Your Guide to Antidepressants and Staying Well
Antidepressants are a class of medications used to manage several mental health issues, and are the quintessential class of pharmacotherapeutic agents prescribed for the treatment of major depressive disorder. Depression is the most common mood disorder in the United States, with a prevalence rate of 14.4%. It affects millions of Americans every year and is a lifelong mental health disorder that can severely impact your ability to work and engage in healthy social relationships. It is most commonly diagnosed among adults between the ages of 18 and 64, but most people experience the onset of depressive symptoms in their 20s.1
In many cases, a combination of therapies will be used to treat depression. This therapeutic strategy may include psychotherapy (talk therapy), a complementary self-care regimen, pharmacotherapy (antidepressant medications), or any combination thereof. Medications commonly used to treat MDD include:2
- Selective serotonin reuptake inhibitors (SSRIs).
- Serotonin-norepinephrine reuptake inhibitors (SNRIs).
- Tricyclic antidepressants (TCAs).
This article discusses in more detail these medications and others, including information about:
- The history and evolution of antidepressants.
- The different types of antidepressants (e.g., SSRIs, MAOIs).
- What conditions they’re typically prescribed for.
- Antidepressants vs. self-medication.
- Withdrawal from antidepressants.
- Resources for help for depression, anxiety, and other mood disorders.
History and Evolution
The first drugs designed specifically as antidepressants were the monoamine oxidase inhibitors (MAOIs). In 1952, Irving J. Selikoff and Edward Robitzek began conducting clinical studies of patients who were given isoniazid (a hydrazine antibiotic). Researchers stumbled upon the mood-boosting effects of the drug while researching new ways to treat patients suffering from tuberculosis. During their clinical trials, the researchers noticed a significant improvement in patients’ moods and began investigating the drug’s efficacy of treating depression.3
During this time, researchers discovered that another hydrazine compound—called iproniazid—had an even greater effect on elevating a patient’s mood. They noted that those who took the drug experienced increased appetite, energy, weight gain, and better sleep. Soon afterward, the term antidepressant was coined, and researchers began studying the efficacy of different drugs among patients with depression. What they found was that the MAOI (iproniazid) lead to increases of serotonin levels in the brain, which significantly improved the person’s social functioning.4
In 1957, at a meeting of the American Psychiatric Association, data on the effects of iproniazid as an antidepressant were presented. More studies were conducted, and within a year more than 400,000 patients affected by depression had been prescribed the drug for treatment. This opened the door for a new class of drugs (later known as MAOIs) designed specifically to treat depression. The demand for MAOIs was enormous because up until that point, there were no pharmacotherapeutic interventions for people with depression.3 Iproniazid was introduced onto the market, but quickly withdrawn in 1961 due to adverse effects among patients, including “cheese reaction”, which will be discussed later.4
Despite the negative reaction to MAOIs and their efficacy, the drug was brought back onto the market by members of the American College of Neuropsychopharmacology, who believed that the benefits of the drug heavily outweighed the risk. Today, MAOIs are not commonly used as the first line of defense against depression. Subsequent clinical trials would challenge their efficacy for the treatment of major depression compared with the then-newer tricyclic antidepressants (TCAs).3 Today, their use has almost entirely been replaced by that of newer-generation antidepressants such as the SSRIs and SNRIs.
What Are the Different Types?
A lot of research has been done since MAOIs were first introduced onto the market, and today there are many types of antidepressants available to treat depression, including:
- Tricyclic antidepressants (TCAs): While researching how to improve antipsychotic drugs, scientists discovered that the drug imipramine (brand name: Tofranil) significantly helped people suffering from severe depression. The discovery was exciting given that the serious side effects people experienced with MAOIs did not exist for people using imipramine. In 1959, the medication was approved by the FDA to treat depression, establishing a new class of drugs called tricyclic antidepressants (TCA). Side effects of TCAs include memory impairments, drowsiness, dizziness, weight gain, potential to overdose, orthostatic hypotension, anticholinergic effects (dry mouth, blurred vision, overheating), and decreased blood pressure.1,5
- Selective serotonin reuptake inhibitors (SSRIs): The first study of an SSRI called fluoxetine was published in 1974. The medication was approved by the FDA in 1987 and introduced onto the US market in 1988 as the now-widely-known Prozac. While the side effects of SSRIs are generally mild, some people experience negative symptoms such as weight gain, nausea, insomnia, sexual dysfunction, and discontinuation symptoms.1,5 Since fluoxetine was introduced, many more SSRIs have been approved by the FDA, including:1
- Sertraline (Zoloft).
