Lithium and other mood stabilisers

About mood stabilising drugs

What should I know before taking these drugs?

Informed consent
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 benefits and possible harms of the treatment, and any alternatives to it. 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 consent to medical treatment.

Patient information leaflets (PIL)

Prescribed medication should come with a patient information leaflet. If you are 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 including:

• the trade and general (generic) names of the drug
• the strength of the medicine
• 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, such as before food, or at night
• 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.

Side effects
The frequency of possible side effects listed in PILs is defined using the following system:

These categories are used in this booklet, under the individual drugs, when this information is available. (It is not available for lithium or valproate.) The side effects listed are those reported during research when the drug was being developed, and those reported by people taking it since. It is important to report side effects to the Medicines and Healthcare products Regulatory Agency (who license the drugs), especially if the effects are troublesome and are not already listed in the PIL. You can do this using a Yellow Card, either online (yellowcard.gov.uk)  or on a card which you should be able to get from your pharmacist.

Further information from your doctor or pharmacist

The PIL contains only the most important information you need to know about the medicine and if you need to know more, you should ask your doctor or your pharmacist.

Many people would like to have the information about their medicine before they receive it at the pharmacy. You might like to make a list of questions to ask your doctor, when your prescription is written, such as whether the medication is likely to make you sleepy, whether you should take it with meals, and whether you are likely to have problems coming off it.

You can also talk 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). Many high-street chemists have space set aside where you can talk privately.

Note: This 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 for Health and Care Excellence) guidelines on the treatment of bipolar disorder use 'anti-manic' for drugs used to treat manic episodes, and 'prophylactic' (meaning protective) for those used for long-term treatment. For many people these are the same drugs.

How they are prescribed

Note on drug names
A drug can have two types of names: the 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 them in brackets.

Which drugs are mood stabilisers and what are they used to treat?

Mood stabilisers

The drugs that are used as mood stabilisers are:

• lithium salts (Camcolit, Liskonum, Li-liquid, Priadel)
• anticonvulsant drugs: valproate semisodium (Depakote), carbamazepine (Tegretol), and lamotrigine (Lamictal) – originally made for treating epilepsy.

Mood stabilisers are licensed to treat:

• bipolar disorder (manic depression)
• recurrent (sometimes called 'unipolar') depression
• schizoaffective disorder
• aggression and self-harm (lithium only).

Some mood stabilisers may also be used for other conditions, at a doctor's discretion.

Drugs for bipolar disorder

For people with a diagnosis of bipolar disorder, the NICE guidelines on treatment say that lithium, olanzapine (an antipsychotic drug) or valproate should be considered for long-term treatment.

Drugs for manic episodes

Other drugs licensed to treat manic episodes are the antipsychotics olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify) and risperidone (Risperdal) which may be combined with lithium or valproate.

Research suggests that antipsychotics may be more effective for manic episodes than lithium or anticonvulsants, and the most effective and acceptable antipsychotics for mania are risperidone and olanzapine. These drugs may not be so suitable for long-term preventive treatment, but NICE suggests that they may be used as preventive treatment in pregnancy, in preference to anticonvulsants or lithium.

Asenapine (Sycrest), a new antipsychotic for treating manic episodes in bipolar disorder, was licensed in the UK in 2012.

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.

Your heart function should be checked (by ECG) before you start taking an antipsychotic, and repeated periodically while you are taking it, because all of these drugs may have effects on heart rhythm. For more information see antipsychotics.

Drugs for depression

Quetiapine is an antipsychotic licensed for the treatment of depression in bipolar disorder.

Antidepressants may be suggested to treat depressive episodes, but should be used with caution as they may cause manic episodes in some people. There is some evidence that if you take SSRI antidepressants for bipolar depression you are more likely to experience rapid switching between mania and depression, and multiple episodes, and this may continue if you stop the antidepressants. For more information see antidepressants.

How do I know which type of medicine might be suitable for me?

