Serious Cardiovascular Events
Sudden Death and Pre-Existing Structural
Cardiac Abnormalities or Other Serious Heart Problems
Children and Adolescents
Sudden death has been reported in association with CNS stimulant treatment at
usual doses in children and adolescents with structural cardiac abnormalities or
other serious heart problems. Although some serious heart problems alone carry
an increased risk of sudden death, stimulant products generally should not be
used in children or adolescents with known serious structural cardiac
abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other
serious cardiac problems that may place them at increased vulnerability to the
sympathomimetic effects of a stimulant drug.
Adults
Sudden death, stroke, and myocardial infarction have been reported in adults
taking stimulant drugs at usual doses for ADHD. Although the role of stimulants
in these adult cases is also unknown, adults have a greater likelihood than
children of having serious structural cardiac abnormalities, cardiomyopathy,
serious heart rhythm abnormalities, coronary artery disease, or other serious
cardiac problems. Adults with such abnormalities should also generally not be
treated with stimulant drugs.
Hypertension and Other Cardiovascular
Conditions
Stimulant medications cause a modest increase in average blood pressure
(about 2-4 mmHg) and average heart rate (about 3-6 bpm), and individuals may
have larger increases. While the mean changes alone would not be expected to
have short-term consequences, all patients should be monitored for larger
changes in heart rate and blood pressure. Caution is indicated in treating
patients whose underlying medical conditions might be compromised by increases
in blood pressure or heart rate, e.g., those with pre-existing hypertension,
heart failure, recent myocardial infarction, or ventricular arrhythmia.
Assessing Cardiovascular Status in Patients being
Treated with Stimulant Medications
Children, adolescents, or adults who are being considered for treatment with
stimulant medications should have a careful history (including assessment for a
family history of sudden death or ventricular arrhythmia) and physical exam to
assess for the presence of cardiac disease, and should receive further cardiac
evaluation if findings suggest such disease (e.g., electrocardiogram and
echocardiogram). Patients who develop symptoms such as exertional chest pain,
unexplained syncope, or other symptoms suggestive of cardiac disease during
stimulant treatment should undergo a prompt cardiac evaluation.
Psychiatric Adverse Events
Pre-Existing Psychosis
Administration of stimulants may exacerbate symptoms of behavior disturbance
and thought disorder in patients with a pre-existing psychotic disorder.
Bipolar Illness
Particular care should be taken in using stimulants to treat ADHD in patients
with comorbid bipolar disorder because of concern for possible induction of a
mixed/manic episode in such patients. Prior to initiating treatment with a
stimulant, patients with comorbid depressive symptoms should be adequately
screened to determine if they are at risk for bipolar disorder; such screening
should include a detailed psychiatric history, including a family history of
suicide, bipolar disorder, and depression.
Emergence of New Psychotic or Manic Symptoms
Treatment emergent psychotic or manic symptoms, e.g., hallucinations,
delusional thinking, or mania in children and adolescents without a prior
history of psychotic illness or mania can be caused by stimulants at usual
doses. If such symptoms occur, consideration should be given to a possible
causal role of the stimulant, and discontinuation of treatment may be
appropriate. In a pooled analysis of multiple short-term, placebo-controlled
studies, such symptoms occurred in about 0.1% (4 patients with events out of
3,482 exposed to methylphenidate or amphetamine for several weeks at usual
doses) of stimulant-treated patients compared to 0 in placebo-treated
patients.
Aggression
Aggressive behavior or hostility is often observed in children and
adolescents with ADHD, and has been reported in clinical trials and the
postmarketing experience of some medications indicated for the treatment of
ADHD. Although there is no systematic evidence that stimulants cause aggressive
behavior or hostility, patients beginning treatment for ADHD should be monitored
for the appearance of or worsening of aggressive behavior or hostility.
Long-Term Suppression of Growth
Careful follow-up of weight and height in children ages 7 to 10
years who were randomized to either methylphenidate or non-medication treatment
groups over 14 months, as well as in naturalistic subgroups of newly
methylphenidate-treated and non-medication treated children over 36 months (to
the ages of 10 to 13 years), suggests that consistently medicated children
(i.e., treatment for 7 days per week throughout the year) have a temporary
slowing in growth rate (on average, a total of about 2 cm less growth in height
and 2.7 kg less growth in weight over 3 years), without evidence of growth
rebound during this period of development. Published data are inadequate to
determine whether chronic use of amphetamines may cause a similar suppression of
growth, however, it is anticipated that they likely have this effect as well.
Therefore, growth should be monitored during treatment with stimulants, and
patients who are not growing or gaining height or weight as expected may need to
have their treatment interrupted.
Seizures
There is some clinical evidence that stimulants may lower the
convulsive threshold in patients with prior history of seizures, in patients
with prior EEG abnormalities in absence of seizures, and, very rarely, in
patients without a history of seizures and no prior EEG evidence of seizures. In
the presence of seizures, the drug should be discontinued.
Visual Disturbance
Difficulties with accommodation and blurring of vision have been
reported with stimulant treatment.
Use in Children Under Six Years of Age
Methylphenidate should not be used in children under 6 years,
since safety and efficacy in this age group have not been established.
Drug Dependence
Methylphenidate should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic espisodes can occur, especially with parenteral abuse. Careful supervision is required during withdrawal from abusive use, since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.
