the upregulation of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), as well as the downregulation of carnitine palmitoyltransferase 1A (CPT1A) in the liver induced by olanzapine, were significantly attenuated by betahistine co-treatment. In addition, betahistine co-treatment significantly enhanced the global expression of H3K4me and the enrichment of H3K4me binding on the promoter of Cpt1a gene as revealed by ChIP-qPCR, but inhibited the expression of one of its site-specific demethylases, lysine (K)-specific demethylase 1A (KDM1A). Betahistine co-treatment also significantly enhanced the global expression of H3K9me and the enrichment of H3K9me binding on the promoter of the Pparg gene, but inhibited the expression of two of its site-specific demethylases, lysine demethylase 4B (KDM4B) and PHD finger protein 2 (PHF2). These results suggest that betahistine attenuates abnormal adipogenesis and lipogenesis triggered by olanzapine through modulating hepatic histone methylation, and thus inhibiting the PPARγ pathway-mediated lipid storage, while at the same time promoting CP1A-mediated fatty acid oxidation.
... Barak et al 28 showed that after 4 weeks of treatment, the average weight increase in the betahistine group 37% less than in placebo group. Although the foregoing studies indicate that betahistine can reduce patients' weight, other studies found that betahistine has no 29 to analyze the effects of betahistine on class I or II obesity in women. The results showed that after a 24-h placebo run-in period, 144 mg betahistine/d did not induce any effect on food intake or appetite. ...
Objective
This study aims to explore the ability of betahistine to inhibit weight gain and abnormal lipid metabolism in patients with chronic schizophrenia.
Methods
A comparison study of betahistine or placebo therapy was conducted for 4 weeks in 94 patients with chronic schizophrenia, who were randomly divided into two groups. Clinical information and lipid metabolic parameters were collected. Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms. Treatment Emergent Symptom Scale (TESS) was used to evaluate treatment-related adverse reactions. The differences in lipid metabolic parameters before and after treatment between the two groups were compared.
Results
Repeated measures analysis of variance (ANOVA) revealed that after 4 weeks of betahistine/placebo treatment, the interaction effect of time and group was statistically significant on low-density lipoprotein cholesterol (F = 6.453, p = 0.013) and waist-to-hip ratio (F = 4.473, p = 0.037), but did not reveal any significant interaction effect of time and group on weight, body mass index or other lipid metabolic parameters, as well as the time main effect and group main effect (all p > 0.05). Betahistine had no significant impact on PANSS, and no side effects related to betahistine were detected.
Conclusion
Betahistine may delay metabolic abnormalities in patients with chronic schizophrenia. It does not affect the efficacy of the original antipsychotics. Thus, it provides new ideas for the treatment of metabolic syndrome in patients with chronic schizophrenia.
... Insulin resistance and type 2 diabetes are frequent companions to weight gain and adiposity. Weight gain and adiposity are also frequent in patients treated with antipsychotic drugs [15]. In the latter case, betahistine, a histaminergic H1 receptor (Gq) agonist and H3 receptor (Gi) antagonist, has been used as a prevention [15]. ...
... Weight gain and adiposity are also frequent in patients treated with antipsychotic drugs [15]. In the latter case, betahistine, a histaminergic H1 receptor (Gq) agonist and H3 receptor (Gi) antagonist, has been used as a prevention [15]. The histaminergic system, including H1 and H3 receptors, has indeed been shown to be a potential target for the treatment of obesity and diabetes [16]. ...
Background:
Diabetes is associated with inner ear dysfunction. Furthermore, C57BL/6J mice fed high fat diet (HFD), a model for insulin resistance and diabetes, develop endolymphatic hydrops (EH).
Aim:
Evaluate if betahistine, spironolactone (aldosterone antagonist) and empagliflozin (sodium -glucose cotransporter2 inhibitor) can prevent EH induced by HFD and explore potential mechanisms.
