Reducing antipsychotic-induced weight gain in schizophrenia: a double-blind placebo-controlled study of reboxetine–betahistine combination

Poyurovsky, Michael; Fuchs, Camil; Pashinian, Artashez; Levi, Adva; Weizman, Ronit; Weizman, Abraham

doi:10.1007/s00213-012-2935-2

Cited by 63 publications

(61 citation statements)

References 26 publications

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“…Overall, in conjunction with previous preclinical and clinical trials in drug-naïve and repeated SGA administration subjects [169,65,174,173], it is necessary to conduct further clinical trials to investigate the effects of co-treatment with betahistine on reducing olanzapine- …”

Section: Discussionmentioning

confidence: 99%

“…The corresponding increase in BMI was 0.65±0.75 in the olanzapine/reboxetine/betahistine group and 1.53±0.99 kg/m 2 in the olanzapine/placebo group (p=0.008) [174] (Table 1). Importantly, there was complementary action in the CNS pathway in combination treatment with betahistine, reboxetine and olanzapine, namely, the weight attenuating effect of this combination was two-fold larger than reboxetine only combination (2.75 kg vs. 1.46 kg) [175,174].…”

Section: Clinical Trials For Co-treatment Of Betahistine and Olanzapimentioning

confidence: 95%

“…In detail, an increase in weight during the initial 2 weeks was observed, followed by no additional weight gain (2 patients) or a minor reduction of body weight (one patient) from week 3 to 6. Overall, no subject gained 7% of baseline weight (a cut-off for clinically significant weight gain) [173] (Table 1) (a selective norepinephrine reuptake inhibitor) for 6 weeks in first episode schizophrenia patients resulted in significantly and clinically attenuated weight gain compared with olanzapine-only treatment (2.02±2.37 and 4.77±3.16kg, respectively, p=0.006) [174]. The corresponding increase in BMI was 0.65±0.75 in the olanzapine/reboxetine/betahistine group and 1.53±0.99 kg/m 2 in the olanzapine/placebo group (p=0.008) [174] (Table 1).…”

Section: Clinical Trials For Co-treatment Of Betahistine and Olanzapimentioning

confidence: 99%

“…Overall, no subject gained 7% of baseline weight (a cut-off for clinically significant weight gain) [173] (Table 1) (a selective norepinephrine reuptake inhibitor) for 6 weeks in first episode schizophrenia patients resulted in significantly and clinically attenuated weight gain compared with olanzapine-only treatment (2.02±2.37 and 4.77±3.16kg, respectively, p=0.006) [174]. The corresponding increase in BMI was 0.65±0.75 in the olanzapine/reboxetine/betahistine group and 1.53±0.99 kg/m 2 in the olanzapine/placebo group (p=0.008) [174] (Table 1). Importantly, there was complementary action in the CNS pathway in combination treatment with betahistine, reboxetine and olanzapine, namely, the weight attenuating effect of this combination was two-fold larger than reboxetine only combination (2.75 kg vs. 1.46 kg) [175,174].…”

Section: Clinical Trials For Co-treatment Of Betahistine and Olanzapimentioning

confidence: 99%

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Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

Lian

Huang

Pai

et al. 2016

Pharmacological Research

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Second generation antipsychotic drugs (SGAs) cause substantial body weight gain/obesity and other metabolic side-effects such as dyslipidaemia. Their antagonistic affinity to the histaminergic H1 receptor (H1R) has been identified as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H3 receptor antagonist) have been investigated for ameliorating SGA-induced weight gain/obesity in both animal models and clinical trials. It has been demonstrated that co-treatment with betahistine is effective in reducing weight gain, associated with olanzapine in drug-naïve patients with schizophrenia, as well as in the animal models of both drug-naïve rats and rats with chronic, repeated exposure to olanzapine. Betahistine co-treatment can reduce food intake and increase the effect of thermogenesis in brown adipose tissue by modulating hypothalamic H1R-NPY-AMPKα (NPY: neuropeptide Y; AMPKα: AMP-activated protein kinase α) pathways, and ameliorate olanzapineinduced dyslipidaemia through modulation of AMPKα-SREBP-1-PPARα-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPARα: Peroxisome proliferator-activated receptor-α) in the liver. Although reduced locomotor activity was observed from antipsychotic treatment in rats, betahistine did not affect locomotor activity. Importantly, betahistine co-treatment did not influence the effects of antipsychotics on serotonergic receptors in the key brain regions for antipsychotic therapeutic efficacy. However, betahistine co-treatment reverses the upregulated dopamine D2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D2 supersensitivity often observed in chronic antipsychotic treatment. Therefore, these results provide solid evidence supporting further clinical trials in treating antipsychotics-induced weight gain using betahistine in patients with schizophrenia and other mental disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Clinical Trials For Co-treatment Of Betahistine and Olanzapimentioning

confidence: 95%

Section: Clinical Trials For Co-treatment Of Betahistine and Olanzapimentioning

confidence: 99%

Section: Clinical Trials For Co-treatment Of Betahistine and Olanzapimentioning

confidence: 99%

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Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

Lian

Huang

Pai

et al. 2016

Pharmacological Research

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“…In addition to metformin, mifepristone, amantadine, zonisamide and betahistine reduce anti-psychotic drug-induced weight gain [43,44,45]. Any novel drug that targets this market would preferably have advantages over these drugs, as they are approved for other indications.…”

Section: Metformin and Anti-psychotic Drug-induced Weight Gainmentioning

confidence: 99%

Horizons in the Pharmacotherapy of Obesity

Arch

2015

Curr Obes Rep

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Abstract:Obesity drugs have had a chequered history. In the recent past, only the low efficacy, pancreatic lipase inhibitor orlistat was available worldwide and it was little used. The 5HT2C agonist lorcaserin, and two combinations of old drugs have been approved in the United States but not in Europe. The diabetes drug liraglutide has been approved in both the US and Europe and seems likely to be most widely accepted. In view of regulators' caution in approving obesity drugs, some (like beloranib) may initially be progressed for niche obesity markets. New drug targets have been identified in brown adipose tissue with the aim of not only activating thermogenesis but also increasing the capacity for thermogenesis in this tissue. Attempts are being made to match the efficacy of bariatric surgery by mimicking multiple gut hormones. Unapproved pharmacotherapies are tempting for some patients. Others remain optimistic about more conventional routes to pharmacotherapy.3

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