The sensation of itching, or pruritus, is one of the predominant

Transcription

1 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 Objectives: To review the use of psychiatric medications in the treatment of 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 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. 5HT hydroxytryptamine; PGE 2 prostaglandin E 2 ; SSRI selective serotonin reuptake inhibitor; TCA tricyclic antidepressant. INTRODUCTION 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. 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). 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. 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 Received for publication September 18, 2006; revision received June 9, DOI: /PSY.0b013e 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 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). 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 970 Psychosomatic Medicine 69: (2007) /07/ Copyright 2007 by the American Psychosomatic Society and the American Psychiatric Association

2 PSYCHIATRIC MEDICATIONS FOR PRURITUS TABLE 1. Dermatological Causes of Pruritus TABLE 3. Subtypes of Psychogenic Excoriation Allergic contact dermatitis Atopic dermatitis Bullous pemphigoid Cutaneous T cell lymphoma Dermatitis herpetiformis Folliculitis Herpes zoster Lichen planus Pediculosis Psoriasis Scabies Sunburn Urticaria Xerosis/asteototic eczema Source. Adapted or Reprinted with permission from Pruritus, 11 September , American Family Physician. Copyright 2003 American Academy of Family Physicians. All Rights Reserved. TABLE 2. Nondermatologic Causes of Pruritus Systemic diseases that can cause pruritus Endocrine disease Diabetes mellitus Hyperparathyroidism Hyperphosphatemia Hyperthyroidism Hypothyroidism Metabolic disease Carcinoid syndrome Cholestasis Chronic renal failure Malignant disease Leukemia Lymphoma Multiple myeloma Polycythemia rubra vera Autoimmune disease Dermatomyositis scleroderma Miscellaneous Anorexia nervosa Drug reaction Human immunodeficiency virus infection Iron deficiency anemia Localized pruritus Brachioradial pruritus Notalgia paresthetica Peripheral neuropathy Pruritus ani Pruritus scroti/vulvi Source. Reprinted from Charlesworth EN, Beltrani VS. Pruritic dermatoses: overview of etiology and therapy. Am J Med 2002;113:S25 S33, Copyright 2002, Elsevier Limited with permission. 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 Psychosomatic Medicine 69: (2007) Compulsive Type Impulsive Type Mixed Type 1. Skin excoriation is performed to avoid increased anxiety or to prevent a dreaded event or situation and/or is elicited by an obsession (e.g., obsession about contamination of skin). 2. It is performed in full awareness. 3. It is associated with some resistance to performing the behavior. 4. There is some insight into its senselessness or harmfulness. 1. Skin excoriation is associated with arousal, pleasure, or reduction of tension. 2. It is performed at times with minimal awareness (e.g., automatically). 3. It is associated with little resistance to performing the behavior. 4. There is little insight into its senselessness or harmfulness. 1. Skin excoriation has both compulsive and impulsive features. Source. Arnold LM, Auchenbach MB, McElroy SL. Psychogenic excoriation: clinical features, proposed diagnostic criteria, epidemiology, and approaches to treatment. CNS Drugs 2001;15: Reprinted with permission. 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 The neuropeptides, prostaglandins, and endogenous opioids also cause pruritus by releasing histamine. In psoriasis and contact allergic dermatitis, an increased concentration of prostaglandin E 2 (PGE 2 ) 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 PGE 2 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 971

3 R. J. SHAW et al. TABLE 4. Conventional Drug Therapy for Pruritus Antihistamines 1st-generation hydroxyzine, diphenhydramine, cyproheptadine 2nd-generation cetirizine, loratidine, ebastine, fexofenadine Immunomodulators Topical corticosteroids, macrolides Systemic corticosteroids, cyclosporine Cholestyramine Opiate antagonists Naltrexone Naloxone Nalmefene Oral cromolyn Rifampin Ondansetron Topical capsaicin Cyproheptadine Cimetidine Pizotifen Aspirin 1st-generation antihistamines, used for histamine-induced pruritus, act by inhibiting the activation of H1 receptors (e.g., allergic conditions such as urticaria and atopic dermatitis). 2nd-generation antihistamines, which have the benefits of minimal effects of somnolence and few antimuscarinic side effects, are useful for the control of histaminic action that is associated with papule formation and erythema, but are generally not helpful for pruritus itself. Anti-inflammatory effect is useful for pruritus associated with inflammation. Useful for pruritus associated with renal failure, cholestasis, and polycythemia vera. Cholestyramine is an anion exchange resin that helps reduce pruritus by binding and sequestering bile acids in the intestine, thus lowering bile acid levels and other potential pruritogenic factors in plasma and tissues. Useful for itching associated with atopic dermatitis, cholestasis, and hemodialysis. Mechanism of action is thought to be due to their inhibitory effect on histamine release and antiopioid effect when endogenous opioids act as central pruritogens. Useful for systemic mast cell disease. Useful for cholestasis-induced This antibiotic acts by inhibiting hepatic bile acid uptake and simulates mixed function oxidases. Useful for cholestasis and uremia induced itching. This 5HT3 receptor antagonist relieves pruritus by lowering levels of serotonin and histamine. Useful for hemodialysis. Mechanism of action is depletion of substance P from peripheral sensory neurons. Useful for pruritus associated with polycythemia vera and other myeloproliferative disorders. Mechanism of action is its antihistamine and antiserotonin effect. Useful for hematopoetic diseases. This H1 and H2 receptor antagonist relieves histamineinduced itching. Useful for polycythemia vera. Potent antihistamine and antiserotonin effects. Useful for polycythemia vera. Source. Adapted from Etter L, Myers SA. Pruritus in systemic diseases: mechanism and management. Dermatol Clinics 2002;20:3: 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. 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). 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 972 Psychosomatic Medicine 69: (2007)

