• Introduction
• What is it used for?
• How does it work?
• Cautions
• Dosage
• Side effects
• Selected links
• Useful Article?

Introduction

Antidepressants are a type of medication that is primarily used in the treatment of depression.

Depending on when they were first introduced, antidepressants are sometimes described as:

• first,
• second, or
• third generation antidepressants.

First generation antidepressants

The discovery of antidepressants could be described as a ‘lucky accident’. During the 1950s, while carrying out trials on a new medication for tuberculosis (TB), researchers noticed that the medication also had a mood improving effect.
 

This initial discovery led to the creation of two classes of first generation antidepressants:

• Tricyclic antidepressants (TCAs), of which the most widely used type was called amitriptyline, and

• Monoamine oxidase inhibitors (MAOIs), of which the two most widely used types were called moclobemide and phenelzine.

Both TCAs and MAOIs proved to be effective in treating depression, but they did cause a wide range of side effects, which were often unpleasant. These included:

• constipation,
• sweating,
• shaking or trembling, and
• difficulty sleeping.

Third generation antidepressants

SNRIs

The third generation of antidepressants, which are collectively known as serotonin-norepinephrine reuptake inhibitors (SNRIs), were introduced during the 1990s. Examples of SNRIs include:

• venlafaxine, and
• mirtazapine.

SNRIs were the result of an attempt to create an antidepressant that was more clinically effective than SSRIs. However, the evidence that SNRIs are more effective at treating everyone with depression is uncertain. It seems that some people respond better to SSRIs while others respond better to SNRIs.

Safety

The biggest safety concern regarding first generation antidepressants is that they can have a potentially fatal effect if a person takes an overdose. This is an obvious concern when treating people who have an increased risk of committing suicide. The same is not true of SSRIs and SNRIs, although taking an overdose can still be dangerous.

There have been reports of young people under 25 years of age experiencing suicidal thoughts when they first begin treatment with antidepressants (usually within the first two weeks of treatment). Because of this, it is recommended that young people are closely monitored when they first begin to take their medication.

The Yellow Card Scheme allows you to report suspected side effects from any type of medicine that you are taking. It is run by a medicines safety watchdog called the Medicines and Healthcare Products Regulatory Agency (MHRA). See the Yellow Card Scheme website for more information.

What is it used for?

Depression

The main use for antidepressants is treating depression.

Antidepressants are usually recommended as a first line treatment for moderate to severe depression, when used in combination with a talking therapy such as cognitive behavioural therapy (CBT). CBT is a type of therapy that uses a problem solving approach to help improve thought, mood and behaviour.

Antidepressants are not usually recommended for treating mild depression because research has found that they have limited effectiveness. However, exceptions can be made if:

• your symptoms of mild depression have lasted for more than two years, and/or
• you have experienced previous episodes of moderate or severe depression.

Initially, a selective serotonin reuptake inhibitor (SSRI) will usually be prescribed for you. If your symptoms have not improved after four weeks, an alternative antidepressant may be recommended. Depending on your personal circumstances, this may be a certain type of antidepressant such as:

• a different type of SSRI,
• a serotonin-norepinephrine reuptake inhibitor (SNRI),
• a tricyclic antidepressant (TCA), or, less commonly,
• a monoamine oxidase inhibitor (MAOI).

Other mental health conditions

Antidepressants can also be used to help treat other mental health conditions, including:

• anxiety disorder,
• obsessive compulsive disorder (OCD),
• panic disorder,
• serious phobias, such as agoraphobia and social phobia,
• bulimia, and
• post-traumatic stress disorder (PTSD).
   

As with depression, SSRIs are usually the first choice treatment for these conditions. If SSRIs prove ineffective, an alternative type of antidepressant can be used.

Chronic pain

Even though TCAs were not originally designed to be painkillers, there is evidence to suggest that they are effective in treating chronic (long-term) nerve pain in some people.

Chronic nerve pain, also known as neuropathic pain, is caused by nerve damage or other problems with the nerves, and is often unresponsive to traditional painkillers, such as paracetamol.

Amitriptyline is the TCA that is usually used to treat neuropathic pain. Conditions that may benefit from treatment with amitriptyline include:

• complex regional pain syndrome,
• diabetic neuropathy,
• multiple sclerosis, and
• conditions where a nerve becomes trapped, such as sciatica.

Antidepressants have also been used to treat cases of chronic pain that do not involve the nerves (non-neuropathic pain). However, they are thought to be less effective for this purpose.

As well as TCAs, SSRIs and SSNIs can also be used to treat chronic non-neuropathic pain.

