* This information is intended for information purposes only. It's not intended to be a substitute for consultation with a physician.

• Tricyclic antidepressants
• Selective Serotonin Reuptake Inhibitors
• Monoamine Oxidase Inhibitors (MAO Inhibitors)
• Other

An estimated one million Canadians suffer from some form of depression. The Canadian Mental Health Association says one in 10 people will suffer from depression during their lifetime. According to the World Health Organization, depression will be the second-leading cause of disability in the world by 2020, trailing heart disease.

Antidepressants are used to treat serious, continuing mental depression that interferes with the person's ability to function. They were first developed in the 1950s and now there are almost 30 different medications on the market. They all work by altering the way in which certain chemicals, called neurotransmitters, work in our brains.

Quick Facts

Canadians being diagnosed and treated for depression: 2.72 million in 1993 to 7.8 million in 2000. Amount spent on antidepressants rose from $161 million in 1993 to $543 million in 2000.

Source: IMS Health statistics

Neurotransmitters are chemicals that transmit signals between the cells in our brains — they are involved in the control of mood and other functions related to eating, sleep, pain and thinking. In depression, some of these chemicals aren't working properly so antidepressants boost the activity of these chemicals in our brains. It may take several weeks for the drugs to start working.

Stan Kutcher, head of the department of psychiatry at Dalhousie University and a leading expert in depression, says medication can help 60 to 80 per cent of people suffering from the condition. (Globe and Mail, Jan. 7, 2002)

Kutcher says the best approach is a combination of medicine and counselling.

Classes of antidepressants

There are three main classes of antidepressant drugs: tricyclic antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors. Some combinations of these classes of drugs can be dangerous.

Quick Facts

Prescriptions for antidepressants have increased 64 per cent between 1996 and 2000. Paroxetene (Paxil) leads the pack and is the eighth most commonly prescribed drug in Canada. More than three million prescriptions were filled for Paxil in 2000.

Source: IMS Health statistics

Tricyclic antidepressants: How do they work?

Neurotransmitter levels are reduced during depression, but scientists don't know how tricyclic antidepressants improve mood. They do know the drugs inhibit the reabsorption of two neurotransmitters, norepinephrine and serotonin, into the transmitting neuron. In the process, the receiving neurons get extra stimulation.

Tricyclic drugs are classified according to their relative sedating or alerting properties. Psychiatrists may prescribe a more sedating drug for a depressed patient who tends to become agitated. If the depression is associated with lethargy, then a more stimulating drug may be chosen.

Advantages

Tricyclics are inexpensive compared to newer antidepressants and are often the first drug prescribed. They were developed in the 1950s and some people with chronic, long-lasting depression have taken tricyclics safely for decades.

Disadvantages

Most common side effect is faintness (syncope) caused by a fall in blood pressure. It is usually not serious but elderly people may be injured in falls and should be started on a smaller dose.

Some possible side effects:

• confusion
• constipation
• difficulty urinating
• feeling faint
• rapid heartbeat

Weight gain and drowsiness are common reasons why patients stop taking tricyclic antidepressants.

Quick Facts

Psychotherapeutics, which include antidepressants, are the second most dispensed drugs in the country, behind heart drugs. Five per cent of the population is severely depressed at any one time.

Source: IMS Health statistics

Examples : Amitriptyline (Elavil), Clomipramine, Desipramine, Doxepin, Imipramine (Tofranil), Nortipyline (Pamelor)

Selective Serotonin Reuptake Inhibitors: How do they work?

As the name suggests, Selective Serotonin Reuptake Inhibitors work selectively to raise the serotonin levels in the brain (as opposed to tricyclics, which act on two neutrotransmitters.) It's thought that reduced transmission of serotonin plays a role in depression.

Advantages

According to the home edition of the Merck Manual of Medical Information, SSRIs tend to cause fewer side effects than tricyclics and are generally safe in people with depression and a coexisting physical disorder. Also, SSRIs have not caused the increased heart rates associated with tricyclics. SSRIs offer a nonsedating, nonaddictive antidepressant for treating anxiety.

