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What should I know before taking these drugs?
What are mood stabilisers used to treat?
Which drugs are used as mood stabilisers?
How does the psychiatrist decide which type of medicine to use?
What sort of tests should I have before starting medication?
How long will I have to go on taking the medication?
Lithium
What is lithium?
Why do I need regular blood tests?
What dose should I be on?
Will lithium affect any other medicines I might be taking?
What are the other dos and don'ts with lithium?
How long does lithium take to work?
What are the side effects?
How long will I have to be on lithium for?
What's the best way to withdraw?
Anticonvulsants
Which anticonvulsant drugs are used as mood stabilisers?
Valproate semisodium
Carbamazepine
Lamotrigine
Mood stabilising drugs during pregnancy, childbirth and breast-feeding
What are the risks of taking anticonvulsants during pregnancy?
What are the risks of taking lithium during pregnancy?
Are there alternatives to taking lithium during pregnancy?
What are the risks of taking mood stabilisers while breast-feeding?
Children and mood stabilisers
Useful organisations
Useful websites
Further reading
The booklet uses the term 'mood stabiliser' because this is the term preferred by mental health service users who take these types of drugs. The NICE (National Institute of Health and Clinical Excellence) guidelines on the treatment of bipolar disorder avoid this term, because there is no agreed definition. They use 'anti-manic' for drugs used to treat manic episodes, and 'prophylactic' (meaning protective) for those used for longterm treatment. For many people these are the same drugs.
Note. Lithium packs (December 2009): The National Patient Safety Agency has produced a set of guidelines for clinicians on Safer lithium therapy, and a Lithium Pack for people taking lithium, which includes information, a record book for keeping track of blood tests, kidney and thyroid tests, weight etc, and a Lithium Alert Card. All patients on lithium should have one of these. Those who are monitored by their GP should make sure they are given a copy.
Drugs can have two types of name: their generic (general) name and the trade name (starting with a capital letter) given by the drug company producing it. The same drug can have several different trade names. In this booklet, drugs are listed using their generic name, with the trade name/s after it in brackets.
The law says that you have the right to make an informed decision about which treatment to have, and whether or not to accept the treatment a doctor suggests. To consent, properly, you need to have enough information to understand the nature, likely effects and risks of the treatment, including its chance of success, and any alternatives to it. Generally, you can only receive treatment that you have specifically agreed to. Once you have given your consent, it isn't final and you can always change your mind. This consent to treatment is fundamental, and treatment given without it can amount to assault and negligence. However, there are times when treatment can be given without consent - see Mind rights guide 3: consent to medical treatment.
If you are prescribed medication as an outpatient, or from your GP, it should come with a patient information leaflet (in accordance with a European Union directive). As an inpatient, you may have to ask for it, specifically. If you do not receive this information with your medicine, or accidentally throw the PIL away, you should ask for it from the person who makes up your prescription.
The PIL contains information such as: the trade and general (generic) names of the drug; the strength of the medicine and the form it takes - for example, tablets; who should take it; what conditions the drug is licensed to treat; any cautions you should be aware of before taking it; how to take it and when; possible side effects; the expiry date of the drugs and how to store them.
It should also contain a full list of all the ingredients, including the extra contents that hold it together as a tablet or capsule, such as maize starch, gelatin, cellulose, and colourings. This information is important because some people may be allergic to one or other of the ingredients, such as lactose or gluten or a colouring. Gelatin is unacceptable to some people because it is an animal product.
Some of the information is quite hard to understand, and the Commission on Human Medicines has been looking at ways of making it easier. They have produced a leaflet Taking medicines - some questions and answers about side effects which you can find on their website or request by telephone, or may be available in your local pharmacy. There is more information on medicines and their use, in the form of Medicines Guides, available from the Medicines Information Project website (See 'Useful websites' for details of both these organisations.)
The final item on the leaflet tells you that it contains only the most important information you need to know about the medicine and that if you need to know more, you should ask your doctor or your pharmacist.
Many people would like to have the information about their proposed treatment before they are given their prescription at the pharmacy. Questions you might like to ask your doctor when he or she gives you a prescription for a drug are:
You may well think of other questions you wish to ask.
You should also consider talking to your pharmacist. Pharmacists are drug specialists, and may be more knowledgeable about your drugs than the doctor who prescribes them. They may be more aware of possible side effects, and also possible interactions with other drugs (this is when a drug changes the effect of other drugs you are taking, making them less effective, or causing additional side effects). Pharmacists are usually very willing to discuss drugs with patients, and some high-street chemists have space set aside where you can talk privately.
Since January 2006, a new scheme has been in place called the 'Medicines Use Review'. People who regularly take more than one prescription medicine, or take medicines for a long-term illness, are encouraged to go to pharmacists who are operating the scheme, for a full discussion of their medicines and any problems they may have with them. The Medicines and Healthcare products Regulatory Agency (MHRA), who are responsible for overseeing the licensing of medicines, have produced a guide to the scheme which is available on
Mood stabilisers are used to treat bipolar disorder (manic depression), recurrent depression, and other mood disorders. Treatment with these drugs should be started by a specialist (psychiatrist) and not by a GP.
