Methylphenidate (
MPH) is a
psychostimulant drug approved for
treatment of
attention-deficit
hyperactivity disorder,
Postural Orthostatic
Tachycardia Syndrome and
narcolepsy.
It may also be
prescribed for
off-label use in treatment-resistant
cases of
lethargy,
depression, neural insult, and
obesity. Methylphenidate belongs to the
piperidine class of
compounds and increases the levels of
dopamine and
norepinephrine in the brain through reuptake
inhibition of the
monoamine transporters.
MPH possesses structural similarities to
amphetamine, and though it is less potent, its
pharmacological effects are even
more closely related to those of
cocaine.
MPH is most commonly known by the trademark name
Ritalin, which is an instant-release
racemic mixture, although a variety of formulations
and generic brand names exist.
History
Methylphenidate was first synthesized in 1944, and was identified
as a stimulant in 1954.
Originally it was marketed as a mixture of two racemates, 80%
(±)-erythro and 20% (±)-threo. Subsequent studies of the racemates
showed that the central stimulant activity was associated with the
threo racemate and were focused on the separation and
interconversion of the erythro isomer into the more active threo
isomer.
Beginning in the 1960s, it was used to treat children with
ADHD or ADD, known
at the time as hyperactivity or minimal brain dysfunction (MBD).
Today methylphenidate is the most commonly prescribed medication to
treat ADHD around the world.
Production and prescription of
methylphenidate rose significantly in the 1990s, especially in the
United
States
, as the ADHD diagnosis came to be better understood
and more generally accepted within the medical and mental health
communities.
Most
brand-name Ritalin is produced in the United States, and methylphenidate is produced in the United
States, Mexico
, Argentina
and Pakistan
.
Other generic forms, such as "methylin", are produced by several
U.S. pharmaceutical companies.
Ritalin is also sold in the United Kingdom
, Germany
and other
European countries (although in much lower volumes than in the
United States). These generic versions of methylphenidate
tend to outsell brand-name Ritalin four to one. In Belgium the
product is sold under the name "Rilatine" and in Brazil and
Portugal as "Ritalina".
Another medicine is Concerta, a once-daily extended-release form of
methylphenidate, which was approved in April 2000. Studies have
demonstrated that long-acting methylphenidate preparations such as
Concerta are just as effective, if not more effective, than IR
(instant release) formulas. Certain time-release medications are
also less prone to abuse as they are not easily crushed for
abuse.
In April 2006, the
U.S. Food and Drug
Administration (FDA) approved a transdermal patch for the
treatment of ADHD called
Daytrana.
Therapeutic uses
Methylphenidate 10 mg Tablet
(Mallinckrodt)
TMP is the most commonly prescribed
psychostimulant and works by increasing the
activity of the
central nervous
system. It produces such effects as increasing or maintaining
alertness, combating fatigue, and improving attention. The benefits
and cost effectiveness of methylphenidate long term are unknown due
to a lack of research. The long term effects of methylphenidate on
the developing brain are unknown. Methylphenidate is not approved
for children under six years of age.
Attention deficit hyperactivity disorder
TMP is approved by the FDA for the treatment of
attention-deficit
hyperactivity disorder The addition of
behavioural modification
therapy (e.g.
CBT) has additional benefits
on treatment outcome. There is a lack of evidence of the
effectiveness in the long term of beneficial effects of
methylphenidate with regard to learning and academic performance. A
meta analysis of the literature
concluded that methylphenidate quickly and effectively reduces the
signs and symptoms of ADHD in children under the age of 18 in the
short term but found that this conclusion may be biased due to the
high number of low quality clinical trials in the literature. There
have been no placebo controlled trials investigating the long term
effectiveness of methylphenidate beyond 4 weeks thus the long term
effectiveness of methylphenidate has not been scientifically
demonstrated. Serious concerns of
publication bias regarding the use of
methylphenidate for ADHD has also been noted. A diagnosis of ADHD
must be confirmed and the benefits and risks and proper use of
stimulants as well as alternative treatments should be discussed
with the parent before
stimulants are
prescribed. The dosage used can vary quite significantly from
individual child to individual child with some children responding
to quite low doses whereas other children require the higher dose
range. The dose therefore should be titrated to an optimal level
which achieves therapeutic benefit and minimal side effects.
