Elsevier

Clinics in Dermatology

Volume 31, Issue 1, January–February 2013, Pages 101-109
Clinics in Dermatology

Psychiatric medications: Adverse cutaneous drug reactions

https://doi.org/10.1016/j.clindermatol.2011.11.014Get rights and content

Abstract

Psychiatric medications are among the most widely prescribed medications in the United States. Adverse cutaneous drug reactions are associated with psychiatric medications in approximately 2% to 5% of the individuals for whom they are prescribed. Although most adverse cutaneous drug reactions associated with psychotropic medications are benign and easily treated, some can be disfiguring or life-threatening, particularly those associated with the mood stabilizers. Adverse cutaneous drug reactions associated with antidepressants, antipsychotics, and mood stabilizers are reviewed, and important issues that are of concern for the dermatologist who must consider when and how to safely discontinue a psychotropic medication in their patients are presented.

Introduction

Adverse cutaneous drug reactions (ACDRs) are the most frequent adverse events in patients receiving drug therapy, with higher rates being associated with psychotropic medications.1 Compounding the concern is that psychotropic medications are among the most highly prescribed medications in the United States. The most recent National Center for Health Statistics report on prescription drug use found that in 2007 to 2008, antidepressants were the most commonly prescribed drugs used by adults in the United States aged 20 to 59 years, surpassing even analgesics in frequency.2 As these data suggest, the prevalence of psychiatric illness is very high. The most recent National Comorbidity Survey Replication estimated the 12-month prevalence of any Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision disorder to be 26.2% in the general population, with 22.3% of these being classified as serious.3

Although most ACDRs associated with psychotropic medications are benign and easily treated, some can be life-threatening, and particularly those associated with the mood stabilizers. Because it is often necessary to use more than one agent concurrently to obtain remission of severe bipolar mood episodes, this risk is increased in the more severely ill patient who is taking combinations of mood stabilizers.4-12 In addition, cross-sensitivity between these medications has been noted.13., 14., 15.

The decision to discontinue a psychotropic medication vs symptomatic treatment of a less serious ACDR can be difficult for the dermatologist, because the severity of a patient’s psychiatric illness and risk of relapse may not be immediately apparent. With severe ACDRs, the appropriate options for the dermatologist to consider with drug discontinuation can also be challenging, particularly in a patient with a severe mental illness. The decision to remove a possibly offending agent should be weighed carefully, because relapse of mania or severe depression poses a serious risk of morbidity and even mortality. In this contribution, the most common, serious, and general ACDRs associated with antidepressants, mood stabilizers, and antipsychotics will be discussed. Advice concerning when and how to safely discontinue a psychotropic medication will also be presented.

Section snippets

Special questions and considerations when discontinuing a psychiatric medication secondary to an ACDR

Any time a medication is discontinued secondary to an ADCR, the decision is based on the severity of the skin reaction vs the risk of relapse or exacerbation of the original condition for which the medication was prescribed. When the offending medication is a psychotropic, however, this process can be even more difficult than with other classes of medications. In a busy dermatology practice, it can be time consuming, and perhaps overwhelming, to evaluate a patient’s current mental stability to

Pruritus

Pruritus usually occurs secondary to another drug reaction, but it can be a common primary adverse effect of any of the antidepressants, mood stabilizers, or antipsychotics.17 Pruritus alone would rarely be a cause of discontinuation of a psychotropic medication when considering the risk of relapse of the patient’s disorder. Although pruritus can occur with any psychotropic agent, see Table 1, Table 2, Table 3 for specific drugs more frequently associated with pruritus.

Exanthematous reactions

Exanthematous reactions

Erythema multiforme

Although rare with antidepressants and antipsychotics, fluoxetine,79 paroxetine,25 bupropion,26 clozapine,25 and risperidone,25 have been associated with erythema multiformelike eruptions. Erythema multiformelike eruptions have also been found in patients being treated with carbamazepine,49 valproic acid,25 lamotrigine,25 gabapentin,25 and oxcarbazepine.25

Treatment must include immediate discontinuation of the offending drug with inpatient psychiatric or medical hospitalization determined by

Acneiform eruptions

Acneiform eruptions have been associated with almost all antidepressants. Lithium,17 topiramate, lamotrigine, gabapentin, and oxcarbazepine are the mood stabilizers that are associated with acne, and the antipsychotics of note are quetiapine and haloperidol.66 Typically occurring on the face, chest, and upper back, the eruption consists of folliculocentric pustules, usually without comedones. Discontinuation of the agent will lead to improvement, but is not necessary as antibiotics with topical

Conclusions

Although ACDRs are frequent with psychotropic medications, most of the skin lesions are benign and easily managed. When serious ACDRs occur, care must be taken to assess safety before withdrawal of the medication. In addition, consideration of the potential for severe morbidity when a drug is withdrawn should not be underestimated. Because many patients with debilitating psychiatric illnesses have almost always had numerous medication trials before an effective regimen is found, a thorough

References (110)

  • S. Garnis-Jones

    Dermatologic side effects of psychopharmacologic agents

    Dermatol Clin

    (1996)
  • Y. Yoon et al.

