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Published online before print November 8, 2007, 10.1097/PSY.0b013e3181572799
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Psychosomatic Medicine 69:970-978 (2007)
© 2007 American Psychosomatic Society

ORIGINAL ARTICLES

Psychiatric Medications for the Treatment of Pruritus

Richard J. Shaw, MB, BS, Shaili Dayal, MB, BS, Julie Good, MD, Anna L. Bruckner, MD and Shashank V. Joshi, MD

From the Department of Psychiatry and Behavioral Sciences (R.J.S., S.D., S.V.J.) and Department of Pediatrics (J.G., A.L.B.), Stanford University School of Medicine, and Lucile Packard Children's Hospital, Palo Alto, California.

Address correspondence and reprint requests to Richard Shaw, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Palo Alto, CA 94305-5719.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 DISCUSSION
 NOTES
 REFERENCES
 
Objectives: To review the use of psychiatric medications in the treatment of pruritus.

Methods: A literature review was conducted using the key words pruritus, psychiatric, and treatment.

Results: Three categories of pruritus are described: dermatologic, systemic, and psychogenic. Peripheral and central nervous system mechanisms of pruritus are reviewed. Conventional dermatologic treatments for pruritus are contrasted with some of the common psychopharmacologic treatment modalities that include anxiolytic, antidepressant, and antipsychotic agents. A treatment algorithm is offered to help guide the treatment of patients with pruritus.

Conclusions: Psychiatric medications have been used successfully in the treatment of pruritus that is associated with both psychocutaneous and systemic disorders, which are resistant to conventional treatment.

Key Words: pruritus • psychopharmacology • treatment • psychocutaneous

Abbreviations: 5HT = hydroxytryptamine; PGE2 = prostaglandin E2; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
DISCUSSION
 NOTES
 REFERENCES
 
The sensation of itching, or pruritus, is one of the predominant symptoms of primary dermatological illness as well as a symptom of systemic disease. Pruritus may also be associated with, or exacerbated by, a number of common psychological disorders that predispose patients to a process of psychogenic excoriation. In this paper, we describe the classification and mechanisms of pruritus and review the common psychopharmacologic agents that have been used in its treatment.

Classification of Pruritus
Pruritus has been classified into three major categories, which include dermatologic, systemic, and psychogenic.

Pruritus Associated With Skin Disease
Pruritus is a frequent symptom of numerous dermatologic diseases of varying etiology (Table 1). The appearance of the primary skin changes is important in helping narrow the differential diagnosis.


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  		TABLE 1. Dermatological Causes of Pruritus

 

Generalized Pruritus Associated With Systemic Disease
Pruritus is a known association of a number of systemic diseases. In these cases, generalized itching may be the presenting complaint, but there is a lack of primary skin lesions on cutaneous examination. The new onset of pruritus without skin disease should always prompt evaluation for an occult underlying medical condition (Table 2).


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  		TABLE 2. Nondermatologic Causes of Pruritus

 

Localized Pruritus
Pruritus without primary skin lesions may be isolated to a particular region of the body (Table 2). This form of itch may be the result of nerve injury or entrapment.

Psychogenic Pruritus
When pruritus occurs in the absence of skin pathology or an underlying medical disease, it can be classified as being primarily psychogenic in nature. Types of psychopathology that may be associated with this type of pruritus include individuals with compulsive or impulsive disorders, or delusional disorders such as delusions of parasitosis (1). Psychogenic pruritus may also occur in conjunction with pruritus due to primary skin disease or systemic illnesses. Literature suggests that 33% to 75% of dermatological patients have a significant psychological component to their cutaneous symptoms (2). Often there is a cycle of cutaneous trauma caused by excoriation that leads to skin lichenification, which in turn causes increased symptoms of pruritus. In some cases, it may be difficult to establish whether it is the sensation of itching that provokes the desire to scratch or whether the pruritus is a consequence of a compulsive scratching.

Patients with psychogenic excoriation exhibit heterogeneous behavior that can span a "compulsivity-impulsivity continuum from purely obsessive-compulsive to purely impulsive, with mixed symptoms between these poles" (Table 3) (1). The compulsive subtype of excoriation resembles obsessive-compulsive disorder in that patients often try to resist the behavior. This compulsion to excoriate is commonly a response to an obsession about an irregularity on the skin. By contrast, patients with the impulsive subtype respond to increased feelings of anxiety or tension and experience transient feelings of relief immediately after excoriation (3).


