Methylphenidate Bupropion

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. 

Triple reuptake inhibitors (TRIs), which inhibit reuptake at all three transporters, have attracted considerable interest in recent years [77]. The involvement of dopamine reuptake in the etiology of depression and other CNS disorders has been recognized [29,30]. As a result, TRIs have been proposed to offer a faster onset of action and improved efficacy for depression over currently prescribed single or dual action monoamine reuptake inhibitors. Historically, the mesocorticolimbic dopamine pathway is thought to mediate the anhedonia and lack of motivation observed in depressed patients [78,79]. In addition, methylphenidate, both immediate release and extended release formula, has been found to be effective as an augmenting agent in treatment-resistant depression [4]. Furthermore, clinical studies using the combination of bupropion and an SSRI or SNRI have showed improved efficacy for the treatment of MDD in patients refractory to the treatment with SSRIs, SNRIs, or bupropion alone [5,80,81]. 

Dopamine-Stimulating Medications. A variety of drugs that increase the availability of dopamine have been studied in cocaine addicts including L-DOPA, bupropion, amantadine, and methylphenidate. In small uncontrolled trials, these have shown some benefit, but definitive studies have yet to be performed. In addition, some dopamine-stimulating medications (in particular, the stimulants like methylphenidate or the amphetamines) are themselves subject to abuse, though, of note, this is typically not a problem when they are prescribed to patients who do not have a history of substance abuse such as, for example, in the treatment of attention deficit-hyperactivity disorder. 

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). 

Barrickman, L.L., Perry, P.J., Allen, A.J., Kuperman, S., Arndt, S.V., Herrmann, K.J., and Schumacher, E. (1995) Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 34 649-657. 

FIGURE 7—41. Adrenergic combo 2 Bupropion can be combined with a stimulant such as d-amphetamine or methylphenidate. The stimulant will add a double dopamine boost to bupropion, which boosts dopamine in its own right. A single boost of norepinephrine from bupropion also is present. 

Antidote Buspirone, bupropion, nefazodone, gingko biloba, sildenafil, cyproheptadine, yohimbine, methylphenidate, etc. 

Fluoxetine, paroxetine, bupropion, duloxetine, and other CYP450 2D6 inhibitors may increase TCA concentrations Cimetidine may increase plasma concentrations of TCAs and cause anticholinergic symptoms Phenothiazines or haloperidol may raise TCA blood concentrations May alter effects of antihypertensive drugs may inhibit hypotensive effects of clonidine Use of TCAs with sympathomimetic agents may increase sympathetic activity Methylphenidate may inhibit metabolism of TCAs... 

Potential drug-drug interactions of ciclosporin with methylphenidate and amfebutamone (bupropion) have been described (43). 

Lewis BR, Aoun SL, Bernstein GA, Crow SJ. Pharmacokinetic interactions between cyclosporine and bupropion or methylphenidate. J Child Adolesc Psychopharmacol 2001 ll(2) 193-8. 

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 amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Clinically important, potentially hazardous interactions with alcohol, bupropion, kava, MAO inhibitors, methylphenidate, selegiline, St John s wort, sumatriptan, valerian... 

George AK+.J Child Adolesc Psychopharmacol 15(4), 693 (with methylphenidate and bupropion)... 

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. 

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. 

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. 

A 14-year-old boy taking methylphenidate 60 mg daily was additionally given bupropion 200 mg increased to 300 mg daily. The patient experienced grand mal seizures 4 weeks after the dosage increase, but remained seizure-free onee the bupropion was discontinued. Another report describes aeute myoeardial infarction in a 16-year-old boy associated with methylphenidate, bupropion and erythromycin. It was proposed that the erythromyein might have eaused elevated levels of bupropion leading to a... 

In a 6-week-randomised, double-blind study, 44 patients diagnosed with ADHD were randomly assigned to receive bupropion 100-150 mg/day or methylphenidate (20-30 mg/day) treatment. No serious events were observed in the study in any of the patients. The most commonly reported adverse events were abdominal pain (30%), anxiety (25%), decreased appetite (55%), agitation (20%), insomnia (50%), dizziness (5%), dry mouth (15%), nervousness (25%), tachycardia (5%), headache (50%) and vomiting (15%) [18 ]. In a randomised, double-blind. 

Chevassus H, Farrett A, Gagnol JP, Poncon CA, Costa F, Roux C, et al. Psychological and physiological effects of bupropion compared to methylphenidate after prolonged administration in healthy volunteers (NCT00285155). Eur J Clin Pharmacol 2013 69 779-87. 

Jafarinia M, Mohammadi MR, Modabbemia A, Ashrafi M, Khajavi D, Tabriz M, et al. Bupropion versus methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder randomized double-blind study. Hum Psychopharmacol Clin Exp 2012 27 411-8. Rosenberg PB, Lanctot KL, Drye LT, Hermann N, Scherer RW, Bachmann DL, ADMET Investigators, et al. Safety and efficacy of methylphenidate for apathy in Alzheimer s disease a randomized, placebo-controUed trial. J Clin Psychiatry 2013 74 810-6. 

---