What You Should Know About Selective Serotonin Reuptake Inhibitors (SSRIs) and The Discontinuation Syndrome

 What are SSRIs?

A selective serotonin reuptake inhibitor (SSRI) is a medication used to treat depression. That is to say, it is an antidepressant medication. Many clinicians prescribe this medication because it tends to have fewer side effects.

This article discusses SSRIs, the types, common side effects caused by these medications, the discontinuation syndrome, and other factors that can help you determine whether or not SSRIs are good for you.

What conditions do SSRIs treat?

Selective serotonin reuptake inhibitors are often used to treat depression. These medications can also treat other conditions as well. Conditions that may be treated with SSRIs include:

·       Panic disorder

·       Obsessive-compulsive disorder

·       Premenstrual dysphoric disorder

·       Post-traumatic stress disorder

·       Bulimia

·       Anxiety

·       Hot flashes (common in women that have reached menopause)

·       Anxiety

SSRIs are often used to treat anxiety, and it has been approved for use by the Food and Drug Administration (FDA) for this purpose. Examples of SSRIs used to treat anxiety include paroxetine, sertraline, and escitalopram.

How do selective serotonin reuptake inhibitors work?

Serotonin is a brain chemical that assists in the transmission of signals between brain cells. It is commonly called the “feel-good hormone” because it makes a person feel relaxed. Serotonin is produced in the Raphe nuclei in the brainstem, the taste receptor cells in the tongue, and also in the Merkel cells of the skin.

A person who is depressed has low levels of serotonin. He or she also has low levels of norepinephrine, dopamine, and other brain chemicals. When you take SSRIs, they will prevent the absorption of some serotonin from your brain. So, you’ll have more serotonin in your brain which can help relieve depression.

It is important to note that SSRIs DO NOT stimulate the production of more serotonin. Instead, they help your body to make effective use of the serotonin it already has.

It is also worth knowing that SSRIs have fairly similar effectiveness. However, there may be slight variations in what they are used to treat, their dosage, side effects, and other factors.

SSRI drug list

There are several types of selective serotonin reuptake inhibitors today. Drugs in this category include:

·       Escitalopram (Lexapro)

·       Citalopram (Celexa)

·       Fluoxetine (Sarafem and Prozac)

·       Sertraline (Zoloft)

·       Paroxetine (Pexeva, Paxil XR, Paxil)

·       Fluvoxamine (Luvox)

The discontinuation syndrome

We have established that selective serotonin reuptake inhibitors are used to treat depression. These drugs normalize brain function in people with mood disorders. It does this by boosting serotonin concentration in the brain. Yes, SSRIs are very beneficial. However, it has some downsides. One of these is that it may cause what is known as SSRI discontinuation syndrome in some people [1].

Discontinuation syndrome occurs if you suddenly stop taking your medications. Sometimes, you may feel like you’ve got the flu. You may feel nervous, have an upset stomach, feel dizzy, or experience shock-like sensations in your arms and legs. People who experience discontinuation syndrome may believe that they are suffering a relapse and even request to continue with the SSRIs.

Why SSRI discontinuation syndrome occurs

We know that serotonin is a neurotransmitter. Its main function is to transmit messages to the brain cells and from them. By modifying this process, the brain chemistry is regulated in a way that improves anxiety or depression.

SSRI medications used for the treatment of mood disorders have similar mechanisms of action. However, the drug's half-life varies. The half-life of a drug refers to how long a drug molecule can remain in the bloodstream before it is removed from the body.

A drug that has a short half-life may require frequent dosing to maintain optimal concentration in the blood (as by extension, the desired effect). If the drug has a long half-life, it will remain in your blood (general circulation) for a longer time.

The thing with SSRIs is that most of them have short half-lives.

Of all the SSRIs listed above, fluoxetine (Prozac), has the longest half-life. When you stop taking Prozac, it clears gradually from the bloodstream [2]. On the other hand, other SSRIs have a shorter half-life, so when you stop taking them, their concentration decreases drastically. When this happens, you’ll experience profound or disconcerting withdrawal symptoms.

What happens in the brain during discontinuation syndrome?

The half-life of an SSRI is not entirely the reason why you may experience the discontinuation syndrome. Prolonged use of SSRIs can cause changes in the brain which alters serotonin receptors [3].

Alterations in serotonin receptors will result in a “downregulation” of the number of receptors that respond to serotonin. That means there will be fewer receptors to respond to the increased volume of serotonin. This mechanism helps to prevent overstimulation of brain cells.

When you stop the treatment, you’ll have fewer receptors than before and of course, a low serotonin activity. Your body will attempt to correct this, so you may likely experience periods of adjustment until your system normalizes.

 Common symptoms of discontinuation syndrome

Most symptoms of discontinuation syndrome appear “flu-like.” It may also seem as if you’re experiencing depression or anxiety again [1]. These symptoms include:

·       Vertigo

·       Dizziness

·       Lightheadedness

·       Irritability

·       Fatigue

·       Nausea & vomiting

·       Insomnia

·       Headaches

·       Chills

·       Diarrhea

·       Shock sensations

·       Psychosis

·       Suicidal thoughts

·       Muscle pain

·       Depersonalization (having an out-of-body, or detached experience)

·       Impaired concentration

·       Visual disturbances

Yes, these symptoms may cause a great deal of discomfort, but they are not severe. Many people experience mild to moderate forms of discontinuation syndrome.

 How can I prevent SSRI discontinuation syndrome?

At least 20% of people using Zoloft, Lexapro, or Paxil may experience some degree of discontinuation syndrome following discontinuation of treatment. The symptoms may last between one to three weeks [4]. For long-term users of SSRIs, the symptoms persist for a longer time.