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  		TABLE 3. Subtypes of Psychogenic Excoriation

 

Mechanisms of Pruritus
Peripheral and Central Neural Pathways
Various central nervous system descending pathways have been demonstrated to modulate itching (4). The sensation of pruritus can be provoked by different exogenous agents that include mechanical, electrical, thermal, or chemical stimuli as well as endogenous causes. Specialized itch receptors are localized on multimodal endings of specific fibers close to the dermo-epidermal junction of the skin, superficial to those responsible for pain. These impulses are transmitted through specific nonmyelinated C fibers to the dorsal horn of the spinal cord, and then via the anterolateral spinothalamic tract to the postcentral gyrus of the cerebral cortex (5). It has been suggested that both opioidergic and serotoninergic systems exert a regulatory action on pruritus-related transmission (6). Serotonin may also play a regulatory role at a supraspinal level and by modulation of the 5-HT3 receptors in the dorsal root ganglia (6). In support of this hypothesis is the finding that ondansetron, a 5HT3 antagonist, has been found effective in the treatment of opioid-induced pruritus (7).

Endogenous Mediators
There are many chemical mediators called pruritogens that stimulate the nerve endings of the specialized C fibers to cause pruritus. Histamine, one of the most important peripheral mediators, acts on H1 receptors to cause a wheal and flare response, and also directly on epidermal nerve endings to cause pruritus. The neuropeptides, prostaglandins, and endogenous opioids also cause pruritus by releasing histamine. In psoriasis and contact allergic dermatitis, an increased concentration of prostaglandin E2 (PGE2) is thought to cause pruritus by decreasing the threshold of serotonin (8). Pruritus in cholestatic liver diseases is associated with increased opiodergic tone (9). Serotonin and PGE2 are responsible for the pathogenesis of certain types of pruritus including uremic pruritus, explaining the efficacy of ondansetron, a selective 5-hydroxytryptamine receptor inhibitor as a treatment agent. However, in pruritus associated with systemic disease, histamine is not thought to be a primary mediator, and antihistamine agents are generally less effective (10).

Management of Pruritus
In addition to treating the underlying skin disease, nonspecific symptomatic measures are often useful in alleviating pruritus associated with common dermatological conditions. Skin lubricants such as petroleum jelly or other bland emollients and topical antipruritic agents such as menthol, camphor, colloidal oatmeal, pramoxine, crotamiton, capsaicin cream, and calamine lotion may provide short-term relief (11). Systemic antihistamines such as diphenhydramine, hydroxyzine, and fexofenadine (a nonsedating antihistamine) are used in allergic and urticarial diseases (Table 4) (11). Antihistamines or medications with potent antihistamine effects, such as doxepin, are also useful adjuncts in the treatment of skin diseases like dermatitis that are not primarily caused by histamine release. Much of this benefit may be due to the sedating effect of these medications, as pruritus can cause significant sleep disturbance. Ultraviolet light phototherapy, either with UVB or psoralen and UVA, is an effective treatment for several generalized skin diseases and for pruritus associated with systemic illnesses such as cholestasis and uremia (10). Topical corticosteroids are also effective at relieving pruritus, acting through both direct and anti-inflammatory effects. Topical corticosteroids and the newer topical immune modulators (tacrolimus and pimecrolimus) are effective treatments for dermatitis, psoriasis, and other inflammatory skin diseases.


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  		TABLE 4. Conventional Drug Therapy for Pruritus

 

Psychiatric Medications for the Treatment of Pruritus
Patients with generalized pruritus, but without primary skin lesions and no evidence of systemic disease, are commonly diagnosed with a primary psychocutaneous disorder. These patients respond well to treatment with antidepressants, antipsychotic agents, or mild sedatives (Table 5). Before considering the use of these agents, it is important to note nonspecific treatment approaches, especially in those cases where the psychogenic nature of the pruritus is secondary or comorbid with physiologic disease. For example, in eczematous dermatitis, scratching behaviors may play a major role in initiating, maintaining, and prolonging the cutaneous inflammatory response. In these cases, an antipruritic agent may suppress symptoms adequately to minimize the development and progression of the eczematous dermatitis, and thereby reduce the need for other agents (12).


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  		TABLE 5. Psychopharmacological Treatment Studies of Pruritus

 


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  		TABLE 5. (Continued)

 


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  		TABLE 5. (Continued)

 


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  		TABLE 5. (Continued)

 
Anxiolytics and Sedatives
Pruritus associated with common dermatological conditions is often exacerbated by psychosocial stress (3,13). In these situations, anxiolytics such as alprazolam may be helpful by alleviating symptoms of anxiety. Clonazepam may be preferred in more chronic situations when longer term treatment is anticipated because it has a longer half life and less potential for rebound or withdrawal symptoms when compared with alprazolam (14). Benzodiazepines may prevent a flare-up in stress-reactive dermatological conditions such as psoriasis and atopic dermatitis (15).

