Antidepressants are medications used to treat depression. The antidepressants most commonly used are the SSRIs and the SNRIs, often referred to as second-generation antidepressants, which have less toxicity and improved safety compared to the first-generation drugs, which include MAOIs and TCAs. The response to antidepressant drug treatment generally takes 3–4 weeks before response becomes evident; however, symptoms respond differentially, with sleep disturbances improving sooner than mood deficits. After the successful control of symptoms, a 6- to 12-month maintenance treatment phase is needed, after which the drug is gradually withdrawn. If a patient is chronically depressed (i.e., has been depressed for more than 2 years), lifelong treatment with an antidepressant is advisable. Approximately two-thirds of patients show a marked decrease in depressive symptoms with an initial course of treatment, with one-third showing complete remission.
Antidepressants help not only in relieving the symptoms of depression, but also anxiety and other disorders. They aim to correct the imbalances of neurotransmitters (chemicals in the brain) that are believed to regulate mood and behavior. Such neurotransmitters are mainly serotonin, norepinephrine, and dopamine. Each type of antidepressant affects these neurotransmitters in slightly different ways. First developed in the 1950s, the use of antidepressants has become more common in the last 20 years, given how effective they can be, particularly the new-generation antidepressants. (Note: The brand names of medicines given below are those available in the US.)
Types of Antidepressants
Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are the most commonly prescribed antidepressants. SSRIs act mainly by blocking the reuptake, or absorption, of the neurotransmitter serotonin in the brain. This more easily facilitates the brain cells to transmit signals, which leads to better regulation of moods. They are called “selective” since they do not affect the other neurotransmitters.
An SSRI is usually the first antidepressant to be prescribed. They cause fewer bothersome side effects and are less likely to cause problems at higher doses than other types of antidepressants. SSRIs include fluoxetine (Prozac), paroxetine (Paxil, Pexeva), sertraline (Zoloft), citalopram (Celexa) and escitalopram (Lexapro).
- Uses: They are effective in treating major depression. SSRIs also are anti-anxiety medications with demonstrated efficacy in the treatment of generalized anxiety, panic, social anxiety, and obsessive-compulsive disorders, premenstrual dysphoric syndrome and for preventing symptoms in postmenopausal women. Sertraline and paroxetine are approved for the treatment of PTSD.
- Side effects: SSRIs may have the following side effects:
- Increased anxiety
- Decreased libido
- Low blood sugar and sodium
- Nausea, vomiting and diarrhea
- Dry mouth
- Weight loss
- Sweating and tremors
- Slowed down thinking
- Decreased concentration
- Paroxetine can lead to congenital cardiac malformations when administered in the first trimester of pregnancy.
The use of SSRIs is not recommended for treating depression in children under 18, in whom efficacy is doubtful and adverse effects, including excitement, insomnia and aggression in the first few weeks of treatment, may occur. The possibility of increased suicidal ideation is a concern in this age group.
- Drug interactions: The MAOIs enhance the effects of SSRIs. Administration of these drugs together can cause high levels of serotonin, leading to the serotonin Syndrome (see below). The SSRIs should not be started until at least 14 days following discontinuation of treatment with an MAOI. For all SSRIs but fluoxetine, at least 14 days should pass prior to beginning treatment with an MAOI following the end of treatment with an SSRI. At least 5 weeks should pass between stopping fluoxetine and beginning an MAOI.
- Serotonin syndrome. Serotonin syndrome occurs when high levels of serotonin accumulate in your body. It most often occurs when two medications that raise the level of serotonin are combined, such as antidepressants, certain pain or headache medications, and the herbal supplement St. John’s wort. Symptoms of serotonin syndrome include anxiety, agitation, sweating, confusion, tremors, restlessness, lack of coordination and a rapid heart rate.
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
Five medications in this group that inhibit the reuptake (absorption) of both serotonin and norepinephrine (two neurotransmitters that stabilize the mood) have been approved for use in the US for treatment of depression, anxiety disorders, pain, or other specific conditions: venlafaxine (Effexor XR), desvenlafaxine (Pristiq, Khedezla), duloxetine (Cymbalta), milnacipran (Ixel, Savella, Dalcipran, Toledomin), and levomilnacipran (Fetzima).
- Uses: SNRIs are found effective in the treatment of major depression and mood disorders. Their less common use is in anxiety disorders, chronic pain, attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), menopausal symptoms, and fibromyalgia. Off-label uses include stress urinary incontinence (duloxetine), autism, binge-eating disorders, hot flashes, pain syndromes, premenstrual dysphoric disorders, and PTSD (venlafaxine).
