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How do SSRIs work?

How do SSRIs work?



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I've found a reasonable explanation on Wikipedia…

SSRIs are believed to increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin in the synaptic cleft available to bind to the postsynaptic receptor.

But I'm confused about one thing. The whole point of reuptake is that after serotonin (or any other neurotransmitter) binds to the postsynaptic receptors, it has to vacate the receptor so that other signals can be conveyed. If SSRIs inhibit the reuptake of serotonin, it remains in the synaptic cleft… but then what happens?

Do the serotonin molecules bind to the receptors multiple times, since they keep on ending up in the synaptic cleft? If so, when would this end, and how would it affect the signal across two neurons?


The serotonin that remains in the cleft continues to bind to receptors again and again, increasing the total membrane potential change in the postsynaptic neuron.

Think of this process as lowering the threshold for generating an action potential in the postsynaptic neuron. The serotonin that remains in the cleft has already changed potential of the postsynaptic neuron somewhat. Now, when a new release of neurotransmitter comes along, it has a greater chance of raising the membrane potential to the point that an action potential is generated.

While the effect of an SSRI on neurotransmitter levels can occur relatively quickly, most patients will not see an effect on their mood for several weeks. It is thought that the antidepressant action of these drugs may be an effect of a longer term downregulation of serotonin receptors. See Eison and Mullins (1996) for greater detail.

  • Eison AS, Mullins UL (1996). "Regulation of central 5-HT2A receptors: a review of in vivo studies". Behavioural Brain Research 73 (1-2): 177-81.

When serotonin (5HT) uptake is inhibited, 5HT diffuses away from the synaptic cleft. It is believed that eventually 5HT disperses in the extracellular space and reaches the dendritic regions.

The delayed action (say, 2 weeks) can be explained by 5HT's action on 5HT1A receptors in the dendritic region. After continuous activation of 5HT1A receptors, they start to downregulate, which in turn changes the firing pattern of the serotonergic neuron into a more fluttering mode over time. This mode of firing tends to release a lot more 5HT (Lucas et al., 2007). Downregulation takes time, explaining the few weeks delayed onset.

Reference
Duman, Neuron 2007;55:679-81


What is serotonin, and what does it do?

Serotonin has a wide variety of functions in the human body. People sometimes call it the happy chemical, because it contributes to well-being and happiness.

The scientific name for serotonin is 5-hydroxytryptamine (5-HT). It is mainly present in the brain, bowels, and blood platelets.

Serotonin is a neurotransmitter, and some also consider it a hormone. The body uses it to send messages between nerve cells.

It appears to play a role in mood, emotions, appetite, and digestion. As the precursor for melatonin, it helps regulate sleep-wake cycles and the body clock.

Many investigations have looked at serotonin and what it does, but there is still a lot to learn.

In this article, we look at the role of serotonin in the body, uses of drugs that affect serotonin, side effects and symptoms of serotonin deficiency, and how to boost serotonin levels.

Share on Pinterest Image credit: Klaus Vedfelt/Getty Images.

Serotonin is a result of tryptophan, a component of proteins, combining with tryptophan hydroxylase, a chemical reactor. Together, they form 5-HT, or serotonin.

The intestines and the brain produce serotonin. It is also present in blood platelets and plays a role in the central nervous system (CNS).

Occurring throughout the body, it appears to influence a range of physical and psychological functions.

Serotonin is also present in animals, plants, and fungi. For this reason, some people have looked at food as a possible source of serotonin.

Serotonin cannot cross the blood-brain barrier. This means that the brain must produce any serotonin that it needs to use. Treatments for depression and other mental health issues do not supply serotonin directly but trigger reactions that can boost serotonin levels in the brain.

However, research suggests that sources of serotonin in other areas, such as the digestive system, may work independently of serotonin in the brain. This could have implications for the treatment and prevention of various physiological conditions, such as bone degeneration.

As a neurotransmitter, serotonin relays signals between nerve cells and regulates their intensity.

Scientists believe it plays a role in mood and the CNS and affects functions throughout the body. It may have an impact on:

  • bone metabolism
  • cardiovascular health
  • eye health
  • blood clotting
  • neurological disorders

However, the relationship between serotonin and many bodily functions remains unclear.

Scientists do not know precisely what causes depression, but one theory is that it stems from an imbalance of neurotransmitters in the body.

Doctors commonly prescribe selective serotonin reuptake inhibitors (SSRIs) as antidepressants. Fluoxetine (Prozac) is one example.

Normally, the body reabsorbs a neurotransmitter after it has transmitted its neural impulse. SSRIs stop the body from reabsorbing serotonin, leaving higher levels of serotonin to circulate.

Many people find SSRIs help relieve their symptoms, although the link between depression and serotonin remains unclear.

One problem for researchers is that, while they can measure serotonin levels in the bloodstream, they cannot measure its levels in the brain.

As a result, they do not know whether serotonin levels in the bloodstream reflect those in the brain. It is also impossible to know whether SSRIs can really affect the brain.

Mouse studies have produced conflicting evidence. Some suggest that increasing serotonin levels can help reduce stress and depression, but others indicate that serotonin levels make no difference .

In 2015, one editorial called the use of SSRIs to treat depression “the marketing of a myth.”

Nevertheless, if scientists have not yet proven the serotonin theory of depression, SSRIs do appear to help many people.

Other disorders

Apart from depression, doctors may prescribe drugs that regulate serotonin levels to treat a number of other disorders , including:

As with depression, some scientists have questioned whether serotonin is the only factor impacting these conditions.


Why Is Reuptake Important in Treatment for BPD Depression?

Depression in BPD and other mental health disorders are associated with low levels of certain brain chemicals, including serotonin, dopamine, and norepinephrine.

If you have BPD and are taking medication to treat depression (in other words, an antidepressant), you may be taking a selective serotonin reuptake inhibitor or SSRI. The most commonly prescribed antidepressants, SSRIs are often used to treat people with BPD by reducing the symptoms of moderate to severe depression.

SSRIs increase the amount of the neurotransmitter serotonin in the brain by, as you're now aware, slowing its reuptake into the cells that transmitted it. As a result, higher-than-normal levels of serotonin are left to circulate in the brain.

Increasing the amount of serotonin in the brain appears to help brain cells communicate, which in turn helps lift depression and improve mood. Serotonin has been called the body's natural "feel-good" chemical because it produces a sense of well-being.

As you can see, SSRIs don't help the body to produce more serotonin. Instead, they help the body circulate more of the serotonin it has.


How SSRIs work

We do not know exactly why or how Selective Serotonin Re-uptake Inhibitor help some people with OCD.

Serotonin is a neurotransmitter, a brain messenger chemical that carries signals between nerve cells in the brain and is thought to be involved in regulating many functions, influencing emotions, mood, memory and sleep.

It’s thought that selective serotonin reuptake inhibitor (SSRIs) medications work by altering and increasing the balance of serotonin levels in the brain. However, it is too simplistic to say that Obsessive-Compulsive Disorder is caused by low serotonin levels, but for reasons we still don’t understand, an increase in serotonin levels can improve symptoms for some people with OCD and make people more responsive to psychological treatments, such as CBT.

But how do SSRI’s actually work?

The brain is made up of millions of interconnected brain cells (neurons). Messages travel along these cells rather like electricity down a wire, but when the message reaches the end of the neuron, it has to jump the gap (synapse) to the next cell or group of cells. To do this the neuron releases tiny amounts of a neurotransmitter into the gap. Serotonin is one of these neurotransmitters.

After carrying a message, serotonin is usually reabsorbed by the nerve cells (known as “reuptake”). It’s thought that SSRIs work by blocking (“inhibiting”) reuptake, meaning more serotonin is available to pass further messages between nearby nerve cells.

In more details…

The job of your nerve cells is to send messages back and forth like a telephone wire. But nerves aren’t a single string — they’re made of lots of interconnected cells. So they act more like the game telephone, where one person whispers a message to the next, and it’s passed down to the end of the line one person at a time. Instead of words, the ‘message’ is passed by chemicals called neurotransmitters that are sent by one cell to the next in line.

