How Antidepressants Work

Understanding the complex chemical processes of antidepressants is a book-worthy endeavor. This article will focus on how some of the most commonly prescribed drugs work.

Antidepressants are medicines used to help people who have depression. With the help of these depression medications, most people can achieve significant recovery from depression.

Antidepressant drugs are not happy pills, and they are not a panacea. They are prescription-only drugs that come with risks as well as benefits, and should only ever be taken under a doctor’s supervision. They are, however, one depression treatment option. Taking medications for depression is not a sign of personal weakness - and there is good evidence that they do help.

Whether antidepressant medication is the best treatment option depends on how severe the person’s depression is, their history of illness, their age (psychological treatments are usually the first choice for children and adolescents), and their personal preferences. Most people do best with a combination of medications for depression and therapy.

For adults with severe depression, says psychiatrist, Petros Markou, M.D., there is strong evidence that antidepressants are more effective than any other treatment. If depression is mild or moderate, psychotherapy alone may be sufficient, though even in this case, short-term antidepressant drug treatment or herbal therapy can help people get to the point where they can engage in therapy and get some exercise (which is also thought to help improve mood).

How do antidepressants work?
In 2001, Americans spent $12.5 billion on antidepressants to treat the debilitating symptoms of depression. Scientists know that antidepressants work by restoring the normal balance of hormones and neurotransmitters in the brain. But no one knows exactly how they do it. Robert Thompson, Ph.D., an assistant professor of psychiatry in the Medical School, is trying to find out.

By analyzing subtle changes in the brains of laboratory rats receiving one of three common antidepressants, Thompson and U-M colleague Juan F. Lopez, M.D., have found 10 to 20 neural genes whose expression patterns change in response to medication. They use advanced DNA microarray technology to analyze the activity of thousands of genes just to find a few that change in response to more than one type of antidepressant. It is
tedious, painstaking - but important - work.

The next step is tracking complex biochemical changes in the brain, which are controlled by changes in gene expression. “Understanding how antidepressants work at a genetic and molecular level could help us address their limitations, like delayed responses and side effects,” Thompson says. “It also could lead to new medications to help people who don’t respond at all to the antidepressants we have today.”

Are physicians too quick to prescribe prescription drugs for depression?
Isn’t psychotherapy more effective?

This is an important question and I would like to use it to launch a key clarifying point. Psychotherapies that are specific and tailored to the patient’s individual needs are effective in treating depression, especially in its earlier stages. Such psychotherapies ideally should be included as part of an optimal package of care. Antidepressant medications also are effective. What is most frustrating to me is the ‘either-or’ debate on the best way to treat depression.

Is it medication or is it therapy?
We can’t come up with the right answer because that’s the wrong question.

If you had diabetes, you wouldn’t be told: ‘Let’s not use medications like insulin; they’ll just get in the way of our psychotherapy efforts to help you deal better with stress (which is a factor in diabetes).’ You also shouldn’t be told, ‘Here’s a bottle of pills. You don’t need to do anything else.’ Similarly, we would never suggest stopping cardiac medication if the patient had cardiovascular disease, but that doesn’t mean one shouldn’t deal with stressors. Depression is analogous to these two diseases. It is a biological illness that is linked to events of living. Medications and psychotherapy should both be used as needed. To be clear, however, antidepressants are often absolutely essential in resolving episodes and preventing recurrences, and evidence suggests that for many, they are started too late. The only goal that counts is achievement and maintenance of remission - continued well-being.

We would all be better off if we ended the ‘either-or’ debate.
Incidentally, every degree of severity in depression can respond to treatment. But for patients whose depression is further along, some type of antidepressant medication therapy is required.

How Antidepressants Work

Most antidepressants are believed to work by slowing the removal of certain chemicals from the brain. These chemicals are called neurotransmitters (such as serotonin and norepinephrine). Neurotransmitters are needed for normal brain function and are involved in the control of mood and in other responses and functions, such as eating, sleep, pain, and thinking.

Antidepressants help people with depression by making these natural chemicals more available to the brain. By restoring the brain’s chemical balance, antidepressants help relieve the symptoms of depression.

Specifically, antidepressant drugs help reduce the extreme sadness, hopelessness, and lack of interest in life that are typical in people with depression. These drugs also may be used to treat other conditions, such as obsessive compulsive disorder, premenstrual syndrome, chronic pain, and eating disorders.

Typically, antidepressants are taken for 4 to 6 months. In some cases, however, patients and their doctors may decide that antidepressants are needed for a longer time.

