Prozac and Wellbutrin combo (A comprehensive overview)

This blog is about Prozac and Wellbutrin combinations that are generally prescribed by clinicians and how effective they may or may not be.

A brief introduction to Prozac and Wellbutrin

Antidepressants were first developed in the 1950s and have become extremely popular in the last 20 years. These medications are mainly used to treat symptoms of depression, social anxiety disorders, seasonal affective disorder, dysthymia, and other conditions as well.

Prozac and Wellbutrin are both medications that are prescribed for depression, but they work in different ways. Antidepressant combos may be effective for improving efficacy, but they are more typically employed to minimize the negative impact of antidepressant medication. E.g. Trazodone is mainly combined with an SSRI to combat the side effects of SSRI treatment which may develop insomnia. However, it is very dangerous to combine antidepressants, and is advisable that you prohibit combining your medication without proper consultation. 

To understand the combination strategies of Prozac and Wellbutrin, We must understand the effects of monotherapy, and the mechanism of both drugs.

Prozac is the brand name for fluoxetine. It mainly functions by preventing the brain from reabsorbing the naturally-occurring serotonin, which is a mood regulator, leaving you with enough serotonin that is efficient to provide you a feeling of well-being and happiness. It is an antidepressant, used to treat bulimia nervosa (an eating disorder), panic attacks, obsessive-compulsive disorder, premenstrual dysphoric disorder. Prozac may help you regain interest in daily activities by improving your mood, sleep, appetite, and energy levels and it may also lessen the symptoms of obsessive behaviors that obstruct daily life. It is also effective in helping you resist premenstrual symptoms like binge eating, irritability, and purging behavior. However, during your first few weeks of treatment, you may experience mild symptoms of nausea, fatigue, trouble sleeping,and anxiety. Contact your clinician if these symptoms may worsen or persist.

Bupropion is sold under several brand names, one of which is Wellbutrin. Wellbutrin is an antidepressant that works by blocking the neurotransmitters norepinephrine and dopamine in the brain. This combination of actions aids in the treatment of major depressive disorders and can even aid in the cessation of smoking. Some possible side effects of bupropion may include headache, sleeplessness, weight loss. loss of appetite, sore throat and dizziness.

Are Wellbutrin and Prozac similar?

According to research, Prozac and Wellbutrin stimulate similar efficacy in depression and anxiety, with similar favorable safety levels, but both of them act in different ways (DUNNER, 2014). Wellbutrin is an aminoketone that acts by boosting norepinephrine and dopamine levels in the brain. Prozac is an SSRI that works by raising serotonin levels in the brain. These prescription medicines can be prescribed by a psychiatrist to treat a variety of mental health disorders, notably depression.

Although Wellbutrin and Prozac are similarly effective in relieving depression and related symptoms, their effects differ in various ways. For e.g in a comparison study for both these drugs, it was found that Prozac is more frequently linked to sexual dysfunction. Bupropion SR may be an effective first-line treatment for depression in people who are concerned about sexual function.  (“A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained-release and fluoxetine – ScienceDirect,” n.d.)

What Is Treatment-Resistant Depression?

Various studies are evidence that 46 % of depressed patients are not satisfied with their antidepressants. This means that the antidepressants showed either partial or no response. Even among the respondents, the side effects of those drugs were dreadful and showed that those patients were more likely prone to relapse. 

Treatment-resistant depression is more common now than ever. It is a clinical term used to describe patients with major depressive disorders that have responded to antidepressant treatment in a given time.

Anxiety disorders are the most common disorders that are linked to treatment-resistant disorders. Studies have also suggested that patients with MDD (major depressive disorder) are most likely prone to non-responsive treatment. This is mostly the reason why clinicians try combining drug treatment to increase their efficacy. Augmentation is described as adding an augmenting compound to induce a response. Hence the main objective behind augmentation is to increase response by adding another element to the treatment; alternatively, clinicians also combine antidepressants with other antidepressants to induce an adequate response.

Combination of Prozac and Wellbutrin

Bupropion with SSRI combination is generally well tolerated. The adverse effects reported by more than 270 individuals who received bupropion in addition to an SSRI for refractory depression or antidepressant-associated sexual dysfunction were similar to those seen with the SSRI, SNRI, or bupropion alone.

According to thorough research, No significant differences were found in adverse event severity between those taking combination therapy versus bupropion or SSRI monotherapy, it was also found that the bupropion–SSRI group had more anxiety, stress, anergia, and mood lability than the SSRI–placebo group, with the SSRI–placebo group having more anxiety, stress, anergia, and mood lability. Serious adverse effects were uncommon in the studies and case reports, although they were consistent with those described with each drug separately. After discontinuing or reducing the dosage of one or both medications, these side effects went away without leaving any lasting effects.