The choice should depend on:

• your response to treatments in the past
• the risk of an episode, and what has triggered episodes in the past
• your physical health, especially kidney disease, weight problems and diabetes
• your preference, and how likely you are to take the medication consistently
• gender (valproate should not be prescribed for women who might become pregnant)
• in older people, a test of mental processes such as the one used to diagnose dementia.

If the drug does not work well for you or suit you, you might need to try a different one, or the doctor may suggest you take two together.

How long will I have to take the medication?

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. Assuming you have no problems with it, you may 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 coming off psychiatric drugs for more information.

Lithium

What is lithium?

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 substances that occur naturally in our bodies and therefore have no effect. Lithium is not a vital substance for the human body, and you are not prescribed it because you have not got enough of it; in fact it is poisonous in large amounts. It must therefore be used with care, and the dosage carefully monitored.

In the UK, lithium carbonate comes in tablet form under the names Camcolit, Lithonate, Liskonum, and Priadel. Lithium citrate comes in liquid form as Li-liquid and in tablets or liquid as 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. If you have to change brands for any reason, you should have blood tests to check your blood levels.

Patient lithium pack: This is a set of guidelines for healthcare professionals on Safer lithium therapy, and a Lithium Pack for people taking lithium, which includes information, a record book for keeping track of your blood tests, kidney and thyroid tests, weight and so on, and a Lithium Alert Card. Having your own record book means that you can remind your doctor, if necessary, when your tests are due. You should carry your Lithium Alert Card with you, and show it to any health professional who is treating you for any condition, including the dentist.

When is lithium prescribed?

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:

• manic episodes that follow a repeating pattern, in which episodes of mania and depression are followed by stable periods
• people who have a family history of bipolar illness
• forms of the problem where there is no rapid cycling between mania and depression.

Lithium is less satisfactory if you mainly have episodes of depression (sometime called unipolar depression). It may be considered as an option if you have had three, or more, periods of serious depression within five years, when you were admitted to hospital – especially if you had symptoms of psychosis. However, in these situations, people often experience repeated episodes, even with lithium treatment.

What sort of tests should I have if I am taking lithium?

If you are prescribed lithium, you should have the following tests before you start taking it, to make sure that your body systems are functioning well enough to tolerate it.

• a heart function test (ECG)
• a kidney test – because lithium is eliminated from your body in the urine and can cause changes in how the kidneys function
• a thyroid test – an overactive or underactive thyroid gland may cause symptoms that resemble mania or depression; or lithium may interfere with thyroid function.

The 2006 guidelines from the National Institute for Health and Clinical Excellence (NICE) set out clear standards for lithium monitoring, including measurement of blood lithium concentrations every three months and thyroid and kidney function tests every six months. Test results should be recorded in your lithium record book (see above), as well as your medical records, and you should have this with you when you see your GP or psychiatrist.

Blood tests

You will need to have regular blood tests to check the level of lithium in your blood to make sure the dose you are taking is both effective and safe. The dose needs to be carefully adjusted, because if you don't take enough it doesn't work, but too much is dangerous. 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 your 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.

Your doctor may also ask for a blood test if there are signs that you are getting manic or depressed, in case this is because your lithium level is too low; or if you are getting more adverse side effects (a sign that the lithium level may be too high).

A recent review of research also suggests that the level of calcium in the blood should be tested regularly as well, as lithium can cause this to increase, and one symptom of this is depression.

What dose should I be on?

There is no standard dose of lithium, because the amount of lithium in your blood depends on your kidney function, and this varies from person to person. Doses are adjusted to keep the blood level within a range of 0.4-1.0 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. 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 excreted more slowly in older people, they are particularly likely to get serious side effects and so often take half the standard dose range.

Some people take their lithium in divided doses, several times a day. Others take a modified-release version as a single dose, usually at night. 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. Once your dosing pattern is agreed, it's a good idea to take your lithium at a regular time each day.

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 talking to you doctor. Always contact your doctor immediately if you think your lithium level may be too high.

Missing a dose

Don't double up a dose of lithium if you forget to take one. 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 take your next dose at the regular time.

Will lithium affect any other medicines I might be taking?

