Tricyclic antidepressants and monoamine oxidase 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. 

Newer antidepressants (eg, fluoxetine, paroxetine, citalopram, venlafaxine) are mostly SSRIs and are generally safer than the tricyclic antidepressants and monoamine oxidase inhibitors, although they can cause seizures. Bupropion (not an SSRI) has caused seizures even in therapeutic doses. Some antidepressants have been associated with QT prolongation and torsade de pointes arrhythmia. SSRIs may interact with each other or especially with monoamine oxidase inhibitors to cause the serotonin syndrome, characterized by agitation, muscle hyperactivity, and hyperthermia (see Chapter 16). 

FIGURE 9-6. Various treatments can be given in combination for panic disorder (i.e., panic combos). The basis of all many combination treatments is a serotonin selective reuptake inhibitor (SSRI). Other antidepressants such as venlafaxine, nefazodone, mirtazapine, tricyclic antidepressants, and monoamine oxidase inhibitors can all have antipanic actions, although they are second-line treatments, as are the benzodiazepines. On the other hand, benzodiazepines are often added to SSRIs, particularly at the initiation of an SSRI and intermittently when there is breakthrough panic. Cognitive and behavioral psychotherapies can also be added to any of these drug treatments. 

From the existing literature, St. John s wort appears to be a safe and effective alternative in the treatment of depression. Tricyclic antidepressants and monoamine oxidase inhibitors can produce serious cardiac side effects, such as tachycardia and postural hypotension, and many unwanted anticholinergic side effects, including dry mouth and constipation. St. John s wort has proved to be free of any cardiac, as well as anticholinergic, side effects normally seen with antidepressant medications. Based upon limited studies, St. John s wort appears to be an acceptable alternative to traditional antidepressant therapy. 

Titier K, Castaing N, Le-Deodic M et al (2007) Quantification of tricyclic antidepressants and monoamine oxidase inhibitors by high-performance liquid chromatography-tandem mass spectrometry in whole blood. J Anal Toxicol 31 200-207... 

The older tricyclic antidepressants and monoamine oxidase inhibitors also cause withdrawal mania and a variety of other adverse withdrawal effects, including cognitive and emotional disturbances and psychosis. Many of them have strong anticholinergic effects and therefore produce severe anticholinergic rebound on withdrawal, including cardiovascular and gastrointestinal symptoms. I have seen patients who have taken tricyclics for many years and then been unable to withdraw from them. 

Ponto LB, Perry PJ, Liskow BI, Seaba HH. Drug therapy reviews tricyclic antidepressant and monoamine oxidase inhibitor combination therapy. Am J Hosp Pharm 1977 34(9) 954-61. 

Tyrer P. Clinical effects of abrupt withdrawal from tricyclic antidepressants and monoamine oxidase inhibitors after long-term treatment. J Affect Disord 1984 6(l) l-7. 

By the 1970s and early 1980s it was recognized that certain tricyclic antidepressants and monoamine oxidase (MAO) inhibitors were effective in treating panic disorder and one tricyclic antidepressant (clomipramine) was effective in treating obsessive-compulsive disorder. Thus, there began to be recognized that some antidepressants overlapped with anxiolytics for the treatment of anxiety disorder sub-types or for mixtures of anxiety and depression (Fig. 8—8). However, either anxiolytics... 

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. 

The first-generation tricyclic antidepressants, the monoamine oxidase inhibitors, and the newer agents can cause sedation, insomnia, orthostatic hypotension, or nausea. Because of their anticholinergic properties, they may also produce cardiac toxicides (Table 43.2). 

Patients taking certain systemic medications are also more sensitive to the pressor effects of phenylephrine. In individuals taking atropine, the pressor effect of phenylephrine is augmented, and tachycardia can occur. Tricyclic antidepressants and monoamine oxidase (MAO) inhibitors also potentiate the cardiovascular effects of topical phenylephrine. The concomitant use of phenylephrine is contraindicated with these agents, even up to 21 days after cessation of MAO inhibitor therapy. Similarly, patients taking reserpine, guanethidine, or methyldopa are at increased risk for adverse pressor effects from topical phenylephrine because of denervation hypersensitivity accompanying the chemical sympathectomy. 

