Monoamine oxidase inhibitors efficacy

Monoamine Oxidase Inhibitors (MAOIs). Controlled trials comparing the M AOl phenelzine to clomipramine or fluoxetine have produced mixed results. Given the limited data regarding any efficacy of MAOIs in the treatment of OCD coupled with their potentially dangerous interactions, we cannot recommend MAOIs in the treatment of OCD until other approaches have been tried. 

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 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... 

E.D. Hendley, S.H. Snyder, The relationship between the action of monoamine oxidase inhibitors on the noradrenaline uptake system and their antidepressant efficacy. Nature 220 (1968) 1330-1331. 

Similar to the discovery of other psychiatric medications, the mood-enhancing effects of monoamine oxidase inhibitors (MAOIs) were identified serendipi-tously mood improvements were observed in patients with tuberculosis treated with iproniazid (Bloch et ah, 1954) The early enthusiasm for the MAOIs was based on significant and unprecedented antidepressant effects and the link between antidepressant efficacy and their... 

Mann, J.J., Aarons, S.R, Wilner, P.J., Keilp, J.G., Sweeney, J.A., Pearl-stein, T, Frances, A.J., Kocsis, J.H., and Brown, R.P. (1989) A controlled study of the antidepressant efficacy and side effects of ( —)-deprenyl. A selective monoamine oxidase inhibitor. Arch Gen Psychiatry 46 45-50. 

Zametkin, A., Rapoport, J.L., Murphy, D.L., Linnoila, M., and Is-mond, D. (1985) Treatment of hypetactive childten with monoamine oxidase inhibitors I. Clinical efficacy. Arch Gen Psychiatry 42 962-966. 

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. 

SRls are currently the most prevalent pharmacological treatment used for panic disorder [see Westenberg and Den Boer, Chapter 24, in this volume], even though tricyclic antidepressants, monoamine oxidase inhibitors [MAOls], and benzodiazepines are also effective. The efficacy of the SRI antidepressants and the observation that initially they may induce deterioration of symptoms [which is usually not the case with treatment of depressed patients with the same medications] raise issues related to the pathobiology of anxiety and its comorbidity with depression. 

In contrast, a less extensive but still convincing database has identified important clinical differences in efficacy for antidepressants used to treat patients with atypical or comorbid depression. Individuals with atypical depression (distinct quality of mood, hyperphagia, hypersomnia, psychomotor retardation, rejection sensitivity, and such unusual atypical features as chocolate craving] have superior responses to monoamine oxidase inhibitors (MAOIs], selective serotonin reuptake inhibitors (SSRIs), and perhaps venlafaxine, and most do not respond well to tricyclic antidepressants (TCAs] (Davidson et al. 1982 Liebowitz et al. 1988 Quitkin et al. 1988, 1991). Despite these data, TCAs unfortunately have been the first choice for most atypical patients until SSRIs were introduced. 

In an early study, Insel et al. [1983b] compared the efficacy of CMI with that of clorgiline, a monoamine oxidase-A inhibitor, in a controlled crossover study of patients with OCD. Although CMl was effective, patients on clorgiline did not improve at all. Vallejo et al. [1992] conducted a controlled clinical trial of the efficacy of CMl and phenelzine in 30 patients with OCD. The authors reported improvement in both groups however, the lack of a placebo control and the small size of the study groups limit the applicability of these findings. Further studies on the therapeutic role of monoamine oxidase inhibitors in OCD, especially in OCD with comorbid panic disorder, are warranted. 

ECT is superior in efficacy when compared with placebo, sham ECT, and active drug therapy. Upon the introduction of effective pharmacotherapy for severe depression, the relative efficacy of drug versus ECT was frequently studied. Our review of the relevant literature led to an extrapolation of the data from selected studies (primarily class I or II designs) for a quantitative analysis of the efficacy of ECT versus other treatments for an acute depressive episode ( 53). The comparisons with ECT included simulated (or sham) ECT, placebo, the standard tricyclic antidepressants, and the monoamine oxidase inhibitors [ Table 8-1 (54, 55, 56, 57, 58 and 59), Table 8 2 (0g 6i 62 and 63), Table 8-3 (56, 61, 62, 63, 64, 65 and 66), and Table 8-4 (55, 60, 61, 62 and 63)]. We also compared the relative efficacy of the bilateral versus the UNID forms of administration [Table 8-5 (42, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77 and 78)]. A meta-analysis was... 