Methods:
C57BL/6J mice fed HFD were treated with respective drug. The size of the endolymphatic fluid compartment was measured using contrast enhanced MRI. Secondarily, mice treated with cilostamide, a phosphodiesterase3 inhibitor, to induce EH and HEI-OC1 auditory cells were used to study potential cellular mechanisms of betahistine.
Results:
HFD-induced EH was prevented by betahistine but not by spironolactone and empagliflozin. Betahistine induced phosphorylation of protein kinaseA substrates but did not prevent cilostamide-induced EH.
Conclusions:
Betahistine prevents the development of EH in mice fed HFD, most likely not involving pathways downstream of phosphodiesterase3, an enzyme with implications for dysfunction in diabetes. The finding that spironolactone did not prevent HFD-induced EH suggests different mechanisms for EH induction/treatment since spironolactone prevents EH induced by vasopressin, as previously observed.
Significance:
This further demonstrates that independent mechanisms can cause hydropic inner ear diseases which suggests different therapeutic approaches and emphazises the need for personalized medicine.
... This suggests that the efficacy of betahistine hydrochloride tablets on VBI is better by more effectively improving the hemodynamics and cerebral blood perfusion of patients. It is well known that betahistine hydrochloride is a partial agonist of H2 receptor, which has obvious dilation effect on cerebral vessels, coronary arteries and peripheral vessels, especially on vertebral artery system, and can increase brain, heart and peripheral blood flow, but does not increase capillary permeability [20,21]. What's more, betahistine hydrochloride also has mild anticoagulant, antiplatelet aggregation and diuretic effects, and is an effective drug for VBIV treatment [22,23]. ...
Objective:
To explore the clinical efficacy and safety of betahistine hydrochloride tablets in patients with vertebrobasilar insufficiency vertigo (VBIV).
Methods:
A total of 133 patients with vertigo caused by vertebrobasilar insufficiency treated in The First People's Hospital of Shangqiu City from March 2019 to August 2021 were selected and analyzed retrospectively. Among them, 63 patients treated with flunarizine tablets were seen as the control group (CG), and 70 with flunarizine tablets combined with betastine hydrochloride tablets were considered as the observation group (OG). The treatment efficacy and adverse reactions were compared, and the vertigo symptom score, quality of life and vertebrobasilar artery hemodynamics were observed before and after treatment.
Results:
The effective rate in the OG was higher than that of the CG (P<0.05), but there was no obvious difference in adverse reactions (P>0.05). Compared with the CG, the arterial hemodynamics and cerebral blood perfusion as well as SF-36 score were higher, while the scores of dizziness assessment rating scale (DARS) and dizziness handicap inventory (DHI) scale were lower in the OG (all P<0.05).
Conclusion:
Betahistine hydrochloride can effectively improve arterial hemodynamics and cerebral blood flow perfusion in vertebrobasilar insufficiency patients and enhance the clinical efficacy with high safety profile, which is worthy of wide application.
... Metformin and psychostimulants have shown good promise as adjunct medication in pediatric. Topiramate, Amantadine, Betahistine, Melatonin, and Vitamin-D were also studied for AIWG in the pediatric population [7][8][9][10][11][12][13][14][15][16][17]. Metformin is FDA approved for type 2 diabetes due to its weight-lowering insulin-sensitizing efficacy [1,9]. ...
... [1,13,14]. Betahistine is a histaminergic H1 receptor agonist and H3 antagonist effect [1,15]. It acts on the hypothalamus and liver, reduces food intake, induces thermogenesis, reduces leptin neuropeptide, and reverses metabolic changes caused by antipsychotics [1,15]. ...
... Betahistine is a histaminergic H1 receptor agonist and H3 antagonist effect [1,15]. It acts on the hypothalamus and liver, reduces food intake, induces thermogenesis, reduces leptin neuropeptide, and reverses metabolic changes caused by antipsychotics [1,15]. Melatonin (5-methoxy-Nacetyltryptamine) is one of the endocrine hormones released by the pineal gland [16]. ...
