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There
are now about 22 FDA approved medicines for Attention Deficit
Hyperactivity Disorder (ADHD) including the new Intuniv plus another
handful of FDA unapproved options. The goal of this article is to make
sense of these many choices and understand where the new Intuniv fits in.
Medicine names are in bold below. Key concepts are in bold or underlined
and are summed up at the end.
Choosing
a medication for ADHD is done after becoming reasonably certain of the
diagnosis and considering which, if any, treatment options are best for
your child or you. Please see my detailed information packet about ADHD at
http://www.leeheymd.com/.
It is also important to be clear what symptoms you want the ADHD medicine
to help, what possible side effects you especially want to avoid, and if
there are any convenience factors to consider. You and/or the youth must
also remember and accept that no medicine can do assignments, turn them
in, or make good choices. These medicines can only assist one's efforts
- moderately usually, sometimes greatly.
ADHD
medicines, especially the stimulants (see Medications
For ADHD) and the non-stimulant Strattera, are most helpful for
distractibility (short attention span, poor concentration, and lack of
focus), for hyperactivity (can't sit still, restless, fidgety, excessive
talking) and impulse control. Persons who have only the Inattentive
(distractible) type of ADHD without any hyperactivity also respond well to
stimulants and Strattera. Stimulants and Strattera are partially helpful
for the common impulse control problems of acting or speaking without
thinking first, blurting out, and butting into conversations, lines,
games, and impulsive temper (Intuniv, guanfacine, clonidine, or imipramine
may help this more). No ADHD
medicines directly help organization problems (which is known as Executive
Functioning Disorder) or correct learning disorders like the various forms
of reading and writing (dyslexia), math, or processing disorders. However,
by helping any associated distractibility or hyperactivity, stimulants and
Strattera can have partial to sometimes substantial indirect benefits for
learning disorders and organization.
Since
stimulants (also known as psychostimulants) and Strattera are usually the
best medicines for ADHD let's next sort through them. Actually there are
only 2 stimulant groups to consider. These are several forms of
methylphenidate and of the amphetamines. (The most effective non-stimulant
medicine for distractibility is Strattera and will be discussed after the
stimulants.)
So, really, this part is simpler than it looks. As you read on, be
aware the ER, SR, CD, LA and XR suffixes all mean extended, slow, or
longer duration forms of the basic medicine. Brand names are capitalized
below while the generic chemical name is not.
Usually
side effects can be avoided by conservative dosing and by fine
tuning dose and form via close monitoring. Decreased
appetite is the #1 side effect.
If the dose is too strong or medicine is wrong speedy effects like
delayed sleep onset, headache, stomach ache, tense muscles, dry mouth or
irritability may occur. Or
the opposite may occur - the person may feel too subdued, too calm, loose
their spirit, spontaneity, spark, or seem "zombie" - like.
Tics may occur especially in persons with a tendency toward them.
Blood pressure or heart rate increases, skipped or irregular heart
beats are possible though rarely significantly.
All these are reversible by decreasing, changing, or stopping the
medicine.
Methylphenidate
(MPH for short)
is the generic or chemical name of the medicine known by the brand names
Ritalin, Ritalin SR, Methylin, Methylin ER, Metadate ER, Metadate CD,
Ritalin LA, Concerta ER and Daytrana (a skin patch form of MPH). Thus,
these medicines all have the same basic ingredient. The main difference is
how long they last and what mechanism is used to make it last longer.
Generic forms, when available, are cheaper. Focalin (dexmethylphenidate)
is the right handed isomer form of MPH which may give better duration and
less "rebound" than MPH.
The
amphetamines include Dexedrine (dextroamphetamine), Dexedrine
spansules (SR), Adderall (generic known as "mixed amphetamine
salts"), Adderall XR, and (the newest) Vyvanse (lisdexamfetamine).
Adderall contains 50% dextro-amphetamine and 50% of the very
closely related isomer levo-amphetamine. The addition of levo-ampetamine
gives Adderall its longer duration. Plain Adderall comes in a generic but
Adderall XR does not yet. Vyvanse lasts longer, is often smoother and is
less abusable.
Let's
next discuss the relative merits and demerits of the MPH and amphetamine
groups. MPH (methylphenidate) is the
gold standard that everything else is compared to; it's been studied
the most. MPH is the mildest and it is cheap. It is a good place to
start. Amphetamines are stronger, generally last a bit longer, can have
more of a rough edge, and are more abusable. Some people do better on MPH
products and some do better on the amphetamine options - there is no
reliable way to tell which is better for you or your child without trying
them.
