LUCIANA VARGAS ALVES NUNES
A acurácia da Escala de Experiência Sexual do Arizona (ASEX) para
identificar disfunção sexual em pacientes do espectro da esquizofrenia
Tese apresentada à Universidade Federal de São Paulo – Escola Paulista de Medicina,
para obtenção do título de Mestre em Ciências.
LUCIANA VARGAS ALVES NUNES
A acurácia da Escala de Experiência Sexual do Arizona (ASEX) para
identificar disfunção sexual em pacientes do espectro da esquizofrenia
Tese apresentada à Universidade Federal de São Paulo – Escola Paulista de Medicina,
para obtenção do título de Mestre em Medicina.
Orientador: Prof. Dr. Jair de Jesus Mari
Nunes, Luciana Vargas Alves
A acurácia da Escala de Experiência Sexual do Arizona (ASEX) para identificar disfunção sexual em pacientes do espectro da esquizofrenia/ Luciana Vargas Nunes.- São Paulo, 2009.
Tese (Mestrado) – Universidade Federal de São Paulo. Escola Paulista de Medicina. Programa de Pós-graduação em Psiquiatria.
Título em Inglês: The accuracy of the Arizona Sexual Experience Scale (ASEX) to identify sexual dysfunction in patients of the schizophrenia spectrum.
Universidade Federal de São Paulo Escola Paulista de Medicina
Departamento de Psiquiatria e Psicologia Médica
Chefe do Departamento: José Cássio Pitta
Luciana Vargas Alves Nunes
A acurácia da Escala de Experiência Sexual do Arizona (ASEX) para
identificar disfunção sexual em pacientes do espectro da esquizofrenia
Banca Examinadora:
Dra. Anna Maria Costa
Prof. Dr. Irismar Reis de Oliveira
Prof. Dra. Cristina Marta Del Ben
Dedicatória:
A meus pais, Sandra e Luiz, que tanto me apoiaram , estiveram ao meu lado,
incentivando e acolhendo nos momentos difíceis, parabenizando e elogiando nas
Agradecimentos:
Ao Prof. Dr. Jair que sempre me incentivou na busca do conhecimento científico,
que possibilitou a realização deste trabalho.
Ao Prof. Dr. Rodrigo Bressan pelo seu entusiasmo e otimismo e por acreditar na
realização deste trabalho.
Ao Dr. Fernando Lacaz que ajudou na criação do projeto inicial e na realização do
estudo transversal.
A Dra Anna Maria Costa que esteve sempre pronta a auxiliar com sugestões e
com o fornecimento de artigos científicos.
Ao Dr Luiz Henrique Junqueira Dieckmann que auxiliou na aplicação de escalas e
na realização do estudo transversal.
A todos os pacientes que participaram do estudo transversal com os quais pude
aprender e avaliar a acurácia da escala ASEX.
Resumo:
Contexto: a disfunção sexual é freqüente entre pacientes com esquizofrenia,
sendo relatada como um dos mais incômodos efeitos adversos dos antipsicóticos e está diretamente relacionada com adesão ao tratamento.
Objetivo: a) avaliar a freqüência da disfunção sexual em uma amostra de
pacientes do espectro da esquizofrenia em tratamento com antipsicóticos; b) investigar o efeito dos diferentes antipsicóticos na função sexual; e c) avaliar a acurácia da Escala de Experiência Sexual do Arizona (ASEX) para identificar disfunção sexual.
Método: pacientes ambulatoriais com esquizofrenia ou transtorno esquizoafetivo
foram entrevistados através de questionários: ASEX e Escala Dickson-Glazer (DGSFi) para avaliação do funcionamento sexual, em uma única entrevista.