- Side effects: The SNRIs have a side-effect profile similar to that of the SSRIs, including nausea, constipation, insomnia, headaches, and sexual dysfunction. The immediate-release formulation of venlafaxine can induce sustained increase in blood pressure in 10%–15% of patients at higher doses; this risk is reduced with the extended-release form.
- Drug interactions: A 7-day period is recommended between ending MAOI therapy and starting venlafaxine treatment. Duloxetine has a similar interval for initiation following MAOI therapy; conversely, only a 5-day waiting period is needed before beginning MAOI treatment after ending duloxetine. Not following these waiting periods can result in the serotonin syndrome.
Tricyclic Antidepressants (TCAs)
TCAs are so named because there are three rings in their chemical structure. They may cause serious side effects and hence are not used as first-line drugs for the treatment of depression. They are usually tried if SSRIs or SNRIs are not having the desired effect. Most TCAs inhibit norepinephrine and serotonin reuptake but have much less effect on dopamine uptake. It has been suggested that improvement of emotional symptoms reflects mainly an enhancement of serotonin-mediated transmission, whereas relief of biological symptoms results from facilitation of norepinephrine transmission.
Examples include amitriptyline (Elavil), amoxapine-clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil) and trimipramine (Surmontil).
- Uses: They are used to treat depression, certain anxiety disorders, fibromyalgia, and chronic pain.
- Side effects: Following are some of the side effects:
- Blurred vision
- Dry mouth
- Difficulty urinating
- Irregular heartbeat
- High BP
- Nausea and vomiting
- Abdominal cramps
- Weight gain
- Sexual dysfunction
- Drug interactions: A number of other drugs have similar side-effect profiles as TCAs, and concurrent use risks enhanced side effects. This includes certain drugs given in psychosis (antipsychotics), irregular heartbeat (arrhythmia), and high blood pressure.
Monoamine Oxidase Inhibitors (MAOIs)
MAOIs are usually prescribed only when other antidepressants haven’t worked, because they can cause serious side effects. Monoamine oxidase, a brain enzyme, helps break down neurotransmitters, such as serotonin. MAOIs inhibit the action of monoamine oxidase. Hence there will be more circulating serotonin, which leads to more stabilized moods and less anxiety.
Examples of MAOIs are tranylcypromine (Parnate), phenelzine (Nardil) and isocarboxazid (Marplan), and selegiline (EMSAM, Eldepryl).
- Side effects: They include:
- Blurred vision
- Fluid accumulation
- Weight loss or weight gain
- Sexual dysfunction
- Diarrhea, nausea, and constipation
- Insomnia and drowsiness
- Irregular heart rhythm
- Fainting or feeling faint when standing up
- High blood pressure
- Drug interactions: MAOIs also interact with medications used commonly in cold and allergy, such as pseudoephedrine, phenylephrine, oxymetazoline, phenylpropanolamine, and amphetamine, which should be avoided. Using an MAOI requires a strict diet because of dangerous interactions with foods, such as certain cheeses, pickles and wines, and some medications, such as oral contraceptives, decongestants and certain herbal supplements. These medications should not be combined with SSRIs.
Atypical antidepressants are not typical, that is, they do not fit neatly into any of the other classes of antidepressants. They work by ultimately effecting changes in neurotransmitters, such as dopamine, serotonin or norepinephrine, which are known to regulate mood, and thus help relieve depression. They are each unique medications that work in different ways from one another.
Examples of atypical antidepressants are:
- Trazodone (Desyrel, Oleptro) (also used in insomnia)
- Mirtazapine (Remeron)
- Vortioxetine (Trintellix)
- Vilazodone (Viibryd)
- Bupropion (Wellbutrin, Aplenzin, Forfivo XL) (also used in smoking cessation)
- Side effects: Because each of the atypical antidepressants works differently, each has unique characteristics and varying possible side effects. For example:
- Most cause dry mouth, dizziness or lightheadedness.
- Some may cause sleeplessness, while others may aid sleep.
- Some may cause constipation, while others may increase the risk of diarrhea.
- Some may increase your appetite, resulting in weight gain, while others may cause nausea.
- Some are less likely than others to cause sexual side effects.
- Safety issues: Atypical antidepressants are safe for most people. However, in some circumstances they can cause problems. For example:
- Bupropion should not be used in those with seizures or eating disorders.
- Mirtazapine can increase in cholesterol.
- Nefazodone should not be used in those with liver disorders.
- Trazodone is best avoided in those with heart disease.
- Vortioxetine can increase the risk of bleeding.
- Drug interactions: Some atypical antidepressants can cause dangerous reactions when combined with certain medications or herbal supplements. Talk to your doctor about any medications or herbal supplements that you may be taking.
