Adderall

The short version: Adderall is an effective treatment for ADHD, generally preferred to Ritalin in adults. Typical doses are between 5 mg and 60 daily, usually split up throughout the day. Adderall XR is long-acting Adderall. Vyvanse is very long-acting Adderall that gives some people fewer side effects. Risks are relatively low if you stick to the prescribed amount. Most common side effects are loss of appetite, feeling wired and jittery, headaches, sleep problems, and a “crash” when it runs out. If you get the crash, taper your doses, switch to XR or Vyvanse, or supplement with l-tyrosine. Anything that makes your stomach more acidic or alkaline will change your level of Adderall, sometimes dramatically.

The long version:

1. Is Adderall the right stimulant for me?

There are two commonly used families of stimulant for ADHD: Adderall and Ritalin. Most adults will find drugs in the Adderall family more effective.

See for example this survey of 4,425 ADHD patients by ADDitude Magazine, where 52% of adult Adderall users described their treatment as very effective, compared to only 41% of adult Ritalin users. Only 12% of Adderall users described it as ineffective, compared to 22% of Ritalin users.

More formal studies find the same thing. Faraone does a meta-analysis comparing both drugs in children (not exactly our population of interest, but this is the best I can find) and finds Ritalin to have an effect size of around 0.9 and Adderall of around 1.3 (higher means more effective). A separate meta-analysis by Stuhec, Lukic, and Locatelli finds two Adderall-family drugs to have effect sizes of 0.6 – 0.9, compared to Ritalin’s 0.5.

About 80% of my patients who have tried both tell me they prefer Adderall (informal estimate). Along with Adderall being more effective, they complain that Ritalin makes them feel more “robotic” (note the Additude survey shows Ritalin users about half again as likely to complain of “dampened personality”). This isn’t to say that Adderall is better for everyone – just that it’s a better choice to try first.

Does Ritalin have any advantages? The main advantage is that it’s considered harder to get addicted to. But addiction to ADHD drugs is already very unlikely (see the section on Addiction below), and realistically it’s less addictive because it is a worse drug which people like less. Also, there are now members of the Adderall family at least equally suitable for people at risk of addiction (see the section on Vyvanse below). Another Ritalin advantage is that it lasts less time, so if you want very fine-grained control over exactly when you are or aren’t stimulated Ritalin may be a better choice. But you probably do not need this much control. I understand Ritalin may have other advantages for children, but I’m not a child psychiatrist and don’t understand it well enough to comment on.

2. What medications are in the Adderall family? What are the advantages and disadvantages of each?

The Adderall family is based around a chemical called amphetamine. Like many organic chemicals, it comes in two mirror-image versions, d-amphetamine (“right-handed amphetamine”) and l-amphetamine (“left-handed amphetamine”). Most of the psychiatric benefits of amphetamine come from d-amphetamine, but a small number of people may respond better to l-amphetamine, or l-amphetamine might modulate the effects of d-amphetamine, or there might be some other reason why l-amphetamine might be good. Nobody understands this very well.

Adderall itself is 75% d-amphetamine and 25% l-amphetamine. More specifically, it’s a combination of four different kinds of amphetamine salts, two of which are 50-50 d/l, and two of which are 100% d (this is why sometimes Adderall bottles will say “mixed amphetamine salts”). In theory, having so many different salts means they all take different amounts of time to dissolve, and so instead of hitting you like a freight train and then crashing like a missile, you’ll gradually get more and more stimulated as the different salts dissolve one by one, then get less and less stimulated as they exhaust themselves one by one. There isn’t a huge amount of research showing this actually works and we currently just take it on faith.

Dexedrine is 100% d-amphetamine. Sometimes if people have side effects on Adderall, they won’t have those side effects on Dexedrine, presumably because the l-amphetamine was causing the side effects. Most people slightly prefer Dexedrine to Adderall, but this one does hit you like a freight train and a lot of people prefer to avoid it for that reason.

Evekeo is a 50-50 d/l mix, ie it has even more of the possibly-useless l-amphetamine than Adderall does. There isn’t any great reason to try this one, although some researchers think a few people with odd genetics might respond better to the l than the d version, so if somebody somehow knew they were one of those people they could give Evekeo a try. Mostly pharma companies just invented this to have a new form of Adderall they could sell for a little extra money since it was newer; unless you have very odd biochemistry you should probably ignore it.

