Atomoxetine dosing

Plasma concentrations of atomoxetine may be increased by drugs that inhibit CYP450 2D6 (e.g., paroxetine, fluoxetine), so atomoxetine dose may need to be reduced if co-administered... 

Paroxetine markedly increases atomoxetine levels in extensive metabolisers of CYP2D6. Fluoxetine also raises atomoxetine levels. There is a possibility that this may increase adverse effects, and a slower titration of atomoxetine dose is su ested for patients taking paroxetine and other CYP2D6 inhibitors. 

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. 

Medications that enhance norepinephrine activity can do so in one of several ways. First, they can block the reuptake of norepinephrine back into the nerve cell once it has been released. This keeps the norepinephrine in the synapse longer and therefore makes it more active. The tricyclic antidepressants (TCAs), duloxetine (Cymbalta), and venlafaxine (Effexor) act in this manner, as does paroxetine (Paxil) at higher doses. Atomoxetine (Strattera), a treatment for ADHD, also works in this way. 

However, these side effects can be experienced with reboxetine or atomoxetine. Although they are seldom severe, one may need to take steps to remedy the side effects. The first step is to use the smallest effective dose. When this fails, using a second medication such as a benzodiazepine to counteract sleep difficulties or anxiety can be tried. However, without compelling reasons to stay with one of these medications, the best remedy is often to change to a different antidepressant. 

Concomitant use In children up to 70 kg body weight administered strong CYP2D6 inhibitors, initiate atomoxetine at 0.5 mg/kg/day and only increase to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well-tolerated. 

Absorption/Distribution - Atomoxetine is well absorbed after oral administration and is minimally affected by food. It is rapidly absorbed after oral administration, with absolute bioavailability of about 63% in extensive metabolizers (EMs) and 94% in poor metabolizers (PMs). Maximal plasma concentrations (Cmax) reached approximately 1 to 2 hours after dosing. At... 

Cardiac effects Use atomoxetine with caution in patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease because it can increase blood pressure and heart rate. Measure pulse and blood pressure at baseline, following dose increases, and periodically while on therapy. 

Atomoxetine (Strattera) [ADHD/Selective Norepinephrine Reuptake Inhioiter] WARNING Severe liver injury may rarely occur D/C w/ jaundice or TLFT, T frequency of suicidal thoughts Uses ADHD Action Selective norepinephrine reuptake inhibitor Dose Adults Children >70 kg. 40 mg X 3 d, T to 80-100 mg -s- daily-bid Feds <70 kg. 0.5 mg/kg x 3 d, then T 1.2 mg/kg daily or bid (max 1.4 mg/kg or 100 mg) Caution [C, /-] Contra ... 

Take the last daily dose of atomoxetine early in the evening to avoid insomnia... 

Michelson, D., Paries, D., Wernicke, J., Kelsey, D., Kendrick, K., Sallee, RR., Spencer, T. (2001) Atomoxetine in the treatment of children and adolescents with attention deficit / hyperactivity disorder a randomized place to controlled, dose response study. Pediatrics 108 E83. 

Spencer, X, Biederman, J., Heiligenstein, J., Wilens, X, Paries, D., Prince, J., Earaone, S.V., Rea, J., Witcher, J., and Zeras, S. (2001) An open-label, dose-ranging study of atomoxetine in children with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 11 ... 

Spencer T, Biederman J, Heiligenstein J, et al An open-label, dose-ranging study of atomoxetine in children with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 11 251-265, 2001... 

ATOMOXETINE DRUG DEPENDENCE THERAPIES-BUPROPION 1. t plasma concentrations of atomoxetine with risk of toxic effects 2. t risk of seizures. This risk is marked in elderly people, in patients with a history of seizures, with addiction to opiates/cocaine/ stimulants, and in diabetics treated with oral hypoglycaemics or insulin 1. Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 2. Bupropion is associated with a dose-related risk of seizures. These drugs, which lower seizure threshold, are individually epileptogenic. Additive effects when combined 1. Initiate therapy of these drugs, particularly those with a narrow therapeutic index at the lowest effective dose 2. Extreme caution. The dose of bupropion should not exceed 450 mg/day (or 150 mg/day in patients with severe hepatic cirrhosis)... 

Initiate therapy of these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. hydrocodone, oxycodone, desipramine, paroxetine, chlorpheniramine, mesoridazine, alprenolol, amphetamines, atomoxetine)... 

In such individuals, use half the usual dose of atomoxetine if tolerated... 

Mirtazapine, modafinil, atomoxetine (add A/ith caution and at lower doses since bupropion could theoretically raise atomoxetine levels) both for residual symptoms of depression and attention deficit disorder... 

Bupropion, mirtazapine, reboxetine, or atomoxetine (add with caution and at lower doses since citalopram could theoretically raise atomoxetine levels) use combinations of antidepressants with caution as this may activate bipolar disorder and suicidal ideation... 

Atomoxetine has a significantly slower onset of therapeutic effect than stimulants (2 to 4 weeks versus 1 hour with an effective stimulant dose). Atomoxetine may be taken once daily or in divided doses in the morning or late afternoon. Table 61-5 provides dosing and titration recommendations for all nonstimulant medications. 

Atomoxetine and bupropion require monitoring to detect changes in appetite, weight, and sleep patterns, or if pulse or blood pressure changes occur. A therapeutic trial of atomoxetine or bupropion consists of 1 month of maximum tolerated doses. ... 

I Although plasma t/, of atomoxetine is short (approx, four hours) the behavioural effects last longer than predicted from the pharmacokinetics and once-daily dosing is effective. 

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... 

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