Wellbutrin vs Zoloft

How they're similar

Bupropion and sertraline are both common antidepressants, and despite working differently they share several features.

• Both treat depression, and both are effective first-line options.
• They follow the same timeline. Early side effects can show in the first week or two, while the fuller effect on mood usually takes four to six weeks, sometimes up to eight.
• Both can cause early side effects before the benefit shows, including headache, dry mouth, and nausea.
• Both must not be combined with MAOI antidepressants, and a gap is needed when switching between them.
• Both carry the antidepressant boxed warning about a possible increase in suicidal thoughts in people under 25, especially early in treatment.
• In people with bipolar disorder, either antidepressant can sometimes trigger a manic or agitated state, which is one reason an accurate diagnosis matters.
• Both have been available as inexpensive generics for years.

How they differ

The biggest difference is how they work, and that shapes most of the rest. The table below sums up the core points, with more detail underneath.

The starting point is mechanism. Bupropion is an NDRI, a norepinephrine-dopamine reuptake inhibitor, so it works on norepinephrine and dopamine. Sertraline is an SSRI, a selective serotonin reuptake inhibitor, so it works on serotonin. Because they act on different messengers, almost every practical difference below follows from that one fact.

That difference drives anxiety. Sertraline is strongly effective and broadly approved for anxiety conditions, including panic disorder, post-traumatic stress disorder, social anxiety disorder, and obsessive-compulsive disorder. It is also commonly used for generalized anxiety disorder. Bupropion is not a first choice for anxiety, and because it is activating it can make anxiety worse for some people. So consider someone whose depression comes with constant worry or panic attacks. Sertraline addresses both the low mood and the anxiety, while bupropion might calm the mood and stir the anxiety at the same time. For depression that comes with anxiety, sertraline is usually preferred.

Sexual side effects also differ, and this is one of the most common reasons people ask about the two. Sertraline commonly causes them. By many measures a third or more of people on an SSRI notice some change, which can include lower sex drive, delayed orgasm, and arousal or erection difficulties. Bupropion rarely causes sexual side effects. That is one reason it is sometimes chosen first, and also why a prescriber may add bupropion alongside an SSRI specifically to offset the SSRI's sexual side effects.

On weight, sertraline is roughly weight-neutral in the short term, with modest gain possible long-term for some people, though it tends to be smaller than with a few other antidepressants. Bupropion is weight-neutral or linked with mild weight loss, and it can reduce appetite. For someone who is concerned about weight gain, that difference matters.

Energy is another difference. Bupropion is activating. It can help with low energy and low drive, and some people notice more energy fairly early, but it can also cause insomnia or jitteriness. Sertraline is more neutral, though it can be mildly activating for some people.

There is one safety difference that stands out. Bupropion lowers the seizure threshold in a dose-related way, so the risk rises at higher doses and with rapid dose increases. It should not be used in people with a seizure disorder, in people with a current or past diagnosis of anorexia or bulimia, or in people stopping alcohol or sedatives abruptly. Daily-dose and single-dose limits exist specifically to keep this risk low. Sertraline does not carry that risk.

On stomach effects, sertraline is more associated with loose stools and diarrhea than some other antidepressants. Bupropion has one extra use worth noting. Under the brand name Zyban, it also helps people quit smoking, and it is approved to prevent seasonal affective disorder. Sertraline is also approved for premenstrual dysphoric disorder, which bupropion is not.

Side effects compared

The two medications have fairly different side effect profiles, which follows from working differently. Sertraline more often causes sexual side effects, loose stools and diarrhea, and other stomach effects, and it can rarely cause low blood sodium or trigger serotonin syndrome. Bupropion more often causes insomnia, jitteriness, dry mouth, and tremor, and it carries the dose-related seizure risk noted above. Bupropion can also worsen anxiety because it is activating.

With both, side effects tend to arrive before the benefit, and many of the early effects ease within a couple of weeks. If a side effect is severe, or it is not improving after a few weeks, that is a conversation to have with a prescriber rather than a reason to stop on your own.

Sleep, weight, and sexual effects

This is where the two differ most.

For sleep, bupropion is activating and more likely to cause insomnia, which is why it is taken earlier in the day. Sertraline is more neutral and is usually taken in the morning, though it can go at night for someone it makes drowsy. For weight, sertraline is roughly weight-neutral with modest gain possible long-term for some people, while bupropion is weight-neutral or linked with mild weight loss. For sexual effects, sertraline commonly causes lower sex drive, delayed orgasm, and arousal or erection difficulties, while bupropion rarely does. These effects are worth raising with a prescriber, because there are real options, including a dose change, a switch, or adding bupropion to an SSRI. Stopping a medication on your own is not the way to handle a side effect.

Why a clinician might choose one over the other

Because the two work differently, the choice often comes down to the symptom picture.

A clinician might choose sertraline for depression that comes with anxiety, or for panic disorder, PTSD, OCD, social anxiety, or PMDD, where sertraline is formally approved. It is a sensible first choice when worry, panic, or intrusive thoughts are part of the picture, since bupropion can stir those up. Sertraline is also one of the more studied SSRIs in pregnancy, which a prescriber may weigh.

A clinician might choose bupropion for depression with fatigue or low energy, since it is activating, or for someone who wants to avoid sexual side effects or weight gain, or who also wants to quit smoking. Bupropion is not a good fit when anxiety is prominent, or when there is a seizure disorder, a current or past eating disorder, or a plan to stop heavy alcohol use. The two are also sometimes prescribed together, with bupropion added to sertraline to broaden the effect or to offset the sexual side effects sertraline can cause. Beyond all of this, prior response, other medications, and other health conditions factor into the decision.

The bottom line

Bupropion and sertraline are two different tools. Neither is clearly better. Sertraline is the broader choice for anxiety, while bupropion is the lower-risk choice for sexual side effects and weight gain and the better fit for low energy. The right choice depends on the symptom picture and which side effects a person most wants to avoid, and it is decided with a prescriber. It is also common to try one and switch to the other, or to use them together, if that is the better fit. A first medication that does not suit someone is a normal step in treatment, not a failure.

Common questions

Can bupropion and sertraline be taken together? Yes, and prescribers sometimes do this on purpose. Bupropion is added to an SSRI such as sertraline to broaden the antidepressant effect, to help with low energy, or to offset the sexual side effects sertraline can cause. This combination is a decision for a prescriber, not something to set up on your own.

Which one is less likely to cause sexual side effects? Bupropion. It rarely affects sexual function, while sertraline commonly does. That is one reason bupropion is sometimes chosen first, and why it is sometimes added alongside sertraline specifically to counter that side effect.

Why isn't bupropion a good choice for anxiety? Bupropion is activating, so for some people it can make anxiety worse rather than better. It is also not broadly approved for anxiety conditions. Sertraline is strongly effective for panic disorder, PTSD, social anxiety, and OCD, so for depression with anxiety, sertraline is usually preferred.

Who should not take bupropion? Bupropion lowers the seizure threshold, so it should not be used by people with a seizure disorder, with a current or past diagnosis of anorexia or bulimia, or who are stopping heavy alcohol or sedative use abruptly. A prescriber screens for these before starting it.

Sources

This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes.

1. U.S. Food and Drug Administration. Bupropion prescribing information.
2. U.S. Food and Drug Administration. Sertraline prescribing information.
3. MedlinePlus, U.S. National Library of Medicine.
4. National Institute of Mental Health. Mental health medications.