Methylphenidate Atomoxetine

Stimulants Stimulant drugs for the treatment of attention deficit hyperactivity disorder (amphetamine and dextroamphetamine, atomoxetine, methylphenidate) can raise blood pressure significantly... 

The proposed mechanism of ADHD pharmacotherapy is to modulate neurotransmitters in order to improve academic and social functioning. Pharmacologic therapy can be divided into two categories stimulants and non-stimulants. Stimulant medications include methylphenidate, dexmethylphenidate, amphetamine salts, and dextroamphetamine, whereas non-stimulant medications include atomoxetine, tricyclic antidepressants (e.g., imipramine), clonidine, guanfacine, and bupropion. 

Atomoxetine is the most recent addition to the ADHD armamentarium in both children and adults. In clinical studies, atomoxetine has demonstrated superior efficacy over placebo and equivalent efficacy when compared with a suboptimal immediate-release methylphenidate dose.17 20 However, it is not clear whether atomoxetine is superior to typical methylphenidate doses or other stimulant formulations. Atomoxetine may be used as a second- or third-line medication for ADHD. 

First-line pharmacotherapy treatments include methylphenidate, dextroamphetamine, the mixed amphetamine salts (Adderall), and atomoxetine (see Table 8.3). When an early evening dose is indicated (e.g., completion of homework) it is typically at 25-50% of the doses prescribed earlier in the day. 

Starting Treatment in Adults with ADHD. Beginning treatment of an adult is not significantly different from doing so in a child. The stimulants and atomoxetine remain the most effective medications. Methylphenidate, dextroamphetamine, and Adderall appear to be equally effective in group trials, but individuals may respond preferentially to one medication or the other. 

Monoamine oxidase inhibitors Paroxetine Protriptyline Sertraline Venlafaxine Stimulants Atomoxetine Dextroamphetamine Methylphenidate Modaflnil Pemoline... 

APPROVED TREATMENTS FOR ATTENTION DEFICIT HYPERACTIVITY DISORDER AMPHETAMINE (ADDERALL ), METHYLPHENIDATE (RITALIN ), AND ATOMOXETINE (STRATERRA )... 

As of 2006, there are several branded medications approved for the treatment of ADHD however, there are only three chemicals that make up the primary active ingredients in these drugs the (5)-enantiomer of amphetamine (1), the 2(/ ),2 (7 )-enantiomer of methylphenidate (2), and the (/ )-enantiomer of atomoxetine (3). An older approved ADHD drug, pemoline (Cylert ), was withdrawn from the market in 2005 due to reported... 

All three ADHD-approved chemical entities have at least one chiral center, a feature that has led to a number of interesting syntheses of these compounds over the years. Amphetamine (1) and methylphenidate (2) were discovered before the modern era of asymmetric and enantioselective synthesis, and are sold as racemic, single-enantiomer, and enantio-enriched formulations. Atomoxetine (3), hrst presented in a 1977 Eli Lilly patent, was developed as a single-enantiomer drug (Molloy and Schmiegel, 1977). 

Kratochvil CJ, Heiligenstein JH, Dittmann R, et al Atomoxetine and methylphenidate treatment in children with ADHD a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry 41 776-784, 2002... 

CNS and cardiovascular actions of d,l-methylphenidate could theoretically be enhanced by combination with agents that block norepinephrine reuptake, such as the tricyclic antidepressants desipramine or protriptyline, venlafaxine, duloxetine, atomoxetine, milnacipran, and reboxetine... 

Atomoxetine, a selective norepinephrine reuptake inhibitor, is the first nonstrmulant approved by the Food and Drug Administration (FDA) for the treatment of ADHD. In contrast to the stimulants, it has no apparent abuse potential and is not a controlled substance. Placebo-controlled, short-term trials (6 to 12 weeks) have shown that atomoxetine is effective in reducing ADHD symptoms in children, teens, and adults. It is not clear whether it is as effective as the stimulants, although one preliminary open study suggested comparable efficacy with methylphenidate. ... 

At this time, the preferred first-line drug therapy for ADHD is either methylphenidate, dexmethylphenidate, mixed amphetamine salts, or dextroamphetamine. Atomoxetine, bupropion, or TCAs are good options for those umesponsive to or unable to tolerate stimulants. Clonidine and guanfacine are third-line options or adjuncts that require careful cardiovascular monitoring. Mood stabilizers (e.g., lithium, divalproex, and carbamazepine) and atypical antipsychotics are adjuncts for control of aggression or comorbid bipolar disorder. Other agents require further investigation before their status in the treatment of ADHD can be fuUy determined. 

