Weight Gain and Changes in Metabolic Variables following Olanzapine Treatment in Schizophrenia and Bipolar Disorder

Abstract BackgroundPrescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant sedation, weight gain, and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated.MethodsTo investigate the efficacy of interventions of statin aimed at reversing SGA-induced dyslipidemia, young Sprague Dawley (SD) rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d.), simvastatin (3.0 mg/kg, t.i.d.), olanzapine plus simvastatin (O+S), or vehicle (control) for 5 weeks.ResultsOlanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O+S co-treatment significantly reversed body weight gain but had no significant effect on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O+S co-treatment significantly ameliorated these changes. A down-regulating of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) expression was observed in brown adipose tissue (BAT) in the olanzapine-only group, following a significant decrease in the ratio of phosphorylated PKA (p-PKA)/PKA. Interestingly, these protein changes could be reversed by co-treatment with O+B. Our results demonstrated simvastatin to be effective in ameliorating TC and TG elevated by olanzapine.ConclusionsModulation of BAT activity could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.

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Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin

10.21203/rs.2.20297/v4 ◽

2020 ◽

Author(s):

Xuemei Liu ◽

Xiyu Feng ◽

Chao Deng ◽

Lu Liu ◽

Yanping Zeng ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

Food Intake ◽

Brown Adipose Tissue ◽

Body Weight Gain ◽

Uncoupling Protein ◽

Peroxisome Proliferator ◽

Sprague Dawley ◽

Olanzapine Treatment ◽

Brown Adipose

Abstract Background Prescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant weight gain and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated.Methods To investigate the efficacy of statin interventions for reversing SGA-induced dyslipidemia, young Sprague Dawley rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d.), simvastatin (3.0 mg/kg, t.i.d.), olanzapine plus simvastatin (O+S), or vehicle (control) for 5 weeks. Results Olanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O+S co-treatment significantly reversed body weight gain but without significant effects on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O+S co-treatment significantly ameliorated these changes. Pronounced activation of lipogenic gene expression in the liver and down-regulated expression of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) in brown adipose tissue (BAT) was observed in the olanzapine-only group. Interestingly, these protein changes could be reversed by co-treatment with O+B. Conclusions Simvastatin is effective in ameliorating TC and TG elevated by olanzapine. Modulation of BAT activity by statins could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.

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Bipolar Disorder, Obesity, and Pharmacotherapy-Associated Weight Gain

The Journal of Clinical Psychiatry ◽

10.4088/jcp.v64n1205 ◽

2003 ◽

Vol 64 (12) ◽

pp. 1426-1435 ◽

Cited By ~ 141

Author(s):

Paul E. Keck ◽

Susan L. McElroy

Keyword(s):

Bipolar Disorder ◽

Weight Gain

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Reassessing Carbamazepine in the Treatment of Bipolar Disorder Clinical Implications of New Data

CNS Spectrums ◽

10.1017/s1092852900023063 ◽

2005 ◽

Vol 10 (6) ◽

pp. 1-2 ◽

Cited By ~ 1

Author(s):

Terence A. Ketter ◽

David L. Ginsberg ◽

Hagop S. Akiskal ◽

Paul E. Keck ◽

Richard H. Weisler ◽

...

Keyword(s):

Bipolar Disorder ◽

Weight Gain ◽

Drug Interactions ◽

Bipolar Depression ◽

Panel Discussion ◽

Current Data ◽

Clinical Implications ◽

Good Tolerability ◽

Long Term Treatment

AbstractThis monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions.Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on weight.) Thus, carbamazepine may be a good option for patients who are concerned about weight gain or who are intolerant of or respond poorly to other medications. Further efforts are needed to update physicians on the use of carbamazepine relative to other medications in the treatment of bipolar disorder.

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Zonisamide

10.1093/med/9780198791577.003.0016 ◽

2018 ◽

Author(s):

Andrea E. Cavanna

Keyword(s):

Bipolar Disorder ◽

Weight Gain ◽

Adverse Effects ◽

Alcohol Dependence ◽

Antiepileptic Drug ◽

Preliminary Evidence ◽

Tolerability Profile ◽

Patients With Epilepsy ◽

Psychiatric Adverse Effects ◽

Acceptable Tolerability Profile

Zonisamide is a second-generation antiepileptic drug characterized by a few antiepileptic indications, with an acceptable interaction profile in polytherapy. Zonisamide has an acceptable tolerability profile in patients with epilepsy, with depression, irritability, agitation and psychosis as the most commonly reported psychiatric adverse effects. Zonisamide has no approved indications or clinical uses in psychiatry, as initial findings from uncontrolled studies suggesting effectiveness in the treatment of patients with bipolar disorder did not find confirmation. There is preliminary evidence for possible usefulness of zonisamide in the treatment of patients with obesity and psychotropic-associated weight gain, as well as alcohol dependence and withdrawal.

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Reassessing Carbamazepine in the Treatment of Bipolar Disorder Clinical Implications of New Data

CNS Spectrums ◽

10.1017/s1092852900024494 ◽

2005 ◽

Vol 10 (S1) ◽

pp. 1-2 ◽

Cited By ~ 1

Keyword(s):

Bipolar Disorder ◽

Weight Gain ◽

Drug Interactions ◽

Bipolar Depression ◽

Panel Discussion ◽

Current Data ◽

Clinical Implications ◽

Good Tolerability ◽

Long Term Treatment

ABSTRACTThis monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions.Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on weight. *) Thus, carbamazepine may be a good option for patients who are concerned about weight gain or who are intolerant of or respond poorly to other medications. Further efforts are needed to update physicians on the use of carbamazepine relative to other medications in the treatment of bipolar disorder.

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Pharmacotherapy Update: Quetiapine use in Bipolar Disorder—What does the evidence tell us?

Clinical Medicine Therapeutics ◽

10.4137/cmt.s1136 ◽

2009 ◽

Vol 1 ◽

pp. CMT.S1136

Author(s):

Mark Taylor ◽

Kirsty Mackay ◽

Polash Shajahan

Keyword(s):

Bipolar Disorder ◽

Weight Gain ◽

Large Scale ◽

Maintenance Treatment ◽

Bipolar Depression ◽

Mood Stabiliser ◽

Serious Illness ◽

Randomized Controlled ◽

Second Generation Antipsychotic

Bipolar disorder is a common and serious illness usually requiring long term medication. We critically review the available evidence surrounding the increasing use of quetiapine, a second generation antipsychotic, in both the acute and maintenance phases of bipolar disorder. Large scale, randomized controlled data supports the use of quetiapine in both acute mania and acute bipolar depression, as a safe and effective treatment and probably best used in combination with a traditional ‘mood stabiliser’ such as lithium or divalproex. Also, quetiapine monotherapy has been shown to be effective in bipolar depression. Two recently published studies also confirm that quetiapine in combination with either lithium or divalproex ‘adds value’ to the maintenance treatment of bipolar disorder in terms of delaying relapse compared to either lithium or divalproex alone. Quetiapine is generally well tolerated, although further work on long term weight gain and emergent diabetes would be helpful.

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