Before prescribing lithium or any medication, your doctor should know about 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 Alert Card and remember to carry it 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. Make sure the doctor prescribing lithium knows if you are taking any of these.

Taking antipsychotic drugs with lithium may increase some of the side effects, such as muscular disorders. 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.

Lithium and haloperidol are often given together during a manic phase, because lithium can be slow to take effect. In this case, haloperidol is normally started at a lower dose than usual. Amisulpride, haloperidol, pimozide, and sertindole with lithium can cause serious problems with heart rhythm.

SSRI antidepressants (such as Prozac) can also affect the central nervous system, if combined with lithium. This can also increase the risk of serotonin syndrome, which causes high temperature, trembling and fits.

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.

What else do I need to know about taking lithium?

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.

Salt and water

Because lithium is chemically very similar to sodium, how much salt and water you have affects the way that it is removed from your body. Therefore, you need to try and stick to whatever is a normal amount of water and salt for you, to ensure that lithium stays at a safe and effective level.

• Fluids

The important thing is not to drink too much or too little fluid. You should drink about the same amount 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 if you feel thirsty, have a drink when you need to.

Avoid sudden changes in the amount you drink of coffee, tea, cola 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.

• Salt

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 to stop taking lithium temporarily, 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.

How long does lithium take to work?

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 mania or depression. 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.

What are the side effects?

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, many people cope very well with taking lithium in the long term, but some have complained that it makes them less able to express themselves and that it dampens down their imagination.

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 in your body, and that you need instant attention to avoid serious poisoning.

Unfortunately, data on the likelihood of getting the following side effects is not published for lithium.

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 the toilet more often; increased thirst; a metallic taste in the mouth; putting on weight.

Intermediate side effects

These continue 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 the toilet 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 your heart. Overactive parathyroid (a small gland next to the thyroid) which may cause back pain, blurred vision, depression and tiredness.

Always report a skin rash or widespread itching at once, since it may be the sign 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:

• Decreased thyroid function (hypothyroid) – this is more common

Symptoms include: sleepiness, tiredness, slowed thinking, depression, feeling cold, headaches, dry skin, constipation, aching muscles, weight gain.

• Increased thyroid function (hyperthyroid)

Symptoms include: nervousness, fast heartbeat, feeling emotional, feeling hot and being uncomfortable in the heat, sweating.

These conditions may be treated with appropriate thyroid medications, or you may be advised to come off lithium. Women who start lithium between the ages of 40 and 59 are more likely than men to develop an underactive thyroid; as one of the main symptoms is depression, this may easily be missed.

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 serious side effects (see below).

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, 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 death.

How long will I have to be on lithium for?

This will vary from person to person, depending on your symptoms, and it's something to discuss with your doctor at the beginning. Lithium is not a cure for bipolar disorder, but is mostly used as a preventive medicine. In this case you are usually expected to take it for at least two years, and doctors may suggest that you need to take it for the rest of your life. But you may find that after it has successfully treated a manic episode, you do not need to continue to take it; and you may find it does not suit you, and come off it after a shorter time.

Psychiatric research shows that a large number of people who have been taking lithium for some time will relapse if they stop taking it, but this may be because they have withdrawn too quickly. Some withdraw successfully, while others who have had difficulty with withdrawal decide that they 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.

What's the best way to withdraw?

There is no evidence to indicate that people taking lithium become physically dependent on it, but some people find their original symptoms coming back when they stop taking lithium, or they may have an episode of 'withdrawal mania'. It is therefore important 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 suggest that if lithium has to be stopped abruptly, prescribers should consider replacing it with an antipsychotic drug or valproate.

Other mood stabilisers

Anticonvulsants

Which anticonvulsant drugs are used as mood stabilisers?

There are two anti-epileptic drugs that are well-established treatments licensed for mania and as mood stabilisers:

• carbamazepine (Tegretol, Tegretol Retard, Carbagen Retard)
• valproate as semisodium valproate (Depakote). Sodium valproate (Epilim) – containing more sodium – is also sometimes used.