These chemicals are sent out by one nerve cell into the space between it and the next. The next cell in line gets the message once those chemicals get to it from across the gap. That nerve cell then releases a chemical toward the next nerve cell so it gets the message.

A key gene for this process is hSERT which has the instructions for making a serotonin transporter. The transporter’s job is to sop up extra serotonin after a nerve spits it toward the next nerve cell in line. In some people it’s thought hSERT might works too fast, and may collect all the serotonin before the next cell has heard the signal. To put it simply, their nerve cells are whispering when they should be speaking out loud.

In order to allow the nerve to recover and receive the next message, the body has a clever way of removing the neurotransmitter from the receptors, and allowing it to be taken back into the originating nerve (re-uptake).

The SSRIs slow down the collection of serotonin by transporters like hSERT and the process of returning the serotonin to the end of the neuron it comes from. This is thought to mean that serotonin stays in the space between the cells longer and increases the chances that the second cell will get the message.

We still don’t know exactly what the influences of serotonin are on OCD, and some people’s symptoms are not improved despite taking SSRIs. So sadly at this time taking medication might help, but can’t be assured, which is why we very much encourage people to focus their treatment on psychological therapy like Cognitive Behavioural Therapy (CBT).


How do antidepressants actually work?

A recent article by Deborah Orr regarding her experiences with antidepressants sparked a lot of debate as to their merits and drawbacks. The truth is, they’re not as simple or as understood as many might think

Very common, but that doesn’t mean they’re perfectly understood. Photograph: Joe Raedle/Getty Images

Very common, but that doesn’t mean they’re perfectly understood. Photograph: Joe Raedle/Getty Images

Last modified on Wed 20 Sep 2017 23.05 BST

Antidepressants the go-to treatment for depression, or generalised anxiety. It’s incredible when you think about it, the fact that you can have a debilitating mood disorder, take a few pills, and feel better. It’s unbelievable that medical science has progressed so far that we now fully understand how the human brain produces moods and other emotions, so can manipulate them with designer drugs.

That’s right, it is unbelievable. Because it isn’t the case. The fact that antidepressants are now so common is something of a mixed blessing. On one hand, anything that helps reduce stigma and lets those afflicted know they aren’t alone can only be helpful. Depression is incredibly common, so this awareness can literally save many lives.

On the other hand, familiarity does not automatically mean understanding. Nearly everyone has a smartphone these days, but how many people, if pushed, could construct a touchscreen? Not many, I’d wager. And so it is with depression and antidepressants. For all the coverage and opinion pieces produced about them, the details around how they work remain somewhat murky and elusive.

Actually, in the case of antidepressants, it’s more a question of why they work, rather than how. Most antidepressants, from the earliest Trycyclics and Monamine Oxidase inhibitors, to the ubiquitous modern day selective serotonin reuptake inhibitors (SSRIs), work by increasing the levels of specific neurotransmitters in the brain, usually by preventing them from being broken down and reabsorbed into the neurons, meaning they linger in the synapses longer, causing more activity, so “compensating” for the reduced overall levels. Antidepressants make the remaining neurotransmitters work twice as hard, so overall activity is more “normal”, so to speak.

But knowing that antidepressants do this doesn’t actually explain how they end up alleviating depression. In a way, neurotransmitters are to the brain what the alphabet is to language the basic elements of much richer, more complex contructs. So, boosting neurotransmitter levels throughout the brain doesn’t really tell us anything specific. It’s like having to restore a classic painting and being told it “needs more green” that may be true, but where? How much? What shade? It’s too unspecific to tell us anything useful.

Depression is so poorly understood that most people illustrate it with someone holding their head in their hands, as a trawl through any image archive will reveal. It doesn’t make your brain heavier or anything. Photograph: Nastia11/Getty Images/iStockphoto

The truth is, antidepressants were discovered largely by accident Swiss scientists looking for treatments for schizophrenia in the 1950s realised a certain experimental substance caused euphoria in their subjects. And lo, antidepressants were born. Nothing unusual here, luck and serendipity are behind the discoveries of many drugs. But this led to the monoamine theory of depression, which argues that, because most antidepressants increase levels of neurotransmitters of the monoamine class, depression is caused by depletion of monoamines in the brain.

Except, the monoamine hypothesis is increasingly seen as insufficient. It’s part of what’s going on, sure, but not the whole story. For one, antidepressants boost neurotransmitter activity pretty much immediately, but therapeutic effects usually take weeks to kick in. Why? It’s like filling your car’s empty tank with petrol and it only starting to run again a month later it means no fuel may have been a problem, but it’s clearly not the only problem.

There are other possible explanations. Neuroplasticity, the ability to form new connections between neurons, has been shown to be impaired in depressed patients. The theory is that this prevents the brain from responding “correctly” aversive stimuli and stress. Something bad happens, and the impaired plasticity means the brain is more ‘fixed’ as is, like a cake left out too long, preventing moving on, adapting, or escaping the negative mindset, and thus depression. Antidepressants also gradually increase neuroplasticity, so this may be actually why they work as they do, long after the transmitter levels are raised. It’s not like putting fuel in a car, it’s more like fertilising a plant it takes time for the helpful elements to be absorbed into the system.

There are other possibilities. Inflammation causing undue stress on the brain is one, an overactive anterior cingulate cortex is another. Essentially, it’s complicated, and we can’t confirm anything yet.

Basically, depression isn’t a broken leg, or a cold. We can’t look at it, say “that’s what’s wrong, right there” and set about fixing it. Psychiatric issues are never that straightforward (and that’s without the many overlaps with more physical ailments). Part of the problem is that “depression” is more of an all-purpose term for something that manifests in many in different ways. It’s a mood disorder, but how mood is affected can vary substantially. Some end up with an unshakable black despair, others experience no mood to speak of, just feeling flat, empty and emotionless. Some (mostly men) become constantly angry and restless.

This is part of the reason why it’s proven so difficult to establish an underlying cause. The human brain is the most complex thing, and even a minor flaw or glitch in the workings can manifest in various, unexpected ways. And there’s no reason to assume that every case of depression has exactly the same cause. It’s not surprising, then, that antidepressants don’t work, or even make things worse, for many patients. There are other approaches too, but then these may not work for you either. If the causes and effects of depression vary considerably from person to person, so would the effectiveness of treatments.

Most therapeutic interventions don’t involve leather couches either. Maybe that’s a Hollywood thing? Photograph: Getty Images/Stockbyte

Antidepressants also have many potential side effects, which themselves vary from person to person. And while the therapeutic effects (which many argue are themselves overstated or based on questionable evidence) take weeks to occur, the same doesn’t apply to the unpleasant side effects, as Deborah Orr recently discovered.

Given all this, you may wonder how antidepressants ended up being so common in the first place? Well, it may boil down to the fact that, for all the flaws and problems they may have, they’re better than nothing, especially when the alternative is untreated depression. Some take a more cynical view, arguing that it’s pharmaceutical companies profiting by pushing profitable pills on people who don’t really need them.

Or, in the UK at least, it may be something to do lack of time and resources. In an ideal world, people with depression would have easy access to CBT or other interventions given how every patient is different and what works for them is often a matter of trial and error. But, in an increasingly-underfunded and overworked NHS, this is increasingly difficult, even impossible, to offer. Many of the interpersonal therapies for depression and other disorders involve many hours of contact time with highly trained (ie expensive) professionals. Given the choice between that or giving someone a box of tablets and saying “see you in a month”, the latter would likely be the go-to option much of the time.

Overall, the widespread use of antidepressants is likely down to numerous complex causes, and the effects are unpredictable and confusing. Much like depression itself, which seems appropriate.

This article is adapted from Dean Burnett’s book The Idiot Brain, released in paperback in the US on 11 July.


Other Antidepressants for PTSD

Antidepressants that affect the balance of serotonergic and noradrenergic neurotransmission, or which alter serotonin neurotransmission through other mechanisms of action, are also helpful in PTSD. Venlafaxine acts primarily as a serotonin reuptake inhibitor at lower dosages and as a combined serotonin and norepinephrine reuptake inhibitor at higher dosages. It is also a conditionally recommended treatment for PTSD. A typical dosage range is:

All of the antidepressants described above are also effective in treating comorbid major depressive disorder (MDD) which, depending upon the study, accompanies PTSD about 50 percent of the time. Dose-related elevations in blood pressure have been noted with venlafaxine. It should be used with caution in patients with hypertension.


