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Depression

25 min read

SSRIs vs. Tricyclics: Which One Should I Take?

Klarity Editorial Team

Written by Klarity Editorial Team

Published: Oct 4, 2022

Medically Reviewed by Dr. Zoe Russell

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SSRIs vs. Tricyclics: Which One Should I Take?
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Are you experiencing symptoms of anxiety or depression and are unsure which treatment option is best for you? With so many different medications available, it may seem difficult to understand which medication to choose. 

In this article, we’ll discuss the difference between SSRIs and tricyclics, two common classes of drugs used to treat anxiety and depression. While both types of medications are proven to be effective, there are differences in their side effects, cost, and warnings associated with each medication. It is important to understand the key differences between prescription medications in order to have an informed discussion with your healthcare provider about which treatment option is right for you. 

Affordable, caring treatment for depression is a click away.
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When researching medications like SSRIs or tricyclics online, you should never attempt to self-diagnose or self-medicate. Always consult with a healthcare professional to find the safest and most effective treatment based on your symptoms, medical history, and more. 

If you need a reliable and affordable way to access treatment for your anxiety or depression,  Klarity can help. We’ll match you with a licensed healthcare provider in your state for convenient, insurance-free online mental health treatment. Your provider will evaluate your symptoms and help you decide if an SSRI or tricyclic is right for you. Schedule an appointment today.

This article discusses suicide, suicidal ideation, and self-harm. If you or someone you know is experiencing suicidal thoughts or is in crisis, contact the Suicide Prevention Lifeline immediately at 800-273-8255.

SSRIsTricyclics
Drug ClassSelective serotonin reuptake inhibitors (SSRIs)Tricyclic antidepressants (TCAs)
Brand / Generic StatusBrand-names and generics available

Most common SSRIs:
• Prozac (fluoxetine)
• Paxil (paroxetine)
• Zoloft (sertraline)
• Celexa (citalopram)
• Luvox (fluvoxamine)
• Lexapro (escitalopram)
• Trintellix (vortioxetine)
• Viibryd (vilazodone)
Brand-names and generics available

Most common TCAs:
• Tofranil (imipramine hydrochloride)
• Pamelor (nortriptyline)
• Asendin (amoxapine)
• Elavil (amitriptyline)
• Surmontil (trimipramine)
• Vivactil (protriptyline)
• Silenor (doxepin)
• Zonalong or Prudoxin (doxepin)
• Norpramin (desipramine)

Form(s) of the DrugCommon forms of SSRIs include:
• Color-coded* capsules
• Color-coded* tablets
• Flavored liquid suspensions

*Color-coding often indicates dosage amount
Common forms of TCAs include:
• Capsules
• Tablets
• Flavored liquid suspensions

Standard DosageVaries, depending on SSRI and condition being treated

Varies, depending on TCA and condition being treated
Conditions TreatedConditions most often treated:
• Major depressive disorder
• Generalized anxiety disorder

Other conditions treated:
• Obsessive-compulsive disorder (OCD)
• Eating disorders
• Premenstrual dysphoric disorder (PMDD)

Different SSRIs are FDA-approved for different uses

Many SSRIs are prescribed off-label to treat certain conditions
Conditions most often treated:
• Depression
• Migraine headaches

Other conditions treated:
• Obsessive-compulsive disorder (OCD)
• Anxiety disorders
• Insomnia
• Chronic pain
• Neuropathic pain
• Nerve pain
• Itching and eczema

Different TCAs are FDA-approved for different uses

Many TCAs are prescribed off-label to treat certain conditions
CostAverage cost of a 30-day supply:
• $4 to $40 for generic formulas*
• $130 or more for brand-name formulas**

*Some SSRIs don’t have a generic formula available for Rx.

**Cost of brand-name SSRIs may be offset by coupons and insurance
Average cost of a 30-day supply:
• $20 for a 30-day supply of:
• Amitriptyline
• Pamelor
• Silenor
• Norpramin
• Tofranil
• $120 or more for most other tricyclics*

