Antidepressants MAOIs and Tricyclics

Because of the strong side effects and risk of dependency associated 

It is likely that depression and anxiety disorders are associated with problems in several brain systems, and, indeed, different drugs appear to be effective in different people. Even though SSRIs are currently the first choice of drugs for treating many anxiety disorders, other classes of antidepressants are tried if the SSRIs prove ineffective. 

Both norepinephrine and serotonin have been implicated in anxiety disorders and depression. Although scientists generally believe that MAOIs and TCAs are beneficial because they target serotonin systems, there is some evidence that specifically targeting the norepinephrine system can help some patients. Certain TCAs preferentially activate norepinephrine systems. These and other norepinephrine-selective drugs have been shown to help alleviate some cases of depression. 

Norepinephrine is made in cells located in the brain stem, mostly in a group of cells called the locus coeruleus. These neurons send widespread projections throughout the brain. This distribution has functional consequences. Small disturbances in the locus coeruleus can have a large impact on many different brain areas at the same time, and thus influence many behaviors. Disorders of emotion and mood are similar in that they simultaneously impact many different behaviors. Therefore, it is reasonable to suggest that norepinephrine might affect emotion in some ways. 

It is important to recognize that different parts of the brain regulate different behaviors. Drugs that raise levels of norepinephrine all over the brain are likely to influence many behaviors. The action of norepinephrine in each area might be very different, depending on what kind of receptor it binds. In the brain, norepinephrine can bind to four types of receptors alpha 1, alpha 2, beta 1, and beta 2. Alpha 2 receptors cause 

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Medications with serotonergic activity may also have other monaminergic or sympathomimetic activity. Combining MAOIs with these medications may result in a complex side effect profile. For example, combining meperidine or dextromethorphan with MAOIs may result in respiratory depression, in addition to symptoms of serotonin excess. Furthermore, interactions between MAOIs and tricyclic antidepressants (TCAs) more commonly result in potentiating shared adverse events such as othostatic hypotension, as opposed to hyperadrenergic crises or the serotonin syndrome. 

It became obvious, however, that psychostimulants were not effective in situations of lowered arousal resulting from mood depression. In the 1950s, antidepressants such as the monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) became recognized as more effective in treating depression. The differentiation between arousal and mood thus became clearer. It is through the action of drugs that sedate and thus reduce anxiety versus those drugs that do not sedate but are anxiolytic that the basic concepts of anxiety have forcibly to be reconsidered. This inevitably led to the need for a reconceptualization of psychotropic modes of action in relation to psychiatric disorders. 

Drug therapy and/or counselling are effective treatments for most patients. Three categories of drugs used as antidepressants are tricyclic antidepressants, MAOIs and SSRIs. 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

The development of specific drugs for the treatment of depression only occurred in the early 1950s with the accidental discovery of the monoamine oxidase inhibitors (MAOIs) and the tricyclic antidepressants (TCAs). This period marked the beginning of the era of pharmacopsychiatry. 

Drugs that may be affected by duloxetine include drugs extensively metabolized by CYP2D6 (eg, flecainide, phenothiazines, propafenone, tricyclic antidepressants, thioridazine), alcohol, CNS-acting drugs, MAOIs, and drugs highly bound to plasma proteins (eg, warfarin). 

MAOIs should not be administered together with or immediately following tricyclic antidepressants (TCAs). At least 14 days should elapse between the discontinuation of the MAOIs and the institution of a TCA. Some TCAs have been used safely and successfully in combination with MAOIs. 

Drugs that may affect methylphenidate include MAOIs. Drugs that may be affected by methylphenidate hydrochloride include guanethidine, anticonvulsants (eg, phenytoin, phenobarbital, primidone), selective serotonin reuptake inhibitors, coumarin anticoagulants, and tricyclic antidepressants. 

The growth during the 1990s in the use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), for the treatment of anxiety disorders represented a major advance in the pharmacotherapy of anxiety. The efficacy of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) had been established alongside their antidepressantw actions several decades... 

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. 

Methylphenidate may decrease therapeutic effects of concomitantly administered antihypertensive medications and may potentiate effects of warfarin, phenytoin, phenylbutazone, and tricyclic antidepressants. When methylphenidate and MAOIs are coadministered, hypertensive crisis may result. 

Because suicide is one of the leading causes of death in elderly people and in other populations, rapid and effective treatment of depression is warranted. Current therapies include the use of electroconvulsive (shock) therapy, psychiatric intervention, and antidepressant drugs such as tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and serotonin-selective reuptake inhibitors (SSRIs). Recently, in the U.S., the use of St. John s wort (Hypericum perforatum) has become more prevalent, especially in the treatment of depression. 

Tricyclic antidepressants + MAOIs —> stroke, hyperpyrexia and convulsions can occur. Potentially a hazardous combination. 

Antidepressants were first introduced into the market in the 1950s with the serendipitous discovery of the antidepressant effect of two drugs initially evaluated for other medical uses Iproniazide, a monoamine oxidase inhibitor (MAOI), and Imipramine, a tricyclic antidepressant (TCA). Since then, a whole new generation of chemically and pharmacologically unrelated compounds have been introduced, which appear to be safer and better tolerated due to a more specific mechanism of action. These include selective serotonin reuptake inhibitors (SSRIs), serotonin and... 

Antidqjressants Combination with tricyclic antidepressants has the potential to precipiate hypertensive crisis complicated by hyperreflexia, rigidity and h)q erpyrexia. MAOTSSRI combinations may provoke the life-threatening serotonin s3mdrome (p. 376). Strict rules apply regarding washout periods when switching between MAOIs and other... 

Most MAOIs are irreversible and the effects take weeks to stabilize. Chemically, they fall into a number of groups, including hydrazines, such as pheneizine and iproniazid, propargylamines, such as pargyline, chlorgyline and selegiline, and cyclopropylamines, such as tranylcypromine. A reversible inhibitor that may be safer under some circumstances is moclobemide. The use of MAOIs has declined and tricyclics and the SSRIs are being used more. See antidepressants. 

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