Avoid the liquid formulation of Zoloft if you are on Antabuse (disulfiram) because it contains alcohol. Wait at least 14 days after your last dose of any MAOI before beginning sertraline treatment.  

Zoloft interacts with a wide range of natural remedies. Ask your doctor before taking tryptophan, St. John's wort, or any other herbal or natural formulation.  

In addition, Zoloft interacts with numerous prescription and over-the-counter medications, including NSAID pain relievers, diuretics, stomach medicines, blood thinners, and treatments for certain mental illnesses.  

Provide your doctor with a full list of all over-the-counter, prescription, and natural products you use, and do not add anything new without your doctor's approval. Avoid alcohol and illegal drugs while using sertraline.


Neuron Function:

There are many biological processes and systems that can be related to mental health struggles, neurotransmitter imbalances are just one however, chemicals such as serotonin are the target for many medications often prescribed to us.


Selective Serotonin Reuptake Inhibitors: How Do SSRIs Improve Mood And What Are Their Side Effects?

When SSRIs were first introduced, they were revolutionary — not only is this class of antidepressants generally very effective at relieving the symptoms of depression, it is also much less likely than some other antidepressants to cause debilitating side effects that would make your life hell in a whole different way. It's no surprise that selective serotonin reuptake inhibitors are among the most popular class of antidepressant out there today.

What Are SSRIs, and how do they work?

"SSRI" is much less of a mouthful than the words it stands for — selective serotonin reuptake inhibitors — but this full name gives important insights into how these antidepressants are believed to relieve depression:

  • Serotonin is a neurotransmitter — a kind of brain chemical that transmits messages in the brain — with a variety of functions relating to mood, memory, learning, and the way in which we process reward.
  • "Reuptake" refers to absorption, and "inhibitor" means blocker — so put very simply, SSRIs prevent the absorption of serotonin within the brain, making more of this neurotransmitter available.
  • "Selective" means that SSRIs specifically target serotonin while leaving other neurotransmitters alone, which is one of the reasons these antidepressants cause fewer side effects than less targeted ones.

SSRIs are also prescribed to help people with other mental health conditions, including anxiety disorders, panic disorders, post-traumatic stress disorder, chronic pain, and obsessive compulsive disorder.

Commonly prescribed SSRIs include:

  • Fluoxetine, the first SSRI to be introduced, also sold under the brand names Prozac and Sarafem.
  • Sertraline (Zoloft)
  • Escitalopram (Lexapro)
  • Paroxetine (Paxil)
  • Citalopram (Celexa)
  • Fluvoxamine (Luvox)
  • Vilazodone

How effective are SSRIs?

It will probably come as no surprise that research has found SSRI antidepressants to be more effective than "treatment" with a placebo. Any antidepressant, of any class, has actually been shown to have about a 50 percent chance of helping any given individual with depression feel better, making antidepressants in general pretty effective.

How do SSRIs measure up to other kinds of antidepressants, though? Some studies have found tricyclic antidepressants (also known as TCAs) to be better at offering relief from the symptoms of depression, while other research has concluded that TCAs and SSRIS are equally effective at treating depressive disorders.

SSRIs, however, have fewer side effects, which translates to a higher chance that patients will actually keep taking them. Since someone must, obviously, take an antidepressant for it to have the chance to be effective, that means a lot. SSNRIs, another class of antidepressants, have also been shown to work just as well as SSRIs.

What are the side effects of SSRIs for depression?

When SSRI antidepressants first hit the market, they were believed to come with basically no side effects. Over time, a more complete picture has emerged. If you were prescribed an SSRI, you should know that they can cause the following side effects:

  • Sexual dysfunction — both a lowered or non-existent libido and erectile dysfunction can fall under this heading, and though studies reveal that only around seven percent of patients will report the fact that their sexual life has suffered since they started taking SSRIs to their doctor without being prompted, closer to half of patients will admit to sexual changes if asked.
  • Weight gain — after initial weight loss, a subset of people taking SSRIs will subsequently gain weight. It appears that citalopram is the SSRI that is least likely to cause this side effect. If you were working on losing weight or hoping to, mention this to your prescribing doctor before you start taking an antidepressant.
  • Some people will experience sleep disturbances while taking an SSRI.
  • Blurred vision is another possible side effect.
  • Some people will feel dizzy, nauseous, or even vomit.
  • A subset of people taking SSRIs will also feel agitated and restless.

Contraindications: Who shouldn't take SSRIs?

While SSRIs generally have a lower risk than some other antidepressants of interacting with other medications you may be taking, it is always important to let your doctor know exactly what other drugs you take. This includes over the counter medications as well as prescription medications. If necessary, your doctor will either prescribe you a different antidepressant, or see if it is possible to switch your other medications to drugs that do not interact badly with your SSRI.

Women who are trying to conceive, pregnant, or breastfeeding aren't generally advised to take SSRIs because it is not clear whether this is safe, but your doctor will determine whether the advantages are greater than the potential risk on an individual basis. Children and teenagers, meanwhile, may be prescribed SSRIs the expected benefits are deemed to outweigh the risks — but with caution. The same holds true for people with underlying conditions like diabetes, kidney disease, and epilepsy.


All About Antidepressants

Antidepressants are the most commonly prescribed meds for depression, but they’re used to treat a number of other conditions as well.

Antidepressants are some of the world’s most prescribed medications.

These meds can be used for a variety of mental health conditions, such as depression and anxiety, but they may also be prescribed to treat pain or sleeping problems.

But with so many types available, how do you know which antidepressant is right for you?

There are several medications used to treat depression, but antidepressants are the most popular.

Antidepressants are one of the primary treatments for depression and one of the most commonly prescribed types of meds in the United States.

More than 13% of U.S. adults — about 1 in 10 people — over the age of 18 used antidepressants in the last 30 days, according to the Centers for Disease Control and Prevention (CDC).

Like the name suggests, antidepressants can help relieve symptoms of depression and may stop them from coming back.

The exact way antidepressants work isn’t totally understood, but they’re believed to work by correcting imbalances of chemicals (aka neurotransmitters) in the brain.

Neurotransmitters regulate our moods and emotions by transmitting nerve signals to receptors in the brain. There are three neurotransmitters that are believed to be specific to depression:

  • Serotonin: regulates mood, appetite, sleep, memory, social behavior, and sexual desire
  • Dopamine: influences motivation, arousal, decision-making, and pleasure
  • Norepinephrine (or noradrenaline): affects alertness and helps the body respond to stress

When you have depression, you may have lower levels of these neurotransmitters in your brain. Antidepressants can help increase the availability of one or more of these neurotransmitters over time.

How they do that, though, depends on what type of antidepressant you’re prescribed.

There are several major types (or classes) of antidepressant medications. Each class works in a slightly different way.

The types of antidepressants include:

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed type of antidepressant. They’re often the first type tried for people who are newly diagnosed with depression.

First developed in the 1970s, SSRIs work by regulating serotonin levels in the brain.

When a neurotransmitter isn’t taken up by other neurons, it’s reabsorbed by the neuron that released it in a process called “reuptake.”

As the name suggests, an SSRI inhibits the reabsorption of serotonin. In other words, it blocks serotonin from quickly leaving your brain. This raises serotonin levels so more is available and active to help regulate your emotions.

  • fluoxetine (Prozac)
  • sertraline (Zoloft)
  • escitalopram (Lexapro)
  • paroxetine (Paxil)
  • citalopram (Celexa)
  • fluvoxamine (Luvox)
  • vilazodone (Viibryd)

SSRIs are often more tolerated than other antidepressants because they tend to have fewer side effects. However, they can have side effects such as:

  • stomach upset or nausea
  • insomnia or other sleep issues
  • nervousness
  • tremors
  • weight changes
  • headaches
  • sexual dysfunction
  • dizziness

Serotonin-norepinephrine reuptake inhibitors

Serotonin-norepinephrine reuptake inhibitors (SNRIs) work similarly to SSRIs, but they inhibit the reuptake of both serotonin and norepinephrine.

