Bupropion for ADHD

Trade names: Elontril, Wellbutrin, Zyban
Active ingredient name before 2000: Amfebutamone

The active ingredient bupropion is an amphetamine derivative.¹
It is not classically classified as a stimulant, although it has a stimulating effect - like nicotine and caffeine.
Bupropion does not require a narcotic prescription.

Bupropion is active as the active ingredient itself and is metabolized to hydroxybupropion as well as threohydrobupropion. All three are potent norepinephrine reuptake inhibitors.² Hydroxybupropion, for example, can reach concentrations up to 16-20 times that of bupropion.[7]

Bupropion acts as a dopamine and norepinephrine reuptake inhibitor. In rats, the dopamine : norepinephrine effect ratio is 2:1³

In addition, bupropion also has a weak dopamine and norepinephrine secreting effect,⁶ as well as a minor serotonergic effect.

Bupropion decreases TNF-alpha levels.⁷

Bupropion is further a non-competitive antagonist of several nicotinic acetylcholine receptors (AChR).⁸

Bupropion is reported to have comparable effect sizes with respect to ADHD as methylphenidate, according to three studies; another study found a weaker effect than methylphenidate⁹

Bupropion has an (even) stronger activating / drive-increasing effect than nortryptiline and is thus indicated for more severe symptoms of ADHD-I (without hyperactivity). The administration of bupropion in ADHD-HI or ADHD-C sufferers (with hyperactivity) can trigger aggression or jitteriness.

Two studies in 30 and 47 adults with AD(HS) with 300 mg and up to 400 mg bupropion/day, respectively, found trends for efficacy of bupropion in ADHD without statistical significance.¹⁰¹¹

Useful results when used alone in ADHD have been found in practice only at quite high doses of 400 to 450 mg/day, which is why the updated European consensus on the diagnosis and treatment of ADHD in adults recommends using bupropion only when neither MPH nor amphetamine medications are effective (double nonresponding).¹²

Bupropion can be a helpful adjunct to stimulant medication in individual cases.
In combination drug use for ADHD, a much lower dosage is required than would be usual for use as an antidepressant.
In ADHD with comorbid depression, bupropion may be helpful.

In depression, a serum hydroxybupropion concentration greater than 860 ng/ml should be achieved for a positive response. The therapeutic reference range for depression is between 850 and 1500 ng/ml hydroxybupropion.⁵

Bupropion is a CYP2D6 inhibitor, so caution should be exercised when administering other drugs that affect CYP2B6. Concomitant administration of CYP2B6 inhibitors such as clopidogrel or ticlopidine increased bupropion AUC levels by 60% and 90%, respectively. Concomitant administration of carbamazepine (inducer of CYP2B6 and CYP3A4) decreased bupropion AUC by 90% and an increase hydroxybupropion AUC by 50%.⁵