Therapy with methylphenidate should not be indefinite. Weaning off
periods to assess symptoms are recommended.
Narcolepsy
Narcolepsy, a chronic sleep disorder
characterized by overwhelming daytime drowsiness and sudden attacks
of sleep, is treated primarily with stimulants. Methylphenidate is
considered effective in increasing wakefulness, vigilance, and
performance. Methylphenidate improves measures of somnolence on
standardized tests, such as the
Multiple Sleep Latency Test, but
performance does not improve to levels comparable to healthy
controls.
Adjunctive
Use of stimulants such as methylphenidate in cases of refractory
depression is controversial. In individuals with cancer,
methylphenidate is commonly used to counteract opioid-induced
somnolence, to increase the analgesic effects of opioids, to treat
depression, and to improve cognitive function. Methylphenidate may
be used in addition to an antidepressant for treatment-refractory
major depressive disorder.
It can also improve depression in several groups including stroke,
cancer, HIV-positive patients. However, benefits tend to be only
partial with stimulants being generally less effective than
traditional antidepressants and there is some suggestive evidence
of a risk of
habituation. Stimulants may
however, have fewer side effects than
tricyclic antidepressants in the
elderly and medically ill. A review of the literature found that
methylphenidate was ineffective for refractory cases of major
depression.
Substance dependence
Methylphenidate has shown some benefits as a replacement therapy
for
methamphetamine addicts. Methylphenidate and
amphetamine have been investigated as a chemical
replacement for the treatment of cocaine dependence in the same way
that
methadone is used as a replacement
for
heroin. Its effectiveness in treatment of
cocaine or other psychostimulant dependence has not been proven and
further research is needed.
Early research began in 2007-8 in some countries on the
effectiveness of methylphenidate as a substitute agent in
refractory cases of cocaine dependence. That it can satisfy
cravings for cocaine in a way which is subjectively and
pharmacologically equivalent but longer-lasting as well as easier
on the body and
somewhat safer and easier to manage has
long been part of the 'street lore' associated with stimulants in
many parts of the world. Methylenedioxymethcathinone (another
closely related phenethylamine derived stimulant) shows particular
potential for this application due to its closer similarity to the
effect of cocaine than amphetamine. This is similar to the way that
other substitution drugs such as methadone, buprenorphine, LAAM,
butorphanol, extended-release oral morphine, dihydrocodeine, and
clonidine were amongst opioid users in various times over the past
century.
Pervasive developmental disorders
Given the high co-morbidity between
ADHD and
autism, a few studies have examined the
efficacy and effectiveness of methylphenidate in the treatment of
autism. However, most of these studies examined the effects of
methylphenidate on attention and hyperactivity symptoms among kids
with
autism spectrum disorders. Aman
and Langworthy (2000) attempted to examine the effects of
methylphenidate on social-communication and self-regulation
behaviors among kids with ASDs.
The sample included 33 children with pervasive developmental
disorder (29 boys) with a mean age of 6.93 years (range 5-13). This
was a 4-week randomized, double-blind, cross-over placebo study,
with treatment changing each week between 4 conditions: placebo,
low dose, medium dose, and high dose. In this design, neither the
experimenters nor the families know which of the 4 treatments the
child is receiving at any given time. In addition, the treatment
condition changes randomly each week, without anyone knowing the
nature of the old or new condition. This allows the experimenters
to assume that consistent changes in behaviors that occur during a
particular treatment is truly due to the effect of that treatment
and not to the expectation of the treatment (placebo effect).
The results indicate that children showed significantly more joint
attention behaviors when receiving methylphenidate than when
receiving the placebo (although the most effective dosage varied by
individual). Furthermore, at a group level, the low dose of
methylphenidate resulted in significantly improved joint attention
behaviors when compared to the placebo, but no differences were
noted between the low, medium, and high doses. Low and medium doses
of methylphenidate also resulted in improved self-regulation
behavior when compared to placebo.