Antihistaminergic and Antidepressant Agents
Tricyclic Antidepressants (TCAs)
Tricyclic compounds are commonly used in the systemic treatment of atopic eczema (16). The efficacy of TCAs in urticaria and other chronic pruritic conditions is likely due to their antihistaminic and anticholinergic activity. Tertiary amines that include amitriptyline and trimipramine are potent H1 and H2 receptor antagonists and have anticholinergic action. Studies have shown that combined H1 and H2 receptors antagonists are more effective in chronic urticaria than H1 receptor antagonists alone because of the presence of both types of receptors in dermal blood vessels (17). The efficacy of trimipramine in nocturnal pruritus may also be related to its sedative effect. Doses of these agents are generally lower for the treatment of pruritus than for their use as antidepressant agents (16).

Doxepin
Several studies have shown the efficacy of oral and topical doxepin in the treatment of pruritus (12,18,19). Doxepin's high affinity and antagonism with histamine receptors make it a strong antipruritic agent. Doxepin has 56 times greater affinity for H1 receptors compared with hydroxyzine and 775 times greater affinity compared with diphenhydramine (16). Doxepin cream has an immediate effect on pruritus, with benefits often apparent within a few minutes of application. Subsequent percutaneous absorption after application inhibits papules in allergen and histamine-induced pruritus (18).

Selective Serotonin Reuptake Inhibitors (SSRIs)
The SSRIs are a group of antidepressant drugs that have been used in a number of the psychocutaneous disorders including psychogenic excoriation, body dysmorphic disorder, trichotillomania, onychophagia, excoriated acne, and psoriasis. The exact mechanism of the antipruritic effect is not known but Zylicz et al. (20) have suggested that it may be mediated by downregulation of the excitatory postsynaptic 5HT3 receptor. Dermatologic improvement seems to be independent of changes in psychiatric symptomatology. Paroxetine, in particular, has proven to be effective in antipruritic therapy associated with uremia (21).

Mirtazapine
Mirtazapine is a piperazinoazepine-derivative tetracyclic that antagonizes noradrenergic, H1, 5HT2, and 5HT3 receptors. Mirtazapine has been shown to be effective in the treatment of pruritus related to renal failure, liver failure, cholestasis, and malignancy (22). Mirtazapine also has the benefits of helping with symptoms of insomnia, anorexia and depression—symptoms that are not uncommon in medically ill patients.

Antipsychotic Agents
Antipsychotic agents, including chlorpromazine, thioridazine, and thiothixene, have been reported as being useful for nonhistamine-induced and psychogenic pruritus (23). Several case reports have shown successful SSRI augmentation with the use of pimozide, risperidone, and olanzapine in the treatment of SSRI-resistant trichotillomania (23). Olanzapine, an atypical antipsychotic agent, is thought to operate by antagonism at 5HT2, 5HT3, 5HT6, and dopamine receptors (24). Olanzapine blocks histamine H1 receptors, which may also explain its antipruritic action. Garnis-Jones et al. (25) reported the successful use of olanzapine to treat psychogenic excoriation in three nonpsychotic patients after the failure of all other modes of treatment, including antidepressants and antipsychotic agents.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 DISCUSSION
NOTES
 REFERENCES
 
Several studies and clinical drug trials have demonstrated the efficacy of psychiatric medications in the treatment of pruritus associated with psychocutaneous and systemic disorders that are resistant to conventional treatment. However, it is important to note that many of the manuscripts reviewed for this paper are based on single case studies, small case series, or nonrandomized studies that did not include placebo arms. There are also virtually no head-to-head studies contrasting the different categories of psychiatric medications. Larger and more rigorously designed studies are needed to help evaluate clinical outcomes as well as to help with clinical decisions as to which adjunctive medications are most effective in the treatment of specific subtypes of pruritus. Despite these limitations, dermatologists have a relatively long history of using these adjunctive medications, often at significantly lower doses than when used for the treatment of psychiatric disorders (17).