The drugs that are used as mood stabilisers are lithium, and some of the anticonvulsant drugs which were originally made for treating epilepsy. The anticonvulsants that are currently used are valproate (Depakote), carbamazepine (Tegretol), and lamotrigine (Lamictal).
Other drugs licensed to treat mania are the antipsychotics olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify) and risperidone (Risperdal) which may be combined with lithium or valproate. Older antipsychotics are also used, but high doses of haloperidol, fluphenazine or flupentixol may be hazardous when used with lithium, and these drugs are not recommended in the NICE guidelines. However, they may be used by people who have a long history of bipolar episodes and have used them successfully in the past.
Antidepressants may be used to treat depressive episodes, but should be used with caution as they may cause manic episodes in some people. For more information about antipsychotics and antidepressants, see Mind's booklets Making sense of antipsychotics and Making sense of antidepressants.
The NICE guidelines on the treatment of bipolar disorder say that lithium, olanzapine (an antipsychotic drug) or valproate should be considered for long-term treatment. The choice should depend on:
If you continue to have frequent episodes in spite of this treatment, you might need to try a different drug, or the doctor may suggest you take two together. Possible combinations are lithium with valproate, lithium with olanzapine, and valproate with olanzapine.
If this strategy does not work, doctors may try carbamazepine or lamotrigine.
Lithium works better for some conditions than others. It's good at helping people diagnosed with bipolar disorder who have been having serious mood swings. It also helps people who have had two, or more, periods of mania or hypomania (a less severe form of mania).
In general, lithium seems to be more successful in treating:
Lithium is less satisfactory for people whose mood swings tend to be towards depression only (sometime called unipolar depression). It's still considered as an option for someone who has had three, or more, periods of serious depression within five years, involving hospital admission, especially if there were symptoms of psychosis. However, in these situations, people often experience repeated episodes, even with lithium treatment.
Anticonvulsant drugs are more effective in treating:
For people who have recurrent depression, NICE guidelines suggest lamotrigine should be tried. People may also take an SSRI (selective serotonin reuptake inhibitors) antidepressant combined with a mood stabiliser, but lithium should be combined with an SSRI with caution, as there is a possibility of interaction between these drugs.
If you are prescribed lithium, you should have the following tests, to make sure that your body systems are functioning well enough to tolerate it.
Once you are taking lithium, you will need to have regular blood tests, to check your lithium level (also see below). You should have a thyroid function test every year, and your kidney function should also be checked periodically.
People taking carbamazepine should also have regular checks of blood levels of the drug to make sure they are safe and effective.
The NICE guidelines recommend that people with bipolar disorder should have an annual physical health review, normally at their GP surgery, to check the following:
NICE guidelines suggest that you should continue with medication for at least two years after an episode of bipolar disorder and up to five years if you have a history of frequent relapses or severe psychotic episodes, or you take street drugs, have a lot of stress in your life, or poor social support. Your treatment should be reviewed regularly, and if you wish to stop taking your medication earlier than recommended you should discuss this with your psychiatrist. You need to take lithium for at least six months to find out whether it will be effective as a long-term treatment.
If you have had previous episodes of illness and treatment with medication, you may have developed your own view about how helpful the treatment is, how long you need to take it for, as well as other ways of managing your condition.
Some people take medication for many years, remaining stable and able to get on with their lives. Others may take medication to start with, but then develop alternative strategies for managing their lives without drugs.
If you decide to come off your medication it is always advisable to withdraw gradually, and with support. See Mind's booklet Making sense of coming off psychiatric drugs.
As lithium is, strictly speaking, not a drug, and has rather different effects from the anticonvulsants, it is discussed separately in this booklet.
Lithium is not a manufactured drug, but an element that occurs naturally in alkaline waters and clays. It is extracted from its natural sources and combined as a salt with either carbonate or citrate, to make a substance that can be taken as a medicine. Carbonate and citrate are widespread in the body and have no effect. Lithium is not a vital substance for the human body, and is not prescribed because there is a deficiency of it; in fact it is poisonous in large amounts. It must therefore be used with care, and the dosage carefully monitored.
Drug companies sell the medicine under a trade name. In the UK, lithium carbonate comes in tablet form under the names Camcolit, Liskonum, Priadel, and Lithonate. Lithium citrate comes as a tablet, Litarex, or in liquid form as Li-liquid and Priadel. It makes no medical difference which one you take, but it's best to stick to either the carbonate or the citrate, because the absorption of lithium varies slightly with each one.