The study presents compelling preliminary evidence suggesting that
methylphenidate is effective in improving some social behaviors
among children with autism spectrum disorders.
Investigational
Animal studies using rats with ADHD like behaviours were used to
assess the safety of methylphenidate on the developing brain and
found that psychomotor impairments, structural and functional
parameters of the dopaminergic system were improved with treatment.
This animal data suggests that methylphenidate supports brain
development and hyperactivity in children diagnosed with ADHD.
However, in normal control animals methylphenidate caused long
lasting changes to the dopaminergic system suggesting that if a
child is misdiagnosed with ADHD they may be at risk of long lasting
adverse effects to brain development. Animal tests found that rats
given methylphenidate grew up to be more stressed and emotional. It
is unclear due to lack of followup study whether this occurs in
ADHD like animals and whether it occurs in humans. However, long
lasting benefits of stimulant drugs have not been found in
humans.
Methylphenidate may reduce the risk of falls in older adults by
treating cognitive deficits associated with aging and
disease.
Delivery formulations
Ritalin 10 mg pill
(Ciba/Novartis)
All media are in milligrams. Ritalin is mostly administered in the
form of a tablet or capsule.
Tablets
- Ritalin: 5, 10 or 20 mg tablets.
- Ritalin SR: 20 mg controlled-release
tablets.
- Attenta: 10 mg tablets.
- Methylin: 5, 10 or 20 mg tablets.
- Methylin ER: 5, 10 and 20 mg
controlled-release tablets.
- Metadate ER: 10 and 20 mg
controlled-release tablets.
- Equasym: 5, 10, 20 or 30 mg tablets.
- Rubifen: 5, 10 or 20 mg tablets.
- Motiron: 5, 10 or 20 mg tablets.
Capsules
- Concerta: 18, 27, 36, and 54 mg osmotic
controlled release capsules. (goes off patent in 2018)
Note: Some adults may take two 36 mg capsules for an effective
dose of 72 mg.
- Ritalin LA: 10, 20, 30 or 40 mg
controlled-release capsules.
- Metadate CD: 10, 20, 30, 40, 50 or 60 mg
controlled-release capsules.
- Biphentin: 10, 15, 30, 40, or 60 mg
suspended release capsules.
Patches
- Daytrana 10, 15, 20 or
30 mg controlled-release patches (1.1, 1.6, 2.2 or
3.3 mg/hour for 9 hours).
Adverse effects
Some adverse effects may emerge during chronic use of
methylphenidate so a constant watch for adverse effects is
recommended. Some adverse effects of stimulant therapy may emerge
during long term therapy but there is very little research of the
long term effects of stimulants.
The most common side effects of taking methylphenidate are
nervousness and insomnia.Other reactions include:
Known or suspected risks to health
Researchers have also looked into the role of methylphenidate in
affectingstature, with some studies finding slight decreases in
height acceleration.Other studies indicate height may normalize by
adolescence. In a 2005 study, only "minimal effects on growth in
height and weight were observed" after 2 years of treatment. "No
clinically significant effects on vital signs or laboratory test
parameters were observed."
A 2003 study tested the effects of dextromethylphenidate (
Focalin), levomethylphenidate, and (racemic)
dextro-, levomethylphenidate (Ritalin) on mice to search for any
carcinogenic effects. The researchers found that all three
preparations were non-genotoxic and non-clastogenic; d-MPH, d,
l-MPH, and l-MPH did not cause mutations or chromosomal
aberrations. They concluded that none of the compounds present a
carcinogenic risk to humans. Current scientific evidence supports
that long-term methylphenidate treatment does not increase the risk
of developing cancer in humans.
The use of ADHD medication in children under the age of 6 has not
been studied. Severe hallucinations may occur. ADHD symptoms
include hyperactivity and difficulty holding still and following
directions; these are also characteristics of a typical child under
the age of 6. For this reason it may be more difficult to diagnose
young children, and caution should be used with this age
group.
