Excess Tyramine Caused by Monoamine Oxidase Inhibitors (Maois) Can Result in What?
The Transdermal Commitment System of Monoamine Oxidase Inhibitors
Monoamine oxidase inhibitors (MAOIs) were in one case widely used as effective treatments for major depressive disorder, particularly for patients with atypical or treatment-resistant low. Today, MAOIs have largely been replaced past newer antidepressants because of concerns over potential serious side furnishings due to their machinery of activeness. Monoamine oxidase (MAO) is an enzyme that metabolizes serotonin, norepinephrine, and dopamine, the neurotransmitters that are most associated with depression; inhibiting MAO, therefore, makes more than of these neurotransmitters available for synaptic action. All the same, MAO also metabolizes tyramine, a trace amine institute in some foods that acts equally a sympathomimetic. Allowing excess tyramine to accumulate via MAO inhibition can event in hypertensive crisis due to the release of norepinephrine; therefore, patients taking an MAOI take had to follow dietary restrictions to avert tyramine-rich foods. Hypertensive crisis may likewise be precipitated by using MAOIs in conjunction with other drugs that have vasoconstrictive properties, that human action as sympathomimetics, or that inhibit the reuptake of norepinephrine. Serotonin syndrome is another serious agin consequence that can potentially occur when using an MAOI with some other drug that inhibits the reuptake of serotonin. In this article, the mechanism of action of MAOIs is reviewed, forth with that of a newer MAOI formulation that lessens the need for dietary restrictions and has a greater safety and tolerability contour than the older oral formulations.
(J Clin Psychiatry 2012;73[suppl 1]:25-xxx)
From the Section of Chemist's Practice and the Centre for Clinical Research, Mercer University College of Pharmacy and Health Sciences, Atlanta, Georgia.
This article is derived from the planning teleconference series "A Fresh Expect at Monoamine Oxidase Inhibitors for Depression," which was held December 2011 through February 2012 and supported by an educational grant from Mylan Specialty Fifty.P. (formerly known as Dey Pharma, L.P.).
Dr VanDenBerg has received grant/research support from Eli Lilly and Cognitive Enquiry Corporation.
Corresponding author: Chad Thousand. VanDenBerg, PharmD, BCPP, 3001 Mercer University Bulldoze, DV-129, Atlanta, GA 30341 (Vandenberg_c@mercer.edu).
doi:10.4088/JCP.11096su1c.04
© Copyright 2012 Physicians Postgraduate Press, Inc.
Beginning with their introduction in the 1950s, and for several decades thereafter, monoamine oxidase inhibitors (MAOIs) were widely used as an effective treatment for major depressive disorder, particularly for atypical depressionone and handling-resistant depression.2 Today, MAOIs have largely been replaced past newer antidepressants due to concerns regarding potential side furnishings from drug and food interactions and the resulting demand for dietary restrictions and careful medical management. Understanding the mechanism of action of MAOIs, all the same, tin help clinicians to preclude these interactions. Additionally, a newer MAOI formulation that is easier to administrate and has a better safety and tolerability contour is available.
MAOI Machinery of Action
The pathophysiology of depression has nonetheless to be fully understood, but all pharmacotherapies for the disorder are based on increasing the synaptic action of 1 or more of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine.three The MAOIs inhibit monoamine oxidase (MAO), a mitochondrial enzyme that acts as a catalyst for converting biogenic amines to their corresponding aldehydes. The MAO enzyme oxidatively deaminates and inactivates backlog neurotransmitter molecules; therefore, inhibiting MAO activity by deactivating the enzyme allows serotonin, norepinephrine, and dopamine to accumulate, increasing their availability for synaptic action.iv Originally, this action was thought to exist the footing for the antidepressant activeness of MAOIs, just one hypothesis proposes secondary adaptive mechanisms, such as downregulation of monoamine receptors and the elevation of other trace amines, as possible factors in the antidepressant effect.five Although MAOIs increase the availability of monoamines almost immediately, the secondary effects occur after chronic administration of the medication over several weeks, which coincides with the delayed onset of antidepressant upshot.
For Clinical Utilize
- MAO is an enzyme that metabolizes serotonin, norepinephrine, and dopamine; inhibiting MAO allows these neurotransmitters to accumulate in the synaptic cleft.
- MAOIs take potentially serious side effects, such as hypertensive crisis and serotonin syndrome, due to nutrition and drug interactions.
