Phenelzine treatment

This belief was further supported by the evidence of a correlation between the clinical response and REM sleep suppression as well as a temporal relationship between the onset of clinical response and REM sleep suppression. However, some of the later studies suggested that REM sleep suppression is not necessary for the antidepressant action (Gillin 1983). For example, some studies show evidence of no change or even an increase in REM sleep with the treatment of depression (Gillin et al. 2001). Recently, Landolt Gillin (Landolt and Gillin 2002) have also demonstrated that the antidepressant response to phenelzine treatment does not depend on elimination of REM sleep or inhibition of slow wave activity in non-REM sleep. However, the generalization of some of these studies is limited because of their small sample size. 

Landolt H. P, Gillin J. C. (2002). Different effects of phenelzine treatment on EEG topography in waking and sleep in depressed patients. Neuropsychopharmacology 27, 462-9. 

MAOIs are associated with a risk of significant weight gain during treatment. This side effect appears to occur less frequently with tranylcypromine therapy than with phenelzine treatment. 

Robinson D, Kayser A, Bennett B, et. al. Maintenance phenelzine treatment of major depression an interim report. Psychopharmacol Bull 1986 22 553-557. 

Monoamine—Oxidase Inhibitors. In the mid-1950s, tuberculosis patients with depression being treated with iproniazid (42) were occasionally reported to become euphoric. This observation led to the discovery of irreversible monoamine—oxidase (MAO) inhibiting properties. Hydrazine and nonhydrazine-related MAO inhibitors were subsequentiy shown to be antidepressants (122). Three other clinically effective irreversible MAO inhibitors have been approved for treatment of major depression phenelzine (43), isocarboxazid (44), and tranylcypromine (45). 

In the discussion of benzylamines, we have met medicinal agents that owe their activity to some particular functionality almost without reference to the structure of the rest of the molecule. The hydrazine group is one such function in that it frequently confers monamine oxidase-inhibiting activity to molecules containing that group. Such agents frequently find use as antidepressants. Thus, reduction of the hydrazone of phenyl-acetaldehyde (84) affords the antidepressant phenelzine (85). Similar treatment of the derivative of phenylacetone (86) gives pheniprazine (87). ... 

Acute treatment with nonselective MAO inhibitors (iproniazid, tranylcypromine, phenelzine), as a consequence of inhibiting both forms of the enzyme, increase, brain levels of all monoamines (phenylethylamine, tryptamine, methylhistamine aminergic neurotransmitters (dopamine, noradr enaline, adrenaline and serotonin). By contrast MAO-A inhibitors (clorgyline) increase serotonin and noradrenaline, while MAO-B inhibitors (selegiline, rasagiline) increase brain levels... 

The MAOI phenelzine and the RIMAs brofaramine and meclobemide are effective in SAD. Phenelzine is effective in 64% to 69% of SAD patients.58 It is generally reserved for treatment-refractory patients owing to dietary restrictions,... 

Phenelzine, an MAOI, is effective, but is reserved for treatment-resistant patients because of dietary restrictions, potential drug interactions, and adverse effects. 

The monoamine oxidase inhibitors (MAOIs) phenelzine and tranylcypromine increase the concentrations of NE, 5-HT, and DA within the neuronal synapse through inhibition of the monoamine oxidase (MAO) enzyme system. Both drugs are nonselective inhibitors of MAO-A and MAO-B. Selegiline is available as a transdermal patch for treatment of major depression. It inhibits MAO-A and MAO-B in the brain, but has reduced effects on MAO-A in the gut. 

Monoamine Oxidase Inhibitors (MAOIs). Shortly after their introduction, MAOIs, snch as phenelzine (Nardil), were found to reduce the frequency of panic attacks. It became a standard treatment for what is now known as panic disorder nntil snpplanted by the benzodiazepines and SSRIs. Although all MAOIs are presumably effective for panic disorder, phenelzine is the best studied and has been shown to be effective at daily doses ranging from 45 to 90 mg. When used to treat panic disorder, phenelzine should be initiated at a dose of 15mg/day and gradually increased in 15 mg increments until reaching a therapeutic dose. 

