Pharmacology, part 18: Nervous System Medications for Depression

by Cathy Parkes

In this article, we cover medications used to treat depression including tricyclic antidepressants, MAOIs and atypical antidepressants. The Nursing Pharmacology video series follows along with our Pharmacology Flashcards, which are intended to help RN and PN nursing students study for nursing school exams, including the ATI, HESI, and NCLEX. 

Cool Chicken When you see this Cool Chicken, that indicates one of Cathy's silly mnemonics to help you remember. The Cool Chicken hints in these articles are just a taste of what's available across our Level Up RN Flashcards for nursing students!

Neurotransmitters affected by antidepressants

The medications that we cover in this article all affect a few neurotransmitters in the brain, including serotonin, norepinephrine, and dopamine. Let’s first review the function of these neurotransmitters and the role they might play in depression.


Serotonin is a neurotransmitter in our bodies that enables brain cells and other nervous system cells to communicate with each other. It’s the key hormone that stabilizes our mood and happiness and helps with sleeping, eating and digestion. It is widely believed that a lack of serotonin can lead to depression.


Norepinephrine is a chemical in our body that acts as both a stress hormone and neurotransmitter. It is released into the blood as a stress hormone when the brain perceives that a stressful event has occurred. You can learn more about norepinephrine in our endocrine system hormone review

It may seem counterintuitive that an antidepressant would seek to increase a stress hormone — if you are depressed, why would you want to be stressed? Norepinephrine is actually related to the body’s alertness and energy. Alertness and energy can be useful in times of stress, but also might be too low as a result of depression. Therefore, some antidepressants seek to increase the stress-related hormone Norepinephrine.


Dopamine acts as a chemical messenger between neurons in the brain, and is released when your brain is expecting a reward. To put it simply, dopamine is an important chemical required for the ability to be happy. Scientists believe that a deficit of dopamine is a key component of depression.

Tricyclic antidepressants - amitriptyline, imipramine

Tricyclic antidepressants such as amitriptyline (Elavil) and imipramine (Tofranil) are medications that are not only used for depression but also neuropathy, fibromyalgia and at times, insomnia. 

Neuropathy is damage or dysfunction of the nerves that typically results in numbness, tingling, muscle weakness and pain in the affected area. 

Fibromyalgia is a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues

Mode of action

Tricyclic antidepressants like amitriptyline and imipramine work by increasing the levels of serotonin and norepinephrine in the central nervous system (CNS) and blocking the action of acetylcholine. It is believed that restoring the balance of these neurotransmitters in the brain alleviates depression and the symptoms of depression.

Side effects

Tricyclic antidepressants like amitriptyline and imipramine carry a lot of side effects. They can include sedation, orthostatic hypotension, dysrhythmias, sweating and seizures. Due to the way the medications block acetylcholine, they can have anticholinergic side effects, which Cathy loves to remember with the saying “can’t see, can’t pee, can’t spit and can’t poop”. These side effects can include urinary retention, constipation, dry mouth, blurry vision, and photophobia (light sensitivity).

Cool Chicken Amy tripped over a tricycle in the desert. It is DRY in the desert, like the anticholinergic effects of amitriptyline. 

Patient teaching

When caring for a patient taking tricyclic antidepressants like amitriptyline and imipramine, it’s important to advise the patient to chew gum, wear sunglasses and increase fluid and fiber intake to help counteract the constipation that comes along with anticholinergic side effects.

Monoamine oxidase inhibitors (MAOIs) - phenelzine, tranylcypromine

Monoamine oxidase inhibitors (MAOIs) such as phenelzine (Nardil) and tranylcypromine (Parnate) were the first type of antidepressants developed to treat depression. They are effective, however, more modern antidepressants have been developed that are safer and cause fewer side effects. MAOIs are prescribed less frequently now than in the past, and are usually not tried first.