Conditions that cause non-neuropathic pain that may benefit from treatment with antidepressants include:

• fibromyalgia,
• chronic back pain, and
• chronic neck pain.

How does it work?

Different types of antidepressants work in different ways, but all antidepressants are based on the same principle. All antidepressants work by increasing the levels of chemicals called neurotransmitters in the brain.

Neurotransmitters are ‘messenger chemicals’ that are used to transmit signals between brain cells. Some neurotransmitters are also thought to have an important effect on your mood.

Examples of ‘mood enhancing’ neurotransmitters include:

• serotonin,
• norepinephrine, and
• dopamine.

The role that these neurotransmitters play in the causes of depression (and other mental health conditions) is still poorly understood. However, most experts would say that depression is not simply the result of a chemical imbalance in the brain.

Depression is a complex condition with many contributing factors. While antidepressants can treat the symptoms of depression, they do not necessarily address its causes. This is why antidepressants are usually used in combination with therapy to treat moderate to severe depression or other mental health conditions, such as obsessive compulsive disorder (OCD).

Increasing the levels of neurotransmitters is a gradual process, so most people will need to take antidepressants for two to four weeks before noticing any improvement in their symptoms.

Increasing the levels of neurotransmitters can disrupt the pain signals that are sent by the nerves, which may be why some antidepressants can also help relieve symptoms of chronic (long-term) pain.

Cautions

Cautions and Interactions

MAOIs

Recommendations on usage
The use of monoamine oxidase inhibitors (MAOIs) is not usually recommended for:

• children,
• pregnant women,
• breastfeeding women,
• people with heart disease,
• people with liver disease,
• people who have a growth on their adrenal glands that is causing high blood pressure (pheochromocytoma),
• people with bipolar disorder (manic depression),
• people with an overactive thyroid gland (hyperthyroidism),
• people who have had a stroke, or another condition that affects the blood supply to the brain.

Interactions

MAOIs have been known to react unpredictably with a number of different medications and substances such as:

• over-the-counter (OTC) cough and cold medications, particularly those that contain an ingredient called dextromethorphan,
• powerful opiate-based painkillers, such as pethidine and morphine,
• selegiline, which is a medication that is used to treat Parkinson’s disease (a condition that affects the way that the brain coordinates body movements, including walking and talking), and
• cimetidine, which is a medication that is used to treat stomach ulcers.

You should not take any of the medications that are listed above in combination with a MAOI unless your GP specifically recommends that you do.
MAOIs can also react unpredictably with illegal drugs such as:

• cannabis,
• amphetamines (speed),
• cocaine,
• heroin, and
• ketamine.

You should avoid using any illegal drugs while taking an MAOI.

You should also never take MAOIs in combination with other types of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), because it can cause dangerous side effects, such as seizures and loss of consciousness.

If you are currently taking another type of antidepressant, it is usually recommended that you discontinue treatment and wait 14 days before beginning to take MAOIs.

One type of MAOI, called phenelzine (sold under the brand name Nardil), can cause a dangerous rise in blood pressure if you eat food containing a substance called tyramine.
Foods containing tyramine include:

• cheese,
• liver,
• yeast extract (Marmite),
• pickled fish, such as herrings, and
• cured meat, such as salami or pepperoni.

If you are prescribed phenelzine, you will be given a list of food to avoid. Some alcoholic drinks also contain tyramine, for example:

• red wine,
• beer, and
• real ales.

Drinks that do not contain tyramine include gin and vodka. However, as MAOIs can increase the effects of alcohol, you should avoid drinking, or at least moderate your consumption, while you are taking your medication.

Another widely used MAOI is called moclobemide (sold under the brand name Manerix). Moclobemide is not as sensitive to the effects of tyramine but, if you are taking it, you should still avoid eating large amounts of food that contains tyramine.

MAOIs can react unpredictably to some anaesthetics and sedatives, so you may be advised to stop taking your medication two weeks before having surgery or major dental treatment that requires sedation.

TCAs

Recommendations on usage

The use of tricyclic antidepressants (TCAs) is not usually recommended for:

• children,
• pregnant women,
• people with a history of heart disease,
• people who have recently had a heart attack,
• people with liver disease,
• people with an inherited blood disorder called porphyria,
• people with bipolar disorder (manic depression),
• people with schizophrenia,
• people who have a growth on their adrenal glands that is causing high blood pressure (pheochromocytoma),
• people with an enlarged prostate gland (benign prostatic hyperplasia),
• people with glaucoma (an eye condition), and
• people with epilepsy.

Interactions

As with MAOIs, you should avoid taking a TCA in combination with other types of antidepressant.