To reduce your risk of withdrawal symptoms, wean off your medication ONLY under the guidance of your doctor. Never do it on your own. If you’ve taken these medications for over 8 weeks, then you can taper off over 1-2 weeks. If treatment has lasted for 6-8 months, then you may wean off over 6-8 weeks.

Avoid making up your course of action. Also, do not stop treatment unless you are advised by your doctor. When you work with your doctor, they will better understand the potential hazards and the limitations of the drugs you’re taking and will be able to guide you the right way.

Let’s take a detailed look at how to prevent SSRI discontinuation syndrome.

1.     Take your time

Some people may face the temptation of discontinuing their medications as soon as the symptoms ease. However, it is important to note that you stand a chance of sliding back into depression if you quit too soon. Clinicians recommend that people taking SSRIs should stay on the medication for at least six months before going off [5]. If you have experienced up to three recurrences of depression, then continue with the medication for at least two years. Discuss with your healthcare provider about the benefits and risks of SSRIs in your situation, and work together to decide when you should stop using them. Before weaning off the drugs, ensure that you’re confident about your wellbeing. Also ensure that your life is stable (career, relationships, etc.). Note that it is very unsafe to quit during stressful conditions, or when you are undergoing significant changes in your life, for instance illness or a new job.

2.    Create a plan

Going off an SSRI or antidepressant involves gradual reductions in your doses, while allowing 2-6 weeks between dose reductions [6]. Your healthcare provider will guide you on how to taper your dose. They will also give prescriptions on the right dosage pills. The dosage and schedule for tapering will depend on the type of SSRI you are taking, how long you’ve been taking your current dose, and the symptoms you’ve had during previous medication changes. You should also create a “mood calendar” where you will keep a record of your mood on a daily basis (using a scale of 1-10).

3.    Psychotherapy helps; consider it

Less than 20% of antidepressant users opt for psychotherapy not minding its importance in recovery from depression. Psychotherapy also prevents recurrence of depression. Studies conducted at Harvard Medical School and other institutions of learning have found that undergoing psychotherapy while discontinuing SSRIs reduces the likelihood of a relapse [7, 8].

4.    Live an active lifestyle

Give your whole body a boost with adequate nutrition, regular sleep, stress reduction, and mostly regular exercise and physical activity. It is important to note that exercise has very potent antidepressant effects. Studies have shown that people who exercise at least three times weekly after recovery from depression are less likely to experience a relapse [9]. Exercise stimulates the release of serotonin, the “feel-good” hormone. This means that exercise can compensate for changes in serotonin levels as you gradually taper off antidepressants, SSRIs, and other medications that affect your serotonin system.

5.    Seek support

Maintain a healthy relationship with your healthcare provider as you undergo the process. Discuss any emotional or physical symptoms that could have a link with discontinuation syndrome. If you have mild symptoms, then be rest assured that they’re temporary – just a side effect of the medication clearing your body system. In some cases, these symptoms may be eased with a short course of anti-anxiety medication, antihistamine, or a sleeping aid. If you’re having very severe symptoms, then you may have to revert to a previous dose and then reduce the levels very slowly. If the SSRI has a short half-life, then you may switch to a longer-acting drug. Fluoxetine is a good example [10].

You may also seek the support of a loved one in your planning. If your loved ones get to know that you’re discontinuing SSRIs and may experience occasional episodes of tearfulness or depression, they will most likely take it less personal. Your loved ones will be able to identify those signs of recurring depression that you may not perceive.

References

1.     Haddad P. The SSRI discontinuation syndrome. J Psychopharmacol (Oxford). 1998;12(3):305-13. doi:10.1177/026988119801200311

2.     Majeroni BA, Hess A. The pharmacologic treatment of depression. J Am Board Fam Pract. 1998;11(2):127-39. doi:10.1056/NEJM199710303371801

3.     Artigas F. Serotonin receptors involved in antidepressant effects. Pharmacol Ther. 2013;137(1):119-31. doi:10.1056/NEJM199710303371801

4.     Warner CH, Bobo W, Warner C, Reid S, Rachal J. Antidepressant discontinuation syndrome. Am Fam Physician. 2006;74(3):449-56. doi:10.1056/NEJM199710303371801

5.     Scholten WD, Batelaan NM, van Oppen P, Smit JH, Hoogendoorn AW, van Megen HJGM, Cath DC, van Balkom AJLM: The efficacy of a group CBT relapse prevention program for remitted anxiety disorder patients who discontinue antidepressant medication: a randomized controlled trial. Psychother Psychosom 2018; 87: 240–242.

6.     Gabriel, Matthew, and Verinder Sharma. “Antidepressant discontinuation syndrome.” CMAJ: Canadian Medical Association journal = journal de l'Association medicale canadienne vol. 189,21 (2017): E747. doi:10.1503/cmaj.160991

7.     Fava GA: Well-Being Therapy. Treatment Manual and Clinical Applications. Basel, Karger, 2016.

8.     Fava GA: Well-being therapy: current indications and emerging perspectives. Psychother Psychosom 2016; 85: 136–145.

9.     Craft, Lynette L., and Frank M. Perna. “The Benefits of Exercise for the Clinically Depressed.” Primary care companion to the Journal of clinical psychiatry vol. 6,3 (2004): 104-111. doi:10.4088/pcc.v06n0301

10. Gabriel, Matthew, and Verinder Sharma. “Antidepressant discontinuation syndrome.” CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne vol. 189,21 (2017): E747. doi:10.1503/cmaj.160991