TREATMENTS FOR DEPRESSION

Drugs known as antidepressants

DRUG GROUP: THE TRICYCLIC ANTIDEPRESSANTS

‘Motipress’ and ‘Motival’ contain a small amount of nortriptyline and fluphenazine.

1. Dothiepin is changing name to dosulepin from 1998 onwards, although both are still in use.

What are the tricyclics used for ?

Tricyclic antidepressants are used to improve mood in people who are feeling low or depressed. The tricyclics may also be used to help the symptoms of anxiety and a number of other symptoms. The tricyclics are the most commonly prescribed antidepressants but there are many other antidepressants. All these drugs seem to be equally effective at the proper dose but have different side effects to each other. If one drug does not suit you, it may be possible to try another.

How do the tricyclics work ?

The brains has many naturally occurring chemical messengers. Two of these are called serotonin (sometimes called 5-HT) and noradrenaline. Both are important in the areas of the brain that control or regulate mood and thinking. It is known that these two chemical messengers are not as effective or active as normal in the brain when someone is depressed. Tricyclic antidepressants increase the amount of these chemical messengers in the brain. This can help correct the lack of action of these messengers and help to improve mood. The tricyclics can also effect another chemical in the brain called "acetylcholine" and this is the cause of some of their side-effects. For a more detailed explanation, click here.

How should I take them ?

Tablets and capsules:

Tablets and capsules should be swallowed with at least half a glass of water whilst sitting or standing. This is to make sure that they reach the stomach and do not stick in the throat.

Liquids:

Your pharmacist should give you a medicine spoon or oral syringe. Use it carefully to make sure you measure the correct amount. Ask your pharmacist for a medicine spoon if you do not have one. Shake the bottle well before use as the drug can settle to the bottom and cause you to get too low a dose at the start and too high a dose at the end of the bottle. Your mouth may feel a little numb after taking one of these liquids as it can have a local anaesthetic effect. This is common and nothing to worry about.

If it is necessary for you to have an injection it will be given by a nurse or doctor.

When should I take my tricyclic ?

Take your medication as directed on the medicine label. Try to take it at regular times each day. Taking it at mealtimes may make it easier to remember as there is no problem about taking any of these drugs with or after food. If the instructions say to take them once a day this is usually best at bedtime as they may make you drowsy at first. They are not, however, sleeping tablets.

How long will the tricyclics take to work ?

It may take as long as two weeks or more before the tricyclics start to have any effect on your mood, and a further three or four weeks for this effect to be reaching its maximum. Unfortunately in some people the effect may take even longer to occur e.g. several months, especially if you are older.

How long will I need to keep taking the tricyclic for ?

This should be discussed with your doctor, as people respond differently. Some people may need to continue taking them for months or even years. It is usually necessary to take them for at the very least a month after you have got better. However, it is usually best to take them for at least 6 to 12 months to make sure you are fully over your illness. If you have been depressed more than once, it is best to keep taking an antidepressant for several years as this will reduce the chance of you becoming ill again. This graph may aid your decisions:

Are the tricyclics addictive ?

Tricyclics are not addictive, but if you have taken them for eight weeks or more you may experience some mild "discontinuation" effects if you stop them suddenly. These do not mean that the antidepressant is addictive. For a drug to be addictive or produce dependence, then it must have a number of characteristics:

• should produce craving for the drug when the last dose "wears off"
• should produce tolerance ie you need more drug to get the same effect
• there should be an inability to cut down or control use
• should produce withdrawal symptoms
• there should be continued use of the drug despite knowing of harmful consequences

Thus antidepressants, if stopped suddenly, may produce some "discontinuation" symptoms but these are more of an "adjustment" reaction from sudden removal of a drug rather than withdrawal. For further discussion, click here.

Can I stop taking the tricyclics suddenly ?

It is unwise to stop taking them suddenly, even if you feel better. Two things could happen. Firstly, your depression can return if treatment is stopped too early (see "How long will I need to keep taking them for?"). Secondly, you might also experience some mild "discontinuation" symptoms (see also above). At worst, these could include headache, restlessness, diarrhoea, nausea, 'flu-like symptoms, lethargy, abdominal cramps, sleep disturbance and mild movement disorders. They can start shortly after stopping or reducing doses, are usually short lived, will go if the antidepressant is started again and can even occur with missed doses.