SNRIs can have the same benefits as SSRIs, but since they also raise levels of norepinephrine, they may help more with stress and anxiety.

SNRIs are a newer class of drugs — the first SNRI was approved by the Food and Drug Administration (FDA) in 1993. They’re approved for use in treating depression, anxiety disorders, and conditions related to chronic pain.

The increased levels of norepinephrine can cause side effects like:

Other common side effects include:

  • headache
  • stomach upset or nausea
  • dizziness
  • appetite changes
  • dry mouth
  • sexual dysfunction

These can become severe for some individuals, so you’ll want to keep your doctor informed of any side effects you have.

Tricyclic antidepressants

Developed in the 1950s, tricyclic antidepressants (TCAs or tricyclics) were one of the first drugs used to treat depression. The name tricyclic comes from its chemical structure that’s made up of three connected rings of atoms.

Tricyclics work by reducing the reabsorption of serotonin and norepinephrine. They also block another neurotransmitter called acetylcholine, which plays a role in muscle movement, heart rate, thinking, and learning.

Common tricyclics include:

  • clomipramine (Anafranil)
  • amitriptyline (Elavil)
  • desipramine (Norpramin) (Pamelor)
  • doxepin (Sinequan)
  • trimipramine (Surmontil)
  • imipramine (Tofranil)
  • protriptyline (Vivactil)

Prescribing tricyclics is less common now because they have more severe side effects than SSRIs and SNRIs.

You may also have a higher chance of overdosing with a TCA compared to other antidepressants. Taking only a small amount over your normal dose can lead to overdose or have life threatening side effects.

Still, tricyclics may be prescribed when someone isn’t responding to other antidepressants. They may also be prescribed for people with bipolar disorder or obsessive-compulsive disorder (OCD).

The most common side effects of tricyclics are:

  • weight gain
  • urinary retention (when your bladder doesn’t fully empty)
  • constipation
  • dry mouth
  • dizziness
  • blurred vision or dry eyes
  • sleepiness
  • confusion

Abruptly stopping tricyclics or missing a couple of doses can lead to withdrawal or discontinuation symptoms. This is why it’s helpful to create a tapering schedule with your doctor.

Monoamine oxidase inhibitors

Another drug type introduced in the 1950s, monoamine oxidase inhibitors (MAOIs) were one of the first types of antidepressants developed.

MAOIs inhibit the brain enzyme called monoamine oxidase, which is responsible for breaking down neurotransmitters. This leads to higher levels of serotonin, dopamine, and norepinephrine in the brain.

They may also be prescribed for depression in bipolar disorder, borderline personality disorder (BPD), post-traumatic stress disorder (PTSD), agoraphobia, social phobia, and bulimia.

  • selegiline (Emsam)
  • isocarboxazid (Marplan)
  • phenelzine (Nardil)
  • tranylcypromine (Parnate)

MAOIs aren’t often prescribed as much today as they were in the past due to side effects and potential interactions.

If you’re prescribed an MAOI, you’ll be required to follow a special diet. This is because monoamine oxidase regulates the breakdown of tyramine, a compound found in food.

You’ll need to limit foods with tyramine — like aged cheeses, cured or smoked meats, or fermented foods — since MAOIs can cause tyramine levels to rise.

If tyramine levels are too high, it can lead to dangerously high blood pressure. Limiting tyramine-rich foods can help prevent hypertensive crisis, which is when your blood pressure gets too high, increasing your chances of having a heart attack or stroke.

MAOIs also tend to have a lot of other interactions so you can’t mix them with certain meds such as:

  • other types of antidepressants
  • herbal remedies like St. John’s wort
  • central nervous system stimulants (for example, Adderall)
  • certain meds for pain, cold, and allergies

Common side effects of MAOIs include:

  • nausea
  • drowsiness
  • dizziness
  • restlessness
  • trouble sleeping
  • dry mouth
  • diarrhea or constipation
  • skin reactions if using the patch

Noradrenergic and specific serotonergic antidepressants

Noradrenergic and specific serotonergic antidepressants (NaSSAs) are a newer class of drugs that affect serotonin and norepinephrine levels in your brain. They block receptors of the stress hormone epinephrine (adrenaline).

They’re often prescribed for depression, as well as anxiety and personality disorders.

The most common NaSSA is mirtazapine (Remeron).

Possible side effects can include:

  • constipation
  • dry mouth
  • weight gain
  • drowsiness
  • blurred vision
  • dizziness

Atypical antidepressants

Atypical antidepressants are those that don’t particularly fit into any other classes. They affect serotonin, norepinephrine, and dopamine levels in the brain.

Common atypical antidepressants include:

  • bupropion (Wellbutrin)
  • trazodone (Oleptro)
  • vortioxetine (Trintellix)
  • olanzapine/fluoxetine (Symbax)

Each one works differently.

For example, bupropion inhibits the reuptake of dopamine, serotonin, and norepinephrine, raising the levels of all three hormones in the brain. It’s often used to treat depression or depression related to seasonal changes (aka seasonal depression). It can also be used to help someone quit smoking.

Meanwhile, trazodone and vortioxetine both inhibit serotonin reuptake. They’re known as serotonin antagonist and reuptake inhibitors (SARIs).

Symbax is a combination drug that includes an SSRI (fluoxetine) and an antipsychotic (olanzapine).

The primary use for antidepressants is to treat the symptoms of depression, ranging from mild to severe.

However, antidepressants can also be prescribed to help manage symptoms of other conditions, including:

Antidepressants may also have “off-label” uses, meaning these aren’t approved by the FDA for these conditions but may still be effective.

Some off-label uses of antidepressants include:

Antidepressants are most commonly taken in tablet or capsule form, but there are some that can be taken in liquid form.

How often you take your antidepressant will be based on your specific needs and can vary from one to three tablets a day. Some antidepressants will be prescribed in extended release form so you won’t have to take as many pills throughout the day.

You’ll often be started on the lowest dose, then given a plan to gradually increase the dose so your body has time to react and adjust to the med. This can also help prevent sudden side effects.

Each class of antidepressants has different side effects, ranging from mild to more severe.

However, the most common side effects across all antidepressants are:

  • headache
  • dry mouth
  • fatigue
  • dizziness
  • weight changes
  • drowsiness
  • sexual issues

In severe instances, antidepressants may lead to an increased likelihood of suicidal thoughts and actions.

For this reason, the FDA has a black box warning on antidepressants for people under the age of 24.

The side effects of antidepressants can feel like a barrier to some people, but it’s important to remember that you may only have one or two of them, or none at all.

Sometimes, side effects are only temporary until your body adjusts to the med, in which case the side effects will be reduced or entirely disappear after the first few weeks of treatment.

In general, if you’re having side effects that last for several weeks without improvement, or you’re concerned that a side effect is having a strong or dangerous impact on your health, reach out to your doctor immediately. They’ll be able to assess what’s happening and plan next steps.

Antidepressants can sometimes interact with other drugs.

In severe cases, drug interactions can lead to serotonin syndrome, which can be dangerous. To avoid this, make sure your doctor is aware of any and all drugs you’re taking, including over-the-counter medications and nutritional supplements.

When choosing the best antidepressant treatment for you, remember that there isn’t one type that’s specifically better or more effective than another.

Since each type does something different, consider talking with a healthcare professional who has experience prescribing antidepressants so they can help find one that will address your specific symptoms.

Study up on antidepressants

Take the time to research and learn about the different types of antidepressants and how they work, especially before you start taking one. By having a better understanding of how they work, you’ll have a better understanding of what’s happening in your body.

Take notes and jot down any questions you may have to discuss at your next appointment.

Track your side effects

It’s always a good idea to check in with yourself to see how you’re feeling while taking an antidepressant.

For example, if you’re feeling increasingly dizzy or start having more headaches, write it down and share it with your doctor.

The more information your doctor has, the better they can adjust your medication or dosage.

Give it some time

It’s important to remember that changes in your mood will be gradual when you start using antidepressants. This is because antidepressants take time to build up their effectiveness.

So don’t expect instantaneous results. Allow some time to start seeing a change.

It can take several weeks to fully feel the effects of most antidepressants.

