Although Adderall is only FDA-approved for the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy, it has been used rarely and off-label to treat depression that has not responded to other treatments. However, this is controversial and there is a lack of good quality evidence to support its use. There is no evidence that Adderall helps with anxiety and in many people with pre-existing mood disorders, Adderall can make depression and/or anxiety worse.

The history of Adderall use for depression

Adderall is a combination of mixed amphetamine salts, and amphetamine was first synthesized in the late 1800s, although it was not used clinically until 1927. By the 1930s, it was found to alleviate hyperactive syndrome in children, and for the next 20 years, it was used to treat conditions such as depression, obsessive-compulsive disorders, and schizophrenia.

But by the 1950s, antidepressants had been discovered, and these largely replaced amphetamines as a treatment for mood disorders. Increasing abuse of amphetamines in the 1960s reduced their use even further.

Nowadays, using psychostimulants such as Adderall for the treatment of depression is not very common and has been criticized by some experts. But some centers, such as the Zurich Psychiatric University Hospital in Switzerland have used amphetamines and methylphenidate to treat severe treatment-resistant depression since the 1930s, especially in people who also have prominent fatigue and apathy.

A retrospective study that looked back on the records of 65 people with treatment-resistant depression who were treated with psychostimulants (17 treated with amphetamines, 35 with methylphenidate, and 13 treated with both amphetamines and methylphenidate, for an average duration of 10 years) at the Zurich hospital reported:

• Psychostimulants were given in combination with tricyclic antidepressants (48 people), SSRIs (35), MAOIs (8), lithium (35), and carbamazepine (22). Some patients received two or more antidepressants and mood stabilizers
• 38 patients improved on treatment with psychostimulants, whereas 26 remained unchanged or deteriorated
• The best response to psychostimulant treatment was seen in people with inhibited or anxious types of depression (27 out of 42 patients improved). In the group of patients with agitated depression, 11 out of 22 patients improved. For bipolar depression, 8 out of 16 patients improved
• Improvement was noted in 6 out of 8 patients who were treated with a psychostimulant and an MAOI; 30 out of 48 patients treated with a psychostimulant and a tricyclic; 21 out of 35 patients treated with a psychostimulant and an SSRI; 21 out of 35 patients treated with a psychostimulant and lithium; and in 12 out of 22 patients treated with a psychostimulant and carbamazepine
• Additional treatment with benzodiazepines was required in 21 out of 30 patients treated with amphetamines and in 36 out of 48 patients treated with methylphenidate (13 patients received both drugs)
• Side effects were reported in 51 out of 65 patients treated with psychostimulants, including nausea and headache in 32 patients, restlessness in 29 patients, agitation in 25 patients, sleep disturbances in 18 patients, and circulatory disorders in 6 patients
• None of the depressed patients developed drug dependency or addictive behavior
• In the 38 patients who experienced a beneficial effect from treatment with psychostimulants, 35 patients reported an improvement in energy, 26 in mood, 26 in motor activity, 15 in symptoms of psychomotor retardation, 11 in vigilance, and 7 in social interactions. Negative symptoms did not improve in the 4 patients with schizoaffective disorders.
• The greatest improvement reported following treatment with psychostimulants was in motor activity, mood, and psychomotor activity. Some patients showed an improvement in memory and concentration and some experienced euphoria.
• Psychostimulants work quickly within 30 minutes to 1 or 2 hours and their effects last approximately 4 hours. Patient response to psychostimulants may vary from year to year.
• Not every person responds in the same way to psychostimulants, due to individual differences in genetics and other factors. If no effect is seen with one psychostimulant, another may be tried.
• The use of psychostimulants, such as Adderall, in people with depression, must be carefully monitored.

Bottomline

Adderall in combination with antidepressants or other mood-stabilizing agents may help improve energy, mood, and activity levels in people with very hard-to-treat depression. However, this is an off-label use, and good quality trials to support this benefit are lacking; evidence mainly comes from specialist psychiatric hospitals and retrospective surveys. Some authors have reported a lack of effect or even deterioration following the addition of psychostimulants to people with depression. There is no evidence that Adderall helps with anxiety, and it may make it worse.