Volume 20.4 
Oct 2004

Anti depressant drugs

What do we mean by 'depression'? And what are the principal drugs used to deal with it? Joan Meakin explains in her latest column for dispensing staff.

A medical dictionary defines .depression. as a mental state characterised by excessive sadness. It goes on to mention that activity may be agitated and restless, or slow and retarded, and that behaviour is governed by pessimistic and/or despairing beliefs with disturbance of sleep, appetite and concentration.

Each one of us experiences different moods and mood changes with times of excitement and elevated mood, and periods of sad, quiet, lower mood. These changes may occur within quite short periods of time, such as a day, and are quite normal.

A person is said to be suffering from depression when the low mood is persistent and it is accompanied by some or all of the associated conditions given in the definition above.

There is seldom a single cause but the depression may be triggered by bereavement, childbirth, an accident or chronic illness. Some types of personalities may be more prone to depression than others. Common types of depression are post natal depression, seasonal affective disorder, disthymic (chronic depression), unipolar (in response to events) and bipolar (formerly known as manic depression).

Before we examine the types of anti-depressant drugs and their mode of action we need to consider the biochemical nature of depression. A widely accepted theory is that in depression, levels of certain key chemicals in the brain are reduced or depleted.

The chemicals include 5-hydroxytryptamine (5HT), also known as serotonin, and noradrenaline, also known as norepinephrine. Chemically these compounds belong to a group called monoamines. Most drug therapy is designed to replenish the levels of these two compounds.

Antidepressant drugs are considered useful in all but the mildest acute depression.

Antidepressant drugs are classified in the BNF into types or groups:

• Tricyclic and related compounds
• Monoamine oxidase inhibitors
• Selective serotonin reuptake inhibitors
• Others

Tricyclic compounds

Some of the drugs in this group, for example amitriptyline and imipramine, have been available for many years. Other compounds such as dosulepin (previously known as diothiepen) and lofepramine are newer. Compounds such as trazodone and mianserin are new closely related drugs.

They are all thought to work by increasing levels of monoamines in the brain by inhibiting the uptake of 5HT and noradrenaline into the neurones thus leaving more of the compounds free in the synaptic areas. There are differences in the side effects of compounds. Some have stronger sedative effects and are therefore useful in the more agitated patient, and those with a less sedating action are useful in the drowsy tired patient. All may take at least two weeks to be effective.

Side effects are common and linked to the anti-muscarinic effects of these compounds. They include dry mouth, drowsiness, urinary retention, blurred vision, and constipation. They should be used with caution in patients with urine retention or prostate problems, glaucoma and liver disease (see BNF for more). Serious side effects include cardiac arrythmias and other complex cardiac problems. Overdosage is dangerous and can result in fatal cardiac events.

Monoamine Oxidase Inhibitors (MAOIs)

When 5HT and noradrenaline are released by nerve endings in the brain their action is terminated extremely rapidly by reuptake into the neurone and by enzyme action. The enzyme that breaks down these monoamines is called monoamine oxidase. Drugs are available that work by inhibiting (blocking) the action of the enzyme, thereby increasing the levels of monoamines in the synapses. These drugs are called monoamine oxidase inhibitors (MAOIs).

Unfortunately their action is not confined to the brain, and they inhibit the enzyme at other sites in the body, notably the liver. This leads to drug interactions and side effects. Tyramine, a component of many foods, is normally broken down by MAO in the liver. When the MAO is inhibited the level of tyramine in the body increases, leading to a rise in blood pressure. Patients receiving MAOIs should be given a card that warns of the dangers of taking other drugs and certain foods at the same time as MAOIs. For this reason MAOIs are not frequently prescribed.

Selective Serotonin Reuptake Inhibitors (SSRIs)

These compounds block the reuptake of serotonin (5 hydroxytriptamine) into the neurones, thus increasing levels of available 5HT. Drugs in this group are less sedating and have fewer anti muscarinic and cardiac side effects than drugs in the tricyclic group. Examples of this type of drug are fluoxetine, fluvoxamine and citalopram. They should not be prescribed for two weeks following the stopping of MAOI treatment and time should also elapse between stopping SSRI treatment and commencing MAOI treatment.

Other drugs

The BNF has a short section that you should read..

St John's Wort (Hypericum)

You may come across the above compound in health food shops and on food supplement counters in some pharmacies. You may have some patients who mention or ask about using it for depression. Its use is controversial, unproven (although in some short term studies it has been shown to be better than placebo) and has been shown to interact with some drugs and foods; it also has interactions with commonly prescribed drugs, eg warfarin. Patients should be advised to discuss this with their GP.

Questions

You will need to read the appropriate section in the BNF and access your software system before answering the following:

1 In the tricyclics the side effect of urinary retention is made use of in the treatment of a different condition. Which drug and which condition?

2 Name two MAOIs. Find out some examples of foods that should be avoided when taking MAOIs. Look at the information leaflet to be given to patients? Is it easy to read and follow and are the warnings clear?

3 List some common side effects of SSRIs.

4 Select a drug from each group and look at these in your drug information soft ware. Note down any drug interactions and other warnings that are shown.

Answers below

For further information about the People’s College distance learning courses for dispensers please contact:

Joan Meakin,
The People’s College, Nottingham,
Maid Marion Way,
Nottingham NG1 6AB.
Tel: 0115 9128660
email: joan_meakin@peoples.ac.uk

Answers

1 The drug is imipramine and it is used to treat enuresis.

2 Examples of MAOIs include phenelzine and tranylcypromine. Foods to be avoided included cheese, Marmite, Bovril, pickled herrings, broad bean pods.

3 Common side effects of SSRIs include gastro intestinal effects, nausea, vomiting, indigestion, diarrhoea, constipation, weight loss, weight gain and rashes.