Don’t give up after the first week just because you don’t feel better right away, and try not to get discouraged if you don’t see fast improvements.

Stay on a schedule

Missing doses or quitting for even short periods of time will slow down your progress and, in some cases, cause you to go through withdrawal symptoms.

Consider taking antidepressants at a time when you know you’ll more reliably take them, like in the morning before work or school. You can also create a phone reminder or leave a note blocking your door if that helps.

Living with depression can feel overwhelming at times, and it’s hard to know where to even start looking for help. You may feel bad about needing to ask for help in the first place or admitting that you’re not feeling well.

But there’s nothing to feel bad or ashamed about. You’re not alone. There are numerous resources available for managing your mental health and depression.

Consider talking to a mental health professional since they can discuss treatment options. Be honest about how you’ve been feeling and what changes you hope to see.

Depending on your symptoms, they may not even prescribe antidepressants for you. It’s possible that talk therapy alone could be just as effective.

Ultimately, you don’t have to make the decision to go on antidepressants alone. A doctor will be there to help you talk through the treatment options that are right for you.


Avoid the liquid formulation of Zoloft if you are on Antabuse (disulfiram) because it contains alcohol. Wait at least 14 days after your last dose of any MAOI before beginning sertraline treatment.  

Zoloft interacts with a wide range of natural remedies. Ask your doctor before taking tryptophan, St. John's wort, or any other herbal or natural formulation.  

In addition, Zoloft interacts with numerous prescription and over-the-counter medications, including NSAID pain relievers, diuretics, stomach medicines, blood thinners, and treatments for certain mental illnesses.  

Provide your doctor with a full list of all over-the-counter, prescription, and natural products you use, and do not add anything new without your doctor's approval. Avoid alcohol and illegal drugs while using sertraline.


Other Antidepressants for PTSD

Antidepressants that affect the balance of serotonergic and noradrenergic neurotransmission, or which alter serotonin neurotransmission through other mechanisms of action, are also helpful in PTSD. Venlafaxine acts primarily as a serotonin reuptake inhibitor at lower dosages and as a combined serotonin and norepinephrine reuptake inhibitor at higher dosages. It is also a conditionally recommended treatment for PTSD. A typical dosage range is:

All of the antidepressants described above are also effective in treating comorbid major depressive disorder (MDD) which, depending upon the study, accompanies PTSD about 50 percent of the time. Dose-related elevations in blood pressure have been noted with venlafaxine. It should be used with caution in patients with hypertension.


Why Is Reuptake Important in Treatment for BPD Depression?

Depression in BPD and other mental health disorders are associated with low levels of certain brain chemicals, including serotonin, dopamine, and norepinephrine.

If you have BPD and are taking medication to treat depression (in other words, an antidepressant), you may be taking a selective serotonin reuptake inhibitor or SSRI. The most commonly prescribed antidepressants, SSRIs are often used to treat people with BPD by reducing the symptoms of moderate to severe depression.

SSRIs increase the amount of the neurotransmitter serotonin in the brain by, as you're now aware, slowing its reuptake into the cells that transmitted it. As a result, higher-than-normal levels of serotonin are left to circulate in the brain.

Increasing the amount of serotonin in the brain appears to help brain cells communicate, which in turn helps lift depression and improve mood. Serotonin has been called the body's natural "feel-good" chemical because it produces a sense of well-being.

As you can see, SSRIs don't help the body to produce more serotonin. Instead, they help the body circulate more of the serotonin it has.


How SSRIs work

We do not know exactly why or how Selective Serotonin Re-uptake Inhibitor help some people with OCD.

Serotonin is a neurotransmitter, a brain messenger chemical that carries signals between nerve cells in the brain and is thought to be involved in regulating many functions, influencing emotions, mood, memory and sleep.

It’s thought that selective serotonin reuptake inhibitor (SSRIs) medications work by altering and increasing the balance of serotonin levels in the brain. However, it is too simplistic to say that Obsessive-Compulsive Disorder is caused by low serotonin levels, but for reasons we still don’t understand, an increase in serotonin levels can improve symptoms for some people with OCD and make people more responsive to psychological treatments, such as CBT.

But how do SSRI’s actually work?

The brain is made up of millions of interconnected brain cells (neurons). Messages travel along these cells rather like electricity down a wire, but when the message reaches the end of the neuron, it has to jump the gap (synapse) to the next cell or group of cells. To do this the neuron releases tiny amounts of a neurotransmitter into the gap. Serotonin is one of these neurotransmitters.

After carrying a message, serotonin is usually reabsorbed by the nerve cells (known as “reuptake”). It’s thought that SSRIs work by blocking (“inhibiting”) reuptake, meaning more serotonin is available to pass further messages between nearby nerve cells.

In more details…

The job of your nerve cells is to send messages back and forth like a telephone wire. But nerves aren’t a single string — they’re made of lots of interconnected cells. So they act more like the game telephone, where one person whispers a message to the next, and it’s passed down to the end of the line one person at a time. Instead of words, the ‘message’ is passed by chemicals called neurotransmitters that are sent by one cell to the next in line.

These chemicals are sent out by one nerve cell into the space between it and the next. The next cell in line gets the message once those chemicals get to it from across the gap. That nerve cell then releases a chemical toward the next nerve cell so it gets the message.

A key gene for this process is hSERT which has the instructions for making a serotonin transporter. The transporter’s job is to sop up extra serotonin after a nerve spits it toward the next nerve cell in line. In some people it’s thought hSERT might works too fast, and may collect all the serotonin before the next cell has heard the signal. To put it simply, their nerve cells are whispering when they should be speaking out loud.

In order to allow the nerve to recover and receive the next message, the body has a clever way of removing the neurotransmitter from the receptors, and allowing it to be taken back into the originating nerve (re-uptake).

The SSRIs slow down the collection of serotonin by transporters like hSERT and the process of returning the serotonin to the end of the neuron it comes from. This is thought to mean that serotonin stays in the space between the cells longer and increases the chances that the second cell will get the message.

We still don’t know exactly what the influences of serotonin are on OCD, and some people’s symptoms are not improved despite taking SSRIs. So sadly at this time taking medication might help, but can’t be assured, which is why we very much encourage people to focus their treatment on psychological therapy like Cognitive Behavioural Therapy (CBT).


Neuron Function:

There are many biological processes and systems that can be related to mental health struggles, neurotransmitter imbalances are just one however, chemicals such as serotonin are the target for many medications often prescribed to us.


Selective Serotonin Reuptake Inhibitors: How Do SSRIs Improve Mood And What Are Their Side Effects?

When SSRIs were first introduced, they were revolutionary — not only is this class of antidepressants generally very effective at relieving the symptoms of depression, it is also much less likely than some other antidepressants to cause debilitating side effects that would make your life hell in a whole different way. It's no surprise that selective serotonin reuptake inhibitors are among the most popular class of antidepressant out there today.

What Are SSRIs, and how do they work?

"SSRI" is much less of a mouthful than the words it stands for — selective serotonin reuptake inhibitors — but this full name gives important insights into how these antidepressants are believed to relieve depression:

  • Serotonin is a neurotransmitter — a kind of brain chemical that transmits messages in the brain — with a variety of functions relating to mood, memory, learning, and the way in which we process reward.
  • "Reuptake" refers to absorption, and "inhibitor" means blocker — so put very simply, SSRIs prevent the absorption of serotonin within the brain, making more of this neurotransmitter available.
  • "Selective" means that SSRIs specifically target serotonin while leaving other neurotransmitters alone, which is one of the reasons these antidepressants cause fewer side effects than less targeted ones.

SSRIs are also prescribed to help people with other mental health conditions, including anxiety disorders, panic disorders, post-traumatic stress disorder, chronic pain, and obsessive compulsive disorder.

Commonly prescribed SSRIs include:

  • Fluoxetine, the first SSRI to be introduced, also sold under the brand names Prozac and Sarafem.
  • Sertraline (Zoloft)
  • Escitalopram (Lexapro)
  • Paroxetine (Paxil)
  • Citalopram (Celexa)
  • Fluvoxamine (Luvox)
  • Vilazodone

How effective are SSRIs?

