Cardiometabolic changes and weight gain

How are cardiometabolic or weight problems related to schizophrenia?

Patient populations that are prescribed antipsychotic agents may experience cardio and metabolic side effects.

What are the cardiometabolic side effects?

Medicated patients versus population or healthy controls

Moderate quality evidence suggests small to medium-sized increased risks of hypertension, low HDL cholesterol, hypertriglyceridemia, diabetes, metabolic syndrome, abdominal obesity and reduced heart rate variability in people with schizophrenia. People with first-episode psychosis and antipsychotic-naïve patients also show increased hypertension and reduced heart rate variability, but not other cardiometabolic indices. There is increased incidence of myocardial infarction in people with any lifetime use of antipsychotics, particularly first generation antipsychotics.

Medicated patients versus unmedicated patients

Moderate to low quality evidence shows that after treatment with antipsychotic medications, there is weight gain in the short and long-term, and increased insulin levels, insulin resistance, cholesterol, triglyceride, leptin, ghrelin, and blood pressure levels in the long-term. There are increased rates of diabetes, metabolic syndrome, high triglycerides, low HDL, and hyperglycaemia in medicated patients, and reduced heart rate variability in medicated patients on clozapine.

Any antipsychotic versus placebo

High quality evidence shows small effects of increased QTc prolongation with haloperidol, quetiapine, olanzapine, risperidone, and iloperidone; medium-sized effects of increased QTc prolongation with ziprasidone and amisulpride; and a large effect with sertindole. No differences in QTc prolongation were reported between placebo and lurasidone, aripiprazole, paliperidone, or asenapine. There are small effects of more weight gain with aripiprazole, amisulpride, asenapine, paliperidone and lurasidone; and medium-sized effects of more weight gain with risperidone, quetiapine, sertindole, chlopromazine, iloperidone, clozapine, zotepine, and olanzapine.

First generation versus second generation antipsychotics

Moderate or moderate to low quality evidence suggests second generation clozapine, olanzapine, risperidone, and quetiapine are associated with a small increased risk of diabetes mellitus when compared to any first generation antipsychotic. There is more total cholesterol increase with second generation olanzapine than first generation haloperidol, and more triglyceride increase with second generation amisulpride than haloperidol. Second generation amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, and zotepine are associated with more weight gain than first generation haloperidol, with no differences when compared to low-potency first generation antipsychotics.

Second generation versus second generation antipsychotics

Moderate or moderate to low quality evidence suggests shorter Bazett’s corrected QT interval with aripiprazole compared to risperidone, and with risperidone compared to sertindole. Olanzapine was associated with more weight gain and glucose increase than amisulpride, aripiprazole, quetiapine, risperidone, and ziprasidone. Clozapine was associated with more weight gain than risperidone, risperidone was associated with more weight gain than amisulpride, and sertindole was associated with more weight gain than risperidone. Olanzapine was associated with more cholesterol increase than aripiprazole, risperidone and ziprasidone. Quetiapine was associated with more cholesterol increase than risperidone and ziprasidone.

Schizophrenia versus affective disorders

Moderate to low quality evidence suggests olanzapine was associated with more weight gain in people with schizophrenia than people with bipolar disorder, with no differences in cholesterol or blood glucose levels. People with schizophrenia treated with quetiapine show more cholesterol increase than patients with affective disorder treated with quetiapine, with no differences in blood glucose, triglyceride levels or weight gain.

Also see the treatments for weight gain topics (pharmaceutical and psychosocial).

July 2017

Diet

How is diet related to schizophrenia?
People with mental disorders may be at increased risk of nutritional deficiencies due to poor diet. Poor diet is a major and modifiable cause of comorbid conditions, including metabolic syndrome and obesity. During pregnancy, it also contributes to the risk of developmental problems in the foetus.