Lithium has been widely used for many mental health problems, but its main purpose has been to prevent relapse in cases of bipolar disorder (manic depression), and in recurring depression (unipolar depression). Studies have shown that it works well as a mood stabiliser, and tends to reduce the number of manic and depressive episodes people have, and may even suppress them altogether. It reduces the incidence of suicide in people with bipolar disorder.
It's also licensed for schizoaffective disorder, managing aggression, and self-harm.
One advantage that lithium has over other drugs is that it doesn't act as a sedative, even though it stabilises mood. On the whole, people cope very well with taking lithium in the long term, but users have complained that it makes them less able to express themselves and that it dampens down their imagination.
When you are first prescribed lithium, you should be given a lithium treatment card which you should carry with you, and show to any health professional who is treating you for any condition, including the dentist.
The dose of lithium you take needs to be carefully adjusted because at too low a dose it is ineffective, but too high a dose is dangerous. Blood tests are important because they enable your doctor to monitor the amount of lithium in the bloodstream, and therefore to ensure that your dosage is both effective and safe. You need to have blood tests more often in the early stages of treatment, or when your dosage is being adjusted. In these circumstances, you may need to have one every week. Once levels have steadied, you will need blood tests only once a month, and every three months later on. Lithium reaches a steady level in the blood about five days after starting a fixed daily dose. People aren't always given blood tests as often as they should be, and because of this, the medication doesn't always work as well as it might.
Your doctor may also ask for a blood level check if there are signs that the bipolar disorder is returning (suggesting that the lithium level may be too low) or if there is an increase in adverse side effects (a sign that the lithium level may be too high).
There can be no standard dose of lithium, because the amount of lithium in the blood depends on kidney function, which varies from person to person. Doses are adjusted to keep the blood level within a range of 0.4-1 millimole (mmol) of lithium per litre of blood serum, which is considered to be the appropriate therapeutic range. (The millimole is a unit of measurement used by biochemists.)
For most people, the appropriate range to maximise benefits and minimise side effects should be 0.5-0.8mmol lithium per litre of blood serum. Some doctors believe a higher level is acceptable, though adverse effects may increase. Levels over 1.5mmol lithium per litre of blood serum are toxic and may be fatal.
The starting dose used by specialists is commonly the equivalent of 0.4-0.8g lithium carbonate daily. This dose will then have to be adjusted according to the results of blood tests. If you have any questions about dosage instructions, ask the pharmacist. Because drugs are eliminated more slowly in older people, they are particularly susceptible to lithium toxicity. They usually need a lower serum level, and often take half the standard dose range.
Some people take their lithium in divided doses, several times a day. Others take a modified-release formulation as a single dose, usually at night. All the tablets, except Camcolit 250mg, are marketed as modified-release formulations. One of the effects of taking lithium is to make people need the toilet more often, but this may happen less with the once-daily dose.
You may need to discuss with your doctor which type is best for you, depending on your symptoms, side effects and any other medicines you may be taking. It's important to discuss any side effects and possible changes in dose. Don't change your prescribed dosage without consultation. Always contact your doctor immediately if you think your lithium level may be too high.
Don't double up a dose of lithium if you forget to take a prescribed dose. If you have missed your regular time by three hours, or less, take the normal dose you missed, and then take the next dose at the usual time. If you have missed your normal dose by over three hours, skip the missed dose and resume your lithium medication at the next regularly scheduled time.
Before prescribing lithium or any medication, your doctor should be aware of all the medicines you are currently taking, so that any possible drug interactions can be avoided. If you are admitted to hospital for any reason, you should tell the medical staff that you are taking lithium. Make sure you are given a lithium treatment card and remember to carry this with you.
Prescription medication
Lithium has potentially serious interactions with a number of different prescribed drugs, including steroids (for treating asthma, for example) and drugs for high blood pressure and for water retention. Antipsychotic drugs (major tranquillisers) may increase side effects, such as muscular disorders, if you take them while on lithium. This particularly applies to the older antipsychotics, such as chlorpromazine (Largactil) and haloperidol (Haldol, Dozic or Serenace). There's also a risk that the two together may have a poisonous effect on the nervous system (neurotoxicity). Lithium and haloperidol are often given together during a manic phase, because lithium can be slow to take effect. In this case, the antipsychotic is normally started at a lower dose than usual.
SSRI antidepressants (such as Prozac) can also affect the central nervous system, if combined with lithium. It can also increase the risk of serotonin syndrome, which causes high temperature (hyperthermia), trembling and fits (convulsions).
Over-the-counter drugs
If you buy medicines over the counter, without a doctor's prescription, you should let the pharmacist know about any other medicines that you are taking, so that he or she can tell you of any potential problem with drug combinations. You should be very cautious with anti-inflammatory drugs such as ibuprofen, because this can reduce lithium excretion, especially at high doses, and therefore increase your lithium levels.
Lithium may also interact with herbal and other complementary medicines. Take advice from a qualified professional before taking any of these with lithium.