To systematically review studies evaluating pharmacological treatment intervention of the atypical antipsychotic induced weight gain in the pediatric population and summarize the current evidence of the pharmacological treatment. According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, we searched the various databases Medline, PubMed, PubMed central (PMC), CINAHL, and clinicaltrial.gov. until Jan 30th, 2022 for relevant clinical studies. Medical subject heading (MeSH) terms or keywords were used, "Body Weight," "Weight Gain," "Weight Loss," "Body Weight Maintenance," "Pediatric Obesity" in "Pediatrics," "Adolescent," "Child" in context of "Antipsychotic Agents" and "Drug Therapy," "Therapeutics," "Treatment Outcome," "Early Medical Intervention." We used the PICO algorithm for our search (Population, Intervention, Comparison, Outcomes, and Study Design) framework. The initial search included 746 articles, nine studies were ultimately selected in the final qualitative review. We included relevant clinical reviews, case series, and randomized clinical trials that evaluated pharmacological intervention for antipsychotic-induced weight gain in the pediatric population. Non-peer-reviewed, non-human, non-English languages article was excluded. Metformin is the most studied medication for antipsychotic-induced weight gain in children. Three studies have shown that adding Metformin to the antipsychotics can significantly reduce the body weight and body mass index with mild transient side effects. Other adjunct medications like topiramate, amantadine, betahistine, or melatonin vary greatly in mitigating weight with various side effects. Lifestyle modification is the first step in dealing with AIWG, but the result is inconsistent. Avoiding the use of antipsychotic in children is preferred. Adding an adjuvant medication to the antipsychotic could prevent or mitigate their negative metabolic effect on the body weight and body mass index. Metformin has the most evidence, topiramate, betahistine, amantadine, and melatonin is possible alternatives in the pediatric patient without changing their antipsychotic medication. Other viable options show some benefits but need further clinical studies to establish efficacy and safety.
... As we know, olanzapine's antagonistic actions at 5-HT2c, histaminergic H1, and muscarinic M3 receptors are associated with increased weight. Despite the fact that a 2010 meta-analysis (Maayan and Correll 2010) found that adding metformin, fenfluramine, sibutramine, topiramate, or reboxetine in combination with olanzapine causes a reduction in weight gain versus placebo (Robert C Smith et al. 2018) but statistical data is not supportive in long term use of any of these medications to relieve metabolic adverse effect (Maayan and Correll 2010;Robert C Smith et al. 2018) Olanzapine has significant negative effects on muscle mass, which must be maintained on a constant basis, in addition to its effects on lipid and glucose metabolism, and bodyweight (Citrome et al. 2011). In a metaanalysis of 13 short-term, placebo-controlled olanzapine single drug studies (duration 6weeks), the minimum increase in weight with olanzapine was 2.6 kg (5.7lb), while weight reduction of 0.6lb is observed in patients exposed to placebo. ...
... As we know, olanzapine's antagonistic actions at 5-HT2c, histaminergic H1, and muscarinic M3 receptors are associated with increased weight. Despite the fact that a 2010 meta-analysis (Maayan and Correll 2010) found that adding metformin, fenfluramine, sibutramine, topiramate, or reboxetine in combination with olanzapine causes a reduction in weight gain versus placebo (Robert C Smith et al. 2018) but statistical data is not supportive in long term use of any of these medications to relieve metabolic adverse effect (Maayan and Correll 2010;Robert C Smith et al. 2018) Olanzapine has significant negative effects on muscle mass, which must be maintained on a constant basis, in addition to its effects on lipid and glucose metabolism, and bodyweight (Citrome et al. 2011). In a metaanalysis of 13 short-term, placebo-controlled olanzapine single drug studies (duration 6weeks), the minimum increase in weight with olanzapine was 2.6 kg (5.7lb), while weight reduction of 0.6lb is observed in patients exposed to placebo. ...