Carbamazepine and valproate are not suitable for recurrent depression.

A third anticonvulsant has antidepressant effects and is licensed for preventing depressive episodes in bipolar disorder:

• lamotrigine (Lamictal)

When are anticonvulsants prescribed?

Anticonvulsant drugs are most effective in treating:

• mixed episodes of mania and depression
• rapid cycling
• people who have little or no family history of bipolar disorder
• very severe mania with psychosis
• additional anxiety disorders or substance abuse
• symptoms that occur after neurological illness or brain injury.

For people who have recurrent depression, NICE guidelines suggest lamotrigine should be tried.

Valproate semisodium (Depakote)

Valproate semisodium is licensed for the treatment of manic episodes in bipolar disorder, as an alternative to lithium.

When not to take valproate
You should not take valproate if you have liver disease or have a family history of liver disease. (You should have a liver function test before starting treatment, and liver and kidney function and blood should be checked regularly.)

You should not take it if you are a woman and might become pregnant (see below).

Cautions
You should be cautious about taking valproate if you have kidney problems. 

Side effects of valproate
Unfortunately, data on the likelihood of getting these side effects is not published for valproate.

The most common side effects of valproate are: feeling or being sick (it may help if you take the drug with food), stomach pain, which may be severe, unsteadiness, shaking, loss of appetite, hair loss (it grows back if you stop the medication).

Less common effects are: fluid retention (puffy hands and feet), blood disorders (may cause bruising or bleeding), getting more infections than usual (due to effects on your white blood cells), yellowing of eyes and skin, 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 in men, hearing loss, abnormal kidney function (resulting in the loss of essential minerals), skin ulceration or blistering, hairiness, acne, bed-wetting, weight gain, pancreatitis, tiredness and loss of energy, hallucinations and confusion, movement disorders (Parkinsonism, tics), very severe rash with high temperature.

Taking valproate with other medicines
Valproate may increase the levels of MAOI (monoamine oxidase inhibitor) and tricyclic antidepressants in the blood. 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 valproate is prescribed.

Dose
Valproate comes as tablets which should be swallowed whole and not crushed or chewed.

Initially 750mg/day in two to three divided doses (as 250mg, 3 times/day), 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 'Children and mood stabilisers' under 'During pregnancy and for children').

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 porphyria (an inherited condition affecting body chemistry). 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

(very common) reduced white blood cells, meaning that you catch infections more easily; dizziness and tiredness; feeling unsteady or finding it difficult to control movements; feeling or being sick; changes in liver enzyme levels (usually without any symptoms); skin reactions which may be severe.

(common) Blood changes and bruising or bleeding more easily; fluid retention and swelling of hands, ankles, feet or lower legs; weight increase; low sodium in the blood which might result in confusion; headache; double or blurred vision; dry mouth.

 (uncommon) Involuntary movements including shaking or tics; abnormal eye movements; diarrhoea; constipation.

(rare) Disease of the lymph glands; folic acid (a vitamin) deficiency; an allergic reaction including rash, joint pain, fever, problems with the kidneys and other organs; hallucinations; depression; loss of appetite; restlessness; aggression; agitation; confusion; speech disorders; numbness or tingling in the hands and feet; muscle weakness; high blood pressure (which may make you feel dizzy, with a flushed face, headache, fatigue and nervousness); low blood pressure (the symptoms of which are feeling faint, light headed, dizzy, confused, having blurred vision); changes to heart beat; stomach pain; liver problems including jaundice (yellowing of your skin or the whites of your eyes); pain in your joints and muscles, a rash across the bridge of the nose and cheeks and problems with breathing (these may be the signs of a rare reaction known as lupus erythematosus).

