Anais
Brasileiros
de
Dermatologia
www.anaisdedermatologia.org.brCONTINUING
MEDICAL
EDUCATION
Use
of
psychiatric
drugs
in
Dermatology
夽,夽夽
Magda
Blessmann
Weber
∗,
Júlia
Kanaan
Recuero
,
Camila
Saraiva
Almeida
DermatologyService,UniversidadeFederaldeCiênciasdaSaúdedePortoAlegre,PortoAlegre,RS,Brazil
Received8October2019;accepted15December2019
Availableonline18February2020
KEYWORDS Antidepressive agents; Dermatology; Psychopharmacology; Psychosomatic medicine; Psychotropicdrugs
Abstract Patients with psychocutaneous disorders often refuse psychiatric intervention in
their first consultations, leaving initial managementto the dermatologist. The use of
psy-chotropicagentsindermatologicalpractice,representedbyantidepressants,antipsychotics,
anxiolytics,andmoodstabilizers,shouldbeindicatedsothatpatientsreceivethemost
suit-abletreatmentrapidly.Itisimportantfordermatologiststobefamiliarwiththemostcommonly
useddrugsforthebestmanagementofpsychiatricsymptomsassociatedwithdermatoses,as
wellastomanagedermatologicsymptomstriggeredbypsychiatricdisorders.
©2020SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan
openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
Introduction
The prevalence of psychiatriccomorbidities is higher and morefrequentindermatological patientsthaninthe gen-eral population.1 It is estimated that 25---30% of patients
have some mental disorder or emotional problem, which may represent the cause, predisposition, or aggravation of the skin condition.1,2 Psychodermatology studies skin
夽 How to cite this article: Weber MB, Recuero JK, Almeida
CS. Use of psychiatric drugs in Dermatology. AnBras Dermatol. 2020;95:133---43.
夽夽StudyconductedattheDermatologyDepartment,Universidade
Federal deCiênciasdaSaúdede PortoAlegre,Porto Alegre,RS, Brazil.
∗Correspondingauthor.
E-mail:mbw@terra.com.br(M.B.Weber).
diseasesresultingfromtheskin-mind interaction, through itsunion withpsychiatry.3 It includes skin manifestations
resulting from or worsened by psychological factors and theassessmentofmentalandsocialdamageresultingfrom thesedermatoses.Themanagementofpsychodermatosesis essentialinthe fieldofdermatology,sincedermatologists are responsible for most outpatient care due to psycho-cutaneous complaints.4 Moreover, many of these patients
refusepsychiatricintervention ---either duetothe stigma associatedwithmental illnessesor thenon-acceptanceof thepsychologicalcomponentintheirskincondition,leaving themanagementtothedermatologist alone.5When there
is resistance to psychiatric treatment, the dermatologist should support the patient from a non-judgmental posi-tion,prescribetheindicatedpsychotropicmedication,and encourageevaluationwithapsychiatristasacomplement andnotasasubstituteforthetherapeuticrelationship.
https://doi.org/10.1016/j.abd.2019.12.002
0365-0596/©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).
134 WeberMBetal. Theassociateduseofpsychotropicdrugs,suchas
antide-pressants,antipsychotics,anxiolytics,andmoodstabilizers, is essential for these patients, as their skin lesions can worseniftheunderlyingpsychopathologiesarenottreated. Thus, knowledge and confidence in prescribing the most usedpsychotropicsaid themanagementofthepsychiatric symptomsassociatedwithdermatoses,aswellasthe mana-gementofdermatologicalsymptomstriggeredbypsychiatric syndromes.
Clinicalsituationsinwhichknowledgeofpsychotropicsis requiredofthedermatologist2:
1. Management of dermatological symptoms associated withpsychiatricdisorders;
2. Management of psychiatric symptoms associated with dermatological conditions, such as social phobia in patientswithvitiligo;
3. Managementofadverseeffectsassociatedwiththeuse ofpsychotropicdrugs;
4. Management of otherpharmacologicaleffects ofthese medications, such as the anticholinergic and antihis-tamineeffectsofantidepressantsandantipsychotics.
Classification
of
psychodermatoses
Psychodermatosescanbeclassifiedintosixcategories6:
1. Psychophysiological disorders:Primarydermatosesthat areexacerbatedbyemotionalfactorsandstress. Exam-ples:psoriasisandatopicdermatitis;
2. Primary psychiatric disorders: Primary psychiatric dis-eases that present self-inflictedskin manifestations as a secondary manifestation of the psychiatric illness. Examples:trichotillomania,parasiticdelirium, dermati-tisartefacta,andneuroticexcoriations;
3. Secondary psychiatric disorders: Psychiatric illnesses thatariseasaresultofthepsychosocialimpactof exist-ingdermatoses.Examples:socialphobia,depressionthat arisesfrompsoriasis,andalopeciaareata;
4. Sensitive skin disease: Psychogenic symptoms, such as pruritusorburning,withoutevidenceofskindiseaseor othermedicalcondition.Examples:vulvodyniaand glos-sodynia;
5. Alterationscausedbytheuseofpsychoactivedrugsfor dermatologicaltreatment.Examples:pruritus,rash,and Stevens---Johnsonsyndrome;
6. Multifactorial diseases:Conditions inwhich psychoneu-roimmunological factors trigger or aggravate skin con-ditions.Examples:atopicdermatitis,psoriasis,alopecia areata,chronicpruritus.
