Antidepressants

What Are Antidepressants?

Antidepressants are a diverse group of prescription psychotropic medications that primarily treat depression and anxiety. They are the most prescribed psychoactive medications.

In the United States, about 1 in 10 people take an antidepressant.

Over the last 10 years, prescriptions of antidepressants have continued to increase. A study out of the University of Michigan identified a 66% increase in antidepressant medications between 2016 to 2022. These medications are most commonly used to treat depression but have many other treatment uses, including post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), chronic pain, and bulimia.

The 2022 National Survey on Drug Use and Health estimates that 22.5 million US adults suffer from depression and 15.9 million adults had depression serious enough to cause significant impairment.

Effective treatment is necessary to reduce the negative impact of depression. Antidepressants are an important treatment option to help return individuals to their regular functioning.

How Do Antidepressants Work?

There are five main classes of antidepressants, and each class works by affecting three primary chemicals in the brain: serotonin, norepinephrine, and dopamine.

Each chemical plays a different role in brain health. Serotonin is the primary target of many antidepressants, as it has a key role in mood regulation, learning, and memory. Norepinephrine is important in the body’s stress response, alertness, and attention. Dopamine is important in cognitive functioning, focus, and the pleasure/reward system of the brain.

Most antidepressants work by increasing the availability of one or more of these chemicals in the brain. This can improve mood, attention, and the ability to enjoy an experience. For example, one class of antidepressants, the selective serotonin reuptake inhibitors, increases the availability of serotonin by preventing it from being broken down.

What Conditions Do Antidepressants Help Treat?

It is a common misconception that antidepressants are only beneficial in the treatment of depression. However, there is a wide range of psychiatric conditions that antidepressants help treat, including:

• Generalized anxiety disorder
• Obsessive-compulsive disorder
• Binge eating disorder
• Body dysmorphic disorder
• Premenstrual dysphoric disorder
• Bulimia nervosa
• Social anxiety disorder

Some antidepressants are also beneficial in the treatment of nonpsychiatric conditions such as chronic pain, fibromyalgia, premature ejaculation, and postmenopausal symptoms such as hot flashes.

What Are The Types Of Antidepressants?

Each of the five classes of antidepressants works by affecting different chemicals in the brain and produces slightly different positive results and negative side effects. These classes include:

• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin and norepinephrine reuptake inhibitors (SNRIs)
• Monoamine oxidase inhibitors (MAOIs)
• Tricyclic antidepressants (TCAs)
• Atypical antidepressants

There are several antidepressant medications within each class.

SSRIs

The most prescribed antidepressants come from the selective serotonin reuptake inhibitor class. These medications primarily increase the availability of serotonin in the brain and include medications such as:

• Sertraline
• Paroxetine
• Escitalopram
• Fluoxetine
• Citalopram

These medications have milder side effects and a very good safety profile, even if overdosed. Most are available as generic medications and are widely available and inexpensive. For these reasons, SSRIs are preferred and considered first-line for depression.

SNRIs

The serotonin and norepinephrine reuptake inhibitors increase the availability of serotonin and norepinephrine in the brain. SNRIs are generally more energizing and more directly target the “sluggish” effects of depression, such as decreased focus, lack of motivation, and low energy. The medications in this class also help chronic pain and fibromyalgia. Medications in this class include:

• Duloxetine
• Venlafaxine
• Desvenlafaxine

Compared to SSRIs, they have more bothersome side effects but are generally still well tolerated.

MAOIs

Monoamine oxidase inhibitors (MAOIs) are an older class of antidepressants. The mechanism of action is unclear, but there seem to be effects that increase the availability of all three main chemicals in the brain.

These medications are typically reserved for conditions that have not responded to usual treatments due to concerns with drug and food interactions and increased risk of lethal outcomes in overdose. Some medications in this class include:

• Selegiline
• Phenelzine
• Tranylcypromine

Certain MAOIs, such as phenelzine and tranylcypromine, require dietary restrictions, as interaction with tyramine can lead to a condition of excessively high blood pressure called a hypertensive crisis. Tyramine is an amino acid found in aged cheeses, fermented meats, and fermented soy products. These foods must be avoided in individuals taking certain MAOIs.