- To avoid these adverse effects, patients should exist educated regarding dietary restrictions and drug interactions.
- A transdermal MAOI conception with a greater tolerability and safe contour than oral MAOIs is available, which, at the minimum effective dosage, avoids the need for dietary restrictions.
MAO Subtypes
2 isoenzymes of MAO have been identified: MAO-A and MAO-B. Both are found in the central nervous organisation (CNS) and in the intestine and liver, merely they take unlike substrates and different relative distributions. MAO-A is mainly constitute in the brain and intestine and is present in serotonin, dopamine, and norepinephrine neurons. In the encephalon, MAO-A preferentially metabolizes serotonin and norepinephrine, and in the intestine, MAO-A catabolizes amines absorbed into the gastrointestinal (GI) tract, including tyramine. The main substrates for MAO-B, which is found in brain regions rich in serotonergic neurons and in platelets and other tissues, are β-phenylethylamine, dopamine, and tyramine. MAO-B preferentially metabolizes trace amines such as two-phenylethylamine. Both MAO-A and MAO-B metabolize dopamine.four,6
Inhibition of MAO-A increases the levels of serotonin and norepinephrine and, to a lesser extent, dopamine, equally dopamine will withal be metabolized past MAO-B (Effigy 1).seven Inhibiting MAO-B has little outcome on serotonin and norepinephrine levels, and dopamine levels will not ascent substantially due to connected metabolism by MAO-A. MAO-A preferentially metabolizes all 3 of the monoamines almost associated with depression, and inhibition of MAO-A in the brain is needed for an antidepressant effect. However, inhibiting both MAO-A and MAO-B leads to a greater increase in all 3 neurotransmitters than inhibition of either alone.7
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MAOIs tin can be either nonselective or selective. Nonselective MAOIs inhibit both isoenzymes, whereas selective MAOIs inhibit either MAO-A or MAO-B. The classic oral MAOIs approved to treat depression in the United states (isocarboxazid, phenelzine, and tranylcypromine) are all nonselective. Oral selegiline is a selective inhibitor of MAO-B and is approved at low doses (ten mg/d) as an adjunct to carbidopa/levodopa to care for Parkinson'due south affliction. However, at doses high enough to induce an antidepressant effect (thirty to 60 mg/d), oral selegiline loses its selectivity and inhibits both MAO-A and MAO-B.8-x
All MAOIs approved to treat depression in the United states of america are irreversible, meaning they bind to MAO for the life of the enzyme. In one case the medication is stopped, a period of 7 to ten days is required for new MAO enzyme to be generated and enzymatic activity to resume.iv
Adverse Effects and Mechanism of Action
The most mutual early side effects of oral MAOIs include insomnia, sedation, orthostatic hypotension, dizziness, and nausea. Later on side furnishings reported for MAOIs include weight proceeds, edema, musculus hurting, myoclonus, paresthesia, and sexual dysfunction.11 The most serious adverse effects associated with MAOIs, nonetheless, are due to nutrient and drug interactions.
Food interactions. Tyramine is a trace amine, found in many foods, that acts as an indirect sympathomimetic.12 MAO-A metabolizes dietary tyramine in the GI system and liver, which restricts the uptake of tyramine into the circulatory system. Irreversible inhibition of abdominal MAO-A, via oral delivery of an MAOI, can therefore lead to serious interactions with foods containing loftier levels of tyramine.
Commonly, MAO-A in the intestinal wall and in the liver can metabolize upward to 400 mg of ingested tyramine.7 When MAO-A is inhibited in the gut, equally fiddling equally 10 mg of ingested tyramine can cause an excessive amount to enter the bloodstream, where it triggers the release of norepinephrine from sympathetic nerve terminals. Excess norepinephrine causes a rapid and sometimes severe increase in blood pressure that can atomic number 82 to hypertensive crisis, perhaps resulting in stroke or even death. Thus, patients taking irreversible, nonselective MAO inhibitors must follow dietary restrictions that limit tyramine intake.thirteen
Reversible inhibitors of MAO-A (RIMAs) have been developed in an try to avoid the tyramine reaction. With these medications, when tyramine is ingested and absorbed in the gut in large enough amounts to increment the release of norepinephrine, the accumulation of norepinephrine displaces the RIMA from the active site on the MAO-A enzyme, assuasive the norepinephrine to be metabolized.14 Dietary restrictions are unnecessary with RIMAs. As tyramine does non cross the blood-brain bulwark, MAO-A in the brain will continue to be inhibited, maintaining the antidepressant event.15 The MAO-A selective RIMA moclobemide is available throughout much of the earth merely is not approved in the U.s.a..
