Zoloft vs Effexor XR: what’s the difference and which one should I take?

Though selective serotonin reuptake inhibitors (SSRIs) are the first choice for treating depression symptoms, they aren’t the only class of medications prescribed for it. When researching treatment options, you’ll likely come across other types of antidepressants, such as SNRIs, or selective norepinephrine reuptake inhibitors. When deciding on the best treatment plan for your depression, you may consider the benefits of Zoloft vs Effexor XR.

While both these medication types are antidepressants, they work on different chemical messengers in the brain. As a result, SSRIs and SNRIs come with different side effects and affect patients differently. 

In this post, we compare Zoloft, an SSRI, to Effexor XR, an SNRI, to illustrate the similarities and differences between the 2. Developing your knowledge of depression medication will help you make the most educated and informed choice regarding your depression treatment with your healthcare provider. 

Are you considering starting or changing an antidepressant to help you better manage symptoms of depression? Klarity has helped 30,000+ people connect with depression specialists. 

Discover what Klarity can do for you, and find a provider on Klarity today for an online or in-person appointment. 

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 National Suicide Prevention Lifeline by calling or texting 988 or dialing the Lifeline’s previous phone number, 1-800-273-TALK (1-800-273-8255) in the U.S. 

Zoloft vs Effexor XR

Zoloft and Effexor XR are both commonly prescribed to treat generalized anxiety disorder (GAD) and major depressive disorder (MDD). Even though both medications are antidepressants and see widespread use, Zoloft and Effexor are different medication classes. 

Both Zoloft and Effexor increase the brain’s access to neurotransmitters, but the significant difference between the two antidepressants is which neurotransmitters are affected. Zoloft is an SSRI. It only affects serotonin levels in the brain. 

Effexor, on the other hand, is an SNRI. It increases the availability of both serotonin and norepinephrine in the brain. This difference has notable implications for how each drug works in the body. 

Which medication should I take?

SSRIs and SNRIs represent distinct types of antidepressants. One does not inherently surpass the other. However, each medication interacts with an individual’s unique body chemistry differently. Some individuals may exhibit greater receptivity to Zoloft over Effexor XR, and vice versa. 

If a close family member has experienced success with either Zoloft or Effexor, that same medication may prove effective for you. It’s crucial to discuss your medical history and any medications or supplements you’re currently taking with your healthcare provider.

Your healthcare provider will assess your symptoms, medical history, and other pertinent factors to determine the most suitable course of treatment for your anxiety or depression. 

What’s Effexor XR?

Effexor (venlafaxine hydrochloride), an SNRI, is a class of antidepressants that increases the amount of norepinephrine and serotonin in the brain by blocking their reuptake in the synapses between neurons. Low levels of serotonin and norepinephrine are associated with an increase in the symptoms of anxiety and depression. 

By making serotonin and norepinephrine more accessible in the brain, Effexor can treat the symptoms of depression and anxiety. Effexor also has other on-label and off-label uses and comes in various forms and doses. Effexor XR is the extended-release form of the medication, meaning the drug stays in your system longer, so you don’t have to take it as often.

Effexor forms and doses

Effexor is primarily administered orally via tablet or capsule and has extended-release (XR) options. The standard dose for an Effexor tablet is 150 milligrams once a day, but it’s available in 37.5 milligrams, 75 milligrams, and 150 milligrams doses. 

Adults usually start Effexor with 75 milligrams per day, taken once a day in the morning or evening. Sometimes, they might start with a lower dose of 37.5 milligrams per day for 4 to 7 days. Your doctor will adjust your dose based on how you’re doing. The most you’ll usually take in a day is 225 milligrams.

The standard dose for extended-release tablets and capsules is 75 milligrams, but 37.5 milligrams and 150 milligrams XR capsules and tablets are also available. This medication should be taken with water but doesn’t need to be taken with food.

Conditions Effexor XR treats

The U.S. Food and Drug Administration (FDA) approves Effexor to treat the symptoms of MDD, GAD, and panic disorder. Healthcare providers also prescribe it as an off-label treatment for certain conditions, including MDD, GAD, and panic disorder.

