Antidepressants and ADHD
Stimulants are the first-line treatment for ADHD, but not everyone responds to or tolerates them. Some antidepressants — particularly those that increase dopamine — may help manage attention, motivation, and executive function, especially when depression or anxiety is also present.
It has been estimated that almost half of individuals with ADHD experience a depressive episode before the age of 30. As such, treating the comorbid disorder with antidepressants can present an opportunity to also alleviate certain ADHD symptoms.
Knowing the connection between antidepressants and ADHD, as well as what antidepressants work on dopamine, is likely to help improve the outcome of individuals with ADHD.
ADHD
ADHD is a neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. Its pathophysiology involves dysregulation in neurotransmitter systems, particularly dopamine and noradrenaline.
Classically, ADHD is treated with stimulant medications such as methylphenidate or amphetamines. These drugs enhance neurotransmitter function, improving attention and impulse control by providing a short-acting increase in synaptic noradrenaline and dopamine.
Various Antidepressants in ADHD
Antidepressants constitute a diverse class of drugs designed to alleviate symptoms of depression and various mental health disorders. They encompass different subclasses, each affecting neurotransmitter levels in distinct ways.
While their primary use revolves around depression management, they have shown efficacy in treating conditions beyond depression, including anxiety disorders, OCD, chronic pain and even ADHD.
When considering antidepressants for managing ADHD symptoms, attention centers on increasing dopamine levels.
How Antidepressants Can Increase Dopamine
Despite the name, selective serotonin reuptake inhibitors (SSRIs) do not solely act on the serotonergic system, and the effects of noradrenaline reuptake inhibitors (NRIs, SNRIs) also serve to increase dopamine.
Lastly, certain antidepressants, like Bupropion, directly inhibit the reuptake of dopamine and are frequently used off-label for ADHD.
The Three Main Mechanisms
1) Stimulation of dopamine release via serotonin 1A receptors (5-HT1A-R), which increases prefrontal cortex dopamine.
2) Inhibition of dopamine reuptake by blocking the noradrenaline transporter (NET), since the noradrenaline transporter is responsible for the dopamine reuptake in the prefrontal cortex.
3) Direct inhibition of dopamine reuptake by blocking the dopamine transporter (DAT).
| Class | Mechanism | Common Drugs | Clinical Impact |
|---|---|---|---|
| SSRI | 5-HT1A receptor stimulation | Fluoxetine, Sertraline | Low |
| SNRI | 5-HT1A receptor stimulation; Blocks NET |
Venlafaxine, Duloxetine | Medium |
| NRI | Blocks NET |
Atomoxetine, Reboxetine | High |
| NDRI | Blocks DAT; Blocks NET | Bupropion | High |
| TCA | Works through several mechanisms | Desipramine, Nortriptyline, Clomipramine | Medium |
SSRIs
SSRI is short for selective serotonin reuptake inhibitors. They are the most commonly used class of antidepressants. Certain SSRIs are not completely selective for serotonin, depending on the dosage. For example, Fluoxetine can increase brain dopamine at higher dosages, which in theory may help to improve attention and energy levels. In reality, they're rarely used as monotherapy for ADHD due to their low clinical impact.
SNRIs
SNRI stands for Serotonin-Noradrenaline Reuptake Inhibitor. The most commonly known drugs are Venlafaxine and Duloxetine. Venlafaxine is occasionally a suitable option in patients with depression and comorbid ADHD symptoms. Treatment generally requires a higher dose, as Venlafaxine only affects the serotonergic system at low doses.
NRIs
NRI stands for Noradrenaline Reuptake Inhibitor. This group of medications is technically not antidepressants as they have little to no effect on antidepressant symptoms. Atomoxetine is an effective non-stimulant ADHD medication. Another NRI, Reboxetine, is available in Europe and has only a minor effect on depressive symptoms.
NDRIs
Noradrenaline-Dopamine Reuptake Inhibitors, which target both noradrenaline and dopamine reuptake. The most commonly known NDRI antidepressant is Bupropion, which is frequently used as a first-line antidepressant and third-line medication in the treatment of ADHD. The primary effect comes from NET inhibition.
TCAs
Tricyclic Antidepressants. This is an older class of antidepressants that impacts multiple neurotransmitters. They block the reuptake of serotonin, noradrenaline and dopamine, while also affecting histamine, alpha, and muscarinic receptors. Due to severe side effects, they are only considered in niche and comorbid cases.
Comorbid Anxiety and Depression in ADHD
In some cases, individuals with ADHD may experience persistent symptoms of anxiety or depression that don't subside with regular ADHD medication. This scenario may require combining antidepressants with ADHD-specific medications.
SSRIs are often the initial choice, as they have been proven beneficial in managing both anxiety and depression. For example, Zoloft and Ritalin are commonly prescribed together in these instances.
For those with ADHD and depression who are not taking stimulants, Bupropion might be prescribed to address symptoms of both conditions. Additionally, some research suggests Atomoxetine's potential in alleviating anxiety in young patients with ADHD and comorbid anxiety.
Get Help With Your ADHD
The decision to incorporate antidepressants into ADHD treatment requires careful consideration and professional guidance. Always consult a psychiatrist to ensure individual, effective and safe treatment strategies.
WhatMedicine.Org also offers a free online tool that can help you in the process of finding a suitable ADHD medication. Do note that it is intended for general informational purposes only and is not a substitute for professional medical advice.
Last update: August 1, 2025
Disclaimer: The information provided is intended for general informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always consult with a qualified healthcare provider, such as a physician, before starting any new treatment or making changes to your existing treatment plan. Individual responses to treatment may vary, and a healthcare professional can provide personalized guidance based on your specific needs and circumstances. If you are experiencing severe or persistent symptoms of disease or mental illness, seek immediate medical attention.