Most patients with psychodermatoses are classified amongthefollowingpsychiatricdiagnoses7:depressive
dis-orders;anxietydisorders;psychoticdisordersanddelirium disorders;obsessive---compulsivedisorder;andimpulse con-troldisorders.
Althoughdermatologistsdonothavespecifictrainingto performpsychiatricdiagnoses,asoliddoctor-patient rela-tionship,developed over several consultations, can assist theminidentifyingunderlyingpsychiatricillnesses.
There-after, they should be able to prescribe the psychotropic drugsindicatedforthespecificpsychiatricillness.7,8
Antidepressants
The use of antidepressants is based on the monoaminer-gictheoryofdepression,inwhichdeficienciesinserotonin, norepinephrine, and/or dopamine are implicated in the genesis of the disease. Thus, the different classes of antidepressants act to increase these neurotransmitters, either by inhibiting their reuptake, or by inhibiting the enzymeresponsiblefortheirdegradation(monoamine oxi-daseinhibitors).9 Furthermore,theyarealsoapprovedfor
the treatment of anxiety disorders, social phobia, and obsessive---compulsivedisorder.
None of the antidepressant classes hasbeen shown to be the most effective in treating depression and none is specificallyindicatedforeachpsychodermatologicdisease. Theyreachtheirtherapeuticdoseinaperiodoffourtosix weeks,buttherecommendationis tostartwithlowdoses andgraduallyincrease---preferablyatleastevery14days. In the absenceof a responseat theend of the initial six weeks, an alternative drugshould be chosen. If a partial improvementinsymptomsisobserved,thedosesshouldbe increased until the ideal dose for each patient, assessed individually,isreached.10Theadverseeffectsaredifferent
for each class,and aremoreoften reportedwiththe use oftricyclicantidepressants.Whilethesedrugsdonotcause dependence,symptomssuchasinsomnia,nausea,sweating, and sensory disturbances are described after abrupt dis-continuation.Forwithdrawal,thedoseshouldbegradually decreasedoverseveralweeks.11Treatmentshouldbe
main-tainedforatleastsixmonthsafteratherapeuticresponse beforeattemptingtowithdraw,inordertominimizetherisk ofrecurrenceofsymptoms.10,12
Selectiveserotoninreuptakeinhibitors10
Selective serotonin reuptake inhibitors (SSRIs), listed in
table 1, act by selectively inhibiting serotonin reuptake, therebyincreasingtheavailabilityofthisneurotransmitter, responsibleforinfluencingmood,cognition,sleep,appetite, andsexualbehavior.13Themonoaminergictheoryof
depres-sionpostulatesthatincreasingtheavailabilityofserotonin in thesynaptic cleft wouldmodulate theimprovement of depressionsymptoms.
Theyhaveagoodsafetyprofileandtendtohavegreater tolerabilitywhencomparedwithtricyclicantidepressants, being the firsttherapeutic choice for many patients. The mostreportedadverseeffectsaregastrointestinalchanges (nauseaanddyspepsia),insomnia,weightchange,and sex-ual dysfunction,suchasanorgasmia and reducedlibido.14
They can beused by pregnantwomen; for such patients, thosewithshorterhalf-life,suchassertralineand paroxe-tine,arepreferred.15
Tricyclicantidepressants10
Thisistheoldestclassofantidepressants,listedintable2. Theyact similarlytoSSRIs,increasingserotonin and
nore-Table1 Maintypesofselectiveserotoninreuptakeinhibitors(SSRI).
Medication Brandname Presentation Initialdose
--- maximum
Observations
Fluoxetine Prozac,Daforin 10and20mgtablet/capsule 10---80mg/day Nomonitoringrequired
Oralsolution
20mg/mL
Extensiveexperiencein
pregnantwomen
Longhalflife
Paroxetine Paxil,Pondera,Aropax 10,20,and30mgtablet 20---60mg Nomonitoringrequired
Sertraline Tolrest,Zoloft,Assert 25,50,and100mgtablet 25---200mg Usedinpatientswithliver
problems
Fluvoxamine Luvox,Revoc 50and100mgtablet 50---300mg Fractionizedose
if>150mg/day
Citalopram Celexa,Procimax 20and40mg
tablet
20---60mg Recommendedinliverdisease
Highercardiacriskat
doses>40mg/day
Escitalopram Lexapro,Reconter 5,10,and20mgtablet 5---20mg
Oralsolution20mg/mL
pinephrineinthesynapticcleft.Theyhave beenreplaced bySSRIsovertheyears,duetotheirmoresedativeeffects and a greater number of other side effects. However, these drugs (especially doxepin) present properties more similar to antihistamines, and are therefore widely used for insomnia and pruritus.15,16 They also perform well in
patients with pain of neural origin. Generally, the doses needed to treat pain and pruritus tend to be lower than antidepressant doses. Nortriptyline has fewer adverse effectsandshouldbechosenforelderlypatients.11
Amongtheadverseeffects,theliteraturedescribesdry mouth,constipation,dizziness,blurredvision,tachycardia, andurinaryretention.17 They shouldbeusedwithcaution
inpatientswithcardiacconditions,suchasconduction dis-order. There is an absolute contraindication for their use in patients after a recent episode (up to six weeks) of acutemyocardialinfarction.15Theycanbeusedduring
preg-nancy, although theyshouldnotbe prescribedinthe first trimester.18
Doxepin(Sinequan®)
Thistricyclicantidepressanthaspotentantihistamine prop-erties; in dermatology, it is usedin patients withchronic pruritusandurticaria,representinganoptionto diphenhy-dramineandhydroxyzine.12,17Furthermore,whenintopical
formulation (5% cream), it does not cause the side reac-tions characteristic of oral tricyclic antidepressants.16,19
When usedorally, the initialdose is25mg/day;it can be increased weekly by 10---25mg, reaching a maximum of 100mg/day.