However, it was documented in 2000, by Zito et al.“that at least
1.5% of children between the ages of two and four are medicated
with stimulants, anti-depressants and anti-psychotic drugs, despite
the paucity of controlled scientific trials confirming safety and
long-term effects with preschool children.”
On March 22, 2006 the FDA Pediatric Advisory Committee decided that
medications using methylphenidate ingredients do not need black box
warnings about their risks, noting that "for normal children, these
drugs do not appear to pose an obvious cardiovascular risk."
Previously, 19 possible cases had been reported of
Cardiac arrest linked to children taking
methylphenidate and the Drug Safety and Risk Management Advisory
Committee to the FDA recommend a
"black-box" warning in 2006 for stimulant
drugs used to treat attention deficit/hyperactivity disorder.
Doses prescribed of stimulants above the recommended dose level is
associated with higher levels of
psychosis,
substance
misuse and psychiatric admissions.
Long term effects
The effects of long-term methylphenidate treatment on the
developing brains of children with ADHD is the subject of study and
debate. Although the safety profile of short-term methylphenidate
therapy in clinical trials has been well established, repeated use
of psychostimulants such as methylphenidate is less clear. The long
term effects of methylphenidate such as
drug addiction,
withdrawal reactions,
psychosis and
depression and effects in
pregnancy has received very little research and
thus the long term effects of using stimulants for ADHD are largely
unknown . There are no well defined withdrawal schedules for
discontinuing long term use of stimulants. There is limited data
which suggests that there may be modest benefits in correctly
diagnosed children with ADHD but there are also overall modest
risks. Short term clinical trials lasting a few weeks show an
incidence of psychosis of about 0.1%. A small study of just under
100 children which assessed long term outcome of stimulant use
found that 6% of children became psychotic after months or years of
stimulant therapy. Typically psychosis would abate soon after
stopping stimulant therapy. As the study size was small, larger
studies have been recommended. The long term effects on mental
health disorders in later life of chronic use of methylphenidate is
unknown. Concerns have been raised that long-term therapy might
cause
drug dependence,
paranoia,
schizophrenia and behavioral sensitisation,
similar to other stimulants. Psychotic symptoms from
methylphenidate can include,
hearing
voices,
visual
hallucinations, urges to harm oneself, severe
anxiety,
euphoria,
grandiosity,
paranoid delusions,
confusion, increased
aggression and
irritability.
Methylphenidate psychosis is
unpredictable in who it will occur. Family history of mental
illness does not predict the incidence of stimulant toxicosis in
ADHD children. High rates of childhood stimulant use is found in
patients with a diagnosis of
schizophrenia and
bipolar disorder independent of ADHD. Individuals
with a diagnosis of bipolar or schizophrenia who were prescribed
stimulants during childhood typically have a significantly earlier
onset of the psychotic disorder and suffer a more severe clinical
course of psychotic disorder. Knowledge of the effects of chronic
use of methylphenidate is poorly understood with regard to
persisting behavioral and neuroadaptational effects.
Tolerance and behavioural
sensitisation may occur with long term use of methylphenidate.
There is also
cross tolerance with
other
stimulants such as
amphetamines and
cocaine. Stimulant
withdrawal or
rebound reactions can occur and should be
minimised in intensity, i.e. via a gradual tapering off of
medication over a period of weeks or months. A very small study of
abrupt withdrawal of stimulants did suggest that withdrawal
reactions are not typical. Nonetheless withdrawal reactions may
still occur in susceptible individuals. The
withdrawal or
rebound
symptoms of methylphenidate can include
psychosis,
depression,
irritability and a temporary worsening of the
original ADHD symptoms. Methylphenidate due to its very short
elimination half life may be
more prone to
rebound effects than
d-amphetamine. Up to a third of ADHD
children experience a
rebound effect
when methylphenidate dose wears off.