Because lithium is chemically very similar to sodium, your salt and water intake affects the way that it is removed from your body, so you need to maintain a sufficient and steady supply of both. Reducing either may allow lithium to build up to dangerous levels, but you also need to keep levels high enough to be effective.
The important thing is not to drink too much or too little fluid. You should drink about the same amount of water every day (the usual range is 4-6 pints) and avoid any dramatic changes in your fluid intake. If you usually drink less than 4-6 pints of fluid per day, and blood tests show that your lithium level is stable, there's no need to drink more water. But don't ignore any feelings of thirst. Have a drink when you feel you need to. Avoid sudden changes in the amount you drink of coffee, tea, colas or other drinks containing caffeine. Caffeine causes water loss and can interfere with lithium treatment. Although it's safe to drink alcohol, in moderation, in most cases, it's best to check this with your doctor.
In the same way, keep to your normal daily amount of salt. Inform your doctor before you begin any new diets, especially low-salt diets, and don't fast while taking lithium. People sometimes gain weight on lithium. This may be due to your body retaining water. You may have to adjust your diet to compensate, for example by reducing the amount of sugary fluids you drink.
Try not to get into situations where you are likely to sweat heavily. Take care not to overdo things in hot weather, and avoid sauna baths, for example. If you are running a temperature, sweating heavily, vomiting, or having diarrhoea, tell your doctor. It may be necessary, temporarily, to stop taking lithium until you're better.
Avoid sudden bursts of heavy exercise. It's safe and beneficial to exercise regularly, provided that you ensure you take in sufficient fluids and salt. It's also advisable to time your lithium dose so that you are not taking it immediately before vigorous exercise.
Lithium can impair coordination, so you need to take particular care when driving or operating dangerous machinery. Be prepared to stop if it's clear that you can't do it safely any more.
Don't keep lithium in direct sunlight or near other sources of heat, and never leave drugs within reach of children.
Although some people feel better as soon as they begin taking lithium, most improve more gradually. It can take anything from a few days to several weeks for a noticeable improvement.
Some people don't respond to lithium therapy at all, or can't tolerate it. Some may respond only partially, and may have fewer or less severe episodes of depression or mania. It's important not to expect too much when starting treatment. It may take six months to a year to achieve a full effect as a preventive treatment.
You may not get any adverse effects at all; side effects are usually related to the amount of lithium in the blood, and many people taking lithium experience none. Some side effects are relatively mild and only occur during the early part of treatment, while your body is adjusting to lithium. Others take longer to appear, but can be treated. A few, however, indicate that lithium is reaching unacceptable levels within the body, and that you need instant attention to avoid serious poisoning.
Early side effects
These happen as the body adjusts to the lithium. They are not usually medically serious, and most get better or go away after a few weeks. You should tell your doctor about them at routine appointments, unless they become particularly unpleasant, in which case you should tell your doctor at once. They include mild gut effects such as mild stomach cramps, mild diarrhoea, feeling sick; feeling dizzy; slight muscle weakness and a dazed feeling; needing to urinate more often; increased thirst; a metallic taste in the mouth; weight gain.
Intermediate side effects
These persist after your body has adjusted to lithium, or may emerge during the course of treatment. You should keep your doctor informed, since persistent side effects may mean that your dosage needs adjusting, or that you may be helped by additional medication. It's also possible that changing your diet and the time of day when you take your dose could help.
Side effects that may persist include shaky hands (which may be helped by low doses of the beta blocker, propranolol), needing to urinate too often, feeling thirsty, gaining too much weight, skin rash, memory problems, loss of mental sharpness, loss of interest in sex, worsening acne or psoriasis. Weight gain may be associated with fluid retention (treating this with diuretics should be done cautiously because of possible interactions). Fluid retention may be associated with the effects of lithium on heart function.
Always report a skin rash or widespread itching at once, since it may be the signal of an allergic reaction.
Long-term side effects
Long-term treatment with lithium may cause permanent changes to the kidney and disturbance of kidney function. You should have regular tests of kidney function, especially if you are experiencing significant frequency of urination and problems with thirst.
Changes to thyroid function may occur, more commonly reduced thyroid activity (hypothyroid). This can cause sleepiness, tiredness, a slow-down in your thinking, feeling cold, headaches, dry skin, constipation, muscle aches and unusual weight gain. Symptoms of increased thyroid activity (or hyperthyroid) include nervousness, a fast heartbeat, feeling emotional, being uncomfortable in the heat and sweating. These conditions may be treated with appropriate thyroid medication, or you may be advised to come off lithium. Long-term effects also include high blood calcium and magnesium.
Lithium may rarely have effects on the heart which can be serious. Any signs of heart problems such as fainting, or disturbances of heart rhythm or heart rate should be taken seriously and investigated further.
Provided that the level of lithium in the blood remains within safe levels, there may be no long-term damage. However, some users have pointed out that it's sometimes difficult to keep to the advised dosage, especially during illness, and this may lead to toxicity.
