BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment

Introduction

In April 2016 the British Association for Psychopharmacology (BAP) published its latest clinical guidelines entitled ‘BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment’ – subsequent ly referred to in this short article as the ‘Guidelines’.  These Guidelines were drawn up to help staff in mental health services to recognise, monitor and manage risk factors for diabetes and cardiovascular disease in people with schizophrenia and other psychotic illnesses, particularly when they are receiving treatment with antipsychotic medications.  This is important because evidence, accumulated during the last 20 years, has demonstrated that this group of people experience premature mortality and that death from cardiovascular disease is the most important reason for this.  These Guidelines, like all BAP guidelines, were written following a meeting of experts involved in various aspects of these problems who came to a consensus view regarding a set of appropriate recommendations.  There was no input into this process from the manufacturers of any drugs or treatments.  The Guidelines are available to read and download at the BAP website. We have written this short article for the public information pages of the BAP website to summarise the key messages of these Guidelines.

The evidence that supports the Guidelines’ recommendations comes mainly from published studies of adults with schizophrenia and other similar severe psychotic illnesses (subsequently referred to here as people with psychotic illness).  An important reason for this was that it is this group of people who are most likely to receive long-term treatment with antipsychotic medications.  Some studies also included other important groups who often receive antipsychotic medicines, for example people with bipolar disorder and young people in the early stages of a psychotic illness.  The evidence suggests that the same risk factors for cardiovascular disease are likely to involved in these groups, that the same monitoring processes should be carried out and that the same interventions for management of these risk factors are likely to be appropriate.  However, it is important to be aware that some variations may be required, for example because of younger age or differences in other medications that a person may be taking for other types of psychotic illness.

Cardiovascular disease in people with psychotic illnesses

Cardiovascular disease refers to disease of the heart or blood vessels and includes heart attack (also termed myocardial infarction or MI) and stroke.  Studies in Britain, and many other countries, have shown that people with schizophrenia, and other psychotic illnesses, are more likely to die from cardiovascular disease than are people in the general population who don’t have a mental health problem.  An increased risk of cardiovascular disease is also seen in people with bipolar disorder.  The difference is large; the average life expectancy of people with schizophrenia is reduced by 15-20 years, with cardiovascular disease being the biggest contributor.  Another way of looking at this is that people with schizophrenia are twice as likely to die from heart disease as are people who don’t have a mental health problem.  Suicide is more common in people with mental health problems than in the rest of the population, and is an important cause of death in younger people with schizophrenia.  Suicide is a tragedy for all involved and the health service, rightly so, regards its prevention as a key priority.  However, the total number of deaths from suicide make up only a small proportion of the excess of premature deaths in people with psychotic illness.

Why is the risk so high?

publicinfo_metabolicguidelines2The high risk of heart disease and stroke in people with psychotic illnesses is due to a number of risk factors for these problems that more commonly affect people with psychotic illnesses compared to people in the rest of the population.  Important ones are: cigarette smoking; being overweight or obese; having a poor diet (i.e. one that is high in saturated fat and refined sugar but low in fibre and containing less fruit and vegetables); taking less regular physical exercise; and drinking too much alcohol.  For example, the rate of cigarette smoking in people with schizophrenia is at least two to three times that in the general population. Furthermore, people with schizophrenia who smoke tend to be heavier smokers than smokers who don’t have a mental health problem. Around 10% of people with schizophrenia misuse alcohol.   Smoking and heavy drinking are both risk factors for high blood pressure, heart disease and stroke as well as various cancers. Not everyone with schizophrenia or another psychotic illness has these cardiovascular risk factors but on average they are more likely to be present than in people without these illnesses.  The reasons for these differences are complex, but include the fact that people with mental illness will, on average, have smaller incomes and so may find it harder to afford healthier foods and to follow a healthier lifestyle.  In addition, many people with mental health problems are socially isolated, which can contribute to inactivity, and some may use alcohol to self-medicate and treat symptoms of their psychosis.

publicinfo_metabolicguidelines1Becoming overweight or obese is a common problem in the general population but even more so in people with schizophrenia.  Many factors can contribute including antipsychotic medication. A significant degree of weight gain can occur in some people within the first 6-12 weeks of starting an antipsychotic.  As well as being an important risk factor for cardiovascular disease, becoming overweight or obese is also an important factor in the development of other physical health problems especially diabetes.  Diabetes is a disorder in which the blood sugar level becomes too high.  Diabetes is twice as common in people with schizophrenia who have been on treatment for some time compared to people in the general population.  Diabetes can cause a variety of other serious health problems but also, importantly, increases a person’s risk of having some form of cardiovascular disease.  Antipsychotic medications, prescribed to treat psychotic illnesses, can cause weight gain and, mainly because of the weight gain, play a part in the development of high blood sugar, diabetes and changes in fat levels in the blood (often referred to by doctors as abnormal lipid levels).

People differ in how susceptible they are to weight gain.  So, for example, for a number of people taking the same antipsychotic medication, some may not gain any weight, some may gain a moderate amount of weight and some may gain a great deal of weight.  Some antipsychotic medications are more likely to increase weight, blood sugar and blood fats than others and discussions about the relative risk of these side effects should form part of the discussion between the doctor and the patient when deciding which medication to use. Significant weight gain in the first year of treatment, for people who have never received an antipsychotic before, is typically found in between 4 and 8 of every 10 people depending on which antipsychotic they receive. People who have received antipsychotics before tend to be at lower risk of weight gain when they start a new antipsychotic but this is because they are on average heavier to start with due to the effects of previous medication.  Weight gain can also occur with some antidepressants, anti-anxiety drugs and mood stabilising drugs as well as some medicines used to treat physical health problems.