Drug interactions. The amount of norepinephrine potentiated by MAOIs alone is non great enough to elevate blood pressure in the absenteeism of tyramine ingestion. Notwithstanding, MAOIs should non be used in combination with other adrenergic medications, including some decongestants, stimulants such equally methylphenidate and amphetamines, opioids or pain medications that contain sympathomimetic vasoconstrictors, and antidepressants or ambition suppressants with norepinephrine uptake inhibition, every bit hypertensive crisis can result.
Combining MAOIs with medications that inhibit serotonin reuptake (including other antidepressants, certain analgesic agents, and the antitussive amanuensis dextromethorphan) can crusade serotonin syndrome, a potentially lethal status caused by the accumulation of excessive serotonin.fourteen When switching a patient to or from an MAOI, a washout period of virtually 2 weeks is recommended; switching from fluoxetine, withal, requires a washout period of five weeks due to its long half-life.
Transdermal Commitment Arrangement for Selegiline
Although simplified over the years, the dietary restrictions that back-trail MAOI utilise have been perceived by patients and clinicians as difficult to manage. One effort to meliorate the prophylactic of MAOIs and limit or avoid the demand for dietary restrictions was the development of the selegiline transdermal organisation (STS). With the STS, the drug is delivered in a controlled mode over 24 hours via the once-daily application of a matrix-type patch. By bypassing the GI tract, the transdermal preparation of selegiline avoids the complete inhibition of MAO-A in the gut that occurs with oral MAOIs.
Pharmacokinetics
The physiochemical properties of selegiline (eg, low molecular weight, high lipid solubility) brand it well-suited for transdermal delivery. Selegiline is a weak base with a molecular weight of 187.three, a pKa of 7.5, and a calculated octanol/water partition coefficient of 3.4.sixteen Delivering a highly lipid-soluble compound such as selegiline transdermally allows it to rapidly penetrate jail cell membranes and quickly attain target sites in the CNS. Upon application of the patch, near 25% to 30%, on average, of the selegiline content is delivered systemically over 24 hours, and steady-state plasma concentrations are accomplished within 5 days of daily dosing.17 Gender does not touch the pharmacokinetics or metabolism of transdermally delivered selegiline. Tabular array 1 summarizes the pharmacokinetics of oral selegiline and the STS.18
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A randomized, open-label study16 demonstrated that transdermal selegiline delivers a college plasma concentration of drug to the CNS over a longer period of fourth dimension, and with a lower dosage, than does oral selegiline. The greater bioavailability of 6 mg of transdermal selegiline (73.four%) versus ten mg of oral selegiline (4.4%) is due to the avoidance of the extremely high commencement-pass metabolism that occurs with the oral medication in the GI organization and liver earlier entering the circulatory organization.16 In addition, transdermal selegiline maintains a sustained plasma concentration during the 24-hour application menstruum, whereas the oral medication plasma concentration peaks within ane hour and then declines rapidly. Because MAO-A is largely unaffected in the gut by the STS, patient sensitivity to dietary tyramine is more than than 20 times less with the selegiline transdermal patch than with oral tranylcypromine.19
Both oral and transdermal selegiline are metabolized through multiple CYP450 isoenzymes and form, in society, the metabolites N-desmethylselegiline, l-methamphetamine, and l-amphetamine; l-methamphetamine is the major metabolite formed.16 However, metabolite levels, which may be associated with neurotoxicity, are greatly reduced with transdermal delivery (see Table 1).18,20
Pharmacodynamics
Transdermal selegiline must be administered at doses high enough to lose its selectivity for MAO-B in order to have an antidepressant effect. While oral selegiline inhibits MAO-A activity in the brain and duodenum to a like extent, to avert reactions to dietary tyramine, the transdermal delivery system preferentially targets MAO-A activity in the brain over peripheral activity. Transdermal selegiline ID50 values for inhibition of brain MAO-A activity are 7.5 times lower than ID50 values for inhibition of intestinal MAO-A activity.21 This means that the antidepressant effect, via inhibition of MAO-A in the encephalon, can occur with a significantly lower potential for tyramine reactions due to inhibition of MAO-A in the gut. Based on road of delivery and avoidance of the first-pass effect, transdermally delivered selegiline is 6 to 8 times more than potent for inhibiting brain MAO-A activity than orally delivered selegiline. Therefore, a lower dose is needed to produce an antidepressant effect.