Schizophrenia is a chronic disease with a diverse psychopathology and multiple phases of illness. Consequently, numerous factors must be considered when assessing the benefits of a given treatment over short-and long-term periods. Olanzapine is a typical antipsychotic reported to be effective without producing many of the disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. Even though olanzapine is still associated with a known risk of metabolic adverse effects such as weight gain, many clinicians continue to prescribe olanzapine for the treatment of schizophrenia with the expectation of significant therapeutic efficacy relative to other first-line atypical antipsychotics. This review focuses on the epidemiology, pathogenesis, and treatment of schizophrenia with a special emphasis on the role of olanzapine in its treatment. Genetic variants associated with the therapeutic efficacy and adverse effects of olanzapine are reviewed and those with the potential to act as clinical predictor therapeutic response and/or adverse effects are discussed. Recommendations are made for the use of some of these genetic variants in clinical medicine.
... As we know, olanzapine's antagonistic actions at 5-HT2c, histaminergic H1, and muscarinic M3 receptors are associated with increased weight. Despite the fact that a 2010 meta-analysis (Maayan and Correll 2010) found that adding metformin, fenfluramine, sibutramine, topiramate, or reboxetine in combination with olanzapine causes a reduction in weight gain versus placebo (Robert C Smith et al. 2018), but statistical data is not supportive in long term use of any of these medications to relieve adverse metabolic effect (Maayan and Correll 2010;Robert C Smith et al. 2018) Olanzapine has significant adverse effects on muscle mass, which must be maintained constantly, in addition to its effects on lipid and glucose metabolism, and bodyweight (Citrome et al. 2011). In a meta-analysis of 13 short-term, placebo-controlled olanzapine single drug studies (duration six weeks), the minimum increase in weight with olanzapine was 2.6 kg (5.7lb), while weight reduction of 0.6lb was observed in patients exposed to placebo. ...
... As we know, olanzapine's antagonistic actions at 5-HT2c, histaminergic H1, and muscarinic M3 receptors are associated with increased weight. Despite the fact that a 2010 meta-analysis (Maayan and Correll 2010) found that adding metformin, fenfluramine, sibutramine, topiramate, or reboxetine in combination with olanzapine causes a reduction in weight gain versus placebo (Robert C Smith et al. 2018), but statistical data is not supportive in long term use of any of these medications to relieve adverse metabolic effect (Maayan and Correll 2010;Robert C Smith et al. 2018) Olanzapine has significant adverse effects on muscle mass, which must be maintained constantly, in addition to its effects on lipid and glucose metabolism, and bodyweight (Citrome et al. 2011). In a meta-analysis of 13 short-term, placebo-controlled olanzapine single drug studies (duration six weeks), the minimum increase in weight with olanzapine was 2.6 kg (5.7lb), while weight reduction of 0.6lb was observed in patients exposed to placebo. ...
Schizophrenia is a chronic disease with diverse psychopathology and multiple phases of illness. Consequently, numerous factors must be considered when assessing the benefits of a given treatment over short- and long-term periods. Olanzapine is an atypical antipsychotic reported to be effective without producing many of the disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. Despite the fact that olanzapine is still associated with a known risk of metabolic side effects, including weight gain, many clinicians continue to prescribe olanzapine for the treatment of schizophrenia with the expectation of additional therapeutic antipsychotic efficacy relative to other first-line atypical antipsychotics. This review focuses on the epidemiology, pathogenesis, and treatment of schizophrenia with special emphasis on the role of olanzapine in the treatment of schizophrenia. Genetic variants associated with the therapeutic efficacy and adverse effects of olanzapine are reviewed and those with the potential to act as a clinical predictor of therapeutic response and/or adverse effects are discussed. Recommendations are made for the use of some of these genetic variants in clinical medicine.