Sedationisthemain adverseeffect,anddose schedule adjustmentmaybenecessaryincaseofpatientcomplaints. Patientswitha historyof heart rhythmalterations should undergo an electrocardiogram before starting treatment. If the dose is increased, it is suggested that the test be repeatedwhenthedosagereaches100mg/day.12Currently,
inBrazil, thismedicineis onlyprovidedbyhandling phar-macy.
Otherantidepressants10
Theseantidepressantdrugsarelistedintable3.
Mirtazapine(Remeron®,Zispin®,Norset®)
Atetracyclicantidepressantthatactsdirectly,byincreasing theamountofserotoninandnorepinephrine.Duetoitshigh potentialforsedationandweightgain,itispreferablyused interminalpatients.11
Bupropion(Wellbutrin®,Zetron®)
Bupropionisaselectivenorepinephrineanddopamine reup-take drug. As it has fewer sexual adverse effects and a similarantidepressantcapacity, itis preferredin patients withcomplaintsof libidoalterations.12 Itsuseshouldalso
beconsideredinpatientswithsleepdisorders.11Dose
frac-tioningisnecessary,exceptincasesofslow-releasetablets. It is a generally well-tolerated medication, and its main side effects are insomnia, agitation, headache, constipa-tion, dry mouth, nausea, and tremors. Seizures are rare effects,buttheycan beobserved;therefore, careshould betakenwhen indicatingusein patientswithahistoryof epilepsy.Bupropionshouldalsobeavoidedinpatientswith ahistoryofalcoholanddrugabuse.12,16Itsuseinpregnancy
isnotrecommended.18
Venlafaxine(Efexor®,Zyvifax®)
Officiallyreleased for use indepression and anxiety, ven-lafaxine appears toact in the receptionof serotonin and norepinephrine.Theinitialrecommendeddoseis75mg/day, increasingeverytwoweeks, reachingamaximum dose of 300mg/daythatshouldbedividedintotwodoses.Themost commonlyreportedadverseeffectsofthisdrugare insom-niaand anxiety; when usedin high doses,blood pressure shouldbemonitored.14,15
136 W eber MB et al.
Table2 Maintypesoftricyclicantidepressants.
Medication Brandname Presentation Initialdose---maximum Observations
Nortriptyline Pamelor 10,25,50,and75mgcapsules 10---150mg/day EKGinwomen>40yearsandmen>30years Oralsolution2mg/mL Saferfortheelderly
Amitriptyline Amytril,Tryptanol 10,25,and75mgtablets 10---150mg/day EKGinwomen>40yearsandmen>30years Doxepin NotavailableinBrazil --- 100---300mg/day Needtobeformulated
Clomipramine Anafranil 10,25,and75mgtablet/dragée 10---250mg/day EKGinwomen>40years andmen>30years Injectablesolution25mg/2mL
Table3 Maintypesofotherantidepressants.
Medication Brandname Presentation Initialdose---maximum Observations Mirtazapine Remeron,Zispin,
Norset
15,30,and45mg tablet
15---45mg/day Sedative Weightgain
Anticholinergiceffects(rare) Bupropion Wellbutrin,
WellbutrinXL Zetron,ZetronXL
150and300mgtablet 150---300mg/day Sloworimmediaterelease
Venlafaxine Effexor,Zyvifax, Zaredrop
37.5,50,75,and150mgtablet/capsule 75---300mg/day Fractionizeddose Oralsolution75mg/mL
Duloxetine Velija,Cymbalta 30and60mgtablet/capsule 60mg/day ---Trazodone Donaren 50and100mgtablet 150---600mg/day Sedative
Fractionizeddosesabove300mg/day Useinhospitalizedpatients
Table4 Maintypesofantipsychotics.
Medication Brandname Presentation Initialdose---maximum
Pimozide Orap 1and4mgtablet 2---4mg/day---20mg/day
Risperidone Risperdal,Riss 1,2,and3mgtablet
1mg/mLsolution
2mg/day---8mg/day
Olanzapine Zyprexa,Zopix 2.5,5,and10mgtablet 2.5---5mg/day---15mg/day
Quetiapine Seroquel,Quetrox,Queropax 25,100,and200mgtablet 25---750mg/day
Aripiprazole Aristab,Abilify 10,15,20,and30mgtablet 10---30mg/day
Ziprasidone Geodon 40and80mgcapsule 40---160mg/day
Haloperidol Haldol 1and5mgtablet
Oralsolution2mg/mL
Injectablesolution5mg/mL
0.5---15mg/day
Regardingtheuseinpregnancy,despitethelackof stud-iesinpregnantwomen,experimentswithanimalshavenot demonstratedteratogenicity.18
Antipsychotics
10Antipsychotics, listed in table 4, are dopamine recep-tor antagonists, acting mainly by blocking D2 subtype receptors.20Theyaredividedintotypical(pimozide,
chlor-promazine, and haloperidol) and atypical antipsychotics (risperidone,olanzapine,sulpiride,andquetiapine). Atyp-icalantipsychoticshavealoweraffinityforD2receptors,so theyhavealowerincidenceofextrapyramidaleffects,such asdystoniaandparkinsonism,thantypicalantipsychotics.