Vyvanse is lisdexamphetamine. That is, it’s 100% d-amphetamine, like Dexedrine, but the d-amphetamine is attached to an inert molecule called lysine. Your body gradually removes the lysine, meaning that the d-amphetamine takes effect only very gradually, instead of hitting you like a freight train. In theory this combines the advantage of Dexedrine (gives you the pure active form without extra side effects from l-amphetamine) with the advantages of Adderall (comes on more gradually). Most of my patients give it very high ratings, and I think it succeeds at being the best of all worlds. Except it’s still on-patent, which means it costs ~10x as much as any other form of Adderall, so most people will want to give it a pass until the price comes down in a few years. One group who may want to consider it are people at high risk of addiction. Because your body processes Vyvanse so slowly, it’s (in theory) impossible to abuse – no matter how much you snort or inject or overdose on or whatever, it will still convert to the active form gently and gradually (but please don’t test this). These people should ask their insurance about helping them afford this medication.

Adderall XR is Adderall in a special capsule that makes it last longer – 8 hours instead of 4. This is useful for people who need Adderall for the entire day, but don’t want to / won’t remember to take a second pill. Some people also find it’s more gradual than taking two pills – instead of up-down-up-down it’s a single smooth “hill”. Other people don’t find this is true (and if someone in this second group of people needs smoother dosing, they will have to get Vyvanse).

Zenzedi is just Dexedrine XR.

Mydayis, Adzenys, Dyanavel, etc, etc, etc, are other attempts to make Adderall last different amounts of time, similar to Adderall XR but using slightly different technology. These all cost more and have ridiculous names and I have never been able to figure out any situation when I would ever want to use them. You can probably safely ignore all of these and get on with your life.

Desoxyn is prescription methamphetamine. Methamphetamine is a faster-acting, stronger, and more addictive form of amphetamine. It is 100% legal to prescribe it for ADHD, but I have never been brave enough to try, so I cannot give expert commentary on it. Anecdotally, patients who have used this say it is amazing. I have no reason to doubt them, but would recommend avoiding it anyway.

3. How should I know which medication in the Adderall family to try?

I tell my patients to start with Adderall. If they get too many side effects, I try to switch them to Dexedrine.

If one of those two works, then we try to determine the right schedule for them. Some patients prefer shorter-acting medications so they have more control over dosing – for example, they might want to take an Adderall in the morning so they can concentrate in class, but have it out of their system in the afternoon so they can relax and hang out with friends. Other patients prefer longer-acting medication because they expect to need it all day. Patients who prefer short-acting can stay on Adderall or Dexedrine; patients who prefer long-acting can switch to Adderall XR or Zenzedi.

If a patient has a history of addiction, or finds that even an XR medication doesn’t last long enough, or experiences their medication as a series of annoying jumps and crashes throughout the day – and has good enough insurance to afford it – I may switch them to Vyvanse.

4. What are possible side effects of Adderall?

The most common side effects of Adderall (percentages cobbled together in an unprincipled way from here and here) are:

Loss of appetite: 35%
Sleep disturbances: 28%
Irritability: 25%
Dampened personality: 11%

…but all of these numbers need big asterisks next to them.

Loss of appetite is most common when first starting Adderall. After a few weeks, most people will find their appetite comes back. If someone keeps having low appetite on Adderall, they can usually find a dosing schedule where they eat breakfast before they take it and dinner after it wears off. If they want lunch too, they might need to use a short-acting form of Adderall so they can eat lunch after it runs out, then take a second one for the afternoon.

Sleep disturbances are very predictable: they happen if Adderall is still in your body when you’re trying to sleep. You can avoid these by taking Adderall earlier in the morning, or by taking a shorter-acting form of the medication. I have only very rarely had any patients who still have trouble with sleep after getting this explained to them.

Irritability can go either way. Some people are very irritable on Adderall. Other people are less irritable.

5. Are there long-term side effects of Adderall?

As with any medication, it’s hard to say for sure because we cannot ethically perform the decades-long randomized controlled trials we would need to do to study this. The most likely answer is that very long term Adderall slightly increases your absolute risk of Parkinson’s disease by about 1-2%. It probably does not substantially increase your risk of heart attack, stroke, or any other major disease.