Resultados: 137 pacientes foram entrevistados. A sensibilidade e especificidade
da ASEX em relação a DGSFi foram: 80.8% ( 95% IC= 70.0%-88.5%) e 88.1% (95% IC=76.5%-94.7%), e a taxa de classificação incorreta foi 9.5%. A curva ROC comparando a pontuação da ASEX e DGSFi revelou valor de 0.93 (IC=0.879-0.970) com o ponto de corte da ASEX encontrando sendo 14/15. A disfunção sexual foi mais alta entre as mulheres (79.2%) do que nos homens (33.3%) (χ2=27.41, gl=1, p<0.001).
Conclusão: pacientes em tratamento com antipsicóticos mostraram alta freqüência
de queixas sexuais e ASEX provou ser um instrumento eficaz para identificar disfunção sexual em amostra de pacientes ambulatoriais do espectro da
Sumário:
Dedicatória... 6
Agradecimentos...7
Resumo...8
1. Introdução...10
2. Métodos...13.
3.Resultados...14
4.Discussão/Conclusão...15
5.Bibliografia...19
6. Anexos...28
6.1. Anexo 1: A acurácia da Escala de Experiência Sexual do Arizona (ASEX) para identificar disfunção sexual em pacientes do espectro da esquizofrenia....28
6.2. Anexo 2: Estratégia de manejo para a disfunção sexual induzida por antipsicóticos: descrição de um relato de caso ………...60
6.3. Anexo 3: An empirical evaluation of the Arizona Sexual Experience Scale in patients with schizophrenia and schizoaffective disorder...………..62
6.4. Anexo 4: Adaptação transcultural e avaliação empírica da escala Arizona Sexual Experience Scale de disfunção sexual em pacientes com esquizofrenia e transtorno esquizoafetivo, versão em português:...64
6.5 Anexo 5: An empirical evaluation of the Arizona Sexual Experience Scale (ASEX) questionnaire to identify sexual dysfunction in patients of the schizophrenia spectrum………...65
6.6 Anexo 6: Parecer do Comitê de Ética e Pesquisa da Unifesp...67
1. INTRODUÇÃO:
As disfunções sexuais, que muitas vezes não é detectada, são mais
freqüentes em adultos com esquizofrenia do que em adultos da população
geral. Pode ser reportada em 60% dos pacientes com diagnóstico de
esquizofrenia e apenas em 31% dos homens na população geral 1. Em um outro estudo, realizado com o relato de 7655 pacientes, a disfunção sexual
afetou aproximadamente 50% dos pacientes com esquizofrenia 2. Um estudo, com 10972 pacientes que tinham diagnóstico de
esquizofrenia e transtorno esquizoafetivo e estavam em uso de antipsicóticos,
demonstrou que a impotência sexual estava presente em 40% dos homens e a
perda de desejo sexual estava presente em 50% dos homens e mulheres 3. McDonald (2003) mostrou em seu estudo queixas sexuais relatadas por
homens com esquizofrenia: falta de desejo para intercurso (34%), baixo
satisfação com orgasmo (33%), ejaculação precoce (26%) e inabilidade em
manter ereção (9%) 4.
Um estudo conduzido por Plevin 5 reportou que 73% dos homens
apresentaram reclamações em pelo menos uma área de disfunção sexual,
quando em uso de antipsicóticos: a) ereção, disfunção ejaculatória e orgástica
6,7,8,9,10,11,12,13 b) baixo desejo sexual 8,10,11,12,13 e priaprismo9 . Embora menos
estudos tenham sido conduzidos com pacientes do sexo feminino, há evidência
Muitos fatores podem causar queixas sexuais, incluindo efeitos
adversos da medicação antipsicótica, outras medicações prescritas, assim
como efeitos da própria esquizofrenia 17 .