If you get these discontinuation symptoms, you have a number of options:

• If they are not severe, you can wait for the symptoms to go - they usually only last for a few days or weeks
• Ask for something to help your symptoms in the short-term e.g. a sedative or sleeping tablet
• Start the medication again (the symptoms should go) and then try reducing the dose more slowly over a longer time e.g. reduce the dose by about a quarter (25%) every 4-6 weeks
• Switch to another antidepressant - this sometimes helps

When the time comes your doctor should withdraw the drug slowly e.g. by reducing the dose gradually every few weeks. You should discuss this with your doctor.

What should I do if I forget to take them ?

Start again as soon as you remember unless it is almost time for your next dose, then go on as before. Do not try to catch up by taking two or more doses at once as you may get more side-effects. You should tell your doctor about this next time you meet.

If you have problems remembering your doses (as very many people do) ask you pharmacist, doctor or nurse about this. There are some special packs, boxes and devices which can be used to help you remember.

What sort of side-effects might occur ?

Table adapted from UK Psychiatric Pharmacy Group leaflets, with kind permission (www.ukppg.org.uk )

Do not be worried by this list of side effects. You may get none at all. There are other rare side-effects. If you develop any unusual symptoms ask your doctor about them next time you meet.

*If you are taking protriptyline ("Concordin") tablets you should avoid exposure of your skin to direct sunlight. This drug makes the skin extremely sensitive to sunlight causing it to go red and burn very easily. If you do go out in the sun make sure you put on a high factor sunscreen first (such as Roc Total Sun Block). Sunbeds and sunlamps are very likely to cause such a reaction and should be avoided.

Will the tricyclics cause me to put on weight ?

Although a few people can lose weight on tricyclic antidepressants, some gain weight. This is partly due to an increased in appetite and/or a craving for sweet food caused by the drugs. It may also be that the drugs reduce your metabolism, so that you do not metabolise food as quickly. So, not only do you eat more, you use the food less well. It is impossible to know what the effect on your weight may be because each person will be affected differently. Unfortunately all the tricyclic antidepressants seem to have the same effect.

If you do start to put on weight or have problems with your weight, your doctor can arrange for you to see a dietician for advice. Any weight you put on can be controlled while you are still taking this medication, with expert advice about diet. In some people this weight gain can be a serious problem. If it causes you distress make sure your doctor knows about this. A change in drug e.g. to a different type of antidepressants, or change in dose may be necessary in extreme cases. Your doctor can arrange for you to see a dietician.

Will it affect my sex life?

Drugs can affect desire (libido), arousal (erection) and orgasmic ability. The tricyclics are know to affect all three stages in some people. Lack of desire and delayed orgasm is known to occur, although the opposite has been reported rarely as well. If this does seem to have happened, you should discuss this with your doctor, as a change in dose, timing or drug may help minimise any problem. Any problem is reversible.

Will the tricyclics make me drowsy ?

These drugs may make you feel drowsy. You should not drive (see below) or operate machinery until you know how they affect you. You should be careful as they may affect your reflexes reaction times. They are not, however, sleeping tablets, although if you take them at night they may help you get to sleep.

Can I drink alcohol while I am taking these ?

You should avoid alcohol while taking these drugs as it may make you feel more sleepy. This is particularly important if you need to drive or operate machinery and you must seek advice on this.

Are there any foods or drinks that I should avoid ?

You should have no problems with any food or drink other than alcohol (see above).

Will they affect my other medication ?

You should have no problems if you take other medications although a few problems can occur. The tricyclic antidepressants can "interact" with "MAOIs", some "SSRIs" (e.g. escitalopam ['Cipralex'], fluoxetine ['Prozac'], paroxetine ['Seroxat'], sertraline ['Lustral'], citalopram ['Cipramil']) and some treatments for epilepsy. This does not necessarily mean they can not be used together, just that you may need to follow your doctors instructions very carefully. Make sure your doctor knows about all the medicines you are taking. Some other medicines e.g. antihistamines can make you drowsy. Combined with your tricyclic antidepressant this could make you even drowsier. There has been much concern about the safety of St. John's wort with antidepressants. Until more information is available, you should avoid taking St. John's wort along with any other antidepressant. You should tell your doctor before starting or stopping these or any other drugs.

If I am taking a contraceptive pill, will this be affected ?

It is not thought that the contraceptive pill is affected by any of these drugs.

What if I want to start a family or discover I'm pregnant?