The Parkinson’s claim comes from studies like this and this finding that lifetime prescription amphetamine users get Parkinson’s at about 60% higher rates than non-users. This corresponds to evidence from methamphetamine abusers finding that their much higher doses give them Parkinson’s at a much higher rate, and it possibly matches preliminary evidence from squirrel monkeys randomized to receive amphetamines. A 60% increase in relative risk of Parkinson’s corresponds to about a 1% increase in absolute risk for Parkinson’s, so for every 100 people who take Adderall, there will be one extra case of Parkinson’s. Adderall-induced Parkinson’s strikes during old age just like most other cases of Parkinson’s. Studies suggest Ritalin probably causes Parkinson’s at about the same amount as Adderall and this is not a consideration when deciding which of the two medications to use.

The claim of safety regarding heart attack and stroke claim comes from my understanding of these three studies (1, 2, 3). The first study incidentally finds an increase of transient ischaemic attack (mini-stroke), but no increase in stroke. It was not really set up to examine TIAs in Adderall users and has not been replicated. The second study finds stimulants reduce heart attack and stroke risk, but this is probably due to healthy user bias (ie healthy people are more willing to risk taking strong medications than sick people). The third study finds no difference either way. Medical evidence summary site UpToDate says that:

Patients receiving stimulant therapy visited the emergency department or clinician office more frequently than those who were not treated with medications because of cardiac symptoms (10.9 versus 9.1 events per 1000 patient-years, adjusted hazards ratio 1.2, 95% CI 1.04-1.38) [26]. The cardiac symptoms included syncope, tachycardia, or palpitations. However, the group that received stimulant therapy was more likely to receive other psychotropic medications (antidepressants and antipsychotic agents), be male, and be non-Hispanic. The incidence of fatal and serious cardiac abnormalities was low and not different between the two groups, and was similar to the rates seen in the general pediatric population.

In other words, Adderall users are more likely to go to the ER for symptoms like fast heartbeat (which is a well-known potential Adderall side effect), but not for serious cardiovascular issues.

Adderall can slightly raise blood pressure; UpToDate and EU guideline-making body EUNETHYDIS agree the effect is on the order of about 1-8 mm systolic. According to prediction algorithms, this increases an average user’s ten-year heart attack risk by about 0.1 percentage points, probably not enough to worry about; it increases high risk users’ risk by about 1 percentage point, arguably still not worth worrying about if the medication is otherwise helpful.

6. Will I get addicted to Adderall?

The risk of getting addicted to Adderall is not literally zero, but it is lower than the risk of getting addicted to alcohol. If you don’t worry about drinking a beer turning you into an alcoholic, you shouldn’t worry about getting addicted to Adderall either.

I base the alcohol comparison on Nutt et al’s Rational Scale To Assess The Harm Of Drugs Of Potential Misuse. Dr. Nutt is the world’s most famous addictionologist and has helped design UK drug policy. He and his coauthors surveyed the UK’s most prestigious psychiatrists and independent experts to rank drugs on various scales, and found amphetamines to be relatively low-risk compared to common legal substances like alcohol and tobacco.

This matches my experience. I’ve worked with a few hundred Adderall patients. None of them self-described as addicted or needed to go to rehab. One person took too much Adderall in order to get high and had to stop the medication. Three or four took somewhat more than prescribed because they wanted stronger effects. The overwhelming majority, 95%+, had no problems.

The most common reason people get addicted to Adderall is that they’re snorting it or injecting it in order to get high. Let me reiterate this: they are trying to get high before they’re addicted, because they like getting high, and eventually they take so much of it that they get addicted. If you are not the sort of person to snort Adderall in order to get high, your risk is low.

The National Admissions To Substance Treatment Centers dataset monitors who goes to rehab and why. They find that methamphetamine/amphetamine is responsible for 6% of total rehab admissions – presumably prescription amphetamines are a tiny sliver of this. They say that the overwhelming majority of their patients (96%) either smoke, inject, or inhale the amphetamines – meaning practically nobody gets to a rehab after taking amphetamines orally. I think this reinforces that it’s very hard to get addicted to prescription amphetamines with regular oral use.

I’m avoiding giving numbers from studies because there is no objective way to judge whether someone is “addicted”, so studies use proxies and those proxies are inaccurate. For example, Wilens et al find that 10% of teens on Adderall use it to get high, and 22% admit to sometimes taking more than prescribed. But many people use alcohol or marijuana to get high without being “addicted” to those substances, and migraine sufferers sometimes take more anti-migraine meds than prescribed if their headaches are really bad. I don’t think it’s fair to use 10% or 22% as an estimate of Adderall addiction (also, teens are a worst-case scenario). A survey of study drug users found that 10% of Adderall users self-reported a “minor” problem with addiction, and 2.5% reported a “major” problem. But many of these people were recreational users, and we don’t know how many of them were injecting or inhaling it, so this is probably an upper bound.

