Antidepressants atomoxetine

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 (Strattera). Atomoxetine has recently been approved as a treatment for ADHD. Atomoxetine, similar to some of the antidepressants discussed later, is a preferential inhibitor of norepinephrine reuptake. Because nerve terminals in the cerebral cortex have no dopamine reuptake sites, dopamine is taken up at nearby norepinephrine reuptake sites. Consequently, all norepinephrine reuptake inhibitors increase the availability of dopamine in the prefrontal cortex, likely the primary mechanism of atomoxetine action in ADHD. 

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. 

Atomoxetine was originally developed as an antidepressant agent (tomoxetine), but failed to realize this potential. It was abandoned until its use for ADHD was conceived and clinical trials were initiated. During clinical trials its name was changed to atomoxetine to avoid confusion with other medications with similar names (e.g., tamoxifen). It is not currently FDA approved for any indication and is not commercially available anywhere. Materials to support an FDA indication for ADHD were submitted in October, 2001. 

Other alternatives to the stimulants that have been studied for treatment of ADHD in children and adults include the tricyclic antidepressants desipramine and nortriptyline the newer antidepressants bupropion, venlafaxine, and atomoxetine the beta-blocker pindolol and the selective monoamine oxidase inhibitor, deprenyl. Across these agents, the number of controlled studies varies from none (nortriptyline) to four (bupropion). Only deprenyl and desipramine have been studied in children with ADHD and tic disorders. 

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

SSRIs, SNRIs, or mirtazapine for treatment-resistant depression (use combinations ot antidepressants with atomoxetine with caution as this may theoretically activate bipolar disorder and suicidal ideation)... 

Preliminary studies and atomoxetine s known mechanism of action as a selective norepinephrine reuptake inhibitor suggest its efficacy as an antidepressant... 

Atomoxetine s mechanism of action and its potential antidepressant actions suggest it has the potential to de-stabilize latent or undiagnosed bipolar disorder, similar to the known actions of proven antidepressants... 

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... 

Bupropion, mirtazapine, reboxetine, or atomoxetine (use combinations of antidepressants with caution as this may activate bipoiar disorder and suicidai ideation)... 

Stimulants are first-line treatment for ADHD atomoxetine, bupropion, and tricyclic antidepressants (TCAs) are second-line agents clonidine, guanfacine, and other medications are adjunctive treatments. 

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. 

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