It will probably come as no surprise that research has found SSRI antidepressants to be more effective than "treatment" with a placebo. Any antidepressant, of any class, has actually been shown to have about a 50 percent chance of helping any given individual with depression feel better, making antidepressants in general pretty effective.

How do SSRIs measure up to other kinds of antidepressants, though? Some studies have found tricyclic antidepressants (also known as TCAs) to be better at offering relief from the symptoms of depression, while other research has concluded that TCAs and SSRIS are equally effective at treating depressive disorders.

SSRIs, however, have fewer side effects, which translates to a higher chance that patients will actually keep taking them. Since someone must, obviously, take an antidepressant for it to have the chance to be effective, that means a lot. SSNRIs, another class of antidepressants, have also been shown to work just as well as SSRIs.

What are the side effects of SSRIs for depression?

When SSRI antidepressants first hit the market, they were believed to come with basically no side effects. Over time, a more complete picture has emerged. If you were prescribed an SSRI, you should know that they can cause the following side effects:

  • Sexual dysfunction — both a lowered or non-existent libido and erectile dysfunction can fall under this heading, and though studies reveal that only around seven percent of patients will report the fact that their sexual life has suffered since they started taking SSRIs to their doctor without being prompted, closer to half of patients will admit to sexual changes if asked.
  • Weight gain — after initial weight loss, a subset of people taking SSRIs will subsequently gain weight. It appears that citalopram is the SSRI that is least likely to cause this side effect. If you were working on losing weight or hoping to, mention this to your prescribing doctor before you start taking an antidepressant.
  • Some people will experience sleep disturbances while taking an SSRI.
  • Blurred vision is another possible side effect.
  • Some people will feel dizzy, nauseous, or even vomit.
  • A subset of people taking SSRIs will also feel agitated and restless.

Contraindications: Who shouldn't take SSRIs?

While SSRIs generally have a lower risk than some other antidepressants of interacting with other medications you may be taking, it is always important to let your doctor know exactly what other drugs you take. This includes over the counter medications as well as prescription medications. If necessary, your doctor will either prescribe you a different antidepressant, or see if it is possible to switch your other medications to drugs that do not interact badly with your SSRI.

Women who are trying to conceive, pregnant, or breastfeeding aren't generally advised to take SSRIs because it is not clear whether this is safe, but your doctor will determine whether the advantages are greater than the potential risk on an individual basis. Children and teenagers, meanwhile, may be prescribed SSRIs the expected benefits are deemed to outweigh the risks — but with caution. The same holds true for people with underlying conditions like diabetes, kidney disease, and epilepsy.


What is serotonin, and what does it do?

Serotonin has a wide variety of functions in the human body. People sometimes call it the happy chemical, because it contributes to well-being and happiness.

The scientific name for serotonin is 5-hydroxytryptamine (5-HT). It is mainly present in the brain, bowels, and blood platelets.

Serotonin is a neurotransmitter, and some also consider it a hormone. The body uses it to send messages between nerve cells.

It appears to play a role in mood, emotions, appetite, and digestion. As the precursor for melatonin, it helps regulate sleep-wake cycles and the body clock.

Many investigations have looked at serotonin and what it does, but there is still a lot to learn.

In this article, we look at the role of serotonin in the body, uses of drugs that affect serotonin, side effects and symptoms of serotonin deficiency, and how to boost serotonin levels.

Share on Pinterest Image credit: Klaus Vedfelt/Getty Images.

Serotonin is a result of tryptophan, a component of proteins, combining with tryptophan hydroxylase, a chemical reactor. Together, they form 5-HT, or serotonin.

The intestines and the brain produce serotonin. It is also present in blood platelets and plays a role in the central nervous system (CNS).

Occurring throughout the body, it appears to influence a range of physical and psychological functions.

Serotonin is also present in animals, plants, and fungi. For this reason, some people have looked at food as a possible source of serotonin.

Serotonin cannot cross the blood-brain barrier. This means that the brain must produce any serotonin that it needs to use. Treatments for depression and other mental health issues do not supply serotonin directly but trigger reactions that can boost serotonin levels in the brain.

However, research suggests that sources of serotonin in other areas, such as the digestive system, may work independently of serotonin in the brain. This could have implications for the treatment and prevention of various physiological conditions, such as bone degeneration.

As a neurotransmitter, serotonin relays signals between nerve cells and regulates their intensity.

Scientists believe it plays a role in mood and the CNS and affects functions throughout the body. It may have an impact on:

  • bone metabolism
  • cardiovascular health
  • eye health
  • blood clotting
  • neurological disorders

However, the relationship between serotonin and many bodily functions remains unclear.

Scientists do not know precisely what causes depression, but one theory is that it stems from an imbalance of neurotransmitters in the body.

Doctors commonly prescribe selective serotonin reuptake inhibitors (SSRIs) as antidepressants. Fluoxetine (Prozac) is one example.

Normally, the body reabsorbs a neurotransmitter after it has transmitted its neural impulse. SSRIs stop the body from reabsorbing serotonin, leaving higher levels of serotonin to circulate.

Many people find SSRIs help relieve their symptoms, although the link between depression and serotonin remains unclear.

One problem for researchers is that, while they can measure serotonin levels in the bloodstream, they cannot measure its levels in the brain.

As a result, they do not know whether serotonin levels in the bloodstream reflect those in the brain. It is also impossible to know whether SSRIs can really affect the brain.

Mouse studies have produced conflicting evidence. Some suggest that increasing serotonin levels can help reduce stress and depression, but others indicate that serotonin levels make no difference .

In 2015, one editorial called the use of SSRIs to treat depression “the marketing of a myth.”

Nevertheless, if scientists have not yet proven the serotonin theory of depression, SSRIs do appear to help many people.

Other disorders

Apart from depression, doctors may prescribe drugs that regulate serotonin levels to treat a number of other disorders , including:

As with depression, some scientists have questioned whether serotonin is the only factor impacting these conditions.


All About Antidepressants

Antidepressants are the most commonly prescribed meds for depression, but they’re used to treat a number of other conditions as well.

Antidepressants are some of the world’s most prescribed medications.

These meds can be used for a variety of mental health conditions, such as depression and anxiety, but they may also be prescribed to treat pain or sleeping problems.

But with so many types available, how do you know which antidepressant is right for you?

There are several medications used to treat depression, but antidepressants are the most popular.

Antidepressants are one of the primary treatments for depression and one of the most commonly prescribed types of meds in the United States.

More than 13% of U.S. adults — about 1 in 10 people — over the age of 18 used antidepressants in the last 30 days, according to the Centers for Disease Control and Prevention (CDC).

Like the name suggests, antidepressants can help relieve symptoms of depression and may stop them from coming back.

The exact way antidepressants work isn’t totally understood, but they’re believed to work by correcting imbalances of chemicals (aka neurotransmitters) in the brain.

Neurotransmitters regulate our moods and emotions by transmitting nerve signals to receptors in the brain. There are three neurotransmitters that are believed to be specific to depression:

  • Serotonin: regulates mood, appetite, sleep, memory, social behavior, and sexual desire
  • Dopamine: influences motivation, arousal, decision-making, and pleasure
  • Norepinephrine (or noradrenaline): affects alertness and helps the body respond to stress

When you have depression, you may have lower levels of these neurotransmitters in your brain. Antidepressants can help increase the availability of one or more of these neurotransmitters over time.

How they do that, though, depends on what type of antidepressant you’re prescribed.

There are several major types (or classes) of antidepressant medications. Each class works in a slightly different way.

The types of antidepressants include:

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed type of antidepressant. They’re often the first type tried for people who are newly diagnosed with depression.

First developed in the 1970s, SSRIs work by regulating serotonin levels in the brain.

When a neurotransmitter isn’t taken up by other neurons, it’s reabsorbed by the neuron that released it in a process called “reuptake.”

As the name suggests, an SSRI inhibits the reabsorption of serotonin. In other words, it blocks serotonin from quickly leaving your brain. This raises serotonin levels so more is available and active to help regulate your emotions.