*Most TCAs are covered under insurance
Side-EffectsCommon side effects:
• Nausea, vomiting, GI upset, or diarrhea
• Dry mouth
• Headache
• Difficulty sleeping or insomnia
• Drowsiness or dizziness
• Increased nervousness, feelings of restlessness, or agitation
• Reduced libido, erectile dysfunction
• Increase or decrease appetite, leading to changes in weight
Common side effects:
• Drowsiness
• Constipation
• Dry mouth
• Blurred vision
• Orthostatic hypotension
• Urine retention
• Increased sweating
• Tremors
• Increased or decreased appetite
• Sexual dysfunction
Warnings For Use• Combination with other medications may cause serotonin syndrome
• Symptoms of serotonin syndrome include:
• Anxiety or agitation
• Fever, sweating
• Tremors
• Restlessness
• Confusion
• Lack of coordination
• Blood pressure and heart rate changes

• Rarely, SSRIs may cause
suicidal thoughts or behaviors
• Contact your doctor immediately if this occurs
• Combination with other medications may cause serotonin syndrome
• Symptoms of serotonin syndrome include:
• Anxiety or agitation
• Fever, sweating
• Tremors
• Restlessness
• Confusion
• Lack of coordination
• Blood pressure and heart rate changes
• May cause seizures or falls in those prone to them
• Do not mix with alcohol
• Rarely, TCAs cause suicidal thoughts or behaviors
• Contact your doctor immediately if this occurs

SSRIs

Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed medications used to treat anxiety and depression. SSRIs are used in both adolescent and adult populations and have been found to be one of the most effective types of drugs for improving mood and reducing anxiety. 

How Do SSRIs Work?

Serotonin is a chemical neurotransmitter that is naturally found in the brain. It acts as a messenger between the nerve cells and plays an important role in many bodily functions, such as mood, sleep, and digestion. 

Research has shown that serotonin levels are reduced in patients that suffer from depression and anxiety. SSRIs work by increasing the amount of available serotonin in the brain by blocking the reabsorption or reuptake of serotonin into neurons. 

What Do SSRIs Treat?

SSRIs are the most commonly prescribed medications for anxiety and depression. They have been found to be the most effective class of medications to improve mood and are safely used in both children and adults. 

Anxiety and depression are often diagnosed concurrently in patients, making this class of medications useful when treating those who are suffering from both. In addition, SSRIs are also used to treat eating disorders, obsessive-compulsive disorder (OCD), panic disorder, and premenstrual dysphoric disorder (PMDD). 

Depression

Depression is a serious mood disorder that affects a patient’s everyday life. This condition impacts the patient’s feelings, alters the thinking process, and disrupts their daily activities. There are many different types of depression, with the most common being known as major depressive disorder. 

Chronic depression, also known as major depressive disorder (MDD), consists of various symptoms of depression that occur for the majority of at least two weeks and interfere with everyday life. Some common symptoms include: 

  • Persistent depressed mood
  • Feelings of hopelessness, helplessness, irritability, or restlessness
  • Loss of interest in pleasurable activities
  • Difficulty concentrating
  • Sleep disruption
  • Changes in appetite 
  • Physical symptoms, such as headaches, fatigue, and various pain throughout the body. 
  • Increased thoughts of death, suicide, or self-harm. 

People with depression tend to have lower levels of serotonin, and SSRIs work by increasing the levels of serotonin in the brain. SSRIs have been shown to be highly effective in improving mood and are one of the most common forms of depression treatment today. 

Anxiety

Anxiety is a normal physiological reaction to any perceived stressor in life. However, patients who suffer from anxiety disorders experience intense, constant, or excessive fear and worry about everyday life events and situations. Similar to depression, there are a number of different types of anxiety disorders, with the most common being Generalized Anxiety Disorder (GAD). 

GAD consists of increased anxiety or worry surrounding everyday life events or situations. The level of worry is considered to be exaggerated or out of proportion with the given circumstances and is often challenging to control. In addition, a patient with anxiety often experiences physical symptoms, such as an increased heart rate, irregular heartbeats, chest pain, or shortness of breath.  

Other common anxiety disorders that are effectively treated with SSRIs include obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and panic disorder. They are also frequently prescribed to treat OCD-related phobias, such as agoraphobia and social phobia. 

By increasing the levels of serotonin in the brain, SSRIs work to calm overwhelming thoughts or feelings of worry. This class of medication has been proven to be one of the most effective forms of treatment for various anxiety disorders. 

What Are the Most Commonly Prescribed SSRIs?

Prozac

Prozac (fluoxetine) is most commonly prescribed for mood disorders, such as depression, OCD, and panic disorder. It is also commonly prescribed to treat eating disorders like bulimia. 

Paxil

Paxil (paroxetine) is primarily prescribed for depression but may also be used to treat generalized anxiety disorders, OCD, panic attacks, PTSD, and PMDD. 