Mode of action

MAOIs elevate levels of norepinephrine, serotonin, and dopamine by inhibiting an enzyme called monoamine oxidase. Monoamine oxidase (MAO) is an enzyme involved in removing norepinephrine, serotonin, and dopamine from the brain. MAOIs are an inhibitor of MAOs, so they prevent MAOs from doing the removal, which makes more of these brain chemicals available. 

Side effects

Side effects of MAOIs can include agitation, anxiety and orthostatic hypotension. The most important side effect to remember is that MAOIs can cause a hypertensive crisis, meaning a severe increase in blood pressure that can lead to a stroke. 


MAOIs interact with many prescriptions, foods and over-the-counter cold medications. Chances are, if you look up a medication on your drug reference guide and look at drug interactions, MAOIs are going to show up for a lot of medications. If your patient is on MAOIs, they will need to be very careful about what other medications they take, due to the many interactions and potential side effects. 

Patient teaching

While caring for a patient that is taking MAOIs, it is very important to inform them that they should avoid eating foods that are rich in tyramine. 

Tyramine is an amino acid that helps regulate blood pressure. It occurs naturally in the body, but it is also found in certain foods. Foods that are rich in tyramine include aged cheese, smoked meat, avocado, red wine, and chocolate.

Cool Chicken With “Phenelzine” you can’t eat life’s finer things because they contain tyramines.

MAO is an enzyme that breaks down excess tyramine in the body. With MAOIs, MAO is inhibited, so the excess tyramine is not being broken down, which can lead to too much tyramine in the body, which can spike blood pressure. The hypertensive crisis side effect seen with MAOIs is often related to tyramine levels in the body being too high, so limiting tyramine-rich foods can help avoid this dangerous side effect. 

Atypical antidepressants

Atypical antidepressants are depressants that are not typical, meaning that they don’t fit into other classes of antidepressants. They are each unique medications that work in different ways from one another.

Bupropion (Wellbutrin, Zyban)

Bupropion (Wellbutrin, Zyban) is an antidepressant medication used to treat depression. The Zyban brand of bupropion is used to help people stop smoking by reducing cravings and other withdrawal effects. 

Cool Chicken Bupropion… “be appropriate” and don’t smoke. 

Mode of action

Bupropion works by inhibiting the reuptake (reabsorption) of dopamine, serotonin, and norepinephrine in the body. This results in more dopamine, serotonin, and norepinephrine to transmit messages to nerves, helping alleviate symptoms of depression.

The reason that bupropion can work as an anti-smoking agent is its effect on dopamine, which is linked to the brain’s habit-reward system, just as smoking is.

Side effects

Side effects of bupropion can include insomnia, headache, GI upset, weight loss, agitation, and a possible increase in the risk for seizures. 

Trazodone (Oleptro)

Trazodone (Oleptro) is in a class of medications called serotonin modulators and is used to treat depression. It can help to alleviate anxiety and insomnia and may help to improve your mood, appetite and energy levels. 

Mode of action

Trazodone works by increasing the availability of the neurotransmitter serotonin in the CNS. It is a serotonin antagonist reuptake inhibitor (SARI), meaning that it primarily blocks the ability of neurons to reabsorb serotonin once it has been released into the central nervous system. Serotonin being reabsorbed means it is not available to be used in the brain.

Side effects

The key side effects to remember with trazodone are sedation, hypotension and dry mouth.

Patient teaching

When caring for a patient taking trazodone, it’s important to advise the patient that they should avoid alcohol due to the side effect of sedation and that they can chew gum or suck on sugar-free candy to help with dry mouth.

Full Transcript

Okay, in this video we are going to focus on medications that are used to treat depression, including tricyclic antidepressants, MAOIs and atypical antidepressants.

Let's start with tricyclic antidepressants. So medications that fall within this class include amitriptyline as well as imipramine.

These medications can be used not only for depression but also neuropathy and fibromyalgia and sometimes we also use them for insomnia.