Monitoring for risk factors for cardiovascular disease and diabetes

Monitoring and interventions for cardiovascular risk factors in people with psychosis has repeatedly been shown to be inadequate.  Even when problems are identified, people with mental illness may receive a lower standard of medical care for physical health problems.  Sometimes this may reflect the person being less likely to attend a follow-up appointment or being less likely to follow the advice or treatment that they were given – common psychiatric symptoms such as depression, forgetfulness, poor concentration and a sense of hopelessness may act as barriers to following advice on physical health including taking medication as prescribed.  Discrimination against the mentally ill in physical health services may be another barrier.  Whatever the reason, a better and more organised response is required from health services.

Only about one third of patients with psychotic illness in the UK have adequate monitoring of physical health risk factors by their mental health services in any 12-month period.  The Guidelines recommend that specific physical health measurements are recorded before an antipsychotic medication is started, or as soon as possible afterwards, and then at regular intervals.  One of the key factors to measure is body mass index (BMI).  Calculating the BMI requires both weight and height measurements but is superior to measuring weight on its own.  Weight needs to be measured more frequently than the other risk factors in the first few weeks after starting an antipsychotic as this is the period when weight gain, if it occurs, is likely to be most rapid.  As a general rule blood sugar levels, blood lipid profile and blood pressure should be measured before starting a new antipsychotic, and then at 12 weeks, 6 months and annually.  Tobacco smoking and alcohol use should be discussed with the patient on a regular basis.

Management of risk factors

If a risk factor for future physical illness is identified, then it is important that some form of intervention is made aimed at reducing or removing that risk factor.  These Guidelines provide recommendations for the management of the important risk factors for cardiovascular disease and diabetes.  These recommendations are based on a review of the best available evidence, in particular evidence from randomised controlled trials.  Wherever appropriate the recommendations follow existing recommendations for the management of the same risk factors in the general population.

Approaches involving a change in lifestyle, particularly reduction in calorie intake, improvements in diet and increased exercise, have been shown to be effective in reducing weight in people who are overweight and take an antipsychotic drug.  These interventions can also minimise weight gain in people starting treatment with antipsychotic drugs.  The decrease in weight can vary considerably between different people but can be sufficient to reduce the risk of future cardiovascular problems.  While many of the studies examining these interventions have been short (up to 12 weeks in length) there have been longer studies, some of which suggest that the benefits can be maintained.  These Guidelines recommended that lifestyle interventions should be a first line of approach to preventing or managing weight gain.

One obvious approach to reducing the risk of weight gain is, as far as is possible at the beginning of treatment, to try to prescribe medications with less risk of weight gain.  However, this is not always possible and sometimes a patient may prefer to risk weight gain rather than another side-effect.  However, if the initial antipsychotic medication does result in excessive weight gain then changing the drug to one with a lower risk of weight gain can result in weight loss for some people.  However, the data supporting this recommendation is complex and benefits very much depend on which antipsychotic is going to be stopped and which is to be started in its place.  It is always important to balance the potential benefits, in terms of weight loss, of changing a person’s antipsychotic medication against the risk of the change triggering a return of symptoms of the illness that the original drug was being used to treat.

There is also some evidence that adding one of two particular medications to a patient’s existing treatment can sometimes assist weight reduction.  The average degree of weight loss is similar to that seen with lifestyle interventions.  However, this should only be considered when the other approaches above have been considered and, where appropriate, tried and is something that requires careful discussion with a psychiatrist. One of the two ‘add on’ medications is another antipsychotic but all but one of the studies assessing its effects on weight involved adding it to clozapine (an antipsychotic used in ‘treatment resistant schizophrenia’) and so it is largely unknown whether it would be helpful if it was added to other antipsychotics.

There have been many studies looking at the addition of a wide variety of other drugs to see if they may reduce the weight gain experienced by patients on antipsychotic medications.  These studies do not provide sufficient evidence to allow us to recommend these drugs. At present, no medications are specifically licensed in the UK for the treatment of weight gain associated with antipsychotic treatment.  Thus, this approach needs to be considered very carefully by the patient and their doctor, considering the risks as well as the possible benefits, before a decision is made.

The interventions in the Guidelines for other risk factors are in keeping with those recommended for the general population.  They include the use of drugs such as metformin in the management of diabetes, the use of a statin to manage abnormal blood fats (i.e. high blood levels of cholesterol and other lipids), an antihypertensive for high blood pressure and nicotine replacement to help people stop smoking.

Summary and conclusions

People with schizophrenia and similar psychoses have a much higher rate of cardiovascular disease than the general population and this is associated with a reduced life expectancy.  The increased risk is due to a higher rate of cardiovascular risk factors and psychiatric medications can contribute to this through their side effects, in particular their ability to cause weight gain and increase blood sugar and lipid levels.  Monitoring of risk factors for physical illness in people with psychotic illness is very important but is frequently inadequately carried out.  Staff in mental health teams as well as in general practice are also often unsure what interventions may be effective for reducing weight gain and other risk factors.  Correcting these shortfalls has the potential to significantly improve both quality of life and life expectancy and should be a priority for services.

By reviewing the available evidence, and making clear recommendations for monitoring and intervention, we hope these Guidelines are an important step in this direction.  The Guidelines were launched with a scientific meeting in London in April 2016.  Like all BAP guidelines, they will be reviewed and updated in response to new evidence.

 

The BAP Guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment are available at www.bap.org.uk/guidelines

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