4 PSYCHIATRIC MEDICATIONS FOR PRURITUS TABLE 5. Psychopharmacological Treatment Studies of Pruritus Author Sample Design Medication Outcome Measures Result Notes (oral) (oral) (topical) (topical) Neittaanmaki et al. (28) Greene et al. (29) n 10. Idiopathic cold urticaria. n 50. Chronic idiopathic urticaria. Drake et al. (19) n 270. Atopic dermatitis. Groene et al. (12) Fluoxetine Gupta and Gupta (30) n 11. Atopic eczema. n year-old female with self-inflicted excoriations associated with OCD. Fluoxetine Stout (31) n year-old female with compulsive facial picking. Fluoxetine Simeon et al. (32) n 21. Chronic pathologic picking. Two randomized 2 week double-blind trials comparing doxepin with antihistamines. Double-blind, crossover study comparing doxepin with diphenhydramine. 1 week, double-blind, vehicle-controlled, multicenter study. 1 week double-blind study of doxepin versus placebo. Wheal and flare provoked by injection of acetylcholine and sodium chloride on day 4 of study. (1) 10 mg, cinnarizine, or placebo. (2) 10 mg, cyproheptadine 4 mg tid, or hydroxyzine 10 mg tid. 10 mg tid versus diphenhydramine 25 mg tid. 5% cream vs. vehicle cream applied bid at baseline, then qid. 5% cream applied qid for 3 days before acetylcholine sodium chloride injection. Case report. Fluoxetine 20 mg Qday for 6 weeks. Case report. Fluoxetine for 12 weeks. Double-blind, placebo-controlled parallel trial. Fluoxetine for 10 weeks in a flexible dose of 80 mg/day. Suppression of wheal and flare response induced by application of ice cubes. Suppression of symptom, diary score of daily itching and frequency, number, size and duration of hives. Physician global evaluation of pruritus and pruritus severity score. Size of wheal and flare response. Reduction in compulsion to scratch and disruption of itch-scratch cycle. Patient had rare compulsion to scratch. Lesion healed after 12 weeks. Clinical Global Impression- Improvement Scale, Skin Picking Treatment Scale, Visual Analog Scale of Change. (1) 8 of 9 subjects preferred doxepin. (2) No statistically significant differences. superior to diphenhydramine for clearing of pruritus and urticarial lesions and partial or total control of the pruritus and hives (p.001). superior to vehicle cream (p.01). superior to placebo in reducing size of wheal and flare response (p.005). superior to placebo in reducing itch intensity (5.9 versus 6.12 arbitrary units). Decreased compulsion to scratch within 2 weeks. Resolution of lesions after 6 weeks, maintained at 3 months. Positive response in terms of reduction in scratching and picking. Fluoxetine at mean dose of 55 mg/day superior to placebo. Subjects reported preference for doxepin over antihistamines due to efficacy and side effect profile. Decreased reports of sedation with doxepin. Topical doxepin effective in reducing symptoms of affects acetylcholineinduced cutaneous reactions in atopic eczema. (Continued) Psychosomatic Medicine 69: (2007) 973