What is the evidence regarding diet ?
Moderate to low quality evidence finds poor dietary patterns in people with schizophrenia, including decreased fibre and fruit intake, and increased saturated fat intake compared to people without a mental disorder. People with schizophrenia may have high LDL and low HDL blood levels, and increased fasting glucose.

Moderate to high quality evidence shows lower vitamin D levels compared to people without a mental disorder (large effect), and compared to people with other psychoses (small effect), with similar vitamin D levels compared to people with major depression.

Moderate quality evidence finds decreased folate levels, particularly in Caucasian and Asian people with schizophrenia, and in people with schizophrenia aged under 50 years. High quality evidence finds no differences in vitamin B12 levels in people with schizophrenia.

Moderate quality evidence shows people with first-episode psychosis also have a large effect of lower vitamin D levels, and a medium-sized effect of lower folate levels than people without a mental disorder. Moderate to low quality evidence also finds lower levels of vitamin C in people with first-episode psychosis, with no differences in B12, vitamin A, vitamin E, or any dietary mineral.

Also see the treatments for weight gain topics (pharmaceutical and psychosocial), and the pharmaceutical side effects topic.

February 2019

Treatments for weight gain

What are psychosocial treatments for weight gain?

Weight gain is a well documented side effect of many antipsychotic medications. Weight management is important to ensure that the benefits of antipsychotic medications are not outweighed by the increased risk of physical disease. Excessive weight gain is a serious health concern, it is associated not only with reduced quality of life and social stigma, but can affect treatment adherence and increase morbidity (both physical and psychological) and mortality. Behavioural therapies are targeted at changing patterns of behaviour and actions that lead to an unfavourable consequence, while reinforcing favourable behaviours. Pharmacological strategies for weight management are, at best, only moderately effective. As such, the ideal behavioural strategies should combine diet, exercise and psychological/behavioural components.

What is the evidence for psychosocial treatments for weight gain?

Moderate to high quality evidence suggests significant benefit of behavioural therapies, including cognitive behavioural therapy, psycho-education, and nutritional counselling for weight reduction and the prevention of weight gain. The largest benefits were found for weight gain prevention strategies rather than weight reduction, individual therapies, and psycho-education, particularly those that incorporate both a diet and exercise regime.

Also see Pharmaceutical treatments for weight gain, the relevant Pharmaceutical side effects topic, and Course and Outcomes diet topic.

August 2018

Treatments for weight gain

How is weight gain relevant for people with schizophrenia? 

Many antipsychotic medications are associated with weight gain, and various adjunctive pharmacological approaches have been investigated for this problem. Effective adjunctive pharmaceutical treatments for side effects such as weight gain increase adherence to antipsychotic medications and reduces the risk of psychotic relapse.

 

What is the evidence for adjunctive pharmaceutical therapies for weight reduction?

Moderate quality evidence suggests a benefit of adjunctive topiramate, metformin, or aripiprazole for reducing weight in people with schizophrenia. Triglycerides, glucose, insulin and cholesterol levels may also be improved with metformin.

Moderate to low quality evidence suggests a benefit of adjunctive sibutramine or reboxetine, but no benefit of adjunctive amantadine, fluoxetine, rosiglitazone famotidine, nizatidine, norepinephrine, orlistat, or metformin + sibutramine.

Moderate quality evidence suggests switching antipsychotic medications from olanzapine to aripiprazole or quetiapine may reduce weight and blood glucose levels. There may also be improved global mental state when switching from olanzapine to aripiprazole.

Also see the relevant Pharmaceutical side effects topic, the Psychosocial treatments for weight gain topic,and the Course and Outcome diet topic.

June 2016

Metabolic abnormalities

How are metabolic abnormalities related to schizophrenia?

People with schizophrenia are often reported to have increased rates of co-occurring disorders, including metabolic or nutritional disorders. The metabolic syndrome is defined as a pre-diabetic state of insulin resistance. Extended insulin resistance increases the risk of type 2 diabetes mellitus and cardiovascular diseases. It is unclear if any increased risk is a consequence of the metabolic impact of antipsychotic administration or unhealthy lifestyle choices, or both.

