Antidepressants

Antidepressants are medicines that treat depression. Your doctor can prescribe them for you. They work to balance some of the natural chemicals in our brains. It may take several weeks for them to help. There are several types of antidepressants. You and your doctor may have to try a few before finding what works best for you.

Antidepressants may cause mild side effects that usually do not last long. These may include headache, nausea, sleep problems, restlessness, and sexual problems. Tell your doctor if you have any side effects. You should also let your doctor know if you take any other medicines, vitamins, or herbal supplements.

It is important to keep taking your medicines, even if you feel better. Do not stop taking your medicines without talking to your doctor. You often need to stop antidepressants gradually.

Depression is a serious medical illness. Also called “major depressive disorder,” or “unipolar depression,” it affects about 350 million people worldwide and is a leading cause of disability, according to the World Health Organization.

If you have depression, you may not recognize the symptoms or may think symptoms are due to a lack of sleep or a poor diet. Or you may realize you’re depressed but feel too tired or ashamed to seek help.

Not all depression requires treatment with medication. But medications approved for the treatment of depression by the U.S. Food and Drug Administration (referred to here as “antidepressants”) can help improve symptoms in some people.

Diagnosing Depression

Diagnosis—which should be from a health care professional—depends on the number, severity, and duration of depressive symptoms, which can include:

depressed mood
loss of interest or pleasure in almost all activities
changes in appetite or weight
disturbed sleep or sleeping too much
slowed or restless movements
fatigue or loss of energy
feelings of worthlessness or excessive guilt
trouble in thinking, concentrating, or making decisions
thoughts of death or suicide

Doctors typically consider your history and review your behavior and mental status when evaluating a possible diagnosis of depression. Then, a doctor can evaluate symptoms, rule out physical causes of depression (such as thyroid disease or Parkinson’s disease), and decide if depression is an appropriate diagnosis.

Doctors should also screen you for bipolar disorder, a brain disorder that causes unusual shifts in mood, energy, and activity levels, as well as changes in your ability to do everyday tasks. If certain medications approved for treatment of depression are wrongly prescribed to a person with bipolar disorder, they can cause mania, a type of unusually elevated or excited mood. If mania is severe, a person can become psychotic. (Read this Consumer Update for more on bipolar disorder.)

Treatment with Medication

Antidepressants are medications that are thought to work by changing brain chemicals called neurotransmitters—primarily serotonin, norepinephrine, and dopamine—which are involved in regulating mood.

Some antidepressants have classifications:

selective serotonin reuptake inhibitors (SSRIs); examples are Prozac (fluoxetine), Celexa (citalopram), and Paxil (paroxetine)
serotonin norepinephrine reuptake inhibitors (SNRIs); examples are Effexor (venlafaxine) and Cymbalta (duloxetine)
tricyclic antidepressants (TCAs); examples are Elavil (amitriptyline), Tofranil (imipramine), and Pamelor (nortriptyline)
monoamine oxidase inhibitors (MAOIs); examples are Nardil (phenelzine) and Parnate (tranylcypromine)

Other antidepressants include:

Remeron (mirtazapine)
Wellbutrin (bupropion)

Medications approved for treatment of depression affect different neurotransmitters in a variety of ways. For example, SSRIs increase the signaling of serotonin in the brain. And MAOIs block monoamine oxidase, an enzyme that breaks down neurotransmitters.

“Some evidence shows that the most effective way to treat many patients with depression is through both talk therapy and prescribed antidepressant medication,” adds Mitchell Mathis, M.D., director of the Division of Psychiatry Products at the FDA. Talk to your doctor about the best treatment for you.

How Antidepressants Block Serotonin Transport

Serotonin is a diminutive and deceptively simple-looking neurotransmitter molecule, yet a very complex “machinery” is required for neurotransmitter recognition, transmission, and recycling. The malfunctioning of this protein machinery can cause conditions such as depression, obsessive-compulsive disorder, aggression, anxiety, and Parkinson’s disease. In addition, drugs of addiction, such as methamphetamines, act on this system, causing serious damage and profoundly affecting the well-being of individuals. At the ALS, researchers were able to obtain x-ray crystallographic structures of the difficult-to-crystallize human serotonin transporter bound to two commonly prescribed antidepressant drug molecules. The resulting details about the transporter structure and mechanism will help in the design of new, more effective therapeutics for treating depression and anxiety.

Moody Clues

Humans have billions of brain cells—neurons—that are in constant communication with each other. This transmission of information is accomplished using neurotransmitters, which are chemicals passed between brain cells, influencing human behavior, cognition, and physiology.

One of those chemicals, serotonin, has substantial influence over all facets of human behavior, from mood to cardiovascular function, digestion to reproduction. Serotonin is found in the central nervous system and gastrointestinal tract as well as the brain, where it exerts a major influence on mood and sense of well-being. This study by Coleman et. al revealed critical details of how and where drugs bind to the serotonin transport protein, laying the groundwork for the design of new antidepressants.