5 R. J. SHAW et al. TABLE 5. (Continued) Author Sample Design Medication Outcome Measures Result Notes Fluoxetine Bloch et al. (33) n 15. Subjects with significant skin picking. Fluvoxamine Arnold et al. (34) n 14. Neurotic excoriation with comorbid psychiatric illness, including depression. Paroxetine Zylicz et al. (6) n 26. Pruritus related to solid tumors, hematological malignancies, nonmalignant or idiopathic conditions, and drug induced, paraneoplastic and cholestatic Paroxetine Biondi et al. (35) n year-old woman with idiopathic 6 week open-label trial of fluoxetine; 8 responders randomized to 6 week double blind trial of fluoxetine versus placebo. 12 week open-label trial of fluvoxamine. 7 week, prospective double-blind, randomized trial of paroxetine versus placebo. Fluoxetine (dose not stated). Fluvoxamine to 300 mg Qday. Paroxetine 20 mg or placebo Q day or placebo for 7 treatment cycles (each cycle is 7 days). Case report. Paroxetine 20 mg Q day for 2 weeks, then 30 mg Q day for 3 weeks. Patients were assessed with standardized rating scales. End-point analysis of all 14 subjects self-report data demonstrated significant improvement in skin sensations appearance, lesions, behaviors involving the skin, control over skin behavior, and global assessment. Numerical analogue rating scale of Primary end-point mean pruritus score measured for 7 days after randomization and after crossover. Secondary endpoint response (50% reduction of intensity of pruritus in the last 3 days of treatment). Improvement in symptoms of itching and scratching. 8 subjects responded to open-label trial of fluoxetine; 4 responders randomized to placebo had recurrence of symptoms; 4 randomized to fluoxetine maintained improvement. Fluvoxamine mg effective in reducing excoriation behaviors independent of mood. Fluvoxamine 300 mg/day effective for skin picking secondary to body dysmorphic disorder and delusional disorder. Subjects treated with paroxetine reported higher satisfaction versus placebo irrespective of the order of treatment (p.027). Resolution of itch started after 3 weeks and improvement in itching and scratching persisted at 9 months of follow-up. Response in a diverse subject sample suggests central rather than peripheral action of paroxetine. (Continued) 974 Psychosomatic Medicine 69: (2007)

6 PSYCHIATRIC MEDICATIONS FOR PRURITUS TABLE 5. (Continued) Author Sample Design Medication Outcome Measures Result Notes Sertraline Browning et al. (36) n 40. Primary biliary cirrhosis. Mirtazapine Davis et al. (22) n 4. Pruritus associated with adenocarcinoma, Hodgkin s disease, chronic lymphocytic leukemia, and advanced renal cancer. Mirtazapine Hundley and Yosipovitch (37) Olanzapine Garnis-Jones et al. (25) Olanzapine Gupta and Gupta (38) n 3. Inflammatory skin diseases and nocturnal pruritus without major depression. n 3. Self mutilation or dermatitis artefacta. n 3. Excoriated acne, selfinduced skin ulcers and trichotillomania. Case reports. Mirtazapine 15 to 30 mg Q day for 2 to 7 days. Case reports. Mirtazapine 15 mg Q day for minimum of 2 weeks. Case reports. Olanzapine 2.5 to 7.5 mg Q day. Case reports. Olanzapine 2.5 to 5 mg Q day for 2 4 weeks. Sertraline Self-reported severity of Reduction in symptoms of Reduction in symptoms of Simultaneously evaluation and treatment by dermatologist and psychiatrist. Resolution of symptoms with or without the change in self-mutilating behavior. No change in 28 of 32 subjects; 4 subjects experienced a sustained resolution of their itching; 86% of patients who continued treatment for 6 months had significant reduction in All subjects reported reduction in symptoms of pruritus within 1 to 7 days. Mirtazepine 30 mg superior to 15 mg. Significant improvement in pruritus, particularly nocturnal itching. All subjects reported excellent clinical response. All subjects had a favorable response. Mirtazapine reported to have benefits for treatment of insomnia, anorexia and depression in medically ill patients. Resolution of psychogenic pruritus with olanzapine after failure of all other treatments. In 2 of 3 patients, the efficacy of olanzapine was reported to be most likely related to an attenuation of dissociative symptoms. (Continued) Psychosomatic Medicine 69: (2007) 975

7 R. J. SHAW et al. TABLE 5. (Continued) Author Sample Design Medication Outcome Measures Result Notes Patients had monosymptomatic hypochondriac psychosis. 10 of 11 patients had significant improvement of delusions along with relief of itching. Brief Psychiatric Rating Scale points decreased significantly. Pimozide 6 week study. Double-blind, crossover study. n 11. Delusions of parasitosis. Pimozide Hamann and Avnstorp (39) The study indicates that a large proportion of patients with monosymptomatic delusions of infestation treated with pimozide may be able to discontinue the medication for years without recurrence of their delusions. 7 patients remained in remission; 3 patients developed relapses but without symptoms with intermittent treatment; 4 patients responded poorly to pimozide. Follow-up study. Patients were followed-up 19 to 48 months after treatment with pimozide was terminated. n 14. Delusions of Infestation. Pimozide Lindskov and Baadsgaard (40) OCD obsessive-compulsive disorder. 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). Several studies have shown the efficacy of oral and topical doxepin in the treatment of pruritus (12,18,19). s high affinity and antagonism with histamine receptors make it a strong antipruritic agent. has 56 times greater affinity for H1 receptors compared with hydroxyzine and 775 times greater affinity compared with diphenhydramine (16). 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. 976 Psychosomatic Medicine 69: (2007)

