How Is Wellbutrin Different From SSRIs?

Wellbutrin (buproprion) and SSRIs (selective serotonin reuptake inhibitors) have different mechanisms of action; meaning that they increase the availability of different brain chemicals, and therefore feel and function very differently for patients. There may be indications for one (and not the other), and their side effect profiles are additionally very different. It’s important that providers explain the differences between Wellbutrin and SSRIs (like Zoloft, Prozac and Lexapro) to patients, and take these differences into consideration, when choosing one versus the other for a patient’s depression (or anxiety) treatment.

This article will discuss both Wellbutrin (buproprion) and SSRIs (selective serotonin reuptake inhibitors), and compare some of the potential risks, benefits, side effects and other considerations, when choosing between them for anti-depressant treatment. This is not meant to be medical advice, and starting, stopping, or changing psychiatric medications should be discussed directly with one’s psychiatrist or prescribing provider. This article will also speak in generalities, and it’s important to consider that no two patients respond the same way to a psychiatric medication.

Wellbutrin (buproprion) increases the availability of norepinephrine and dopamine in the brain. It’s referred to as a norepinephrine dopamine reuptake inhibitor (or NDRI). NDRIs can be utilized to treat depression, but do not typically treat anxiety (they can actually make anxiety worse). Wellbutrin is utilized not only for depression treatment, but for smoking cessation as well. It’s also used off-label for ADHD treatment. Wellbutrin tends to have a “stimulant” effect, increasing energy, motivation, and libido (it can be used to treat sexual dysfunction from other anti-depressants). It’s not uncommon for patients to report weight loss on Wellbutrin, or for it to affect sleep (causing insomnia). Wellbutrin can increase the risk of seizures (particularly at its highest dose) more-so than SSRIs, and therefore, it’s typically not recommended in patients with a history of seizures, an alcohol use disorder, or an active eating disorder.

SSRI’s (such as Zoloft, Prozac, Lexapro, Paxil and Celexa) increase the availability of serotonin in the brain. They can be effective in treating both depression AND anxiety, and are typically first line for both conditions. SSRIs are more-likely to cause fatigue (particularly when first starting, or adjusting to a higher dose), than wellbutrin, and they’re additionally more likely to cause sexual side effects. Sexual side effects are often transient (and dose related), and discussing any concerns with your provider is important, as they may be able to make recommendations to mitigate them (or they may go away with time). Of note, SSRIs are commonly used to treat premature ejaculation in men, while Wellbutrin is more likely to speed things up.

Wellbutrin vs SSRIs: Key Differences at a Glance

How Wellbutrin and SSRIs Work in the Brain

There are several healthy neurotransmitters (brain chemicals) that are frequently targeted in patients with depression, and various other psychiatric conditions. The main three, include serotonin, norepinephrine and dopamine.

Brain cells (neurons) will release these healthy brain chemicals into the fluid filled space between brain cells (the synaptic cleft) so that they are available to other neurons (basically, so they’re available where needed, to promote stable emotions, manageable anxiety, and a healthy mood).  “Reuptake inhibitors” prevent these healthy brain chemicals from going backwards (from the synaptic cleft, back to the neuron that they came from). By doing so, there are more of these healthy brain chemicals available to brain cells, to be utilized by the central nervous system, where indicated.

Serotonin can be utilized to improve mood (treat depression) and it also has a role in anxiety regulation (treating generalized anxiety, panic, OCD, PTSD and other conditions). Norepinephrine and Dopamine typically do not treat anxiety, but are frequently used to treat depression (they have an anti-depressant effect). Norepinephrine and Dopamine also tend to have a stimulant effect, increasing energy, motivation and focus. Dopamine is involved in the “reward pathway,” and therefore, dopamine reuptake inhibitors (like Wellbutrin) can decrease cravings for nicotine, and are used in smoking cessation.

The exact mechanism of action of serotonin reuptake inhibitors (SSRIs) and norepinephrine dopamine reuptake inhibitors (NDRIs) is not fully understood (I.E. the above is an oversimplification), but none-the-less, this explanation may help someone to understand why an SSRI may be used to treat anxiety, why Wellbutrin (buproprion) may be used to treat ADHD off label, and why the two classes of medications have distinct side effect profiles.

Conditions They Treat and Matching Medication to Symptoms

Selective Serotonin Reuptake Inhibitors are first line medications for BOTH anxiety disorders (such as generalized anxiety disorder, panic disorder, obsessive compulsive disorder and PTSD) and depressive disorders (such as Major Depressive Disorder, Postpartum depression, pre-menstrual dysphoric disorder and seasonal affective disorder). SSRIs are also frequently utilized to treat bulimia and binge eating disorder. Since SSRIs (like Prozac, Zoloft and Lexapro) can treat anxiety, if a patient has a depression that causes anxiety as a symptom, SSRIs may be a good choice.

* Of note, anti-depressants should be used very cautiously in bipolar disorder, and bipolar “mixed episodes” require an expert psychiatrist or mental health clinician to differentiate between them and “anxious depressions.”

While side effects are generally thought of as problems, the expert psychiatrist can utilize side effects, as a positive. For example, if someone’s depression has a great deal of low energy or cognitive dulling associated with it, Wellbutrin (buproprion) and it’s stimulant-like effect, may be a good choice. Alternatively, if a patient has co-occurring panic disorder, an SSRI, such as Lexapro or Prozac, may be a good option.

*Working with a psychopharmacologist who understands the nuances of not only SSRI’s and NDRIs, but of SNRI’s, TCA’s, Remeron (mirtazine), Trintellix (vortioxetine), Viibryd (vilazodone), MAOIs and other anti-depressants can be extremely beneficial, so that treatment is completely tailored to the individual. The more options that a skilled clinician has at their disposal, the higher the chance of the right fit.