Zoloft

Zoloft (sertraline) is used to treat depression, OCD, panic disorders, PTSD, PMDD, and social anxiety. This is one of the more popular medications prescribed compared to other drugs in this class. 

Celexa

Celexa (citalopram) is typically used to treat depression, but tends to be slightly less popular than other SSRIs. This is likely because this Celexa has been shown to be less effective than other SSRI options in research studies. 

Luvox

Luvox (fluvoxamine) is an SSRI used to treat OCD. While it is not FDA-approved to treat generalized anxiety or depression, it is sometimes prescribed off-label for patients with severe depression.

Lexapro

Lexapro (escitalopram) is a common medication to treat depression and most types of anxiety disorders. This drug is fairly popular and commonly prescribed. 

Trintellix

Trintellix (vortioxetine) is a serotonin modulator and is pharmacologically unique compared to other SSRIs. This is commonly used to treat major depressive disorder. There is no generic alternative available, making this medication more expensive compared to other SSRIs. 

Viibryd

Viibryd (vilazodone) is a newer SSRI used to treat depression. This medication tends to be less popular than other SSRIs and does not have a generic alternative. 

Costs

The cost of SSRIs varies drastically depending on the specific medication, as well as generic versus name-brand formulations. Overall, this class of medication is fairly inexpensive, and the majority of SSRIs come available in both generic and name-brand versions. Some of the most affordable SSRIs include Zoloft, Prozac, Lexapro, Celexa, and Paxil. 

The average cost of a 30-day supply of SSRIs ranges from $4 – $40 for generic name medications when using a coupon card at the pharmacy. Some SSRIs do not have a generic formulation and are more expensive, such as Luvox, with a higher cost for a 30-day supply at around $130. The majority of these medications are covered by insurance, and prescription coupon cards are available at most pharmacies. 

Common Side Effects

The most common side effects of SSRIs include: 

  • Nausea, vomiting, GI upset, or diarrhea
  • Dry mouth 
  • Headache 
  • Difficulty sleeping or insomnia 
  • Drowsiness or dizziness 
  • Increased nervousness, feelings of restlessness, or agitation
  • Reduced libido, erectile dysfunction 
  • Weight changes related to increased or decreased appetite

Warnings for Use

Serotonin Syndrome

Serotonin Syndrome is a rare but serious condition that occurs when high serotonin levels accumulate in the body. Signs and symptoms include:

  • Anxiety or agitation
  • Fever
  • Increased sweating
  • Tremors
  • Feelings of restlessness
  • Lack of coordination or confusion
  • Changes in the patient’s blood pressure and heart rate

This is commonly seen in patients who are taking multiple medications that increase serotonin levels in the body simultaneously. It is important to immediately seek medical attention if you begin to experience these symptoms and inform your healthcare provider of all the medications you are taking before being started on an antidepressant. 

Suicidal Thoughts or Behaviors

An increase in suicidal thoughts or behaviors has been seen in some patients that are started on SSRIs. This is rare, but is most frequently seen in adolescents and young adults under the age of 25. Contact your healthcare provider immediately if you begin to experience suicidal thoughts, ideations, or behaviors like self-harm.

Withdrawal

Abrupt discontinuation of an SSRI may result in withdrawal-like symptoms. If you are unhappy with your prescription, you should work with your healthcare provider to gradually taper off the medication or modify your dosage. Common withdrawal symptoms include: 

  • Flu-like symptoms: muscle aches or pain, chills, fatigue 
  • Sleep disturbances, such as insomnia or nightmares 
  • Nausea, vomiting, abdominal discomfort
  • Imbalance or lack of coordination 
  • Sensory disturbances, such as tremors or sensations of electric shock

Tricyclics

Tricyclic antidepressants, or TCAs, are another common treatment used for depression and anxiety. This class of medications is among some of the oldest forms of antidepressant medications developed, but due to their side effect profile, they have become less popular in treating the general population. However, this type of medication remains to be a good option for some. 

How Do Tricyclics Work?

TCAs work by acting on a number of different chemical neurotransmitter pathways or messaging systems in the brain. Similar to SSRIs, tricyclics block the reuptake of serotonin. In addition, these antidepressants block the reuptake of another neurotransmitter, norepinephrine, leading to increased levels of both in the brain. 

Tricyclic antidepressants have been phased out as a popular treatment because they also target other chemicals in the brain unrelated to mood, which can lead to an increased risk of side effects. However, patients who find SSRIs ineffective may benefit from tricyclics. 

