WHAT ARE THE SIDE EFFECTS OF ANTIPSYCHOTICS?
People's sensitivity and response to drugs varies enormously. One person may be able to tolerate standard doses with no significant side effects, while someone else may find the same dose has intolerable results.
Neuromuscular effects
Antipsychotics, as a group, have a large number of side effects in common. Because they interfere with dopamine, which is important in controlling movement, many of the side effects are to do with the neuromuscular system. These neuromuscular effects include: Parkinsonism, loss of movement, restlessness and muscle spasms.
Parkinsonism
Some side effects resemble Parkinson's disease, which is caused by the loss of dopamine:
Muscles become stiff and weak, so that your face may lose its animation, and you find fine movement difficult.
You may develop a slow tremor (shaking), especially in your hands.
Your fingers may move as if you were rolling a pill.
When walking, you may lean forward, take small steps, and find it difficult to start and stop.
Your mouth may hang open and produce excessive saliva.
Loss of movement (akinesia)
You may find it difficult to move, and your muscles may feel very weak. This may be mistaken for a symptom of depression.
Restlessness (akathisia)
You may feel intensely restless and unable to sit still. This is more than just a physical restlessness and can make you feel emotionally tense and uneasy, as well. The compulsion to move may be overwhelming. You may rock from foot to foot, shuffle your legs, cross or swing your legs repeatedly, or continuously pace up and down. Nursing staff sometimes misread this as a sign of agitation or anxiety, and may wish to treat it by increasing your dose of antipsychotics. If you are very troubled by akathisia, your doctor may be able to prescribe something to reduce it.
Muscle spasms/dystonia (dysphonia and oculogyric crisis)
These are acute muscle contractions that are uncontrolled and may be painful. They particularly affect young men. Sometimes the problem affects the muscles of the larynx (voice box), which makes it difficult to speak normally (dysphonia). It can be socially disabling, but is treatable.
Another form of muscle spasm affects the muscles that control eye movements. Called 'oculogyric crisis', it makes the eyes turn suddenly, so that you can't control where you look. This is very unpleasant and can make it dangerous crossing the road, or pouring hot water, for instance. It's also very disconcerting for people around you.
Such neuromuscular symptoms can be reduced with the sorts of drugs that are prescribed to treat Parkinson's disease (see below for more information on these drugs). These symptoms die down while you are asleep, so if you take the antipsychotics as a single daily dose in the evening, you could avoid the worst of them (as well as avoiding daytime sedation). You may want to discuss this with your doctor to find out whether it would be an option for you.
Sexual side effects
Many antipsychotic drugs cause levels of the hormone prolactin to rise, which is related to some very common sexual side effects for both women and men, who may feel embarrassed to talk about them:
Breast development and the production of breast milk can affect men as well as women.
A drop in sexual desire can make men and women less easily aroused, and cause impotence and sterility in men. Some drugs can interfere with erection and affect ejaculation.
Priapism, a persistent erection of the penis without sexual arousal, sometimes results. This is rare, but if it occurs you should treat it as an emergency and seek medical advice, because it may cause serious harm to the penis.
Spontaneous ejaculation is sometimes a problem.
Loss of periods, vaginal dryness, unwanted hair and acne may occur in women.
Osteoporosis (loss of bone density) as a consequence of hormone changes is a serious risk for men and women, and increases the risk of fractures.
Some of the atypical antipsychotics have less effect on prolactin and produce fewer of these problems. Note: women who change from an older antipsychotic to an atypical should bear in mind that this may cause prolactin levels to drop back down. This may cause their periods to return and they may need to think about contraception.
Antimuscarinic or anticholinergic effects
The drugs affect acetylcholine (another chemical messenger) and this may cause drowsiness, dry mouth, blurred vision, dizziness, constipation, feeling sick, difficulty passing water and rapid heartbeat. Constipation may be severe, and should be taken seriously. Low blood pressure can be a problem, especially in older and frail people, and it may contribute to falls; hot baths increase the risk.