The main dopaminergic pathways in the central ner-voussystem arethe mesocorticolimbic, nigrostriatal, and tuberoinfundibular. Dysfunctions in the mesocorticolim-bicpathway areassociatedwithpsychosis, schizophrenia, and attention deficit disorder, while dysfunction in the nigrostriatalpathway is related toParkinson’sdisease, as well as tomotor side effects when used in dopaminergic therapy, including extrapyramidal effects. In turn, dys-functionsinthetuberoinfundibularpathwaycausechanges in prolactin secretion, which can cause galactorrhea and amenorrhea,asdopamineisresponsibleforinhibiting pro-lactinsecretion.13
Antipsychotics maycausesideeffectsduetobindingto otherreceptors,suchasweightgain(histaminereceptors), orthostatichypotension(␣-adrenergics),constipation, and xerostomia(muscarinicreceptors).20Theymayalsoincrease
the risk of myocardial infarction and transient ischemic eventsinelderlypatients.10
In dermatology, antipsychotics can be used mainly in delusionaldisorders,suchasparasiticdeliriumand dermati-tisartefacta.17
Haloperidolisthebeststudieddruginrelationtouse dur-ingpregnancy,beingthepreferredantipsychoticfor these patients.21
Pimozide(Orap®)
Thisis thefirstgenerationantipsychotic mostwidelyused inpsychodermatology.Itactsasapotentantagonistofthe central dopamine receptor. It is indicated to start with 1mg/day,withaprogressiveincreaseeverytwoweeks,until reaching the target dose (2---6mg/day). This dose should
bemaintained for at least onemonth afterthe improve-ment of symptoms. Although rare, due to the low dose usedforskindiseases,theliteraturedescribessomeadverse effects,suchasakathisia,musclestiffness,andrestlessness. Due to the possibility of altering the QT interval, an electrocardiogram is recommended before treatment in patientswithahistoryofheartdiseaset.Inyoung/healthy patients,theneed forelectrocardiographicexaminationis stillcontroversial.16
Risperidone(Risperdal®,Riss®)
Themainmedicationusedforparasiticdelirium,risperidone isanewgenerationantipsychoticandshouldbestartedat adoseof0.5mgbeforebedtime,andshouldbeincreased weekly until reaching a maximum dose of 4mg/day. It cancausehyperprolactinemiaand,consequently, galactor-rhea,amenorrhea, and sexualdysfunction. Other adverse effects,suchassedation,areuncommonandusuallyresolve withinthe first few days. This medication should alsobe usedwith caution in patients with a history of abnormal electrocardiogram.11,22
Olanzapina(Zyprexa®,Zopix®)
Olanzapineisrecommendedinlowdosesfor psychoderma-tologicdiseases.Thesuggestedinitialdoseis5---10mg/day until reaching a target dose of 15mg/day. Despite being a generally well-tolerated medication, its main adverse effect is weight gain and, consequently, metabolic syn-drome and increased cardiovascular risk. As a result, it is necessary to control weight and monitor blood pressure, glucose, and lipids during treatment with this medication.11,14,17
Quetiapine(Seroquel®,Quetrox®,Queropax®)
Quetiapineiswellindicatedinpatientsresistanttoprevious treatmentsandinelderlypatients.Inthetreatmentof non-dermatologicalpsychoses,itisinitiallyprescribedatadose of 25mg twice a day and increased to750mg/day. How-ever,for dermatological useit is recommendedtoreduce thestarting andmaintenancedoses.Forexample, 150mg divided intotwo doses, is indicated for the treatment of parasiticdelirium.12,23
138 WeberMBetal. Weightgain,drowsinessandorthostatichypotensionare
amongthemostcommonlyreportedsideeffects.11,14
Aripiprazole(Aristab®,Abilify®)
Aripiprazoleisanewgenerationantipsychotic,noteworthy due to its low relationship with metabolic disorders and cholinergiceffects.Ithasbeenusedforpatientswith par-asiticdeliriumandneuroticexcoriations,withgoodresults atdosesbetween2and30mg/day.Itusuallydoesnotcause changesinweight.14
Ziprasidone(Geodon®)
Similarto aripiprazole, ziprasidone is also a new genera-tionantipsychotic.Itdiffersfromtheothersduetolackof anticholinergiceffectsandthelowpropensitytometabolic syndrome,inadditiontolowincidenceofsedativeeffects. However,ithasmorerisksofcausingQTintervalalterations thanotheratypicalantipsychotics.Itissuccessfullyusedin thetreatmentofpatientswithparasiticdeliriumwithdoses rangingfrom20mgto80mg/twicedaily.11
Mood
stabilizers
Mood stabilizers, such asantiepileptic drugs and lithium, areapprovedforuseinbipolardisorderandepilepsy.Their mechanismsare notcompletely understood, but they are believed to act on the central nervous system, with the powertocontrolneuronalexcitation.24
Manyofthesemedications,asmentionedintable5,are usedinneuropathicskinpainandarealsoeffectiveinthe managementofchronic pruritus, inadditiontoother skin sensorydisorders,suchasself-induceddermatoses. Primar-ilyduetotheircompulsioncontrolpower,theyareincluded inthetreatmentofdermatosesrelatedtoself-excoriation, such as nodular prurigo and lichen simplex chronicus, as wellasinself-inflictedlesions,suchastrichotillomaniaand dermatitis artefacta. These medications areknown tobe teratogenic and shouldbe avoided, ifpossible, in female patientsofchildbearingage.14