In particular, MAOIs and TCAs should not be taken together because in combination they can cause seizures and, in some cases, death.

There are also several medications that can react unpredictably with TCAs. While these reactions are not as potentially dangerous as with MAOIs, they can still be serious.

Therefore, before starting treatment with TCAs, you should seek advice from your GP or pharmacist if you are currently taking, have recently taken or are planning to take any of the following:

• the herbal remedy St John’s Wort,
• over-the-counter (OTC) cough and cold medication,
• medications that are used to lower high blood pressure, such as guanethidine, debrisoquine, betanidine, and clonidine,
• medications that are used to treat Parkinson’s disease, such as selegiline,
• medications that are used to treat underactive, or overactive, thyroid glands,
• ethchlorvynol, which is a medication that is used to treat insomnia,
• phenobarbital, which is a medication that is used to treat epilepsy,
• methylphenidate, which is a medication that is used to treat attention deficit hyperactivity disorder (ADHD),
• disulfiram, which is medication that is used to treat alcohol dependency,
• cimetidine, which is a medication that is used to treat stomach ulcers,
• ritonavir, which is a medication that is used to treat HIV and AIDS, and
• thioridazine, which is a medication that is used to treat schizophrenia.

You should avoid drinking alcohol when you are taking a TCA because the combined effects can make you feel very drowsy.

Do not use cannabis when taking TCAs as it can cause:

• rapid heart beat (tachycardia),
• confusion,
• restlessness,
• mood swings and
• hallucinations.

SSRIs

Recommendations on usage

The use of selective serotonin reuptake inhibitors (SSRIs) is not usually recommended for children and pregnant women, unless it is thought that the benefits of treatment outweigh any potential risks.

In the case of children, an SSRI called fluoxetine is usually recommended.

In the case of pregnant women, fluoxetine, citalopram and sertraline are usually the SSRIs that are recommended (although they are not suitable for breastfeeding women).

Some SSRIs may also not be suitable for you if you have:

• mania (an extremely elevated mood, sometimes with hallucinations),
• bipolar disorder (alternating bouts of depression and mania) and you are in a manic phase,
• angina (chest pain), or if you have had a heart attack,
• a bleeding disorder, or if you are taking medicines that make it more likely that you may bleed, for example, warfarin,
• diabetes,
• epilepsy (SSRIs should only be taken if your epilepsy is well controlled, and the medication should be stopped if your epilepsy gets worse),
• liver problems,
• narrow angle glaucoma (increased pressure in the eye), or
• kidney problems.

Interactions

As with MAOIs and TCAs, it is very important to avoid taking SSRIs in combination with other types of antidepressants.

Before starting treatment with SSRIs, you should seek advice from your GP or pharmacist if you are currently taking, have recently taken or are planning to take any of the following:

• St John’s Wort,
• sibutramine, which is a medication that is used to treat obesity,
• antiplatelets, which is a medication that is used to prevent blood clots, such as aspirin and clopidogrel,
• medications that are used to treat schizophrenia, such as pimozide and clozapine,
• medications that are used to treat epilepsy, such as carbamazepine, ethosuximide and gabapentin,
• medications that are used to treat Parkinson’s disease, such as rasagiline and selegiline,
• medications that are used to treat migraines, such as almotriptan and eletriptan, and
• non-steroidal anti-inflammatory drugs (NSAIDs), which are a type of painkiller, such as ibuprofen, diclofenac and naproxen.

You should avoid drinking alcohol while you are taking SSRIs because it can make related side effects more severe.

SNRIs

Recommendations on usage

The use of serotonin-norepinephrine reuptake inhibitors (SNRIs) is not usually recommended for:

• children,
• pregnant women,
• breastfeeding women,
• people with heart disease, and
• people with poorly controlled high blood pressure (hypertension).

Interactions

As with all antidepressants, you should not take SNRIs in combination with other types of antidepressant medication.

Before starting treatment with SNRIs, you should seek advice from your GP or pharmacist if you are currently taking, have recently taken or are planning to take any of the following medication:

• St John’s Wort,
• sibutramine,
• antiplatelets,
• medications that are used to treat schizophrenia,
• medications that are used to treat migraine, and
• medications that are used to treat HIV and AIDS.

Dosage

When prescribing antidepressants for you, your GP will usually select the lowest possible dose that is thought to be needed to improve your symptoms. This is to reduce your risk of experiencing side effects. If this dose proves to be ineffective, the dosage can be gradually increased.

Antidepressants are usually taken in tablet form. Depending on the type of antidepressant that is prescribed and the severity of your depression, you will usually have to take one to three tablets a day.