Finding the Right Antidepressant
People may react differently, with a particular antidepressant working better — or not as well — for you than for another person. Or you may have more, or fewer, side effects than someone else does. The first antidepressant you try may work fine. But if it doesn’t relieve your symptoms or it causes side effects that bother you, you may need to try another. So don’t give up. Given the number of antidepressants available, you’ll most likely find one that works well for you. And sometimes a combination of medications may be an option.
The effectiveness of a certain antidepressant in a close family member, or results of special blood tests, may offer clues about how you may respond to a specific antidepressant. In addition, your doctor takes into account your symptoms, any health problems, other medications you take and what has worked for you in the past.
How long does treatment last?
Typically it takes several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. Around 5-6 people out of every 10 will experience a significant improvement after 3 months. Treatment should continue for at least 6 months to 1 year after starting to feel better. Those who stop before may see a return of the symptoms. Those who have had one or more relapses should continue the treatment for at least 2 years. Those who regularly experience relapses may need to use the medication for several years. Some may need to use it lifelong, particularly those with longstanding symptoms of 2 years or more.
Stopping Treatment with Antidepressants
Antidepressants aren’t considered addictive because it is not necessary to keep raising their dose to get the same effect. 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, stopping an antidepressant abruptly or missing several doses may cause withdrawal-like discontinuation symptoms unless you slowly taper off your dose. Quitting suddenly may cause a sudden worsening of depression. So, never stop an antidepressant on your own without consulting your doctor. Doctors should reduce the dose gradually to minimize the risk of unpleasant withdrawal-like symptoms.
For SSRIs or SNRIs, the symptoms of sudden discontinuation may include dizziness, headache, nervousness, nausea, and insomnia. This discontinuation syndrome appears most intense for paroxetine and venlafaxine. Few patients experience any withdrawal symptoms with discontinuation of fluoxetine. Discontinuation symptoms may be entirely new or similar to some of the original symptoms of the illness, and so cannot be attributed to other causes. The onset of symptoms is usually within a few days of stopping treatment or occasionally during taper or after missed doses. They are usually mild and self‐limiting but can occasionally be severe and prolonged.
Antidepressants and Risk of Suicide
Although most antidepressants are generally safe, the FDA requires that all antidepressants carry black box warnings, the strictest warnings for prescriptions, of this possible side effect, because in some cases, children, teenagers and young adults under 25 may have an increase in suicidal thoughts or behavior when taking antidepressants. This is so especially in the first few weeks after starting or when the dose is changed. Anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior. If a worsening occurs, immediately contact your doctor or get emergency help. But, in the long run, antidepressants are more likely to reduce suicide risk by improving mood.
Antidepressants in Pregnancy and Breastfeeding
Talk to your doctor about the risks and benefits of using specific antidepressants. Some antidepressants may harm your baby if you take them during pregnancy or while you’re breast-feeding. A decision to use antidepressants during pregnancy and breast-feeding is based on the balance between risks and benefits. Overall, the risk of birth defects and other problems for babies of mothers who take antidepressants during pregnancy is low. Still, certain antidepressants, such as paroxetine (Paxil, Pexeva), may be discouraged during pregnancy.
Watch this video on Antidepressants
This 11-min YouTube video by Brooke Miller explains well about antidepressants.
Natural doesn’t always mean safe. Though certain herbal and dietary supplements do seem to work well in some people with depression, more studies are needed. Here are some supplements that are promoted by marketers as helping with depression:
- John’s wort.This herbal supplement is not approved by the FDA to treat depression. It may be helpful for mild or moderate depression. However, use it with caution because it can interfere with many medications, including blood-thinning drugs, birth control pills, chemotherapy, HIV/AIDS medications and drugs to prevent organ rejection after a transplant. Taking St. John’s wort while taking antidepressants can cause serious side effects. So, do not combine them.
- SAMe (S-adenosylmethionine).This dietary supplement is a synthetic form of a chemical that occurs naturally in the body. It is not approved by the FDA to treat depression. More research is needed on it. In higher doses, SAMe can cause nausea and constipation. Do not use SAMe if you’re taking a prescription antidepressant because the combination may lead to serious side effects. SAMe may trigger mania in people with bipolar disorder.
- Omega-3 fatty acids.These fats are found in cold-water fish, flaxseed, flax oil, walnuts and some other foods. Omega-3 supplements are being studied as a possible treatment for depression and for depressive symptoms in people with bipolar disorder. While considered generally safe, in high doses it may interact with other medications. More research is needed to determine if it has an effect on preventing or improving depression.
