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SNRI Vs. SSRI: Differences, Uses, Side Effects, and More

Written by:
Umar Javed
Dr. MBBS
Reviewer:
Dr. David Toomey
DO
Medical Disclaimer
The medications listed on this website are provided for informational purposes only. Their inclusion does not guarantee that they will be prescribed to any individual, as treatment decisions are ultimately at the discretion of healthcare providers. This list is not exhaustive, and healthcare providers may prescribe other medications, including non-stimulant options, based on the patient’s unique health circumstances and needs. Read more

SNRIs (selective serotonin-norepinephrine reuptake inhibitors) and SSRIs (selective serotonin reuptake inhibitors) are the two most widely used classes of antidepressants prescribed for various mental health problems. They belong to the new group of antidepressants that are safer and have fewer side effects than the old ones, and bring noticeable improvement in mental health.

Despite their numerous similarities, some vital differences exist in their working pattern, potential uses, side effects, and drug interactions. This article will answer questions about these medications and help you have a more detailed discussion with your doctor about which antidepressant class might be more suitable for you, SNRI or SSRI.

Feeling depressed for a long time? Contact us to get a personalized treatment plan that may consist of therapy, medications, or both.

SNRI Vs. SSRI: Overview

FDA approved SSRIs in 1987, whereas SNRIs were introduced into the market in 1993 to usher in the new era of antidepressant medications. Initially, these medications were developed to treat depression, but with continued research [1*] , it has been found that they effectively manage various other psychological and physical conditions. The list of medications belonging to each class is given:

SSRIs

SNRIs

Escitalopram (Lexapro)

Desvenlafaxine (Pristiq)

Citalopram (Celexa)

Duloxetine (Cymbalta)

Fluoxetine (Prozac)

Venlafaxine (Effexor)

Paroxetine (Paxil, Pexeva)

Levomilnacipran (Fetzima)

Sertraline (Zoloft)

Milnacipran (Savella)

Fluvoxamine (Luvox)

 

Vilazodone (Viibryd)

 

Overall, these new antidepressants have better tolerability, safety profile and less dosing issues. They help improve the quality of life in the long run by lowering and diminishing the symptoms of various psychological problems, including depression, anxiety disorders, phobias, OCD, PTSD, etc.

SNRI Vs. SSRI: Differences and Similarities

The key difference between SNRI and SSRI lies in their mechanism of action. SSRIs work by delaying serotonin uptake in the brain by nerve cells. As a result, more serotonin is available for a longer duration in the brain, which lessens depressive symptoms in patients.

SNRIs also follow the same principle of working with one crucial alteration. In addition to blocking serotonin uptake, they also block the reuptake of norepinephrine in the brain.

Here it is important to mention the role of serotonin in balancing mood. Serotonin is one of the neurochemicals that plays a key biological role in happiness [2*] . Whenever we are involved in pleasurable activities, our brain releases certain “happy hormones and chemicals”, including dopamine and serotonin. In depression, it is hypothesized that there is a lack of serotonin in the brain and antidepressants (SSRIs and SNRIs) work to balance these “happy hormones” in the brain.

In contrast, norepinephrine is vital in the body’s reaction to any emergency — fight or flight response. Whenever a person experiences intense stress for any reason, e.g., an exam, job interview, etc., the levels of norepinephrine increase in the body. It also impacts a person’s sleep, reasoning, motivation, and mood [3*] . Hence, it is hypothesized that its imbalance in the body can also result in depression.

Apart from these differences in their functioning, there are also many similarities between SSRIs and SNRIs, including their safety, efficacy, and duration of treatment. The following table summarizes the important aspects of SNRIs and SSRIs:

Feature

SSRIs (Selective serotonin reuptake inhibitors)

SNRIs (Selective serotonin-norepinephrine reuptake inhibitors)

 

Differences

Mechanism of Action

Targets serotonin receptors

Targets serotonin and norepinephrine receptors

FDA-Approval

1987

1993

Half-life

Relatively long as compared to other antidepressants

Relatively short as compared to other antidepressants

 

Similarities

Safety

Relatively safe as compared to older antidepressants

Efficacy

Comparable to older antidepressants

Duration of Treatment

Long (usually 6 months or more depending on the patient’s condition)

Dosage

Depends on the specific medication and the condition treated

Cost

Variable and depends on the specific medication

Insurance Coverage

Depends on the insurance provider

Online prescription

Available at MEDvidi

Ask a mental health professional which medication will help you manage your symptoms.