Unfortunately, some patients respond poorly to these first-line interventions. In particular, patients with a long duration of illness, extreme agoraphobic avoidance, and comorbid personality disorders are more likely to exhibit a poor treatment response. For such patients, TCAs such as imipramine or clomipramine and MAOIs such as phenelzine remain viable strategies. 

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. 

Benzodiazepines. The best studied of the benzodiazepines for social anxiety disorder, clonazepam has been demonstrated in controlled trials to be effective during both acute treatment (at an average dose of 2.4mg/day) and long-term maintenance therapy lasting up to 2 years. A controlled study of another high potency benzodiazepine, alprazolam, also proved effective, though it was outperformed by the MAOI antidepressant phenelzine and exhibited response rates lower than those reported with clonazepam. 

Early controlled studies demonstrated the effectiveness of irreversible MAOIs, particularly phenelzine and tranylcypromine, for generalized social anxiety disorder. Prior to the advent of the SSRIs, MAOis were considered the gold standard treatment for social anxiety disorder. The best studied of the MAOis, phenelzine, has proved snperior to both beta blockers and the benzodiazepine alprazolam in treating generalized social anxiety disorder. 

Generalized Sociai Anxiety Disorder, Treatment Resistance. A significant minority of patients will not experience a satisfactory treatment response to antidepressant therapy, even after a trial of adequate duration at full strength doses. For those with comorbid depression who are experiencing no benefit from SSRI treatment for either the anxiety or depression, then switching treatment is advisable. The options include switching to another SSRI, a SNRI (venlafaxine or perhaps dulox-etine), or, when other alternatives fail, phenelzine. 

Antidepressants. In the early 1980s, the recognition that depression is a frequent comorbid feature of BN coupled with the observation that appetite changes are a common feature of depression led researchers to evaluate antidepressant treatment for BN. Since that time, a series of controlled studies have demonstrated efficacy for a wide assortment of antidepressants including the TCAs imipramine (Tofranil) and desipramine (Norpramin), the MAOl phenelzine (Nardil), the SSRl fluoxetine (Prozac), and the atypical antidepressants trazodone (Desyrel) and bupropion (Wellbutrin). Overall, approximately two-thirds of antidepressant-treated patients with bulimia experience symptomatic improvement while nearly one-third achieves complete remission of binging and purging. In addition, the improvement in the symptoms of BN is not dependent on the presence of comorbid depression. 

In the United States, the three MAOIS available for the treatment of psychiatric conditions are phenelzine (Nardil), tranylcypromine (Parnate), and isocarboxazid (Marplan). All three agents have indications for adult major depression (>16 years old) and, more specifically, atypical depression (anergia, hypersomnia, hy-perphagia, somatization, and anxiety symptoms). Although not indicated for anxiety, the MAOIs can also be particularly helpful in treatment of these disorders. Selegiline or L-deprenyl (Eldepryl) is also available in the United States and indicated for symptoms of Parkinson s disease and depression. 

Phenelzine and tranylcypromine are both effective in the treatment of social phobia. Many practitioners continue to be hesitant to use this class of medications, given the dietary restrictions required of patients and the potential risk of hypertensive crises when combined with dietary tyramine and sympathomimetic medications. However, the proven effectiveness of this class makes it an important option in the treatment of social phobia. 

Clonidine. As with the rationale for P-blockers in the treatment of social phobia, clonidine hydrochloride, an a-adrenergic agonist, has been used in an attempt to target the physiological symptoms of the disorder. In a case report by Goldstein [1987], one subject with social phobia who experienced a primary symptom of blushing was treated with clonidine 0.1 mg twice a day after trials with alprazolam, phenelzine, and propranolol failed to provide symptom relief. The patient reported a dramatic decrease in the frequency and intensity of blushing episodes after 1 week of treatment. At 4-month follow-up, his symptoms remained well controlled and he denied any side effects. 

Robinson DS, Lerfald SG, Bennett B, et al Continuation and maintenance treatment of major depression with the monoamine oxidase inhibitor phenelzine a double-blind placebo-controUed discussion study. Psychopharmacol Bull 27 31-39, 1991... 

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