Treating depression

• Introduction - treating clinical depression

• Drugs used for depression

• Antidepressant drugs

• Other drug treatments and ECT

• Talking therapies and support

• Alternative therapies

• The future

Introduction - treating clinical depression

When a doctor diagnoses clinical depression, there are a number of possible treatment options.These will depend on how severe the depression is, how long it has been present and the extent to which it is disrupting the person's life.

It can be treated by medication, talking therapies, alternative therapies or a combination of methods. Severely depressed people may find that drug treatment is all they are offered on the NHS. Anti-depressant drugs can help people over a crisis, but talking therapies can help in understanding the depression and possibly preventing it returning. Alternative therapies and self help or support groups can also help depressed people, especially when they are over the worst and able to help themselves.

Most people recognise that emotional, social and physical factors all play a part in depression. It may be a normal reaction to life events, and many people get better on their own. But if depression continues for a long time it can cause a lot of disruption to people's lives. Depressed people can find it hard to seek help, but deciding to do something about depression is the most important step they can take.

Drugs used for depression

Antidepressant drugs

The drugs used for treating depression are called antidepressants. All of these drugs are thought to work by interacting with brain neurotransmitter systems. There are several classes of antidepressant based on their chemical and pharmacological properties.

Antidepressants usually take between two and eight weeks to work. Some experts recommend that if a 20% improvement is not seen in the first 2-4 weeks, the antidepressant should be changed. ¹ Others advise their patients to stay on a treatment for 6 months.

There is no evidence that any one antidepressant works better than another for depression. ^{2 3} 40% of people do not benefit at all from them. ⁴ About 35% of people with depression recover without any treatment. ⁵ A further group gets some help from antidepressants but continue to have some symptoms of depression. ⁶

The side effects of antidepressants are important in deciding which drug is prescribed. Other considerations are the costs of the drugs and their potential toxicity. Newer antidepressants are generally less toxic, which means they are safer in overdose. But some have the potential to cause dependence; for this reason, people considering changing or stopping antidepressants should consult their GP's.

The types of side-effects associated with the various classes of antidepressant drugs are discussed below.

Tricyclic and tetracyclic antidepressants

The tricyclic and tetracyclic antidepressants (TCAs) have been used since the 1950s when they replaced barbiturates in the treatment of depression and anxiety. All effective tricyclic antidepressants inhibit the reuptake of noradrenaline and serotonin to varying degrees; ⁷ this finding has influenced our understanding and knowledge of the biological causes of depression.

Side effects of TCAs can include:

• dry mouth, constipation, urinary retention, blurred vision and increased heart rate
• ringing in the ears (tinnitus), muscular pains
• postural hypotension - fainting or 'blacking out' when moving from lying or sitting to a standing position
• gastric irritation, weight change, allergic skin reactions and jaundice
• cardiovascular effects including irregular heart beat
• hormonal effects such as loss of libido, impotence
• manic or delusional symptoms (rare)
• potential for dependence

Monoamine oxidase inhibitors (MAOIs)

The MAOI drugs were developed for treating depression in the 1960s when it was observed that an anti-tuberculosis drug, isoniazid, improved the mood of TB patients. Isoniazid was subsequently withdrawn due to safety concerns, but other MAOIs such as phenelzine and tranylcypromine have been used as antidepressants for many years.

MAOIs work in depression by preventing the natural breakdown of important brain chemicals such as noradrenaline. This action is irreversible, so MAOIs can be extremely dangerous. MAO_A and MAO_B are two different forms of MAOI in the body. MAO_A is mostly confined to the brain, whereas MAO_B is present in the gut where it breaks down certain chemicals in food. The older MAOIs can't distinguish between the two. This means that certain chemicals in food may not be broken down, with potentially fatal results.

People taking MAOIs must follow medical advice on what food should be avoided (for example, cheese and grapefruit). A newer and safer MAOI, Moclobemide does not interact with food in this way, because it only acts on MAO_A.

Other side effects of MAOIs are similar to the tricyclics.