Animal studieseighteen prove that STS doses that inhibit more than ninety% of the activeness of both MAO-A and MAO-B in the encephalon have a maximal inhibition of 40% of MAO-A and 70% to 75% of MAO-B activeness in GI tissue. Doses that inhibit brain MAO-A by 55% to 60% and brain MAO-B by 85% to 90% prove no inhibition of GI MAO-A activity and show simply twoscore% to lx% inhibition of GI MAO-B activity. In these studies, college doses lost their selectivity for inhibiting MAO-B in the brain merely non in GI tissue.
Condom Profile
In placebo-controlled trials22,23 of STS for treatment of astute depression, the tolerability profile of STS was similar to that of placebo except for application site reactions. No significant differences between the treatment groups and the placebo groups were noted for agin effects for cardiovascular, nervous, digestive, respiratory, urogenital, or musculoskeletal systems or for sexual function. A 52-week report24 that assessed maintenance treatment with STS also reported a rubber profile like to that of placebo except for application site reactions.
Transdermal selegiline is classified as a nonallergen; application site reactions are similar to those of other transdermally delivered medications and probably due to the agglutinative used in the patch.25 Application site reactions are generally a class of irritant contact dermatitis (rather than allergic contact dermatitis) and are mild to moderate, transient in nature, and resolve spontaneously subsequently patch removal.26 Pare reactions can be minimized past rotating the patch site, advisedly removing the patch and so washing the site with warm soapy h2o, and using moisturizers and topical corticosteroids.
The available STS patches deliver vi mg, nine mg, or 12 mg of medication per 24 hours, and no hypertensive crises accept been reported at any dose of the patch. A study19 of tyramine pressor sensitivity found no meaning effects for the minimum effective dose (vi mg/24 h) after 33 days of handling. Dietary restrictions are not necessary at the 6 mg/24 hours dose but are recommended at higher doses due to a lack of rubber information.
Although the STS reduces the hazard of food interactions, information technology does not protect against potential hypertensive crunch and serotonin syndrome due to drug interactions. The aforementioned precautions against drug interactions should be taken when using STS equally when using other MAOIs.
Efficacy for Major Depressive Disorder
Three placebo-controlled trials demonstrated efficacy for STS over placebo for the astute treatment of depression (Tabular array ii).eighteen In the first trial,23 patients were randomly assigned to take either half dozen mg/24 hours STS (northward = 89) or placebo (due north = 88) for 6 weeks. Patients in the STS group experienced significantly amend outcomes on all outcome measures. In the 2nd trial,22 145 patients received STS 6 mg/24 hours and 144 patients received the placebo patch for viii weeks. This trial showed a pocket-size just significant benefit for the STS over placebo. A third placebo-controlled study27 investigated the efficacy of STS administered in a dose range (6 mg/24 h to 12 mg/24 h) for 8 weeks and showed antidepressant efficacy over placebo beyond the dose range for both primary and secondary consequence measures.
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A 52-week trial24 investigated relapse rates for patients randomly assigned to have STS (n = 149) or placebo (n = 163) after responding to 10 weeks of acute treatment with STS 6 mg/24 hours. Compared with patients receiving placebo, significantly fewer patients receiving STS experienced relapse (P = .0025), and patients receiving STS experienced a significantly longer fourth dimension to relapse (P = .0048).
Advantages of Transdermal Commitment
Peel patches accept become adequately familiar to patients over the past few decades, as they have been used in the handling of diverse illnesses including motility sickness, Alzheimer's disease, restless legs syndrome, Parkinson's affliction, hurting from postherpetic neuralgia, smoking habit, attention-deficit/hyperactivity disorder, and angina.28,29 Patches are also used for contraception and hormone replacement.29 The STS uses a matrix-type patch, which has several advantages over the older reservoir-type patch. With many reservoir patches, the drug is contained in an alcohol solution, which irritates the pare. Matrix patches are smaller and thinner, adhere better to the skin, and are mostly better tolerated than reservoir patches.28
With a transdermal patch, some of the side effects that occur when the same drug is delivered orally can be avoided because the drug is delivered straight into the circulatory system. The transdermal patch avoids certain side furnishings created due to first-laissez passer metabolism in the intestine and liver. The patch also maintains steady plasma drug levels, thereby reducing tolerability problems that are associated with fluctuations in plasma concentrations.29 The reduction in agin effects may assistance patients to more easily reach and maintain therapeutic levels of the drug, which should provide greater efficacy and, in turn, increment treatment adherence.
