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A file with information concerning Pharmaceudical
From netcom.com!csus.edu!wupost!udel!news.intercon.com!panix!zip.eecs.umich.edu!umn.edu!news-feed-2.achnet.edu!concert!hearst.acc.Virginia.EDU!murdoch!faraday.clas.Virginia.EDU!mem4k Tue Apr 5 21:453 1994
Xref: netcom.com alt.support.attn-deficit:1412
Newsgroups: alt.support.attn-deficit
Path: netcom.com!csus.edu!wupost!udel!news.intercon.com!panix!zip.eecs.umich.edu!umn.edu!news-feed-2eachnet.edu!concert!hearst.acc.Virginia.EDU!murdoch!faraday.clas.Virginia.EDU!mem4k
From: mem4k@faraday.clas.Virginia.EDU (Mark Edward Mitch)
Subject: ADD and access to treatment
Message-ID: <CnB4Ly.Dx1@murdoch.acc.Virginia.EDU>
Sender: usenet@murdoch.acc.Virginia.EDU
Organization: University of Virginia
Date: Sun, 27 Mar 1994 05:01:09 GMT
Lines: 448
To all:
In lieu of our ongoing discussions on ritalin use, dosage, effectiveness,
and most recently, access, I think the following will prove interesting
reading. I stumbled across it in the compuserve ADD forum library.
There is also a more detailed article on ritalin use in treatment that
I plan to post in the future. This might be something for the
ADD FTP site archives. Even something to show your doctor. I plan
to talk to mine.
Enjoy,
Mark
PHARM.TXT/Text Bytes: 20648
Title : Pharmocotherapy for ADHD in Adults
Keywords: RATEY HALLOWELL ADULT ADD MEDICATION
An interesting article on the different types of medication used for Adult
ADHD by John J.Ratey, M.D., Edward M. Hallowell, M.D., & Catherine L.
Leveroni, B.A.
PHARMACOTHERAPY FOR ADHD IN ADULTS
by John J. Ratey, M.D., Edward M. Hallowell, M.D. and
Catherine L. Lereroni, B.A.
ADHD in adults is very responsive to pharmacotherapy;
however, treatment strategies for the disorder have not been
as well established as they have for children. In this
paper we will discuss our clinical experience in treating
adults with ADHD, in hopes that others will benefit from the
years of trial and error.
The challenge to treating the ADHD adult is finding the drug
or combination of drugs that work for the individual.
Zametkin et al (1990) found evidence of hypometabolism of
the brains of ADHD adults as compared with matched controls,
and the constellation of symptoms found in the individual
with ADHD, particularly the distractibility and motor
hyperactivity, may be explained by these differences. A
useful metaphor for ADHD that we have adopted, supported in
part by Zametkin's findings, may be the problem of
underactivity in the frontal lobes. The frontal lobes are
thought to be mainly inhibitory and integrative in function,
thus hypoactivity may translate phenomenologically into
problems with inhibition and control in ADHD patients --
problems with stopping the flow of attention, thoughts,
emotions, movements, ideas. The precise patho-physiology of
ADHD, however, has yet to be determined, and the
inconsistent results of research and clinical drug trials
indicate that ADHD is not of homogeneous neuro-chemical or
anatomical origin. It is thus difficult to predict to which
drug an individual will best respond. The clinician and the
patient should try several medications at carefully adjusted
doses until the individual's optimal response is found and
side effects are minimized. There's no cookbook recipe and
no cure for ADHD, however the positive effect of the right
drug or the right combination of medications is often life
changing for the patient and for those affected by the
patient.
Antidepressants
Research and clinical experience have shown that the
antidepressants Norpramin (desipramine) and Tofranil
(imipramine) effectively increase attentiveness and reduce
distractibility in children and adults. Tricyclic
antidepressants exert their effect by acting upon
norepinephrine and dopamine, the two major neurotransmitters
in the attention system. They block the re-uptake of
norepinephrine and dopamine into the presynaptic neuron and
indirectly modify the rate of release, thus increase the
activity of these two chemicals in the brain (McCracken,
1991).
