Other off-label ADHD medications for adults

Beyond the stimulants and the two adult-approved non-stimulants (atomoxetine and viloxazine), a handful of other medicines are sometimes mentioned for adult ADHD. The most common are modafinil, tricyclic antidepressants such as desipramine, and, in specialist settings, antipsychotics added to ADHD treatment. None is FDA-approved for ADHD. This page explains what each one is approved for, what the adult ADHD evidence shows, and why guidelines do not treat them as first-line choices. Labels and studies were checked on October 19, 2026. Nothing here suggests starting or stopping a medication.

Two other off-label options have their own pages: bupropion (Wellbutrin) and guanfacine and clonidine.

What "off-label" means here

The FDA explains that once a drug is approved, healthcare providers generally may prescribe it for an unapproved use when they judge it medically appropriate, but that the FDA has not determined the drug is safe and effective for that use. The FDA suggests patients ask what the drug is approved for, whether approved alternatives exist, and what studies support the unapproved use. Those questions fit every medicine on this page.

The short version

Modafinil

Modafinil is a wakefulness-promoting drug. The Provigil label indicates it "to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD)." It is a Schedule IV controlled substance, so it is not an escape from controlled-substance rules.

The adult ADHD evidence is negative:

• A nine-week, randomized, double-blind trial of 330 treated adults with ADHD (J Atten Disord) found no statistically significant difference from placebo at any of four doses. The authors concluded modafinil "did not demonstrate a benefit on ADHD symptoms in adults."
• The 2018 Lancet Psychiatry network meta-analysis found that in adults, amphetamines, methylphenidate, bupropion and atomoxetine were better than placebo on clinician ratings, "but not modafinil." Modafinil was also less well tolerated than placebo in adults.

Label points worth knowing: serious rash, including Stevens-Johnson syndrome, has been reported, and the label says to stop at the first sign of rash unless it is clearly unrelated. It can also reduce the effectiveness of hormonal contraceptives during use and for one month after stopping, and the label recommends alternative or additional contraception. Psychiatric symptoms and known heart disease call for caution.

Tricyclic antidepressants (desipramine)

Tricyclic antidepressants are a class of depression medicines. Desipramine is one that has been tested in a placebo-controlled trial in adults with ADHD. Its current label lists one indication: "treatment of depression."

Evidence in adults comes mainly from a 1996 six-week, double-blind, placebo-controlled trial of 41 adults published in the American Journal of Psychiatry. ADHD symptoms improved significantly more with desipramine, and 68% of treated participants met the study's responder criteria compared with none on placebo. That is a single small study from three decades ago, and the 2018 network meta-analysis did not include tricyclics among the drugs it compared.

Safety is the main reason tricyclics sit low on the list:

• Boxed warning: like all antidepressants, an increased risk of suicidal thinking and behavior in children, adolescents and young adults in short-term studies.
• Heart effects: the label urges extreme caution in people with cardiovascular disease because of conduction defects, arrhythmias and heart attack, and in people with a family history of sudden death or heart rhythm problems. It also describes reports of sudden death in children treated with desipramine.
• Contraindications: use with or within 14 days of an MAOI, and the acute recovery period after a heart attack.
• Anticholinergic effects: caution with urinary retention or glaucoma.

A prescriber considering any tricyclic would typically review heart history first. More background is in ADHD medication, heart health and blood pressure.

Antipsychotics and other add-ons

The UK's NICE guideline NG87 says not to offer atypical antipsychotics in addition to stimulants for people with ADHD and coexisting pervasive aggression, rages or irritability without advice from a tertiary ADHD service. They are not ADHD treatments in their own right, and none is FDA-approved for ADHD.

Why these are not first-line

Three threads of evidence point the same way:

1. Comparative trials. A 2025 component network meta-analysis of 113 trials in adults found that stimulants and atomoxetine "were the only interventions with evidence of beneficial effects" on core ADHD symptoms in the short term, supported by both self-ratings and clinician ratings.
2. Guidelines. NICE recommends lisdexamfetamine or methylphenidate first for adults, then atomoxetine, and says not to offer medication outside its list for ADHD without advice from a tertiary ADHD service.
3. FDA review. None of these drugs has been through FDA review for ADHD, so their labels contain no ADHD efficacy or dosing information.

That does not mean they are never used. When approved options have not worked or are not suitable, a specialist may weigh one of them, ideally with a clear goal and a way to measure whether it helps. The general approach is described in how doctors choose an ADHD medication.

New York and New Jersey notes

Modafinil is a Schedule IV controlled substance. New York's Schedule II rules in 10 NYCRR 80.67 and New Jersey's telehealth rules in P.L.2026, c.40, which address Schedule II drugs, do not apply to it; federal law allows up to five refills of a Schedule IV prescription within six months (21 CFR 1306.22). Desipramine and antipsychotics are not controlled. For how prescription rules work for ADHD stimulants, see New York's rules and New Jersey's rules.

Questions to ask if one of these is suggested

• What is this drug approved for, and are there approved ADHD options I have not tried?
• What studies support it for adults with ADHD?
• What safety checks are needed first, such as an ECG or a review of contraception?
• How will we decide whether it is working, and when would we stop?

Dr. Shershow evaluates adults for ADHD and discusses medication options, including their evidence and FDA status, as part of a treatment plan. See adult ADHD treatment, or read about the medications approved for adults in 2026.