Monoamine oxidase inhibitors panic disorder

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. 

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 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. 

Based on some intriguing case reports (Jenike et al. 1983), a trial with a monoamine oxidase inhibitor (MAOI) may be an option in OCD patients who have comorbid panic disorder. In a double-blind trial, both phenelzine and clomipramine were found to be effective in reducing symptoms in OCD, as reflected on two of four OC measures [Vallejo et al. 1992). None of the patients in this study had panic disorder. This study suggests that MAOIs may be helpful in some patients with OCD even in the absence of panic disorder. However, in an earlier comparison trial, clomipramine, but not the MAOI clorgiline, resulted in significant reduction in OC symptoms [Insel et al. 1983b). Additional studies are needed to evaluate the place of MAOIs (including the newer reversible inhibitors of monoamine oxidase A [RIMAs], such as moclobemide) in the pharmacotherapy of OCD. 

TABLE 13-7. Monoamine oxidase inhibitor versus placebo treatment of panic disorder... 

Sheehan DV, Claycomb JB, Surnam OS. Monoamine oxidase inhibitors and alprazolam in the treatment of panic disorder and agoraphobia. Psychiatr Clin North Am 1985 8 49-62. 

Arguably the first modern class of antidepressants, monoamine oxidase inhibitors (MAOIs) were introduced in the 1950s but are now rarely used in clinical practice because of toxicity and potentially lethal food and drug interactions. Their primary use now is in the treatment of depression unresponsive to other antidepressants. However, MAOIs have also been used historically to treat anxiety states, including social anxiety and panic disorder. In addition, selegiline is used for the treatment of Parkinson s disease (see Chapter 28). 

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. 

Patients with panic disorder have usually been treated with TCAs [93], monoamine oxidase inhibitors (MAOIs) [94], and high-potency BZDs (i.e., alprazolam, clonazepam) [95, 96], Although the MAOIs had demonstrated effectiveness for panic disorder in several studies, they left the sleep complaint relatively unaffected [97],... 

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. 

Monoamine oxidase inhibitors are used to treat depression, atypical depression, bulimia, posttrau-matic stress reactions, obsessive-compulsive disorder, panic attacks, narcolepsy, phobias, hypochondria, anxiety, and many other psychiatric disorders as well as night tremors, parkinsonism, postural hypotension, headache, and aphthous stomatitis. 

The mood and anxiety disorders in their various permutations constitute a major source of personal suffering and impaired ability to engage in productive Avork and interpersonal relationships. Between 5 and 9% of women and between 2 and 3% of men meet the diagnostic criteria for major depression at any time 10-25% of all women suffer major depression sometime in their lives, while 5-10% of men will develop major depressive disorder (American Psychiatric Association, 1994). The anxiety disorders obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, and generalized anxiety disorder (GAD) show lifetime prevalence rates of approximately 2.5%, 7%, 2.5%, and 5% respectively. Between 3 and 13% of individuals in community samples are regarded to meet the diagnostic criteria for social phobia. Mood and anxiety disorders are common comorbidities (American Psychiatric Association, 1994) and the most common antidepressant medications including the serotonin reuptake inhibitors, the mixed serotonin-catecholamine reuptake inhibitors, the tricyclic antidepressants, and the monoamine oxidase inhibitors, are all effective treatments for anxiety and panic attacks. 

Monoamine oxidase inhibitors, such as SSRIs, have been shown to be effective in the treatment of depression, and they have become among the most widely used prescription drugs in the United States. Prozac is used not only to treat major depressive disorders but also bulimia nervosa, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder. Multiple serotonin receptor subtypes are involved. Specific serotonin receptor subtype agonists and antagonists have been radiolabeled with positron-emitting tracers to assess the state of the serotonergic system. 

Bakish D The use of the reversible monoamine oxidase-A inhibitor brofaromine in social phobia complicated by panic disorder with agoraphobia. J Clin Psychopharmacol 14 74-75, 1994... 

Bakish D, Saxena BM, Bowen R, et al Reversible monoamine oxidase-A inhibitors in panic disorder. Clin Neuropharmacol 16 (suppl 2 S77-S82, 1993a Bakish D, Lapierre Y, Weinstein R, et al Ritanserin, imipramine and placebo in the treatment of dysthymic disorder. J Chn Psychopharmacol 13 409-414, 1993b Bakish D, Ravindran A, Hooper C, et al Psychopharmacological treatment response of patients with a DSM-111 diagnosis of dysthymic disorder. Psychopharmacol Bull 30 53-59, 1994... 

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... 

Monoamine Oxidase (MAO) Inhibitors. The classical irreversible MAO inhibitors are effective in treating panic disorder, with anecdotal observations suggesting that they may be even more effective than imipramine. Clinical experience with reversible inhibitors of MAO A (RIMAs) (see Chapter 6) is also favorable for the treatment of panic disorder. However, the RIMAs may be somewhat less effective than the irreversible MAO inhibitors, but this is not well established. The disadvantages of the MAO inhibitors make them second- or third-line treatments for panic disorder these include orthostatic hypotension, weight gain, sexual dysfunction, and dietary restrictions (low tyramine diet), with the potential for a tyramine-induced hypertensive crisis. The RIMAs appear safer, with lessened potential for side effects, as discussed in Chapter 6, but also possibly with less efficacy. 

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