Wellbutrin vs. Zoloft: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Wellbutrin and Zoloft are two prescription medications indicated in the treatment of major depressive disorder (MDD). MDD is one of the most common mental health conditions in the United States. It is characterized by a period of two weeks or more where a person experiences a depressed mood or loss of interest in activities that typically elicit happiness.

MDD is also typically accompanied by troubles with sleeping, eating, concentrating, and energy. Wellbutrin works by increasing available dopamine and norepinephrine, while Zoloft increases available serotonin. While both drugs work to treat depression, they do so by acting on different neurotransmitters which affect mood.

What are the main differences between Wellbutrin and Zoloft?

Wellbutrin (bupropion) (Wellbutrin coupons | Wellbutrin details) is a prescription medication indicated in the treatment of major depressive disorder (MDD) and seasonal affective disorder. The active ingredient of Wellbutrin, bupropion, was previously marketed under the brand name Zyban and is approved for use in smoking cessation in its sustained-release formulation. Wellbutrin works as a dopamine and norepinephrine reuptake inhibitor at the neuronal level. This leaves more dopamine and norepinephrine available. Higher dopamine and norepinephrine levels are associated with improved mood and affect. Wellbutrin is available in an immediate-release tablet in 75 mg and 100 mg. The sustained-release tablet indicated for every 12-hour dosing is available in 100 mg, 150 mg, and 200 mg. The extended-release tablet indicated for once every 24-hour dosing is available in 150 mg and 300 mg.

Zoloft (sertraline) (Zoloft coupons | Zolofts details) is also a prescription medication indicated in the treatment of depression. Zoloft is classified as a selective serotonin reuptake inhibitor and works by blocking the reuptake of serotonin at the neuronal synapse. This leaves more free serotonin available. Higher levels of available serotonin are associated with improved mood and energy levels. Zoloft is available as an oral tablet in strengths of 25 mg, 50 mg, and 100mg. It is also available in an oral concentrated solution that is 20 mg/ml.

Main differences between Wellbutrin and Zoloft
	Wellbutrin	Zoloft
Drug class	Dopamine/ Norepinephrine reuptake inhibitor	Selective serotonin reuptake inhibitor
Brand/generic status	Brand and generic available	Brand and generic available
What is the generic name?	Bupropion	Sertraline
What form(s) does the drug come in?	Immediate-release, sustained-release, and extended-release tablet	Oral tablet, concentrated oral solution
What is the standard dosage?	150 mg XL once per day	50 mg once per day
How long is the typical treatment?	Long-term (months to years)	Long-term (months to years)
Who typically uses the medication?	Adolescents, adults	Children, adolescents, and adults

Conditions treated by Wellbutrin and Zoloft

Wellbutrin and Zoloft share an indication for the treatment of major depression, but each drug carries unique indications as well.

The active ingredient in Wellbutrin, bupropion, is indicated to help with smoking cessation. Studies have shown that patients taking bupropion are more likely to achieve smoking cessation, though the exact mechanism is not entirely understood. These studies have also shown that bupropion may have more side effects than other smoking cessation therapies.

Zoloft is approved in the treatment of social anxiety disorder and is used off-label in generalized anxiety disorder and separation anxiety disorder. Off-label use indicates that the intended use has not been approved by the Food and Drug Administration (FDA).

The following table lists some of the known uses of Wellbutrin and Zoloft. Only your doctor can decide which medication may be right for your condition.

Condition	Wellbutrin	Zoloft
Major depressive disorder	Yes	Yes
Seasonal affective disorder	Yes	No
Smoking cessation	Yes	No
Attention deficit hyperactivity disorder(ADHD)	Off-label	No
Neuropathic pain	Off-label	No
Obsessive-compulsive disorder (OCD)	No	Yes
Social anxiety disorder	No	Yes
Generalized anxiety disorder	No	Off-label
Separation anxiety disorder	No	Off-label
Panic disorder	No	Yes
Post-traumatic stress disorder (PTSD)	No	Yes
Premenstrual dysphoric disorder (PMDD)	No	Yes
Hot flashes associated with menopause	No	Off-label
Premature ejaculation	No	Off-label

Is Wellbutrin or Zoloft more effective?

A randomized, controlled trial published in The New England Journal of Medicine compared depression remission and tolerability of bupropion, sertraline, and a third antidepressant, venlafaxine. This study focused on patients who had depression which was not responsive to other treatments.  This study found that all three treatment options were effective and did not differ significantly from each other with regard to remission rates, tolerability, or adverse events. A separate retrospective analysis of two other studies also found that these two drugs have similar depression remission rates.

Wellbutrin and Zoloft would both be considered effective treatments, therefore choosing the best treatment may be determined by potential side effects. Wellbutrin is less likely to cause sexual dysfunction and somnolence, therefore some patients and healthcare providers may prefer Wellbutrin.