Heart rhythm
Several antipsychotics have been implicated in sudden deaths. Although these have been investigated, with no clear conclusion, sudden deaths have been linked to high doses of antipsychotics (above the BNF maximum) and to polypharmacy, when people are on several different antipsychotics at the same time. Many of these drugs affect the heart rhythm. The Royal College of Psychiatrists' guidelines suggest that people on high doses of antipsychotics should be given an ECG before treatment starts and every one to three months, while the dose remains high. Whatever your dose, if you have unexplained blackouts, you should have your heart rhythm monitored. Be cautious with grapefruit and grapefruit juice, because it's thought this might increase the impact on heart rhythm.
Sedation
Sleepiness is a common side effect with antipsychotics, but some, such as chlorpromazine, are more sedating than others.
Eye problems
Various antipsychotics may be responsible for different eye disorders. These include blurred vision and difficulty reading, a build up of granular deposits in the cornea and lens (which doesn't usually affect sight), degeneration of the retina (the light-sensitive part of the eye) that restricts vision and may be serious, an oculogyric crisis (see above), and glaucoma (increased pressure inside the eye). Any antipsychotic can cause narrow-angle glaucoma, which is a medical emergency. You should not take the low-potency antipsychotics if you have had glaucoma.
Weight gain
Weight gain is a very common side effect with a number of antipsychotics, including some of the atypical drugs, and causes a lot of distress. It is linked to increased appetite and decreased activity, but is mainly caused by changes in metabolism - the way your body uses food and converts it to energy or stores it as fat. This means that dieting may be of limited use. You may put on a lot of weight, and this may increase your risk of developing diabetes, and other physical health problems.
Metabolic syndrome, including diabetes
Some side effects, associated especially, but not exclusively, with atypical antipsychotics, are linked, and have begun to be referred to as 'metabolic syndrome'. This group of symptoms: weight gain and obesity; high blood sugar; high blood pressure, and high cholesterol, puts people at risk of heart disease, stroke and diabetes. The risk is increased by dietary factors, such as drinking sugary carbonated drinks and eating a lot of fatty, sugary foods. Everyone, especially those with a family history of diabetes, should have their blood glucose monitored while they are taking these drugs. You should also tell your doctor if you have a family history of cardiovascular disease such as high blood pressure or heart attack. Metabolic syndrome is thought to cause a two- to three-fold increase in the risk of death from cardiovascular disease.
Agranulocytosis
A number of blood disorders are linked to antipsychotics. The most serious is agranulocytosis, a serious blood disorder, which involves the loss of one type of white blood cell. It reduces resistance to infection and has led to deaths in the past. It's very rare with the older antipsychotics, and is a particular risk of clozapine.
Other physical effects
Some people develop blood clots in the veins (thromboembolism), linked to low-potency drugs as well as clozapine.
Liver disorders and jaundice are sometimes linked to using these drugs.
There are various skin problems that may occur. If you get a rash, you should go to the doctor straight away. Any allergic rashes usually occur within the first two months of starting treatment and disappear when the drug is stopped. Some types of skin may develop a blue-grey discoloration. Your skin may become more sensitive to sunlight, especially at high doses, so you should protect your skin from the sun.
You may have problems with regulating body temperature. It may be too high or too low, both of which may make you feel a little unwell.
Another problem that might occur is difficulty urinating.
Emotional effects
Antipsychotics can sometimes make people more excited, agitated and aggressive. They can also cause emotional changes, such as depression. Others may have an antidepressant effect, although the available information about this is contradictory. Some drugs cause an emotional unease, making people restless, giving them bizarre dreams and disturbing their sleep. They can make people feel out of touch with reality or strange in familiar surroundings (depersonalised and derealised). It may also cause them to become more withdrawn, socially.
What is neuroleptic malignant syndrome (NMS)?
This neurological complication is thought to occur in about one per cent of hospital patients taking antipsychotic drugs. It can be very dangerous if it's not detected and treated, but the symptoms can be mistaken for an infection.
The symptoms are: sweating or fever, with a high temperature; tremor, rigidity or loss of movement; difficulty speaking and swallowing; changes in consciousness, from lethargy and confusion to stupor or coma; rapid heartbeat, very rapid breathing and changes in blood pressure. Blood tests show abnormal results. NMS develops rapidly over 24 to 72 hours, and rigidity and a high temperature are usually the first symptoms to appear.
The condition mostly affects people under forty, and is twice as common in men. It can occur if you are taking standard doses of antipsychotics, and if you have been taking the drugs for many years. The main trigger seems to be a change of dose within the last 4 to 11 days. High-potency antipsychotics may produce greater risk, but it can happen with all of these drugs, including the atypical group.