Examples of drugs used to treat ADHD are dexamfetamine, methylphenidate and atomoxetine. These drugs inhibit the re-uptake of noradrenaline and dopamine. Increase in levels of these two transmitters in the prefrontal cortex is thought to increase inhibitory control in the limbic system. 

OTHER THERAPEUTIC USES OE THESE DRUGS The various antidepressant agents have found broad utility in other disorders that may not be related psychobiologicaUy to the mood disorders. Current applications include rapid but temporary suppression of enuresis with low (e.g., 25 mg) pre-bedtime doses of tricyclic antidepressants, including imipramine and nortriptyline, by uncertain mechanisms in children and in geriatric patients, as well as a beneficial effect of duloxetine on urinary stress incontinence. Antidepressants have a growing role in attention-deficit/hyperactivity disorder in children and adults, for which imipramine, desipramine, and nortriptyline appear to be effective, even in patients responding poorly to or who are intolerant of the stimulants (e.g., methylphenidate). Newer NE selective reuptake inhibitors also may be useful in this disorder atomoxetine is approved for this application. Utility of SSRIs in this syndrome is not established, and bupropion, despite its similarity to stimulants, appears to have limited efficacy. 

A critical part of the assessment must be to determine the patient s impairment at various times throughout the day to ensure that medication coverage overlaps with the time when the patient is most likely to benefit. As with all medication trials, it is important to start with a low dose of medication and keep increasing it slowly until the optimal risk-to-benefit ratio has been determined. Stimulant medication (methylphenidate, mixed amphetamine salts, and pemoline) and atomoxetine (a non-stimulant selective norepinephrine reuptake inhibitor, approved by the FDA for adult ADHD) are the first-line treatments of adult ADHD. Pemoline is not recommended as first-line treatment due to the risk of hepatoxicity. Stimulant drugs used to treat adults with ADHD are considered safe and effective, and have been well studied. There are several new long-acting formulations of... 

Atomoxetine is used as a safe and well-tolerated nonstimulant treatment of ADHD in both adults and children and of depression. Among children and adolescents aged 8 to 18 years, atomoxetine was superior to placebo in reducing symptoms of ADHD and in improving social and family functioning symptoms. Oral atomoxetine is promoted as an alternative to conventional ADHD therapy with methylphenidate, dextroamphetamine, and pemoline. It also can be a replacement for bupropion or for TCAs. Onset of action is approximately 7 days. 

Easton N., Steward C., Marshall R, Fone K. and Marsden C. 2006b. Effects of amphetamine isomers, methylphenidate and atomoxetine on synaptosomal and synaptic vesicle accumulation and release of dopamine and noradrenaline in vitro in the rat brain. Neuropharmacology 52 405 14. Epub 3 October 2006... 

Steifel G, Besag FMC. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder. Drug Saf 2010 33 821 2. 

In an open study in children aged 6-17 years the addition of OROS methylphenidate increased the rates of insomnia, irritability, and loss of appetite compared with atomoxetine alone [M ]. 

In a study based on the UK General Practice Research Database (GPRD) in patients with ADHD, aged 2-21 years, from 1993 to 2006 with prescriptions for methylphenidate, dexamfetamine, or atomoxetine, there was no increase in the risk of sudden death but there was an increased risk of suicide [55 ]. Seven patients died in a cohort of 18 637 patient-years, and cause of death was obtained in six none was deemed to be a case of sudden death (incident rate ratio 1.63 95% Cl = 0.04, 9.71). The standardized mortality ratios for suicide were 162 (95% Cl = 20, 585) in patients aged 11-14 years and... 

Hammerness P, Georgiopoulos A, Doyle RL, Utzinger L, Schillinger M, Martelon M, Brodziak K, Biederman J, Wilens TE. An open study of adjunct OROS-methylphenidate in children who are atomoxetine partial responders II. Tolerability and pharmacokinetics. J Child Adolesc Psychopharmacol 2009 19(5) 493-9. 

A 25-year-old man experienced spontaneous ejaculation without sexual arousal following testicular pain after micturition with the use of methylphenidate. His drug history included atomoxetine, which also gave spontaneous ejaculations following micturition. After 2 years, the patient mainly used the long-acting variant of methylphenidate (Concerta ) and sometimes the shorter-acting variant of methylphenidate (Ritalin ) [26 ]. 

The ratio of NAA/tCr decreased in the left dorsolateral prefrontal cortex and Cho/tCr increased in the right after atomoxetine medication. The ratio of Gbc/tCr increased in the left prefrontal white matter after methylphenidate medication. 

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