- Citalopram (Celexa).
- Paroxetine (Paxil).
- Escitalopram (Lexapro).
- Monoamine oxidase inhibitors (MAOIs): As discussed previously, MAOIs were the first successful pharmacological treatment for depression. Monoamine oxidase is an enzyme that breaks down biogenic amines (including serotonin, dopamine, epinephrine, and norepinephrine that contribute to pleasurable feelings) as well as peripherally acting sympathomimetic amines such as tyramine. MAOIs were taken off of the US market at one point due to unwanted side effects from patients after one doctor traced the effects back to the ingestion of certain cheeses, dubbing the phenomenon “cheese reaction.” Doctors discovered that when MAOIs were taken with foods high in tyramine (some fermented foods, alcoholic beverages, aged cheeses, etc.), the combination increased concentrations of tyramine and norepinephrine in a person’s nervous system. This led to side effects such as increased heart rate, hypertension, and sweating. In response to having MAOIs taken off the market, pharmaceutical companies created more effective, reversible, and selective MAOA inhibitors, including moclobemide (Manerix) and brofaromine (Consonar). Although these drugs also produced side effects like nausea and insomnia, they are available in parts of the world. Moclobemide is not available in the United States, however, and brofaromine is no longer being developed as an antidepressant drug.1 Today, MAOIs are not the first choice for doctors prescribing antidepressants and are only prescribed when a person does not respond well to newer antidepressant drugs.4
- Bupropion: The immediate-release drug bupropion, which goes by the brand name Wellbutrin, was approved in 1989. It is referred to as an atypical antidepressant drug because it is in the category of chemicals called aminoketones that interacts with neurotransmitter systems in the brain much differently than other antidepressant drugs do. Bupropion is a dopamine-norepinephrine reuptake inhibitor, and research shows that it is as effective as other antidepressant drugs to treat depression when taken in 3 daily doses. The sustained-release (SR) version was introduced in 1996 and the extended-release (XL) version in 2003. Compared to other antidepressants, it has the lowest risk of sexual dysfunction with the most common side effects being nausea, dry mouth, and insomnia.1 This medication is contraindicated for people with a current or past history of seizures or eating disorders.5
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): SNRIs also fall under the atypical antidepressant classification. One of the first drugs in this category, venlafaxine (Effexor), was introduced onto the U.S. market in 1993, and the extended release form of venlafaxine was approved for the treatment of depression in 1997. SNRIs work by selectively targeting the serotonin and norepinephrine transporters in the brain. Some studies suggest that SNRIs are more effective than SSRIs at treating depression, but more studies are needed. Side effects include sexual dysfunction.1 Since the approval of venlafaxine, other SNRIs have been approved by the FDA for the treatment of depression, including:1
- Duloxetine (Cymbalta).
- Desvenlafaxine (Pristiq).
- Milnacipran (Savella).
What Are They Prescribed For?