In our clinical experience, 40% or more of ADHD adults
respond to between 5 mg/day and 40 mg/day of Norpramin.
This dose range is considerable lower than that reported in
current research reports (Biederman et al, 1985; Biederman,
1988). We see the return to the use of low doses as a
significant contribution to the practice of pharmacotherapy
for ADHD because we have found the most dramatic responses
at low dose levels. Further, most of our patients report
that the positive effect experienced at a very low dose
range is often lost as the dose is increased. In the mid
1960's, Rapoport reported that the majority of children with
"behavior problems" he studied showed marked improvement on
10 mg/day of Tofranil; in fact, a number responded most
dramatically to 5 mg/day, and were maintained at that dose
without a waning of response (Rapoport, 1965). As
experience with antidepressants accumulated, researchers and
clinicians became aware that large doses and therapeutic
blood levels of antidepressants were useful in treating
refractory depression. This conflicted, buried, and colored
the early experience of using lower doses for anxiety, panic
and especially for ADHD. The rapid time frame for drug
effect in ADHD patients, however, suggests that tricyclics
have a different mechanism of action in ADHD than they do in
depression. It makes sense, then, that the therapeutic dose
range for ADHD would be different. In clinical practice the
superior efficacy of low doses has been documented
throughout the years (Heussy, 1983, 1989, 1992; Bellak et
al, 1987). In fact Heussy has contended that there is a 90%
chance individuals with ADHD will have a positive response
to a low dose of tricyclics, which is between 1/10 to 1/3 of
the dose used for depression.
We typically start people on 10 mg/day for a week to 10 days
to see if there is any improvement in the individual's
ability to sustain attention and regulate mood, and then
proceed to raise the dose to 20 or 30 mg/day if there is
little or no response. We have found that Norpramin not
only increases the ability to direct and maintain attention,
but also can have a calming effect on the individual. It
can decrease impulsive behavior, stop temper tantrums,
regulate frequent mood shifts and increase reading and
learning abilities. Norpramin also effectively treats the
"mini panic state" to which so many individuals with ADHD
are prone. This state begins as a startle response when the
individual is flooded with stimulation, and develops into a
full blown feeling of panic which predisposes the individual
towards impulsive action, defense rumination or the
repetition of trauma experiences. This is a particularly
salient problem for ADHD adults, whose tolerance for
stimulation is lowered because they have spent most of their
lives trying to sustain focus over an inner state of chaos
and turbulence. The effect of the antidepressant in
treating ADHD symptoms, especially the mood instability,
mini panic episodes, fuzziness of the environment, and the
chronic state of disorganization can be sometimes altered
with the first dose of medication. In others the effect can
be subtle and gradual. These changes can be very exciting
for people who have struggled with these symptoms for their
entire life. Often patients will call the clinician
proclaiming Norpramin to be a "miracle drug." Both the
patient and physician should be skeptical of this effect
until they see positive markers of change in the patient's
life such as higher test scores and assignments completed in
class for adolescents and young adults; projects done on
time, punctuality in meetings, checkbooks balanced, tantrums
a distant memory, and loved ones finding a new attentive,
intimate being for adults. The use of low doses also
protects against the adverse effects on memory and learning
that is seen at higher doses.
Another antidepressant that is currently popular among
clinicians treating adult ADHD is Wellbutrin (buproprion),
which is a potent dopamine re-uptake inhibitor. Research
reports have attested to the moderate efficacy of this agent
(Wender and Reimherr, 1990).
Stimulants
If response to antidepressants is not apparent or begins to
wane within 4-6 weeks, we would try psychostimulants such as
Ritalin (methylphenidate), Dexedrine (amphetamine), and
Cylert (pemoline). The calming effect of these agents in
hyperactive children is paradoxical, but advances in the
understanding of how these drugs work have provided insight
into their clinical effect. These drugs potently increase
the concentration and activity of both dopamine and
norepinephrine, and thus possibly enhance activity and
inhibition in the brain. According to some reports, Ritalin
and Dexedrine increase attentiveness, reduce
distractibility, enhance concentration, and decrease motor
restlessness and hyperactivity in roughly 70% of adults with
ADD (Barkely, 1977).
