By Christian Nordqvist
Reviewed by Timothy J. Legg, PhD, CRNP
Antidepressants are medications that can help relieve symptoms of depression, social anxiety disorder, anxiety disorders, seasonal affective disorder, and dysthymia, or mild chronic depression, as well as other conditions.
They aim to correct chemical imbalances of neurotransmitters in the brain that are believed to be responsible for changes in mood and behavior.
Antidepressants were first developed in the 1950s. Their use has become progressively more common in the last 20 years.
According to the Centers for Disease Control and Prevention (CDC), the percentage of people aged 12 years and over using antidepressant in the United States rose from 7.7 percent in 1999-2002 to 12.7 percent in 2011-2014. Around twice as many females use antidepressants as males.
Antidepressants can be divided into five main types:
SNRIs and SSRIs
Antidepressants treat major depressive disorder and other conditions.
These are the most commonly prescribed type of antidepressant.
Serotonin and noradrenaline reuptake inhibitors (SNRIs) are used to treat major depression, mood disorders, and possibly but less commonly attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxietydisorders, menopausal symptoms, fibromyalgia, and chronic neuropathic pain.
SNRIs raise levels of serotonin and norepinephrine, two neurotransmitters in the brain that play a key role in stabilizing mood.
Examples include duloxetine (Cymbalta), venlafaxine (Effexor) and desvenlafaxine (Pristiq).
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. They are effective in treating depression, and they have fewer side effects than the other antidepressants.
SSRIs block the reuptake, or absorption, of serotonin in the brain. This makes it easier for the brain cells to receive and send messages, resulting in better and more stable moods.
They are called “selective” because they mainly seem to affect serotonin, and not the other neurotransmitters.
SSRIs and SNRIs may have the following side effects:
• hypoglycemia, or low blood sugar
• low sodium
• dry mouth
• constipation or diarrhea
• weight loss
• sexual dysfunction
• anxiety and agitation
• abnormal thinking
Examples include citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil) and sertraline (Zoloft).
There have been reports that people who use SSRIs and SNRIs, and especially those under the age of 18 years, may experience thoughts of suicide, especially when they first start using the drugs.
All antidepressants carry a black-box warning to this effect, as required by the Food and Drug Administration (FDA).
Tricyclic antidepressants (TCAs)
Tricyclic antidepressants (TCAs) are so named because there are three rings in the chemical structure of these medications. They are used to treat depression, fibromyalgia, some types of anxiety, and they can help control chronic pain.
Tricyclics may have the following side effects:
• arrhythmia, or irregular heartbeat
• nausea and vomiting
• abdominal cramps
• weight loss
• urinary retention
• increased pressure on the eye
• sexual dysfunction
Examples include amitriptyline (Elavil), amoxapine- clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil) and trimipramine (Surmontil).
Monoamine oxidase inhibitors (MAOIs)
This type of antidepressant was commonly prescribed before the introduction of SSRIs and SNRIs.
It inhibits the action of monoamine oxidase, a brain enzyme. Monoamine oxidase helps break down neurotransmitters, such as serotonin.
If less serotonin is broken down, there will be more circulating serotonin. In theory, this leads to more stabilized moods and less anxiety.
Doctors now use MAOIs if SSRIs have not worked. MAOIs are generally saved for cases where other antidepressants have not worked because MAOIs interact with several other medications and some foods.
Side effects include:
• blurred vision
• weight loss or weight gain
• sexual dysfunction
• diarrhea, nausea, and constipation
• insomnia and drowsiness
• arrhythmia, or irregular heart rhythm
• fainting or feeling faint when standing up
• hypertension, or high blood pressure
Examples of MAOIs include phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan) and selegiline (EMSAM, Eldepryl).
Noradrenaline and specific serotoninergic antidepressants (NASSAs)
These are used to treat anxiety disorders, some personality disorders, and depression.
Possible side effects include:
• dry mouth
• weight gain
• drowsiness and sedation
• blurred vision
More serious adverse reactions include seizures, white blood cell reduction, fainting, and allergic reactions.
Examples include Mianserin (Tolvon) and Mirtazapine (Remeron, Avanza, Zispin).
How do antidepressants work?
This YouTube video by Paul Bogdan explains how antidepressants work.
Any side effects will likely occur during the first 2 weeks, and then gradually wear off.
Common effects are nausea and anxiety, but this will depend on the type of drug used, as mentioned above.
If the side effects are very unpleasant, or if they include thinking about suicide, the doctor should be informed at once.
In addition, research has linked the following adverse effects with antidepressant use, especially among children and adolescents.
Excessive mood elevation and behavior activation
This may include mania or hypomania. It should be noted that antidepressants do not cause bipolar disorder, but they may unmask a condition that has not yet revealed itself.
There have been a few reports of a higher risk of having suicidal thoughts when first using antidepressants.
This could be due to the drugs or other factors, such as the time taken for the medication to work, or possibly an undiagnosed bipolar disorder which may require a different approach to treatment.
The FDA requires that antidepressants carry a black box warning of this possible effect.
Unlike some drugs, it is not necessary to keep raising the dose to get the same effect with antidepressants. In that sense, they are not addictive.
When you stop using an antidepressant, you will not experience the same type of withdrawal symptoms that occur, for example, when giving up smoking.
However, nearly 1 in 3 people who used SSRIs and SNRIs report some withdrawal symptoms after stopping treatment.