Another advantage of the patch delivery system is ease of use; patches are practical once a solar day, simplifying the handling regimen for those taking multiple daily doses of oral formulations, and are a visual reminder that treatment has been administered.29 Transdermal delivery can also be helpful for patients with certain medical weather condition, such every bit swallowing difficulties.
Conclusion
Classic MAOIs are effective for depression only have serious potential side effects, including hypertensive crisis due to either ingestion of dietary tyramine or drug interactions and serotonin syndrome due to drug interactions. A modified nutrition that restricts tyramine intake is necessary with the oral MAOIs that are bachelor in the U.s.a.; still, a transdermal conception for selegiline has lessened the demand for these restrictions. Avoiding other medications that boost norepinephrine or serotonin levels can prevent hypertensive crisis and serotonin syndrome due to drug interactions. With a better safety and tolerability contour than that of oral MAOIs, STS offers some other option for treating depression, particularly for patients with atypical or treatment-resistant depression.
Drug names: carbidopa/levodopa (Parcopa, Sinemet, and others), fluoxetine (Prozac and others), isocarboxazid (Marplan), methylphenidate (Focalin, Daytrana, and others), phenelzine (Nardil and others), selegiline oral conception (Eldepryl, Zelapar, and others), selegiline transdermal arrangement (EMSAM), tranylcypromine (Parnate and others).
Disclosure of off-label usage: The author has determined that, to the best of his noesis, oral selegiline and moclobemide are not approved by the U.s. Food and Drug Assistants for the treatment of depression.
References
one. Henkel V, Mergl R, Allgaier AK, et al. Handling of depression with atypical features: a meta-analytic approach. Psychiatry Res. 2006;141(1):89-101. PubMed doi:x.1016/j.psychres.2005.07.012
2. Amsterdam JD, Shults J. MAOI efficacy and safe in advanced stage treatment-resistant depression—a retrospective study. J Affect Disord. 2005;89(1-3):183-188. PubMed doi:10.1016/j.jad.2005.06.011
three. Owens MJ. Selectivity of antidepressants: from the monoamine hypothesis of low to the SSRI revolution and across. J Clin Psychiatry. 2004;65(suppl 4):5-10. PubMed
four. Krishnan KR. Revisiting monoamine oxidase inhibitors. J Clin Psychiatry. 2007;68(suppl 8):35-41. PubMed
v. Baker GB, Coutts RT, McKenna KF, et al. Insights into the mechanisms of action of the MAO inhibitors phenelzine and tranylcypromine: a review. J Psychiatry Neurosci. 1992;17(5):206-214. PubMed
6. Schatzberg AF, Nemeroff CB. The American Psychiatric Printing Textbook of Psychopharmacology. 2nd ed. Washington, DC: American Psychiatric Press; 1998.
seven. Stahl SM, Felker A. Monoamine oxidase inhibitors: a modern guide to an unrequited class of antidepressants. CNS Spectr. 2008;13(10):855-870. PubMed
8. Mann JJ, Aarons SF, Wilner PJ, et al. A controlled written report of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor. Arch Gen Psychiatry. 1989;46(ane):45-50. PubMed doi:x.1001/archpsyc.1989.01810010047007
9. Schulz R, Antonin KH, Hoffmann E, et al. Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline. Clin Pharmacol Ther. 1989;46(v):528-536. PubMed doi:x.1038/clpt.1989.181
ten. Heinonen EH, Anttila MI, Lammintausta RA. Pharmacokinetic aspects of 50-deprenyl (selegiline) and its metabolites. Clin Pharmacol Ther. 1994;56(half-dozen pt 2):742-749. PubMed doi:10.1038/clpt.1994.204
11. Fiedorowicz JG, Swartz KL. The role of monoamine oxidase inhibitors in current psychiatric exercise. J Psychiatr Pract. 2004;10(4):239-248. PubMed doi:10.1097/00131746-200407000-00005
12. Culpepper L, Kovalick LJ. A review of the literature on the selegiline transdermal system: an effective and well-tolerated monoamine oxidase inhibitor for the treatment of depression. Prim Care Companion J Clin Psychiatry. 2008;ten(1):25-xxx. PubMed doi:10.4088/PCC.v10n0105
thirteen. Gardner DM, Shulman KI, Walker SE, et al. The making of a user friendly MAOI nutrition. J Clin Psychiatry. 1996;57(three):99-104. PubMed
14. Stahl MS. Stahl'due south Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York, NY: Cambridge Academy Press; 2008.