The main trends from the literature review are as follows. Doxepin has been shown to be consistently effective in the treatment of pruritus and to have greater efficacy compared with placebo. The SSRIs similarly have been shown to have greater efficacy compared with placebo, and there may be particular indications for the choice of an SSRI in patients who have pruritus with a predominantly compulsive quality. Comparing individual SSRIs, all have similar efficacies and mechanisms of action. However, side effect profiles and the patient's underlying medical condition may guide the choice of medication. Both citalopram and escitalopram are thought to have less potential for drug interactions that may be important for medical patients who are being treated with other medications. Studies on mirtazapine suggest that this is a particularly helpful agent, especially in cases of nocturnal pruritus due to its strong sedative effect. However, in patients for whom sedation is a problem, a more activating agent such as fluoxetine may be a better choice. Our anecdotal experience with mirtazapine has led to it being one of our first-line adjunctive agents. However, there is no empirical evidence to support one specific antidepressant agent over any of the others. With regard to the antipsychotic agents, there are a small number of studies that support their use and knowledge of their mechanism of action suggests that they may be particularly useful for patients whose pruritus has a predominantly impulsive quality, or for the rarer case of patients who have delusional disorders about infestation (26). Caution needs to be exercised with use of antipsychotic agents due to their relatively higher risk of side effects that include cardiac toxicity, specifically prolongation of the QTc interval, (especially for pimozide), as well as the risk of tardive dyskinesia and other movement disorders in long-term use (27).

Although data on the relative efficacy of these agents is still lacking, we offer a treatment algorithm to guide the management approach for the patient presenting with pruritus (Figure 1). The classification of psychogenic pruritus based on the relative degree of compulsive or impulsive characteristics may help guide the choice of the psychotropic agent (Table 3). Careful diagnosis and an effort to delineate the characteristics of the patient's symptoms, in particular the underlying medical diagnosis or relative degree of compulsive or impulsive characteristics, may help guide the choice of adjunctive treatment based on considerations described above. Finally, it is important to note that the presence of dermatological symptoms out of proportion to the underlying skin condition should alert the physician to the possibility of an underlying psychiatric illness that may require independent psychiatric evaluation and treatment.


Figure 124
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  		Figure 1. Treatment algorithm for pruritus.

 


   NOTES
TOP
 ABSTRACT
 INTRODUCTION
 DISCUSSION
 NOTES
REFERENCES
 
Received for publication September 18, 2006; revision received June 9, 2007.

DOI:10.1097/PSY.0b013e3181572799


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 DISCUSSION
 NOTES
 REFERENCES
 