A slice through a surface representation of the serotonin transporter, SERT, which is a membrane protein. Molecules of the antidepressant drug, S-citalopram, are shown as spheres bound to central (magenta) and secondary (yellow) sites in a “vestibule” near the outer membrane surface.

Because serotonin has such a major impact on mood, proteins that bind and metabolize serotonin have been the target of intense pharmacological research. Drugs known as SSRIs—selective serotonin reuptake inhibitors—work by stopping serotonin from being reused by binding to the serotonin transporter (SERT) and blocking serotonin transport. Prozac, for example, is an antidepressant in this drug class, as are (S)-citalopram and paroxetine (commercial names are Lexapro and Paxil, respectively). These drugs work on the serotonin transporter, which is responsible for terminating serotonin signaling. When this transporter is blocked, serotonin accumulates in the synaptic space, effectively keeping the serotonin signal “on,” which can help alleviate symptoms of depression. Several illegal drugs, such as MDMA (“ecstasy”), also act on the serotonin transporter, but lead to a short-term feeling of euphoria and to permanent damage of neurons.

Here, the researchers focused on SERT, which belongs to a class of neurotransmitter transporter proteins that also transport dopamine and norepinephrine. SERT is a membrane protein and was extremely challenging to crystallize due to its poor stability after extraction from the membrane; however, the researchers were able to make SERT more tractable for crystallization by introducing a small number of mutations that improved stability, which in turn allowed successful collection of x-ray diffraction data at the Advanced Photon Source and at ALS Beamline 5.0.2 (part of the Berkeley Center for Structural Biology).

The study describes the high-resolution structure of SERT bound to the antidepressants (S)-citalopram and paroxetine, revealing many interesting characteristics of drug binding. Overall, SERT is embedded in the membrane of neurons by 12 membrane-spanning helices that house the central site that carries out the binding and transport of serotonin across the membrane. An opening, or “vestibule,” located in the transporter on the outside of the neuron allows access of serotonin and other ligands to the central binding site of SERT.

The antidepressants studied lock SERT in a configuration that is open to the outside of the neuron by physically binding to the central binding site, precluding serotonin binding and further motion. Interestingly, (S)-citalopram was also shown to bind to a site directly adjacent to the central binding site in the vestibule. Binding of SSRIs to the central site “wedges” the helices of SERT in an inactive configuration, and binding to the second site blocks drug release from the central site. Extensive interactions with specific amino-acid residues lining the binding site explain the selectivity of SERT for SSRIs. In addition, the research showed that the secondary binding site is extremely malleable, physically changing shape in response to ligands, and this plasticity could be exploited in future drug design work.

List of antidepressants

List-of-Antidepressant-Drugs-with-Medication-Guides

Antidepressant Effectiveness

In general, you must take regular doses of a prescribed antidepressant for several weeks before you’re likely to have the medication’s full effect.

You shouldn’t stop taking medication without talking with your doctor—even if you feel better. Stopping can result in withdrawal symptoms like anxiety and irritability. Or depression could return.

Note: A significant percentage of people may not respond to a prescribed antidepressant. In these cases, switching to a different medication or adding another medication can sometimes help treat symptoms. Some people may not respond to medication at all, Mathis notes. If you have concerns about antidepressants you are taking, talk with your doctor.

Common Side Effects

Common side effects of antidepressants can include:

Nausea and vomiting
Weight gain
Diarrhea
Sleep disturbances
Sexual problems

It may take some time for your doctor to determine the medication that works best for you.

Serious Risks

Some antidepressants can have serious risks. Discuss these risks with your doctor. Some of the relevant risks are listed below.

Suicidal thinking: In 2004, the FDA asked manufacturers to add a boxed warning to the labeling of all antidepressant medications. This labeling warns about the increased risk of suicidal thinking or suicidal behavior in children and adolescents taking antidepressants during initial treatment and with dose increases. In 2007, FDA requested that the warning be extended to include young adults through age 24.

If you or someone you know is having thoughts of suicide, you can immediately call your doctor; go to a hospital emergency room; or call the confidential and toll-free National Suicide Prevention Lifeline at 1-800-273-TALK (8255).

Birth defects: Some antidepressant medications might harm a fetus if taken during pregnancy. If you are considering an antidepressant medication and are pregnant, plan to become pregnant, or breastfeeding, talk to your doctor about benefits and risks.

High blood pressure: Those taking monoamine oxidase inhibitors must avoid certain foods that contain high levels of the chemical tyramine. This chemical is in many cheeses, wines and pickles, and some medications including decongestants. If you take MAOIs and consume this chemical, they may interact and cause a sharp increase in blood pressure, which could lead to a stroke or other complications. Talk to your doctor about the best diet for you.

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