Do Prozac and Abilify work well together? (3+ benefits)

In this article, we will answer the question “Do Prozac and Abilify work well together?”. We will also discuss the benefits and side effects of this combination, what research suggests and how to find the right combination.

Do Prozac and Abilify work well together?

Yes, Prozac (Fluoxetine) and Abilify (Aripiprazole) work well together in the treatment of depressive disorders. The FDA has approved the use of Prozac and Abilify as adjunctive therapy for major depressive disorder (MDD), in patients who show inadequate response to monotherapy with either medication (1,2).

The FDA recommends dose increments to occur gradually and also periodic reassessment of patients to adjust the dosage of both medications according to their needs. The patients receiving combination therapy should also be closely monitored for adverse effects.

In what way does Prozac and Abilify complement each other?

Prozac, a selective serotonin reuptake inhibitor (SSRI), increases the amount of serotonin in the brain thereby regulating the mood in various depressive disorders (3). Abilify is an antipsychotic medication, which is a partial agonist at dopamine and serotonin receptors in the brain. It helps with symptoms of hallucinations and poor motivation (4).

Prozac also has a role in the elimination of Abilify. Fluoxetine is an inhibitor of the CYP enzyme pathway and aripiprazole needs this pathway to be eliminated from the body. When taken as adjunctive therapy, Prozac increases the time taken for the elimination of Abilify. This prevents Abilify from fully breaking down and further increases the effects of aripiprazole on dopamine. This combination requires continuous monitoring of patients to prevent side effects like serotonin syndrome (5).

What does research suggest?

Prozac and Abilify, when used in combination show enhanced efficacy in treating depression and anxiety because of their complementary mechanisms of action. They also have a synergetic effect on mood stabilization. Both medications when used in adjunct to each other show an augmented antidepressant response (1).

Research assessing the combination of fluoxetine and aripiprazole supports the conclusion that adjunctive therapy may be effective in some individuals, but the adverse effect profile should also be kept in mind (6).

A case study suggests that aripiprazole is responsible for the protection of a patient from serotonin syndrome, which was likely to be caused as a result of taking fluoxetine. Aripiprazole was responsible for protecting the brain cells from surplus serotonin. This study suggests that both medications can help each other not only in treating depressive symptoms but also in inhibiting side effects (7).

Another study also assessed that aripiprazole when given with fluoxetine for OCD was more efficacious than fluoxetine monotherapy. Fluoxetine dosage was decreased when aripiprazole was added to the regimen (8).

What are the benefits of adjunctive therapy?

Adjunctive therapy of Prozac and Abilify can have many benefits. Some of these are as follows:

Enhanced efficacy

This combination when used for the treatment of depression and anxiety in individuals has shown better results regarding drug efficacy for the condition. It does need extensive monitoring but if the benefits outweigh the risks of side effects, your healthcare provider may prescribe this combination.

Better mood regulation

If you have been prescribed Prozac and Abilify together, you will notice that these medications in adjunct can regulate your mood better than any single medication you were on before your combination.

Reduced incidence of side effects

Although the combination of Prozac and Abilify can produce side effects, it can also reduce the incidence of side effects. This is due to its mechanism of keeping excess serotonin in check.

The adjunctive therapy of Prozac and Abilify may be beneficial but please make sure that you take these medications on the guideline of a healthcare professional only.

What are the side effects of adjunctive therapy?

Some side effects which can be experienced by patients on adjunctive therapy of Prozac and Abilify include suicidal thoughts, anxiety, increased nausea and lightheadedness. Some life-threatening conditions that can develop due to this combination include:

  • Serotonin syndrome (SS)- SS is caused by increased activity of serotonin in the brain. The symptoms of SS include altered mental state, insomnia, twitching of muscles, high blood pressure and restlessness.
  • Neuroleptic malignant syndrome (NMS)- Any medication which blocks dopamine can cause NMS. The symptoms of NMS include fever, irregular pulse, muscle rigidity and autonomic dysfunction.

Please note that not all people experience side effects and you should consult your healthcare provider to find the right treatment option and dosing for your symptoms. In any case, if you do experience any side effects please inform your doctor and do not make changes in medications or dosages on your own.

Tips for enhancing adjunctive therapy of Prozac and Abilify

Some strategies that can help you along with the combination of Prozac and Abilify are as follows:

Cognitive behavioural therapy (CBT)

CBT has always proven to be effective in depression patients. The patient must think that their depressive episodes are manageable and CBT helps them achieve this positive thinking. CBT combines many methods which help individuals manage their symptoms.

Lifestyle changes

Having a healthy lifestyle is beneficial for anyone on medication because this influences a positive outcome. Light exercise, yoga and meditation can prove to be helpful for people in this regard.


In this given article, we answered the question “Do Prozac and Abilify work well together?”. We discussed how they affect each other’s mechanism of action. We also discussed what research has to say in this regard, and what are the possible benefits and side effects seen with this combination. 

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The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. ABILIFY (aripiprazole) Tablets. Available from:,021713s030,021729s022,021866s023lbl.pdf


The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. PROZAC (fluoxteine capsules) for oral use. Available from:


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Bostankolu G, Ayhan Y, Cuhadaroglu F, Yazıcı MK. Serotonin syndrome with a combination of aripiprazole and fluoxetine: a case report. Therapeutic Advances in Psychopharmacology. 2015 Apr;5(2):138-40.


Rogóż Z. Combined treatment with atypical antipsychotics and antidepressants in treatment-resistant depression: preclinical and clinical efficacy. Pharmacological Reports. 2013 Nov;65(6):1535-44.


Rittmannsberger H, Werl R. Does aripiprazole protect from serotonin syndrome?. Psychiatria Danubina. 2012 Mar 25;24(1.):100-1.


Curtis AR, Richards RW. The treatment of psychogenic excoriation and obsessive compulsive disorder using aripiprazole and fluoxetine. Annals of Clinical Psychiatry. 2007 Jan 1;19(3):199-200.

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