So the mode of action of tricyclic antidepressants is to increase the effect of serotonin and norepinephrine in the central nervous system.

There are a lot of side effects with this class of medication, so this includes sedation, orthostatic hypotension, as well as anticholinergic side effects, so remember with anticholinergic side effects I have my little PG13 tip, which is can't see, can't pee, can't spit and can't poop, right?

So you're going to get things like urinary retention, which is the can't pee part of that, constipation, can't poop, dry mouth, blurry vision, and photophobia. Those are going to be really important side effects to know with amitriptyline.

Other side effects can include dysrhythmias, sweating, and seizures.

So the way I remember this class of medication and some of the side effects is, I think of a girl named Amy who is walking along in the desert and trips over a tricycle. So that helps me to remember that amitriptyline is a key medication that is a tricyclic antidepressant. And because it's in the desert, she's sedated, she's sweating, and is very dry. So that helps me to remember all of the anticholinergic or drying side effects of amitriptyline. So hopefully, that's helpful for you as well. I know that little story has definitely helped people in the past to remember the key side effects with this medication.

So in terms of patient teaching, in order to kind of counteract those anticholinergic side effects, you should encourage your patient to chew gum, wear sunglasses, and increase their fluid and fiber intake to help counteract that constipation.

Now, let's talk about MAOIs, which are monoamine oxidase inhibitors. MAOIs include medications such as phenelzine and tranylcypromine.

MAOIs are used to treat depression.

And they work by inhibiting monoamine oxidase, which increases levels of dopamine, epinephrine, norepinephrine, and serotonin in the body.

Side effects can include agitation or anxiety as well as orthostatic hypotension, but the most important side effect to remember with MAOIs is that they can cause a hypertensive crisis. So it can send that blood pressure way up.

MAOIs interact with many, many medications. Chances are if you look up a medication on your drug reference guide and look at drug interactions, MAOIs are going to show up for a lot of medications. So they interact with many things, including over-the-counter cold products. So your patient who's on an MAOI will need to be very very careful about what other medications they take.

Another thing is that you're going to have to provide some important teaching to your patient who is on an MAOI. They are going to need to avoid foods that are rich in tyramines because this can also cause a hypertensive crisis. So foods that are rich in tyramines include kind of all these bougie foods like aged cheese, smoked meat, avocado, red wine, chocolate. So really all the yummy foods, they should avoid those because it can cause a hypertensive crisis.

So a rhyme that was submitted to us from a member of our Level Up RN crew is the following. With phenelzine, you can't eat life's finer things because they contain tyramines. So that's an amazing rhyme. I love it, and it will hopefully help you to remember that with MAOIs, which includes phenelzine, you can't have those tyramines.

Now, let's talk about some atypical antidepressants, which includes bupropion as well as trazodone.

Bupropion can be used not only for depression but as a smoking deterrent.

So a tip that my son gave me was, "Be appropriate with bupropion and don't smoke." So be appropriate, bupropion kind of sound similar, and it will help you to remember that, "Be appropriate and don't smoke."

So the mode of action of bupropion is to decrease reuptake of dopamine and norepinephrine.

Side effects can include insomnia - that's very common - in addition to headache, GI upset, weight loss, agitation, and a possible increase in the risk for seizures.

Trazodone is another atypical antidepressant.

It doesn't work as a smoking deterrent, but it is used for depression.

The mode of action is that it serves as a serotonin antagonist and reuptake inhibitor.

The key side effect with trazodone is sedation, so you're definitely going to want to advise your patient to avoid alcohol while taking trazodone because that can really exacerbate that side effect.

In addition, it can cause hypotension and dry mouth, and just like with all of our medications that cause dry mouth, you can advise your patient to chew gum or suck on hard candy to help with that dry mouth.

Okay. So in my next video, I will be talking about a few medications that can be used for both depression and anxiety, such as SSRIs and SNRIs, so hang in there with me!

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