fifteen. Lotufo-Neto F, Trivedi M, Thase ME. Meta-assay of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the handling of depression. Neuropsychopharmacology. 1999;20(3):226-247. PubMed doi:10.1016/S0893-133X(98)00075-Ten
16. Azzaro AJ, Ziemniak J, Kemper E, et al. Pharmacokinetics and absolute bioavailability of selegiline following handling of salubrious subjects with the selegiline transdermal system (vi mg/24 h): a comparison with oral selegiline capsules. J Clin Pharmacol. 2007;47(10):1256-1267. PubMed doi:10.1177/0091270007304779
17. EMSAM (selegiline patch) [parcel insert]. Napa, CA: Dey Pharma LP; 2010. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b891bd9f-fdb8-4862-89c5-ecdd700398a3. Accessed April twenty, 2012.
xviii. Pae CU, Lim HK, Han C, et al. Selegiline transdermal system: current awareness and promise. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(6):1153-1163. PubMed doi:ten.1016/j.pnpbp.2007.04.020
19. Azzaro AJ, Vandenberg CM, Hulk LF, et al. Tyramine pressor sensitivity during treatment with the selegiline transdermal organisation half-dozen mg/24 h in healthy subjects [published correction appears in J Clin Psychopharmacol. 2006;46(ten):1225-1226]. J Clin Pharmacol. 2006;46(8):933-944. PubMed doi:10.1177/0091270006289852
20. Wagner GC, Walsh SL. Evaluation of the effects of inhibition of monoamine oxidase and senescence on methamphetamine-induced neuronal damage. Int J Dev Neurosci. 1991;9(2):171-174. PubMed doi:x.1016/0736-5748(91)90008-A
21. Mawhinney M, Cole D, Azzaro AJ. Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues. J Pharm Pharmacol. 2003;55(one):27-34. PubMed doi:10.1111/j.2042-7158.2003.tb02430.x
22. Amsterdam JD. A double-bullheaded, placebo-controlled trial of the safety and efficacy of selegiline transdermal organisation without dietary restrictions in patients with major depressive disorder. J Clin Psychiatry. 2003;64(2):208-214. PubMed doi:10.4088/JCP.v64n0216
23. Bodkin JA, Amsterdam JD. Transdermal selegiline in major low: a double-blind, placebo-controlled, parallel-group study in outpatients. Am J Psychiatry. 2002;159(xi):1869-1875. PubMed doi:ten.1176/appi.ajp.159.eleven.1869
24. Amsterdam JD, Bodkin JA. Selegiline transdermal system in the prevention of relapse of major depressive disorder: a 52-week, double-blind, placebo-commutation, parallel-group clinical trial. J Clin Psychopharmacol. 2006;26(6):579-586. PubMed doi:10.1097/01.jcp.0000239794.37073.lxx
25. Pauporte M, Goodhead M, Azzaro AJ, et al. Selegiline transdermal organisation (STS): preclinical assays of dermal condom. Cutan Ocul Toxicol. 2005;23(3):173-178. doi:ten.1081/CUS-200035363
26. Ale I, Lachapelle JM, Maibach Howdy. Pare tolerability associated with transdermal drug commitment systems: an overview. Adv Ther. 2009;26(10):920-935. PubMed doi:10.1007/s12325-009-0075-9
27. Feiger Advertizement, Rickels K, Rynn MA, et al. Selegiline transdermal system for the handling of major depressive disorder: an 8-week, double-blind, placebo-controlled, flexible-dose titration trial. J Clin Psychiatry. 2006;67(9):1354-1361. PubMed doi:10.4088/JCP.v67n0905
28. Farlow MR, Somogyi M. Transdermal patches for the handling of neurologic conditions in elderly patients: a review. Prim Care Companion CNS Disord. 2011;thirteen(6):doi:x.4088/PCC.11r01149. doi:10.4088/PCC.11r01149
29. Oertel W, Ross JS, Eggert K, et al. Rationale for transdermal drug administration in Alzheimer disease. Neurology. 2007;69(suppl 1):S4-S9. PubMed doi:ten.1212/01.wnl.0000281845.40390.8b
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