The overall efficacy of ECT was 78%, which is significantly superior to that of tricyclic antidepressants, whose overall efficacy was 64%, as well as to placebo, simulated ECT, and the monoamine oxidase inhibitors, whose overall response rates ranged from 28% to 38%. This difference was particularly striking because many patients in the ECT-treated groups had failed previous drug trials. The adequacy of some of these, however, was questionable. Furthermore, in contrast to other reports, our analysis did not find a significant difference favoring BILAT over UND ECT (i.e., only a 7% overall difference). 

Although behavioral treatments for social phobia have been well studied, there are very limited data on its pharmacological management, b- Blockers (propranolol, atenolol) have been recommended, but available evidence indicates their effect may be no different than that of placebo ( 78). In a controlled study, the monoamine oxidase inhibitor (MAOl) phenelzine has been shown to be more effective than placebo (78, 79). Anecdotal reports have also described efficacy with alprazolam, clonidine, and fluoxetine, but systematic data are lacking (80, 81, 82 and 83). 

The depressive phase of manic-depressive disorder often requires concurrent use of an antidepressant drug (see Chapter 30). Tricyclic antidepressant agents have been linked to precipitation of mania, with more rapid cycling of mood swings, although most patients do not show this effect. Selective serotonin reuptake inhibitors are less likely to induce mania but may have limited efficacy. Bupropion has shown some promise but—like tricyclic antidepressants—may induce mania at higher doses. As shown in recent controlled trials, the anticonvulsant lamotrigine is effective for many patients with bipolar depression. For some patients, however, one of the older monoamine oxidase inhibitors may be the antidepressant of choice. Quetiapine and the combination of olanzapine and fluoxetine has been approved for use in bipolar depression. 

Plasma levels of doxepin similar to those achieved during oral therapy may be obtained with topical application the usual drug interactions associated with tricyclic antidepressants may occur. Therefore, monoamine oxidase inhibitors must be discontinued at least 2 weeks prior to the initiation of doxepin cream. Topical application of the cream should be performed four times daily for up to 8 days of therapy. The safety and efficacy of chronic dosing has not been established. Adverse local effects include marked burning and stinging of the treatment site which may necessitate discontinuation of the cream in some patients. Allergic contact dermatitis appears to be frequent, and patients should be monitored for symptoms of hypersensitivity. 

Panic disorder is one of the most prevalent psychiatric disorders in industrialized countries. It is often associated with agoraphobia and has an estimated prevalence of between 1% and 6%. The use of imipramine in the treatment of anxiety by Klein and Fink, and the discovery by William Sargant that monoamine oxidase inhibitors (MAOIs) were effective in the treatment of "atypical depression" over 30 years ago led to the investigation of the efficacy of such treatments in patients with panic disorder. Since that time, such drugs have been shown to attenuate the symptoms of panic in addition to those of phobic avoidance and anticipatory anxiety. As both the... 

Antidepressant drugs of various classes (tricyclics, monoamine oxidase inhibitors, SSRIs) have broad efficacy in generalized anxiety and in panic disorder, for which they are the treatments of choice (6,7). While not likely to cause benzodiazepine-like dependence or abuse, they do have a significant therapeutic latency, and the older drugs are very toxic in overdose. 

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). 

The bulk of literature examining antidepressant use in AD is made up of case reports and uncontrolled studies. Most of these report a favorable response to antidepressants, but several placebo-controlled trials have demonstrated mixed results. Of the antidepressants studied, citalopram, sertraline, clomipramine, and moclobe-mide (a monoamine oxidase inhibitor not marketed in the U.S.) were considered efficacious in at least one study but fluoxetine and imipramine were no better than placebo. It should be noted that citalopram and sertraline have both been studied in other placebo-controlled trials in this population with no difference over placebo. ... 

Monoamine oxidase inhibitor (MAOI) antidepressants have been in use for nearly 40 years. At the present time, they are viewed as second- or third-line antidepressant medications for reasons of both efficacy and safety. The available MAOIs are phenelzine sulfate (Nardil), isocarboxazid (Marplan), and tranylcypromine sulfate (Parnate). Two additional MAOI antidepressants, moclobemide and brofaromine, are approved for use in Europe and/or Canada. 

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