Treatment varies and can include reducing the fever, giving drugs to relax the muscles, and drugs to counter the chemical imbalance that is thought to cause NMS. Electroconvulsive therapy has also been used effectively.
The symptoms may last for days, or even weeks, after stopping the drugs. Although the criteria for making the diagnosis are not clear, it seems that only about one per cent of people on antipsychotics are likely to get NMS. Out of these, 11 per cent may be fatal. Many people who have had NMS once go on to get it again, so you should only take antipsychotics afterwards if they are absolutely essential, and then only the low-potency drugs at the lowest doses.
What is tardive dyskinesia (TD)?
TD is a disorder of the central nervous system, which causes abnormal, uncontrollable, disfiguring, and embarrassing movements. These usually start in the face and mouth, as involuntary tongue movements and slight grimacing. The problem can spread to the rest of the body, with writhing movements in the limbs, muscle spasms, tremors and tics.
Most psychiatrists agree that TD is caused by antipsychotics, mainly affecting people who have been taking moderate to high doses for long periods of time, and who have had quite severe Parkinson's symptoms. It's rare in someone who has been taking antipsychotics for less than six months, if the doses have been small. It seems that people are more likely to get TD if they get bad Parkinson's effects. Women, children and older people may be more vulnerable, and possibly those with a mood disorder such as manic depression (bipolar disorder).
The problem may not be discovered until after you stop taking the antipsychotics, because they mask the symptoms of TD. Unfortunately, stopping and starting the drugs may make TD more persistent, once it has developed.
Some people remain on the drugs as a way of dealing with the symptoms, although this may result in further damage. Sometimes when drugs are withdrawn, withdrawal dyskinesias may occur, but this is not necessarily the same as TD.
There's disagreement about how common TD is, and about the number of people who are permanently affected. Estimates of the risks of developing TD, after long-term use, range from 5 to 56 per cent, but 20 per cent is a widely accepted estimate for those treated for four years, or longer. The risk is higher for people on depot preparations. There is believed to be much less risk of TD with the atypical drugs.
People's sensitivity and response to drugs varies enormously. One person may be able to tolerate standard doses with no significant side effects, while someone else may find the same dose has intolerable results.
Neuromuscular effects
Antipsychotics, as a group, have a large number of side effects in common. Because they interfere with dopamine, which is important in controlling movement, many of the side effects are to do with the neuromuscular system. These neuromuscular effects include: Parkinsonism, loss of movement, restlessness and muscle spasms.
Parkinsonism
Some side effects resemble Parkinson's disease, which is caused by the loss of dopamine:
Muscles become stiff and weak, so that your face may lose its animation, and you find fine movement difficult.
You may develop a slow tremor (shaking), especially in your hands.
Your fingers may move as if you were rolling a pill.
When walking, you may lean forward, take small steps, and find it difficult to start and stop.
Your mouth may hang open and produce excessive saliva.
Loss of movement (akinesia)
You may find it difficult to move, and your muscles may feel very weak. This may be mistaken for a symptom of depression.
Restlessness (akathisia)
You may feel intensely restless and unable to sit still. This is more than just a physical restlessness and can make you feel emotionally tense and uneasy, as well. The compulsion to move may be overwhelming. You may rock from foot to foot, shuffle your legs, cross or swing your legs repeatedly, or continuously pace up and down. Nursing staff sometimes misread this as a sign of agitation or anxiety, and may wish to treat it by increasing your dose of antipsychotics. If you are very troubled by akathisia, your doctor may be able to prescribe something to reduce it.
Muscle spasms/dystonia (dysphonia and oculogyric crisis)
These are acute muscle contractions that are uncontrolled and may be painful. They particularly affect young men. Sometimes the problem affects the muscles of the larynx (voice box), which makes it difficult to speak normally (dysphonia). It can be socially disabling, but is treatable.
Another form of muscle spasm affects the muscles that control eye movements. Called 'oculogyric crisis', it makes the eyes turn suddenly, so that you can't control where you look. This is very unpleasant and can make it dangerous crossing the road, or pouring hot water, for instance. It's also very disconcerting for people around you.
