The tricyclic antidepressants

The tricyclic antidepressants have been used for many years, so their side effect profile and problems associated with their use are well known. They are also known to be highly effective when used correctly.

They are used mainly for depression, but can be used for depression with anxiety and depression associated with other medical problems such as fibromyalgia. They can also be used effectively during the depressive phase of bipolar disorder.

Some, particularly imipramine, have shown themselves to be effective in panic states and phobic disorders and they can also be used in chronic pain.

Tricyclic antidepressants act by preventing the absorption of noradrenaline and serotonin, both implicated in the development of depression. How this action is then translated into an antidepressant effect is not fully understood.

Generally antidepressants will take some time to start working. Clinical problems such as difficulties sleeping and poor appetite can start to improve within two weeks, but in general, the full antidepressant effect does not start to be evident for about six weeks. This means that it is important to give the drug a chance and not assume that it is not working if there is no immediate improvement.

Side effects of these antidepressants are related to the way in which they work and are called anticholinergic effects. The term anticholinergic refers to the type of transmitter of nerve impulses (neurotransmitter) which is affected.

The most common side effects are sedation, a dry mouth, blurred vision and difficulties passing urine. These side effects are related to the dose used and can be minimised by starting at a low dose and increasing it gradually. They will generally pass off after about one to two weeks.

They can also affect the blood pressure and heart rate, precipitate epileptic seizures, cause tremors, restlessness and weakness and allergic skin reactions, although these side effects are uncommon. Very rarely they can cause problems with the blood and the liver.

As with all antidepressants and drugs used for mental health problems generally, they can negatively affect sex drive and cause weight gain.

They are very dangerous in overdose, killing by causing major problems with the heart and blood pressure.

Some commonly used tricyclics are amitriptylene (Tryptanol®, Trepiline®), imipramine (Tofranil®) and clomipramine (Anafranil®).

Selective serotonin re-uptake inhibitors

The most famous of this class of antidepressants is fluoxetine (Prozac®). This class of drug selectively blocks the re-uptake of serotonin at the nerves in the brain, increasing the amount of serotonin in the brain, which is probably the reason they act as antidepressants. However, again, the full mechanism is not known.

They are as effective as the tricyclics in the management of depression and related problems and cause fewer anticholinergic and cardiac side effects. They also do not tend to cause weight gain to the same extent, but do still affect sex drive.

The selective serotonin re-uptake inhibitors (SSRIs) are generally well tolerated. However, there is a relatively high incidence of headache and gastrointestinal problems such as nausea, diarrhoea, dry mouth, appetite loss and heartburn.

Less common side effects are nervousness, insomnia, drowsiness, confusion and tremor. Skin rashes have been reported, as with almost every drug.

Again, it takes a few weeks before the full antidepressant effects are felt.

Other commonly used SSRIs are paroxetine (Aropax®), sertraline (Zoloft®) and citralopram (Cipramil®).

St John's Wort

This herbal preparation is increasingly used, both by people treating themselves and on the advice of doctors. It certainly seems to be effective in mild depression, but its effects in more serious cases are doubtful.

However, as with all herbal and alternative preparations, there are many misconceptions about its use. Because herbal preparations are not regulated in the same way as other drugs, the quantity of the active ingredient is not always the same in different preparations, making it difficult to know how much is needed to produce an effect.

Because the active ingredient in St John's Wort is similar in effect to the SSRIs, similar side effects may be experienced. St John's Wort is also now known to interact with many prescription drugs, so should not be taken by people using other prescription medicines unless they have discussed it with their doctor.

Self diagnosis of depression can also sometimes be a problem, since the symptoms of depression are also found in many other problems, so people may take St John's Wort inappropriately. Mild depression often does not need drug treatment in any case.

Antidepressants and pregnancy

Antidepressants are not generally recommended in pregnancy unless they are regarded as essential to the well-being of the mother - and this will also be the case for St John's Wort. Generally, the continued use of antidepressants in pregnancy is something which must be discussed in detail with the doctors looking after the woman.

In general

Few people need to be on more than one antidepressant and St John's Wort should not be taken along with prescription antidepressants. They should generally not be mixed with tranquilisers such as benzondiazepines.

In moderate to severe depression treatment should be continued for six to 12 months to prevent relapse. Antidepressants should not be stopped abruptly, but in consultation with a doctor who will suggest a way of tapering the dose.

Within the last 18 months or so it has become increasingly apparent that there is a specific withdrawal syndrome associated with SSRIs - with paroxetine causing the most problems. This will be covered in detail in a separate article.