Quick Facts

• Depression rates among people aged 65 and older exceed 11 per cent
• Serious symptoms of depression are found in 15 per cent of the elderly population
• The rate is as high as 50 per cent in nursing homes

Source: IMS Health statistics

Disadvantages

Unlike tricyclics, SSRIs lack a track record of long-term use and are more expensive. CBC Radio's Quirks & Quarks medical columnist Dr. Miriam Shuchman said there are about 25 individual case reports of patients becoming acutely suicidal within a week or two of taking a common SRRI, Prozac. Many more, larger scale studies haven't found an increased risk of suicide among patients on Prozac.

Possible side effects

• Gastrointestinal: nausea, vomiting, diarrhea
• Nervous system effects: insomnia, anxiety and tremor
• Sexual dysfunction, including loss of sexual desire

Examples: Fluoxetine (Prozac), Paroxetine (Paxil), Sertaline (Zoloft)

Note: Health Canada warns that newborns may be adversely affected when pregnant women take SSRIs and other newer anti-depressants during the third trimester of pregnancy. The drugs involved are bupropion (whether used for depression or for smoking cessation), citalopram, fluoxetine, fluvoxamine, mirtazapine, paroxetine, sertraline and venlafaxine.

Some newborns whose mothers took these medications during pregnancy have developed complications at birth including feeding and/or breathing difficulties, seizures, muscle rigidity, jitteriness and constant crying. In some cases, the infants required extended hospital stays.

It's not clear whether the reactions were due to the medications or were the result of sudden withdrawal from the anti-depressants.

Health Canada has also warned that people of all ages who take newer antidepressant drugs may experience behavioural and emotional changes that may increase the risk of harming themselves or others. The agency notes only a small number of patients face the risk of feeling worse instead of better. The UK has banned the use of most SSRIs in children.

Monoamine Oxidase Inhibitors (MAO Inhibitors): How do they work?

Monoamine oxidase is an enzyme that normally breaks down neutrotransmitters. Monoamine oxidase inhibitors inactivate this enzyme leaving more of the neutrotransmitter to produce an antidepressant effect.

Advantages

Monoamine oxidase inhibitors may be particularly helpful for people with atypical depression symptoms such as overeating, excessive sleeping and anxiety, panic attacks and phobias; those who failed to improve on tricyclics; or anyone with a history of responding to MAO inhibitors or who has a family member successfully treated with these drugs.

Quick Facts

• Only about 6 per cent of Canadians with depression are properly diagnosed and treated
• Depression is now the chief cause of disability in companies
• Disability costs four to 12 per cent of a company's payroll
• Depression costs the Canadian economy $16 billion annually in time off and lower production

Source: IMS Health statistics

Disadvantages

People taking MAO inhibitors must follow strict dietary restrictions and precautions, such as not eating foods or drinks containing tyramine. Tyramine is found in beer on tap, red wine, and in foods that have been aged, fermented, pickled or smoked, or contaminated with bacteria. These include salami, aged cheese, fava beans, yogurt and soy sauce. Combining MAO inhibitors with these foods and drinks can lead to a rare but severe high blood pressure or even a stroke or heart attack. Other classes of antidepressants and some over-the-counter cough and cold drugs must also be avoided when taking MAO inhibitors.

Possible side effects

The side effects of monoamine oxidase inhibitors are similar to those of tricyclics:

• Fall in blood pressure which may cause fainting
• Dizziness
• Fainting
• Headaches (may worsen migraine headaches)
• Insomnia

Examples: Moclobemide, Phenelzine (Nardil), Tranylcypromine (Parnate)

Other

The Merck Manual of Medical Information lists psychostimulants such as methylphenidate for depressed people who are withdrawn, slowed and fatigued or haven't improved on the other classes of antidepressants, but it warns the abuse potential is high.

Psychotherapy and electroconvulsive (shock) therapy are two non-drug treatments for depression. Some studies suggest the natural remedy St. John's Wort may help in treating milder forms of depression. Lithium is used to treat people with bipolar depression (manic depression).

Sources:

Merck Manual of Medical Information, home edition (17th edition, 2000)

Berner, Mark and Gerald Rotenberg (eds.) Canadian Medical Association: New Guide to Prescription and Over-the-Counter Drugs (1996, Reader's Digest Association (Canada) Ltd., Montreal

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