Unless you have a long history of getting addicted to substances (eg alcohol), a family history of amphetamine abuse, or you plan to abuse your prescription in order to get high, your risk of Adderall addiction is very low, I think probably one percent or less.

7. If I stop Adderall, will I go into withdrawal?

If you stop taking Tylenol for headaches, you will go into withdrawal; it’s called rebound headaches. Almost all medications have a “rebound” effect where you can get the opposite of the normal effect for a few hours or days after stopping them. This is just how the human body works: whenever you take a medication, your metabolism changes to compensate for its effect; when you stop, it takes a little while for your metabolism to change back, and you get a little while feeling the opposite of however the drug made you feel. When doctors want to reassure people about a medication, they call this effect a “rebound” or “discontinuation syndrome”; when they want to scare people away from it, they call it “withdrawal”. So this question is more political than scientific. Adderall can occasionally have rebound symptoms like everything else, but it probably doesn’t rise to a level worth worrying about.

If you take a short-acting form of Adderall, like Adderall IR, you might (or might not) have a rebound effect in the evening when a dose wears off – the famous “Adderall crash”. See below for suggestions on dealing with this.

If you take Adderall on weekdays and stop on the weekends, you may feel more lethargic and irritable on the weekends. About 10% of people seem to have this effect. Again, see below for more.

If you take Adderall every day for several years and then stop cold turkey, you might have a few weeks of feeling more lethargic and irritable than usual. This is probably the closest thing to what most people mean when they think of “withdrawal”. It’s not dangerous and it doesn’t make people desperate to get more of the medication by any means necessary, it’s just a few weeks of being more lethargic and irritable than usual. Probably you can avoid this by taking weekends of Adderall like most people do, but I can’t prove this.

8. If I keep taking Adderall for too long, will I develop tolerance to it?

Most people develop some tolerance over the first few weeks, but still find it helpful overall. Some people will develop more tolerance than others, and a few will develop tolerance to the point where the medication stops working. Exactly how this works is still unclear.

In the Multimodal Treatment Of ADHD Study, ADHD children taking Adderall did much better than the placebo group for one year. By the second year, they were doing only a little better, and by the third year, they were the same. This could be because the Adderall stopped working. But more likely it’s because the study didn’t put any effort into keeping people in the right groups, so by year three 34% of the experimental group had stopped Adderall, and 43% of the placebo group had started it. This is probably not a great situation for detecting differences and I mention this study only so that you know why I don’t believe it.

I informally surveyed 59 people who had been using Adderall for more than five years. 39% said they had no tolerance, 67% said they had some tolerance but it still worked well in general, and 5% said they had developed complete tolerance and it no longer worked. These numbers agree with my clinical experience. While most people will get at least some tolerance after long enough, it’s really rare for people to say the medication has stopped working entirely.

9. How can I avoid becoming tolerant to Adderall?

Not everyone develops tolerance to Adderall, but some people will. There are no great studies on how to solve it and we mostly have to go off folk wisdom and common sense. The most comprehensive collection of advice I’ve found on this is this article, but it speaks way too authoritatively when presenting a lot of what are basically wild guesses.

Many psychiatrists, including me, recommend patients take Adderall only five days a week and take the last two – usually the weekend – to recover. Since you would not be on Adderall consistently, you would make tolerance less likely. A few people will still develop tolerance on this schedule; they can try going down to four days a week, and if that doesn’t work, to three days and so on. This usually works eventually, at the cost of preventing you from taking full advantage of the Adderall. Some people will find they crash on their days off and may need to take it every day or not at all.

If you’re already tolerant to Adderall, you can take a “drug holiday” – a few days or weeks where you stay off Adderall consistently. When you restart it, you’ll probably be sensitive again, and you can take it fewer days a week from then on to preserve the sensitivity.

There are anecdotal reports that taking NMDA antagonists can prevent Adderall tolerance. The most commonly recommended regimens are magnesium glycinate 200 mg three times a day, zinc glycinate 30 mg daily, or memantine 10 mg once a day. Magnesium is more commonly used and more frequently recommended, but zinc has a tangentially-related study sort of backing it up. Some people also report that the prescription-only NMDA antagonist memantine can reduce Adderall tolerance; talk to a doctor if you are interested in this.