What is the evidence for comorbid metabolic abnormalities?

Moderate quality evidence suggests the prevalence of metabolic syndrome is higher in people with schizophrenia compared to the general population, with rates around 32%. There are increased rates of diabetes, high triglycerides, low high-density lipoprotein cholesterol, and hyperglycaemia (>100 mg/dl) in medicated patients compared to people in their first-episode of psychosis, and compared to unmedicated patients with an established disorder. There is also increased prevalence of high blood pressure in first-episode patients compared to unmedicated patients with an established disorder, and increased waist size in unmedicated patients with an established disorder compared to first-episode patients.

Moderate to low quality evidence suggests people with first-episode psychosis who have little or no exposure to antipsychotic medication show no differences in cardio-metabolic indices compared to people without schizophrenia. After treatment with antipsychotic medications, patients show weight gain, increased insulin levels, insulin resistance, increased total and low-density lipoprotein cholesterol, triglyceride, leptin, ghrelin and blood pressure levels. There were no consistent differences reported between particular antipsychotic agents.

There is often inadequate monitoring of weight, blood pressure, triglycerides, glucose, lipids, cholesterol and diabetes in people with schizophrenia. Following the implementation of screening guidelines, weight and blood pressure monitoring increased to adequate levels, glucose monitoring increased to suboptimal levels, but lipid monitoring remained inadequate.

 

March 2016

Cardiovascular disease and obesity

How is cardiovascular disease related to schizophrenia?

People with schizophrenia may show increased rates of co-occurring conditions. These include cardiovascular disorders such as coronary heart disease, hypertension, obesity and altered lipid levels, which may be associated with antipsychotic use.

What is the evidence for cardiovasulcar disease and related disorders?

Moderate to low quality evidence suggests people with schizophrenia show an increased risk of cardiovascular disease and congestive heart failure compared to the general population. They also show increased rates of cardiovascular risk factors, including smoking and poor physical health. There is evidence for increased rates of abdominal obesity, hypertension, and hypertriglyceridemia. and low HDL cholesterol and heart rate variability. The use of first generation antipsychotics is particularly associated with increased incidence of myocardial infarction. Moderate to high quality evidence suggests exercise, diet and education have benefits for weight loss, preventing weight gain, and improving triglycerides, fasting glucose, insulin and cholesterol levels.

Also see the treatment side effects topic on cardiometabolic changes, and the exercise treatment topic.

June 2017

Diabetes

How is diabetes related to schizophrenia?

People with schizophrenia may show increased rates of unrelated co-occurring illnesses, one example is diabetes. Diabetes is a state of impaired insulin function, either as a result of reduced insulin production (type I diabetes) or reduced insulin responsiveness (type II diabetes). Insulin regulates blood glucose levels, and reduced insulin function effectively increases blood glucose levels (hyperglycaemia). This is a dangerous state in the long term, and can ultimately damage the retina, kidneys, nerves and blood vessels. Consequently, effective management of diabetes is crucial. It is unclear if any increased risk in people with schizophrenia is purely a consequence of biological risk, the metabolic impact of antipsychotic administration, or unhealthy lifestyle choices, but it is likely a combination of many factors.

What is the evidence for comorbid diabetes?

Moderate to high quality evidence suggests people with schizophrenia have an increased risk of diabetes compared to people without a severe mental illness, with no differences in risk when compared to people with bipolar disorder or major depressive disorder. Moderate to low quality evidence suggests people with first-episode psychosis who have little or no exposure to antipsychotic medication show no differences in diabetes or insulin levels when compared to people without schizophrenia. Moderate to high quality evidence suggests second generation antipsychotics clozapine, olanzapine, risperidone or quetiapine may be associated with a small increased risk of diabetes mellitus compared to first generation antipsychotics.

 

May 2016