Atypical depression, treatment

The MAOIs are indicated in patients with atypical (exogenous) depression and in some patients who are unresponsive to other antidepressive therapy. They rarely are a drug of first choice. Unlabeled uses have included bulimia (having characteristics of atypical depression), treatment of cocaine addiction (phenelzine)... 

Normally, dietary tyramine is broken down in the gastrointestinal tract by MAO and is not absorbed. In the presence of MAOI, however, all of its potent sympathomimetic actions are seen. Other side effects of MAOI include excessive CNS stimulation, orthostatic hypotension, weight gain, and in rare cases hepatotoxicity. Because the monoamine oxidase inhibitors exhibit greater toxicity, yet no greater therapeutic response than other, newer agents, clinical use has been markedly curtailed. The primary use for MAOIs is in the treatment of atypical depressions, eg, those associated with increased appetite, phobic anxiety, hypersomnolence, and fatigues, but not melancholia (2). 

The main limitation to the clinical use of the MAOIs is due to their interaction with amine-containing foods such as cheeses, red wine, beers (including non-alcoholic beers), fermented and processed meat products, yeast products, soya and some vegetables. Some proprietary medicines such as cold cures contain phenylpropanolamine, ephedrine, etc. and will also interact with MAOIs. Such an interaction (termed the "cheese effect"), is attributed to the dramatic rise in blood pressure due to the sudden release of noradrenaline from peripheral sympathetic terminals, an event due to the displacement of noradrenaline from its mtraneuronal vesicles by the primary amine (usually tyramine). Under normal circumstances, any dietary amines would be metabolized by MAO in the wall of the gastrointestinal tract, in the liver, platelets, etc. The occurrence of hypertensive crises, and occasionally strokes, therefore limited the use of the MAOIs, despite their proven clinical efficacy, to the treatment of atypical depression and occasionally panic disorder. 

Tranylcypromine ( rans-2-phenylcyclopropylamine, TCP, 8a) has close structural similarity to amphetamine (2-amino-1-phenylpropane) and is known as a nonhydrazine, nonselective, and irreversible inhibitor of both MAO A and B. It is also a potent reversible inhibitor of CAOs [36,37], Tranylcypromine has an important clinical use for treatment of certain depressive illnesses, particularly of nonendo-genous and atypical depressions and depressions associated with anxiety, agitation, phobias, and anergia [38-40], In combination with lithium, it is also applied for treatment of refractory depression [41], Recent reports also discussed MAO inhibitors as useful agents against neurodegenerative disorders such as Parkinson s or Alzheimer s diseases [42], Despite impressive clinical successes, clinical use of tranylcypromine and other MAO inhibitors is limited by various problems, including the cheese effect discussed in Section 1,... 

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. 

Dassa D, Kaladjian A, Azorin JM, et al Clozapine in the treatment of psychotic refractory depression. Br J Psychiatry 163 822-824, 1993 Dauge V, Steimes P, Derrien M, et al CCK8 effects on motivational and emotional states of rats involve CCKA receptors of the postero-median part of the nucleus accumbens. Pharmacol Biochem Behav 34 157-163, 1989 Davidson J Seizures and bupropion a review. J Clin Psychiatry 50 256-261, 1989 Davidson J, Pelton S Eorms of atypical depression and their response to antidepressant drugs. Psychiatry Res 17 87-95, 1986 Davidson JR, Miller R, Turnbull CD, et al Atypical depression. Arch Gen Psychiatry 39 527-534, 1982... 

MAOIs may be the treatment of choice for atypical depressive disorders. As noted in Chapter 6, features of this subgroup usually include the following ... 

Phenelzine has been studied for the treatment of anxiety, phobic and obsessive-compulsive disorders, as well as typical and atypical depressions. Its antidepressant efficacy has been correlated with an 80% to 85% inhibition of the MAO enzyme. Studies by Ravaris, replicated by this text s authors, indicate that 60 mg per day are usually needed to inhibit MAO by at least 80% (353, 354). Although monitoring of platelet MAO inhibition during treatment may permit more optimal dosing, the assay is not readily available commercially. This, coupled with the infrequent use of MAOIs, has hampered the widespread application of this specialized form of TDM. 

It is also possible that there may not be a strict isomorphism between personality disorders and other diagnostic entities. Thus, a personality disorder may be a psychological condition that only exists in patients who have a major psychiatric disorder, such as schizophrenia, atypical depression, or social phobia. One example is mania, which can present with interpersonal behaviors such as attacking people s weaknesses, sensitivity to division, and manipulative behavior with staff. This syndrome disappears completely, however, when the patient undergoes treatment with a mood stabilizer. 

Rothschild R, Quitkin HM, Quitkin FM, et al. A double blind placebo-controlled comparison of phenelzine and imipramine in the treatment of bulimia in atypical depressives. Int J Eat Disora 1994 9 1-9. 

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... 

MAO inhibitors are indicated for depressed patients who are unresponsive or allergic to tricyclic antidepressants or who experience strong anxiety. Patients with low psychomotor activity may benefit from the stimulant properties of MAO inhibitors. These drugs are also useful in the treatment of phobic states. A special subcategory of depression, called atypical depression, may respond to MAOIs. Atypical depresssion is characterized by labile mood, rejection sensitivity and appetite disorders. 

Several subtypes of depression require specific treatment strategies that go beyond a simple course of conventional antidepressant therapy (these subtypes include bipolar depression, major depression with psychotic features, seasonal depression, atypical depression, comorbid anxiety disorder, comorbid substance abuse, double depression [major depression... 

Mood stabilizers or atypical antipsychotics tor bipolar depression, psychotic depression, treatment-resistant depression, or treatment-resistant anxiety disorders... 

Nierenberg AA, Alpert JE, Pava J, et al. Course and treatment of atypical depression. J Clin Psychiatry 1998 59(Suppl 18) 5-9. 

A 38-year-old divorced woman who lived alone visited a psychiatrist because she was depressed. Her symptoms included low self-esteem, with frequent ruminations on her worthlessness, and hypersomnia. She was hyperphagic and complained that her limbs felt heavy. An initial diagnosis was made of a major depressive disorder with atypical symptoms. Treatment was initiated with amitriptyline, but after 2 months the patient had not improved significantly. Which one of the following drugs is MOST likely to have therapeutic value in this depressed patient ... 

Treatment of Major Depression. Dmgs commonly used for the treatment of depressive disorders can be classified heuristicaHy iato two main categories first-generation antidepressants with the tricycHc antidepressants (TCAs) and the irreversible, nonselective monoamine—oxidase (MAO) inhibitors, and second-generation antidepressants with the atypical antidepressants, the reversible inhibitors of monoamine—oxidase A (RIMAs), and the selective serotonin reuptake inhibitors (SSRIs). Table 4 fists the available antidepressants. 

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Non-motor signs of the disorder are also treatable with symptomatic medications. The frequent mood disorder can be treated with standard antidepressants, including tricyclics (such as amitryptiline) or serotonin reuptake inhibitors (SSRIs, such as fluoxetine or sertraline). This treatment is not without risks in these patients, as it may trigger manic episodes or may even precipitate suicide. Anxiety responds to benzodiazepines, as well as to effective treatment of depression. Long-acting benzodiazepines are favored over short-acting ones because of the lesser abuse potential. Some of the behavioral abnormalities may respond to treatment with the neuroleptics as well. The use of atypical neuroleptics, such as clozapine is preferred over the typical neuroleptics as they may help to control dyskinesias with relatively few extrapyramidal side-effects (Ch. 54). 

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