Does Prozac potentiate Vyvanse? (3+ interactions)

In this article, we will discuss the interaction between Prozac and Vyvanse. We will also discuss how Prozac potentiates Vyvanse. The potential side effects of taking Prozac with Vyvanse and the measures to minimize the side effects. 

Does Prozac potentiate Vyvanse? 

Yes, Prozac increases the action of Vyvanse by increasing its concentration. (1). Prozac (fluoxetine) is an antidepressant belonging to the class of selective serotonin reuptake inhibitors (SSRI), which is used to treat depression, anxiety disorders, treatment-resistant depression, etc. (2)

Whereas Vyvanse is a stimulant which is used to treat Attention Deficit/Hyperactivity disorder (ADHD). Sometimes, when ADHD is associated with depression, antidepressants are prescribed. Some antidepressants can increase the concentration of Vyvanse, intensifying both its positive and negative effects. (3)

If you are experiencing any unwanted changes, consult your healthcare provider. They will adjust your treatment regimen accordingly to minimize the side effects. 

How does Prozac potentiate Vyvanse? 

Drugs belonging to the class of SSRIs inhibit an enzyme called CYP2D6, which is essential for the metabolism of Vyvanse. When Vyvanse is not properly metabolized, Its concentration in the blood builds up, leading to increased activity and toxicity. (3) 

Antidepressants such as Prozac act by increasing the level of serotonin, and amphetamines (Vyvanse) are also associated with an increase in serotonin release. Hence, the combination of Prozac and Vyvanse causes a synergistic effect, leading to a high level of serotonin. (3)

An increased level of serotonin can put you at risk of serotonin syndrome. The symptoms of serotonin syndrome can range from mild to life-threatening conditions. The symptoms of serotonin syndrome are as follows: (3,4)

  • Agitation
  • Shivering
  • Anxiety
  • Restlessness
  • Disorientation 
  • Increased sweating
  • Increased temperature 
  • Increased heart rate
  • Nausea, vomiting 
  • Diarrhoea
  • Muscle rigidity
  • Increased bowel sounds
  • Seizures 
  • Shock

What are the side effects of Prozac potentiating Vyvanse? 

Prozac increases the concentration of Vyvanse by inhibiting the enzyme CYP2D6. An increased concentration of Vyvanse can enhance the risk of side effects caused by Vyvanse, such as (5,6)

  • Lack of appetite
  • Dry mouth
  • Insomnia
  • Increased blood pressure, heart rate, and body temperature
  • Increased pupil size
  • Upper abdominal pain
  • Diarrhea
  • Nausea 
  • Fatigue
  • Jittery feeling
  • Headache

If you experience any of the above side effects, seek medical attention. Your physician will make the necessary adjustments to your regimen to minimize the side effects. 

What does the research suggest?

A study by Sills et al. on acute fluoxetine treatment potentiating amphetamine hyperactivity concluded that a 5mg/kg dose of Prozac (fluoxetine) increased the locomotor activity and dopamine overflow caused by Vyvanse (amphetamine) along with an increase in Vyvanse concentration in the brain. This indicates that Prozac can increase the concentration of Vyvanse and its effect. 

In a pre-clinical study, results showed that fluoxetine (Prozac) and sertraline (Zoloft) both increase the effect of amphetamine-induced hyperactivity and the concentration of amphetamines in the brain of rats. (7)

SSRIs, in combination with stimulants such as Vyvanse, are used to treat major depression associated with ADHD, but combining SSRIs with Vyvanse comes with a risk and needs to be monitored carefully to avoid side effects. Prozac has shown effectiveness in minimising suicidal thoughts and self-injury in patients. (8)

Other drugs, such as sertraline (an SSRI) in combination with Vyvanse, can also help treat depression. The safer alternative to be combined with a stimulant is tricyclic antidepressants (e.g. imipramine), which have shown positive results in treating depressive symptoms and have fewer side effects compared to SSRIs.(8)

What are the other factors that can potentiate Vyvanse effects?

There are other factors which can influence how Vyvanse affects the body. 

  • Individual variability: Not all individuals respond to the drug in the same way. Genetic variability also plays a role in how Vyvanse affect the body. (9) 


  • Metabolism: Vyvanse is metabolized in the liver by the enzyme CYP2D6. Individuals who are poor metabolizers tend to have little activity of this enzyme, which affects the action of Vyvanse in the body. This may decrease the action of Vyvanse and increase its toxicity. 