Do tell your doctor immediately about any adverse effects you notice. Remember that although many symptoms may be caused by lithium, they could also be an indication of a separate illness, so it's important to talk it over with your GP.
Serious side effects
These may occur at any stage of treatment. Although there may be other causes for these symptoms, they could indicate that the lithium level in your blood is becoming dangerously high. If you get any of the following symptoms, stop taking lithium and contact your doctor at once: loss of appetite, persistent diarrhoea, vomiting or severe nausea, serious hand tremors, frequent muscle twitching, muscle weakness and lack of coordination, blurred vision, confusion, drowsiness, severe discomfort, swelling of legs and feet, and any severe abnormality.
Signs of severe overdose
Symptoms of lithium overdose include: loss of coordination, heavy shakes, muscle stiffness, difficulty speaking, confusion. In very severe cases, this may lead to stupor, coma and then death.
This will vary from person to person, depending on your symptoms, and it's something to discuss with your doctor at the beginning. You should not start on the drug if you are not prepared to take it for quite a long period. Lithium is not a cure for bipolar disorder, but a preventive medicine. It usually needs to be taken for two years to be beneficial, and doctors may suggest that you need to take it for the rest of your life. Psychiatric research shows that a large number of lithium users will relapse if they stop taking lithium, but this may be because they have withdrawn too quickly. Many people are able to withdraw successfully, while others who have had difficulty with withdrawal decide that they do need to continue taking it.
The information produced by one of the drug companies states that people should only be maintained on lithium after three to five years if assessment shows that they are still benefiting from it. You should have regular reviews with your doctor to discuss whether you still need to take it. If you have been completely free of relapses while taking lithium for three to four years, it may be appropriate to see if you can manage without it.
There is no evidence to indicate that people taking lithium become physically dependent on it. However, some people may find their original symptoms coming back when they stop taking lithium, or they may have an episode of 'withdrawal mania'. It is therefore advisable to withdraw slowly, and with the help of your doctor if possible.
Ideally, you should reduce the dose gradually over two to three months at least, depending on how long you have been taking it, and not less than four weeks. If you stop taking lithium over a very short period, you are more likely to relapse, or have an episode of mania with the withdrawal.
Lithium treatment can be safely stopped for brief periods, and it's wise to stop taking it for 24 hours before any major operation. Usually, it's safe to restart it soon after the operation. NICE guidelines suggest that if lithium is to be stopped abruptly, prescribers should consider replacing it with an antipsychotic drug or valproate.
There are two anti-epileptic drugs that are well-established treatments licensed for mania and as mood stabilisers. They are carbamazepine (brand names, Tegretol, Tegretol Retard, Carbagen Retard) and valproate as semisodium valproate (Depakote). Sodium valproate (Epilim) - containing more sodium - is also used, but is not licensed as a mood stabiliser.
Carbamazepine and valproate are not suitable for recurrent depression. A third anticonvulsant, lamotrigine (Lamictal) has been used more recently because of its antidepressant effects; however, it is not yet licensed as a mood stabiliser.
Valproate semisodium (Depakote)
Valproate semisodium is licensed for the treatment of manic episodes in bipolar disorder.
When not to take valproate
Valproate should not be given to people who either have liver disease, or have a family history of liver disease. (Liver function should be monitored before starting treatment, and liver and kidney function and blood should be checked regularly.) It should also not be used generally in women who might become pregnant (see below).
Cautions
Valproate should be used with caution in people with kidney problems.
Side effects of valproate
The most common side effects of valproate are stomach irritation, feeling sick, unsteadiness, shaking, increased appetite and weight gain. Less common effects are hair loss, fluid retention (puffy hands and feet), blood disorders, liver problems (fatal liver failure has occurred). Rarer side effects are rashes, sedation, aggression and hyperactivity, pancreatitis, dementia, irregular or loss of periods, breast growth, hearing loss, abnormal kidney function (resulting in the loss of essential minerals), skin ulceration, hairiness, acne.
Is it safe to take valproate with other medicines?
Valproate may increase blood levels of MAOI (monoamine oxidase inhibitor) and tricyclic antidepressants, and may also increase the activity of aspirin. It is not thought to affect the contraceptive pill. You should make sure your doctor knows all the other medicines you are taking, including over-the-counter and herbal medicines, at the time when these drugs are prescribed.
Dose
Initially 750mg/day in two to three divided doses, increased according to response. Usual dose 1-2g/day; however, the advice to prescribers suggests that daily dosage should be established according to age and body weight. Individual sensitivity to this drug may be very variable. It is not usually recommended for children under 18 (however, see below).
Valproate comes as tablets which should be swallowed whole and not crushed or chewed.
Withdrawal
There is very little evidence about withdrawal effects with valproate, but people taking it for epilepsy who have had to come off suddenly have reported experiencing fast heart rate, excessive sweating, and tremor which lasted for a few days and may be withdrawal effects. As with other drugs, it is advisable to withdraw gradually to minimize any effects that may occur.