    New antiepileptic drugs and preparations

    Emerg Med Clin North Am

    (2000)
  • J.R. Panuska et al.

    Hypersensitivity reaction to desipramine

    J Allergy Clin Immunol

    (1987)
  • S.A. Cullinan et al.

    Acute pulmonary hypersensitivity to carbamazepine

    Chest

    (1975)
  • K. Fogh et al.

    Toxic epidermal necrolysis after treatment with lamotrigine (Lamictal)

    Seizure

    (1997)
  • G.P. Pavlidakey et al.

    Chlorpromazine-induced lupus-like disease: case report and review of the literature

    J Am Acad Dermatol

    (1985)
  • C.K. Svensson et al.

    Cutaneous drug reactions

    Pharmacol Rev

    (2001)
  • Q. Gu et al.

    Prescription drug use continues to increase: U.S. prescription drug data for 2007-2008

    NCHS Data Brief

    (2010)
  • R.C. Kessler et al.

    Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication

    Arch Gen Psychiatry

    (2005)
  • C.R. Culy et al.

    Lamotrigine. A review of its use in childhood epilepsy

    Paediatr Drugs

    (2000)
  • J.A. Messenheimer et al.

    The tolerability of lamotrigine in children

    Drug Saf

    (2000)
  • N. Schaub et al.

    Severe hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro

    Allergy

    (2000)
  • A.H. Guberman et al.

    Lamotrigine-associated rash: risk/benefit considerations in adults and children

    Epilepsia

    (1999)
  • R.G. Schlienger et al.

    Lamotrigine-induced severe cutaneous adverse reactions

    Epilepsia

    (1998)
  • R.L. Page et al.

    Fatal toxic epidermal necrolysis related to lamotrigine administration

    Pharmacotherapy

    (1998)
  • B. Sachs et al.

    Lamotrigine-induced Stevens-Johnson syndrome: demonstration of specific lymphocyte reactivity in vitro

    Dermatology

    (1997)
  • L.M. Li et al.

    Allergic skin rash with lamotrigine and concomitant valproate therapy: evidence for an increased risk

    Arqu Neuropsiquiatr

    (1996)
  • R.J. Troost et al.

    Allergy to carbamazepine: parallel in vivo and in vitro detection

    Epilepsia

    (1996)
  • M. Dam

    Practical aspects of oxcarbazepine treatment

    Epilepsia

    (1994)
  • R.G. Beran

    Cross-reactive skin eruption with both carbamazepine and oxcarbazepine

    Epilepsia

    (1993)
  • P. Qin et al.

    Suicide risk in relation to psychiatric hospitalization: evidenced based on longitudinal

    Arch Gen Psychiatry

    (2005)
  • A. Srebrnik et al.

    Adverse cutaneous reactions to psychotropic drugs

    Acta Derm Venereol Suppl (Stockh)

    (1991)
  • T.E. Steele et al.

    Desipramine-related slate-gray skin pigmentation

    J Clin Psychopharmacol

    (1993)
  • V. Narurkar et al.

    Desipramine-induced blue-gray photosensitive pigmentation

    Arch Dermatol

    (1993)
  • Z. Tunca et al.

    Clomipramine- induced pseudocyanotic pigmentation

    Am J Psychiatry

    (1989)
  • C. Hemlock et al.

    Fluoxetine-induced psoriasis

    Ann Pharmacother

    (1992)
  • J.H. Barth et al.

    Generalized pustular psoriasis precipitated by trazodone in the treatment of depression

    Br J Dermatol

    (1986)
  • J.J. Skonicki et al.

    Drug Eruptions

    Curr Psychiatry

    (2008)
  • E. Gaufberg et al.

    Photosensitivity reaction to fluoxetine

    J Clin Psychiatry

    (1995)
  • M.N. Gillet-Terver et al.

    Fluvoxamine photosensitivity

    Australas J Dermatol

    (1996)
  • J.H. Epstein et al.

    Photosensitivity due to drugs

    Drugs

    (1985)
  • G.L. Cooper

    The safety of fluoxetine: an update

    Br J Psychiatry Suppl

    (1988)
  • L.G. Miller et al.

    A case of fluoxetine-induced serum sickness

    Am J Psychiatry

    (1989)
  • J.K. Warnock et al.

    Drug-related alopecia in patients treated with tricyclic antidepressants

    J Nerv Ment Dis

    (1991)
  • R.A. McCollom et al.

    Bupropion-induced serum sickness-like reaction

    Ann Pharmacother

    (2000)
  • P.M. Peloso et al.

    Serum sickness-like reaction to bupropion

    JAMA

    (1999)
  • J.C. Yolles et al.

    Serum sickness induced by bupropion

    Ann Pharmacother

    (1999)
  • S. Taniguchi et al.

    Photosensitivity and thrombocytopenia due to amitriptyline

    Am J Hematol

    (1996)
  • B. Ljunggren et al.

    A case of photosensitivity and contact allergy to systemic tricyclic drugs, with unusual features

    Contact Dermatitis

    (1991)
  • J.D. Case et al.

    Photosensitive reaction to phenelzine: a case report

    Photodermatol

    (1988)
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