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Prescribing antidepressant drugs for pemphigus patients: An important point to keep in mind

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Prescribing antidepressant drugs for pemphigus patients: An important point to keep in mind
MR Namaz, MD
Dermatology Online Journal 10 (1): 22

Dermatology Department, Shiraz University of Medical Sciences, Shiraz, Iran.

The term pemphigus refers to three autoimmune diseases: pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. These conditions are characterized by loss of epidermal cell-cell adhesion manifesting as blistering and erosions of epithelial surfaces [1]. Blisters are associated with the binding of IgG autoantibodies to keratinocyte cell-surface molecules. These "intercellular" or "pemphigus" antibodies bind to keratinocyte desmosomes and muscarinic cholinergic receptors. Intercellular spaces enlarge, desmosomes decrease in number and eventually disappear, and the cells round up and detach from one another without cell death. This phenomenon is called acantholysis [2].

Muscarinic receptors are expressed mainly on the basal cells of the epidermis and decrease in number in the upper layers [3]. Because these receptors control keratinocyte adhesion [4] and motility [2], their inactivation by autoantibodies is believed to elicit intracellular signals that cause disassembly of desmosomes, contributing to acantholysis and blistering [2].

Acetylcholine, synthesized by keratinocytes, regulates keratinocyte adhesion in an autocrine and paracrine manner and reverses pemphigus IgG-induced acantholysis in keratinocyte monolayers [2, 5]. Noteworthy, suramin sodium, a drug acting on acetylcholine receptor, has been used to treat pemphigus [2].

As pemphigus destroys the patient's appearance and is a relapsing, difficult- to-treat illness requiring long-term hospitalization and immunosuppressive treatment, it inflicts significant psychological trauma to the subjects and may lead to profound depression and even suicide. The author observed a young female patient with extensive pemphigus vulgaris who committed suicide by throwing herself out of the window of the second floor of the Dermatology Ward of Razi Hospital located in Tehran. Therefore, pemphigus patients should be carefully assessed for co-morbid psychiatric disorders and treated appropriately.

Keratinocyte muscarinic receptors control keratinocyte adhesion, hence, the psychotherapeutic drugs with high muscarinic receptor blocking activity might worsen the skin blistering and are best avoided.

Therefore, for treating the depression of pemphigus patients, it might be advisable to prescribe non-TCA (TCA: tri- and tetra-cyclic antidepressants) antidepressants, such as fluoxetine, which do not show anticholinergic effect. Among the TCAs, desipramine, which exerts the lowest muscarinic acetylcholine receptor blockade, might be the best choice and amitryptiline, followed by doxepin and trimipramine, might be the worst choices. The other agents of the TCA family lie between these two poles. Clinical studies on this commentary are warranted.


1. Dover JS. Pocket Guide to Cutaneous Medicine and Surgery, 1st edn, Philadelphia: W.B. Saunders Company, 1996: 232-8.

2. Nguyen VT, Lee TX, Ndoye A, Shuhz LD, Pittelkow MR, Dahl MV, et al. The pathophysiological significance of nondesmoglein targets of pemphigus autoimmunity. Arch Dermatol 1998; 134: 971-80.

3. Grando SA. Biological functions of keratinocyte cholinergic receptors. J Invest Dermatol Symp Proc 1997; 2: 41-8.

4. Nguyen VT, Arredondo J, Chernyavsky AI, Kitajima Y, Grado SA. Keratinocyte acetylcholine receptors regulate cell adhesion. Life Sci 2003; 72(18-19): 2081-5.

5. Grando SA, Dahl MV. Activation of keratinocyte muscarinic acetylcholine receptor reverses pemphigus acantholysis. J Eur Acad Dermatol Venereal 1993; 2: 72-86.

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