Let's
talk duration.
Plain MPH (Ritalin, Methylin) lasts 3 to 4 hours, Focalin lasts 4 to 5
hours, Dexedrine lasts a good 4 hours, and plain Adderall 5 to maybe 6
hours. Each requires at least 2 doses to cover school hours while MPH and
Dexedrine often require a third dose around 3 or 4 pm to also cover
homework or work. Three doses a day (even two doses) can be a hassle
leading to missed doses or lack of confidentiality due to having to take
it at lunch at school or at day care after school, etc. Except for
Strattera, the big growth of new ADHD medicine options is in new forms to
extend the duration of existing medicines, not in creating new medicines
to treat ADHD. Longer duration stimulant options are not only more
convenient, they are also often smoother (less side effects and more
consistent benefit through the day) and are less likely to cause the
sometimes unpleasant "rebound" as the medicine "wears
off". There are now 5 ways companies have developed to increase
the number of effective hours. First (and the oldest way), is to make
a hard coated pill that dissolves slower - Ritalin SR and the generic MPH
SR were made this way. In 2000 two companies came out with minor
modifications of this MPH form and a new 10 mg size (as well as the
generically priced 20 mg) - Methylin ER and Metadate ER.
These last 6 to 8 hours usually. A second method to extend duration was
brought out later in 2000 as Concerta, which uses a 3 layer OROS
osmotic pressure release system to make plain MPH last 8 to 13 hours,
usually 10 hours. In 2001 Metadate CD and Ritalin LA arrived
as MPH based capsules containing pellets of 2 different release time
targets which lasts about 8 hours. Adderall XR does the same with
amphetamine and lasts closer to 10 hours.
This capsule design containing time release pellets is the third
method for making stimulants last longer.
The fourth method came out in 2006 as the Daytrana
transdermal system. This is a skin patch designed to be placed daily on one hip
early each morning and removed about 9 hours later.
The patch can thus avoid an oral dose and its duration can be
changed by when you take off the patch. The fifth method appeared in 2007
as Vyvanse which is Dexedrine (dextroamphetamine) bonded to the
amino acid lysine which results in a duration of 10 to 12 hours. This
"pro-drug" (meaning pre or before) is not active until enzymes
in the gastrointestinal tract or liver cut the lysine bond to free up the
dextroamphetamine. This takes time and both results in extra duration of action
and makes 'snorting" or injecting it not worthwhile, thereby reducing
abuse potential. The Daytrana
skin patch (and less so Concerta) also reduce abusability.
Dexedrine
(SR) "spansule" capsules were the first of the capsule strategy
and typically last 6 to 8 hours. In late 2001 Adderall XR became available
in its 2 pellet type capsule system to last 8 to 10 hours thereby avoiding
need for a mid day dose at school or work. Concerta or Daytrana skin
patch (with MPH) and Adderall XR or Vyvanse (with amphetamine) are the
longest duration stimulant options. They may cover the whole day with only
one morning dose. Focalin XR is next longest.
Concerta, Adderall XR, Vyvanse, Metadate CD, Ritalin LA, Strattera,
Focalin XR, and Daytrana are brands costing over $3 a day and may be a
high co-pay choice or are not covered on some insurance formularies. Some
patients will still require a dose of regular MPH or amphetamine around 4
PM to cover the rest of the day. Cylert (pemoline) is an effective,
truly once a day non abusable stimulant option that is little used since
it has about a 1 in 10,000 risk of unpredictable severe liver damage or
failure.
Preparation
types
available thus include tablets both short and longer duration (MPH,
Focalin, Adderall, Methylin ER, Metadate ER, Ritalin SR, MPH SR), capsules
that release 50% quickly and 50% in about 4 hours (Focalin XR, Ritalin LA,
Dexedine Spansues, Adderall XR - all of which can be sprinkled on food to
ease swallowing; Metadate CD does the same except it releases 30%
immediately and 70 % later), the Concerta 3 layer techno pill, capsules
not designed for splitting (Vyvanse and Stratera are also not good for
splitting), and the Daytrana skin patch.
Methylin also makes a liquid dose form that lasts up to 4
hours for situations where a liquid is preferred. All Methylin forms
contain no dyes.
