Maprotiline effects

The answer is c. (Hardman, p 436.) The tricyclics and second-generation antidepressants act by blocking serotonin or norepinephrine uptake into the presynaptic terminal. Fluoxetine selectively inhibits serotonin uptake with minimal effects on norepinephrine uptake. Protriptyline, maprotiline, desipramine, and amoxapine have greater effect on norepinephrine uptake... 

Maprotiline and amoxapine are inhibitors of NE reuptake, with less effect on 5-HT reuptake. 

Pharmaceutical Comparison. At least 8 studies to date have examined the effectiveness of hypericum compared to the pharmaceutical antidepressants imipramine, amitriptyline, and maprotiline. Preliminary results indicate that hypericum is equivalent to standard antidepressants in effectiveness (Linde et al. 1996 Vorbach 1997). Similar to the pharmaceutical antidepressants, there is a 10-14 day lag for therapeutic effects of hypericum (Harrer et al. 1994). Indeed, the differences seen between hypericum and placebo groups becomes apparent between 2 and 4 weeks (Sommer and Harrer 1994). Hypericum has been reported to have a more favorable side-effect profile than several pharmaceutical antidepressants as well (Vorbach et al. 1994 Harrer et al. 1994). In double-blind studies, subjects have reported fewer and less-severe side effects. Although these initial results are promising, Linde and colleagues (1996) have concluded that the present evidence is inadequate to establish... 

Harrer G, Hubner WD, Podzuweit H. (1994). Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline a multicenter double-blind study. J Geriatr Psychiatry Neurol. 7(suppl 1) S24-28. 

Reboxetine is the only selective and reasonably potent noradrenaline reuptake inhibitor available clinically at the present time. Reboxetine has a chemical structure not dissimilar from viloxazine, an antidepressant which was of only limited clinical interest in the 1970s because of its weak efficacy and unacceptable side effects (nausea, vomiting and occasionally seizures). Unlike the secondary amine TCA antidepressants, such as maprotiline, desipramine, nortriptyline and protriptyline, reboxetine does not affect any other transporter or receptor system and therefore is largely devoid of TCA and SSRI-like side effects. In clinical trials, reboxetine has been shown to be as effective as the SSRIs in the... 

With the possible exception of maprotiline, which is chemically a modified TCA with all the side effects attributable to such a molecule, all of the newer non-tricyclic drugs have fewer anticholinergic effects and are less cardiotoxic than the older tricyclics. Lofepramine is an example of a modified tricyclic that, due to the absence of a free NH2 group in the side chain, is relatively devoid of anticholinergic side effects. Thus by slightly modifying the structure of the side chain it is possible to retain the efficacy while reducing the cardiotoxicity. 

MAPROTILINE HYDROCHLORIDE For the treatment of depressive illness in patients with depressive neurosis (dysthymic disorder) and manic-depressive illness, depressed type (major depressive disorder) also effective for the relief of anxiety associated with depression. 

MAPROTILINE HYDROCHLORIDE May be given as a single daily dose or in divided doses. Therapeutic effects are sometimes seen within 3 to 7 days, although as long as 2 to 3 weeks are usually necessary before improvement is observed. 

Pharmacology Tetracyclics enhance central noradrenergic and serotonergic activity. They do not inhibit monoamine oxidase. Although maprotiline and mirtazapine are in the same chemical class, they each affect different neurotransmitters and thus have different side effect profiles. Maprotiline primarily acts by blocking reuptake of norepinephrine at nerve endings. 

Maprotiline and amoxapine are selective norepinephrine uptake inhibitors. They share most of the properties of the tricyclic antidepressants. Maprotiline has less sedating effect than mianserin and it is more epileptogenic than any other antidepressant. It shows considerable cardiotoxicity when taken in overdose. 

Geriatric Considerations-Summary Given the side-effect profile, and potential drug interactions, maprotiline is not recommended for treatement of depression in older adults. 

Most child and adolescent studies published thus far have focused on the effects of the tricyclic antidepressants (TCAs) and, more recently, the SSRIs. A few open studies have also shown that monoamine oxidase inhibitors (MAOIs) can be used safely with children and adolescents (Ryan et ah, 1988b), but noncompliance with dietary requirements may present a significant problem for minors. Other antidepressants, including the heterocyclics (HTC) (e.g., amoxapine, maprotiline), buproprion, venlafaxine, and nefazodone, have been found to be efficacious for the treatment of depressed adults (APA, 2000), but they have not been well studied for the treatment of MDD in children and adolescents. Therefore, this chapter mainly describes the use of SSRIs and TCAs for youth with MDD. 

HCA is the term is used to refer to both TCAs and analogues of these agents, such as maprotiline and amoxapine. TCAs are by far the most commonly used HCAs and include tertiary amines such as amitriptyline, doxepin, and imipramine and secondary amines such as desipramine and nortriptyline. Most secondary amines could also be viewed as NE-selective antidepressants, while the hallmark of tertiary amine TCAs is their effects on multiple neurotransmitters over their clinically relevant dosing range. 

