y, e.g., repeated diets, group programs, and other drugs. the limited usefulness of amphetamines (see clinical pharmacology) should be weighed against possible risks inherent in use of the drug, such as those described below.

hood 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 (see contraindications). hypertension and other cardiovascular conditions stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mmhg) and average heart rate (about 3 to 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 (see contraindications). 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 3482 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 methylphenidatetreated 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. peripheral vasculopathy, including raynaud's phenomenon stimulants, including amphetamine sulfate tablets, used to treat adhd are associated with peripheral vasculopathy, including raynaud's phenomenon. signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. effects of peripheral vasculopathy, including raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. signs and symptoms generally improve after reduction in dose or discontinuation of drug. careful observation for digital changes is necessary during treatment with adhd stimulants. further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. serotonin syndrome serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (maois), selective serotonin reuptake inhibitors (ssris), serotonin norepinephrine reuptake inhibitors (snris), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and st. john's wort (see drug interactions). amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome p450 2d6 (cyp2d6) and display minor inhibition of cyp2d6 metabolism (see clinical pharmacology). the potential for a pharmacokinetic interaction exists with the co-administration of cyp2d6 inhibitors which may increase the risk with increased exposure to amphetamine sulfate tablets. in these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit cyp2d6 (see drug interactions). serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). concomitant use of amphetamine sulfate tablets with maoi drugs is contraindicated (see contraindications). discontinue treatment with amphetamine sulfate tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. if concomitant use of amphetamine sulfate tablets with other serotonergic drugs or cyp2d6 inhibitors is clinically warranted, initiate amphetamine sulfate tablets with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome. visual disturbance difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

a barbiturate. experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendation in this regard. acidification of the urine increases amphetamine excretion. if acute, severe hypertension complicates amphetamine overdosage, administration of intravenous phentolamine has been suggested. however, a gradual drop in blood pressure will usually result when sufficient sedation has been achieved. chlorpromazine antagonizes the central stimulant effects of amphetamines and can be used to treat amphetamine intoxication.

sity is primarily one of appetite suppression. other central nervous system actions or metabolic effects, may be involved, for example. adult obese subjects instructed in dietary management and treated with "anorectic" drugs lose more weight on the average than these treated with placebo and diet, as determined in relatively short-term clinical trials. the magnitude of increased weight loss of drug-treated patients over placebo-treated patients is only a fraction of a pound a week. the rate of weight loss is greatest in the first weeks of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks. the origins of the increased weight loss due to the various possible drug effects are not established. the amount of weight loss associated with the use of an "anorectic" drug varies from trial to trial, and the increased weight loss appears to be related in part to variables other than the drug prescribed, such as the physician-investigator, the population treated, and the diet prescribed. studies do not permit conclusions as to the relative importance of the drug and nondrug factors on weight loss. the natural history of obesity is measured in years, whereas the studies cited are restricted to few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered clinically limited.