Symptoms of anxiety Effexor can treat

Effexor is prescribed to help treat or reduce the following symptoms of anxiety:

• Excessive anxiety, panic, or feelings of doom
• Irritability
• Restlessness
• Fatigue
• Muscle tension
• Difficulty concentrating
• Sleep disturbances

Symptoms of depression Effexor can treat

Effexor is prescribed to treat or reduce the following symptoms of depression:

• Depressed mood
• Crying
• Loss of interest in activities that used to bring joy
• Feelings of worthlessness, guilt, hopelessness, and helplessness
• Fatigue
• Trouble concentrating
• Psychomotor agitation — or having nervous energy
• Psychomotor retardation — or feeling trapped in slow motion
• Changes in appetite
• Suicidal thoughts or behaviors

Off-label uses for Effexor

“Off-label” means that while the FDA hasn’t conducted clinical trials to approve using Effexor XR to treat these conditions, it has been shown to have positive effects. Healthcare providers may also prescribe Effexor to treat the following conditions off-label.

• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)
• Premenstrual dysphoric disorder (PMDD)
• Attention-deficit hyperactivity disorder (ADHD)
• Fibromyalgia
• Diabetic neuropathy
• Hot flashes
• Migraine
• Complex pain syndromes

Effexor XR costs

Costs for all types of medication vary based on insurance coverage and other factors, so prices are approximate. Generally, the price of 30 capsules of 150 milligrams of generic Effexor (venlafaxine) is around $49. 

Effexor XR side effects

SNRIs have potential side effects that you want to be aware of before starting treatment. Most people don’t experience severe side effects, and medical providers prescribe SNRIs because the benefits usually outweigh the potential risks. However, if you notice side effects that are ongoing or worsening, contact your medical provider

Here are the most commonly reported side effects of Effexor:

• Nausea
• Hypertension
• Yawning
• Constipation
• Sweating
• Abnormal sexual function
• Decreased libido
• Flatulence
• Dry mouth
• Loss of appetite
• Dizziness
• Insomnia

Effexor XR warnings

Don’t stop taking Effexor XR as prescribed without consulting your healthcare provider, even if your symptoms improve. If you decide Effexor isn’t suitable for you, your medical provider will help you reduce your dose until you’re no longer taking the medication. 

Stopping the medication suddenly or missing several doses can lead to withdrawal symptoms, which include:

• Recurring symptoms of anxiety and depression
• Feeling dizzy 
• Irritability 
• Vomiting
• Nightmares
• Paresthesias
• Nausea
• Headaches

If you have bipolar disorder, antidepressants may cause you to switch from a depressive phase into a manic phase.

Effexor may not be right for you if you have certain pre-existing conditions:

• Hypertension
• Interstitial lung disease
• Glaucoma
• Hyponatremia, or Syndrome of inappropriate antidiuretic hormone secretion (SIADH))
• Seizure disorder
• Liver disease
• Kidney disease
• Bipolar disorder

Medications that increase serotonin levels in the brain may lead to a rare but serious condition called serotonin syndrome. This condition usually occurs hours after starting a medication that elevates serotonin levels. Symptoms of serotonin syndrome include: 

• Agitation 
• Trouble sleeping
• Confusion
• Rapid heart rate 
• Dilated pupils
• Loss of muscle coordination 
• High blood pressure
• Muscle rigidity
• Heavy sweating
• Diarrhea
• Headache
• Shivering
• Goosebumps

If you experience any of those side effects, including more severe ones like: high fever, tremors, seizures, irregular heartbeats, or unconsciousness, contact emergency medical services immediately and let your healthcare provider know. 

Boxed warning 

Effexor XR, like other antidepressants, comes with a boxed warning. A boxed warning is the most serious type of warning issued by the FDA, indicating that the medication carries a significant risk of serious or life-threatening adverse effects. This means that for some, Effexor increased thoughts of self-harm and suicide. Though this risk is greater in children, it can also happen in adults. 