Antidepressants are mainly prescribed to treat the symptoms of extreme sadness and exhaustion most often associated with depression. As a class of drugs, antidepressants are thought to work by restoring a person’s emotional balance via specific neurotransmitter activity so that they can function in their day-to-day lives. People may also be prescribed these medications to relieve anxiety, sleeping issues, suicidal thoughts, and restlessness.6
So how do antidepressants actually work? In our brains, certain nerve cells, or neurons, interact with each other via the release of signaling molecules called neurotransmitters. When these chemicals (e.g., serotonin and dopamine) are out of balance, it can lead to mental health problems such as depression. Although scientists continue to study and learn more about the exact mechanisms of depression, experts believe that when a person is depressed, there may actually be a problem occurring between interconnected neurons. Taking medications, such as SSRIs or TCAs, can help increase the availability of certain neurotransmitters throughout the brain to improve the symptoms of depression and some other mental health conditions.6
Generally, antidepressants are taken on a daily basis. During the first weeks and months of taking one, the primary goal is to manage depressive symptoms. It’s not always the case that symptoms will disappear completely, but they should improve and feel manageable. To achieve this, most people stay on their medication for a year or two, after which your doctor will assess your condition and make a recommendation for the next phase of treatment. Staying on your antidepressant consistently helps prevent symptoms from reappearing or becoming unmanageable. Those who are ready to discontinue medication (at their doctor’s approval) do well to continue with individual therapy or counseling to manage any minor symptoms that linger. Regardless of what works best for you, this decision should always be made between you and your doctor.6
As you near the end of treatment, your doctor will gradually reduce your dose over a period of several weeks in a process known as tapering. Though antidepressants are not thought to result in the development of physical dependence in the same manner as some prescription medications, such as sedatives, while you taper, you may experience side effects such as trouble sleeping, nausea, or restlessness. This is normal, and it is important that you adhere to whatever regime your doctor has given to you even if you experience these problems. Sometimes, people stop taking their medication as soon as they start feeling better, but this can increase your chances of the depressive symptoms returning. Your improved mood and energy levels are a sign that your medication is working and that you should continue taking it—not that you no longer need it.6
It is important to keep regular appointments with your doctor while you are taking antidepressants. There are many variables that come into play when taking a medication for a mental health disorder, so it’s essential to talk with your doctor about whether your symptoms have improved or worsened, or whether you are experiencing any side effects. Depending on how you are affected by the medication, your doctor may adjust your dose, but you should never adjust the dose on your own. The primary risk of doing this is that the medication may not work as it is intended, and you could experience unpleasant side effects.6
Antidepressants vs. Self-Medication
It is often common for people to turn to negative or maladaptive “self-medicating” activities like drinking alcohol or using drugs to temporarily avoid experiencing the feelings of depression. Other self-medicating activities might include the misuse of prescription medications, self-harming behaviors, or engaging in risky sexual activities, such as anonymous sex with multiple partners.
The safest and most effective way to treat depression is to see a trained medical or mental health professional to receive behavioral therapy, medication, or both. Some people object to taking medication for a mental health disorder because they believe it’s a problem of that can be overcome by sheer will. However, depression is thought to be a disease of the brain that arises from impaired neurochemical functioning. Medication is designed to help correct this brain imbalance. It is often a first step to stabilize symptoms with an antidepressant so you can more effectively take part in other therapeutic options, such as psychotherapy or peer support groups.
It is important to remember that not everyone responds positively to antidepressants, so you should share your full medical history with your doctor before you begin any medication and work closely with an experienced psychiatrist to determine the best way to manage your depression. Like all drugs, these medications can have a number of side effects that could be uncomfortable enough to prompt you to discontinue use or switch to another medication. Unfortunately, side effects often lead people to stop refilling their prescriptions or to stop taking their medication once they start feeling better. In fact, studies show that many patients take their antidepressant for 14 weeks or less.7 What research shows is that long-term treatment is necessary in order prevent depression from returning. Nevertheless, if you are experiencing adverse reactions to medication, speak to your doctor about your options.
Compared to choosing common methods of self-medicating, such as abusing alcohol, gambling, or compulsive sexual behavior, a treatment course with an option to include antidepressants and ongoing therapy presents the wiser choice.
What Happens When You Stop Taking Your Medication?