Page
2 of my ADHD Medication chart shows non stimulant medicines that
may help ADHD. Strattera
(atomoxetine) is the FDA approved (early 2003) non stimulant ADHD medicine
that may rival the stimulants for at least some persons in helping
distractibility (attention, concentration, focus) and perhaps
hyperactivity and impulsivity. It works via norepinephrine reuptake
inhibition (NRI) to increase primarily norepinephrine in the brain but has
little effect on dopamine. Stimulants increase both these
neurotransmitters but in a different way. Thus, Strattera helps ADHD while
often causing less appetite suppression, sleep disturbance, rebound,
irritability, tics, or other stimulant side effects. Strattera is not
abusable. As a convenience plus, Strattera can be called in, refills can
be written, and there is no need for handwritten prescriptions like all
stimulants need. Strattera works to increase norepinephrine (NRI) in a way
similar to how the antidepressants Prozac, Zoloft, Paxil, Luvox, Celexa,
and Lexapro increase serotonin (SRI). Strattera may occasionally have some
antidepressant or, more often, anxiety benefit. Strattera must be taken
7 days a week to give a smooth and effective level in the body and must
build up for 2 to 4 weeks before it is fully effective. In contrast,
stimulants can be given when needed and work for a certain number of hours
and then are gone. The potential advantage to the steady blood level
effect of Strattera is that it should be present and working 24 hours a
day - even on awakening before the morning dose is taken and late into the
evening when stimulants have usually worn off. Because of this slow build
up effect it may be better when changing from a stimulant to Strattera to
overlap both meds the first few weeks. For some patients it may be helpful
to take a stimulant and Strattera (or
other non stimulant medicine) at the same time on an ongoing basis. In
addition to a usually milder and less frequent group of possible stimulant
like side effects, Strattera may bother the stomach by causing nausea, or
cause sleepiness. Taking it with food, switching the medicine to evening,
or giving half in the am and half in the pm may work better.
Strattera comes in capsules of several strengths, is usually
started in the morning, and the dosage increases with body weight.
Response may be better if the dose is set at the higher end of the
recommended range although some people respond and tolerate it better at
low doses. Two to four weeks should be given to gauge response. Studies
and clinical experience show that some people respond better to Strattera
than a stimulant or vice versa. If
one doesn't work well the other may still help.
Other
options on page 2 of my ADHD medication chart are less helpful for attention, concentration, focus,
and distractibility than Strattera and the stimulants but may have other
advantages. These medicines include the antidepressants Wellbutrin (buproprion)
and imipramine (as well as its cousins). Generally, if I am trying to
mainly treat ADHD, especially distractibility and inattention, I will use
a stimulant or possibly Strattera first for that and then add an
antidepressant or anti anxiety medicine if depression or anxiety are also
present.
Tenex
(guanfacine), Intuniv (guanfacine ER) or clonidine are not usually as helpful for
distractibility and inattention as the stimulants are but are just as good
or better for hyperactivity and impulsivity. They also don't cut appetite
and do suppress tics (which stimulants may precipitate or worsen). They
are given 2 or 3 times a day. With guanfacine lunch dosing can often be
avoided. Intuniv is a good new (2009) extended release guanfacine
that allows once a day dosing (usually am), less sedation, smoother
effect, plus all the other advantages of guanfacine or clonidine. This
family of central nervous system calmers also often help sleep, reduce the
"hyperarousal" symptoms of Post Traumatic Stress Disorder (PTSD),
and opiate (pain killers) and nicotine withdrawal.
The
other nonstimulants in this paragraph are infrequently used options. Amantadine
is a generic (Symmetrel is the brand name) that increases primarily
dopamine and not norepinephrine. Thus some patients respond better to its
similar but more limited actions. Amantadine (and its cousin rimantadine)
is mainly used to treat parkinsonism of various types and also prevents
and treats Influenza type A (not B). Amantadine comes as a capsule or
liquid without much dose adjusting possible except via the liquid and is
usually given twice a day for ADHD. (Two brand name and more pure dopamine
agonists, Mirapex or Requip, could also be tried.)
Provigil (modafinil) was approved by the FDA in 2000 for
"excessive daytime sleepiness" caused by certain sleep disorders
like sleep apnea and narcolepsy. Neither it or amantadine are approved by
the FDA for ADHD although doctors may use them for ADHD. There are only a
few studies so far showing that amantadine or Provigil helps ADHD.
Provigil (and its even longer duration isomer armodafiil known as Nuvigil)
is only available as an expensive brand. It comes as a tablet given once a
day in the morning. Although it is similar to other stimulants in several
ways it also has differences that make it an alternative when other
stimulants fail or aren't tolerated. All stimulants except Cylert may be
abused but the non-stimulants Intuniv, guanfacine, and Strattera are not
abusable which gives another reason to consider these options in certain
situations. The top three abused substances (plus nicotine) in middle
school through college are now alcohol, marijuana, and Adderall.