It is important to consider that there will be a risk to you and your child from taking a medicine during pregnancy but also a possible risk from stopping the medicine e.g. getting ill again. Unfortunately, no decision is risk-free. It will be for you to decide which is the least risk. All we can do here is to help you understand some of the issues, so you can make an informed decision. For your information, major malformations occur "spontaneously" in about 2-4% of all pregnancies, even if no drugs are taken. The main problem with medicines is termed "teratogenicity" i.e. a medicine causing a malformation in the unborn child. A medicine causing teratogenicity is called a "teratogen". Since a baby has completed it's main development between days 17 and 60 of the pregnancy (the so-called "first trimester") these first 2-16 weeks are the main concern. After that, there may be other problems e.g. some medicines may cause slower growth. The infant may also be affected after birth e.g. withdrawal effects are possible with some drugs.

If possible, the best option is to plan in advance. If you think you could become pregnant, discuss this with your doctor and it may be possible to switch to medicines thought to carry least risk, and take other risk-reducing steps e.g. adjusting doses, taking vitamin supplements etc. If you have just discovered you are pregnant, don't panic, but seek advice from your GP within the next few days if possible. He or she may also want to refer you on to someone with more specialist knowledge of your medicine.

Very few medicines have been shown to be completely safe in pregnancy and so no manufacturer or advisor can ever say any medicine is safe. They will usually advise not to take a medicine during pregnancy, unless the benefit is much greater than the risk. In the UK, there is the NTIS (National Teratology Information Service) who offer individual risk assessments. However, their advice should always be used to help you and your doctor decide what is the risk to you and your baby. There is a risk from taking the medicine and a risk should you stop a medicine e.g. you might become ill again and need to go back on the medication again. The advice offered here is just that i.e. advice, but may give you some idea about the possible risks and what (at the time of writing) is known through the medical press.

It may be helpful to know that in the USA, the FDA (Food and Drug Administration) classifies medicines in pregnancy in five groups:

The tricyclics are classified as either "C" or "D" (amitriptyline "D", amoxapine "C", clomipramine "C", doxepin "C", nortriptyline "D" and trimipramine "C"). The others are not available in the USA and so are not classified. One large study showed no evidence of a teratogenic effect and no increase in spontaneous abortions, although another study showed a very slightly increased rate of problems. Animal tests show a low risk of danger but some problems have been reported and so you should seek personal advice from your GP, who may then if necessary seek further specialist advice. There have been some reports of discontinuation effects (e.g. jitteriness) in the newborn child and so it may be possible to reduce your dose a bit before your due date. A recent study has shown no evidence of any short or long-term effects on intelligence and language development, although there was a slight reduction in the length of pregnancy (by about 6 days).

Will I need a blood test ?

Not usually. Some people who need to take higher doses occasionally need a blood test to make sure they are getting enough, but not too much, of the drug.

Can I drive while I am taking the tricyclic ?

These drugs can affect your driving in two ways. Firstly, you may feel drowsy and/or suffer from blurred vision at first when taking any of these drugs. Secondly, the drugs can slow down your reactions or reflexes. This is especially true if you also have a dry mouth, blurred vision, constipation etc. (the so-called "anticholinergic side effects"). Until these wear off, or you know how your drug affects you, do not drive or operate machinery. You should be careful as they may affect your reaction times or reflexes even though you feel well.

It is against the law to drive, attempt to drive or be in charge of a vehicle when unfit, either through illness or from the side effects of medication. Under UK law, it is the drivers responsibility to let the DVLA and insurance company know if you may be "unfit" to drive. If you do not, and you have an accident, it could effect your insurance cover. Your doctor will be able to advise you, and may wish to access the UK Driver and Vehicle Licensing Agency (DVLA) guidelines website, which has the current DVLA guidelines on anxiety/depression, psychotic disorders, mania and other conditions. If your doctor advises you not to drive, and you continue to do so, the doctor can inform the DVLA directly, as he or she would be lawfully responsible were you to have an accident. Once told, the DVLA may wish to carry out an enquiry, but you are entitled to drive until a decision is made.

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Information here is based on published data. References include the UK British National Formulary (BNF, published by the British Medical Association and Royal Pharmaceutical Society of Great Britain), Martindale (the extra pharmacopoea, published by RPSGB Pharmaceutical Press), Psychotropic Drug Directory (latest edition), Data Sheet Compendium (UK Manufacturers Data Sheets, published by the Association of British Pharmaceutical Industry), MicroMedex (an independent and extensive CD-ROM based drug information source), UK Psychiatric Pharmacy Group leaflets, Royal College of Psychiatrists advice and guidelines and the current medical literature. Thanks also to all those people who left e-mail comments, suggestions and requests, who have helped shape the site.