What Do Tricyclics Treat?

Tricyclics are primarily used to treat depression and prevent migraines. In some circumstances, they are used to treat OCD, anxiety disorders, insomnia, as well as chronic neuropathic pain due to dysfunction of the nerves. Tricyclic antidepressants may also be used to treat migraine headaches, bed-wetting, insomnia, itching, and eczema. 

Depression

Tricyclic antidepressants remain to be one of the earliest pharmacologically developed medications used to treat depression. There are a number of different depressive disorders, with the most common being major depressive disorder (MDD). MDD consists of various symptoms of depression that occur for the majority of at least two weeks and interfere with everyday life. 

Some common symptoms of MDD include:

  • Persistent depressed mood
  • Los of interest in pleasurable activities 
  • Feelings of hopelessness or helplessness
  • Irritability or restlessness
  • Difficulty concentrating 
  • Sleep disruption, including insomnia or increased need for sleep
  • Changes in appetite, leading to weight loss or gain
  • Physical symptoms: headaches, fatigue, pain in various areas
  • Severe can increase thoughts of death, suicide, or self-harm

Those who suffer from severe depression tend to have lower levels of serotonin and norepinephrine in the brain. Tricyclic antidepressants work by increasing these two neurochemical messengers to improve depressive symptoms. 

Anxiety

Anxiety is known to be an exaggerated biological response to a perceived threat or life stressor. Anxiety disorders include generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and panic disorder. Of these, GAD is the most commonly diagnosed. 

TCAs were one of the first medications to be developed for the treatment of anxiety and are still used today. By acting on two different neurotransmitters in the brain, they have been shown to be effective in easing feelings of worry and controlling racing thoughts in those who suffer from anxiety.

What Are the Most Commonly Prescribed Tricyclics?

Tofranil

Tofranil (imipramine hydrochloride) is commonly prescribed to treat depression, as well as nighttime bed wetting in children. 

Pamelor

Pamelor (nortriptyline) is used to treat depression. It remains to be slightly less popular compared to other tricyclic medications, due to an increase in negative interactions with other common medications. It is also slightly more expensive than other TCAs. 

Asendin

Asendin (amoxapine) is used to treat depression and anxiety disorders. This drug typically needs to be taken right before bedtime due to drowsiness. 

Elavil

Elavil (amitriptyline) is a commonly prescribed drug used to treat migraine headaches and major depressive disorder. It is one of the most commonly prescribed tricyclic medications. Amitriptyline is only available as a generic drug, and in addition to Elavil, other generic names include Amitid, Amitril, and Endep. 

Surmontil

Surmontil (trimipramine) is another TCA used to treat depression. This medication is available as a capsule and is taken one to three times a day. 

Vivactil  

Vivactil (protriptyline) is prescribed to treat depression. This medication is less popular because it is more expensive than other tricyclics, and patients typically need to take multiple doses per day. 

Doxepin

Silenor (doxepin) is primarily used to treat insomnia and helps you sleep throughout the night. There are currently no available generic alternatives for this medication, and it remains to be less popular than other comparable medications. 

Zonalong or Prudoxin (doxepin) is another form of this tricyclic medication and is prescribed to reduce itching that is caused by various skin conditions, such as eczema. 

Norpramin

Norpramin (desipramine) is used to treat depression. It is not as commonly prescribed compared to other tricyclics.

Costs

The cost of tricyclic antidepressants varies based on the specific drug prescribed. Overall, tricyclics are more expensive than SSRIs. The least expensive tricyclics include Amitriptyline, Pamelor, Silenor, Norpramin, and Tofranil. A 30-day supply of these medications is under $20 with a coupon card that is available at most pharmacies. 

Other tricyclics are more expensive, and a 30-day supply can reach over $120 with a coupon card. The majority of these medications are covered by insurance. 

Common Side Effects

Due to the side effect profile of this class of medications, other drugs have become more popular in the treatment of depression. 

Some of the most common side effects include: 

  • Drowsiness
  • Constipation
  • Dry mouth
  • Blurred vision 
  • Orthostatic hypotension, or a drop in blood pressure when the patient moves from a sitting to a standing position, causing lightheadedness while standing up 
  • Urine retention 
  • Increased sweating 
  • Tremors 
  • Increased or decreased appetite, leading to changes in weight  
  • Sexual dysfunction, including decreased libido or inability to maintain an erection 

Warnings for Use

Falls

Due to the physical side effects associated with tricyclics, safety is a major concern when starting one of these medications, especially in the elderly or when on a high dose. Falls are a common safety concern due to disorientation or confusion. 

