Reply: H1-histamine Receptor Affinity Predicts Short-term Weight Gain for Typical and Atypical Antipsychotic Drugs

Kroeze, Wesley K.; Hufeisen, Sandra J.; Popadak, Beth A; Renock, Sean; Steinberg, S; Ernsberger, Paul; Jayathilake, Karu; Meltzer, Herbert Y.; Roth, Bryan L.

doi:10.1038/sj.npp.1300292

Cited by 5 publications

(5 citation statements)

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“…As APs have complex pharmacological actions and interact with most biogenic amine receptors in the brain, a large number of candidate receptors have been targeted. Kroeze et al (91) showed that the most robust predictor of a drug’s propensity to induce weight gain was its affinity for the H 1 -histamine receptor (H1R). Through this mechanism, clozapine and olanzapine have been shown to cause hyperphagia and weight gain in rats by selective stimulation of the intra-neuronal enzyme adenosine monophosphate (AMP)-activated protein kinase (AMPK) in the hypothalamus, thereby blocking the action of the anorexigenic hormone leptin (92).…”

Section: Possible Causes Of Increased Risk For Cvd-related Deaths In mentioning

confidence: 99%

Increased Mortality in Schizophrenia Due to Cardiovascular Disease â€“ A Non-Systematic Review of Epidemiology, Possible Causes, and Interventions

et al. 2014

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Background: Schizophrenia is among the major causes of disability worldwide and the mortality from cardiovascular disease (CVD) is significantly elevated. There is a growing concern that this health challenge is not fully understood and efficiently addressed.Methods: Non-systematic review using searches in PubMed on relevant topics as well as selection of references based on the authors’ experience from clinical work and research in the field.Results: In most countries, the standardized mortality rate in schizophrenia is about 2.5, leading to a reduction in life expectancy between 15 and 20 years. A major contributor of the increased mortality is due to CVD, with CVD mortality ranging from 40 to 50% in most studies. Important causal factors are related to lifestyle, including poor diet, lack of physical activity, smoking, and substance abuse. Recent findings suggest that there are overlapping pathophysiology and genetics between schizophrenia and CVD-risk factors, further increasing the liability to CVD in schizophrenia. Many pharmacological agents used for treating psychotic disorders have side effects augmenting CVD risk. Although several CVD-risk factors can be effectively prevented and treated, the provision of somatic health services to people with schizophrenia seems inadequate. Further, there is a sparseness of studies investigating the effects of lifestyle interventions in schizophrenia, and there is little knowledge about effective programs targeting physical health in this population.Discussion: The risk for CVD and CVD-related deaths in people with schizophrenia is increased, but the underlying mechanisms are not fully known. Coordinated interventions in different health care settings could probably reduce the risk. There is an urgent need to develop and implement effective programs to increase life expectancy in schizophrenia, and we argue that mental health workers should be more involved in this important task.

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Section: Possible Causes Of Increased Risk For Cvd-related Deaths In mentioning

confidence: 99%

Increased Mortality in Schizophrenia Due to Cardiovascular Disease â€“ A Non-Systematic Review of Epidemiology, Possible Causes, and Interventions

et al. 2014

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“…31 The minimal effect of lurasidone on weight appears to be largely attributable to its absence of activity at 5HT 2C and histamine H 1 receptors. 32,33 In a previously reported double-blind (DB), placebo-controlled, fixed-dose, 6-week trial in adolescents with schizophrenia, patients randomized to lurasidone 40 mg/d or 80 mg/d demonstrated significantly greater improvement in schizophrenia symptoms than placebo-treated patients; and lurasidone treatment was found to be generally safe and well tolerated. 34 We report here the results of the 2-year, open-label (OL) follow-up of that study designed to evaluate the long-term safety and effectiveness of lurasidone in this adolescent population.…”

Section: Introductionmentioning

confidence: 99%

Safety and effectiveness of lurasidone in adolescents with schizophrenia: results of a 2-year, open-label extension study

et al. 2020

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Background Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia. Methods Patients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score. Results About 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of −15.6 at week 52 and −18.4 at week 104. Conclusion In adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.

