Editing Maprotiline (section)

== Interactions ==

Maprotiline does have a wide range of possible interactions. Some are typical for TCAs and TeCAs, others are caused by specific metabolic effects (e.g., high plasma-protein-binding) of maprotiline:

'''Increased drug actions:'''
* Other antidepressants, barbiturates, narcotics, sedating antihistamines, anticonvulsive drugs, [[alcohol (drug)|alcohol]]{{snd}} resulting in increased central depression and necessitating some caution when using any of these drugs alongside maprotiline 
* Drugs with potential anti-muscarinic/anti-cholinergic activity (antiparkinsonian agents, [[atropine]], [[amantadine]], [[clozapine]] and [[tricyclic antidepressants]] besides maprotiline){{snd}} resulting in increased anti-muscarinic effects (dry mouth, constipation, etc.)
* Sympathomimetics (also those used in local anesthetics like noradrenaline){{snd}} sympathomimetic effects increased (increased blood-pressure, pulse-rate, paleness of skin, etc.)
* Nitrates and antihypertensives (e.g., beta-blockers){{snd}} increased antihypertensive action with pronounced fall in blood pressure

Although concurrent administration of tricyclic antidepressants (likewise with [[selective serotonin reuptake inhibitors|SSRIs]]) and MAOIs has been considered particularly dangerous, even fatal, across various medical and pharmaceutical lines across the decades, the premise for this line of thinking, although commonly accepted, may be erroneous. Specialist-research into this<ref name="pmid28148312">{{cite journal | vauthors = Gillman K | title = "Much ado about nothing": monoamine oxidase inhibitors, drug interactions, and dietary tyramine | journal = CNS Spectrums | volume = 22 | issue = 5 | pages = 385–387 | date = October 2017 | pmid = 28148312 | doi = 10.1017/S1092852916000651 | s2cid = 206312818 | url = | doi-access = free }}</ref> and practical clinical experience involving the co-administration of tricyclics and MAOIs have suggested that it is only tricyclics with strong specific serotonin-reuptake inhibitory action ([[clomipramine]] and, to a lesser extent, [[imipramine]]) that are dangerous to give in combination with MAOIs. Other antidepressants; which may or may not have a significant serotoninergic background otherwise but either way lack in particularly appreciable reuptake-inhibition therein specifically (e.g., [[mirtazapine]], [[amitriptyline]], [[trazodone]], [[lofepramine]], [[nortriptyline]]); may be safe to take alongside MAOIs, where the likes of [[venlafaxine]], [[selective serotonin reuptake inhibitor|SSRIs]] and [[clomipramine]] are not. With maprotiline, this has been demonstrated to be the case with [[moclobemide]],<ref name="pmid2677241">{{cite journal | vauthors = Laux G, Beckmann H, Classen W, Becker T | title = Moclobemide and maprotiline in the treatment of inpatients with major depressive disorder | journal = Journal of Neural Transmission. Supplementum | volume = 28 | issue = | pages = 45–52 | date = 1989 | pmid = 2677241 | doi = | url = }}</ref> a drug it is often compared and considered somewhat analogous (along certain lines) to, and, tentatively, [[brofaromine]]<ref name="pmid8006248">{{cite journal | vauthors = Hoencamp E, Haffmans PM, Dijken WA, Hoogduin CA, Nolen WA, van Dyck R | title = Brofaromine versus lithium addition to maprotiline. A double-blind study in maprotiline refractory depressed outpatients | journal = Journal of Affective Disorders | volume = 30 | issue = 3 | pages = 219–27 | date = March 1994 | pmid = 8006248 | doi = 10.1016/0165-0327(94)90082-5 | url = }}</ref> (a research-agent MAOI which was never brought to full marketing development). Moclobemide specifically, however, may increase maprptiline plasma-levels<ref name="pmid9271778">{{cite journal | vauthors = König F, Wolfersdorf M, Löble M, Wössner S, Hauger B | title = Trimipramine and maprotiline plasma levels during combined treatment with moclobemide in therapy-resistant depression | journal = Pharmacopsychiatry | volume = 30 | issue = 4 | pages = 125–7 | date = July 1997 | pmid = 9271778 | doi = 10.1055/s-2007-979497 | s2cid = 35570626 | url = }}</ref> and may necessitate dose-modification(s).

In any case, however, it is very-strongly advised that an MAOI is added to the (compatible) tricyclic and not the other way around, as adding a tricyclic to an existing treatment-regime involving an MAOI may significantly increase the risk of going into hypertensive crisis.

'''Decreased drug actions:'''
* [[Guanethidine]], [[reserpine]], [[guanfacine]]: anti-hypertensive effects decreased
* [[Clonidine]]: anti-hypertensive effects decreased and risk of (massive) rebound hypertension.

'''Other types of interaction:'''
* Drugs which induce certain enzymes in the liver, e.g., barbiturates, [[phenytoin]], [[carbamazepine]] and oral anti-conceptive drugs, enhance the elimination of maprotiline and decrease its antidepressant effects. Additionally the blood-concentrations of phenytoin or carbamazepine may be increased, leading to a higher incidents of side effects.
* The concomitant use of maprotiline and [[antipsychotics|neuroleptics]] can lead to increased maprotiline blood-levels and to seizures. Combining maprotiline and thioridazine could induce severe arrhythmias.
* Additionally, increased blood-levels of maprotiline are possible, if certain beta-blocking agents (e.g., [[propranolol]]) are given concomitantly.
* Maprotiline may amplify the actions of [[coumarin]]-type anticoagulants (e.g., [[warfarin]], phenprocoumon). The plasma-prothrombin-activity must be assessed closely in order to avoid overt bleedings.
* Maprotiline can increase the actions of oral antidiabetic drugs (sulfonylureas) and [[insulin]]. Diabetic patients should have regular assessments of their blood-glucose-levels.
* The concomitant application with fluoxetine or fluvoxamine may lead to significantly increased plasma-levels of maprotiline, with a correspondingly (and substantially) incidence of maprotiline side effects. Owing to the long half-lives of fluoxetine and fluvoxamine, this effect may persist for quite-some time.