Stimulants with desipramine

The prevalence of concurrent prescriptions raises concern regarding drug interactions with stimulants. Stimulants, especially MPH, have been used to augment the effects of tricyclic antidepressants in the treatment of refractory depression. Although one early report claimed that circulating levels of imipramine can rise seven fold when taken concurrently with MPH (Wharton et al., 1971), a more recent study found that combining stimulants with desipramine (DMI) did not increase the plasma level of DMI relative to children treated with DMI alone (Cohen et al., 1999). 

Treatment with imipramine, the most studied TCA, leaves 45% to 70% of patients panic free. Both desipramine and clomipramine have demonstrated effectiveness in PD as well. Despite their efficacy, TCAs are considered second- or third-line pharmacotherapy due to poorer tolerability and toxicity on overdose.48,49 TCAs are associated with a greater rate of discontinuation from treatment than SSRIs.53 PD patients taking TCAs may experience anticholinergic effects, orthostatic hypotension, sweating, sleep disturbances, dizziness, fatigue, sexual dysfunction, and weight gain. Stimulant-like side effects occur in up to 40% of patients.49... 

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... 

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

Medications play an important part in the treatment of ADD. Stimulants are the mainstay of the treatment of ADD methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and pemoline (Cylert). These differ in their half-lives, with Ritalin having the shortest and Cylert the longest. A warning has recently been issued about Cylert because of reports of sometimes fatal liver toxicity. Thus, it is recommended that it be used only if methylphenidate and dextroamphetamine are ineffective. There is individual variability in resporise, so that a person who does not respond to one may respond well to another. Other medications can also be effective in the treatment of ADD and may be useful, especially in residual ADD, where substance abuse may be an issue. These include tricyclic antidepressants (especially desipramine and imi-pramine) SSRIs, bupropion, venlafaxine, and clonidine. There are reports of antipsy-chotics and lithium being helpful in selected cases, as well. 

The stimulation of the octopaminergic nervous system of invertebrates is a proven strategy for the control of important pest species. This has been achieved in the past by the use of octopamine receptor agonists such as formamidine and imidazoline derivatives. However, other potential strategies to achieve this end include the inhibition of cyclic nucleotide phosphodiesterase, inhibition of the neural reuptake of octopamine, and inhibition of octopamine N-acetyltransferase. Using the American cockroach nervous system, formamidines were found to inhibit both the uptake and acetylation of octopamine, but not with a potency comparable to their effect on octopamine receptors. The tricyclic antidepressant, desipramine, and the benzylamine, xylamine, were the most active inhibitors of these octopamine removal systems. The pharmacological profiles for uptake and N-acetylation appear to be quite similar, but differ from that of the adenylate cyclase-linked octopamine receptor. 

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. 

Antidepressants tend to provide a more sustained and continuous improvement of the symptoms of attention-deficit/hyperactivity disorder than do the stimulants and do not induce tics or other abnormal movements sometimes associated with stimulants. Indeed, desipramine and nortriptyhne may effectively treat tic disorders, either in association with the use of stimulants or in patients with both attention deficit disorder and Tourette s syndrome. Antidepressants also are leading choices in the treatment of severe anxiety disorders, including panic disorder with agoraphobia, generalized anxiety disorder, social phobia, and obsessive-compulsive disorder, as weU as for the common comorbidity of anxiety in depressive illness. Antidepressants, especially SSRIs, also are employed in the management of posttraumatic stress disorder, which is marked by anxiety, startle, painful recollection of the traumatic events, and disturbed sleep. Initially, anxious patients often tolerate nonsedating antidepressants poorly (Table 17-1), requiring slowly increased doses. Their beneficial actions typically are delayed for several weeks in anxiety disorders, just as they are in major depression. 

Sedation Sedation is a common CNS effect of tricyclic drugs (although less so with protriptyline and desipramine) and of most heterocyclic agents (Table 30-2). MAO inhibitors, selective serotonin reuptake inhibitors, and bupropion are more likely to cause CNS-stimulating effects. 

In contrast, a retrospective review in 142 children and adolescents taking either desipramine alone, or desipramine with dexamfetamine or methylphenidate, indicated the absence of a clinically significant interaction between desipramine and either stimulant. Pharmacokinetic parameters were similar in each group. ... 

The pretreatment of rats with desipramine resulted in delayed stomach emptying and, hence, slowed absorption of phenylbutazone, oxyphenbutazone, hydrocortisone, and salicylate.On the other hand, desipramine had no apparent effect on the absorption of orally administered amphetamine or phenobarbital. In another study, the interactions of a variety of acutely and chronically administered contraceptive agents and their effect on pentobarbital narcosis in the rat, as well as on certain metabolic transformations in vitro, were examined. Medroxyprogesterone, alone or in combination with ethynylestradiol, stimulated the metabolism of 7nitroanisole, aminopyrine, and aniline in vitro, although these effects cure not as marked as those seen with well-known Inducers such as phenobarbital and pesticides. 

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