(very rare) Blood changes including anaemia; porphyria (an inherited metabolic condition); meningitis (inflammation of the brain); breast development and milk production which may occur in both men and women; abnormal thyroid function; loss of bone minerals (which may be noticed as pain on walking and bow legs); osteoporosis (weakened bones); increased blood fat levels; taste disturbances; conjunctivitis (sore eyes); glaucoma (increased pressure in the eyes); cataracts; hearing disorders; heart and circulatory problems including deep vein thrombosis (DVT), the symptoms of which could include tenderness, pain, swelling, warmth, skin discoloration and prominent superficial veins; lung or breathing problems; rashes, red skin, blistering of the lips, eyes or mouth, or skin peeling with high temperature (these reactions may be more common if you are of Chinese or Thai origin); sore mouth or tongue; liver failure; increased sensitivity of the skin tosunlight; alterations in skin pigmentation; acne; excessive sweating; hair loss; increased hair growth on the body and face; muscle pain or spasm; sexual difficulties which may include reduced male fertility, loss of libido or impotence; kidney failure; blood spots in the urine; increased or decreased desire to pass urine or difficulty in passing urine.

Taking 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
Carbamazepine comes as tablets, chewtabs, liquid, and suppositories. The modified release forms are all tablets.

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.

If you are taking carbamazepine, you should have regular checks of blood levels of the drug to make sure they are safe and effective.

Withdrawal
There is almost no evidence on possible withdrawal symptoms when coming off carbamazepine. You should withdraw gradually to minimize the possibility of withdrawal effects.

Lamotrigine (Lamictal)

Lamotrigine is licensed in the UK for treating depression in bipolar disorder.

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. (If you have anaemia you will feel tired and the inside of your eyelids will be very pale.)

(very common) headache, skin rash.

 

(common) agitation, aggression, irritability, sleepiness, tiredness, dizziness, shaking, insomnia, dry mouth, joint pain, back pain, feeling or being sick, diarrhoea.

(uncommon) blurred vision, double vision; problems with balance and coordination.

(rare) Stevens-Johnson syndrome (see above), inflamed eyes (conjunctivitis), uncontrolled eye movement (nystagmus); confusion, hallucination, muscle tics; liver problems.

(very rare) Symptoms similar to lupus; toxic epidermal necrolysis; blood disorders; hypersensitivity (leading to multi-organ failure); inflammation of the brain.

(frequency unknown) swollen glands

 

Taking 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
Lamotrigine comes as standard tablets and dispersible tablets.

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.

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.

Asenapine (Sycrest)

Asenapine is a new antipsychotic for manic episodes. At the time of writing, it is licensed only for moderate to severe manic episodes in bipolar disorder, and not for other psychoses.

Cautions
You should not take asenapine if you have severe liver problems, and it is not suitable for people with dementia. It may cause low blood pressure, so may not be suitable if you have heart disease or already have low blood pressure. It also may not be suitable if you have diabetes, Parkinson's disease, epilepsy (fits), difficulty swallowing, poor temperature regulation, or you sometimes have thoughts about suicide.

Side effects

(very common) anxiety, feeling very sleepy

 

(common) weight gain and increased appetite; muscle spasms, extreme restlessness, Parkinsonism, and involuntary movements; feeling showed down; dizziness; unusual taste sensations; numb lips and mouth; raised liver enzymes; stiff muscles; feeling tired.

(uncommon) raised blood sugar; fainting; fits; abnormal muscle movements, including tics, shaking, spasms of eye muscles, slowed movements; difficulty speaking; slow heart beat, changes to heart rhythm; low blood pressure; swollen tongue, difficulty swallowing, burning or tingling sensations in your tongue and mouth; sexual problems (in men and women) and loss of menstrual periods.

(rare) changes in level of white blood cells; neuroleptic malignant syndrome (confusion, loss of consciousness, high temperature and severe muscle stiffness); blurred vision; blood clot on the lung; muscle damage with aches and pains; breast development and milk production (this can affect men as well as women).

(frequency unknown) allergic reactions (anaphylactic shock) with difficulty breathing, swollen tongue or throat, skin rash, itching and increased heart rate. This is a medical emergency.

Asenapine is a new drug, so it is especially important to report any side effects you experience which are not listed above to the MHRA.

Dose
It comes as a rapidly dissolving tablet which you put under your tongue. You should not take it out of its foil until you are ready to take it, and you should handle it gently, with dry hands.