We would typically begin by starting Ritalin at 5 mg twice
daily, then increase the dose upward, with most people
ending at a dose between 30-40 mg/day. Many people find
adequate calming and attention enhancing effects at lower
doses (10-30 mg/day). This response can be immediate, and
often dramatic. If the individual does not respond to
Ritalin we switch to Dexedrine. It is crucial to note that
Ritalin and Dexedrine, while widely regarded as very similar
drugs, are not. They have a different pharmacological
profile, a different mechanism of action at the cellular
level, and a not-so subtly different effect on patients.
The two drugs act upon separate neurotransmitter storage
pools. For instance, Ritalin is a more potent re-uptake
blocker of dopamine, while Dexedrine may exert some of its
effect through feedback inhibition (Zametkin et al, 1985).
We have found that when Dexedrine is successfully tried on
people who have had an unsatisfactory trial of Ritalin, they
report that the Dexedrine is a "softer drug." Some patients
feel Dexedrine is enormously beneficial in alerting their
brain to activity without causing them to feel somatically
driven, as compared to Ritalin which sometimes makes
patients feel like their body is in "overdrive." One
patient described Dexedrine as a "caffeine-less" Ritalin.
Most clinicians, however, use Dexedrine as the second or
third choice stimulant because of its reputation in the drug
abusing community.
Side effects with the psychostimulants on the whole are low
as compared to other psychoactive agents that psychiatrists
and neurologists use. Major complaints involve appetite
suppression, insomnia or multiple varieties of sleep
disturbance such as waking up in the middle of the night and
interference with dreams. Ten percent of patients on
Ritalin complain of headaches, and the clinician must watch
blood pressure and pulse when either psychostimulant is
used. A more important issue in prescribing
psychostimulants is the difficulty in achieving a
therapeutic dose of medication. Sometimes a patient needs
very little medication, for instance we have those in our
practice who find that as little as 1/4 mg Ritalin or
Dexedrine a few times a day provides them with the necessary
enhancement of focusing ability. Others need much higher
doses to sustain an effect, and require levels well beyond
the recommended upper limit of 60 mg/day of Ritalin.
Gittleman-Klein has stated that the most commonly made error
in the treatment of ADHD is inadequate dosing
(Gittleman-Klein, 1987). This is most likely due to a
cookbook dogma that deflates the role of the patient's
report as the primary measure of drug response. For these
individuals there is the problem of maintaining an adequate
dose of medication. The drug is available in 5 mg tablets,
and adults may need 20 mg per dose to get a calming,
focusing effect, and this lasts only 3-4 hours. For many
people there is a limit to the number of pills that one can
take or will remember to take. We sometimes use a slow
release stimulant to counter this problem, particularly in
individuals who are likely to forget to take a 2nd or 3rd
dose of medication; however, it has been our observation
that Cylert generally does not induce as dramatic results as
Ritalin or Dexedrine. Dexedrine slow release, which is
available in 10 mg spansules, seems to be more effective
than slow release Ritalin. It would be wonderful to have a
long acting stimulant, but currently there is not a
clinically efficacious one available. Scientists have
discovered a way to chemically purify Ritalin into a more
effective drug with fewer side effects; however, the
development of this specifically targeted drug is pending
funding (Jaffe, 1992).
Another frequently encountered problem in prescribing
psychostimulants is negotiating with pharmacists. There is
a persistent dark cloud hanging over the use of stimulants
because of their tarnished history as drugs of abuse. Even
in the most enlightened states it is difficult to prescribe
psychostimulants for adults due to the prevailing myths that
ADHD is 1) not a disorder but merely moral corruptness and
2) something that disappears in adolescence. It is thus
often thought that adults who are taking prescription
psychostimulants are simply looking for their next high. In
many cases, the physician must call the pharmacy before the
drug will be dispensed.