Carbamazepine (Carbagen SR, Tegretol,Tegretol Retard and Teril Retard)
When not to take carbamazepine
Carbamazepine should not be taken by people with certain heart conditions; a history of bone marrow disease; or prophyria (an inherited condition). It is not recommended for acute mania.
Cautions
Carbamazepine should be used with caution in people with kidney or liver problems, heart disease, blood disorders, glaucoma, and those who abuse alcohol. In diabetics it may increase the amount of sugar in the urine.
Side effects of carbamazepine
(Commonest first) nausea and vomiting, dizziness, drowsiness, headache, unsteadiness, confusion and agitation (older people), visual disturbances such as double vision; constipation or diarrhoea, loss of appetite, skin rash, blood disorders; rarely jaundice, hepatitis, and kidney failure; a severe reaction with ulceration and fever; hair loss; blood clots; joint pain; fever; swollen glands; heart problems; movement disorders; pins and needles; depression; impotence; breast growth; lactation; aggression; psychosis; sensitivity to sunlight; breathing or lung problems; low blood sodium; fluid retention; disturbances of bone metabolism.
Is it safe to take carbamazepine with other medicines?
Carbamazepine affects the metabolism of many other drugs. If you are taking any other medication at the time when carbamazepine is prescribed, including over-the-counter and herbal medicines, it is very important that you discuss this with your doctor.
Carbamazepine can make oral contraceptives less effective, so your doctor may suggest you change to a different type of pill, or you may want to consider alternative methods of contraception.
If carbamazepine is taken with antipsychotics or lithium it may increase the side effects.
It should not be used with MAOI (monoamine oxidase inhibitor) antidepressants or within two weeks of taking them. It may reduce the effectiveness of tricyclic antidepressants and some antipsychotics, such as haloperidol. Blood levels of carbamazepine are increased by fluoxetine (Prozac) and fluvoxamine (Faverin).
Dose
The usual starting dose for bipolar disorder is 200mg twice a day, increasing to 600-1,000mg/day, to give a blood level of 8-12mg/l. Modified release tablets (Carbagen SR, Tegretol Retard or Teril Retard) are normally prescribed, and doses increased slowly. Once the dose is established, blood levels should be checked every six months, because the effective level and the dangerous level are close. The maximum dose is 1.6 g (1,600mg) daily. Carbamazepine comes as tablets, chewtabs, liquid, and suppositories. The modified release forms are all tablets.
Withdrawal
There is almost no evidence on possible withdrawal symptoms when coming off carbamazepine. It is advisable to withdraw gradually to minimize the possibility of withdrawal effects.
Lamotrigine (Lamictal)
Lamotrigine is not licensed in the UK for treating bipolar disorder, so the information provided by the drug company relates only to its use in epilepsy. It is approved for use in bipolar disorder in the USA. Several different research studies have shown that in addition to mood stabilising effects, lamotrigine has antidepressant effects as well. It is not recommended for acute mania, and may be more appropriate for people whose bipolar symptoms are mostly depressive.
Cautions and side effects
This drug should be used with caution in people with liver or kidney problems.
As its main side effect is rashes, which affect 1 in 10 people, it is usually started cautiously, with a gradual increase in dose; this decreases the likelihood of the rash. While most rashes are mild, a rash may occur as part of a hypersensitivity syndrome associated with various symptoms including fever, facial oedema (puffiness) and abnormalities of the blood and liver. The syndrome (Stevens-Johnson syndrome) is potentially life-threatening. You should go to a doctor immediately if you develop a rash or fever while taking this drug and stop taking it if no other explanation for your symptoms can be found. Many people with a mild rash can continue to take lamotrigine, sometimes together with an antihistamine.
A rash is more likely to develop when the initial doses of lamotrigine are high or when lamotrigine is too rapidly started when someone is already taking valproate.
The Commission for Human Medicines has issued a warning about possible bone marrow failure with lamotrigine; the symptoms of this are anaemia, bruising or infection. You should see your doctor immediately if you have any of these symptoms.
Other side effects: fever, feeling unwell, flu-like symptoms, sleepiness, lymph node problems, blood disorders, blistering of skin, sensitivity to sunlight; double vision, blurred vision, conjunctivitis, dizziness, drowsiness, difficulty sleeping, headache, unsteadiness, tiredness, gastrointestinal disturbance (including vomiting and diarrhoea), irritability and aggression, shaking, agitation, confusion; headache, feeling sick, aplastic anaemia, serious blood disorders.
Is it safe to take this drug with other medicines?
Lamotrigine interacts with carbamazepine so that blood levels of lamotrigine are somewhat lower in people taking carbamazepine than in those not taking carbamazepine.
Valproate may double blood levels of lamotrigine, therefore if the two drugs are taken together, the initial dose of lamotrigine should be halved.
Its effect may be reduced by antidepressants.