Serotonin reuptake inhibitors

The selective serotonin reuptake inhibitors (SSRIs) were introduced in the 1980s - as new antidepressants, with milder side-effects than earlier drugs. They were named SSRIs because they affect the serotonin-containing nerves in the brain.

SSRIs are often preferred to other antidepressants because they are safe, easy to use and their side-effects are usually less severe than the tricyclics. They are less toxic in overdose than TCAs, and do not require laboratory testing of blood levels.

Side-effects of SSRIs can include:

• gastrointestinal disturbance including nausea, vomiting, diarrhoea
• headache, insomnia, anxiety (especially at the start of treatment)
• loss of libido, impotence
• allergic skin reactions (treatment should be stopped)
• weight gain
• serotonin syndrome -a rare but potentially fatal disorder caused by combining different drugs that interact with serotonin. Symptoms include agitation, sweating/shivering, talking/acting with uncontrollable excitement

Noradrenaline reuptake inhibitors

Similar to the SSRIs in terms of safety and tolerability, reboxetine is the only drug of this class currently available.

Side-effects of reboxetine are similar to the SSRIs and can include:

• dry mouth, constipation
• insomnia
• excess sweating
• urinary retention
• loss of libido, impotence
• serotonin syndrome (see SSRI's above)

Combined noradrenaline/serotonin reuptake inhibitors

This is another 'class' of drug with only one member, venlafaxine. It affects both noradrenaline and serotonin activity in the brain, and is thought to act more quickly than many antidepressants, (although this claim is unproven). Venlafaxine is similar in tolerability and safety to the SSRI's.

Side-effects of venlafaxine can include:

• nausea
• headache
• dry mouth, constipation
• weakness or lack of energy
• skin complaints such as rashes
• raised blood pressure
• rarely, kidney function may be impaired leading to excessive build-up of sodium in the body - hyponatraemia

Other antidepressants

Mirtazapine and nefazodone are atypical antidepressants; they enhance the activity of noradrenaline and serotonin by blocking certain receptors in the brain. Trazodone appears similar, but with little effect on noradrenaline.

Buspirone is also atypical and is used for the treatment of anxiety with or without depression. There is evidence that used with other medications, it may help people who do not benefit from antidepressants alone.

L-tryptophan is used for treating severe depression is in specialist in-patient settings.

Other drug treatments and ECT

Mood stabilisers

Lithium and the anticonvulsant drug carbamazepine are sometimes given for severe depression where antidepressants have failed to help. These drugs are more commonly used in the treatment of bipolar illness (or manic depression). See Treatment of bipolar disorder. They have a range of side-effects and people taking them need to be monitored closely. Lithium is expensive and generally unpopular for treatment of depression. Newer anticonvulsant drugs such as gabapentin and lamotrigine have shown some antidepressant activity, but more research is needed. ⁸

Side-effects of lithium can include:

• increased frequency/volume of urine
• excessive thirst
• skin complaints and rashes
• cognitive defects, such as memory problems, difficulty in decision making
• long term kidney problems

Side-effects of carbamazepine can include:

• nausea, vomitting, indigestion
• confusion, dizziness, drowsiness
• skin reactions and jaundice
• hair loss
• weight gain

Benzodiazepines

Drugs such as diazepam, lorazepam and bromazepam are commonly used for treating anxiety disorders. Because they enable people to sleep easily, they are also sometimes used for treating the sleep disturbance, which is a symptom of some forms of depression. These drugs have the potential to cause dependence, so they should not be used for more than 2-4 weeks at a time.

Side effects of benzodiazepines are generally not severe, but may include:

• drowsiness
• light-headedness
• muscle weakness/lack of co-ordination (ataxia)
• visual disturbances
• skin rash
• reduced blood pressure

Electro Convulsive Therapy

Electro convulsive therapy (ECT) is one of the most controversial forms of treatment for depression. Its effects on the brain are unclear, but clinically it is reported to improve cases of severe depression, and it is the quickest available form of antidepressant treatment. The treatment involves a series of electric shocks to the head, which produce seizures. Muscle relaxant drugs are given beforehand to prevent the seizures running through the body and causing convulsions which could damage it.