Lithium(Carbolitium®)
Lithiumcarbonate,usedinthetreatmentofbipolardisorder andsevere depression, altersthe metabolism ofneuronal catecholamines. Serum lithium dosage should be moni-toredinitially every 60---90 days,and this intervalcan be extendeduptosixmonths,dependingonthetimeofuse. Bloodsamplesshouldbecollectedeightto12haftertaking the previous dose and before the nextdose. It is recom-mendedtomaintainserumlithiumlevelsbetween0.5and 1.0mEq/L,equivalenttoadoseof600---900mg/day.Signsof toxicitymaybegintoappearasearlyas1.0---1.5mEq/L.The useofthisdrugalsorequiresfrequentmonitoringofrenal and thyroid functions. Caution should beused when pre-scribinglithium,duetoitshighrateofadverseskineffects, suchasworseningor triggering the onsetof psoriasisand acne.11,24,25Lithiumisindicatedforthecontrolofimpulsive
behaviorin patientswithtrichotillomania, due toitshigh T
able 5 Main types of mood stabilizers and anticonvulsants. Medication Brand name P resentation Initial dose ---Maximum Observations Lithium Carbolitium 300 and 450 mg tablet 600---2.400 mg/day Serum lithium level assessment is required Lamotrigine Lamitor , Lamictal 25, 50, and 100 mg tablet 50---200 mg/day SJS/TEN Carbamazepine Tegretol, Tegrex, Carmazin, Tegretard 200 and 400 mg tablet 200---1600 mg/day SJS/TEN (HLA-B1502 allele) Oral solution 20 mg/mL Sodium valproate Depakote, Depakene 300 and 500 mg tablet 15---60 mg/kg/day Hepatotoxicity 250 mg/5 mL syrup P ancreatitis Teratogenic Topiramate Amato, Sigmax 25, 50, and 100 mg tablet 50---200 mg/day Myopia, closed-angle glaucoma Metabolic acidosis Cognitive dysfunction Suicidal behavior P regabalin Lyrica 75 and 150 mg capsule 150---600 mg/day Suicidal behavior , convulsion in case of rapid withdrawal, angioedema Gabapentin Gabaneurin, Gamibetal, P rogresse 300 and 400 mg capsule 900---3600 mg/day
---associationwithobsessive---compulsivedisorder,withdoses varyingbetween900and1500mg.12,26Skinpickingpatients
canalsobenefitfromtheuseoflithiumforimpulsecontrol, althoughthereisnodosespecifiedintheliterature.11
Lamotrigine(Lamitor®,Lamictal®)
Lamotrigine is a medication used to treat seizures. Phar-macologically,itactsonneuronalsodiumchannels,mainly bystabilizingmembranesandinhibitingthereleaseof glu-tamate. Itsbenefits in thetreatment ofskin pickinghave beendemonstrated,11andtheliteraturesuggeststheuseof
dosesbetween12.5and300mg/day.11
Carbamazepine(Tegretol®,Tegrezin®,Tegretard®,
Tegrex®,Carmazin®)
Although its action has not been fully understood, car-bamazepine is known tostabilize the hyperexcited nerve membrane. It is indicated for the treatment of epilepsy, bipolar disorder, depression, and painof neural origin. In dermatology, the use of this medication in post-herpetic neuralgiaisnoteworthy. Inadditiontodose fractioning,it isrecommendedtostartwithlowerdoseswithprogressive increase. The recommended dose for neuropathic pain is 600---1200mg/day.Adverse effects suchasgastrointestinal symptoms, dizziness, and blurred vision are reported, as wellasskineffects,reportedlaterinthisarticle.The liter-aturealsoreportsmorerarerisks,suchasagranulocytosis andaplasticanemia.24
Sodiumvalproate(Depakote®,Depakene®,
Zyvalprex®)
Theactivityofsodiumvalproate,whichconvertstovalproic acidin thebody,appears toberelatedtotheincreasein GABAin thecentral nervous system. The doses indicated forepilepsystartat10---15mg/kg/day,andcanbeincreased by5---10mg/kg/dayweekly.Dosesbelow60mg/kg/dayare considered to have a good clinical response. For neuro-pathicpain,theliteraturesuggestsdosesbetween250and 1500mg/day,withafractioneddose.Inadditiontotheuses inchronicpain,therearereportsoftreatmentswithsodium valproate inpatients withinflammatoryverrucous epider-malnevi(ILVEN).24
Topiramate(Amato®,Sigmax®)
Ananticonvulsantmedication,withmultiplemechanismsto reduce neuronal hyperexcitability, used to treat epilepsy and migraine prophylaxis. It is recommended to start at a dose of 25---50mg daily for at least one week, and increasethedose everyoneortwoweeks.Thedailydose shouldrange between 200 and400mg/day andthe maxi-mumdose is1600mg.11,24 Therearereports of theuseof
topiramate in thetreatment oftrichotillomania, however studieswithlargerpopulationsarenecessarytoconfirmits effectiveness.26
Pregabalin(Lyrica®)
This medication acts in the neuronal calcium channels. Itsformalindicationisforneuropathic pain,epilepsy,and fibromyalgia. Pregabalin has a good action in the control ofneuropathicpainandhasagoodsafetyprofile,because it interacts with fewer drugs when compared with other medications in this class. Some authors also indicate its useforuremicpruritus.Adose of300---600mg/day is indi-cated.Generally,ithasnoserioussideeffects;theliterature reportssideeffectssuchasdrowsiness,dizziness,andeven peripheraledema.11,19,24