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“…The putative mechanisms of antipsychotic-induced weight gain are related to the medications' combination of dopamine blockade at D2 receptors, antagonism or inverse agonism at 5HT2C serotonin receptors, antagonism at 5HT2A serotonin receptors, antagonism at alpha-1A adrenergic receptors, and especially antagonism at histamine-1 receptors (14). Blocking the activity of dopamine-particularly in the subcortical, limbic, and striatal areas of the brain-leads to an upregulation of postsynaptic receptors as well as increased dopamine within the synaptic cleft, which may create a "reward deficiency" syndrome that prevents satiety (15).…”

Section: Introductionmentioning

confidence: 99%

“…Serotonin receptor inverse agonism or antagonism may lead to decreased satiety and hyperphagia (16,17). Finally, weight gain has long been associated with centrally active drugs that have high affinity for the histamine-1 receptor, and H1 antagonism is known to increase feeding (18,19) and sedation, with predictable reductions in caloric expenditure (14). Although treatment-related weight gain is pharmacologically driven, it could potentially be addressed by behavioral strategies that affect decreased satiety, increased food seeking, and sedentary behavior.…”

Section: Introductionmentioning

confidence: 99%

Behavioral Weight Loss Treatment for Youth Treated With Antipsychotic Medications

Nicol¹,

Kolko

Mills³

et al. 2016

Scandinavian Journal of Child and Adolescent Psychiatry and Psychology

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Newcomer, John W.; and Wilfley, Denise, ,"Behavioral weight loss treatment for youth treated with antipsychotic medications." Scandinavian Journal of Child and Adolescent Psychiatry and Psychology.4,2. 96-104. (2016 Objective: We describe a rationale for behavioral weight loss intervention for high-weight youth being treated with antipsychotic medications. We report behavioral, anthropomorphic, and metabolic findings from a case series of obese adolescents taking antipsychotic medications who participated in a short-term, family-based behavioral weight loss intervention. Methods:We adapted the Traffic Light Plan, a 16-week family-based weight loss intervention that promotes healthy energy balance using the colors of the traffic light to categorize the nutritional value of foods and the intensity of physical activity. We then added a social and ecological framework to address health behavior change in multiple social contexts. The intervention was administered to three obese adolescents with long-term antipsychotic medication exposure. The efficacy of the intervention was evaluated with a battery of anthropomorphic and metabolic assessments, including weight, body mass index percentile, whole body adiposity, liver fat content, and fasting plasma glucose and lipid levels. Participants and their parents also filled out a treatment satisfaction questionnaire after study completion. Results: Two boys and one girl, all of whom were 14 years old, participated in this study. All three participants attended all 16 sessions of the intervention and experienced beneficial changes in adiposity, fasting lipid levels, and liver fat content associated with weight stabilization or weight loss. Adolescents and their parents all reported a high level of satisfaction with the treatment. Conclusions: Family-based behavioral weight loss treatment can be feasibly delivered and is acceptable to youth taking antipsychotic medications and their families. Randomized controlled trials are needed to fully evaluate the effectiveness and acceptability of these treatments for these individuals.

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Reply: H1-histamine Receptor Affinity Predicts Short-term Weight Gain for Typical and Atypical Antipsychotic Drugs

Cited by 5 publications

References 6 publications

Increased Mortality in Schizophrenia Due to Cardiovascular Disease â€“ A Non-Systematic Review of Epidemiology, Possible Causes, and Interventions

Increased Mortality in Schizophrenia Due to Cardiovascular Disease â€“ A Non-Systematic Review of Epidemiology, Possible Causes, and Interventions

Safety and effectiveness of lurasidone in adolescents with schizophrenia: results of a 2-year, open-label extension study

Behavioral Weight Loss Treatment for Youth Treated With Antipsychotic Medications

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