As with most data for reboxetine, this information primarily comes from summary papers rather than primary sources (473, 474). With this caveat, the adverse-effect profile of reboxetine is consistent with its pharmacology as an NSRI. Thus, it is similar to that of desipramine and maprotiline but without the risk of serious CNS (i.e., seizures, delirium) or cardiac (i.e., conduction disturbances) toxicity. The most common adverse effects of reboxetine are dry mouth, constipation, urinary hesitancy, increased sweating, insomnia, tachycardia, and vertigo. Whereas the first three adverse effects are commonly called anticholinergic, they are well known to occur with sympathomimetic drugs as well. In other words, these effects can be either the result of decreased cholinergic tone or increased sympathetic tone, although they tend to be more severe with the former than the latter. In contrast to TCAs, reboxetine does not directly interfere with intracardiac conduction. The tachycardia produced by reboxetine, however, can be associated with occasional atrial or ventricular ectopic beats in elderly patients. 

Kasper S, Dotsch M, Vieira A, et al. Plasma concentration of fluvoxamine and maprotiline in major depression implications on therapeutic efficacy and side effects. Eur Neuropsychopharmacol... 

A number of antidepressants do not fit neatly into the other classes. Among these are bupropion,mirtazapine, amoxapine, and maprotiline (Figure 30-5). Bupropion has a unicyclic aminoketone structure. Its unique structure results in a different side-effect profile than most antidepressants (described below). Bupropion somewhat resembles amphetamine in chemical structure and like the stimulant, has central nervous system (CNS) activating properties. 

Mirtazapine, amoxapine, and maprotiline have tetracyclic structures. Amoxapine is the /V-methylated metabolite of loxapine, an older antipsychotic drug. Amoxapine and maprotiline share structural similarities and side effects comparable to the TCAs. As a result, these tetracyclics are not commonly prescribed in current practice. Their primary use is in MDD that is unresponsive to other agents. 

Amoxapine is also rapidly absorbed with protein binding of about 85%. The half-life is variable, and the drug is often given in divided doses. Amoxapine undergoes extensive hepatic metabolism. One of the active metabolites, 7-hydroxyamoxapine, is a potent D2 blocker and is associated with antipsychotic effects. Maprotiline is similarly well... 

Maprotiline (bupropion) NET > SERT inhibition (amoxapine, maprotiline) t increased release of norepinephrine, 5-HT (mirtazapine) but no effect on 5-HT (bupropion) amoxapine and maprotiline resemble TCAs (mirtazapine) amoxapine and maprotiline rarely used bupropion) sedation and weight gain (mirtazepine) Interactions CYP2D6 inhibitor (bupropion)... 

An often troublesome adverse effect of antidepressant medication is weight gain. Two cases of this adverse effect have been reported in patients taking low doses of maprotiline (710). 

None of the newer antidepressants have been shown to be more effective overall than the tricyclics with which they have been compared. Solid evidence to support a claim of more rapid onset of action has been difficult to obtain. Amoxapine and maprotiline seem to have as many sedative and autonomic actions as most tricyclics more recently introduced antidepressants such as bupropion and venlafaxine have fewer, although nefazodone and mirtazapine are very sedating. Amoxapine and maprotiline are at least as dangerous as the tricyclics when taken in overdoses the other newer agents seem to be safer. 

Realini R, Mascetti R, Calanchini C. Efficacite et tolerance du moclobemide (Ro 11-1163 Aurorix) en comparaison avec la maprotiline chez des patients ambulatoires presen-tant un episode depressif majeur. [Effectiveness and tolerance of moclobemide (Ro 11-1163 Aurorix) in comparison with maprotiline in ambulatory patients presenting with a major depressive episode.] Psychol Med 1989 21 1689. 

Speech blockage, so called, has been reported in a 34-year-old woman who had taken phenelzine 45 mg/day for 2 months (3). The adverse effect disappeared on withdrawal and did not recur when her depression was successfully treated with maprotiline 175 mg/day. 

Maprotiline Tetracyclic Strong inhibitory effect on noradrenaline uptake Skin rashes (3%) Increased incidence of seizures in overdose Similar adverse effects profile to tricyclic compounds... 

Maprotiline has a tetracyclic structure, in which the tricyclic nucleus adjoins a fourth ring formed by an ethylene bridge vertical to the major plane of the molecule (SEDA-5, 34). It has a strong inhibitory effect on noradrenaline uptake across cell membranes, and relatively weak effects on serotonergic mechanisms. The half-life averages 43 hours (1), allowing once-daily dosing. 

There have been several comparisons of maprotiline with other antidepressants. There was no significant difference in adverse effects compared with doxepin (5), amitriptyline (6), or imipramine (7). 

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