Which is better, paroxetine or bupropion? A Detailed Comparison

October 10, 2025 •

4 min read

In 2021, an estimated 21 million adults in the U.S. had at least one major depressive episode [1.6.1]. When considering treatment, a common question is: which is better, paroxetine or bupropion? The answer depends on individual needs, as they work differently and have distinct side effect profiles.

Quick Summary

Paroxetine (an SSRI) and bupropion (an NDRI) are both effective antidepressants but have different mechanisms and side effects. Paroxetine is often used for anxiety, while bupropion has fewer sexual side effects and may aid smoking cessation.

Key Points

Different Mechanisms: Paroxetine is an SSRI that increases serotonin, while bupropion is an NDRI that boosts norepinephrine and dopamine [1.2.1].
Anxiety vs. Activating: Paroxetine is FDA-approved for several anxiety disorders [1.3.7], whereas bupropion is more activating and may be better for depression with fatigue [1.5.7].
Sexual Side Effects: Paroxetine commonly causes sexual dysfunction, while bupropion is known for having a much lower risk of these side effects [1.2.1, 1.4.3].
Weight Gain: Paroxetine is associated with a risk of weight gain, while bupropion is often weight-neutral or may lead to weight loss [1.5.2].
Seizure Risk: Bupropion is contraindicated in patients with a history of seizures or eating disorders due to an increased risk of seizures [1.4.1].
Efficacy: Both medications have shown comparable effectiveness in treating major depressive disorder [1.2.3].
Other Uses: Bupropion is also approved for smoking cessation and seasonal affective disorder [1.2.7].

Understanding Paroxetine and Bupropion

Choosing an antidepressant is a significant decision made in collaboration with a healthcare provider. Among the many options, paroxetine (brand name Paxil) and bupropion (brand name Wellbutrin) are two commonly prescribed medications that, while both treating depression, operate in fundamentally different ways [1.2.1, 1.2.5]. In 2021, 8.3% of all U.S. adults experienced a major depressive episode, underscoring the importance of effective and personalized treatment options [1.6.3].

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) [1.3.7]. Its primary mechanism is to increase the levels of serotonin, a neurotransmitter associated with mood, in the brain [1.3.4]. By blocking the reabsorption (reuptake) of serotonin into neurons, more of it is available in the synaptic cleft, which can help alleviate symptoms of depression and anxiety [1.3.2].

Bupropion belongs to a different class of drugs called norepinephrine-dopamine reuptake inhibitors (NDRIs) [1.5.2]. It works by increasing the levels of norepinephrine and dopamine, two neurotransmitters linked to motivation, focus, and pleasure [1.4.7]. Unlike SSRIs, bupropion has minimal effect on the serotonin system [1.4.5]. This unique mechanism is key to its different side effect profile and specific uses.

Conditions Treated: A Head-to-Head Look

Both medications are FDA-approved for Major Depressive Disorder (MDD), but their applications diverge from there.

Paroxetine's Approved Uses

Paroxetine has a broader range of FDA-approved uses for anxiety-related conditions [1.2.4, 1.3.7]:

Major Depressive Disorder (MDD)
Obsessive-Compulsive Disorder (OCD)
Panic Disorder
Social Anxiety Disorder (SAD)
Generalized Anxiety Disorder (GAD)
Post-Traumatic Stress Disorder (PTSD)

Studies suggest SSRIs like paroxetine may have a modest advantage over bupropion in treating depression with high levels of anxiety [1.5.1].

Bupropion's Approved Uses

Bupropion's approved uses are more focused [1.2.1, 1.2.7]:

Major Depressive Disorder (MDD)
Seasonal Affective Disorder (SAD)
Smoking Cessation (under the brand name Zyban) [1.5.2]

While bupropion can be used for anxiety, some clinicians have been hesitant due to a belief it could exacerbate anxiety symptoms. However, recent large-scale studies suggest that bupropion is as effective as SSRIs for anxiety symptoms in patients with comorbid depression [1.5.3, 1.5.7]. It may be particularly useful for depression characterized by fatigue and low energy [1.4.4].

Side Effect Profiles: The Deciding Factor?

For many, the choice between these two drugs comes down to their distinct side effect profiles. While both show similar efficacy for depression, their impact on weight, sexual function, and sleep can differ significantly [1.2.2].