Coverage and cost comparison of Wellbutrin vs. Zoloft

Wellbutrin is a prescription medication that is typically covered by both commercial and Medicare drug plans. The out-of-pocket price for Wellbutrin XL 150 mg can be as high as $180, but with a coupon from SingleCare, you could get the generic for less than $12.

Get the SingleCare prescription discount card

Zoloft is also a prescription medication that is generally covered by both Medicare and commercial drug plans. The out-of-pocket price of brand-name Zoloft may be over $400, but with a coupon from SingleCare, you could pay as little as $10 for the generic.

	Wellbutrin	Zoloft
Typically covered by insurance?	Yes	Yes
Typically covered by Medicare Part D?	Yes	Yes
Standard dosage	30, 150 mg XL tablets	30, 50 mg tablets
Typical Medicare copay	$10 or less	$10 or less
SingleCare cost	$11+	$10+

Common side effects of Wellbutrin vs. Zoloft

The tolerability of antidepressants is an important factor when choosing a therapy. Antidepressants do not provide immediate relief of depressive symptoms. It can take up to four to six weeks to see the full potential of an antidepressant medication in treating depression symptoms. Adverse events related to drug therapy, however, may start immediately. If side effects are too bothersome, patients may be tempted to discontinue therapy before realizing the full benefit.

Zoloft is much more likely than Wellbutrin to cause nausea and vomiting. This can affect daily activities and functioning. Somnolence, or excessive drowsiness, is also much more common with Zoloft. This can affect productivity and safety and may be an important consideration for patients and providers.

Wellbutrin is not known to cause sexual dysfunction or decreased libido like SSRIs such as Zoloft can. This is an important effect to discuss with patients prior to starting therapy.

The following list is not intended to be a complete list of adverse events. Please consult a pharmacist, doctor, or another medical professional for a complete list of possible side effects.

	Wellbutrin		Zoloft
Side effect	Applicable?	Frequency	Applicable?	Frequency
Asthenia	Yes	2%	No	n/a
Nausea	Yes	13%	Yes	26%
Dry mouth	Yes	17%	Yes	14%
Sweating	Yes	6%	Yes	7%
Vomiting	Yes	4%	Yes	20%
Diarrhea	Yes	5%	Yes	4%
Constipation	Yes	10%	Yes	6%
Dyspepsia	No	n/a	Yes	8%
Dizziness	Yes	7%	Yes	12%
Somnolence	Yes	2%	Yes	11%
Agitation	Yes	3%	No	n/a
Headache	Yes	26%	No	n/a
Decreased appetite	Yes	5%	Yes	3%
Decreased libido	No	n/a	Yes	6%
Weight loss	Yes	14%	No	n/a
Weight gain	Yes	3%	No	n/a

Source: Wellbutrin (DailyMed) Zoloft (DailyMed)

Drug interactions of Wellbutrin vs. Zoloft

Wellbutrin and Zoloft each have multiple possible drug interactions primarily due to their metabolism by the cytochrome P450 system. Wellbutrin, for instance, potently inhibits CYP2D6, and therefore doses of CYP2D6 substrates may need to be decreased in patients taking Wellbutrin. Examples of CYP2D6 substrates include codeine, haloperidol, risperidone, and metoprolol. Zoloft is a minor inhibitor of CYP2D6 and may cause the same interactions but to a lesser degree.

Other drugs with serotonergic actions when combined with Zoloft may increase the risk for serotonin syndrome. Serotonin syndrome is the result of abnormally high levels of free serotonin and can result in agitation, dizziness, and increased heart rate.

Zoloft may cause a specific type of cardiac arrhythmia known as a prolonged QTc interval when taken with certain classes of medication.  It is important that your healthcare professional and pharmacist have a complete list of medications you are taking in order to appropriately screen for potential interactions.

The following list is not intended to be a complete list of drug interactions. Your doctor or pharmacist can provide a complete list.

Drug	Drug Class	Wellbutrin	Zoloft
Almotriptan Eletriptan Oxitriptan	5HT Agonist/Triptans (antimigraine agents)	No	Yes
Dexmethylphenidate Methylphenidate	Amphetamines	No	Yes
Alosetron Ondansetron Ramosetron	5HT3 Antagonists (anti-nausea agents)	No	Yes
Aripiprazole	Antipsychotic	Yes	Yes
Aspirin Ibuprofen Naproxen Diclofenac	Nonsteroidal anti-inflammatory drugs (NSAIDS)	No	Yes
Atomoxetine	Selective norepinephrine reuptake inhibitor (SNRI)	Yes	No
Bemiparin Enoxaparin Heparin	Anticoagulants	No	Yes
Buspirone	Antianxiety	No	Yes
Carbamazepine	Anticonvulsant	Yes	Yes
Enzalutamide	Chemotherapy agent	No	Yes
Esomeprazole Omeprazole	Proton pump inhibitor	No	Yes
Fluconazole	Antifungal	No	Yes
Fluoxetine Paroxetine Citalopram Escitalopram	SSRIs	Yes	Yes
Hydroxychloroquine	Aminoquinolone/Antimalarial	No	Yes
Linezolid	Antibiotic	No	Yes
Cyclobenzaprine Metaxalone	Muscle relaxers	No	Yes
Pimozide	Antipsychotic	No	Yes
Selegiline Phenelzine Rasagiline	Monoamine oxidase inhibitor (MAOI)	No	Yes
St. John’s Wort	Herbal supplement	No	Yes
Hydrochlorothiazide Chlorthalidone Metolazone	Thiazide diuretics	No	Yes
Tramadol	Opiate pain reliever	Yes	Yes
Amitriptyline Clomipramine Doxepin Nortriptyline	Tricyclic antidepressants	Yes	Yes
Venlafaxine	Selective norepinephrine reuptake inhibitor (SNRI)	No	Yes

