Methylphenidate Imipramine

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). 

Burke, M.S., Josephson, A., and LIghtsey, A. (1995) Combined methylphenidate and imipramine complication [letter]. Am Acad Child Adolesc Psychiatry 34 403 04. 

Loof et al. (1995) reported the use of carbamazepine (300-1200 mg/day, serum levels 10-11.5 pg/mL) in 28 children and adolescents with sexual abuse histories. By treatment end, 22 of 28 patients were asymptomatic of PTSD. The remaining six were significantly improved in all PTSD symptoms except for continued abuse-related nightmares. Half of this cohort had com-orbid ADHD, depression, ODD or polysubstance abuse and were treated with concomitant medications, e.g., methylphenidate, clonidine, sertraline, fluoxetine, or imipramine. 

In recent years the psychostimulant male/female ratio appears to have narrowed to 1 6, in contrast to the 1 12 ratio in the mid-1980s (Safer, 1994). Similarly, Zito et al. (2000) noted that the male/female ratio for prescription frequency has also narrowed among preschoolers in two of three data sets (roughly 4-7 1 to 3-4 1). One interesting exception to this general male female ratio has been noted, however. Zito et al. (1998b) report that for children under the age of 15 years, males are more likely to receive psychotropic treatments (specifically methylphenidate, desipramine, and imipramine) than females. But in youth ages 15 years and older, females received the majority of psychotropic prescriptions. 

Simeon et al. (1995) mailed questionnaires to 135 child psychiatrists in 43 countries to obtain more precise information on the views and approaches to the diagnosis and treatment of childhood psychiatric disorders. Of 43 questionnaires returned, data from 38 respondents representing 24 different countries were included. The study indicated that child psychiatrists in Europe and elsewhere outside the United States would use methylphenidate to treat 58% of ADHD patients, with their second choice being imipramine (18%), and 11% would not use medication. The investigators reported that one of the controversies that remained was the diagnosis and treatment of ADHD, as the prescription rates varied extremely from one country to another. In Italy, for example, the diagnosis of ADHD was rarely made and psychostimulants were rarely used. The authors concluded that the choice of medication was frequently restricted by lack of availability as well as by political or social attitudes (Simeon et al., 1995). 

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. 

Cooper TB, Simpson GM. Concomitant imipramine and methylphenidate administration a case report. Am J Psychiatry 1973 130(6) 721. 

INDIRECT TCAs 1. Methylphenidate T TCA levels, which may improve their efficacy, but cases of toxicity with imipramine have been reported 2. TCAs possibly 1 efficacy of indirect sympathomimetics 1. Uncertain postulated to be due to inhibition of the hepatic metabolism of TCAs 2. Indirect sympathomimetics cause release of norepinephrine from the nerve endings this is blocked by TCAs 1. Warn patients to watch for early signs of t TCA efficacy such as drowsiness and dry mouth 2. Watch for poor response to indirect sympathomimetics... 

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

The electrospray stability of this device was studied with two different samples 1 pg mL 1 imipramine- 3 directly dissolved in 75% methanol, 25% water and 0.1% formic acid and extracted urine sample containing only methylphenidate-d3, which corresponds to the blank calibration standards. Figure 6.13A shows the total ion current of full mass range scan (m/z 250 to 350) of the imipramine-J3 sample over 15 min with a scan speed of 1.16 s per scan while Figure 6.13B shows the extracted ion current of the base peak (m/z 284.2) from Figure 6.13A. The RSD for the total ion current over the 15 min periods was 10.7% and the protonated molecule ion was even more stable with an RSD of 5.7%. Figure 6.13C shows the total selected ion current for the SRM data (m/z 234.2 > m/z 84.1, m/z 234.2 > m/z 84.1) from 150ngmL 1 methylphe-nidate-fi 3 sample. The SRM mode was also very stable with an RSD of 3.05% over a period of 5 min. 

Figure 6.13 Electrospray stability of the device. (A) Total ion current of m/z from 250 to 350 with solution of lpgmL-1 imipramine-d3 in 75% methanol, 25%water and 0.1 % formic acid. (B) Extracted ion current of imipramine-d3 (m/z 284.2) from (A). (C) Selected reaction monitoring of extracted urine sample containing 150ngmL 1 methylphenidate-<73 (from ref. 13).

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

Also analyzed acebutolol, acetaminophen, alprazolam, amphetamine, atenolol, betaxolol, brotizolam, caffeine, camazepam, captopril, chloroquine, clobazam, clomipramine, cloth-iapine, clotiazepam, cloxazolam, cocaine, codeine, diclofenac, dihydralazine, dihydrocodeine, dihydroergotamine, diphenhydramine, domperidone, doxepin, droperidol, ergota-mine, ethyl loflazepate, fenethylline, fluoxetine, flupentixol, flurazepam, furosemide, gliclazide, hydrochlorothiazide, hydroxyzine, ibuprofen, imipramine, ketazolam, loprazo-1am, lorazepam, lormetazepam, maprotUine, medazepam, mepyramine, methadone, methaqualone, methyldopa, methylphenidate, metoclopramide, metoprolol, mexiletine, mianserin, midazolam, minoxidil, morphine, nadolol, nitrazepam, oxprenolol, papaverine, pentazocine, phenprocoumon, phenylbutazone, pipamperone, piritramide, practolol, pra-zepam, prazosin, promazine, promethazine, propoxyphene, propranolol, prothipendyl, quinine, sotalol, sulpride, thioridazine, trazodone, triazolam, trimipramine, tripelennamine, lyramine, verapeunil, yohimbine... 

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