In the first few months of taking Effexor, monitor yourself for thoughts of self-harm and suicide and ask others to look out for unusual changes in your behavior, acting withdrawn, or increased depressive symptoms.

If you have thoughts of suicide, seek help immediately. You can contact the 988 Suicide and Crisis Lifeline by texting or dialing 988 24×7.

Effexor XR drug interactions

Effexor shouldn’t be taken within 2 weeks of taking monoamine oxidase inhibitors (MAOIs). Common MAOIs include:

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

Other antidepressants, migraine medications, and certain pain medications can increase serotonin levels, potentially leading to a condition known as serotonin syndrome. This syndrome can cause symptoms ranging from mild (such as shivering and diarrhea) to severe (such as high fever and seizures).

Effexor has been shown to increase the effects of blood thinners and other medications that increase the chance of bleeding:

• Advil
• Motrin
• Coumadin (warfarin)
• Aspirin

Before prescribing Effexor XR, your healthcare provider will review your medical history, any medications you currently take, and other factors that may impact its usefulness in safely treating your depression or anxiety. 

What is Zoloft?

Zoloft (sertraline) is an SSRI or selective serotonin reuptake inhibitor. It’s a class of antidepressants that increase serotonin levels in the brain’s synapses. Because Zoloft elevates levels of serotonin,it’s used to treat various mood disorders, including depression and anxiety. Additionally, Zoloft has off-label uses for conditions such as obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). 

Zoloft only elevates levels of serotonin and is different from Effexor, an SNRI, which boosts both serotonin levels and norepinephrine levels.

Zoloft forms and doses

Zoloft comes in 2 dosage forms — tablets and oral solutions. Zoloft is taken orally once per day, and doses range between 25 milligrams and 100 milligrams, depending on the severity of the condition being treated. The standard daily dosage ranges between 50 milligrams and 200 milligrams. Unlike Effexor, which can be taken without food, Zoloft is best absorbed when taken with food.

When taken as an oral solution, Zoloft must be mixed with another liquid.

Conditions Zoloft treats

Zoloft is FDA-approved to treat major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD).

Symptoms of anxiety Zoloft is prescribed to treat

Zoloft has been shown to help treat or reduce the following symptoms of anxiety:

• Excessive anxiety, panic, or feelings of doom
• Irritability
• Restlessness
• Fatigue
• Muscle tension
• Difficulty concentrating
• Sleep disturbances

Symptoms of depression Zoloft is prescribed to treat

Zoloft has been prescribed to help treat or reduce the following symptoms of depression:

• Depressed mood
• Crying
• Loss of interest in activities that used to bring joy
• Feelings of worthlessness, guilt, hopelessness, and helplessness
• Fatigue
• Trouble concentrating
• Psychomotor agitation — or having nervous energy
• Psychomotor retardation — or feeling trapped in slow motion
• Changes in appetite
• Suicidal thoughts or behaviors

Off-label uses for Zoloft

Medical providers prescribe Zoloft as an off-label treatment for the following conditions:

• Premature ejaculation
• Binge eating disorder
• Bulimia nervosa
• Body dysmorphic disorder
• Generalized anxiety disorder (GAD)

Zoloft costs

For generic sertraline, 30 100-milligram tablets generally cost between $10 and $27. Prices may vary due to many factors, including insurance coverage. The brand name Zoloft costs around $460 for 30 100-milligram tablets, at an average price of about $15.50 per pill.

Zoloft side effects

SSRIs often have side effects that you need to be aware of before beginning treatment. In most people, the side effects aren’t severe and dissipate with time. The many benefits of Zoloft often outweigh potential side effects. Discuss whether or not the side effects are worth taking Zoloft with your healthcare provider.