Warnings of Wellbutrin and Zoloft

Wellbutrin and Zoloft therapy may increase suicidal ideation and thoughts among teens and young adults, especially in the early stages of treatment before any type of remission is achieved. These patients must be monitored closely if this treatment is deemed medically necessary. A therapy change may be necessary if symptoms suddenly arise or get worse. All patients with depression may experience a worsening of their depression or suicidal thoughts whether or not they are taking antidepressant medications.

Some patients who take Wellbutrin for smoking cessation, and who have no previous history of depression, may experience mental changes when they begin therapy. These changes may include mood changes, hallucinations, paranoia, delusions, aggression, and anxiety. Speak with your healthcare provider immediately if any of these changes occur when you initiate Wellbutrin therapy.

Wellbutrin has been shown to increase the risk of seizure, and for this reason, the total daily dose should not exceed 300 mg. Patients on Wellbutrin may also experience increased blood pressure, leading to hypertension, even if they had no previous cardiovascular conditions or events.

Depression symptoms will not start to resolve immediately with either Wellbutrin or Zoloft. Typically, changes in symptoms take a minimum of two weeks to observe, with most patients needing at least four to six weeks to see if the drug is having an impact on their symptoms.

Serotonin syndrome has been reported with Zoloft and all other SSRIs. This can be brought on by the use of two serotonergic drugs together. Symptoms may include agitation, dizziness, or palpitations.

Frequently asked questions about Wellbutrin vs. Zoloft

What is Wellbutrin?

Wellbutrin is a prescription antidepressant medication. It is a selective dopamine and norepinephrine reuptake inhibitor. It is prescribed in the treatment of major depressive disorder and other related psychiatric disorders. The generic form, bupropion, is also approved in the treatment of smoking cessation in its sustained-release form (bupropion SR). Wellbutrin is available in immediate, sustained, and extended-release tablet formulations.

What is Zoloft?

Zoloft is a prescription antidepressant medication used in the treatment of major depressive disorder as well as other anxiety and psychiatric disorders. Zoloft is in a class of drugs known as selective serotonin reuptake inhibitors (SSRIs). Zoloft is available as oral tablets as well as an oral liquid concentrate.

Are Wellbutrin and Zoloft the same?

While Wellbutrin and Zoloft are both classified as antidepressants, they are not the same type of drug. Wellbutrin works by increasing free levels of dopamine and norepinephrine in the neuronal synapse. Zoloft works by increasing free levels of serotonin. These neurotransmitters have a positive effect on mood and affect.

Is Wellbutrin or Zoloft better?

Multiple studies have shown Wellbutrin and Zoloft to be relatively comparable in achieving remission of depression symptoms. Wellbutrin may be favored over Zoloft due to the fact that its side effect profile is less severe.

Can I use Wellbutrin or Zoloft while pregnant?

Wellbutrin is categorized as pregnancy category B by the Food and Drug Administration (FDA), meaning it is generally considered safe during pregnancy. Zoloft is pregnancy category C, meaning there have not been adequate human studies to determine safety. In general, either drug should only be used with the benefit to the mother clearly outweighs the risk to the fetus.

Can I use Wellbutrin or Zoloft with alcohol?

Patients should avoid alcohol if taking Wellbutrin or Zoloft. Alcohol can increase the toxic effects of both medications and can cause significant psychomotor impairment. Alcohol specifically lowers the seizure threshold in patients taking Wellbutrin, and patients with a history of seizure should avoid this combination.

Does Wellbutrin help with anxiety?

Wellbutrin is not indicated in the treatment of anxiety. For some patients, anxiety may worsen while on Wellbutrin. Patients with anxiety may benefit from other medication classes, and their healthcare professional can help them select the best agent.

Is there a better antidepressant than Zoloft?

Zoloft is an effective antidepressant, but may not work for everyone. Studies have shown that patients who fail to achieve remission with Zoloft may find success with a new serotonergic antidepressant known as Trintellix (vortioxetine). Its mechanism of action increases free serotonin in two different ways and may be more effective for some patients.