If you forget to take your tablets on a certain day, don't take an extra dose the next day in order to ‘make up’ your dose. Instead, carry on taking your tablets as usual.

If you take more tablets than you should, contact your GP as soon as possible for advice. However, if this is not possible, contact your local out of hours service, or NHS Direct Wales on 0845 46 47.

It will probably take between two and four weeks before you begin to notice the effects of the antidepressants.

It is usually recommended that a course of antidepressants lasts for at least six months. However, if you have experienced previous episodes of depression, a two-year course of antidepressants may be recommended.

You should not suddenly stop taking antidepressants that have been prescribed for you, even if you feel better. Stopping taking antidepressants suddenly can lead to withdrawal symptoms such as:

• stomach upsets,
• flu-like symptoms,
• anxiety,
• dizziness,
• vivid dreams at night, and
• sensations in the body that feel like electric shocks.

If your GP decides to stop your course of antidepressants, they will reduce the dose gradually, over time

Side effects

Antidepressants and suicide risk

Some people have experienced suicidal thoughts and a desire to self-harm when they first start to take antidepressants. Those who are under 25 years of age seem to be particularly at risk.

Contact your GP, or go to hospital immediately, if you have thoughts of killing or harming yourself at any time while you are taking antidepressants.

It may be useful to tell a relative or a close friend that you have started taking antidepressants and to ask them to read the leaflet that comes with your medication. You should then ask them to tell you if they think your symptoms are getting worse, or if they are worried about changes in your behaviour.

MAOIs

Common side effects of monoamine oxidase inhibitors (MAOIs) include:

• blurred vision,
• dizziness,
• drowsiness,
• increased appetite,
• nausea,
• restlessness,
• shaking or trembling, and
• difficulty sleeping.

In rare cases, MAOIs have the potential to cause a wide range of other side effects. You should check with your GP if you are concerned about any unusual symptoms that you have.

There have been cases where MAOIs have caused a dangerous rise in blood pressure. This can cause symptoms such as:

• a stiff neck,
• severe headache,
• chest pains,
• vomiting or nausea, and
• an abnormally fast heartbeat (tachycardia).

If you experience the combination of the symptoms that are listed above, seek emergency medical help immediately by dialling 999 to ask for an ambulance.

TCAs

Common side effects of tricyclic antidepressants (TCAs) include:

• dry mouth,
• constipation,
• sweating,
• problems passing urine,
• slight blurring of vision, and
• drowsiness.

The side effects should ease after 7-10 days as your body begins to get used to the medication.

However, if the side effects continue, or they become troublesome, you should inform your GP because it may be possible to switch to a different antidepressant that may suit you better.

SSRIs

Common side effects of selective serotonin reuptake inhibitors (SSRIs) include:

• nausea (feeling sick),
• low sex drive, lack of orgasm and, in men, abnormal erection or ejaculation,
• blurred vision,
• diarrhoea or constipation,
• dizziness,
• dry mouth,
• feeling agitated or shaky,
• insomnia (not sleeping well) or feeling very sleepy,
• loss of appetite (not feeling hungry),
• sweating, and
• yawning.

These side effects should improve over time. However, if they become troublesome, you should talk to your GP because you may need to switch to a different type of antidepressant.

SNRIs

The common side effects of serotonin-norepinephrine reuptake inhibitors (SNRIs) are the same as those that are associated with SSRIs (see above).

SSRIs, SNRIs and serotonin syndrome

Serotonin syndrome is an uncommon, but potentially serious, set of side effects that is linked to SSRIs and SNRIs.

Serotonin syndrome occurs when the levels of serotonin in your brain become too high. It is usually triggered when you take an SSRI or SNRI in combination with another medication (or substance) that also raises serotonin levels, such as another antidepressant or St John’s Wort.

Symptoms of mild to moderate serotonin syndrome include:

• confusion,
• agitation,
• muscle twitching,
• sweating,
• shivering, and
• diarrhoea.

If you experience the symptoms listed above, you should stop taking the medication and seek immediate advice from your GP. If this is not possible, call NHS Direct on 0845 46 47.

Symptoms of severe serotonin syndrome include:

• a very high temperature (fever) of 39.4°C (103°F) or above,
• seizures (fits),
• irregular heartbeat (arrhythmia), and
• unconsciousness.

If you experience these severe symptoms, you should dial 999 and ask for an ambulance.

Selected links

NHS Direct Wales Encyclopaedia links

Counselling

Depression

External links

Depression Alliance - Depression Alliance

Antidepressants - Royal College of Psychiatrists

Mind - National Association for Mental Health

Meeting the Challenge of Mental Illness SANE

Samaritans

Yellow Card Scheme