Depression is a naturally fluctuating condition. Many people begin feeling much better after taking medication for a few weeks and believe that they can stop using antidepressants as a result. However, these early improvements in mood are simply an acute response to the medication and not a true remission.7 Studies show that stopping antidepressant medication prematurely can actually increase the risk of relapse or recurrence, especially when the withdrawal is abrupt.
When people use antidepressants consistently for a long time, it can protect them from experiencing the following:7
- Relapse and recurrence of depressive symptoms
- Worsening of existing depressive symptoms
- Discontinuation symptoms (aka, withdrawal)
The question of when to stop taking antidepressants is one that every person must consider at some point. Because complete remission of depressive symptoms is the goal of therapy, it is important to confirm that your depression has sufficiently resolved before you discontinue your medication. Your doctor will work with you to determine the severity and improvement of your depression using clinical scales. New recommendations state that treatment should be continued for 9 months to prevent relapse, while other experts believe that medication should continue anywhere between 3 years to a lifetime.7
Most drugs use the term withdrawal syndrome when referring to stopping use of a drug. However, in the case of antidepressants, experts prefer the term discontinuation syndrome since the effects of stopping TCAs, MAOIs, SRIs, SSRIs, and SNRIs are usually mild and not long-lasting. In most cases, drug withdrawal symptoms peak in the first week and gradually fade away, however, discontinuation symptoms differ depending on the drug taken and can range widely in their severity.7,8
Some of the discontinuation syndrome symptoms you may experience include:7,9
- Vivid dreams.
- Urinary retention.
- Sexual dysfunction.
- Parkinsonian symptoms.
- Lowered seizure threshold.
- Crying spells.
- Depressed mood.
- Suicidal thoughts.
How to Get Help for Depression
Depression affects every person differently, but a few common signs of the disorder include:10
- Pervasive feelings of sadness.
- Feeling empty.
- Forgetting things.
- Losing interest in things you used to find enjoyment in.
- Trouble making decisions.
- Sleeping a lot.
- Not sleeping enough.
- Feeling hopeless.
- Gaining weight.
- Losing weight without intending to.
- Suicidal thoughts.
Fortunately, depression can be treated, starting by making an appointment with your primary care physician and asking for a referral to a mental health clinician or a psychiatrist. Having an open conversation with your doctor will help them refer you to the appropriate mental health professional.
If you do not have a primary health care provider or you do not feel comfortable visiting with one, a few other places you can go to get help for depression include:
- Community clinics.
- Church resource centers.
- Inpatient treatment centers.
- Outpatient treatment centers.
- Support groups.
- Counselors or social workers.
- Family service agencies.
- Social services.
During your visit with your doctor, they may check to see if you have other health conditions that need to be addressed. For example, a thyroid disease can lead to depression or worsen symptoms.
Getting the help you need will improve not only your life, but those closest around you. Don’t be afraid to reach out to your family, friends, neighbors, community, or religious leaders for support as you begin working through your depression. It can be scary and overwhelming to admit you have a mental health problem, but it is an important and necessary step to healing.
Tips for Staying Well
Once you have gone through the appropriate steps to get treatment for depression and are managing the symptoms well with your treatment team, there are healthy ways to continue to take care of yourself and keep your depression at bay.
In some cases, individuals are able to lessen the impact of their depression by making certain healthy choices in their daily routines. Taking some time to look at areas of your life that may be causing you stress can reveal where to make adjustments. Take an inventory of your physical, emotional, spiritual, economic, and social wellbeing and go from there.
