Does taking extended release Adderall (amphetamine and dextroamphetamine) feel different than taking immediate release Adderall (amphetamine and dextroamphetamine)?

From the Guidelines

Taking extended release Adderall can feel different than taking immediate release Adderall due to its gradual and sustained effect, which can last about 10-12 hours, compared to the more rapid onset and shorter duration of immediate release Adderall, which lasts 4-6 hours. The difference in how these two formulations are experienced by patients is largely due to their distinct pharmacokinetic profiles. Extended release Adderall is designed to provide a smoother onset of effects, with fewer fluctuations throughout the day, and a more gradual decline in effectiveness 1. This is achieved through a formulation that releases the medication in two phases, with approximately 50% of the dose released immediately and the remaining 50% released about 4 hours later.

In contrast, immediate release Adderall tends to produce a more noticeable onset of effects, potentially stronger peak effects, and a more abrupt wearing off period, which some patients may describe as a "crash" 1. The choice between extended release and immediate release Adderall often depends on the patient's specific symptoms, daily schedule, and how their body metabolizes the medication. For instance, patients who require a more consistent level of medication throughout the day may prefer the extended release formulation, while those who need a quicker onset of action might prefer the immediate release version.

Some key considerations when choosing between these formulations include the potential for rebound effects, which may be lower with long-acting formulations, and the flexibility in dosing frequency and titration, which is greater with short-acting formulations 1. Additionally, factors such as decreased appetite, sleep disturbances, and increases in blood pressure and heart rate, which are common adverse effects of both methylphenidate and amphetamine, should be monitored and considered in the decision-making process 1. Ultimately, the decision to use extended release or immediate release Adderall should be based on the individual patient's needs and response to the medication, with careful consideration of the potential benefits and risks.

From the FDA Drug Label

The pharmacokinetics of the tablet and sustained-release capsule were compared in 12 healthy subjects The extent of bioavailability of the sustained-release capsule was similar compared to the immediate-release tablet. Following administration of three 5 mg tablets, average maximal dextroamphetamine plasma concentrations (Cmax) of 36. 6 ng/mL were achieved at approximately 3 hours. Following administration of one 15 mg sustained-release capsule, maximal dextroamphetamine plasma concentrations were obtained approximately 8 hours after dosing.

The pharmacokinetics of extended release Adderall and immediate release Adderall are different, with the extended release formulation having a later peak concentration (8 hours vs 3 hours) and a lower peak concentration (23.5 ng/mL vs 36.6 ng/mL) 2. This difference in absorption rate and peak concentration may result in a different subjective experience, with the extended release formulation potentially providing a more gradual onset and sustained effect, while the immediate release formulation may produce a more rapid onset and intense effect.

From the Research

Comparison of Extended Release and Immediate Release Adderall

• The main difference between extended release and immediate release Adderall is the way the medication is released into the body. Extended release Adderall is designed to release the medication slowly over a longer period of time, while immediate release Adderall releases the medication quickly [ 3, 4 ].
• Studies have shown that extended release Adderall can provide symptom control for a longer period of time, reducing the need for multiple doses throughout the day [ 3, 4,5 ].
• In terms of efficacy, both extended release and immediate release Adderall have been shown to be effective in reducing the symptoms of ADHD [ 6, 7 ].
• However, the extended release formulation may be associated with reduced immediate-release supplementation in adults with ADHD, regardless of baseline patient variables 5.

Pharmacokinetics and Bioavailability

• The pharmacokinetics of extended release Adderall have been studied, and it has been shown that the medication has a longer time to maximum concentration (Tmax) compared to immediate release Adderall 4.
• The bioavailability of extended release Adderall has also been studied, and it has been shown to be comparable to immediate release Adderall 3.
• The extended release formulation has been shown to be suitable for once-daily dosing, with a reduced need for multiple doses throughout the day 4.

Adverse Events and Safety

• Both extended release and immediate release Adderall have been associated with adverse events, including decreased appetite, insomnia, and abdominal pain [ 6, 7 ].
• The extended release formulation may be associated with a reduced risk of adverse events, particularly when compared to multiple doses of immediate release Adderall throughout the day 5.
• However, the overall quality of the evidence for the safety and efficacy of extended release Adderall is generally low to very low, due to the limited number of studies and the high risk of bias in many of the included studies [ 6, 7 ].