This brings up the issue frequently faced by mental health
professionals, parents, and concerned others of whether it
is wise to use stimulant medication in individuals with a
history of drug or alcohol abuse. This is fraught with
anxiety on everyone's part; however it has been our
experience that an adult with a history of drug and/or
alcohol abuse who has been diagnosed with ADHD is committed
to changing his/her life will not use the medication in an
illegal or abusive fashion. This obviously presupposes a
very strong therapeutic relationship with the prescriber as
well as with other involved mental health professionals.
Further, Huessey has written that no cases of
psychostimulant abuse in ADHD adolescents have been reported
because the drugs are not used to "tune out" of the
environment as are most recreational drugs, but to "tune in"
(Huessy, 1985).
Other Agents
It has been suggested that a number of other agents, such as
fenfluramine, L-dopa, and amantadine, may be used to treat
ADHD. These are possible useful drugs where others fail,
but neither research (Zametkin and Rapoport, 1987) nor
clinical experience has shown these agents to be as
effective as the psychostimulants and tricyclic
antidepressants. These drugs should be tried as a last
resort in the rare case of a treatment failure to the latter
agents.
Adjuncts
While treatment with stimulants and tricyclics are extremely
effective in enhancing concentration and attention, they
often cannot sufficiently ameliorate the concomitant
impulsivity, explosiveness, and irritability experienced by
many ADHD adults. There are many adjunct medications that
can be added to the treatment regimen to help with these
symptoms.
Beta-blockers can be used to decrease anxiety and tension.
They also reduce hyperresponsiveness to stimulation, and the
agitation that predisposes many ADHD adults to impulsive
behavior and tantrums. Corgard (nadolol) is preferable to
Inderal (propranol) because it can be taken once a day and
it mainly has a peripheral mechanism of action, therefore
reduces the chronic somatic tension, hyperarousal, and
impulsivity without interfering with the effects of other
medications. Lithium, Depakoate (valproate), and Tegretol
(carbamazepine) can also be very useful adjuncts in violent
and difficult to manage individuals, especially in those who
behavior is secondary to extreme fluctuations of mood.
Another drug that is often useful as an adjuctive treatment
for ADHD is Clonidine, an agent which alters
alpha-adrenergic functioning. (Hunt, 1987). Clonidine is
especially helpful in increasing calmness and frustration
tolerance, particularly in a patient who cannot take
beta-blockers because of a past history of asthma.
Clonidine may also enhance the efficacy of a stimulant at
the receptor level (Hunt, 1985), thus enabling the clinician
to lower the stimulant dose. Clonidine's use in adults,
however, can be complicated because of its tendency to
induce somnolence.
An extremely common concurrent complaint in ADHD adults is
that of depression and irritability, particularly in ADHD
women who suffer from PMS. It seems no matter how effective
the stimulants or tricyclics are in increasing the ability
to focus, symptoms in these individuals fluctuate with the
monthly variations in mood. These symptoms respond very
well to the serotonergic agents BuSpar (buspirone) and
Prozac (fluoxetine). The improvement gained with the
addition of these drugs to the treatment regimen of
individuals prone to irritability and depression is often
dramatic. We typically start patients on standard doses, 10
mg/T.I.D., of BuSpar or 20 mg qAM of Prozac for an entire
month until symptoms have been obliterated, then switch to
an attempt to use medication only 2 weeks of the month.
Prozac can also reduce the obsessive/compulsive symptoms
some patients develop in response to their ADHD. We have
not found traditional doses of Anafranil (clomipramine) to
be useful in adults with ADHD.
It is important to note that none of the drugs used as
adjuncts induce cognitive impairment. This is crucial
because as the ability to remember, learn, organize, and
relate all tend to be impaired with ADHD adults, the
enhancement of these functions is an important aspect or
treatment.