  • Food and acidic pH: Acidic pH in the stomach, acidic food and high-fat foods can affect the absorption of Vyvanse and the time taken for its action. 


  • Medications: Other antidepressants, such as tricyclic antidepressants (amitriptyline, desipramine), SNRIs (Venlafaxine, duloxetine), and MOAI (Isocarboxazid, selegiline), as well as some analgesics can increase the concentration of Vyavnse. (3)

How can you minimize the side effects of Prozac and Vyvanse? 

Minimizing the side effects of Vyvanse while taking Prozac involves careful monitoring and management. Here are some tips to manage the side effects: 

  • Ensure you talk to your physician if you notice any unwanted side effects.
  • Do not stop taking your medication without a physician’s guidance, as it can cause withdrawal symptoms and worsen your condition.
  • If you want to discontinue your medication, your physician will taper the dose and eventually stop your medication. 
  • Side effects can be minimized by reducing the dose of the drug, which should be done under a physician’s guidance.
  • Vyvanse usually causes insomnia. Hence, it is recommended to take Vyvanse in the morning to avoid insomnia. 
  • If Vyanse is causing any gastrointestinal problems like nausea and vomiting, try taking it with food. Avoid eating a high-fat diet and acidic food as it may decrease the absorption time of Vyvanse. 
  • Stay hydrated, as dehydration can increase the risk of side effects by minimizing the removal of drugs causing the build-up of drugs in the body. 
  • Avoid alcohol and limit your intake of caffeine, as it may decrease the effectiveness of Vyvanse and Prozac.
  • Monitor your symptoms regularly and attend regular follow-ups with your physician.
  • You can consider other therapies, such as cognitive behavioural therapy and counselling, along with the drug to help treat your illnesses. 
  • Maintain a healthy lifestyle. Exercise regularly, have a balanced diet, adequate sleep and stress management. Taking care of your body can help minimize the occurrence of side effects.


In my perspective, antidepressants such as Prozac can increase the effectiveness of Vyvanse. Therefore, it is necessary to monitor it carefully to prevent the occurrence of side effects. Make sure you visit your healthcare provider for proper guidance and management. 

Was this helpful?

Thanks for your feedback!



Sills TL, Greenshaw AJ, Baker GB, Fletcher PJ. Acute fluoxetine treatment potentiates amphetamine hyperactivity and amphetamine-induced nucleus accumbens dopamine release: possible pharmacokinetic interaction. Psychopharmacology. 1999 Feb;141:421-7. Available from:


Sohel AJ, Shutter MC, Molla M. Fluoxetine. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:



Vo K, Neafsey PJ, Lin CA. Concurrent use of amphetamine stimulants and antidepressants by undergraduate students. Patient preference and adherence. 2015 Jan 22:161-72. Available from:


Simon LV, Keenaghan M. Serotonin Syndrome. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


Dolder PC, Strajhar P, Vizeli P, Hammann F, Odermatt A, Liechti ME. Pharmacokinetics and pharmacodynamics of lisdexamfetamine compared with D-amphetamine in healthy subjects. Frontiers in pharmacology. 2017 Sep 7;8:617. Available from:


Goodman DW. Lisdexamfetamine dimesylate (vyvanse), a prodrug stimulant for attention-deficit/hyperactivity disorder. Pharmacy and Therapeutics. 2010 May;35(5):273. Available from:


Sills TL, Greenshaw AJ, Baker GB, Fletcher PJ. The potentiating effect of sertraline and fluoxetine on amphetamine-induced locomotor activity is not mediated by serotonin. Psychopharmacology. 1999 Apr;143:426-32. Available from:


Turgay A, Ansari R. Major Depression with ADHD: In Children and Adolescents. Psychiatry (Edgmont). 2006;3(4):20-32. Available from:


Hart AB, de Wit H, Palmer AA. Genetic factors modulating the response to stimulant drugs in humans. Behavioral neurogenetics. 2012:537-77. Available from:

Find a supportive therapist who can help with Depression.

Discover the convenience of BetterHelp, an online therapy platform connecting you with licensed and accredited therapists specialized in addressing issues such as depression, anxiety, relationships, and more. Complete the assessment and find your ideal therapist within just 48 hours.


AskYourPharm is user-supported. We may earn a commission if you sign up for BetterHelp’s services after clicking through from this site