Contraindications
Methylphenidate should not be prescribed concomitantly with
tricyclic antidepressants,
such as
desipramine, or
monoamine oxidase inhibitors,
such as
phenelzine or
tranylcypromine, as methylphenidate may
dangerously increase plasma concentrations, leading to potential
toxic reactions (mainly,
cardiovascular effects). Methylphenidate
should not be prescribed to patients who suffer from severe
arrhythmia,
hypertension or
liver
damage. It shouldn't be prescribed to patients who demonstrate
drug-seeking behaviour,
pronounced agitation or nervousness. Care should be taken while
prescribing methylphenidate to children with a family history of
Paroxysmal Supraventricular Tachycardia (PSVT).
Special precautions
Special precaution is recommended in individuals with epilepsy with
additional caution in individuals with uncontrolled epilepsy due to
the potential for methylphenidate to lower the seizure
threshold.
Pregnancy
Use of methylphenidate during pregnancy is not recommended as there
is some evidence of developmental effects, particularly
neurobehavioral alterations.
Overdose
In
2004, over 8000 methylphenidate ingestions
were reported in US poison center data. The most common reasons for
intentional exposure were drug abuse and suicide attempts. An
overdose manifests in agitation, hallucinations, psychosis,
lethargy, seizures, tachycardia, dysrhythmias, hypertension, and
hyperthermia.
Benzodiazepines may be
used as treatment if agitation, dystonia, or convulsions are
present. MPH is prescribed at 1/100th of the estimated lethal
dose.
Pharmacology
Methylphenidate is a chain substituted
amphetamine derivative, although its chemical
structure is more closely related to cocaine. Similar to
amphetamines and
cocaine,
a key target of methylphenidate is the dopamine transporter (DAT).
Although methylphenidate is an amphetamine derivative subtle
differences exist in its pharmacology; amphetamine works as a
dopamine transport substrate where as methylphenidate works as a
dopamine transport blocker. Methylphenidate is most active at
modulating levels of
dopamine and to a
lesser extent
noradrenaline.
Pharmacokinetics
Methylphenidate has both
DAT
and
NET binding affinity,
with the dextromethylphenidate enantiomers displaying a prominent
affinity for the norepinephrine transporter. Both the dextro- and
levorotary enantiomers displayed receptor affinity for the
serotonergic 5HT
1A and
5HT
2B subtypes, though direct binding to the
serotonin transporter was not
observed.
The enantiomers and the relative psychoactive effects and CNS
stimulation of dextro- and levo-methylphenidate is analogous to
what is found in amphetamine, where dextro-amphetamine is
considered to have a greater psychoactive and CNS stimulatory
effect than levo-amphetamine.
Pharmacodynamics
Methylphenidate exerts its therapeutic effects via blocking the
reuptake of dopamine into nerve terminals (as well as stimulating
the release of dopamine from dopamine nerve terminals) resulting in
increased
dopamine levels in the
synapse. The onset of
central nervous system effects occurs
rapidly after intake of methylphenidate and persist for about 4
hours. The mechanism of action and chemical structure of
methylphenidate is extremely similar to cocaine with usual doses of
both drugs occupying 50% of dopamine transporters. However, cocaine
effects such as
euphoria are rare at doses
prescribed clinically.
The means by which methylphenidate affects people diagnosed with
ADHD are not well understood. Some researchers have theorized that
ADHD is caused by a
dopamine imbalance in
the
brains of those affected. Methylphenidate
is a norepinephrine and
dopamine reuptake inhibitor,
which means that it increases the level of the dopamine
neurotransmitter in the brain by partially
blocking the dopamine transporter (DAT) that removes dopamine from
the
synapses. This inhibition of DAT blocks
the reuptake of dopamine and norepinephrine into the presynaptic
neuron, increasing the amount of dopamine in the synapse. It also
stimulates the release of dopamine and norepinephrine into the
synapse. Finally, it increases the magnitude of dopamine release
after a stimulus, increasing the salience of stimulus. An alternate
explanation which has been explored is that the methylphenidate
affects the action of
serotonin in the
brain. However, benefits with other stimulants which have a
different mechanism of action indicates that support for a deficit
in specific
neurotransmitters is
unsupported and unproven by the evidence and remains a speculative
hypothesis.
