According to Wikipedia, antidepressants can treat ADHD, not just depression. How exactly?

So far I know, ADHD is caused partly (primarily?) by a dopamine deficiency. Do antidepressants do something to address the dopamine deficiency? What is it? Is it in the same way that stimulants or methylphenidate address the dopamine deficiency?

Wikipedia describes how methylphenidate treats ADHD:

Methylphenidate's mechanism of action involves the inhibition of catecholamine reuptake, primarily as a dopamine reuptake inhibitor. Methylphenidate acts by blocking the dopamine transporter and norepinephrine transporter, leading to increased concentrations of dopamine and norepinephrine within the synaptic cleft. This effect in turn leads to increased neurotransmission of dopamine and norepinephrine. Methylphenidate is also a 5HT1A receptor agonist.[11]

Wikipedia describes antidepressants:

most antidepressants function by inhibiting the reuptake of neurotransmitters serotonin, dopamine, and norepinepherine

Okay so both methylphenidate and most antidepressants inhibit reuptake of dopamine, but do those antidepressants also block the dopamine transporter, leading to an increased concentration of dopamine within the synaptic cleft leading to an increased neurotransmission of dopamine?

  • Are you asking if these antidepressants are DRIs?
    – HDE 226868
    Dec 22, 2015 at 1:13
  • @HDE226868 So antidepressants that are DRIs can treat ADHD?
    – BCLC
    Dec 23, 2015 at 20:52
  • From what I understand, yes, but I'm not positive.
    – HDE 226868
    Dec 24, 2015 at 13:29
  • @HDE226868 Got a paper related to what you understand? :)
    – BCLC
    Dec 26, 2015 at 2:45
  • Bupropion (a NDRI) is indicated for the treatment of depression in the USA. Here is a study on bupropion for ADHD: ncbi.nlm.nih.gov/pmc/articles/PMC2416755. As I mentioned in my answer, SNRIs and TCAs (where their effect on ADHD is meditated through their reuptake of norepinephrine) are more commonly used for ADHD. Modafinil is also a weak DRI, which was almost approved for ADHD... But wasn't as it caused SJS in some patients
    – user1571
    Jan 25, 2016 at 23:40

1 Answer 1


An overview of the monoamine neurotransmitters

Dopamine (DA) is a catecholamine neurotransmitter associated with attention and motivation (9). It is implicated in various other conditions such as psychosis, and Parkinson's disease (9).

Noradrenaline (NE - norepinephrine in North America) is a catecholamine neurotransmitter that plays a role in attention and arousal (9). NE is produced from DA. (5)

Serotonin (5-HT) in an indolamine. 5-HT modulates mood, aggression, dominance, appetite, and sleep (9).

The pathogenesis of ADHD

The most prevalent theory of the pathogenesis of ADHD is that it results from an "deficiency" of some of the various monoamine neurotransmitters. DA, NE, and to a lesser degree 5-HT, are all implicated (5)(6). DA is the neurotransmitter most heavily associated with ADHD, and its role in the mediation of the disease was primarily elucidated by methylphenidate's effect on dopaminergic neurotransmission (6).

Pharmacodynamics of antidepressants

Different antidepressants work through different mechanisms. The major antidepressants are segregated into three classes: Monoamine Oxidase Inhibitors (MAOIs), TCAs, and SSRIs.

MAOIs "increase" the levels of all of the monoamine (DA, NE, and 5-HT, among others) neurotransmitters by preventing the deamination of these neurotransmitters by inhibiting the activity of the monoamine oxidase (8).

The affinities for different transporter proteins varies widely in the TCA class. TCAs are generally considered to inhibit the reuptake of NE and 5-HT, although this varies greatly from TCA to TCA. Clomipramine, for instance, has a much higher affinity for the serotonin transporter (SERT) than the noradrenaline transporter (NET) (7). Amitriptyline has relatively balanced 5-HT and NE action, whereas desipramine and nortriptyline very selective for NET. (7)

SSRIs (as the name suggests) are most potent at inhibiting SERT.

The role of antidepressants in the treatment of ADHD

Tricyclic Antidepressants (TCAs) are the main class of antidepressants used to treat ADHD typically in conjunction with a stimulant. Most TCAs inhibit the reuptake of NE into the presynaptic clef. This is a mode of action shared with stimulant medications. Their efficacy in the remediation of ADHD symptoms is inferior to that of the stimulants (3). Due to the lack of action on dopamine neurotransmission, TCAs only treat the hyperactive element of ADHD - in other words, they often fail to improve concentration (3). Desipramine, because of its selectivity for NE reuptake inhibition, is the TCA most frequently used for ADHD (2).

Selective Serotonin Reuptake Inhibitors (SSRIs) such as fluoxetine are occasionally used in conjuction with stimulants (3). Contaminant use of fluoxetine with a stimulant results in a significant increase in school performance, and attenuation of irritability: "things that used to bother me a whole don't seem to bother me much anymore" (3). Low serotonin is associated with impulsivity and aggression (3). It's hypothesized in (3) that fluoxetine may influence the brain's response to DA.


  1. Treatment of adults with attention-deficit/hyperactivity disorder, http://www.ncbi.nlm.nih.gov/pubmed/1938791
  2. Tricyclic antidepressants for attention deficit hyperactivity disorder (ADHD) in children and adolescents. http://www.ncbi.nlm.nih.gov/pubmed/25238582
  3. Fluoxetine and methylphenidate in combination for treatment of attention deficit disorder and comorbid depressive disorder, http://www.drthomasebrown.com/pdfs/fluoxetine.pdf
  4. Treatment of ADHD with fluoxetine: a preliminary trial, http://www.ncbi.nlm.nih.gov/pubmed/1938791
  5. Functional Roles of Norepinephrine and Dopamine in ADHD http://www.medscape.org/viewarticle/523887
  6. Attention-deficit hyperactivity disorder (ADHD):an updated review of the essential facts
  7. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014120/
  8. The Role of Monoamine Oxidase Inhibitors in Current Psychiatric Practice
  9. Chapter 12: Biogenic Amine Neurotransmitters http://neuroscience.uth.tmc.edu/s1/chapter12.html

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