Gabapentin(Gamibetal®,Progresse®, Gabaneurin®)
Generally used for epilepsy and neuropathic pain, gabapentin is an anticonvulsant derived from the neu-rotransmitterGABA.Itisthemoststudiedmoodstabilizer in dermatology; it is especially effective in situations where sensitization of the central nervous system is a mediating factor. It is used more widely in post-herpetic neuralgia,but it canalso beused inchronic pruritus and other pains of neural origin, such as paresthetic notalgia andbrachioradial itching.25,27,28 It can be prescribed at a
dosage of 300---3600mg/day. This medication has a good safety standard regarding drug interactions and its most reportedadverse effects are:drowsiness, nausea,double vision, anddysphasia, amongothers. There is insufficient dataforuseinpregnancyandlactation.15,29
Anxiolytics
Anxiolytic drugs are used to relieve anxiety symptoms, actingdirectlyonthelimbicsystem.Usedinspecial situa-tions,suchaspanicdisorderandpost-traumaticstress,for example,theyhaveahigh sedative powerandmaycause dependence. They are divided into benzodiazepines and non-benzodiazepines.15
Benzodiazepines
Pharmacologically, benzodiazepines act as GABA modu-lators. The use of these drugs should be limited to a period of three to four weeks, due to the high poten-tial for dependence and abuse. Some authors mention a maximum use of six weeks. Moreover, it is neces-sary to be careful when withdrawing the medication, due to the possibility of withdrawal symptoms16 They
can be divided into short duration: triazolam (Halcion®),
midazolam (Dormonid®); short-intermediate: alprazolam
(Frontal®, Alfron®); intermediate-prolonged: bromazepam
(Lexotan®), nitrazepam (Sonebon®), Lorazepam (Lorax);
prolonged: clonazepam (Rivotril®), diazepam (Valium®),
clobazam(Frisium®,Urbanil®),flurazepam(Dalmadorm®).
Amongtheadverseeffectsofthesemedications, learn-ingdifficulties,amnesia,aggressiveness,andconfusioncan bementioned.There isa riskof respiratorydepression in patientswithchroniclungdiseases,aswellaswiththeuse
140 WeberMBetal. ofcentralnervoussystem-depressantdrugs(alcohol).They
arecontraindicatedinthefirsttrimesterofpregnancy.15,17
Non-benzodiazepines
Buspirone(Ansitec®)
Buspironeisanon-benzodiazepineanxiolyticdrugthathas no potential for dependence. Its onset of action is a bit slower,twotofourweeks,andtherefore itshouldnotbe usedinmoreacutecases.Duetoitsprofile,itispreferred incaseswherelongertherapiesneedtobeinstituted.The initialdosesuggestedis15mg/day,increasing15mgevery week,withamaximumdoseof60mg/day,dividedintotwo doses,duetoitsshorthalf-life.11,16
Zolpidem(Stilnox®)
Usedasasleepinducer,zolpidemshouldbeusedatadoseof 5---10mgbeforebed.Thisdrugactsinasimilarwayto benzo-diazepines,andcanleadtomentalconfusionandtolerance overtime;therefore,itshouldbeusedforshortperiods.
Adverse
skin
reactions
to
psychiatric
drugs
Adverseskinreactionstriggeredbytheuseofpsychotropic drugsareestimateddependingonthedruginupto39%of cases,withanincreasedrisk associatedwithfemales,the elderly,andthoseofAfricandescent.30 Among
psychotrop-ics, mood stabilizers present the highest prevalence and severityofskinreactions,whichcanbepotentiallyfatal.31
Themanagementof skinreactionsassociatedwith psy-chiatric drugs and the decision to discontinue treatment mustbeevaluatedtakingintoaccounttheseverityofthe skinmanifestationandofthepsychiatricillness.Moreover, thepossible harmin relation toabruptdiscontinuationof medicationmustbeconsideredandevaluated.
Pruritus30---36
Prurituscanoccurwiththeuseofanyantidepressant,mood stabilizer, and antipsychotic. It is also reported by those usingbenzodiazepines,althoughlessfrequently.
Antidepressants:bupropionhasthehighestincidenceof pruritus,whilethelowestratesarefoundwithfluoxetine, paroxetine,sertraline,andvenlafaxine.
Moodstabilizers:alldrugsinthisclass.
Antipsychotics:risperidone,olanzapine,quetiapine,and clozapine.
Benzodiazepines:thereisahigherincidencefortheuse ofalprazolam.
Rash30---36
Itis the most commonadverse skin reaction triggered by the use of psychotropics. It is associated withthe use of antidepressants,moodstabilizers,andantipsychotics.
Antidepressants:inalldrugsinthisclass.Amongtricyclic antidepressants, the highest incidencewas observed with theuseofclomipramine.
Mood stabilizers: carbamazepine, gabapentin, lithium, valproicacid,lamotrigine,andtopiramate.
Antipsychotics: risperidone, olanzapine, quetiapine, clozapine,haloperidol,andziprasidone.
Benzodiazepines: the highest incidence was observed withtheuseofalprazolam.
Urticariaandangioedema30---36
Theyarecommonadversemanifestations.Theyare associ-atedwiththeuseofantidepressants,moodstabilizers,and antipsychotics.
Antidepressants:inalldrugsinthisclass.
Moodstabilizers:carbamazepineandlamotrigine. Antipsychotics:risperidone, olanzapine,clozapine, and haloperidol.