Such neuromuscular symptoms can be reduced with the sorts of drugs that are prescribed to treat Parkinson's disease (see below for more information on these drugs). These symptoms die down while you are asleep, so if you take the antipsychotics as a single daily dose in the evening, you could avoid the worst of them (as well as avoiding daytime sedation). You may want to discuss this with your doctor to find out whether it would be an option for you.
Sexual side effects
Many antipsychotic drugs cause levels of the hormone prolactin to rise, which is related to some very common sexual side effects for both women and men, who may feel embarrassed to talk about them:
Breast development and the production of breast milk can affect men as well as women.
A drop in sexual desire can make men and women less easily aroused, and cause impotence and sterility in men. Some drugs can interfere with erection and affect ejaculation.
Priapism, a persistent erection of the penis without sexual arousal, sometimes results. This is rare, but if it occurs you should treat it as an emergency and seek medical advice, because it may cause serious harm to the penis.
Spontaneous ejaculation is sometimes a problem.
Loss of periods, vaginal dryness, unwanted hair and acne may occur in women.
Osteoporosis (loss of bone density) as a consequence of hormone changes is a serious risk for men and women, and increases the risk of fractures.
Some of the atypical antipsychotics have less effect on prolactin and produce fewer of these problems. Note: women who change from an older antipsychotic to an atypical should bear in mind that this may cause prolactin levels to drop back down. This may cause their periods to return and they may need to think about contraception.
Antimuscarinic or anticholinergic effects
The drugs affect acetylcholine (another chemical messenger) and this may cause drowsiness, dry mouth, blurred vision, dizziness, constipation, feeling sick, difficulty passing water and rapid heartbeat. Constipation may be severe, and should be taken seriously. Low blood pressure can be a problem, especially in older and frail people, and it may contribute to falls; hot baths increase the risk.
Heart rhythm
Several antipsychotics have been implicated in sudden deaths. Although these have been investigated, with no clear conclusion, sudden deaths have been linked to high doses of antipsychotics (above the BNF maximum) and to polypharmacy, when people are on several different antipsychotics at the same time. Many of these drugs affect the heart rhythm. The Royal College of Psychiatrists' guidelines suggest that people on high doses of antipsychotics should be given an ECG before treatment starts and every one to three months, while the dose remains high. Whatever your dose, if you have unexplained blackouts, you should have your heart rhythm monitored. Be cautious with grapefruit and grapefruit juice, because it's thought this might increase the impact on heart rhythm.
Sedation
Sleepiness is a common side effect with antipsychotics, but some, such as chlorpromazine, are more sedating than others.
Eye problems
Various antipsychotics may be responsible for different eye disorders. These include blurred vision and difficulty reading, a build up of granular deposits in the cornea and lens (which doesn't usually affect sight), degeneration of the retina (the light-sensitive part of the eye) that restricts vision and may be serious, an oculogyric crisis (see above), and glaucoma (increased pressure inside the eye). Any antipsychotic can cause narrow-angle glaucoma, which is a medical emergency. You should not take the low-potency antipsychotics if you have had glaucoma.
Weight gain
Weight gain is a very common side effect with a number of antipsychotics, including some of the atypical drugs, and causes a lot of distress. It is linked to increased appetite and decreased activity, but is mainly caused by changes in metabolism - the way your body uses food and converts it to energy or stores it as fat. This means that dieting may be of limited use. You may put on a lot of weight, and this may increase your risk of developing diabetes, and other physical health problems.
Metabolic syndrome, including diabetes
Some side effects, associated especially, but not exclusively, with atypical antipsychotics, are linked, and have begun to be referred to as 'metabolic syndrome'. This group of symptoms: weight gain and obesity; high blood sugar; high blood pressure, and high cholesterol, puts people at risk of heart disease, stroke and diabetes. The risk is increased by dietary factors, such as drinking sugary carbonated drinks and eating a lot of fatty, sugary foods. Everyone, especially those with a family history of diabetes, should have their blood glucose monitored while they are taking these drugs. You should also tell your doctor if you have a family history of cardiovascular disease such as high blood pressure or heart attack. Metabolic syndrome is thought to cause a two- to three-fold increase in the risk of death from cardiovascular disease.