TCAs

Tricyclic antidepressants are another older class of antidepressants that increase the availability of serotonin and norepinephrine. This class of medications is also typically reserved for treatment-resistant conditions due to more significant side effects and the risk of overdose. There is a higher risk of the development of abnormal heart rhythms, retention of urine, and slowing of gut motility. Some medications in this class include:

• Amitriptyline
• Nortriptyline
• Doxepin
• Imipramine

These medications are used more commonly in other fields of medicine to treat migraines, sleep, and chronic pain at much lower doses than would be needed to treat depression and anxiety.

Atypical Antidepressants

Atypical antidepressants do not fall neatly into any other category because they work differently than other antidepressants. These include:

• Mirtazapine
• Bupropion
• Nefazodone
• Trazodone

Mirtazapine blocks central receptors to cause an increase in the release of norepinephrine and serotonin. It is known for being generally well tolerated, with few drug-drug interactions and fewer side effects. It is sedating and stimulates appetite and works well for individuals with depression and anxiety that cause disturbed sleep and appetite. It is a popular choice among older adults because of its favorable side effects, tolerability profile, and minimal drug-drug interactions.

Bupropion is a norepinephrine and dopamine reuptake inhibitor (NDRI) that increases the availability of dopamine and norepinephrine. It is considered the most energizing of the antidepressants. While other antidepressants typically treat both depression and anxiety, classically, bupropion is thought to be too energizing to treat anxiety and can sometimes increase anxiety, so it is not a usual first-line medication for treating anxiety disorders. However, there are individuals whose PTSD or generalized anxiety disorder responds to bupropion.

How Do You Take Antidepressants?

Antidepressants work best when taken daily. They do not have immediate effects and must build up in your system to become effective.

Most come in tablet and capsule form, and some are liquid formulations.

What Time Of Day Should You To Take Antidepressants?

It usually does not matter what time of day the antidepressant is taken, so the best time to take the medication is the time that you are most likely to remember to take it.

There are some exceptions, though, as some antidepressants are sedating and help with sleep. These medications should be taken before bedtime to help with falling and staying asleep. Alternatively, some antidepressants are energizing and may cause insomnia if taken too close to bedtime, so these should be taken earlier in the morning.

Try to take it around the same time every day. Keeping this routine helps you to remember to take it consistently and ensures a steady level in your system. If you forget to take your medication and it is still the same day, it is appropriate to take it when you remember it unless it may interfere with your sleep.

If you miss a day or two, there is no need to double up on your dose. Just resume your antidepressant as you normally would when you remember it.

How Long Do You Take Antidepressants?

For a first episode of depression, it is generally recommended to continue your antidepressant for at least 9–12 months. If your symptoms have resolved after this time, you can discuss with your doctor about tapering off the antidepressant if you so desire.

Can You Get Dependent On Antidepressants?

There is little risk of physical dependence with antidepressants. However, some antidepressants can cause discontinuation symptoms, particularly if stopped abruptly. These symptoms can be very bothersome and include:

• Flu-like symptoms
• Electric sensations in the legs
• Brain zaps
• Dizziness (particularly when moving the eyes back and forth)

It is important to note that the development of these physical symptoms is not a sign of addiction.

Antidepressants do not cause the symptoms seen with substance use disorders, such as intoxication or craving the antidepressant. The mechanism of action of antidepressants is more complex than can be explained in words. Some changes occur on a microscopic level that contributes to physical symptoms when the medication is stopped. This is why it is important to discuss with your doctor before stopping your medication so you can gradually reduce the dose over time and minimize these effects.

Can You Develop A Tolerance To Antidepressants?

You do not develop a tolerance for antidepressants over time, meaning that the effectiveness does not change over time. If it seems as though it is not as effective as it once was, this is often due to external factors, like an increase in stress or the addition of other medications, which may be lowering the effective dose of your antidepressant.

