Tricyclic antidepressants (TCAs) are a group of medicines which have been available for many years. They include amitriptyline (Lentizol, Tryptizol), amoxapine (Asendis), clomipramine (Anafranil), dothiepin (Prothiaden), doxepin (Sinequan), imipramine (Tofranil), lofepramine (Gamanil), nortriptyline (Allegron), protryptyline (Concordin), and trimipramine (Surmontil). They are often used to treat depression, but are also used to treat other problems, including anxiety, panic, pain, and irritable bowel syndrome. Until the introduction of selective serotonin reuptake inhibitors (SSRIs), they were the most commonly prescribed type of antidepressant.

Their effects

How they work
Our brains contain chemicals called neurotransmitters. In depression, the levels of certain neurotransmitters can be disturbed. TCAs help to return the levels of these chemicals towards normal, by reducing their uptake into brain cells.

How well they work
There has been a lot of research done on the use of tricyclics for the treatment of depression. The research shows that tricyclics work as well as another type of antidepressants, the SSRIs, in the initial treatment of depression. They also work as well as cognitive behavioural therapy (CBT), a psychological treatment. Patients who are depressed and have physical illness also benefit from the use of TCAs.

To work, antidepressants need to be taken regularly, as prescribed. It may take two weeks or more for improvement to be noticed. Evidence seems to show that TCAs should be taken regularly for at least four months after recovery from the depression to prevent the illness from returning. A review of the evidence for this area is due to be published soon.

It is likely that drinking alcohol will prevent recovery from depression.

If the depression has not improved after 6 weeks of taking a tricyclic regularly at a full dose, changing to another type of antidepressant, such as an SSRI, may help. Tricyclics reduce the risk of relapse in people who have had two or more episodes of depression. However, it is unclear for how long preventative treatment should be continued.

Who should take them
Tricyclics are a useful treatment for many people with depression. This includes people with: depression; dysthymia; depression and a physical illness; who have had more than one episode of depression, who may benefit from taking tricyclics long-term as a preventive measure. There are several treatments available for depression, with different side-effects. Therefore, people may prefer other antidepressants (SSRIs or monoamine oxidase inhibitors (MAOIs)), herbal remedies such as St John's wort, or psychological treatment such as CBT.

Their side-effects

Side-effects
Some people suffer from side-effects when they take tricyclics. The common side-effects are shown in the table below. These often settle after a few days. Therefore, if the side-effects are tolerable, it is worth continuing to take the medicine. If in doubt, see your doctor. Building the dose up slowly over several days can minimise side-effects.

Tricyclics have a different range of side-effects to the SSRIs. They are also slightly less well tolerated:

	% of patients who experience side effect
Side effect	SSRI	TCA
Dry mouth	21%	55%
Constipation	10%	22%
Dizziness	13%	23%
Nausea	22%	12%
Diarrhoea	13%	5%
Anxiety	13%	7%
Agitation	14%	8%
Insomnia	12%	7%
Nervousness	15%	11%
Headache	17%	14%

In addition to the side-effects in the table, blurred vision and drowsiness are also common complaints. Evidence comparing the likelihood of these side effects when taking SSRIs and TCAs is not currently available.

Some tricyclics (e.g. lofepramine) have less side-effects than others (e.g. amitriptyline). This is why tricyclics are usually taken before bedtime. People taking tricyclics who are drowsy or have blurred vision should not drive or work machinery. If these side-effects persist and cause problems, discuss other treatment options with your doctor. Of course, one benefit of the side-effect of drowsiness is that it can improve sleep, which is often disturbed in depression.

Tricyclics should not be stopped suddenly as this may cause withdrawal side effects. Consult your doctor, who will advise you how to stop them.

Tricyclics are not addictive.

Who should avoid taking them
Some tricyclics (such as dothiepin and amitriptyline) are very dangerous in overdose. Therefore, patients who are highly suicidal should either not take these tricyclics or should be closely supervised while doing so. Other tricyclics (such as lofepramine) are safer in overdose, as are SSRIs.

Patients who have had a recent heart attack, have certain heartbeat abnormalities, have severe liver disease, or are taking MAOIs, should not take tricyclics.

Tricyclics should be used carefully in:

• the elderly
• people with epilepsy, thyroid disease, liver disease or closed-angle glaucoma
• people with a history of psychosis, mania, or urinary retention
• pregnant or breast-feeding women
• people who drink excessive alcohol