Benzodiazepines:alprazolam.
Fixeddrugeruption30---36
Lesionsappearwithineighthoursaftertakingthe medica-tion,andareusuallyasymptomatic.
Antidepressants:inalldrugsinthisclass.
Moodstabilizers:carbamazepine,lithium,gabapentin. Antipsychotics:risperidone,olanzapine,quetiapine,and haloperidol.
Photosensitivity30---36
Photosensitivityreactions(dividedintophototoxicand pho-toallergic)aretriggeredbyexposuretoultravioletradiation withtheuseofcertainmedications.
Antidepressants:fluoxetine,paroxetine,sertraline,and escitalopram.Therearefewcasesreportedwiththeuseof tricyclicantidepressants.
Moodstabilizers:carbamazepineandlamotrigine. Antipsychotics:chlorpromazine,risperidone,olanzapine, quetiapine,clozapine,andhaloperidol.
Skindiscoloration30---36
Skindiscolorationusuallyoccursafterprolongeduseofsome psychotropicdrugs.Inmostcases,itdisappearsslowlyafter treatmentdiscontinuation.Itcantakemonthsoryearsfor thepigmentationtocompletelydisappear.
Antidepressants:thehighest incidenceisobservedwith tricyclicantidepressants.
Moodstabilizers:carbamazepine, gabapentin,and lam-otrigine.
Antipsychotics:chlorpromazine,risperidone,olanzapine, quetiapine,clozapine,andhaloperidol.
Alopecia30---36
Itusuallyoccursdiffusely.Hairlossceaseswiththe discon-tinuationofmedication.Itisassociatedwiththeuseofsome antidepressants,moodstabilizers,andantipsychotics.
Antidepressants:selectiveserotoninreuptakeinhibitors. Mood stabilizers: lithium, carbamazepine, lamotrigine, andvalproicacid.
Antipsychotics:risperidone,olanzapine.
Acneiformrashes30---36
The lesions usuallypresent as follicular pustules,without comedones.Theyoccurontheface,chest,andupperback. Theyaremainlyassociatedwiththeuseofantidepressants.
Antidepressants:inalldrugsinthisclass.
Mood stabilizers: lithium, carbamazepine, lamotrigine, andtopiramate.
Antipsychotics:quetiapineandrisperidone.
Psoriasiformreactions30---36
Thelesionsareusuallyobservedbilaterallyontheelbows, knees,andscalp.
Antidepressants:fluoxetine,escitalopram,and venlafax-ine.
Mood stabilizers: lithium, carbamazepine, and valproic acid.
Antipsychotics:risperidoneandquetiapine.
Seborrheicdermatitis30---36
Itisacommonmanifestationofpsychiatricdrugs,especially duetotheuseofantidepressantsandmoodstabilizers.
Antidepressants: fluoxetine, paroxetine, and venlafax-ine.
Mood stabilizers: lithium, carbamazepine, and valproic acid.
Antipsychotics: risperidone,olanzapine, clozapine, and haloperidol.
Erythemamultiforme30---36
Itisarareandseriousadversereaction.Casesoferythema multiforme-likelesionswiththeuseofantidepressantsand antipsychoticshavebeendescribedintheliterature.
Antidepressants: fluoxetine, paroxetine, sertraline, duloxetine,andbupropion.
Mood stabilizers: carbamazepine, lamotrigine, gabapentin,andvalproicacid.
Antipsychotics:risperidoneandclozapine.
Stevens---Johnsonsyndromeandtoxicepidermal necrolysis30---36
Theseareseriousadversereactionsmainlyassociatedwith theuseofmoodstabilizers.Theyarerarelyobservedwith theuseofantidepressants.Theinvolvedmedicationshould neverbeprescribedagain.
Antidepressants: fluoxetine, sertraline, paroxetine, bupropion,andduloxetine.
Mood stabilizers: carbamazepine, lamotrigine, and val-proicacid.
Antipsychotics:quetiapineandclozapine.
Exfoliativeerythroderma30---36
Itisaseriousadverse reaction.Itis moreassociatedwith theuseofsometricyclicantidepressants,andrarelyoccurs withtheuseofantipsychotics.
Antidepressants: amitriptyline, nortriptyline, clomipramine,andmirtazapine.
Moodstabilizers:lithiumandcarbamazepine. Antipsychotics:risperidoneandquetiapine.
DRESSsyndrome30---36
Itisaseriousadversereaction;inadditiontoskin involve-ment,thereisfeverandinvolvementofseveralorgans.
Antidepressants:amitriptyline,imipramine, and fluoxe-tine.
Mood stabilizers: carbamazepine, lamotrigine,and val-proicacid.
Antipsychotics:olanzapine.
Hypersensitivityvasculitis30---36
Initially,itismanifestedbypurpurainthelowerlimbs.There maybesystemicinvolvementofdifferentorgans.
Antidepressants:paroxetine,fluoxetine,andsertraline. Moodstabilizers:carbamazepineandlamotrigine. Antipsychotics:clozapineandhaloperidol.
Conclusion
Theidentificationandpsychopharmacologicalmanagement of psychocutaneous disorders should notbe neglected by the dermatologist, since dermatological patients have a highprevalenceofpsychiatriccomorbidities.Theabilityto prescribepsychotropicdrugsbecomesevenmorerelevant when psychiatric treatment is neglected by the patient. Furthermore, the prescription of psychiatric drugs by a dermatologist (rather than a psychiatrist) may be better accepted,duetothestigmasurroundingmentalhealthand treatmentwiththoseprofessionals.