  • fluoxetine (Prozac)
  • sertraline (Zoloft)
  • escitalopram (Lexapro)
  • paroxetine (Paxil)
  • citalopram (Celexa)
  • fluvoxamine (Luvox)
  • vilazodone (Viibryd)

SSRIs are often more tolerated than other antidepressants because they tend to have fewer side effects. However, they can have side effects such as:

  • stomach upset or nausea
  • insomnia or other sleep issues
  • nervousness
  • tremors
  • weight changes
  • headaches
  • sexual dysfunction
  • dizziness

Serotonin-norepinephrine reuptake inhibitors

Serotonin-norepinephrine reuptake inhibitors (SNRIs) work similarly to SSRIs, but they inhibit the reuptake of both serotonin and norepinephrine.

SNRIs can have the same benefits as SSRIs, but since they also raise levels of norepinephrine, they may help more with stress and anxiety.

SNRIs are a newer class of drugs — the first SNRI was approved by the Food and Drug Administration (FDA) in 1993. They’re approved for use in treating depression, anxiety disorders, and conditions related to chronic pain.

The increased levels of norepinephrine can cause side effects like:

Other common side effects include:

  • headache
  • stomach upset or nausea
  • dizziness
  • appetite changes
  • dry mouth
  • sexual dysfunction

These can become severe for some individuals, so you’ll want to keep your doctor informed of any side effects you have.

Tricyclic antidepressants

Developed in the 1950s, tricyclic antidepressants (TCAs or tricyclics) were one of the first drugs used to treat depression. The name tricyclic comes from its chemical structure that’s made up of three connected rings of atoms.

Tricyclics work by reducing the reabsorption of serotonin and norepinephrine. They also block another neurotransmitter called acetylcholine, which plays a role in muscle movement, heart rate, thinking, and learning.

Common tricyclics include:

  • clomipramine (Anafranil)
  • amitriptyline (Elavil)
  • desipramine (Norpramin) (Pamelor)
  • doxepin (Sinequan)
  • trimipramine (Surmontil)
  • imipramine (Tofranil)
  • protriptyline (Vivactil)

Prescribing tricyclics is less common now because they have more severe side effects than SSRIs and SNRIs.

You may also have a higher chance of overdosing with a TCA compared to other antidepressants. Taking only a small amount over your normal dose can lead to overdose or have life threatening side effects.

Still, tricyclics may be prescribed when someone isn’t responding to other antidepressants. They may also be prescribed for people with bipolar disorder or obsessive-compulsive disorder (OCD).

The most common side effects of tricyclics are:

  • weight gain
  • urinary retention (when your bladder doesn’t fully empty)
  • constipation
  • dry mouth
  • dizziness
  • blurred vision or dry eyes
  • sleepiness
  • confusion

Abruptly stopping tricyclics or missing a couple of doses can lead to withdrawal or discontinuation symptoms. This is why it’s helpful to create a tapering schedule with your doctor.

Monoamine oxidase inhibitors

Another drug type introduced in the 1950s, monoamine oxidase inhibitors (MAOIs) were one of the first types of antidepressants developed.

MAOIs inhibit the brain enzyme called monoamine oxidase, which is responsible for breaking down neurotransmitters. This leads to higher levels of serotonin, dopamine, and norepinephrine in the brain.

They may also be prescribed for depression in bipolar disorder, borderline personality disorder (BPD), post-traumatic stress disorder (PTSD), agoraphobia, social phobia, and bulimia.

  • selegiline (Emsam)
  • isocarboxazid (Marplan)
  • phenelzine (Nardil)
  • tranylcypromine (Parnate)

MAOIs aren’t often prescribed as much today as they were in the past due to side effects and potential interactions.

If you’re prescribed an MAOI, you’ll be required to follow a special diet. This is because monoamine oxidase regulates the breakdown of tyramine, a compound found in food.

You’ll need to limit foods with tyramine — like aged cheeses, cured or smoked meats, or fermented foods — since MAOIs can cause tyramine levels to rise.

If tyramine levels are too high, it can lead to dangerously high blood pressure. Limiting tyramine-rich foods can help prevent hypertensive crisis, which is when your blood pressure gets too high, increasing your chances of having a heart attack or stroke.

MAOIs also tend to have a lot of other interactions so you can’t mix them with certain meds such as:

  • other types of antidepressants
  • herbal remedies like St. John’s wort
  • central nervous system stimulants (for example, Adderall)
  • certain meds for pain, cold, and allergies

Common side effects of MAOIs include:

  • nausea
  • drowsiness
  • dizziness
  • restlessness
  • trouble sleeping
  • dry mouth
  • diarrhea or constipation
  • skin reactions if using the patch

Noradrenergic and specific serotonergic antidepressants

Noradrenergic and specific serotonergic antidepressants (NaSSAs) are a newer class of drugs that affect serotonin and norepinephrine levels in your brain. They block receptors of the stress hormone epinephrine (adrenaline).

They’re often prescribed for depression, as well as anxiety and personality disorders.

The most common NaSSA is mirtazapine (Remeron).

Possible side effects can include:

  • constipation
  • dry mouth
  • weight gain
  • drowsiness
  • blurred vision
  • dizziness

Atypical antidepressants

Atypical antidepressants are those that don’t particularly fit into any other classes. They affect serotonin, norepinephrine, and dopamine levels in the brain.

Common atypical antidepressants include:

  • bupropion (Wellbutrin)
  • trazodone (Oleptro)
  • vortioxetine (Trintellix)
  • olanzapine/fluoxetine (Symbax)

Each one works differently.

For example, bupropion inhibits the reuptake of dopamine, serotonin, and norepinephrine, raising the levels of all three hormones in the brain. It’s often used to treat depression or depression related to seasonal changes (aka seasonal depression). It can also be used to help someone quit smoking.

Meanwhile, trazodone and vortioxetine both inhibit serotonin reuptake. They’re known as serotonin antagonist and reuptake inhibitors (SARIs).

Symbax is a combination drug that includes an SSRI (fluoxetine) and an antipsychotic (olanzapine).

The primary use for antidepressants is to treat the symptoms of depression, ranging from mild to severe.

However, antidepressants can also be prescribed to help manage symptoms of other conditions, including:

Antidepressants may also have “off-label” uses, meaning these aren’t approved by the FDA for these conditions but may still be effective.

Some off-label uses of antidepressants include:

Antidepressants are most commonly taken in tablet or capsule form, but there are some that can be taken in liquid form.

How often you take your antidepressant will be based on your specific needs and can vary from one to three tablets a day. Some antidepressants will be prescribed in extended release form so you won’t have to take as many pills throughout the day.

You’ll often be started on the lowest dose, then given a plan to gradually increase the dose so your body has time to react and adjust to the med. This can also help prevent sudden side effects.

Each class of antidepressants has different side effects, ranging from mild to more severe.

However, the most common side effects across all antidepressants are:

  • headache
  • dry mouth
  • fatigue
  • dizziness
  • weight changes
  • drowsiness
  • sexual issues

In severe instances, antidepressants may lead to an increased likelihood of suicidal thoughts and actions.

For this reason, the FDA has a black box warning on antidepressants for people under the age of 24.

The side effects of antidepressants can feel like a barrier to some people, but it’s important to remember that you may only have one or two of them, or none at all.

Sometimes, side effects are only temporary until your body adjusts to the med, in which case the side effects will be reduced or entirely disappear after the first few weeks of treatment.

In general, if you’re having side effects that last for several weeks without improvement, or you’re concerned that a side effect is having a strong or dangerous impact on your health, reach out to your doctor immediately. They’ll be able to assess what’s happening and plan next steps.

Antidepressants can sometimes interact with other drugs.

In severe cases, drug interactions can lead to serotonin syndrome, which can be dangerous. To avoid this, make sure your doctor is aware of any and all drugs you’re taking, including over-the-counter medications and nutritional supplements.

When choosing the best antidepressant treatment for you, remember that there isn’t one type that’s specifically better or more effective than another.

Since each type does something different, consider talking with a healthcare professional who has experience prescribing antidepressants so they can help find one that will address your specific symptoms.

Study up on antidepressants

Take the time to research and learn about the different types of antidepressants and how they work, especially before you start taking one. By having a better understanding of how they work, you’ll have a better understanding of what’s happening in your body.