Symptoms lasted from 2 weeks to 2 months and included:
• nightmares or vivid dreams
• electric shock-like sensations in the body
• flu-like symptoms
• abdominal pain
In most cases, symptoms were mild. Severe cases are uncommon and are more likely after stopping Seroxat and Effexor.
Doctors should reduce the dose gradually to minimize the risk of unpleasant withdrawal symptoms.
These medications are used not only to treat depression but for other conditions too.
The primary, or approved, uses of antidepressants are to treat:
• obsessive-compulsive disorders (OCD)
• childhood enuresis, or bedwetting
• depression and major depressive disorder
• generalized anxiety disorder
• bipolar disorder
• posttraumatic stress disorder (PTSD)
• social anxiety disorder
Sometimes a medication is used “off-label.” This means the use is not approved by the FDA, but a doctor may decide that it should be used as it may be an effective treatment.
Off-label uses of antidepressants include:
Studies suggest that 29 percent of antidepressant use is for an off-label purpose.
It can take several weeks for a person to notice the effects of an antidepressant. Many people stop using them because they believe the medications are not working.
Reasons why people may not see an improvement include:
• the drug not being suited to the individual
• a lack of monitoring by the health provider
• a need for additional therapies, such as cognitive behavioral therapy (CBT)
• forgetting to take the medication at the right time
Keeping in contact with the doctor and attending follow-up appointments helps improve the chances of the drug working. It may be that the dosage needs changing or another medication would be more suitable.
It is important to take the antidepressant according to instructions, or it will not be effective. Most people will feel no benefits during the first or second week. The full effect will not be present until after 1 or 2 months. Perseverance is vital.
How long does treatment last?
According the United Kingdom’s Royal College of Psychiatry, 5 to 6 people out of every 10 will experience a significant improvement after 3 months.
People who use medication should continue for at least 6 months after starting to feel better. Those who stop before 8 months of use may see a return of symptoms.
Those who have had one or more recurrences should continue the treatment for at least 24 months.
Those who regularly experience recurrences depression may need to use the medication for several years.
However, a literature review published in 2011 found that long-term use of antidepressants may worsen symptoms in some people, as it can lead to biochemical changes in the body.
A doctor will help weigh up the pros and cons of taking antidepressants during pregnancy
In the United States, 8 percent of womenare reported to use antidepressant drugs during pregnancy.
The use of SSRIs during pregnancy has been linked with a higher risk of pregnancy loss, preterm birth, low birth weight, and congenital birth defects.
Possible problems during delivery include excessive bleeding in the mother.
After birth, the newborn may experience lung problems known as persistent pulmonary hypertension.
A study of 69,448 pregnancies found that using SNRIs or TCAs during pregnancy may increase the risk of pregnancy-induced hypertension or high blood pressure, known as pre-eclampsia. However, it remains unclear whether this is due to the drugs or the depression.
Findings published in JAMA in 2006 suggested that almost 1 in 3 infants whose mothers used antidepressants during pregnancy experienced neonatal abstinence syndrome. Withdrawal symptoms included disturbed sleep, tremors, and high-pitched crying. In some cases, the symptoms were severe.
A lab study found that rodents that were exposed to citalopram—an SSRI antidepressant—just before and after birth showed considerable brain abnormalities and behaviors.
However, for some women, the risk of continuing the medication is smaller than the risk of stopping, for example, if her depression could trigger an action that might harm herself or her unborn child.
The doctor and patient need to discuss fully the benefits and potential harms of stopping antidepressants at this time.
If possible, other therapies should be considered, such as cognitive CBT, meditation, or yoga.
Tiny amounts of some antidepressants enter the breast milk, for example, sertraline and nortriptyline.
Within a few weeks after birth, infants can break down the medication’s active ingredients in the liver and kidneys as effectively as adults do.
The decision to use antidepressants at this time will involve several factors:
• Is the infant healthy?
• Were they born preterm?
• Will the mother’s condition deteriorate?
How much of the active ingredients will enter the breast milk, which depends on the type of drug
One study, published in The Journal of Clinical Endocrinology and Metabolism, found that for women who use antidepressants during pregnancy, it may take longer to be able to breastfeed.
The researchers explain that the breast glands are regulated by serotonin, so their ability to produce milk at the right time is linked to the production and regulation of this hormone.
CBT and other types of counselling and therapy can also help with depression.
St John’s wort
Hypericumwhich is made from the herb St. John’s wort, has been shown to help some people with depression. It is available over-the-counter as a supplement.
However, it should only be taken after speaking to a doctor, as there are some possible risks.
• Combined with certain antidepressants, St. John’s wort can lead to a potentially life-threatening increase in serotonin.
• It can worsen symptoms of bipolar disorder and schizophrenia. A person who has or may have bipolar-related depression should not use St. John’s wort.
• It might reduce the efficacy of some prescription medications, including birth control pills, some heart medications, warfarin, and some therapies for HIV and cancer.
It is important to tell your doctor or pharmacist if you plan on taking St. John’s wort.
Some evidence supports the use of St. Johns’ wort to treat depression, but some studies have found it no more effective than a placebo.
People who experience seasonal affective disorder (SAD), or “winter blues,” may benefit from light therapy. This involves sitting in front of a light box first thing in the morning for 20 to 60 minutes. Light boxes are available to purchase online.
Vitamin D supplements may or may not help treat SAD. Evidence is not conclusive.
Diet and exercise
Some studies have shown that a healthy, well-balanced diet, plenty of exercise, and staying in touch with family and friends can reduce the risk of depression and recurrences.
Depression is a serious condition that may need medical treatment. Anyone who experiences the symptoms of depression should seek medical advice.