It is commonly asked why a stimulant should be used to treat
hyperactivity, which seems paradoxical. However,
MRIs of ADHD brains previously
drugged with stimulants show decreased activity in the brain
centers critical to concentration and impulse control.
One study finds that methylphenidate reduces the increases in brain
glucose metabolism during performance of a cognitive task by about
50%. This suggests that, similar to increasing dopamine and
norepinephrine in the striatum and prefrontal cortex,
methylphenidate may focus activation of certain regions and make
the brain more efficient. This is consistent with the observation
that stimulant drugs can enhance attention and performance in some
individuals. If brain resources are not optimally distributed (for
example, in individuals with ADHD or sleep deprivation), improved
performance could be achieved by reducing task-induced regional
activation. Stimulant delivery when brain resources are already
optimally distributed may then adversely affect performance.
A paper published in
Biological Psychiatry reports that
methylphenidate fine-tunes the functioning of neurons in the
prefrontal cortex - a brain region
involved in attention, decision-making and impulse control - while
having few effects outside it. The team studied PFC neurons in rats
under a variety of methylphenidate doses, including one that
improved the animals' performance in a working memory task of the
type that ADHD patients have trouble completing. Using
microelectrodes, the scientists observed both the random,
spontaneous firings of PFC neurons and their response to
stimulation of the
hippocampus. When
they listened to individual PFC neurons, the scientists found that
while cognition-enhancing doses of methylphenidate had little
effect on spontaneous activity, the neurons' sensitivity to signals
coming from the hippocampus increased dramatically. Under higher,
stimulatory doses, on the other hand, PFC neurons stopped
responding to incoming information.
Interactions
Intake of
adrenergic agonist
drugs or
pemoline with methylphenidate
increases the risk of
liver toxicity.
Antidepressants taken in conjunction with methylphenidate may cause
hypertension,
hypothermia and
convulsions. When methylphenidate is coingested
with ethanol, a metabolite called
ethylphenidate is formed via hepatic
transesterification, not unlike the hepatic formation of
cocaethylene from
cocaine and alcohol.
Coingestion of alcohol (ethanol) also increases the blood plasma
levels of d-methylphenidate by up to 40%. It is more selective to
the
dopamine transporter (DAT)
than methylphenidate, having approximately the same efficacy as the
parent compound, but has significantly less activity on the
norepinephrine
transporter (NET).
Abuse potential
.jpg/300px-Ritalin_(AU).jpg)
Legal warning printed on Ritalin
carton (AU)
Methylphenidate is a
drug of abuse.
Methylphenidate like other stimulants increases dopamine levels but
at therapeutic doses the increase is slow and thus euphoria does
not typically occur except in rare instances. The abuse potential
is increased when methylphenidate is crushed and snorted or when it
is injected producing effects almost identical to cocaine.
Cocaine-like effects can also occur with very large doses taken
orally. The dose however, which produces euphoric effects varies
between individuals. Methylphenidate is actually more potent than
cocaine in its effect on dopamine transporters. Methylphenidate
should not be viewed as a weak stimulant as has previously been
hypothesised. The primary source of methylphenidate for abuse is
diversion from legitimate prescriptions rather than illicit
synthesis. Those who use it to stay awake do so by taking it
orally, while intranasal and intravenous are the preferred means
for inducing euphoria. IV users tend to be adults whose use may
cause panlobular
pulmonary
emphysema. Methylphenidate has a high potential for
drug dependence and addictive abuse due to
its similarity pharmaologically to
cocaine
and
amphetamines. Abuse of prescription
stimulants is higher amongst college students than non-college
attending young adults. College students misuse methylphenidate
either as a study aid or to stay awake longer. The increased
alcohol consumption due to stimulant misuse has additional negative
effects on health.
Methylphenidate's pharmacological effect on the central nervous
system is almost identical to that of cocaine. Studies have shown
that the two drugs are nearly indistinguishable when administered
intravenously to cocaine addicts. However, cocaine has a slightly
higher affinity for the dopamine receptor in comparison to
methylphenidate, which is thought to be the mechanism of the
euphoria associated with the relatively short-lived cocaine high.