The drug has an important interaction with oral contraceptives so that the dosage of both drugs needs to be carefully adjusted. Women are advised to use alternative methods of contraception if possible.
Dose
The dosage recommendations relate primarily to its use for epilepsy. The starting dose is 25mg/ day for 14 days, increased to 50mg/day for a further 14 days, then increased by a maximum of 50-100mg every 7-14 days. The usual maintenance dose (for epilepsy) is 100-200mg per day as one or two doses. Lamotrigine comes as standard tablets and dispersible tablets.
Withdrawal
Withdrawal symptoms have been reported for lamotrigine, including headaches, depression, and suicidal feelings. There seems to be some risk of fits if you stop taking it suddenly, even if you have not had fits before. As with other drugs it is advisable to withdraw gradually and cautiously to minimize possible effects.
As a general rule all drugs are best avoided in pregnancy unless essential, so as to minimise possible risk to the developing and newborn infant.
Lithium, valproate, carbamazepine, and lamotrigine should not normally be taken during pregnancy because of known risks to the developing infant.
NICE guidelines say, 'Women with bipolar disorder who are considering pregnancy should normally be advised to stop taking valproate, carbamazepine, lithium and lamotrigine, and alternative prophylactic drugs (such as an antipsychotic) should be considered.' The use of anticonvulsants in pregnancy is associated with children having developmental delay and needing special educational support. The following problems are also recorded:
NICE suggests that, during pregnancy, a low dose of antipsychotic is preferable to any of the anticonvulsants above or lithium, because they carry a smaller risk of harm to the foetus.
Lithium may be taken during pregnancy providing it is done cautiously with awareness of the possible hazards, discussed below. For a few women, lithium maintenance treatment may be thought to be essential.
In the first three months of pregnancy there is a risk of malformation of the heart in the developing infant, though the risks of this are not now considered to be as great as was once thought.
If lithium is given in late pregnancy there is risk of dangerous levels of lithium in mother and infant, as the way in which lithium is cleared from the body alters suddenly at childbirth. Lithium is also associated with a higher than expected frequency of stillbirths and deaths soon after birth.
If lithium is to be taken at any stage of pregnancy, careful monitoring of lithium levels is most important if toxic effects are to be avoided.
Planned pregnancy
If you are planning to get pregnant, it's a good idea to discuss this with your doctor. If you decide to come off lithium, this should be done gradually over six to eight weeks, or longer, depending how long you have been taking it for. Afterwards it is advisable to wait a few weeks before trying to conceive, in case your bipolar symptoms recur and you decide you need to go back on the lithium.
Unplanned pregnancy
If you find you are pregnant while you are taking lithium and it is early in pregnancy, you might stop taking lithium immediately if your doctor feels it is appropriate.
If you have been pregnant for some time without realising it, you should discuss with your doctor whether you should have an ultrasound scan. This can usually identify any possible problems in your baby's development, looking especially at the heart.
Continuing lithium during pregnancy
If your doctor thinks it is necessary for you to continue with the lithium treatment, then he or she may need to adjust your dose. For example, the kidneys clear lithium from the body differently during pregnancy, so your dose may need to be increased to cope with this.
During the first half of pregnancy, blood lithium levels should be checked monthly; towards the end this should be done weekly. It may also be better to split the total daily dose into three or more doses a day, so that the level of lithium in your blood does not reach such high peaks as it does if you take larger doses less often.
In late pregnancy it is very important that the doctor who is prescribing and monitoring your lithium treatment consults closely with the obstetrician responsible for your baby's delivery.
Lithium and childbirth
In childbirth, the way that the body clears lithium alters suddenly. If you have continued taking lithium during pregnancy, some doctors may prefer to withdraw lithium treatment gradually in the weeks leading up to the estimated date of delivery, in order to minimise the risk of toxic effects in both the mother and the child. Others may prefer to continue with lithium treatment until the date the baby is due or until labour begins. They may want to continue with lithium as long as possible as a protective factor against the risk of serious mental illness (puerperal or postnatal psychosis).
Lithium should be stopped as soon as labour begins. The obstetrician will need to carefully check your fluid and salt balance and the level of lithium in the blood.
After childbirth
For those who have already had a bipolar episode there is a significant risk of serious mental illness (puerperal psychosis) during the weeks after the birth. Because of this, lithium is often started again as a preventive measure a few days after childbirth. Frequent monitoring of the level of lithium in the blood will be needed at this time to achieve a therapeutic dose. Continuing use of the drug would need to be reviewed in the normal way at the end of the period of risk.
If drug treatment is considered to be essential, then antidepressants or antipsychotic drugs may be prescribed instead. The type of drug given would depend on the pattern of your mood changes and your symptoms. The following information indicates particular risk periods associated with these alternative drugs.
Tricyclic antidepressants given in late pregnancy have been associated with withdrawal symptoms in newborn babies. Irritability, muscle spasms, restlessness, sleeplessness, fever and fits have been reported.