Sexual Dysfunction: This is a well-known side effect of SSRIs. Paroxetine is associated with sexual side effects, such as decreased libido and difficulty with orgasm [1.2.4]. Bupropion, in contrast, has a significantly lower incidence of sexual dysfunction and is sometimes prescribed to counteract this side effect from other antidepressants [1.2.1, 1.4.3].
Weight Changes: Paroxetine is linked to a higher risk of weight gain compared to other antidepressants [1.2.4, 1.3.1]. Bupropion is more likely to be weight-neutral or may even cause modest weight loss [1.5.2, 1.5.7].
Sleep: Bupropion can cause insomnia and restlessness, especially when starting the medication [1.4.1, 1.4.3]. Paroxetine, on the other hand, can cause somnolence (drowsiness) [1.2.3, 1.3.1].
Seizure Risk: A critical consideration for bupropion is its potential to lower the seizure threshold. It is contraindicated for individuals with a history of seizures or eating disorders like anorexia or bulimia, as these conditions increase seizure risk [1.2.1, 1.4.1]. The seizure incidence for sustained-release bupropion at doses up to 300 mg/day is around 0.1% [1.4.5].

Comparison Table


Feature	Paroxetine (Paxil)	Bupropion (Wellbutrin)
Drug Class	SSRI (Selective Serotonin Reuptake Inhibitor) [1.2.4]	NDRI (Norepinephrine-Dopamine Reuptake Inhibitor) [1.5.2]
Mechanism	Increases serotonin [1.3.4]	Increases norepinephrine and dopamine [1.4.7]
Primary Uses	Depression, various anxiety disorders (OCD, GAD, PTSD) [1.3.7]	Depression, Seasonal Affective Disorder, smoking cessation [1.2.7]
Sexual Side Effects	Common [1.2.2]	Rare; sometimes used to treat SSRI-induced sexual dysfunction [1.4.3]
Weight Effect	Often associated with weight gain [1.3.1]	Generally weight-neutral or slight weight loss [1.5.7]
Common Side Effects	Nausea, drowsiness, dry mouth, sweating, sexual dysfunction [1.3.1, 1.2.4]	Dry mouth, insomnia, headache, nausea, anxiety [1.4.2, 1.4.3]
Seizure Risk	Low risk [1.2.4]	Increased risk; contraindicated in seizure or eating disorders [1.2.1]
Discontinuation	Higher risk of discontinuation syndrome (dizziness, nausea) [1.3.1]	Lower risk compared to SSRIs

Conclusion: Which One Is Better?

Neither paroxetine nor bupropion is definitively "better"; they are simply different tools for different clinical situations. The most suitable choice depends on a careful evaluation of the patient's specific symptoms, medical history, and tolerance for potential side effects.

Choose Paroxetine if the primary issue is depression coupled with significant anxiety, panic attacks, or OCD, and if the potential for drowsiness is not a major concern [1.2.4, 1.3.7].
Choose Bupropion if the patient's depression includes symptoms of fatigue, lack of motivation, or hypersomnia [1.5.7]. It is also a strong choice if avoiding sexual side effects or weight gain is a priority, or if the patient also wishes to quit smoking [1.2.1, 1.5.9]. However, it must be avoided in patients with a seizure history [1.4.1].

Ultimately, the decision rests with a qualified healthcare professional who can weigh these factors and monitor the patient's response to treatment. Both medications have demonstrated comparable efficacy in treating major depression, making the choice a matter of individual patient profiling [1.2.2, 1.2.3].

Authoritative Link: National Institute of Mental Health (NIMH) on Depression

Frequently Asked Questions

Yes, bupropion is sometimes added to an SSRI like paroxetine. This strategy is often used to augment the antidepressant effect or to counteract SSRI-induced side effects like sexual dysfunction. This combination should only be used under the direct supervision of a healthcare provider [1.5.7].

Paroxetine is FDA-approved for several anxiety disorders, including GAD and social anxiety disorder [1.3.7]. While historically there were concerns that bupropion could worsen anxiety, studies show it can be as effective as SSRIs for anxiety symptoms in people with depression [1.5.3]. However, SSRIs like paroxetine are often considered a first-line treatment for anxiety-predominant conditions [1.5.2].

Paroxetine is often associated with weight gain [1.2.4]. In contrast, bupropion is generally considered weight-neutral and is sometimes associated with modest weight loss [1.5.2, 1.5.7]. This makes it a preferred option for patients concerned about weight.

Bupropion has a significantly lower incidence of sexual side effects compared to SSRIs like paroxetine [1.2.1, 1.4.3]. It is a well-established alternative for individuals who experience sexual dysfunction on other antidepressants.

The most significant risk associated with bupropion is that it can lower the seizure threshold, increasing the risk of seizures [1.4.1]. It should not be used by individuals with a current or past seizure disorder or an eating disorder like bulimia or anorexia [1.2.1].

Both medications typically take several weeks to show their full effects, though some improvement may be noticed sooner [1.2.1]. It is important to continue taking the medication as prescribed even if you do not feel an immediate change.

No, you should not stop taking either medication suddenly without consulting a healthcare provider [1.2.1]. Abruptly stopping paroxetine can lead to a discontinuation syndrome with symptoms like dizziness and nausea [1.3.1]. Your doctor will provide a plan to taper the dosage safely.