Very rarely, after being on an antidepressant for a very long time (on the order of decades), it can suddenly lose its effectiveness. This is a condition called tachyphylaxis.

The Effects Of Antidepressants

Antidepressants help to even out mood and “turn down the volume” of anxious thoughts, making them easier to dismiss. They can also help prevent anxiety attacks so the attacks become less frequent and severe. Sometimes, the anxiety attacks may go away altogether.

Antidepressants also help individuals feel less reactive. They give people a few extra minutes to pause and think before responding. Energizing ones such as bupropion can more directly improve concentration. Bupropion helps improve motivation, enjoyment, and pleasure, so getting out of bed in the morning is easier as is doing the tasks you don’t find interesting.

Antidepressants are effective in improving the rates of treatment response and achieving remission of depression. Quality of life may also improve with antidepressant treatment. A recent meta-analysis published in The Lancet compared the effectiveness and acceptability of 21 antidepressants and found that they all performed better than a placebo.

Individual Factors

While antidepressants are generally considered equally effective, they are not equally effective in every person. An antidepressant that works for one individual may not work for you. Sometimes, finding the right fit for you takes a few trials. Your treatment should be tailored to address your specific symptoms, increasing the likelihood that the selected medication will work for you.

How The Type Of Depression Impacts The Efficacy Of Antidepressants

There are different subtypes of depression, and different antidepressants are effective depending on the type.

• Atypical depression is characterized by overeating, oversleeping, a sensation of feeling weighed down, and being sensitive to criticism. MAOIs are more effective for atypical depression.
• Melancholic depression is characterized by a loss of pleasure, early morning awakening, slowed speech and thoughts, excessive guilt, and weight loss. TCAs work better for melancholic depression.
• Individuals with sleep disturbance and poor appetite respond better to a sedating option such as mirtazapine or paroxetine, which can help with sleep and appetite in addition to improving mood.
• Duloxetine can be more beneficial for individuals with other medical conditions, such as chronic pain and fibromyalgia.

What Are The Side Effects Of Antidepressants?

In general, these medications are well tolerated. There are side effects that are more common and specific to each class of antidepressants.

The main four classes of antidepressants (SSRIs, SNRIs, MAOIs, and TCAs) can all cause decreased libido, difficulty achieving orgasm, and erectile dysfunction. These are reversible side effects that would resolve with discontinuation of the antidepressant. If you otherwise find your medication beneficial and would like to continue on it but do not enjoy the sexual side effects, there are strategies to mitigate these side effects.

SSRIs

SSRIs tend to cause:

• Nausea
• Heartburn
• Diarrhea or constipation
• Headaches

This is because serotonin receptors also line our gastrointestinal tracts. You may also experience easier bruising since serotonin can affect platelet function.

SNRIs

SNRIs can also have some of the gastrointestinal side effects that are seen in SSRIs and may also cause:

• Mild blood pressure elevation
• Insomnia
• Dry mouth
• Excessive sweating

This class is also more likely to cause discontinuation symptoms if one or two doses are missed, particularly if you take a higher dose. These symptoms include electric sensations in the legs, brain zaps, and dizziness, particularly when moving your eyes back and forth. These symptoms can be very uncomfortable but are temporary. If the SNRI is not resumed after one or two missed doses, these discontinuation symptoms can persist for up to several months.

MAOIs

MAOIs can also cause the previously mentioned gastrointestinal side effects in addition to:

• Blurry vision
• Dizziness
• Restlessness

TCAs

Side effects of TCAs include gastrointestinal side effects and the development of:

• Abnormal heart rhythms
• Dry mouth
• Urinary retention

Many of these side effects tend to improve within a few weeks as an individual adjusts to the medication in their body.

Mirtazapine And Bupropion

Mirtazapine most commonly causes drowsiness and weight gain but rarely has sexual side effects.