Agranulocytosis
A number of blood disorders are linked to antipsychotics. The most serious is agranulocytosis, a serious blood disorder, which involves the loss of one type of white blood cell. It reduces resistance to infection and has led to deaths in the past. It's very rare with the older antipsychotics, and is a particular risk of clozapine.
Other physical effects
Some people develop blood clots in the veins (thromboembolism), linked to low-potency drugs as well as clozapine.
Liver disorders and jaundice are sometimes linked to using these drugs.
There are various skin problems that may occur. If you get a rash, you should go to the doctor straight away. Any allergic rashes usually occur within the first two months of starting treatment and disappear when the drug is stopped. Some types of skin may develop a blue-grey discoloration. Your skin may become more sensitive to sunlight, especially at high doses, so you should protect your skin from the sun.
You may have problems with regulating body temperature. It may be too high or too low, both of which may make you feel a little unwell.
Another problem that might occur is difficulty urinating.
Emotional effects
Antipsychotics can sometimes make people more excited, agitated and aggressive. They can also cause emotional changes, such as depression. Others may have an antidepressant effect, although the available information about this is contradictory. Some drugs cause an emotional unease, making people restless, giving them bizarre dreams and disturbing their sleep. They can make people feel out of touch with reality or strange in familiar surroundings (depersonalised and derealised). It may also cause them to become more withdrawn, socially.
What is neuroleptic malignant syndrome (NMS)?
This neurological complication is thought to occur in about one per cent of hospital patients taking antipsychotic drugs. It can be very dangerous if it's not detected and treated, but the symptoms can be mistaken for an infection.
The symptoms are: sweating or fever, with a high temperature; tremor, rigidity or loss of movement; difficulty speaking and swallowing; changes in consciousness, from lethargy and confusion to stupor or coma; rapid heartbeat, very rapid breathing and changes in blood pressure. Blood tests show abnormal results. NMS develops rapidly over 24 to 72 hours, and rigidity and a high temperature are usually the first symptoms to appear.
The condition mostly affects people under forty, and is twice as common in men. It can occur if you are taking standard doses of antipsychotics, and if you have been taking the drugs for many years. The main trigger seems to be a change of dose within the last 4 to 11 days. High-potency antipsychotics may produce greater risk, but it can happen with all of these drugs, including the atypical group.
Treatment varies and can include reducing the fever, giving drugs to relax the muscles, and drugs to counter the chemical imbalance that is thought to cause NMS. Electroconvulsive therapy has also been used effectively.
The symptoms may last for days, or even weeks, after stopping the drugs. Although the criteria for making the diagnosis are not clear, it seems that only about one per cent of people on antipsychotics are likely to get NMS. Out of these, 11 per cent may be fatal. Many people who have had NMS once go on to get it again, so you should only take antipsychotics afterwards if they are absolutely essential, and then only the low-potency drugs at the lowest doses.
What is tardive dyskinesia (TD)?
TD is a disorder of the central nervous system, which causes abnormal, uncontrollable, disfiguring, and embarrassing movements. These usually start in the face and mouth, as involuntary tongue movements and slight grimacing. The problem can spread to the rest of the body, with writhing movements in the limbs, muscle spasms, tremors and tics.
Most psychiatrists agree that TD is caused by antipsychotics, mainly affecting people who have been taking moderate to high doses for long periods of time, and who have had quite severe Parkinson's symptoms. It's rare in someone who has been taking antipsychotics for less than six months, if the doses have been small. It seems that people are more likely to get TD if they get bad Parkinson's effects. Women, children and older people may be more vulnerable, and possibly those with a mood disorder such as manic depression (bipolar disorder).
The problem may not be discovered until after you stop taking the antipsychotics, because they mask the symptoms of TD. Unfortunately, stopping and starting the drugs may make TD more persistent, once it has developed.
Some people remain on the drugs as a way of dealing with the symptoms, although this may result in further damage. Sometimes when drugs are withdrawn, withdrawal dyskinesias may occur, but this is not necessarily the same as TD.
There's disagreement about how common TD is, and about the number of people who are permanently affected. Estimates of the risks of developing TD, after long-term use, range from 5 to 56 per cent, but 20 per cent is a widely accepted estimate for those treated for four years, or longer. The risk is higher for people on depot preparations. There is believed to be much less risk of TD with the atypical drugs.
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