Side effects of ECT can be severe and include:

• Nausea/vomiting
• Muscle aching
• headache

Talking therapies and support

Psychological therapies such as counselling, cognitive behaviour therapy (CBT) or psychotherapy can help depression. They can be most useful when a severe depression has passed, alongside or instead of medication. They can help people who want to understand themselves and their depression better and can prevent depression in the future by helping people notice symptoms and take action to stay well. Self-help and support groups can help ease the isolation and low self esteem that people with depression often feel.

Psychological therapies are available on the NHS, but they are in short supply in some areas. People may need to ask their GP or psychiatrist to refer them for this treatment. Many voluntary organisations and self help groups offer free or low cost counselling and support for people with depression. Private counsellors, psychologists and psychotherapists also offer these therapies for a fee.

Counselling

Counselling helps people look at what they are facing now and to find ways of coping. There is evidence that it can help people adjusting to life events such as bereavement, postnatal depression, illness, disability or loss. Many GP's now employ counsellors in their practices.

Cognitive Behaviour Therapy (CBT)

CBT aims to help people change patterns of thinking or behaviour that are causing problems. It is a structured therapy where tasks are given in between sessions. It is usually provided by a NHS psychologist, nurse or counsellor. It has been proven effective for depression and anxiety.

Psychotherapy

Psychotherapy involves looking for connections between present feelings and actions and past events. It is especially useful in helping people with long term or recurring problems to get to the root of their difficulties. There is some evidence that it can help depression. NHS psychotherapists normally work in hospitals or specialist clinics.

Alternative therapies and other non drug treatments

A number of non-drug approaches are said to help depression, both alongside and instead of antidepressant drugs. These include light therapy, Transcranial Magnetic Stimulation (TMS), aromatherapy, acupuncture or meditation. Only those therapies proven to help are discussed here.

St John's Wort

St John's Wort, a plant available as an over-the-counter food supplement, has become a popular treatment for depression. In 1996 a research paper published in the British Medical Journal ⁹ concluded that St John's Wort was as effective as the antidepressant imipramine for mild to moderate depression. St John's Wort was better tolerated than the imipramine, with milder side effects.

Little is known about how St John's Wort works in depression. The active chemical in the plant has some MAOI activity, but it is unclear whether this accounts for its effect.

People thinking of using St John's Wort, especially those taking other medication should seek medical advice before using it. Several types of medication, including oral contraceptives, diuretics, and other antidepressants, may interact with the chemicals in St John's Wort. A few cases of mania/hypomania have been reported in people taking it. ¹⁰

Exercise

Exercise releases mood improving chemicals - endorphins into the brain. It is especially helpful in preventing depression returning. A recent study compared the benefits of exercise with and without antidepressants over a four-month period in people with major depression. There was no difference between the two groups after four months, but six months after finishing the treatment, relapse rates were significantly lower in the exercise group. ¹¹ Also, individual exercise during the follow-up period reduced the chances of having major depression at the end of the study.

The future

More and more people are diagnosed with depression every year, but there is surprisingly little research into its causes and treatment. Not much is known about the chemical changes caused by depression, or how anti depressant drugs actually work. The role of psychological therapies in the prevention and treatment of depression also needs to be explored. The causes and effective treatments for depression vary between people and the best depression treatment is likely to take into account each individual in the context of their life.

New potential therapies for depression are on the horizon. The success of the newer antidepressants has focussed attention on the role of neurotransmitter systems in depression, Other brain changes such as hormonal disruption also occur in depression. Early trials suggest that oestrogen may have a role as a treatment for depression. ¹²

Corticotrophin-releasing factor (CRF), which is released in response to stress, may also have a role in future depression treatments. ¹³ More CRF is present in the cerebro-spinal fluid (the liquid that bathes the brain and spinal chord) of depressed people who are not on medication. Chemicals that block the action of CRF in the brain might be a new way of treating depression; ¹⁴ they might act more quickly and work for a greater proportion of people.

Mark Waterlow - February 2001