As medicações antipsicóticas são um grande benefício para a maior parte
das doenças psicóticas, mas o tratamento pode estar associado com efeitos
adversos pouco prazerosos 18. Os antipsicóticos podem recuperar o baixo desejo sexual de pacientes esquizofrênicos em crise, mas podem também
piorar a performance sexual do paciente 19,20,21. Antipsicóticos podem levar à disfunção sexual através de múltiplos mecanismos, incluindo sedação,
hiperprolactinemia (que pode causar disfunção sexual diretamente e
indiretamente por causar hipogonadismo) e antagonismo de receptores
α-adrenérgicos, dopaminérgicos, histamínicos e muscarínicos 18. Alguns
antipsicóticos estão associados com elevação dos níveis de prolactina; a
hiperprolactinemia pode levar a vários efeitos adversos hormonais, incluindo
disfunção sexual, ginecomastia, amenorréia e galactorréia 22. Níveis
aumentados de prolactina parecem exercer o maior papel com relação aos
efeitos adversos sexuais, mas o mecanismo que está por trás da disfunção
sexual induzida por antipsicóticos permanece ainda pobremente
compreendido 23.
Além dos antipsicóticos, existem outros fatores que podem levar às
queixas sexuais em pacientes com esquizofrenia. Os sintomas negativos da
doença, como anedonia, avolia e afeto embotado, relacionados à atividade
aproveitar a prática sexual. Estes pacientes também enfrentam dificuldade em
estabelecer relacionamentos em decorrência dos episódios psicóticos
recorrentes, obesidade e baixa auto-estima 24.Outras comorbidades
psiquiátricas, como depressão e abuso de substâncias, e também outras
doenças endócrinas, vasculares ou genito-urinárias, podem levar à disfunção
sexual 17.
Disfunção sexual induzida pelo tratamento antipsicótico pode ser
responsável pela não adesão ao tratamento25 , que é um dos maiores
obstáculos para um adequado controle dos sintomas presentes em pacientes
com esquizofrenia26. A disfunção sexual é taxada como um dos mais
incômodos efeitos adversos do tratamento antipsicótico27,28 e é experimentada pelos pacientes como significativamente mais incômoda do que sedação ou
efeitos extra-piramidais27. Finn (1990) conduziu um estudo que mostrou que o
efeito adverso mais citado como desconfortável pelos pacientes que estavam
em uso de antipsicóticos foi a disfunção erétil28. Disfunções sexuais são importantes causas de abandono ao tratamento, um estudo demonstrou que
aproximadamente 41,7% dos homens e 15, 4% das mulheres tiveram o
tratamento descontinuado em algum momento devido questões sexuais 25. Disfunções sexuais são freqüentemente mascaradas por que tanto
pacientes quanto clínicos acham desconfortável discutir sobre este tema. As
escalas estruturadas podem facilitar a abordagem da disfunção sexual, tanto
para os pacientes quanto para os médicos que avaliam os sintomas. Três
Assessment of Sexual Functioning Inventory (DGSFi) 29; b) Arizona Sexual Experience Scale (ASEX), 30 c) Psychotropic-Related Sexual Dysfunction (PRSexDQ-SALSEX) 31.
A ASEX, ao contrário de escalas mais tradicionais e que levam mais
tempo para serem preenchidas, pode ser completada em aproximadamente 5
minutos 32 e foi designada para ser autopreenchível ou administrada pelo médico clínico. Além disto, a ASEX pode ser usada para populações
heterossexuais ou homossexuais, assim como para pacientes que possuem ou
não parceiros 33.
Disfunções sexuais induzidas por antipsicóticos são pobremente
reconhecidas e não são adequadamente investigadas pela maioria dos
clínicos 34. Entretanto, é muito importante ter instrumentos com adequada acurácia para ajudar os clínicos no diagnóstico de disfunções sexuais
induzidas por antipsicóticos 33. Os principais objetivos deste estudo são: a) avaliar a freqüência da disfunção sexual em uma amostra de pacientes do
espectro da esquizofrenia em tratamento com antipsicóticos;
b) investigar o efeito dos diferentes antipsicóticos na função sexual; e c) avaliar
a acurácia da Escala de Experiência Sexual do Arizona (ASEX) para identificar
disfunção sexual.