Other substances which have been recommended for Adderall tolerance include inositol, choline, sulbutiamine, and practically everything else.

What about increasing the dose? I sometimes do this if people’s original dose was very low or it took them a very long time to develop tolerance. Otherwise, I worry that they will just develop tolerance to the new dose and have to keep repeating the process until they reach the maximum safe dose, at which point they’ll have a worse problem than they did before. This is kind of a last-ditch solution.

Many people report that their Adderall works less well when they don’t get enough sleep. I don’t know if this is just that it’s hard to concentrate when you’re tired, or if this actually increases Adderall tolerance development. In either case, I would strongly recommend you combine getting enough sleep with any other method you’re using to remain sensitive to Adderall.

10. Help! I get a “crash” every evening when my Adderall runs out!

About half of patients report something like this. It usually feels like a few hours when they’re very unmotivated, very irritable, tired without being able to get good sleep, and otherwise miserable.

My understanding is that this is most likely a result of dopamine depletion. Adderall makes your brain consume dopamine more quickly than usual, and you can “run out” (it’s actually much more complicated than this, sorry).

First, you can make your comedown off Adderall as gradual as possible. Adderall XR and Vyvanse are both more gradual than Adderall IR, and many people find these cause less of a crash. If you want to stick with Adderall IR, you can artificially taper it by taking a lower supplementary dose around the end of the day, eg 20 mg in the morning, 10 in the afternoon, and 5 in the early evening.

Second, you can take 500 mg of the supplement tyrosine an hour or two before the Adderall starts wearing off. An elegant explanation for why this works is that tyrosine is the chemical precursor of dopamine, so this helps you synthesize more instead of “running out”. An inelegant explanation is that tyrosine itself is a very mild stimulant, and coming off a strong stimulant onto a mild stimulant is more gradual than coming off a strong stimulant and being left with nothing. I’m not sure which of these explains its effect but many people say this helps them a lot.

Along with these solutions, you should try to make sure you otherwise feel as well as possible by eg getting good sleep the night before and eating and drinking enough throughout the day. Remember that Adderall can spoil your appetite – at least some Adderall crashes happen when a day without eating food finally catches up to you!

11. What does Adderall interact with?

Adderall doesn’t exactly “interact with” other stimulants in some complicated chemical sense. But if you take two stimulants at once, they will both stimulate you, and you will end up stimulated at some unpredictable level which might be more than you bargained for. I especially see this with caffeine. I have stopped trying to get patients not to drink coffee – it never works. But I do recommend they not drink coffee the first few days they try Adderall, so that they get a good understanding of its effects. Then they can gradually reintroduce coffee and make sure however much coffee they’re taking isn’t leaving them too stimulated.

Adderall is very sensitive to the acidity of your stomach. The more acidic your stomach, the less you absorb and the weaker it gets. The more alkaline (basic) your stomach, the more you absorb and the stronger it gets. Orange juice, coffee, soda, and beer can all be acidic. Antacids are alkaline. Try not to use these just before using Adderall or you will get an unpredictable effect. There’s not much point in deliberately taking alkaline substances to enhance effectiveness; just take a higher dose.

(you’ll notice that coffee is mentioned in this paragraph too, meaning that it might make you more stimulated or less stimulated. Watch out for it)

Some people find Adderall decreases their alcohol tolerance. Others find that just as Adderall can help them keep studying long past the point where they would otherwise have stopped, it pushes them to keep drinking long past the point where they would otherwise have stopped. This is a bad combination. So even though there isn’t an official complicated chemical interaction here, I recommend you start very low. If you absolutely must drink on Adderall, start with one beer (or glass of wine), then call it a night. See how you do. If you’re fine, you can gradually go up from there. Don’t drink the normal amount you drink right away.

Psychedelic users report that although psychedelics + Adderall is not a dangerous or deadly combination, it is not fun and you should not try it. You usually just end up paranoid and unhappy. There is more theoretical concern around MDMA; some animal studies suggest a higher risk of neurotoxicity when combined with amphetamines. These studies are very preliminary, but please just skip your Adderall dose on whatever day you take MDMA.

Ask your doctor or an online drug interaction checker about interactions between Adderall and particular prescription medications.