Does Fluoxetine make ADHD worse? (3+ facts)

In this article, we will discuss whether Fluoxetine can worsen ADHD symptoms and the underlying mechanism. We will also highlight the research studies conducted on ADHD patients treated with Fluoxetine.

Does Fluoxetine make ADHD worse? 

Yes, Fluoxetine is said to increase ADHD symptoms. Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. Patients with ADHD can develop anxiety, and it has been found that Fluoxetine tends to exacerbate anxiety and hyperactivity. (1)   

Fluoxetine is sometimes used in combination with CNS stimulants to treat depression and anxiety in patients with ADHD. Your doctor may prescribe Fluoxetine if its benefits outweigh the potential risks. If you are experiencing any side effects or you suspect that your anxiety is worsening, report to your physician. 

What does the research suggest?

Selective Serotonin reuptake inhibitors have been shown to aggravate ADHD symptoms. Antidepressants can help treat impulsive and hyperactive behaviour, but they are not effective in treating attentional and cognitive symptoms of ADHD. Tricyclic antidepressants have been found to have a significant impact on alleviating behavioural symptoms. (1)

A study compared the use of Fluoxetine in Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) and found that Fluoxetine had a negative effect on tasks performed by ADHD patients. Fluoxetine upregulated the action of mPFC in ASD patients but downregulated the activation of the mPFC in ADHD patients. (2)

According to a study conducted by Riddle et al., 12 children between the ages of 8 and 16 who were given Fluoxetine at a dosage of 20-40 mg/day for symptoms of depression or OCD reported side effects such as motor restlessness and sleep disturbance. Additionally, three children who were diagnosed with ADHD and treated with Fluoxetine showed a worsening of their ADHD symptoms. (4)

How does Fluoxetine worsen ADHD?

Fluoxetine is said to cause “behavioural activation”, which leads to motor restlessness, sleep disturbances, disinhibition and feelings of excitement in patients with ADHD. This disinhibition caused by Fluoxetine, which is an SSRI, is associated with frontal lobe dysfunction and frontal apathy. The frontal lobe plays a role in voluntary movement, expressing language and performing high-level executive functions. 

The medial prefrontal cortex (mPFC) in the brain plays a crucial role in regulating cognitive processes, emotions, motivation, and sociability. Dysfunction of the mPFC is observed in various neurological and psychiatric disorders. (3) One way to treat ADHD is to activate the mPFC, but Fluoxetine tends to downregulate the mPFC, which decreases cognitive functioning. 

Does Fluoxetine interact with ADHD medications? 

Yes, Fluoxetine, which is an SSRI, interacts with amphetamines. Amphetamines are the drugs that are primarily prescribed to treat ADHD in children and adults. Amphetamines are metabolized by the enzyme CYP450 2D6, which is inhibited by Fluoxetine. This can increase amphetamine levels in the body and worsen side effects.

If you have anxiety or depression along with ADHD, your physician may prescribe you an antidepressant if the benefits outweigh the risks. If you notice unusual symptoms such as jitteriness, nervousness, or increased anxiety, report to your physician for further management. 

What to do if Fluoxetine is exacerbating ADHD symptoms? 

Medication: Consult your healthcare professional to determine the appropriate medication for your condition. If Fluoxetine is exacerbating your ADHD symptoms, other medications like stimulants (e.g. methylphenidate or amphetamines) and non-stimulants (e.g. atomoxetine, guanfacine) can help improve attention and impulse control.

Behavioural therapy: Consider behavioural interventions, such as Cognitive Behavioral Therapy (CBT) or parent training and psychoeducation, which can provide practical strategies to manage ADHD-related challenges. 

Organise tasks: The basic trait of ADHD is the inability to pay attention to a particular work. You can break down your tasks into smaller steps and use daily planners and reminders to maintain an organized plan. 

Alternative therapies: Alternative approaches such as mindfulness meditation, acupuncture or yoga may help some individuals with ADHD to manage their symptoms. 

Keep a symptoms journal: Monitoring ADHD symptoms involves close observation and communication with a healthcare provider. Maintain a journal and record daily observations related to your ADHD symptoms, such as mood, behavioural and cognitive changes. Any changes in focus, attention, impulsivity, or hyperactivity should be noted in the journal. 

Communicate with your healthcare provider: Attend regular follow-up appointments with your physician. Discuss any concerns about your medication with your physician. Have an open conversation regarding your side effects. 


The article above discusses the impact of Fluoxetine on ADHD. Studies have shown that Fluoxetine can exacerbate symptoms of ADHD, but the drug’s effects can differ from person to person. If you experience any side effects or a worsening of your current symptoms, it is recommended that you seek professional help.

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Popper CW. Antidepressants in the treatment of attention-deficit/hyperactivity disorder. Journal of Clinical Psychiatry. 1997 Jan 1;58(14):14-31. Available from:,cause%20frontal%20apathy%20and%20disinhibition.


Chantiluke K, Barrett N, Giampietro V, Brammer M, Simmons A, Murphy DG, Rubia K. Inverse effect of fluoxetine on medial prefrontal cortex activation during reward reversal in ADHD and autism. Cerebral Cortex. 2015 Jul 1;25(7):1757-70. Available from:


Xu P, Chen A, Li Y, Xing X, Lu H. Medial prefrontal cortex in neurological diseases. Physiological genomics. 2019 Sep 1;51(9):432-42. Available from:,emotion%2C%20motivation%2C%20and%20sociability.


Riddle MA, King RA, Hardin MT, Scahill L, Ort SI, Chappell P, Rasmusson A, Leckman JF. Behavioral side effects of fluoxetine in children and adolescents. Journal of Child and Adolescent Psychopharmacology. 1990;1(3):193-8. Available from:

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