What psychotropic medications interact with Adderall (amphetamine and dextroamphetamine)?

From the Guidelines

Adderall should not be taken with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis, and caution is advised when combining it with serotonergic drugs, such as SSRIs, SNRIs, and certain tricyclic antidepressants, as they can increase the risk of serotonin syndrome 1. When considering the use of Adderall with other psychotropic medications, it is essential to weigh the potential benefits against the risks of adverse interactions.

• MAOIs, such as phenelzine, tranylcypromine, and selegiline, should be discontinued at least 14 days before starting Adderall to avoid hypertensive crises 1.
• Serotonergic drugs, including SSRIs (e.g., fluoxetine, sertraline), SNRIs (e.g., venlafaxine, duloxetine), and certain tricyclic antidepressants, can increase the risk of serotonin syndrome when combined with Adderall 1.
• Antipsychotics like haloperidol or risperidone may reduce Adderall's effectiveness or worsen side effects.
• Medications that acidify urine (e.g., ascorbic acid) can decrease Adderall absorption, while those that alkalinize urine (e.g., sodium bicarbonate) can increase its effects and potential toxicity.
• Stimulants like modafinil or methylphenidate can have additive effects when combined with Adderall, potentially increasing cardiovascular risks. It is crucial to carefully monitor patients for signs of adverse interactions, such as serotonin syndrome, and to adjust treatment regimens accordingly 1. In clinical practice, a conservative approach is recommended, with careful consideration of the potential risks and benefits of combining Adderall with other psychotropic medications 1.

From the FDA Drug Label

Acidifying agents – Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid hydrochloride, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines. Antidepressants, tricyclic – Amphetamines may enhance the activity of tricyclic or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated MAO inhibitors – MAOI antidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism. Antihistamines – Amphetamines may counteract the sedative effect of antihistamines. Chlorpromazine – Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines, and can be used to treat amphetamine poisoning. Lithium carbonate – The stimulatory effects of amphetamines may be inhibited by lithium carbonate.

The psychotropic medications that interact with Adderall (amphetamine and dextroamphetamine) are:

• Tricyclic antidepressants: may enhance the activity of amphetamines and potentiate cardiovascular effects
• MAO inhibitors: slow amphetamine metabolism and potentiate amphetamines, increasing the risk of hypertensive crisis
• Antihistamines: may have their sedative effect counteracted by amphetamines
• Chlorpromazine: blocks dopamine and norepinephrine reuptake, inhibiting the central stimulant effects of amphetamines
• Lithium carbonate: may inhibit the stimulatory effects of amphetamines 2

From the Research

Psychotropic Medications Interacting with Adderall

The following psychotropic medications may interact with Adderall (amphetamine and dextroamphetamine):

• Monoamine oxidase inhibitors (MAOIs) due to the risk of serotonin toxicity and hypertensive crises 3, 4
• Selective serotonin reuptake inhibitors (SSRIs) as they can increase the risk of serotonin syndrome 4, 5
• Other serotonergic drugs, such as dextromethorphan, chlorpheniramine, and brompheniramine, which can increase serotonin levels 3
• Sympathomimetic drugs, such as phenylephrine and oxymetazoline, which can elevate blood pressure 3
• Certain opioid analgesics, like pethidine (meperidine), tramadol, methadone, and dextromethorphan, that have serotonergic activity 4

Mechanisms of Interaction

These interactions can occur through various mechanisms, including:

• Pharmacodynamic interactions, where the combination of drugs enhances central nervous system serotonin activity 4, 5
• Pharmacokinetic interactions, where one drug affects the metabolism of another, potentially leading to increased or decreased concentrations of the affected drug 6, 7

Clinical Implications

It is essential to be aware of these potential interactions to avoid adverse consequences, such as serotonin syndrome or hypertensive crises, which can be life-threatening 3, 4, 5. Healthcare providers should carefully monitor patients taking Adderall and other psychotropic medications, and patients should be educated about the risks and symptoms of these interactions 3, 7.