Bupropion can cause insomnia, jitteriness, heart racing, and increased anxiety. Like mirtazapine, it does not typically cause sexual side effects, and both medications can be started to address the sexual side effects of other antidepressants.

What Are The Possible Complications Of Taking Antidepressants?

There has been no conclusive evidence to show long-term harm to any of the organ systems from chronic antidepressant use. However, all antidepressants have a black box warning on them regarding the increased risk of suicidal thoughts.

Since these medications affect the chemicals in the brain, this sometimes leads to new and unusual thoughts. This happens more commonly in adolescents to young adults up to the age of 24. If this occurs, contact your doctor immediately and stop your medication. If it is after hours and you cannot reach your doctor, go to your nearest emergency room. Discontinuing the antidepressant typically resolves this side effect. Overall, antidepressants usually help reduce the frequency and intensity of pre-existing suicidal thoughts.

Do Antidepressants Cause Weight Gain?

Several antidepressants are known to cause weight gain, including an SSRI, paroxetine, and an atypical antidepressant, mirtazapine. Both stimulate appetite and can contribute to weight gain. Most others are considered weight-neutral but can sometimes lead to weight gain.

Some of this results from the effect of depression and anxiety on an individual. Some individuals have decreased appetite and lose weight when they are depressed and anxious. As treatment improves their depression and anxiety, they will eat more and gain weight.

Others have increased appetite and gain weight when they are depressed and anxious. As treatment improves their depression and anxiety, their appetites return to their baseline, and they start losing weight.

Fluoxetine is an SSRI that is least likely to cause weight gain and can potentially decrease appetite. Bupropion is an atypical antidepressant that can suppress appetite and lead to weight loss.

How Long Does It Take For Antidepressants To Work?

Antidepressants take an average of four to six weeks to start being effective. Many factors play into the efficacy of an antidepressant. Every antidepressant has a therapeutic dose, which is a target dose found to be most effective at addressing a specific condition. The therapeutic dose for anxiety is typically higher than the therapeutic dose for depression.

For example, a standard depression dose for a common SSRI, sertraline, is around 100–150 mg daily. A standard anxiety dose for sertraline is 200 mg daily. For OCD, the dose can be increased up to 400 mg daily.

Antidepressants are started at much lower doses to let the body adjust and reduce adverse side effects. The dose is increased gradually until the therapeutic dose is reached. Before the therapeutic dose is reached, you may not notice much, if any, of the positive effects.

When Should I Call My Healthcare Provider?

You should call your healthcare provider to be evaluated for depression if you are consistently experiencing:

• Low moods
• Difficulty getting motivated to get out of bed or take a shower
• Difficulty sleeping or sleeping too much
• Feeling hopeless
• Thoughts of suicide

If you are taking an antidepressant already, call your healthcare provider right away if you experience new thoughts of suicide.

Contact your healthcare provider if you develop a rash on your body, shortness of breath, or other evidence you may be having an allergic reaction to your antidepressant.

If you notice you are going several nights in a row not sleeping or sleeping very little (less than four hours a night) but feel energized and are more impulsive and reckless and behaving unlike yourself, contact your healthcare provider. In some cases, this could be isolated to the antidepressant you are taking and may not recur. However, this could also show that the diagnosis is not correct, and an antidepressant might not be the right class of medication for you.

In the beginning, you should check in with your healthcare provider at least every one to two months to monitor your progress in treatment. If you haven’t noticed any benefit to your medication and it has been over two months, a dose adjustment may be needed. Work closely with your healthcare provider and keep a log of changes in your symptoms and the response to the antidepressant to speed up your recovery time.

Antidepressants And Your Mental Health

Antidepressants are prescribed to treat a variety of mental health conditions. Due to their chemical makeup and mechanism of action, prescribing antidepressants is an individualized process, and it is not unusual for it to take a few trials to find the right fit for you.

If you experience consistently low moods, low motivation, low energy, difficulty sleeping, and a change in appetite, contact your doctor to discuss whether you have depression and whether you may benefit from taking an antidepressant.