- Saffron extract may improve symptoms of depression, but more study is needed. High doses can cause significant side effects.
- 5-HTP.The supplement called 5-hydroxytryptophan (5-HTP), may improve serotonin levels, a chemical that affects mood, and thereby helps in depression. But evidence is only preliminary and more research is needed. There is a safety concern that 5-HTP could increase the risk of serotonin syndrome if taken with certain prescription antidepressants.
- Dehydroepiandrosterone (DHEA) is a hormone. Changes in levels of DHEA have been linked to depression. Although several preliminary studies show effectiveness of DHEA as a dietary supplement in treating depression, more research is needed. DHEA has potentially serious side effects, especially if used in high doses or long-term. This supplement comes from the gnarled root of the American or Asian ginseng plant. Ginseng has been used in Chinese medicine for thousands of years to help people improve mental clarity and energy and reduce the effects of stress. Some people associate these properties of ginseng with potential solutions for the low energy and motivation that can occur with depression. However, the National Center for Complementary and Integrative Health (NCCIH) advise that none of the many studies that people have conducted on ginseng have been of sufficient quality to form health recommendations. A study in 2012 reviewed data about chamomile, and its role in helping to manage depression and anxiety, which showed that it produced more significant relief from depressive symptoms than a placebo. However, further studies are necessary.
- Lavender oil is a popular essential oil, used for relaxation and reducing anxiety and mood disturbances. A 2013 review of several studies suggested that it might have significant potential in reducing anxiety and improving sleep. However, there is very little evidence in support of its effectiveness as a treatment for ongoing depression.
The FDA does not monitor the herbal, nutritional and dietary supplements, so you can’t always be certain of what you’re getting and whether it’s safe. It’s best to do some research to make sure you’re buying your supplements from a reputable company, and find out exactly what they contain. Mention to your health care provider before taking any supplements because they can interfere with the actions of certain prescription antidepressants.
Alternatives to Antidepressants
Several alternatives to antidepressants are available for treating depression and other mental health conditions.
Cognitive behavioural therapy (CBT)
It is a type of talking therapy. Most experts recommend that people with moderate to severe depression are treated with a combination of CBT and antidepressants. However, if you’re unable or unwilling to take antidepressants, you have the option of receiving CBT on its own.
CBT helps you understand your thoughts and behavior, and how they affect you. It helps you recognize that events in your past may have shaped you, but it concentrates mostly on how you can change the way you think, feel and behave in the present. It also teaches you how to overcome negative thoughts.
You need a short course of sessions, usually 6 to 8 sessions, over 10 to 12 weeks, on a one-to-one basis, with a therapist trained in CBT. Sometimes, you may be offered group CBT. Computerized CBT works through a computer screen, rather than face-to-face with a therapist.
Interpersonal therapy (IPT)
Interpersonal therapy (IPT) focuses on your relationships with other people and on problems you may be having in your relationships, such as difficulties with communication or coping with bereavement. A course of IPT is usually structured in the same way as a course of CBT. There’s some evidence that IPT can be as effective as antidepressants or CBT, but more research is needed.
It is a form of therapy that helps you think about the problems you’re experiencing in your life to find new ways of dealing with them. You talk in confidence to a counselor, who supports you and offers practical advice. Counselors help you in finding solutions, but don’t tell you what to do. Counseling usually consists of 6 to 12 sessions lasting an hour each. It is ideal for people who are healthy but need help coping with a current crisis, such as anger, relationship issues, bereavement, redundancy, infertility or the onset of a serious illness.
Research suggests that regular exercise may be a more effective treatment for mild depression than antidepressants. Exercise helps boost levels of chemicals called serotonin and dopamine in the brain, which can lift your mood. Exercising on a regular basis can boost self-esteem and confidence, which can help to relieve symptoms of depression.
Talking through your feelings can be helpful. You can either talk to a friend or relative, or you can ask your doctor to suggest a local self-help group. There are also chat rooms on the internet that offer support.
Brain Stimulation Therapies
- Electric shock treatment (ECT): This may be effective if you have severe depression and other treatments haven’t worked. During ECT, you’ll first be given an anesthetic and medicine to relax your muscles. Then you’ll receive an electric current to your brain through electrodes placed on your head. You may be given a series of ECT sessions, usually given twice a week for 3 to 6 weeks. ECT may help reduce connections in an area of the brain linked to depression. The beneficial effect of ECT tends to wear off after several months. Some may have side effects, such as headaches, memory problems, nausea and muscle aches.
- Others: They include vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS). Techniques under trial are Deep brain stimulation and MST (magnetic seizure therapy).
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