Common side effects of Zoloft include:

• Diarrhea
• Confusion
• Hallucinations
• Tremor
• Disorder of ejaculation
• Fatigue
• Female sexual dysfunction
• Nausea
• Sweating
• Dry mouth
• Fainting
• Lightheadedness

Zoloft warnings

Like Effexor, Zoloft also comes with a boxed warning. There is a chance that Zoloft can cause an increase in suicidal thoughts and thoughts of self-harm in both children and adults. Though rarer in adults, you need to monitor their depressive symptoms for increases in suicidal and self-harm ideation.

If taking Zoloft, be sure to monitor for an increase in the following symptoms:

• Increased hostility, aggression, and irritability
• Increased anxiety
• Unusual changes in behavior
• Manic behavior
• Insomnia
• Panic attacks
• Increase or emergence of suicidal thoughts
• Increase or emergence of thoughts of self-harm

If you experience any of these severe symptoms, seek medical help immediately. If you have thoughts of suicide, contact the National Suicide Prevention Lifeline, by calling or texting 988 or dialing the Lifeline’s previous phone number, 1-800-273-TALK (1-800-273-8255) in the U.S. 

Zoloft drug interactions

Like Effexor, Zoloft shouldn’t be taken within 2 weeks of taking MAOIs or monoamine oxidase inhibitors. Because Zoloft increases serotonin levels in the brain, there is an increased risk of developing serotonin syndrome if you also take other medication that elevates serotonin levels. 

Serotonin syndrome is rare and usually occurs when you start treatment that elevates serotonin levels.

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Frequently asked questions about Zoloft vs Effexor XR

Can I drive when taking Zoloft or Effexor XR?

Dizziness, confusion, and sedation are all potential side effects of Zoloft and Effexor XR, especially when you first start taking the medication. Before driving, operating heavy machinery, or engaging in behaviors that require coordination, wait and see how either drug affects you. 

Many people don’t experience serious side effects, and those that do report side effects subsiding after a few days or weeks. It’s still smart to wait and see if you experience side effects that would make driving dangerous.

Your healthcare provider will discuss potential side effects before prescribing the medication.

Does Zoloft or Effexor XR harm pregnancy?

SSRIs like Zoloft are generally considered safe for women to take during pregnancy. However, according to the CDC, pregnant women who use Effexor early in pregnancy have a slightly increased chance of giving birth to babies with congenital disabilities, including heart defects, brain and spinal defects, cleft lip, and cleft palate, among others.

Other studies indicate a slightly increased risk of premature birth for babies whose mothers were taking both SSRIs and SNRIs. 

Your medical provider will work with you to find the medication that will safely treat your anxiety or depression.

Can I drink alcohol while using Zoloft or Effexor XR?

Drinking alcohol while on Zoloft or Effexor may increase the risk of unwanted side effects, including:

• Dizziness
• Headaches
• Nausea
• Diarrhea
• Drowsiness
• Depression
• Suicidal thoughts
• Anxiety

Drinking alcohol while on antidepressants isn’t recommended. 

Does it matter what time of day I take Zoloft or Effexor XR?

It doesn’t typically matter what time of day either Zoloft or Effexor is taken. However, sleepiness and drowsiness are potential side effects of both. 

If you experience these side effects, taking the medication at night may make more sense. Whether you take your medicine in the morning or at night, it’s recommended that you consistently take it at the same time each day.

Your healthcare provider will discuss when it’s best to take your medication.

Can Zoloft or Effexor XR make anxiety worse?

For some, SSRIs and SNRIs may worsendepression and anxiety symptoms. If the worsening symptoms don’t subside, you must talk to your health provider about weaning you off the medication. Remember, never suddenly stop your antidepressant — this can lead to withdrawal symptoms.

What’s better for anxiety and depression? Zoloft vs Effexor XR?

Both medications are similarly effective at treating the symptoms of anxiety and depression. However, some studies show that Effexor XR may be slightly advantageous for severely depressed individuals. This could be due to the fact that Effexor XR works on 2 neurotransmitters as opposed to Zoloft’s 1.

Your healthcare provider will work with you to determine the best course of treatment for your anxiety or depression.