Tricyclic antidepressants monoamine oxidase inhibitors

Serious adverse effects of epinephrine potentially occur when it is given in an excessive dose, or too rapidly, for example, as an intravenous bolus or a rapid intravenous infusion. These include ventricular dysrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in blood pressure, and cerebral hemorrhage. The risk of epinephrine adverse effects is also potentially increased in patients with hypertension or ischemic heart disease, and in those using (3-blockers (due to unopposed epinephrine action on vascular Ui-adrenergic receptors), monoamine oxidase inhibitors, tricyclic antidepressants, or cocaine. Even in these patients, there is no absolute contraindication for the use of epinephrine in the treatment of anaphylaxis [1,5,6]. 

Specific antidepressant agents that the reader should now understand include the monoamine oxidase inhibitors, tricyclic antidepressants, serotonin selective reuptake... 

Monoamine oxidase inhibitors Tricyclic antidepressants Antipsychotics... 

Graham PM, Potter JM, Paterson J. Combination monoamine oxidase inhibitor/tricyclic antidepressants interaction. Lancet 1982 2(8295) 440. 

Graham PM, Potter Paterson JW. Combinaticn monoamine oxidase inhibitor/tricyclic antidepressant interaction. Lancet (1982) ii, 440. 

The discovery of the antidepressant effect of medications was coincidental to their use for other disorders. Initial work published in 1952 reported that iproniazid (originally used for the treatment of tuberculosis) could elevate mood. Although the use of iproniazid was discontinued due to toxicity, many other additional medications have been tested and approved for the treatment of depression. These include monoamine oxidase inhibitors, tricyclics, selective serotonin reuptake inhibitors, and a heterogeneous class of atypical drugs. 

The uses, drug interactions, and adverse effects of the monoamine oxidase inhibitor tricyclic, selective serotonin reuptake inhibitor, and heterocyclic antidepressants are discussed. 

The amphetamines and the anorexiants should not be given during or within 14 days after administration of monoamine oxidase inhibitors (see Chap. 31) because the patient may experience hypertensive crisis and intracranial hemorrhage. When guanethidine is administered with the amphetamines or the anorexiants, the antihypertensive effect of guanethidine may decrease. Coadministration of the amphetamines or the anorexiants with the tricyclic antidepressants may decrease the effects of the amphetamines or the anorexiants. 

CYP. cytochrome P450 isoenzyme HIV, human immunodeficiency vims INR, International Normalized Ratio LFTs, liver function tests MAOI, monoamine oxidase inhibitor PT, prothrombin time TCA, tricyclic antidepressant. 

MAOI, monoamine oxidase inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

MAOI, monoamine oxidase inhibitor SARI, serotonin antagonist and reuptake inhibitor SNRI, serotonin and norepinephrine reuptake inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

Tricyclic antidepressants Monoamine oxidase inhibitors Selective serotonin reuptake inhibitors Antipsychotics Phenothiazines Risperidone Lithium... 

Two rather broad structural classes account for the large majority of drugs that have proven useful in the clinic for treating depression. Each of these has associated with it some clearly recognized side effects the monoamine oxidase inhibitors, most commonly derivatives of hydrazine, tend to have undesirable effects on blood pressure the tricyclic compounds on the other hand may cause undesirable changes in the heart. Considerable effort has thus been expended toward the development of antidepressants that fall outside those structural classes. An unstated assumption in this work is the belief that very different structures will be associated with a novel mechanism of action and a different set of ancillary activities. One such compound, trazodone... 

Virtually all types of drug that have been shown to be effective in major depression exert profound effects on the functioning of the serotoninergic or noradrenergic systems, or both. Although some treatments have been shown to decrease the sensitivity of certain postsynaptic 5-HT and NE receptors, it is generally believed that it is an enhancement of neurotransmission in these systems that is responsible for the improvement of the core symptoms of depression. For instance, long-term administration of tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) decreases the density of (3-adrenoceptors and cortical 5-HT2 receptors (Blier and Abbott 2003). 

A number of medications used in the treatment of anxiety have effects on serotonin neurotransmission (Ch. 13). These medications include tricyclic antidepressant medications, SSRIs, and monoamine oxidase inhibitors (MAOIs). However, because these medications take weeks to exert their full anxiolytic effects, it is unlikely that blocking the reuptake (and thus increasing synaptic levels) of either serotonin or norepinephrine selectively is responsible for their anxiolytic properties — rather it is suspected that the therapeutic effects are due to changes in gene expression, protein levels, and eventually changes in synaptic connections between neurons. 

Blockers are contraindicated in patients with decompensated heart failure unless it is caused solely by tachycardia (high output). Other contraindications include sinus bradycardia, concomitant therapy with monoamine oxidase inhibitors or tricyclic antidepressants, and patients with spontaneous hypoglycemia. Side effects include nausea, vomiting, anxiety, insomnia, lightheadedness, bradycardia, and hematologic disturbances. 

AUC, area under the curve, Cmax, maximum concentration MAOI, monoamine oxidase inhibitor TCA, tricyclic antidepressant. Recommended first-line drug interaction search engines Lexi-Comp, Inc Lexi-Comp Online, http //online.lexi.com and Thomson MICROMEDEX Healthcare Series https //www.thomsonhc.com. 

Lucki, I., and Frazer, A. (1982) Prevention of the serotonin syndrome in rats by repeated administration of monoamine oxidase inhibitors but not tricyclic antidepressants. Psychopharmacology, 77 205-211. 

Bonson KR, Buckholtz JW, Murphy DL. (1996). Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology. 14(6) 425-36, Bonson KR, Murphy DL. (1996). Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors, or lithium. Behav Brain Res. 73(1-2) 229-33. 

Listing of antidepressants in traditional groupings. Abbreviations TCAs = tricyclic antidepressants MAOls = monoamine oxidase inhibitors SSRls = selective serotonin reuptake inhibitors. 

The so-called atypical antidepressants such as venlafaxine and bupropion can be tried, but their safety and efficacy in treating patients with dementia have not been well studied. The older tricyclic antidepressants and monoamine oxidase inhibitors are not tolerated well by demented patients and should be avoided. Two possible exceptions are nortriptyline (Pamelor) and desipramine (Norpramin), but even these should be tried only after the newer antidepressants have proved ineffective. 

Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models... 

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. 

Citalopram is a selective serotonin re-uptoke inhibitor (SSRI). These tend to have fewer ontimuscarinic effects than tricyclic antidepressant (TCA) drugs, such as dry mouth and constipation however, SSRIs tend to cause gastrointestinal effects, such as nausea and vomiting. MAOIs are monoamine oxidase inhibitors. 

Lorazepam is a short-acting benzodiazepine indicated for use in relieving anxiety and insomnia. Lorazepam may also be administered perioperatively to alleviate pain and in status epilepticus. Imipramine is a tricyclic antidepressant, paroxetine is a selective serotonin re-uptake inhibitor, venlafaxine is a serotonin and adrenaline re-uptake inhibitor and moclobemide is a reversible monoamine oxidase inhibitor. Imipramine, paroxetine, venlafaxine and moclobemide are all classified as antidepressants. 

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