In an uncontrolled trial of 27 patients with depressive disorders, the combination of fluoxetine and bupropion appeared to be more efficacious and safe than monotherapy(Li, Perry, & Wong, 2002)

A study of SSRI and bupropion in 1993 observed 23 patients who had a partial response to either Prozac or Wellbutrin. After considerations, the other drug was added to the first treatment. 8 of these tested with positive or moderate results but 9 of these 23 patients were unable to withstand its effects. Moreover, the level of Prozac also rises in the bloodstream, if combined with Wellbutrin and the patient is likely to experience strokes or tremors if they are elderly, have a history of seizures, are struggling with withdrawal, or have any central nervous system disorder. Both drugs Wellbutrin and Prozac contain warnings about suicidal thoughts and behaviors. They may also increase or worsen your depression.

The combination of Wellbutrin and Prozac, as previously indicated, may trigger tremor and panic attacks, while the favorable effects of Wellbutrin on SSRI-induced sexual problems may be a considerable advantage of this strategy. These combinations are based on the similar principle of SSRI and desipramine, i.e. noradrenergic agents and serotonergic agents when combined, enhance the effects. 

Pros and cons of augmentation or combinations

The advantages and disadvantages of using augmentation or combination strategies are considerable. Combination treatment is more challenging than single-agent treatment because drug interactions may emerge, adverse effects may be enhanced, and some combinations are more costly. Perhaps most importantly, treatment complexity increases and treatment with a single medication is easier and may enhance compliance in a patient with questionable compliance. These considerations may be especially important when treating depression in a patient who hasn’t been highly resistive and whose depression isn’t particularly severe. On the other hand, augmentation and combination strategies do have advantages. First, there’s the possibility of a quick response. Responses have been noted within 48 hours for various types of augmentation, such as lithium augmentation. From a practical perspective, adding a second agent to a patient with a partial response may help to preserve the improvement associated with the first agent, but it’s important to emphasize that augmentation strategies’ effectiveness isn’t restricted to partial responders. In one study42, lithium supplementation was found to be beneficial in patients who had a poor first response to a TCA. Another benefit of mixing two drugs is that there is no time wasted reducing one and then gradually raising the other. Another benefit of mixing two treatments is that there is no time wasted reducing one and then gradually raising the other. The patient may benefit from a combination of treatments, after which the initial antidepressant can be discontinued. As a result, combination treatment can be employed as a bridge to the second agent’s final treatment.

The side effects of the augmentation of different strategies may vary. When taken with antidepressants, T3, L-tryptophan, buspirone, and pindolol have low adverse effects. Stimulants, lithium, risperidone, and SSRIs (like Prozac) combined with bupropion (Wellbutrin) or mirtazapine are all linked to mild adverse effects. The SSRI-TCA combination has significant side effects, and blood level monitoring is likely to be required. The use of MAOIs and TCAs together is potentially dangerous, therefore it should be avoided. The severity of adverse effects noticed, in this author’s opinion, reflects the efficacy of the combination to some degree.

Other first-hand experienced narratives

From information gathered over the internet and consulting some of the first-hand experiences of combined treatment, we have concluded that combined treatment has proven useful to many. Prozac alone has stimulating effects but combined with or followed by Wellbutrin seems to amplify the anxiety side effects of Prozac. Even so, the patients are relieved of depression. Although the dosage may also play a huge role as to why you are not improving in any treatment, It is mandatory that you consult your clinician before ingesting any kind of antidepressant.

Even though most of us have heard of Prozac and Wellbutrin strategies as a successful therapy and most recommend Wellbutrin with an SSRI, but some do not. This is because Wellbutrin and Prozac both are stimulating and may cause other problems. Some suggest other SSRI combinations with Wellbutrin that have proven quite effective.


This blog post addresses the combination strategy of Prozac and Wellbutrin that is applied by clinicians, what research has proven over the years, and what the people who have been treated with the combined treatment of Wellbutrin and Prozac have to say about it.

FAQ (Frequently Asked Questions)

Why do doctors prescribe antidepressant combinations?

The combinations may usually be prescribed to counter side effects,  although they are often used to enhance efficiency. 

How does Wellbutrin work with Prozac?

Wellbutrin is a norepinephrine-dopamine reuptake inhibitor, whereas Prozac is a serotonin reuptake inhibitor. Activation of multiple neurotransmitter systems is proven effective in attaining remission for a subset of depressed individuals with the most refractory depressed patients. In such instances, it is beneficial to stimulate both serotonin and noradrenaline neurotransmission because efficacy is enhanced by combining the two, minimizing or countering the side effects of the other.

Does Wellbutrin and Prozac combination help in weight loss?

In the journal article of The therapeutic advances in psychopharmacology authored by Priyadarshini P. Ravindran,  it was found that the combination of Wellbutrin with fluoxetine causes a general increases in BMI. So the average increase in weight has been found to follow with the combined treatment of Wellbutrin and Prozac.


A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained-release and fluoxetine – ScienceDirect. (n.d.). Retrieved October 17, 2021, from

DUNNER, D. L. (2014). Combining antidepressants. Shanghai Archives of Psychiatry, 26(6), 363.

Li, S. X. M., Perry, K. W., & Wong, D. T. (2002). Influence of fluoxetine on the ability of bupropion to modulate extracellular dopamine and norepinephrine concentrations in three mesocorticolimbic areas of rats. Neuropharmacology, 42(2), 181–190.