Wellbutrin vs. Zoloft: Similarities & Differences
Medically reviewed by Alex Yampolsky, PharmD
Mental health conditions can be challenging and debilitating, and depending on the severity of the condition, they can upend a person's ability to effectively go about their day or engage in healthy, productive relationships with others.
Fortunately, however, safe and effective prescription medication options exist for those with mental health conditions, such as major depressive disorder (MDD), seasonal affective disorder (SAD), or obsessive-compulsive disorder (OCD).
Two examples include bupropion (brand-names Wellbutrin XL and Wellbutrin SR or generic bupropion) and and Zoloft (sertraline).
Bupropion and Zoloft are orally administered, Food and Drug Administration (FDA)–approved prescription antidepressants used for the treatment of different forms of depression.
While similar, bupropion and Zoloft have several differences. For example, they're used for different purposes (treating different conditions), carry different dosing guidelines, have different age requirements (depending on the condition being treated), and, in some cases, have differing side effects.
This article will provide an in-depth comparison of Wellbutrin SR, XL, and bupropion vs. Zoloft.
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What Is Wellbutrin?
Wellbutrin SR and XL contain the active ingredient bupropion. Bupropion is also available in generic form. It is classified as a norepinephrine-dopamine reuptake inhibitor (NDRI).
Bupropion works by increasing levels of norepinephrine and dopamine in the brain.
Norepinephrine and dopamine are chemical messengers associated with mood and other functions in the brain.
The most common formulations and indications of bupropion include:
Bupropion, a generic immediate-release (IR) tablet that treats depression in adults (there is no brand name product available)
Bupropion sustained-release (SR), a 12-hour SR formulation that treats depression in adults (brand-name Wellbutrin SR)
Bupropion extended-release (ER), a 24-hour ER formulation that treats depression and prevents SAD in adults (brand-name Wellbutrin XL). SAD is a type of depression that occurs seasonally and lasts about four to five months yearly.
Bupropion is also available as:
A generic sustained-release formulation, formerly sold under the brand name Zyban, that is used to help people stop smoking (smoking cessation)
Forfivo XL, an ER high dose of bupropion hydrochloride that treats depression
Aplenzin, an ER bupropion hydrobromide that treats depression and prevents seasonal affective disorder
Off-Label Uses
Sometimes, healthcare providers prescribe a medication for a use that the FDA did not originally approve the drug for. This is called off-label prescribing.
Bupropion is sometimes prescribed off-label for:
Sexual problems associated with antidepressant medication use
Attention deficit hyperactivity disorder (ADHD) in adults and children
Depression associated with bipolar disorder
What Is Zoloft?
Zoloft, containing the active ingredient sertraline, is a selective serotonin reuptake inhibitor (SSRI).
Zoloft works by increasing levels of serotonin in the brain. Serotonin is a chemical messenger associated with mood, memory, and many other behaviors.
Zoloft is available in the following forms of administration:
Tablet
Solution (liquid)
Zoloft can be used to treat:
MDD (a serious mood disorder that is sometimes also referred to as clinical depression) in adults 18 and older
OCD (a mental health condition in which obsessive thoughts lead to repetitive behaviors, called compulsions) in adults and children 6 and older
Panic disorder (a type of anxiety associated with sudden attacks of panic or fear) in adults
Post-traumatic stress disorder (PTSD; a mental health condition triggered by experiencing or witnessing a terrifying event) in adults
Social anxiety disorder (anxiety about interacting with others) in adults
Premenstrual dysphoric disorder (PMDD; a severe form of premenstrual syndrome that causes both mental and physical symptoms) in adults
Additionally, there is a sertraline capsule available that is not associated with a brand name.
Sertraline capsules contain higher doses of the drug than the tablets do. They can be used to treat depression in adults or OCD in adults and children 6 and older when higher doses are required after using tablets in lower doses.
Off-Label Uses
Examples of off-label uses of Zoloft include but are not limited to:
Binge eating disorder or other eating disorders
Dosing Comparison
Dosing for each medication is covered below. In general, the healthcare provider increases doses gradually, if needed.
When it's time to stop taking an antidepressant, the healthcare professional will provide a tapering schedule so you can stop taking the medication slowly and safely and avoid withdrawal symptoms.
Wellbutrin Dosing
General bupropion dosing is as follows:
IR bupropion:
This formulation is available in 75 and 100 milligram (mg) tablets.
The starting dose is 100 mg twice daily for a total daily dose of 200 mg.
If needed, the healthcare provider may gradually increase the dose to a target of 100 mg three times daily (total daily dose of 300 mg).
The maximum dose is 150 mg 3 times daily (total daily dose of 450 mg).
SR bupropion (Wellbutrin SR):
This formulation is available in 100, 150, and 200 mg tablets.
The starting dose is 150 mg once daily.
If needed, the healthcare provider may gradually increase the dose to a target dose of 150 mg twice daily (total daily dose of 300 mg).
For individuals who do not respond to the target dose, the maximum dose is 200 mg twice daily (total daily dose of 400 mg).
ER bupropion (Wellbutrin XL):
This formulation is available in 150 mg and 300 mg tablets.
For MDD, the starting dose is 150 mg once daily.
If needed, the healthcare provider may increase the dose to a target dose of 300 mg once daily.
For SAD, treatment generally begins in the fall before symptoms start. Treatment should be continued throughout the winter. The starting dose is 150 mg once daily.
If needed, the healthcare provider may increase the dose to a target dose of 300 mg once daily.
Those with kidney or liver problems may need a lower or less frequent dose.