Take notes and jot down any questions you may have to discuss at your next appointment.

Track your side effects

It’s always a good idea to check in with yourself to see how you’re feeling while taking an antidepressant.

For example, if you’re feeling increasingly dizzy or start having more headaches, write it down and share it with your doctor.

The more information your doctor has, the better they can adjust your medication or dosage.

Give it some time

It’s important to remember that changes in your mood will be gradual when you start using antidepressants. This is because antidepressants take time to build up their effectiveness.

So don’t expect instantaneous results. Allow some time to start seeing a change.

It can take several weeks to fully feel the effects of most antidepressants.

Don’t give up after the first week just because you don’t feel better right away, and try not to get discouraged if you don’t see fast improvements.

Stay on a schedule

Missing doses or quitting for even short periods of time will slow down your progress and, in some cases, cause you to go through withdrawal symptoms.

Consider taking antidepressants at a time when you know you’ll more reliably take them, like in the morning before work or school. You can also create a phone reminder or leave a note blocking your door if that helps.

Living with depression can feel overwhelming at times, and it’s hard to know where to even start looking for help. You may feel bad about needing to ask for help in the first place or admitting that you’re not feeling well.

But there’s nothing to feel bad or ashamed about. You’re not alone. There are numerous resources available for managing your mental health and depression.

Consider talking to a mental health professional since they can discuss treatment options. Be honest about how you’ve been feeling and what changes you hope to see.

Depending on your symptoms, they may not even prescribe antidepressants for you. It’s possible that talk therapy alone could be just as effective.

Ultimately, you don’t have to make the decision to go on antidepressants alone. A doctor will be there to help you talk through the treatment options that are right for you.


How do antidepressants actually work?

A recent article by Deborah Orr regarding her experiences with antidepressants sparked a lot of debate as to their merits and drawbacks. The truth is, they’re not as simple or as understood as many might think

Very common, but that doesn’t mean they’re perfectly understood. Photograph: Joe Raedle/Getty Images

Very common, but that doesn’t mean they’re perfectly understood. Photograph: Joe Raedle/Getty Images

Last modified on Wed 20 Sep 2017 23.05 BST

Antidepressants the go-to treatment for depression, or generalised anxiety. It’s incredible when you think about it, the fact that you can have a debilitating mood disorder, take a few pills, and feel better. It’s unbelievable that medical science has progressed so far that we now fully understand how the human brain produces moods and other emotions, so can manipulate them with designer drugs.

That’s right, it is unbelievable. Because it isn’t the case. The fact that antidepressants are now so common is something of a mixed blessing. On one hand, anything that helps reduce stigma and lets those afflicted know they aren’t alone can only be helpful. Depression is incredibly common, so this awareness can literally save many lives.

On the other hand, familiarity does not automatically mean understanding. Nearly everyone has a smartphone these days, but how many people, if pushed, could construct a touchscreen? Not many, I’d wager. And so it is with depression and antidepressants. For all the coverage and opinion pieces produced about them, the details around how they work remain somewhat murky and elusive.

Actually, in the case of antidepressants, it’s more a question of why they work, rather than how. Most antidepressants, from the earliest Trycyclics and Monamine Oxidase inhibitors, to the ubiquitous modern day selective serotonin reuptake inhibitors (SSRIs), work by increasing the levels of specific neurotransmitters in the brain, usually by preventing them from being broken down and reabsorbed into the neurons, meaning they linger in the synapses longer, causing more activity, so “compensating” for the reduced overall levels. Antidepressants make the remaining neurotransmitters work twice as hard, so overall activity is more “normal”, so to speak.

But knowing that antidepressants do this doesn’t actually explain how they end up alleviating depression. In a way, neurotransmitters are to the brain what the alphabet is to language the basic elements of much richer, more complex contructs. So, boosting neurotransmitter levels throughout the brain doesn’t really tell us anything specific. It’s like having to restore a classic painting and being told it “needs more green” that may be true, but where? How much? What shade? It’s too unspecific to tell us anything useful.

Depression is so poorly understood that most people illustrate it with someone holding their head in their hands, as a trawl through any image archive will reveal. It doesn’t make your brain heavier or anything. Photograph: Nastia11/Getty Images/iStockphoto

The truth is, antidepressants were discovered largely by accident Swiss scientists looking for treatments for schizophrenia in the 1950s realised a certain experimental substance caused euphoria in their subjects. And lo, antidepressants were born. Nothing unusual here, luck and serendipity are behind the discoveries of many drugs. But this led to the monoamine theory of depression, which argues that, because most antidepressants increase levels of neurotransmitters of the monoamine class, depression is caused by depletion of monoamines in the brain.

Except, the monoamine hypothesis is increasingly seen as insufficient. It’s part of what’s going on, sure, but not the whole story. For one, antidepressants boost neurotransmitter activity pretty much immediately, but therapeutic effects usually take weeks to kick in. Why? It’s like filling your car’s empty tank with petrol and it only starting to run again a month later it means no fuel may have been a problem, but it’s clearly not the only problem.

There are other possible explanations. Neuroplasticity, the ability to form new connections between neurons, has been shown to be impaired in depressed patients. The theory is that this prevents the brain from responding “correctly” aversive stimuli and stress. Something bad happens, and the impaired plasticity means the brain is more ‘fixed’ as is, like a cake left out too long, preventing moving on, adapting, or escaping the negative mindset, and thus depression. Antidepressants also gradually increase neuroplasticity, so this may be actually why they work as they do, long after the transmitter levels are raised. It’s not like putting fuel in a car, it’s more like fertilising a plant it takes time for the helpful elements to be absorbed into the system.

There are other possibilities. Inflammation causing undue stress on the brain is one, an overactive anterior cingulate cortex is another. Essentially, it’s complicated, and we can’t confirm anything yet.

Basically, depression isn’t a broken leg, or a cold. We can’t look at it, say “that’s what’s wrong, right there” and set about fixing it. Psychiatric issues are never that straightforward (and that’s without the many overlaps with more physical ailments). Part of the problem is that “depression” is more of an all-purpose term for something that manifests in many in different ways. It’s a mood disorder, but how mood is affected can vary substantially. Some end up with an unshakable black despair, others experience no mood to speak of, just feeling flat, empty and emotionless. Some (mostly men) become constantly angry and restless.

This is part of the reason why it’s proven so difficult to establish an underlying cause. The human brain is the most complex thing, and even a minor flaw or glitch in the workings can manifest in various, unexpected ways. And there’s no reason to assume that every case of depression has exactly the same cause. It’s not surprising, then, that antidepressants don’t work, or even make things worse, for many patients. There are other approaches too, but then these may not work for you either. If the causes and effects of depression vary considerably from person to person, so would the effectiveness of treatments.

Most therapeutic interventions don’t involve leather couches either. Maybe that’s a Hollywood thing? Photograph: Getty Images/Stockbyte

Antidepressants also have many potential side effects, which themselves vary from person to person. And while the therapeutic effects (which many argue are themselves overstated or based on questionable evidence) take weeks to occur, the same doesn’t apply to the unpleasant side effects, as Deborah Orr recently discovered.

Given all this, you may wonder how antidepressants ended up being so common in the first place? Well, it may boil down to the fact that, for all the flaws and problems they may have, they’re better than nothing, especially when the alternative is untreated depression. Some take a more cynical view, arguing that it’s pharmaceutical companies profiting by pushing profitable pills on people who don’t really need them.

Or, in the UK at least, it may be something to do lack of time and resources. In an ideal world, people with depression would have easy access to CBT or other interventions given how every patient is different and what works for them is often a matter of trial and error. But, in an increasingly-underfunded and overworked NHS, this is increasingly difficult, even impossible, to offer. Many of the interpersonal therapies for depression and other disorders involve many hours of contact time with highly trained (ie expensive) professionals. Given the choice between that or giving someone a box of tablets and saying “see you in a month”, the latter would likely be the go-to option much of the time.

Overall, the widespread use of antidepressants is likely down to numerous complex causes, and the effects are unpredictable and confusing. Much like depression itself, which seems appropriate.

This article is adapted from Dean Burnett’s book The Idiot Brain, released in paperback in the US on 11 July.