2. MÉTODOS:
Um estudo transversal para avaliar função sexual foi conduzido no período
ambulatoriais do Programa de Esquizofrenia (PROESQ). Os pacientes que
entraram para o estudo preenchiam os critérios DSM IV para esquizofrenia e
transtorno esquizoafetivo.
Em uma única entrevista preencheram as escalas ASEX e DGSFi.
Buscando atender a Resolução 196/96, do Conselho Nacional de Saúde
(1998), este estudo foi aprovado pelo Comitê de Ética em Pesquisa da
UNIFESP e todos os pacientes e controles assinaram o consentimento por
escrito, para que fossem incluídos na pesquisa
3. RESULTADOS:
Um total de 137 pacientes entraram para o estudo (86 homens e 51
mulheres).
A sensibilidade e especificidade da escala ASEX para identificação de
disfunção sexual em relação à pontuação da DGSFi foram, respectivamente:
80.8%, (95% IC= 70.0%-88.5%) e 88.1% (95% IC= 76.5%-94.7%), e a taxa de
classificação incorreta foi de 9.5%. A curva ROC, comparando a pontuação da
ASEX e da DGSFi, revelou um valor de 0.93 (IC= 0.879-0.970), com o ponto
de corte da ASEX para disfunção sexual encontrado sendo 14/15.
Disfunção sexual medida pela ASEX foi mais alta em pacientes do sexo
feminino (79.2%) do que no sexo masculino(33.3%), e esta diferença foi
Pacientes em uso de antipsicóticos apresentaram disfunção sexual
estatisticamente significativa em relação à disfunção sexual e lubrificação
vaginal. A mais alta porcentagem de disfunção ocorreu com pacientes que
usavam combinação de antipsicóticos (61.5%), seguido pela combinação de
antipsicóticos e antidepressivos (50)%. Pacientes em tratamento com
antipsicóticos de segunda geração apresentaram maior probabilidade de
disfunção (28.1%) do que aqueles em uso de antipsicóticos de primeira
geração (13.6%), sendo a diferença estatisticamente significativa (Teste Exato
de Fisher, p=0.00108).
4. DISCUSSÃO E CONCLUSÃO:
O questionário ASEX provou ser um instrumento de boa acurácia para
identificar disfunção sexual quando comparado à validade do questionário
DGSFi. A sensibilidade e a especificidade foram consideradas adequadas. É
um questionário auto-administrável amigável, que leva poucos minutos para
ser completado e é apropriado para indivíduos com e sem parceiros sexuais
estáveis 32,33.
A freqüência das disfunções sexuais foi muito alta, um achado consistente
com estudos prévios e conduzidos em diversos países 4,8,17,35,36,37,38. As
pacientes do sexo feminino apresentaram taxas de disfunção sexual muito
mais altas do que pacientes do sexo masculino. Esta diferença entre gêneros
pode ser atribuída à fatores biopsicossociais, em especial: hormônios sexuais
ambiente (controlador X estimulante) 39. As pacientes do sexo feminino são claramente mais sensíveis aos efeitos dos antipsicóticos na prolactina 40,41,42. Em um estudo de 6 semanas, 63% dos homens tratados com haloperidol,
comparados à 98% das mulheres tratadas com haloperidol, tiveram um nível
de prolactina acima do limite normal 40.