Zoloft Dosing
General Zoloft dosing in adults is as follows:
For depression: The starting dose is 50 mg per day. The maximum dose is 200 mg per day.
For OCD: The starting dose is 50 mg per day. The maximum dose is 200 mg per day.
For panic disorder, the starting dose is 25 mg per day. The maximum dose is 200 mg per day.
For SAD, the starting dose is 25 mg per day. The maximum dose is 200 mg per day.
For PTSD, the starting dose is 25 mg per day. The maximum dose is 200 mg per day.
For PMDD, Zoloft may be taken every day (50 mg per day) or only during part of the menstrual cycle.
For OCD, Zoloft dosing in children and adolescents is:
Ages 6 to 12: The starting dose is 25 mg daily. The maximum dose is 200 mg per day.
Ages 13 and older: The starting dose is 50 mg daily. The maximum dose is 200 mg per day.
Which Is More Effective?
A New England Journal of Medicine study evaluated people who tried the SSRI Celexa (citalopram), which is in the same drug class as Zoloft, but who could not tolerate Celexa or found that Celexa did not work.
These people then switched to either Wellbutrin SR, Zoloft, or another antidepressant called. Effexor XR (venlafaxine). The study showed similar efficacy, side effects, and tolerability results whether they took Wellbutrin SR, Zoloft, or Effexor XR.
In a study on many clinical trials, bupropion and Zoloft were similarly effective.
Everyone has unique symptoms, medical conditions, and other factors that may affect how well a medication works or whether the medicine is appropriate to take. Remember, bupropion and Zoloft have some different uses, so your diagnosis plays a significant role in what medication is appropriate
Side Effects & Safety
Boxed Warning
Bupropion and Zoloft, as well as every antidepressant medication, have a boxed warning, the most severe warning required by the FDA.
Antidepressants cause an increased risk of suicidal thoughts and suicidal behavior in children, adolescents, and young adults (ages 18 to 24).
Because of this risk, people of any age who take an antidepressant should be closely monitored by caregivers, family, and close friends for changes in mood and behavior.
If any changes in mood and behavior or suicidal thoughts occur, contact the healthcare provider immediately.
Allergic and Skin Reactions
In rare cases, an allergic or skin reaction may occur with either medication, which could be life-threatening.
If you have any of the following symptoms, get emergency medical help:
Allergic reaction symptoms: Hives, shortness of breath, swelling of the face, lips, tongue, or throat
Skin reaction symptoms: Fever, sore throat, skin pain, burning eyes, red or purple rash, blistering or peeling skin
Wellbutrin Side Effects
Common bupropion side effects include but are not limited to:
Anxiety
Insomnia (trouble falling or staying asleep)
Stomach problems such as nausea, vomiting, or constipation
Appetite and weight loss
Excess sweating
Changes in taste sensation
Serious bupropion side effects may include but are not limited to:
Hallucinations (seeing or hearing things that are not there)
Irrational fears
Muscle pain
Zoloft Side Effects
Common Zoloft side effects include but are not limited to:
Stomach problems such as nausea, vomiting, heartburn, diarrhea or constipation
Dry mouth
Appetite loss
Weight changes (children will be monitored for growth)
Dizziness
Feeling very tired
Headache
Nervousness
Shaking
Excess sweating
Sexual problems
Serious Zoloft side effects may include but are not limited to:
Seizures
Abnormal bruising or bleeding
Low sodium levels
Serotonin syndrome (a life-threatening condition caused by the buildup of too much serotonin)
Angle-closure glaucoma (an emergency eye condition due to excess pressure requires immediate medical attention)
Suicide Prevention Hotline
If you are having suicidal thoughts, contact the 988 Suicide & Crisis Lifeline at 988 for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.
For more mental health resources, see our National Helpline Database.
Precautions
Bupropion and Zoloft may not be safe for everyone, and each drug has a long list of contraindications (reasons a medication should not be taken due to safety concerns) and potential drug interactions to consider.
Before taking one of these medications, be sure to speak openly with your healthcare provider and inform them of the following:
Any allergies to medications
Your current and past medical conditions
Your family history
All of the medications you take, including prescription medicines, over-the-counter (OTC) drugs, and vitamins or supplements
This information will help your healthcare provider determine if one of these medications is safe and appropriate.
Summary
Because depression is so prevalent worldwide, antidepressant medications are commonly prescribed (often in combination with nondrug therapy). Bupropion and Zoloft are prescription antidepressants.
Although they have some common features, they have many differences, such as their uses, dosing guidelines, age requirements, and potential side effects.
It may take some trial and error to find the best medication for you based on dosage and efficacy.
If you are experiencing symptoms of depression, talk to your healthcare provider.
Frequently Asked Questions
How do I store Wellbutrin vs. Zoloft?
Bupropion or Zoloft should be stored at room temperature (between 68 and 77 degrees F), away from direct light, heat, and moisture. Do not store it in the bathroom.
Keep the bottle tightly closed when not in use. Keep this medication, and all others, out of the sight and reach of children and pets.
Can Wellbutrin or Zoloft affect weight loss?
Bupropion can cause appetite and weight loss. Bupropion is one of two ingredients in the weight loss medication Contrave (bupropion/naltrexone). Zoloft can cause either a small weight gain or weight loss.
How quickly does Wellbutrin vs. Zoloft begin to work?
When taking either antidepressant, some symptoms (such as sleep or energy) may improve within a week or two. However, it may take up to eight weeks to see the full benefit of antidepressant medication.
Read the original article on Verywell Health.