Controversy has surrounded whether methylphenidate is as commonly
abused as other stimulants with many believing that its rate of
abuse is much lower than other stimulants. However, the majority of
studies assessing its abuse potential and drug liking scores have
determined that it has a similar abuse potential as
cocaine and
amphetamine.
Reports of users experimenting with mixing methylphenidate with
caffeine and benzocaine to produce a powder for insufflation for an
even more cocaine-like effect began to appear in the middle 1970s;
this is apparently an incrementation upon a mixture known as Toot
containing
phenylpropanolamine,
caffeine, and benzocaine in the search for legal highs. As moderate
doses of cocaine have caffeine-like effects and benzocaine produces
a slight stimulant effect of its own perhaps 5 per cent the
strength of cocaine with a ceiling in that range, the mixture is
reported to have at least some of the sought effects.
Legal status
In the
United
States, methylphenidate is classified as a Schedule II controlled substance, the designation
used for substances that have a recognized medical value but
present a high likelihood for abuse because of their addictive
potential. Internationally, methylphenidate is a Schedule II
drug under the
Convention on Psychotropic
Substances.
In the United Kingdom, methylphenidate is a controlled 'Class B'
substance (the same category as Cannabis),
and possession without prescription is illegal, with a maximum
sentence of prison.
Controversy
Japanese bottle of Ritalin
Methylphenidate (usually referred to by the brand name Ritalin) has
been the subject of controversy in relation to its use in the
treatment of ADHD. Criticism generally revolves around alleged or
established side effects , concerns of illicit use and abuse, and
the ethics of giving
psychotropic drugs
to children to reduce ADHD symptoms. There is growing concern of
the widespread use of methylphenidate and its long term effects,
which include concerns of life threatening effects. Calls have been
made that methylphenidate be severely restricted in its use. The
pharmacological effects of methylphenidate, a schedule II drug are
almost identical to
cocaine and the
amphetamines. The abuse pattern of
methylphenidate is very similar to cocaine and amphetamines. In
2002, a study showed that rats treated with methylphenidate are
more receptive to the reinforcing effects of cocaine. The
contention that methylphenidate acts as a
gateway drug been discredited by multiple
sources, though this point is still under debate. A study found
that a group which had received stimulants during childhood showed
a higher rate of cocaine abuse in later adulthood—twice that of the
other groups, possibly suggesting that stimulant use during
childhood was associated with sensitising or predisposing children
to cocaine abuse later in life . Smoking tobacco also appeared to
increase the risk of cocaine abuse in this population but even
after controlling for tobacco exposure cocaine abuse was still
significantly higher in adults who had been medicated with
stimulants as children. This risk was still present 15 years after
stimulant medication exposure.
Controversy also surrounds whether ADHD is a disorder or a
personality trait with some in the medical profession believing
that it is a myth that hyperactivity is a disorder . They further
point out that as a group ADHD children have in general healthy
brains with no gross
neurological
deficits.
Richard Bromfield claims that
Ritalin is often prescribed not because of an underlying
neurological disorder, but as an easy way to calm down children
whose misbehavior actually results from ordinary causes such as bad
parenting.
Treatment of ADHD has led to legal actions including
malpractice suits regarding
informed consent, inadequate information on
side effects,
misdiagnosis and coercive use of medications by
school systems.
Chemistry of MPH
Four isomers of methylphenidate are known to exist. One pair of
threo isomers and one pair of erythro are
distinguished, from which only
d-threo-methylphenidate exhibits the
pharmacologically usually desired effects. When the drug was first
introduced it was sold as a 3:1 mixture of erythro:threo
diastereomers. The erythro diastereomers are
also
pressor amines. "TMP" is
referring only to the threo product that does not contain any
erythro diastereomers. Since the threo isomers are energetically
favored, it is easy to
epimerize out any
of the undesired erythro isomers. The drug that contains only
dextrorotary methylphenidate is called
d-TMP.
Satendra Singh (2000), pages 81-87.
See also
- Related drugs
References
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