There are three main pharmacological classes of antidepressant compounds tricyclic antidepressants (TCA), monoamine oxidase inhibitors (MAOI) and serotonin reuptake inhibitors (SSRI). Members of each class have been tried in BN. According to a survey of 19 controlled clinical trials, all are more effective than placebo, with little to choose between them in terms of efficacy (Bacaltchuk and Hay 2003). 

A central African term for a substance prepared from the cortex of the roots of Taber-nanthe iboga. Large doses are said to produce catalepsy and death. Main active component is ibogaine and twelve other alkaloids. Psychological effects like those of tricyclic antidepressants, plus monoamine oxidase inhibitors and anticholinesterases. 

The first-generation tricyclic antidepressants, the monoamine oxidase inhibitors, and the newer agents can... 

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. 

Dmg-induced serotonin syndrome is generally mild and resolves when the offending drugs are stopped. However, it can be severe and deaths have occurred. A large number of drugs have been implicated including tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), selective serotonin re-uptake inhibitors (SSRIs), pethidine, lithium, and dextromethorphan. The most severe type of reaction has occurred with the combination of selective serotonin re-uptake inhibitors and monoamine oxidase inhibitors. Both non-selective MAOIs such as phenelzine and selective MAOIs such as moclobemide and selegiline have been implicated. 

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... 

With the introduction of the SSRIs, the safety and tolerability of antidepressants improved remarkably. As a class, these medications have little or no affinity for cholinergic, (3-adrenergic or histamine receptors and do not interfere with cardiac conduction. They are well tolerated by patients with heart disease and by the elderly, who are especially sensitive to the anticholinergic and orthostatic effects of the tricyclic antidepressant agents (TCAs) and monoamine oxidase inhibitors (MAOIs). 

The first psychotropics of the modern era (e.g., lithium, neuroleptic antipsychotics, tricyclic and monoamine oxidase inhibitor antidepressants) were discovered serendipitously. These agents were not engineered to have selective actions, but instead produce a wide range of central biochemical effects and generally affect more than one neurotransmitter system simultaneously, resulting in multiple repercussions ... 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

Onset of therapeutic effects of the major antidepressant drugs (tricyclic antidepressants, serotonin reuptake inhbitors, and monoamine oxidase inhibitors) requires several weeks. 

Discontinuing selective serotonin reuptake inhibitors (SSRIs) may induce a syndrome wherein the main neuropsychiatric symptoms are dizziness, shock-like sensations, anxiety, irritability, agitation, and insomnia. These symptoms usually develop 1 to 7 days after abrupt or gradual discontinuation. Antidepressant discontinuation may also induce mania, mainly reported with tricyclics and monoamine oxidase inhibitors but also observed with SSRIs. 

Adverse interactions of lithium with tricyclic antidepressants, SSRIs, and monoamine oxidase inhibitors have been reviewed (581). In reviews of antidepressants and the serotonin syndrome, a possible contributory role has been suggested for lithium, based on case reports with tricyclic antidepressants, SSRIs, trazodone, and venlafax-ine (204,582). 

Key-Drugs classes in boxed, shaded fields represent the three major antidepressants groups, tricyclics (TCAs), selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors. 

Contents Introduction, history and brain basics—Older antidepressants tricyclics and monoamine oxidase inhibitors—Selective serotonin reuptake inhibitors—Second generation antidepressants—Lithium, a medication for bipolar depression—Natural depressants—Teens and antidepressants trends and attitudes—Case study one girl s experience with antidepressants. 

Older Antidepressants Tricyclics and Monoamine Oxidase Inhibitors... 

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