Types of Antidepressants

There are many different kinds of antidepressants, including:

  • Selective serotonin reuptake inhibitors (SSRIs)  
  • Tricyclic antidepressants (tricyclics)  
  • Others

Like most medicines, antidepressant drugs can cause side effects. Not all people get these side effects. Any side effects you have will depend on the medicine your doctor has chosen for you. Your doctor should talk to you about your medicine.

About Depression

To understand how SSRIs work, it is helpful to understand the chemistry behind depression. Serotonin is a chemical in the brain that helps to regulate everything from sleep and appetite to mood and behavior. When the amount of serotonin in the brain is knocked off balance, patients may experience symptoms of depression. It is this imbalance that SSRIs and other families of antidepressant drugs work to correct.

In short, the delicate balance of chemicals in the brain has faltered and needs assistance to stabilize itself. This is why people with medical depression cannot just “snap out of it.”

There is a stigma attached to depression and mental illness. But unlike the assumption asserted by this stigma, people with depression are suffering from an actual disease. Medical depression is not just a “funk,” but is a real problem that needs real treatment.

SSRIs are a group of antidepressants that includes drugs such as escitalopram (brand name: Lexapro) citalopram (brand name: Celexa), fluoxetine (brand name: Prozac), paroxetine (brand name: Paxil) and sertraline (brand name: Zoloft). Selective serotonin reuptake inhibitors act only on the neurotransmitter serotonin, while tricyclic antidepressants and MAO inhibitors act on both serotonin and another neurotransmitter, norepinephrine, and may also interact with other chemicals throughout the body.

Selective serotonin reuptake inhibitors have fewer side effects than tricyclic antidepressants and MAO inhibitors, perhaps because selective serotonin reuptake inhibitors act only on one body chemical, serotonin. Some of the side effects that can be caused by SSRIs include dry mouth, nausea, nervousness, insomnia, headache and sexual problems. People taking fluoxetine might also have a feeling of being unable to sit still. People taking paroxetine might feel tired. People taking sertraline might have runny stools and diarrhea.

By affecting the uptake of serotonin, SSRIs help to rebalance the brain’s chemical processes and alleviate symptoms of depression. Correct treatment and relief is a matter of finding the proper dosage for each individual patient. Doing so can take some experimentation.

SSRIs are commonly prescribed because they tend to have fewer interactions with other types of drugs and can be used to treat depression in all its various forms, from common anxiety to severe depression. SSRIs are part of a relatively new class of antidepressant treatments and are considered ideal to use for long term therapy.

Because patients tend to tolerate SSRIs better than Tricyclic Antidepressants, these drugs are more commonly prescribed. Fluoxetine is a common SSRI found in popular prescribed drugs like Zoloft and Prozac.

Patients should not take SSRIs within two weeks of stopping Monoamine Oxidase Inhibitors (drugs like Parnate and Marplan, for example). SSRIs may take anywhere from four to eight weeks to produce results. However, some patients experience a robust reaction to the drug and begin to feel better in a relatively short period of time.


The tricyclics have been used to treat depression for a long time. They act on both serotonin and another neurotransmitter, norepinephrine, and may also interact with other chemicals throughout the body. They include amitriptyline (brand name: Elavil), desipramine (brand name: Norpramin), imipramine (brand name: Tofranil) and nortriptyline (brand names: Aventyl, Pamelor). Common side effects caused by these medicines include dry mouth, blurred vision, constipation, difficulty urinating, worsening of glaucoma, impaired thinking and tiredness. These antidepressants can also affect a person’s blood pressure and heart rate.

Other Antidepressants
Other antidepressants exist that have different ways of working than the SSRIs and tricylics. Commonly used ones are venlafaxine, nefazadone, bupropion, mirtazapine and trazodone. Less commonly used are the monoamine oxidase inhibitors (MAOIs).

Some of the most common side effects in people taking venlafaxine (brand name: Effexor) include nausea and loss of appetite, anxiety and nervousness, headache, insomnia and tiredness. Dry mouth, constipation, weight loss, sexual problems, increased blood pressure, increased heart rate and increased cholesterol levels can also occur.

Nefazodone (brand name: Serzone) can give people headaches, blurred vision, dizziness, nausea, constipation, dry mouth and tiredness.

Bupropion (brand name: Wellbutrin) can cause agitation, insomnia, headache and nausea. Mirtazapine (brand name: Remeron) can cause sedation, increased appetite, weight gain, dizziness, dry mouth and constipation. Some of the most common side effects of trazodone (brand name: Desyrel) are sedation, dry mouth and nausea. MAOI antidepressants like phenelzine (brand name: Nardil) and tranylcypromine (brand name: Parnate) commonly cause weakness, dizziness, headaches and tremor.

Provided by ArmMed Media
Revision date: June 11, 2011
Last revised: by Jorge P. Ribeiro, MD