What you need to know about: SSRIs


There is a lot of information all over the internet regarding medications. My goal with Rxplanation has always been to offer clear, practical and easier-to-understand information on health topics. “What you need to know about…” posts like this one aim to offer a condensed overview of certain medications. While I may not cover every single detail, the hope is that this post can answer the more frequently asked questions and serve as a great starting point in your personal research.

What is an SSRI?

Selective serotonin reuptake inhibitors (or SSRIs) are a class of antidepressants that has been around since the 1980s. The very first SSRI that was approved by the FDA in the United States was fluoxetine (also known as Prozac), which was approved in 1987.

How many different SSRIs are there?

There are currently six SSRIs that are approved for use in both Canada and the United States:

Generic NameBrand Name(s)
EscitalopramCipralex; Lexapro

What are SSRIs used for?

SSRIs can be used for a wide variety of mental illnesses, and are often one of the first classes of medications that is tried.

As the name antidepressant implies, SSRIs are often used in the treatment of depression. However, there are many other potential uses for this family of medications. SSRIs are also very commonly used in several anxiety disorders (such as generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder).

Beyond the previous two most common uses (depression and anxiety), they can also be used in a host of other conditions, such as: bulimia nervosa, body dysmorphic disorder, somatic symptom disorder, and even menopausal hot flashes.

How do SSRIs work?

Prior hypotheses for depression were that it was caused by a chemical imbalance; particularly, they thought that low serotonin levels might cause depression. However, this theory has since fallen out of favor. Now, it’s thought that these chemical imbalances may only be a symptom of mental illness (not a cause).

I won’t go into detail on the many roles and functions that serotonin has in our bodies (it would take way too long), so I’ll keep it short and sweet. Serotonin is a type of neurotransmitter; neurotransmitters are a substance in the brain that allows signals to travel between nerve cells.

SSRIs act on this region where two nerve cells in the brain meet, called a synapse. This is actually a space in between two cells, but is only separated by an extremely miniscule distance. For an impulse to travel from one cell to the other, the first nerve cell releases neurotransmitters (like serotonin).

How SSRIs work is by stopping the reuptake of serotonin by the first nerve cell, which will lead to higher serotonin levels.

SSRIs are almost like a bathtub drain plug. By blocking how the serotonin gets taken out of the synapse (like blocking a drain), it ends up increasing the amount of serotonin which could then go on to do its thing to the next nerve cell.

For those who are more visual, here is a quick (low budget) animation I made:

While SSRIs end up increasing the amount of serotonin in the brain, it’s now thought that it’s the downstream effects of increasing serotonin which will actually have an impact. In this case, more serotonin is thought to lead the brain to make other physiologic changes (which would be what is actually helping the mental illness in question).

What are the side effects of SSRIs?

SSRIs are generally seen as one of the better-tolerated antidepressant classes. However, like any other foreign substance that you ingest, there can be potential side effects. It’s also important to note that not all SSRIs are equal; in other words, some might be more likely to cause specific side effects. So, if you don’t tolerate one SSRI, it doesn’t mean you won’t tolerate another.

This section will only be an overview of possible side effects; so, I won’t be listing every single one. For more detailed information, consider referring to the product information from Health Canada or the FDA.

More common side effects

Side effectComments
Gastrointestinal intolerances:
Nausea, stomach upset, abdominal discomfort, diarrhea
More common when first starting or increasing a dose; usually resolves relatively quickly
HeadacheMore common when first starting or increasing a dose; usually resolves relatively quickly
Sleep disturbancesMore commonly insomnia; but sometimes drowsiness. If insomnia occurs, take the SSRI in the morning
Weight gainAll SSRIs can sometimes be associated with weight gain; paroxetine tends to be the worst (for more information on weight gain from antidepressants, check out my other article here)
Sexual dysfunction:
Decreased libido, inability to climax, erectile dysfunction
More common than people think (many people probably don’t report due to fear of stigma). Other than in very rare case reports, sexual dysfunction is expected to resolve quite quickly once the SSRI is stopped

Less common side effects

Some of the following side effects are more severe, but it’s important to note that they are rare:

Side effectComments
Increased risk of bleedingOn their own, SSRIs are generally not seen as high risk. More problematic when combined with other medications (such as low-dose aspirin).
Arrhythmia (Torsade de pointe)Very rare. More with high doses in those at high risk (e.g. those who take other medications that also increase the risk)
Suicide riskCan possibly increase the risk of suicidal ideations in younger patients (24 and under). However, it’s also important to note that untreated depression may also have a suicidal ideation risk.
Serotonin syndromeRare but serious effect of too much serotonin; exceedingly rare when using only one drug that acts on serotonin. More often seen in those who take multiple medications that act on serotonin and/or take very high doses.

How long do SSRIs take to work?

I have already covered this topic in a previous post (click here to read it). However, if you want the TL;DR here it is:

For mental illnesses, SSRIs are expected to have an initial effect within the first 1-2 weeks; however, a more significant benefit is usually seen at 4-6 weeks and maximal benefit is usually within 2-3 months.

This is important to note in order to avoid giving up too early, since initially there can be more side effects than benefit (and in some anxiety disorders, some symptoms of anxiety may even increase temporarily before getting better).

Are SSRIs addictive?

SSRIs (or any other antidepressant) are not addictive, and there are no plausible mechanisms to suggest that antidepressants could be addictive. These false notions add to the stigma that surrounds mental illness.

If you want a more detailed look into this, check out my other article here.

What is antidepressant discontinuation syndrome? How can it be prevented?

One thing that can occur with SSRIs is antidepressant discontinuation syndrome. This syndrome is thought to be caused by the fact that the SSRI will artificially increase the amount of serotonin. If this is maintained for a long time, your brain can “get used to” this increased serotonin.

So, if all of a sudden you abruptly remove the medication that helps achieve that equilibrium, there can be a temporary lag before a new equilibrium can be achieved. A good analogy would be like if you are in a tug of war and both sides are pulling equally. If all of a sudden one side lets go, then the equilibrium is disturbed (and the other team falls on their asses).

The antidepressant discontinuation syndrome usually manifests as flu-like symptoms (headache, tiredness, muscle aches, chills/sweats). Other less common symptoms can include things like jitteriness, tingling/electric-shock sensations, and mild agitation or anxiety. The duration of the discontinuation syndrome is usually a couple of weeks if left untreated.

Antidepressant discontinuation syndrome can usually be prevented by gradually tapering off (i.e. reducing the dose progressively) over a few weeks. This is why it’s extremely important for people NOT to suddenly stop taking an SSRI that they have been taking for an extended period of time. If you want to stop taking an SSRI, talk to your doctor and/or pharmacist to set up a plan to taper off.

The Bottom Line

SSRIs are one of the most commonly used antidepressant classes; due to their effectiveness and the fact that they are generally well tolerated. It’s important to note that SSRIs, like any other antidepressant, don’t work instantaneously. It can take weeks (or months) for the full effect to be seen.

Dan Landry

Daniel (Dan) Landry, founder of Rxplanation.com, is an infectious diseases pharmacist at the Dr-Georges-L.-Dumont University Hospital Centre in Moncton, NB, Canada.

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