Ways that you can practice self-care while you are being treated for depression and afterward might include:
- Eating healthy: Research shows that adopting a healthy diet can help prevent cancer, dementia, and depression. What you put into your body has a huge effect on your mind. You can talk to your doctor or a nutritionist about what foods they recommend, but some experts emphasize the importance of eating unprocessed fruits and vegetables, seeds, lean protein, nuts and avoiding the consumption of alcohol, processed meats, sugar, flours, and other meats.11
- Getting enough sleep: Many people who suffer from depression also experience sleep problems. Conversely, having a sleep disorder increases the odds you’ll develop depression. Avoid using caffeine, alcohol, or nicotine before bed. You can also practice good sleep hygiene by creating a sleep schedule. Download an app on your phone to track your sleep or to make sure you always get to bed at a certain time. Clear your bedroom of any distractions and, if possible, remove all electronics from your bedroom. You can buy blackout curtains to darken your room and ensure no light disrupts your sleep. Practicing meditation or guided imagery before bed also helps your body relax and calms any racing thoughts. Free apps like Insight Timer have hundreds of sleep meditations to choose from. If you suffer from insomnia, talk to a medical professional before taking medication—some SSRIs can cause or worsen insomnia.12
- Drinking enough water: You could treat yourself to a fancy new water bottle to make drinking water more fun, or you can infuse water to make it taste better. Some people like to squeeze a lemon or drop mint into your bottle for extra (and healthy) flavor.
Explore activities to help improve your mood, including:
- Volunteering: Pick a cause or charity that you feel passionate about because volunteering your time and being of service can be huge contributors to your overall wellbeing. In fact, studies show that people who donate their time feel more socially connected, which helps prevent feelings of loneliness.13
- Doing yoga: Studies show that yoga can be helpful for anxiety and depression because it helps relieve stress, reduces heart rates, lowers blood pressure, and helps people respond better to stress.14
- Getting a pet: Animal-assisted therapy may offer numerous health benefits, with some studies supporting a role in lowered blood pressure, improved cholesterol levels, and a decreased risk of heart disease. They also provide unconditional love, something that feels great if you are struggling with depression. When you interact with an animal, your brain produces oxytocin, the connection hormone that mothers feel when holding their children. This helps boost the levels of serotonin in your brain and leads to feelings of calmness and wellbeing. People with animals tend to experience less loneliness, depression, and anxiety.15
- Hillhouse, T. M. & Porter, J. H. (2015). A brief history of the development of antidepressant drugs: From monoamines to glutamate. Experimental and Clinical Psychopharmacology, 23(1), 1–21.
- Institute for Quality and Efficiency in Health Care. (2017). Depression: How effective are antidepressants?
- López-Munoz, F., Alamo, C., Juckel, G., & Assion, H. J. (2007). Half a century of antidepressant drugs: on the clinical introduction of monoamine oxidase inhibitors, tricyclics, and tetracyclics. Part I: monoamine oxidase inhibitors. Journal of Clinical Psychopharmacology, 27(6), 555–559.
- Ramachandraih, C. T., Subramanyam, N., Bar, K. J., Baker, G., & Yeragani, V. K. (2011). Antidepressants: From MAOIs to SSRIs and more. Indian Journal of Psychiatry, 53(2), 180–182.
- Sansone, R. A. & Sansone, L. A. (2008). Pain, Pain, Go Away: Antidepressants and Pain Management. Psychiatry (Edgmont), 5(12), 16–19.
- Institute for Quality and Efficiency in Health Care. (2017). Depression: How effective are antidepressants?
- Shelton, R.C. (2001). Steps Following Attainment of Remission: Discontinuation of Antidepressant Therapy. Primary Care Companion to The Journal of Clinical Psychiatry, 3(4), 168–174.
- Harvard Medical School. (2014). What are the real risks of antidepressants?
- Carvalho, A.F., Sharma, M.S., Brunoni, A.R., Vieta, E., & Fava, G.A. (2016). The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature. Psychother Psychosom, 85, 270–288.
- U.S. Department of Health and Human Services. (2018). Talk with Your Doctor about Depression.
- Harvard Medical School. (2018). Diet and Depression.
- Harvard Medical School. (2018). Sleep and Mental Health.
- Yeung, J.W.K., Zhang, Z., & Kim, T. Y. (2018). Volunteering and health benefits in general adults: cumulative effects and forms. BMC Public Health, 18, 8.
- Harvard Medical School. (2018). Yoga for anxiety and depression.
- Harvard Medical School. (2016). Talk to the animals.