  1. McElroy SL, Phillips KA, Keck PE Jr. Obsessive compulsive spectrum disorder. J Clin Psychiatry 1994; 55:S33–S51.
  2. Koblenzer CS: Psychocutaneous Diseases. Orlando: Grune & Stratton; 1987.
  3. Arnold LM. Dermatology. In: Levenson J, editor. The American Psychiatric Publishing Textbook of Psychosomatic Medicine. Washington, DC: American Psychiatric Publishing, Inc.; 2005.
  4. Teofoli P, Procacci P, Maresca M, Lotti M. Itch and pain. Int J Dermatol 1996;35:159–66.[CrossRef][Medline]
  5. Paus R, Schmelz M, Biro T, Steinhoff M. Frontiers in pruritus research: scratching the brain for more effective itch therapy J. Clin. Invest 2006;116:1174–85.[CrossRef][Medline]
  6. Zylicz Z, Krajnik M, Sorge AA, Costantini M. Paroxetine in the treatment of severe non-dermatological pruritus: a randomized controlled trial. J Pain Symptom Manage 2003;26:1105–12.[CrossRef][Medline]
  7. Borgeat A, Stirnemann HR. Ondansetron is effective to treat spinal or epidural morphine-induced pruritus. Anesthesiology 1999;90:432–6.[CrossRef][Medline]
  8. Greaves MW, Gibson WM. Itch: the role of prostaglandins. BMJ 1973;608–9.
  9. Jones EA, Bergasa NV. Pruritus of cholestasis and the opioid system. JAMA 1992;268:3359–62.[Abstract/Free Full Text]
  10. Gupta MA, Gupta AK. Psychodermatology: an update. J Am Acad Dermatol 1996;34:1030–46.[CrossRef][Medline]
  11. Moses S. Pruritus. Am Fam Physician 2003;68:1135–42.[Medline]
  12. Groene D, Martus P, Heyer G. Doxepin affects acetylcholine induced cutaneous reactions in atopic eczema. Exp Dermatol 2001;10:110–7.[CrossRef][Medline]
  13. Arnold AJ, Simpson JG, Jones HE, Ahmed AR. Suppression of histamine-induced pruritus by hydroxyzine and various neuroleptics. J Am Acad Dermatol 1979;1:509–12.[Medline]
  14. Chouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004;65(Suppl 5):7–12.[Medline]
  15. Gupta MA, Gupta AK. The use of psychotropic drugs in dermatology. Dermatol Clin 2000;18:711–25.[CrossRef][Medline]
  16. Richelson E. Tricyclic antidepressants and histamine H1-receptors. Mayo Clin Proc 1979;54:669–74.[Medline]
  17. Gupta MA, Gupta AK, Ellis CN. Antidepressant drugs in dermatology. An update. Arch Dermatol 1987;123:47–52.
  18. Keskin G, Inal A, Ali Sari R, Engul AS, Ahin MS, Turgay, M, Kinikli G. Doxepin incorporated into a dermatologic cream: an assessment of both doxepin antipruritic action and doxepin action as an inhibitor of papules, in allergen and histamine caused pruritus. Allergol Immunopathol (Madrid) 1999;27:265–70.
  19. Drake LA, Fallon JD, Sober A. Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream. The doxepin study group. J Am Acad Dermatol 1994;31:613–6.[Medline]
  20. Zylicz Z, Smits C, Krajnik M. Paroxetine for pruritus in advanced cancer. J Pain Symptom Manage 1998;16:121–4.[CrossRef][Medline]
  21. Greaves MW. Itch in systemic disease: therapeutic options. Dermatol Ther 2005;18:323–7.[Medline]
  22. Davis MP, Frandsen JL, Walsh D, Andresen S, Taylor S. Mirtazapine for pruritus. J Pain Symptom Manage 2003;25:288–91.[CrossRef][Medline]
  23. Koo JY. Psychotropic and neurotropic agents in dermatology: unapproved uses, dosages, or indications. Clin Dermatol 2002;20:582–94.[CrossRef][Medline]
  24. Hyun J, Gambichler T, Bader A, Altmeyer P, Kreuter A. Olanzapine therapy for subacute prurigo. Clin Exp Dermatol 2006;31:464–5.[CrossRef][Medline]
  25. Garnis-Jones S, Collins S, Rosenthal D. Treatment of self mutilation with Olanzapine. J Cutan Med Surg 2000;4:161–3.[Medline]
  26. Johnson GC, Anton RF. Delusions of parasitosis: differential diagnosis and treatment. South Med J 1985;78:914–8.[CrossRef][Medline]
  27. Birmaher B. Treatment of psychosis in children and adolescents. Psychiatr Ann 2003;33:257–64.
  28. Neittaanmaki H, Myohanen T, Fraki JE. Comparison of cinnarizine, cyproheptadine, doxepin and hydroxyzine in the treatment of idiopathic cold urticaria: usefulness of doxepin. J Am Acad Dermatol 1984;11:483–9.[Medline]
  29. Greene SL, Reed CE, Schroeter AL. Double blind cross-over study comparing doxepin with diphenhydramine for the treatment of chronic urticaria. J Am Acad Dermatol 1985;12:669–75.[Medline]
  30. Gupta MA, Gupta AK. Fluoxetine is an effective treatment for neurotic excoriations: case report. Cutis 1993;51:386–7.[Medline]
  31. Stout RJ. Fluoxetine for the treatment of compulsive facial picking. Am J Psychiatry 1990;147:370.[Medline]
  32. Simeon D, Stein DJ, Gross S Islam N, Schmeidler J, Hollander E. A double-blind trial of fluoxetine in pathologic skin picking. J Clin Psychiatry 1997;58:341–7.[Medline]
  33. Bloch MR, Elliott MA, Thompson H, Koran L. Fluoxetine in pathologic skin picking. Psychosomatics 2001;42:314–9.[Abstract/Free Full Text]
  34. Arnold LM, Mutasim DF, Dwight MM, Lamerson CL, Morris EM, McElroy SL. An open clinical trial of fluvoxamine treatment of psychogenic excoriation. J Clin Psychopharmacol 1999;19:15–8.[Medline]
  35. Biondi M, Arcangeli T, Petrucci RM. Paroxetine in a case of psychogenic pruritus and neurotic excoriations. Psychother Psychosom 2000;69:165–6.[CrossRef][Medline]
  36. Browning J, Combes B, Mayo MJ. Long term efficacy of sertraline as a treatment for cholestatic pruritus in patients with primary biliary cirrhosis. Am J Gastroenterol 2003;98:2736–41.[CrossRef][Medline]
  37. Hundley JL, Yosipovitch G. Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study. J Am Acad Dermatol 2004;50:889–91.[CrossRef][Medline]
  38. Gupta MA, Gupta AK. Olanzapine is effective in the management of some self induced dermatoses: three case reports. Cutis 2000;66:143–6.[Medline]
  39. Hamann K, Avnstorp C. Delusions of infestation treated by pimozide: a double-blind crossover clinical study. Acta Derm Venereal 1982;62:55–8.
  40. Lindskov R, Baadsgaard O. Delusions of infestation treated with pimozide: a follow-up study. Acta Derm Venereol 1985;65:267–70.[Medline]




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