8 PSYCHIATRIC MEDICATIONS FOR PRURITUS Figure 1. Treatment algorithm for DISCUSSION 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 Despite these limitations, dermatologists have a relatively long history of using these adjunctive medications, often at significantly lower Psychosomatic Medicine 69: (2007) doses than when used for the treatment of psychiatric disorders (17). The main trends from the literature review are as follows. 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 977

9 R. J. SHAW et al. 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. REFERENCES 1. McElroy SL, Phillips KA, Keck PE Jr. Obsessive compulsive spectrum disorder. J Clin Psychiatry 1994; 55:S33 S Koblenzer CS: Psychocutaneous Diseases. Orlando: Grune & Stratton; Arnold LM. Dermatology. In: Levenson J, editor. The American Psychiatric Publishing Textbook of Psychosomatic Medicine. Washington, DC: American Psychiatric Publishing, Inc.; Teofoli P, Procacci P, Maresca M, Lotti M. Itch and pain. Int J Dermatol 1996;35: 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: 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: Borgeat A, Stirnemann HR. Ondansetron is effective to treat spinal or epidural morphine-induced Anesthesiology 1999;90: Greaves MW, Gibson WM. Itch: the role of prostaglandins. BMJ 1973; Jones EA, Bergasa NV. Pruritus of cholestasis and the opioid system. JAMA 1992;268: Gupta MA, Gupta AK. Psychodermatology: an update. J Am Acad Dermatol 1996;34: Moses S. Pruritus. Am Fam Physician 2003;68: Groene D, Martus P, Heyer G. affects acetylcholine induced cutaneous reactions in atopic eczema. Exp Dermatol 2001;10: Arnold AJ, Simpson JG, Jones HE, Ahmed AR. Suppression of histamine-induced pruritus by hydroxyzine and various neuroleptics. J Am Acad Dermatol 1979;1: Chouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004;65(Suppl 5): Gupta MA, Gupta AK. The use of psychotropic drugs in dermatology. Dermatol Clin 2000;18: Richelson E. Tricyclic antidepressants and histamine H1-receptors. Mayo Clin Proc 1979;54: Gupta MA, Gupta AK, Ellis CN. Antidepressant drugs in dermatology. An update. Arch Dermatol 1987;123: Keskin G, Inal A, Ali Sari R, Engul AS, Ahin MS, Turgay, M, Kinikli G. 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 Allergol Immunopathol (Madrid) 1999;27: 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: Zylicz Z, Smits C, Krajnik M. Paroxetine for pruritus in advanced cancer. J Pain Symptom Manage 1998;16: Greaves MW. Itch in systemic disease: therapeutic options. Dermatol Ther 2005;18: Davis MP, Frandsen JL, Walsh D, Andresen S, Taylor S. Mirtazapine for J Pain Symptom Manage 2003;25: Koo JY. Psychotropic and neurotropic agents in dermatology: unapproved uses, dosages, or indications. Clin Dermatol 2002;20: Hyun J, Gambichler T, Bader A, Altmeyer P, Kreuter A. Olanzapine therapy for subacute prurigo. Clin Exp Dermatol 2006;31: Garnis-Jones S, Collins S, Rosenthal D. Treatment of self mutilation with Olanzapine. J Cutan Med Surg 2000;4: Johnson GC, Anton RF. Delusions of parasitosis: differential diagnosis and treatment. South Med J 1985;78: Birmaher B. Treatment of psychosis in children and adolescents. Psychiatr Ann 2003;33: 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: 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: Gupta MA, Gupta AK. Fluoxetine is an effective treatment for neurotic excoriations: case report. Cutis 1993;51: Stout RJ. Fluoxetine for the treatment of compulsive facial picking. Am J Psychiatry 1990;147: 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: Bloch MR, Elliott MA, Thompson H, Koran L. Fluoxetine in pathologic skin picking. Psychosomatics 2001;42: 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: Biondi M, Arcangeli T, Petrucci RM. Paroxetine in a case of psychogenic pruritus and neurotic excoriations. Psychother Psychosom 2000;69: 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: Hundley JL, Yosipovitch G. Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study. J Am Acad Dermatol 2004;50: Gupta MA, Gupta AK. Olanzapine is effective in the management of some self induced dermatoses: three case reports. Cutis 2000;66: Hamann K, Avnstorp C. Delusions of infestation treated by pimozide: a double-blind crossover clinical study. Acta Derm Venereal 1982;62: Lindskov R, Baadsgaard O. Delusions of infestation treated with pimozide: a follow-up study. Acta Derm Venereol 1985;65: Psychosomatic Medicine 69: (2007)