The Myth that the Doctor Knows All
In assessing an individual's response to a particular
medication or dose, the best advice we have is to listen
carefully to the patient because their feelings are more
accurate gages of drug efficacy than are so-called objective
scales or doctor's impressions. This can be complicated
because many ADHD adults are poor observers of their own
activity, and have difficulty with retrospective assessments
of their behavior or mood state. It is also helpful to
enlist the help of other observers such as spouses, friends,
and co-workers, as these people are often the most sensitive
to changes in ADHD adults once treatment has begun.
The treating clinician should also be aware that there are a
few patients among ADHD adults, perhaps 1 in 10, who have
extremely sensitive brains. There are many possible causes
of this hypersensitivity, such as a history of brain injury,
premature delivery or birth trauma. It is important that
this reaction not be interpreted as resistance, a negative
therapeutic reaction, or passive-aggression. We have seen
a number of individuals for whom even 10 mg of
antidepressant or 5 mg of methylphenidate is far too much.
Unfortunately for some of these patients there is not a dose
low enough: even if they chop off tiny pieces of medication,
they still have too many side effects. In these cases, both
the clinician and patient are left in a quandry without
medication as a treatment option.
REFERENCES
Zametkin AJ, Nordahl, TE, Gross M, et al: Cerebral glucose
metabolism in adults with hyperactivity of childhood onset.
New England Journal of Medicine 323:1361-1366, 1990.
McCracken JT: A two-part model of stimulant action on
Attention-Deficit Hyperactivity Disorder in Children.
Journal of Neuropsychiatry and Clinical Neurosciences
3:201-209, 1991.
Biederman J, Gastfriend DR, Jellineck MS, Goldblatt A:
Cardiovascular effects of desipramine in children and
adolescents with attention deficit disorder. Journal of
Pediatrics 106:1017-1020, 1985.
Biederman J: Pharmacological treatment of adolescents with
affective disorders and attention deficit disorder.
Psychopharmacology Bulletin 24:81-87, 1988.
Rapoport J: Childhood behavior and learning problems
treated with imipramine. International Journal of
Neuro-science, 635-642, 1965.
Huessy H: Imipramine for attention deficit disorder.
American Journal of Psychiatry 140: 272, 1983.
Huessy H: Medication vs behavioral management. American
Journal of Orthopsychiatry 59: 153-155, 1989.
Huessy H: Comorbidity of attention deficit hyperactivity
disorder and other disorders. American Journal of
Psychiatry 149: 148-149, 1992.
Bellak L, Stanley RK, Lewis AO: Attention Deficit Disorder
Psychosis as a diagnostic category. Psychiatric
Developments 3: 239-262, 1987.
Wender PH, Reimherr FW: Bupropion treatment of
Attention-Deficit Hyperactivity Disorder in adults.
American Journal of Psychiatry 147: 1018-1020, 1990.
Barkely R: A review of stimulant drug research with
hyperactive children. Journal of Child Psychology and
Psychiatry 18: 137-165, 1977.
Zametkin AJ, Karoum F, Linnoila M, et al: Stimulants,
urinary catecholamines, and indoleamines in hyperactivity.
Archives of General Psychiatry 42: 251-255, 1985.
Gittleman-Klein R: Prognosis of attention deficit disorder
and its management in adolescence. Pediatric Review 21:
178-191, 1985.
Jaffe P: Will the real Ritalin please stand up? Addendum
Newsletter 10: Fall 1992.
Huessey HR: Adolescents and Ritalin. Pediatrics 75: 614,
1985.
Hunt RD, Minderaa RB, Cohen DJ: Clonidine benefits children
with attention deficit disorder and hyperactivity: report of
a double-blind, placebo-crossover therapeutic trial.
Journal of the American Academy of Child and Adolescent
Psychiatry 24: 617-629, 1985.
******************************
Address Correspondences to:
John J. Ratey, M.D.
328 Broadway
Cambridge, MA 02139
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