Os pacientes que estavam em uso de antipsicóticos de segunda geração
(em relação ao item da ASEX ereção peniana/ lubrificação vaginal) tiveram
maior probabilidade de apresentar disfunção sexual do que os pacientes em
uso de antipsicóticos de primeira geração. Não podemos concluir que esta
afirmação seja verdadeira, já que se trata de um estudo transversal, que não é
o mais apropriado para este tipo de conclusão. Além disto não excluímos
pacientes com outras comorbidades, como depressão, diabetes, uso de álcool
ou cigarro e os pacientes não foram randomizados em sua seleção. O tamanho
da amostra é pequeno e não foram levadas em conta as doses de medicações
e medicações concomitantes que o paciente estava fazendo uso. Embora se
espere que os antipsicóticos de segunda geração estejam associados com
menor incidência de disfunção sexual 43,44,45,46,47,48,49,50 , outros estudos não
confirmaram estes achados 4,17, 27, 51. Acredita-se que o aumento de prolactina seja o principal responsável pela indução de efeitos adversos sexuais, mas o
mecanismo que está por trás da disfunção sexual causada por antipsicóticos é
metodológicas e dados conflitantes, a interpretação dos achados existentes na
literatura em relação a antipsicóticos levando à disfunção sexual é
inconclusiva 18.
Este estudo mostrou que a combinação de medicações (dois ou mais tipos
de antipsicóticos ou antipsicóticos e antidepressivos) levou a altas taxas de
disfunções sexuais. Portanto, tentar usar antipsicóticos em monoterapia ou
doses mais baixas, pode contribuir para uma vida sexual um pouco mais
saudável.
Pacientes com esquizofrenia apresentam certo nível de vida sexual que
não pode ser ignorada pelos médicos. Quando os pacientes estão estáveis do
quadro psicótico eles querem manter sua vida sexual. Por causa das altas
taxas de disfunção sexual, psiquiatras deveriam prestar mais atenção e
perguntar questões mais específicas sobre a rotina sexual de seus pacientes
na prática clínica. Escalas estruturadas podem ser úteis para diminuir o
desconforto e a vergonha dos médicos e pacientes quando esta questão é
levantada. Estudos controlados deveriam perguntar diretamente sobre efeitos
colaterais sexuais e investigar como tais efeitos adversos alteram a adesão à
medicação e a qualidade de vida. O desenvolvimento de instrumentos válidos
e confiáveis para uso em ensaios clínicos, como ASEX e DGSFi, podem
contribuir para obtenção de dados futuros relacionados à disfunção sexual
como efeito adverso 54 . Um estudo mostrou que a prevalência de disfunção sexual associada a quetiapina ou risperidona foi 11.7% baseada em relatos
espontâneos, mas subiu para 32% quando foi usada uma entrevista
disfunção sexual. Os estudos precisam levar em conta a variação individual
que constitui o funcionamento sexual normal e fatores de confusão que podem
afetar o funcionamento sexual 18 como diferença entre gêneros, uso de tabaco
e álcool, dificuldades no relacionamento, medicações prescritas e outros
sintomas clínicos e psiquiátricos. Já que a disfunção sexual apresenta alta
prevalência em pacientes do espectro da esquizofrenia, o cuidado e a
sensibilidade em relação a este importante efeito adverso e escolher o
tratamento certo pode contribuir para uma melhor qualidade de vida para estes
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47- Lambert M, Haro JM, Novik D, Edgell ET, Kennedy L, Ratcliffe M et al.
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48- Bobes J, Garcia-Portilla MP, Rejas J et al. Frequency of sexual dysfunction
and other reproductive side effects in patients with schizophrenia treated with
risperidone, olanzapine, quetiapine, or haloperidol. J Sex Marital Ther. 2003;
29: 125-147.
49- Gonzalez ALM, Villademoros R, Tafalla M. A 6-month prospective
observational study on the effects of quetiapine on sexual functioning. Journal
of Clinical Psychopharmacology 2005; 25(6): 533-538.
50- Kelly Deanna L, Conley RR. A randomized double-blind 12-week study of
51-Costa AMN, Lima MS, Faria M, Filho SR, Oliveira IR, Mari JJ. A naturalistic,
9-month follow-up, comparing olanzapine and conventional antipsychotics on
sexual function and hormonal profile for males with schizophrenia. J
Psychopharmacol 2006; May 19.