SNRI Vs. SSRI: Uses

SNRIs and SSRIs are widely used in the treatment of various mental health conditions as well as in the treatment of some physical problems. Each medication in these antidepressant classes is prescribed for different label and off-label treatments.

Here’s a breakdown of different conditions treated by SSRIs and SNRIs.

Examples of SSRI and SNRI

FDA-Approved Uses

Depression

All the SSRIs are recommended by the FDA to treat depression except fluvoxamine (Luvox), which is used for OCD treatment. Certain SSRIs (sertraline and fluoxetine) decrease the symptoms of depression (PMDD), associated with women’s menstrual cycle.

Currently, four SNRI drugs have the approval for depression treatment; the medication that does not is milnacipran (Savella) which is approved for treating fibromyalgia in the US. These medications are usually prescribed for moderate to severe depression because they are not as effective in the treatment of mild depression.

Panic Disorder

Both SNRIs and SSRIs are approved by the FDA to treat panic disorders associated with or without agoraphobia. Three drugs in the family of SSRIs — paroxetine, fluoxetine, and sertraline — are prescribed to manage panic disorders. These agents are especially helpful in cases of comorbid depression with panic disorder.

MEDvidi doctors are certified to prescribe SNRIs and SSRIs and will find the meds that will suit your treatment goals best.

Obsessive-compulsive Disorder

Fluvoxamine (Luvox), which is an SSRI, is specifically licensed to manage OCD in people. Along with fluvoxamine, other SSRIs, including paroxetine, sertraline, and fluoxetine, are also used for OCD treatment. The doses to treat OCD are typically higher than depression doses, and it takes a long time before their beneficial effects become evident in OCD patients. In comparison, no SNRI has been approved by the FDA for OCD treatment. However, they are prescribed off-label for this condition.

Generalized and Social Anxiety Disorder

Some SSRIs and SNRIs are used to treat generalized and social anxiety disorders and specific phobias. The choice of drug depends on the diagnosis and symptoms intensity of a specific condition. FDA has approved paroxetine, escitalopram, duloxetine, and venlafaxine for generalized anxiety disorder (GAD), whereas sertraline, paroxetine, and extended-release venlafaxine are the drugs of choice for social anxiety.

Posttraumatic Stress Disorder

Therapy is the first-choice treatment for PTSD. However, medications may also be required to manage symptoms. For this purpose, doctors mostly recommend SSRIs, as they are effective in controlling intrusive and avoidant symptoms associated with PTSD.

Bulimia Nervosa

Bulimia and anorexia are compulsive disorders related to eating habits and are also treated with SSRIs. In particular, fluoxetine is used for this purpose. Although psychotherapy is the treatment of choice for these disorders, adding SSRI to the management plan can help reduce binge eating and vomiting associated with bulimia.

Neuropathic Nerve Pain

In addition to mental health problems, these medications are also prescribed to manage some physical conditions. SNRIs are prescribed for controlling different nerve pains in the body. The FDA has approved Duloxetine [4*] to treat neuropathic pain associated with diabetes and fibromyalgia (chronic muscular pain).

Off-Label Uses

Off-label use is defined: when a doctor prescribes a medication approved for one condition and not yet approved by the FDA to treat another condition. The SSRIs and SNRIs are used off-label for the following medical ailments.

Premature Ejaculation

SSRIs are prescribed off-label to treat premature ejaculation in men due to their anorgasmic effects. Usually, fluoxetine and sertraline are used for this purpose.

Migraines

Long-standing migraine headaches are also sometimes treated with SSRIs, especially in patients with associated depression.

Autism

Some SSRIs are prescribed to manage the symptoms associated with autism spectrum disorders.

Stress Urinary Incontinence

Duloxetine is currently under review by the FDA for approval to treat the most common type of urinary incontinence (inability to hold urine) in women — stress incontinence.

Condition

FDA-Approved Use

Off-label Use

SSRIs

SNRIs

SSRIs

SNRIs

Major depressive disorder

Obsessive-Compulsive Disorder (OCD)

Generalized Anxiety Disorders (GAD)

Panic Disorder

Social anxiety disorder (SAD)

Premenstrual dysphoric disorder (PMDD)

Post-traumatic stress disorder (PTSD)

Bulimia nervosa

Bipolar Disorder

Diabetic neuropathy

Fibromyalgia

Premature ejaculation

ADHD

Autism

SNRI Vs. SSRI: Side Effects and Interactions

SSRIs and SNRIs cause similar side effects that, in turn, these side effects vary from person to person. The most common side effects of SSRIs and SNRIs include:

The most common side effects of SSRIs and SNRIs include:

  • Dizziness
  • Blurred vision
  • Dry mouth
  • Sweating
  • Sexual dysfunction
  • Problems with the gut (diarrhea or constipation)
  • Problems with sleep
  • Nausea and vomiting
  • Weight changes (increase or decrease)

The more serious side effects of these medications are disclosed below in detail.