Remember, this is not medical advice, but rather general information and patients should always discuss starting, stopping, or changing medications directly with their mental health provider.

Side Effects: Energy, Anxiety, Sex, and Weight

Wellbutrin (buproprion) is more likely to increase energy than SSRIs. This can be beneficial for some, and problematic for others. For example, some feel “jittery” when taking Wellbutrin, have increased anxious energy (or panic), or develop insomnia. Wellbutrin can increase sexual energy as well, and is even used to treat SSRI induced sexual dysfunction or delayed orgasm. Wellbutrin tends to curb appetite and can cause weight loss.

SSRI’s can sometimes cause lower energy (often transient). Even though they’re more likely to cause tiredness at first, as the patient comes out of their depression, energy typically improves greatly (back to baseline). SSRIs are more likely to cause lower libido (or delayed climax), and although they’re generally thought of as weight neutral, they’re more likely to cause weight gain than Wellbutrin.

Many side effects of both Wellbutrin and SSRIs (like Lexapro and Prozac) are transient, and any concerns about side effects (or side effects) should be directly discussed with one’s psychiatrist or other mental health specialist. Side effects do not occur in all patients, and if they persist, there are often ways to mitigate them, or cause them to be a non-issue.

Safety, Contraindications, and Drug Interactions

Wellbutrin (buproprion) typically should be avoided in individuals with seizure disorders (such as epilepsy), or in those who are high risk of seizure (such as individuals with eating disorders and/ or alcohol use disorders). Wellbutrin is also often avoided in patients with anxiety disorders, such as generalized anxiety disorder, or panic disorder, particularly if the patient is not already on an SSRI (which could provide some protection from increased anxiety as a side effect).

SSRI’s (such as Lexapro, Prozac and Zoloft) also have the potential for various side effects (and although rare, some serious). Examples may include a higher risk of bleeding (for example, for patients on blood thinners), and a risk of Serotonin Syndrome (which is a potentially life threatening emergency). Of note, Serotonin Syndrome is rare, and typically only seen if a patient is on many serotonergic medications/ supplements, and/or using recreational drugs, such as Ecstasy, in combination with their anti-depressants.

Many do not realize, but both recreational drug use and the use of supplements (such as St. John’s Wart) can be very dangerous for patients on either SSRIs or Wellbutrin. It’s incredibly important to disclose any medications, supplements and/or drug use to your psychiatric provider.

Can You Take Wellbutrin and an SSRI Together?

It is not uncommon for a psychiatrist, or mental health provider, to concurrently prescribe both an SSRI and Wellbutrin, for the same patient. Let’s say that I start a patient on an SSRI for depression, and they become 70 or 80% better. If we’re at a maximum dose of the SSRI (or if side effects are causing us to be unable to increase the SSRI further), then adding Wellbutrin (buproprion) may be a reasonable next step, to get someone 90-100% better. Being on one, is not a contraindication for taking the other. Additionally, when you think about the mechanisms of action of these medications, it’s reasonable to assume that someone’s depression may need not just serotonin, but also an increase in norepinephrine and dopamine (or vice-a-versa). Sometimes increasing all three healthy brain chemicals, is needed to get someone well.

Another example, could be if a patient is taking Wellbutrin, and it works extremely well to bring them out of their depression, but they’ve started to have anxiety as a side effect (of the Wellbutrin). Ideally, a patient would get 100% better on one medication (without any side effects), but sometimes when a patient’s depression is severe, and Wellbutrin brings them out of it, they may not want to “start from scratch” by completely changing medications (risking falling back into depression). Thus, an SSRI may be added in this type of scenario.

Additionally, Wellbutrin is also often added to an SSRI, if the SSRI causes sexual dysfunction, delayed orgasm, or low energy/ fatigue.

Of note, I personally have concern for when psychiatric providers start more than one medication (such as an SSRI and wellbutrin) at the same time. The truth is, that I would always prefer to have a patient on fewer medications (and at the lowest effective dose), and I never want would assume that someone would need more than 1 medication. Thus, while I have many patients on both an SSRI and Wellbutrin, they were started on each medication individually, and we only started the second, when there was significant evidence that we needed to.

Talking With Your Prescriber About Wellbutrin vs SSRIs

The decision to start anti-depressant treatment is a personal one, and should only occur after a thorough discussion and evaluation with one’s mental health professional. Once the decision is made to start medication management, it’s incredibly important to thoroughly discuss the indications, risks, benefits, and idiosyncrasies of each treatment option. As discussed, Wellbutrin (buproprion) and SSRIs are two options that treat depression, yet, they work on completely different neurotransmitters, have different indications, and each has their own side effect profile and risks.

We recommend being prepared for your psychiatric evaluation and your discussion about anti-depressants. Bringing the following to your appointment, may prove very beneficial:

• A list of current symptoms, and your priorities for treatment.
• A list of previous medications trialed (dose, duration, effect and side effects).
• Information on previous side effects with medications, and information on your concerns around potential side effects (such as energy levels, appetite, sexual side effects and treating co-occurring conditions).
• A family history for psychiatric illness (diagnosis) and medications that have worked well (or not worked so well), for close relatives.

Finally, it may be helpful to put some thought into whether you’d be best off with an in-office appointment (seeing your psychiatric provider face-to-face), or having visits by telemedicine. While in-office visits are often recommended, if they’re not feasible (or if visits would have to be very sporadic due to work or travel), then telemedicine may be best.

Either way, we’re happy to provide both in-office and telemedicine visits for our patients.