The dermatologist must be aware of the mechanisms, indications,andsideeffectsofthemostusedpsychotropic agents so that they can provide the best treatment and preventtheworseningofpsychodermatoses.However,itis necessarytoestablishan attitudeofempathyandsupport forthesepatients, sothattheyacceptandadheretothe psychotropicintervention.The choiceof the psychotropic drug must be based on the underlying psychopathology; depressive disorders, anxiety disorders, psychotic, delu-sionaldisorders,andobsessive---compulsivedisordersarethe mostcommonlyfoundindermatologicalpractice.
Itshouldalsobenotedthattheuseofpsychotropicdrugs is one of the components of a comprehensive treatment for patients with psychodermatoses.One should continue to encourage the search for psychiatric treatment and psychotherapeutic supportso that the patient has better therapeuticresultsandabetterqualityoflife.
142 WeberMBetal.
Financial
support
None.
Authors’
contributions
Magda Blessmann Weber: Conception and planning of thestudy; effective participation in researchorientation; critical review of the literature; critical review of the manuscript.
Júlia Kanaan Recuero: Elaboration and writing of the manuscript;criticalreviewoftheliterature;criticalreview ofthemanuscript.
CamilaSaraiva Almeida:Preparation andwritingofthe manuscript;criticalreviewoftheliterature;criticalreview ofthemanuscript.
Conflicts
of
interest
Nonedeclared.
CME
Questions.
1.Checktheincorrectstatement:
a)Psychophysiologicaldisordersincludeprimary
dermatosesthatcanbeaggravatedbyemotionalfactors
orstress.
b)Primarypsychiatricdisorderscanleadtoskin
manifestations.
c)Secondarypsychiatricdisordersarenotrelatedto
psychodermatoses.
d)Sensitivediseasesoftheskinormucousmembranesdo
notpresentprimarydermatologicallesions.
2.Checkthecorrectstatementregarding
antidepressants:
a)Antidepressantshavespecificindicationsforcertain
dermatoses.
b)Itmaytakeuptotwomonthsforthedesiredtherapeutic
effectstobeobserved.
c)Tricyclicantidepressantspresentthegreatestnumberof
sideeffects.
d)Treatmentcanbewithdrawnassoonasthedesired
therapeuticeffectsareachieved.
3.RegardingSSRIs,itiscorrecttostatethat:
a)Theyshouldnotbeusedduringpregnancy.
b)Theyhavegoodtolerabilityandoneofthemainside
effectsislibidoreduction.
c)Regularfollow-upofpatientsisrequired,regardlessof
age.
d)Sertralineshouldnotbeusedinpatientswithliver
disease.
4.Fortricyclicantidepressants,checktheincorrect
statement:
a)Itistheoldestclassofantidepressants.
b)Themostrelevantsideeffectsaredrymouth,
constipation,dizziness,tachycardia,andurinary
retention.
c)Neuropathicpainandpruritusrespondtotreatmentat
doseslowerthanthosegenerallyused.
d)Patientswithcardiovasculardiseaseandthosewitha
recenthistoryofmyocardialinfarctioncanusethedrug
withoutrestrictions.
5.Checkthecorrectstatementregardingantipsychotics:
a)Theyaredividedbetweentypicalandatypical,and
atypicalantipsychoticsarethenewest.
b)Theycanbeusedintheelderlypopulationwithoutthe
needforspecializedcare.
c)Theyrarelycauseadverseskinreactions.
d)Theyhavelittleeffectwhenusedforthetreatmentof
parasiticdeliriumanddermatitisartefacta.
6.Regardingmoodstabilizers,checktheincorrect
statement:
a)Theyincludeanti-epilepticsandlithium.
b)Theyareveryeffectiveinthetreatmentofneuropathic
painandpruritus.
c)Theyhavenoteratogeniceffectsandcanbeused
withoutrestrictionduringpregnancy.
d)Theycanalsobeusedinpsychodermatosesrelatedto
compulsion.
7.Checktheincorrectstatementregarding
benzodiazepines:
a)Theyareaddictivedrugsandshouldnotbeusedfora
longtime.
b)Rapidwithdrawalofthedrugcancausewithdrawal
symptoms.
c)Sideeffectssuchasamnesia,aggressiveness,andmental
confusioncanoccurwiththeuseofthesedrugs.
d)Thecanbeusedwithoutrestrictionsinpatientswith
chroniclungdisease.
8.Checktheincorrectstatement:
a)Psychotropicdrugs,ingeneral,cancauseunwantedskin
reactionsinpatientstreatedwiththesedrugs.
b)Commonmanifestationsarepruritus,rash,and
urticaria/angioedema.
c)Theuseofantidepressantsofallclassesmaycausefixed
drugeruptions.
d)Photosensitivityreactionsarerareinalldrugsusedfor
psychodermatoses.
9.Psoriasiformreactionsandseborrheicdermatitisare
morecommonwith:
a)Antidepressantsandmoodstabilizers
b)Benzodiazepines
c)Tricyclicantidepressants
d)Lithium
10.SJSandTENoccurmostfrequentlywithwhichofthe
followingmedications: a)Antidepressants b)Moodstabilizers c)Antipsychotics d)Benzodiazepines ANSWERS
Update on parasitic dermatoses. An Bras Dermatol. 2020;95(1):1---14.
1.b 3.b 5.c 7.b 9.d
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