Contraindications with other Diseases or Drugs

All past and current health conditions should be disclosed and discussed with your healthcare provider before starting a tricyclic antidepressant. Of note, certain comorbid conditions may impact the safety of using a tricyclic medication, including glaucoma, heart issues, diabetes, enlarged prostate, liver disease, or a seizure disorder. 

Tricyclics may also cause elevated or irregular heartbeat, as well as an increased risk of seizure in those who are prone to seizures. Do not drink alcohol while taking a tricyclic antidepressant, as this can worsen the side effects of the medication. 

Overdose & Suicide

Overdose with tricyclic antidepressants can be dangerous and even lethal in some cases. All medications, including over-the-counter medications and supplements, should be reviewed with your physician before starting an antidepressant. 

Tricyclics should be avoided in patients with a history of suicidal thoughts or attempts. As with SSRIs, there is also a rare but serious concern for increased suicidal thoughts or behaviors, and should be closely monitored in adolescents and young adults under the age of 25. 

If you are experiencing thoughts of self-harm or suicide, contact your healthcare provider immediately or go to the emergency department. The suicide hotline number is 988, and this service is available 24/7. 

Serotonin Syndrome

Serotonin syndrome is a rare but serious condition that occurs when serotonin levels accumulate in the body. Signs and symptoms include anxiety or agitation, fever, increased sweating, tremors, feelings of restlessness, lack of coordination or confusion, and changes in the patient’s blood pressure and heart rate. 

This is commonly seen in patients who are taking multiple medications that increase serotonin levels in the body simultaneously. It is important to immediately seek medical attention if you begin to experience these symptoms and inform your physician of all the medications you are taking before being started on an antidepressant. 

Discontinuation Syndrome

Abrupt discontinuation or missing several doses of a tricyclic antidepressant may result in withdrawal-like symptoms. If you are no longer happy with your tricyclic antidepressant, you should work with your physician to gradually and safely stop the medication. Common discontinuation syndrome symptoms include: 

  • Increased agitation, irritability, or anxiety 
  • Flu-like symptoms, such as muscle aches or pains, chills, fatigue 
  • Insomnia 
  • Nausea, vomiting, abdominal discomfort
  • Increased sweating
  • Headache 

SSRIs or Tricyclics: Which is Right For You?

With so many different treatment options available for anxiety and depression, it can be overwhelming to decide which medication is the right one for you. Everyone reacts differently to antidepressants, and the dose or type of medication may also need to be adjusted throughout your treatment process.

While SSRIs are a more popular choice when treating depression, some patients may feel that tricyclics are more effective. However, others may feel that the complex side effects of tricyclics are too risky, and would prefer taking an SSRI as a safer form of treatment. 

For these reasons, you should never attempt to self-diagnose or self-medicate online, and should instead always consult with a medical professional before starting any antidepressant medications. 

Get Depression Treatment Online With Help From Klarity

If you need a reliable and affordable way to access depression medication, Klarity can help. The healthcare providers on Klarity offer quality depression treatment online, including diagnosis and prescription medications such as SSRIs or tricyclics, if deemed necessary. 

Your healthcare provider will help navigate this process with you to find the best individualized treatment plan for your depression. Schedule your first telehealth appointment on Klarity today, and in just 48 hours you could receive a prescription to help you finally take control of your depression. 

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All professional services are provided by independent private practices via the Klarity technology platform. Klarity Health, Inc. does not provide any medical services.
Fax:
(855) 975-3008

PO Box 5098 Redwood City, CA 94063

100 Broadway Street, Redwood City CA, 94063

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All professional services are provided by independent private practices via the Klarity technology platform. Klarity Health, Inc. does not provide any medical services.
If you’re having an emergency or in emotional distress, here are some resources for immediate help: Emergency: Call 911. National Suicide Prevention Hotline: Call 988. Crisis Text Line: Text Home to 741-741
Fax:
(855) 975-3008

PO Box 5098 Redwood City, CA 94063

100 Broadway Street, Redwood City CA, 94063

If you’re having an emergency or in emotional distress, here are some resources for immediate help: Emergency: Call 911. National Suicide Prevention Hotline: Call 988. Crisis Text Line: Text Home to 741-741
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