The usual starting dose of asenapine is 10mg twice a day if you are taking asenapine on its own, which may be reduced to 5mg; and 5mg if you are taking something else as well.

Withdrawal
There is no published information on withdrawal of asenapine. As with other antipsychotics, it is advisable to withdraw gradually if you have been taking it for more than two weeks.

During pregnancy and for children

Mood stabilising drugs during pregnancy, childbirth and breastfeeding

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. As asenapine is a new drug, there is very little evidence on its safety in pregnancy. Newborns who have been exposed to asenapine in the last three months of pregnancy show side effects in the first weeks of life, including agitation, abnormal muscle tone, tremor, extreme sleepiness, breathing problems, and difficulty feeding.

What are the risks of taking anticonvulsants during pregnancy?

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:

• Carbamazepine taken in the first three months of pregnancy increases the risk of spina bifida and related conditions; the risk may be reduced by taking folate supplements. In the last three months of pregnancy there is a risk of vitamin K deficiency in the infant, who should be monitored closely for signs of bleeding.
• Valproate should be avoided in pregnancy as it may cause defects and delay in development in the foetus. The possible harms include heart defects, spinal defects such as spina bifida, hare lip and cleft palate, malformed penis, and extra fingers or toes, as well as bleeding and liver disease in the newborn. The NICE guidelines on treatment of bipolar disorder state that valproate should not generally be given to women of child-bearing potential; if no effective alternative to valproate can be found, 'adequate' contraception should be used and women should be informed about the risk of harm to the foetus.
• Lamotrigine carries a risk of malformations, including cleft lip and palate.

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.

What are the risks of taking lithium during pregnancy?

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 some risk of malformation of the heart in the developing infant.

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 to avoid toxic effects.

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 might be an idea to wait a few weeks before trying to conceive, in case your bipolar symptoms recur and you decide you need to go back on lithium.

Unplanned pregnancy

If you find you are pregnant while you are taking lithium and it is early in pregnancy, you and your doctor might decide you should stop taking lithium immediately.

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 you and your doctor decide it's best to continue with the lithium treatment, then you 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 suggest you 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 you and the child.

Others may suggest continuing with lithium treatment until the date the baby is due or until labour begins. They may think you should continue with lithium as long as possible as a protective factor against the risk of serious mental illness (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.

Are there alternatives to taking lithium during pregnancy?

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 antidepressants, antipsychotics and 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.

What are the risks of taking mood stabilisers while breastfeeding?

You should not breastfeed 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 breastfeeding is not recommended. However the British National Formulary suggests that amounts are not considered sufficient to be harmful.

You should not breastfeed while taking asenapine.

Children and mood stabilisers

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' says that carbamazepine and valproate may be useful in children unresponsive to lithium. It gives no guidance on the use of lamotrigine as a mood stabiliser in children.

Asenapine is not recommended for anyone below the age of 18.

All drugs should be used with caution, and at doses appropriate to the child's age and size.

Useful contacts

Coming off psychiatric medication
web: www.comingoff.com

Depression Alliance 
web: www.depressionalliance.org 
Information about depression and local self-help groups

Department of Health
web: www.dh.gov.uk 
Search for the MHRA 'Medicines use review: understand your medicines'

Bipolar UK
tel. 08456 340 540 
web: www.mdf.org.uk 
Charity supporting those with bipolar, their families and carers

Electronic Medicines Compendium 
web: www.medicines.org.uk/emc
Patient Information Leaflets on individual drugs

Medicines and Healthcare products Regulatory Agency 
web: www.mhra.gov.uk 
The body which licenses drugs for use in the UK

National Institute of Health and Clinical Excellence
web: www.nice.org.uk 
Clinical guidelines on conditions and treatments

Yellow Card Scheme
hotline: 0808 100 3352 (business hours) 
web: www.yellowcard.gov.uk 
Report drug side effects and withdrawal effects to the MHRA

Published 2012 
To be revised 2014
See our guidance on reproducing information