Uses of SSRI and SNRI

Effects on the Heart

SSRIs and SNRIs can cause prolongation of QT intervals in the heart, leading to rhythm abnormalities in the heart. The risk is especially high in people who are also taking antipsychotic medications in addition to antidepressants. In these classes of medications, Citalopram affects the QT interval the most.

Some mental conditions have similar symptoms. Consult with a doctor to get a diagnosis and start treatment.

Headaches

SSRIs and SNRIs can cause increased incidences of headaches in patients, according to a study [5*] .

Seizures

Higher doses of SSRIs and SNRIs can cause seizures [6*] in patients, although it is a rare side effect.

Effects on Blood

SSRIs and SNRIs cause certain blood-related problems like impairment of platelet aggregation. This may potentially lead to an excessive bleeding risk especially in the case of severe trauma. Hence, these medications are used with extra caution when taken alongside NSAIDs like ibuprofen or blood thinners, such as aspirin.

Effects on Blood Sugar and Electrolytes

These antidepressants can lower blood sugar levels in patients with diabetes. Therefore, these medications must be used cautiously in patients with blood sugar issues. Also, they can affect the levels of certain electrolytes, especially sodium, in the body, causing tiredness.

Effects on Hormones

The SSRIs can increase prolactin hormone levels, primarily associated with breast enlargement and milk production, in both women and men. The breast changes that might occur while on these medications are reversible after discontinuation of the treatment.

Extrapyramidal Effects

SSRIs can cause movement problems in patients like akathisia (inability to remain still), torticollis (neck twisting), dystonia (involuntary movements), bradykinesia (slow movements), and opisthotonos (muscle spasms).

Serotonin Syndrome

If SSRIs or SNRIs are taken with other antidepressants like monoamine oxidase inhibitors (MAOIs), lithium, or l-tryptophan, they can increase serotonin in the body to dangerously high levels causing a myriad of symptoms known as serotonin syndrome [7*] . The main characteristics of this disorder are:

  • Restlessness
  • Diarrhea
  • Extreme nervousness
  • Involuntary body movements
  • High temperature
  • Seizures
  • Delirium
  • Coma
  • Cardiovascular collapse

Consult with a doctor if you have any side effects. MEDvidi professionals are there to help tailor your plan and adjust the dosage of the medications you take.

Acute Withdrawal Effects

If these medications are stopped abruptly, there is a potential for withdrawal effects. The symptoms of sudden discontinuation of these medications may include:

  • Tiredness
  • Dizziness
  • Headache
  • Anxiety
  • Insomnia
  • Rebound depression
  • Numbness
  • Concentration problems

*Black Box Warning. FDA has placed some SSRIs and SNRIs (fluvoxamine, paroxetine, fluoxetine, sertraline, citalopram, and venlafaxine) on the list of medications that carry serious side effects. In the case of SSRIs and SNRIs, this warning is due to their risk of causing suicidal thoughts in children, adolescents, and young adults up to the age of 24. Therefore, these age groups are monitored very closely during the early phase of their treatment.

The table below lists the common and serious side effects associated with SSRIs and SNRIs.

Common side effects of SSRIs and SNRIs

Serious side effects of SSRIs and SNRIs

  • Dry mouth
  • Nausea or vomiting
  • Headaches
  • Diarrhea
  • Sexual dysfunction
  • Increased sweating
  • Changes in weight (gain or loss)
  • Sleeping problems
  • Sweating
  • Nightmares
  • Lethargy
  • Indigestion
  • Emotional blunting
  • Yawning
  • Heartbeat irregularities (QT prolongation)
  • Impaired motor, cognitive, and judgment
  • Blood problems
  • Allergic reactions
  • Serotonin syndrome
  • Congenital anomalies 
  • The onset of mania or hypomania
  • Vision problems (angle-closure glaucoma)
  • Seizures
  • Low blood salt levels
  • Issues controlling blood sugar
  • Suicidal thoughts

Tell a prescriber about all the medications you currently take before an antidepressant is prescribed for you. A thorough overview allows the doctor to help you avoid potentially dangerous medication interactions.

Serotonin syndrome symptoms

Interactions with Other Medications

SSRIs and SNRIs are typically safe to use with other medications. Still, there are some interactions that you should be aware of and it’s imperative that you report all medications that you are taking to your doctor before commencing antidepressant treatment.