One antipsychotic drug, prochlorperazine (Stemetil), is associated with malformations in the developing baby when given during the first three months of pregnancy. The use of antipsychotic drugs in late pregnancy may cause temporary reactions in newborn infants: Parkinson's reactions have occasionally been reported. These include muscular rigidity, involuntary movements and shaking. If long-acting drugs are taken they take time to clear from the body. The last dose should be taken six to eight weeks before the expected birth.
For further information about these drugs see Mind's booklets Making sense of antidepressants, Making sense of antipsychotics, and Making sense of coming off psychiatric drugs.
You should be able to get further information from your doctor regarding any drug you are advised to take during pregnancy. It is very important to discuss all aspects of your drug treatment and any concerns you may have with your doctor, obstetrician, midwife and pharmacist.
You should not breast-feed while taking lithium, as lithium passes into the breast milk in sufficient amounts to be dangerous to the baby.
Carbamazepine, valproate and lamotrigine all appear in breast milk in small amounts so breast feeding is not recommended. However the British National Formulary suggests that amounts are not considered sufficient to be harmful.
The British National Formulary (BNF) and the Summaries of Product Characteristics (produced by the drug manufacturers) say that lithium is not suitable for children. However, the BNF for children states that lithium may be given to children, only on the advice of a specialist. Because of the long-term effects, the need for treatment should be reviewed regularly.
The BNF for children does say that carbamazepine and valproate may be useful in children unresponsive to lithium.
All drugs should be used with caution, and at doses appropriate to the child's age and size.
British Association for Behavioural and Cognitive Psychotherapies (BABCP)
tel. 0161 797 4484
web: www.babcp.com
Can provide details of accredited therapists
British Association for Counselling and Psychotherapy (BACP)
tel. 01455 883 300 (general enquiries)
tel: 0870 443 5220 (to find a therapist)
web: www.bacp.co.uk
For details of local practitioners
MDF The Bipolar Organisation
Castle Works, 21 St. George's Road, London, SE1 6ES
tel: 08456 340 540; fax: 020 7793 2639
email: mdf@mdf.org.uk
web: www.mdf.org.uk
UK Council for Psychotherapy (UKCP)
tel. 020 7014 9955
web: www.psychotherapy.org.uk
Maintains a voluntary register of qualified psychotherapists
Yellow Card Scheme
hotline: 0808 100 3352 (business hours)
web: www.yellowcard.gov.uk
For reporting side effects and withdrawal effects of drugs. Also has a translation service for those whose first language is not English
www.comingoff.com
Advice on coming off psychiatric medicines
www.depressionalliance.org
Information about depression and local self help groups
www.dh.gov.uk
For the MHRA Medicines use review: understand your medicines leaflet. http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/
PublicationsPolicyAndGuidance/DH_4126843
http://emc.medicines.org.uk
Electronic Medicines Compendium - for Patient Information Leaflets and data sheets on most prescribed drugs, including the half-lives of individual drugs.
http://medguides.medicines.org.uk
Medicines Information Project for Medicine Guides on individual drugs
www.mhra.gov.uk
Medicines and Healthcare products Regulatory Agency (MHRA) (and Commission on Human Medicines)
www.nice.org.uk
Clinical guidelines on conditions and treatments
The bipolar disorder survival guide D Miklowitz (Guilford 2002)
A lifelong journey: staying well with manic depression/bipolardisorder
Coming off psychiatric drugs: successful withdrawal from neuroleptics, antidepressants, lithium, carbamazepine and tranquillisers ed. Peter Lehmann (Peter Lehmann Publishing 2004)
How to cope with suicidal feelings (Mind 2008)
Inside out: a guide to the self-management of manic depression (MDF The Bipolar Organisation 1995)
Making sense of antidepressants (Mind 2008)
Making sense of antipsychotics (Mind 2007)
Making sense of coming off psychiatric drugs (Mind 2005)
Mind guide to food and mood (Mind 2008)
Mind rights guide 3: consent to medical treatment (Mind 2009)
Overcoming mood swings Jan Scott (Robinson 2001)
Toxic psychiatry: a psychiatrist speaks out Peter Breggin (Harper Collins 1993)
Understanding bipolar disorder (Mind 2009)
Understanding depression (Mind 2008)
Understanding schizoaffective disorder (Mind 2003)
Understanding self-harm (Mind 2007)
Your drug may be your problem: how and why to stop taking psychiatric medications Peter Breggin and David Cohen (Da Capo Press 2007) Sarah Russell (Michelle Anderson Publishing 2005)
For a catalogue of publications from Mind, send an A4 SAE to:
Mind Publications
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tel. 0844 448 4448
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email: publications@mind.org.uk
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This booklet was written by Katherine Darton
First published by Mind 2004 © Mind 2009
ISBN: 978-1-874690-04-7
No reproduction without permission