Adderall for Depression Off-Label: Risky, but Effective

Is Adderall Prescribed for Depression?

It sounds crazy, but Adderall is an effective off-label treatment for treatment-resistant depression. Adderall is a mixture of four different amphetamine salts.

Adderall is never prescribed as a first-line treatment for depression. Most psychiatrists start with conventional antidepressants with the fewest side effects, like SSRIs. Adderall is not approved for depression by the FDA, and thus doctors prescribe it off-label. Adderall use carries greater risk compared with more conventional antidepressants. Adderall is a tightly controlled, schedule II drug.

Ever since Freud treated patients for depression with Cocaine, psychostimulants have gotten a bad wrap. But amphetamines do have a place in the treatment of mood disorders. Vyvanse was recently reported to effectively treat postpartum depression,  with a low incidence of adverse effects. (Here’s a review comparing Vyvanse and Adderall, if you’re wondering what the difference is between the two drugs).

Some kinds of depression may be particularly responsive to Adderall (and other drugs in the same class).  Adderall shines when it’s used as an augmentation agent (added onto another drug) for treatment-resistant depression (TRD). Believe it or not, TRD is not a rare phenomenon. A significant fraction of patients are non-responders to conventional agents like SSRIs and are labeled TRD.

Amphetamines have a number of notable advantages and disadvantages compared with conventional antidepressants:

  • Adderall works rapidly; conventional antidepressants take 3+ weeks
  • Adderall improves social confidence and addresses anhedonic/apathetic symptoms; conventional antidepressants are not very effective for this purpose
  • Adderall may help address some of the cognitive effects of long-term depression (e.g., impaired concentration)
  • Adderall is a drug of abuse; it is associated with dependence, dose-escalation and withdrawal
  • Adderall is potentially neurotoxic in higher doses
  • Adderall adversely affects the cardiovascular system. It can exacerbate hypertension and stress the heart.

Some people will be very uncomfortable with the idea that amphetamines are ever used to treat depression. But there are sufferers of TRD that would be unable to function were it not for low-dose psychostimulants. The majority of patients prescribed Adderall for depression never escalate their dose and continue to derive benefits.

The Problem With Conventional Antidepressants

Adderall also addresses depressive symptoms that other conventional antidepressants don’t touch.

There’s actually some tentative evidence that SSRIs and other similar agents may worsen apathy, motivational problems and anhedonia in depressed patients, despite uplifting mood overall. This effect may stem from the fact that SSRIs globally increase serotonin in the brain. Serotonin inhibits dopamine release in specific brain regions, which can result in apathy and anhedonia. This state is sometimes referred to as “hypofrontality.” Adderall directly relieves this state of hypofrontality, by eliciting dopamine and norepinephrine release which restore executive function and motivation.

Disadvantages of Adderall

SSRIs may make exacerbate apathy and anhedonia, but Adderall is not a benign substance either. At high doses, Adderall is associated with neurotoxicity to the dopamine system. Adderall’s side effect burden can also be hard to swallow. Adderall is associated with cardiovascular side effects like hypertension, and can worsen anxiety (or paradoxically alleviate anxiety) for some or bring out latent schizophrenia. Excessive doses of Adderall may cause paranoia and hallucinations in predisposed individuals.

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