Tricyclic antidepressants methylphenidate

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. 

There are four classes of antidepressants tricyclic antidepressants (imipramine, trimipramine, amitriptyline, doxepin, desipramine, protriptyline, nortriptyline, amoxapine, maprotiline) monoaminooxidase (MAO) inhibitors (phenelzine, isocarboxazid, tranylcypromine) second-generation antidepressants or atypical antidepressants, which are a chemically dissimilar group of recently proposed drugs (bupropion, trazodone, fluoxetine) and amphetamines and other stimulators of the CNS (dextroamphetamine, methylphenidate). 

Drugs that may be affected by dexmethylphenidate or racemic methylphenidate include antihypertensive agents, pressor agents, coumarin anticoagulants, anticonvulsants, tricyclic antidepressants, selective serotonin reuptake inhibitors, and clonidine. 

Methylphenidate may decrease therapeutic effects of concomitantly administered antihypertensive medications and may potentiate effects of warfarin, phenytoin, phenylbutazone, and tricyclic antidepressants. When methylphenidate and MAOIs are coadministered, hypertensive crisis may result. 

The interaction with methylphenidate may be of particular significance, because of claims that tricyclic antidepressants and methylphenidate have a synergistic effect on mood, owing to interference by methylphenidate with the metabolism of imipramine, resulting in increased blood imipramine concentrations (182). The occurrence of this hypertensive interaction calls for caution in the use of such combinations, for which there is no established evidence. 

Flemenbaum A. Hypertensive episodes after adding methylphenidate (Ritahn) to tricyclic antidepressants. [Report of three cases and review of clinical advantages.] Psychosomatics 1972 13(4) 265-8. 

Wharton RN, Perel JM, Dayton PG, Malitz S. A potential clinical use for methylphenidate with tricyclic antidepressants. Am J Psychiatry 1971 127(12) 1619-25. 

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... 

Clonidine, tricyclic antidepressants md antipsychotic agents (e.g. risperidone, sulpiride) may have a role in ADHD where methylphenidate and dexamfetamine are contraindicated or have failed to produce benefit. 

Hypertensive episodes occurred in three adults who combined methylphenidate with tricyclic antidepressants (SED-9,11). Methylphenidate increases serum concentrations of imipramine (55). 

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. 

Clinically important, potentially hazardous interactions with amphetamines, aprepitant, astemizole, atazanavir, azithromycin, azole antifungals, clarithromycin, darunavir, dirithromycin, erythromycin, fluoxetine, fosamprenavir, grapefruit juice, imatinib, indinavir, itraconazole, ketoconazole, methylphenidate, nefazodone, nelfinavir, nilotinib, pemoline, phenothiazines, protease inhibitors, quinidine, ritonavir, saquinavir, sertraline, sparfloxacin, sulpiride, telithromycin, thioridazine, tipranavir, tricyclic antidepressants, troleandomycin, voriconazole, zileuton, ziprasidone... 

FIGURE 61-1. Algorithm for management of ADHD. Treat predominant disorder first, reassess, and consider alternative or adjunct medications for optimal symptom control. MPHD, methylphenidate DEX, dextroamphetamine MXA, mixed amphetamine salts TCA, tricyclic antidepressant AD, antidepressant. (Adapted from Pliszka et al, Pliszka et al, MTA Cooperative Group, Caballero, Daviss et al, State et al, Schur et al, Hughes et al, Muller-Vahl, and Jimenez-Jimenez. )... 

Antidepressants selective serotonin reuptake inhibitors, tricyclic antidepressants Antihypertensives felodipine Antibiotics quinolones, isoniazid Bronchodilators albuterol, theophylline Corticosteroids prednisone Dopa agonists levodopa Herbals ma huang, ginseng, ephedra Nonsteroidal anti-inflammatory drugs ibuprofen Stimulants amphetamines, methylphenidate, caffeine, cocaine Sympathomimetics pseudoephedrine Thyroid hormones levothyroxine Toxicity anticholinergics, antihistamines, digoxin Withdrawal alcohol, sedatives... 

The tricyclic and other NE-active antidepressants do not block dopamine (DA) transport via DAT) they thereby differ from central nervous system (CNS) stimulants, including cocaine, methylphenidate, and amphetamines see Chapter 10). Nevertheless, they may indirectly facilitate effects of DA by inhibiting the nonspecific transport of DA into noradrenergic terminals in the cerebral cortex. Tricyclic antidepressants also can desensitize D antoreceptors through uncertain mechanisms and with uncertain behavioral contributions. 

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. 

Alprazolam Cimetidine Contraceptives Diazepam Erythromycin Fluoxetine Fluvoxamine Haloperidol Levomepromazine Methylphenidate Paroxetine Perphenazine Tricyclic antidepressants Thioridazine Thyroxine... 

Methylphenidate can increase the levels and rate of response to tricyclic antidepressants. This has led to both increased beneficial and adverse effects. No significant pharmacokinetic interaction has been reported between desipramine and dexamfetamine or methylphenidate. An isolated report describes a blood dyscrasia in a child given methylphenidate and imipramine. 

In vitro experiments with human liver slices indicate that methylphenidate inhibits the metabolism of imipramine, resulting in raised blood levels. The accelerated response to tricyclic antidepressants may also be partly due to increased serum levels in the presence of methylphenidate, although the adverse effects observed were not entirely consistent with elevated levels of tricyclics. There are also reports suggesting that... 

Information is limited. Some therapeutic improvement including accelerated response is seen in some patients. This may be partially because of the very marked rise in the blood levels of the antidepressant due to methylphenidate, but may also be due to an additional effect on mood attributable to methylphenidate. Concurrent use may cause adverse effects sufficiently severe to necessitate withdrawal of methylphenidate, but it is not certain whether this can solely be attributed to increases in serum levels of tricyclic antidepressants. Information about other tricyclic antidepressants is lacking. However, it has been suggested that concurrent use in children and adolescents may be undesirable, due to case reports of adverse behavioural effects. If concurrent use is deemed necessary it would seem prudent to monitor concurrent use for adverse tricyclic effects (e.g. dry mouth, blurred vision, urinary retention) and adjust the dose as necessary. 

A potentially related interaction has been reported between tricyclic antidepressants and methylphenidate which acts as an indirectly acting sympathomimetic amine. Cases have been reported (40 ) of patients taking tricyclic antidepressants (imipramine 200 mg, protriptyline 30 mg, and imi-... 

Gwirtsman HE, Szuba MP, TcrenL, Feist M The antidepressant re nse to tricyclics in major depressives is accelerated with adjunctive use of methylphenidate. Psychopharmacol Bull (199 30, 157-64. 

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