The medication interactions of SNRIs and SSRIs are similar, and the most common ones are given in the table below:

Drug

Drug Class

Possible Reaction with SSRIs and SNRIs

Phenelzine

Isocarboxazid

MAOIs 

Serotonin Syndrome

Lithium

Antimanic agents

Serotonin Syndrome

L-Tryptophan

α-amino acid

Serotonin Syndrome

Amitriptyline

Nortriptyline

TCAs

TCA clinical toxicity

Codeine

Oxycodone

Hydrocodone

Opioids

Decreased effectiveness in controlling pain

Tamoxifen

Non-steroidal antiestrogen

Reduced effectiveness

Ibuprofen

Naproxen

Diclofenac

NSAIDs

Increased risk of gastric bleeding

Clozapine

Atypical antipsychotics

Increased risk of seizures

Warfarin

Apixaban

Anticoagulants

Increased risk of bleeding

*For information about all the possible different interactions, consult with a doctor or pharmacist.

SNRI Vs. SSRI: FAQs

Which is better: SSRIs or SNRIs?

Many studies [8*] have been conducted to compare the efficacy of a SSRI and a SNRI; however, no clinical advantage has been found in favor of one over the other. The SNRIs have a slight advantage in the mechanism of action as they target serotonin and noradrenaline receptors in the brain as compared to SSRIs that only target serotonin receptors. However, the choice of medication will depend on the patient’s symptoms, diagnosis, and the doctor’s decision, which is based on the overall assessment.

Can you take SSRIs and SNRIs together for faster results?

SSRIs and SNRIs are relatively safe medications; however, no evidence suggests combining these can help bring faster results. Additionally, it is highly advisable to follow only your doctor’s instructions while using these medications to avoid any serious complications.

Is it possible to switch from SNRIs to SSRIs?

Yes, it is possible to switch from SNRIs to SSRIs. But before making such a change in your treatment plan, your doctor has to consider many things: medical and medication history, response to treatment, side effects, etc. Only after proper evaluation and ruling out the red flags can a doctor switch your medication from SNRIs to SSRIs.

Which is the safer medication: SSRI or SNRI?

SSRIs and SNRIs share more or less the same common side effects. No medical evidence suggests that one of them is safer than the other. The choice of medication for the treatment depends on your medical condition, medical history, and other factors like age and genetics.

Is it safe to use SSRIs or SNRIs during pregnancy?

Most SSRIs and SNRIs are safe to use during pregnancy. But paroxetine (SSRI) can increase the risk of congenital defects, especially heart abnormalities; therefore, it should be avoided during pregnancy.

How to get SSRI or SNRI prescribed?

To get a prescription for SSRIs or SNRIs, you have to first be assessed by a doctor to determine your need for any of these medications. Telemedicine has made this process much easier. You can be prescribed medication from the comfort of your home — a simple and cost-effective process without requiring you to visit a doctor’s office.

Ending Note

The above information concludes that SSRIs and SNRIs are more or less similar in their uses, tolerability, efficacy, and safety profile, with only a few minor differences. With that being said, only a qualified physician can figure out which medication is best for your condition, and this occurs after thoroughly evaluating your medical information. At MEDvidi, we have an experienced medical team that is available 24/7 to answer all your queries regarding antidepressant medications. Book your online appointment now and speak to one of our doctors if you are experiencing signs and symptoms of depression or other related mental health conditions.

To get an online consultation with a licensed prescriber, contact MEDvidi. Our mental health experts offer treatment for various mental health issues such as general anxiety disorder, depression, stress, ADHD, and other mental health problems.

Sources

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8 sources
  1. Selective Serotonin Reuptake Inhibitors. (2023)
    Source link
  2. Happiness & Health: The Biological Factors- Systematic Review Article. (2014)
    Source link
  3. The importance of norepinephrine in depression. (2011)
    Source link
  4. Duloxetine in the treatment of chronic pain due to fibromyalgia and diabetic neuropathy. (2011)
    Source link
  5. Duloxetine in the treatment of chronic pain due to fibromyalgia and diabetic neuropathy. (2018)
    Source link
  6. Duloxetine in the treatment of chronic pain due to fibromyalgia and diabetic neuropathy. (2016)
    Source link
  7. Serotonin Syndrome. (2023)
    Source link
  8. Comparison of SSRIs and SNRIs in major depressive disorder: a meta-analysis of head-to-head randomized clinical trials. (2010)
    Source link
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Written by:
Umar Javed
Dr. MBBS
Reviewer:
Dr. David Toomey
DO
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