52- Breier AF, Malhotra AK, Su TP et al. Clozapine and risperidone in chronic
schizophrenic: effects on symptoms, Parkinson an side effects, and
neuroendocrine response. Am J Psychiatry 1999;156: 294-298.
53- Hummer M, Kemmler G, Kurz M et al. Sexual disturbances during
clozapine and haloperidol treatment for schizophrenia. Am J psychiatry
1999;156: 631-633.
54- Compton MT, Miller AH. Sexual side effects associated with conventional
and atypical antipsychotics. Psychopharmacolol Bull. 2001; 35: 89-108.
6. ANEXOS:
6.1 ANEXO 1: A acurácia da Escala de Experiência Sexual do Arizona (ASEX) para identificar disfunção sexual em pacientes do espectro da
esquizofrenia
Artigo enviado à Revista de Psiquiatria Clínica em 18/01/2009, recebido em 23/01/2009.
São Paulo, 18 de janeiro de 2008
REF.: ENVIO DE CARTA AOS EDITORES PARA PUBLICAÇÃO
Ao corpo editorial da Revista de Psiquiatria Clínica:
Estamos enviando o trabalho “A acurácia da Escala de Experiência Sexual do Arizona (ASEX) para identificar disfunção sexual em pacientes do espectro da esquizofrenia” para publicação
na seção de Artigos Originais desse conceituado periódico.
Cordialmente,
Luciana Vargas Alves Nunes Jair de Jesus Mari
Carta de recebimento do editor: Revista de Psiquiatria Clínica
Il.ma Sra.
Dra. Luciana Nunes
Prezada Dra. Nunes,
obrigado pela submissão do manuscrito:
”A acurácia da Escala de Experiência Sexual do Arizona (ASEX) para identificar disfunção em pacientes do espectro da esquizofrenia”
O trabalho será enviado a pareceristas e em breve lhe comunicarei a decisão editorial.
Com os cumprimentos cordiais,
A acurácia da Escala de Experiência Sexual do Arizona (ASEX) para identificar disfunção sexual em pacientes do espectro da esquizofrenia
Luciana Vargas Alves Nunes, M.D, MSc. Student, Department of Psychiatry , Universidade Federal de São Paulo, São Paulo, Brazil *.
Luiz Henrique Junqueira Dieckmann, M.D., Department of Psychiatry , Universidade Federal de São Paulo, São Paulo, Brazil.
Fernando Sargo Lacaz, M.D., Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil.
Rodrigo Bressan, M.D, PhD. , Department of Psychiatry , Universidade Federal de São Paulo, São Paulo, Brazil.
Tiemi Matsuo, phD, Department of Statistics, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
Jair de Jesus Mari , M.D., PhD, Department of Psychiatry , Universidade Federal de São Paulo, São Paulo, Brazil.
Resumo:
Contexto: a disfunção sexual é freqüente entre pacientes com esquizofrenia, sendo relatada como um dos mais incômodos efeitos adversos dos antipsicóticos e está diretamente relacionada com adesão ao tratamento.
Objetivo: a) avaliar a freqüência da disfunção sexual em uma amostra de pacientes do espectro da esquizofrenia em tratamento com antipsicóticos; b) investigar o efeito dos diferentes antipsicóticos na função sexual; e c) avaliar a acurácia da Escala de Experiência Sexual do Arizona (ASEX) para identificar disfunção sexual.
Método: pacientes ambulatoriais com esquizofrenia ou transtorno esquizoafetivo foram
entrevistados através de questionários: ASEX e Escala Dickson-Glazer (DGSFi) para avaliação do funcionamento sexual, em uma única entrevista.
Resultados: 137 pacientes foram entrevistados. A sensibilidade e especificidade da ASEX em relação a DGSFi foram: 80.8% ( 95% IC= 70.0%-88.5%) e 88.1% (95% IC=76.5%-94.7%), e a taxa de classificação incorreta foi 9.5%. A curva ROC comparando a pontuação da ASEX e DGSFi revelou valor de 0.93 (IC=0.879-0.970) com o ponto de corte da ASEX encontrando sendo 14/15. A disfunção sexual foi mais alta entre as mulheres (79.2%) do que nos homens (33.3%) (χ2=27.41,
gl=1, p<0.001).
Conclusão: pacientes em tratamento com antipsicóticos mostraram alta freqüência de queixas sexuais e ASEX provou ser um instrumento eficaz para identificar disfunção sexual em amostra de pacientes ambulatoriais do espectro da esquizofrenia. Mulheres mostraram freqüência mais alta de disfunção, e desejo sexual e habilidade para alcançar orgasmo foram áreas mais afetadas. O uso de antipsicóticos, principalmente o uso de combinações, foi associado com piora do funcionamento sexual.
Palavras-chaves:
The accuracy of the Arizona Sexual Experience Scale (ASEX) to identify sexual dysfunction in patients of the schizophrenia spectrum
Abstract
Background: sexual dysfunction is frequent in patients with schizophrenia, it is reported as one of the most distressing antipsychotic’s adverse effects and it is directly related to treatment
compliance.
Objective: a) to assess the frequency of sexual dysfunction in a sample of outpatients with
schizophrenia and schizoaffective disorder under antipsychotic therapy; b) to investigate the effect of different antipsychotics on sexual function; and c) to evaluate the accuracy of the Arizona Sexual Experience Scale (ASEX) to identify sexual dysfunction.
Method: Outpatients with schizophrenia or schizoaffective disorder were asked to fulfill both the ASEX and the Dickson Glazer Scale for the Assessment of Sexual Functioning Inventory (DGSFi) at a single interview.
Results: 137 patients were interwied. The sensitivity and specificity of the ASEX in relation to
DGSFi were: 80.8%, (95% CI= 70.0%-88.5%) and 88.1% (95% CI= 76.5%-94.7%), and the misclassification rate was 9.5%. The ROC curve comparing the ASEX and the DGSFi scores revealed a value of 0.93 (CI= 0.879-0.970),with the optimum cut-off point of ASEX being 14/15. Sexual dysfunction measured was higher in females (79.2%) than in males (33.3%) (χ2 = 27.41,
d.f.=1, p<0.001).
Discussion: Patients under antipsychotic treatment showed a high level of sexual complaints, and the ASEX proved to be an accurate instrument to identify sexual dysfunction in an outpatient sample of patients with schizophrenia spectrum. Females showed a higher frequency of sexual dysfunctions and sexual drive and ability to reach orgasm were the most affected areas. The use of antipsychotics, especially the combinations, was more likely to impair sexual functioning.
Keywords:
1.Introduction
Long term treatment is indicated for all patients with schizophrenia 1. Antipsychotic drugs can be of great benefit for a wide range of psychotic disorders, although
treatment can be associated with potential and unpleasant adverse effects 2.
Antipsychotic drugs may restore sexual desire lost for patients with schizophrenia,
but they can also impair the patient’s sexual performance 3,4,5. Antipsychotics can cause sexual dysfunction through multiple mechanisms, including sedation,
hyperprolactinaemia (wich can cause sexual dysfunction directly and indirectly by
causing secondary hypogonadism) and antagonism of α-adrenergic, dopaminergic,
histaminic and muscarinic receptors 2. Moreover, there are many other factors that may cause sexual problems for patients with schizophrenia, including concomitant
medications, the effect of the disease itself, comorbidity with other psychiatric
disorders and various endocrine, vascular or genitourinary diseases 6. Negative symptoms of the disorder, such as anhedonia, avolition and blunted affect related
to hypodopaminergic activity in the frontal cortex, severely harm the ability to enjoy
sexual life. These patients face difficulties in establishing relationships due to
recurrent psychotic episodes, obesity and low self-steem 7.
It is noteworthy that a recent study conducted by Plevin 8 reported that 73% of men
presented complaints in at least one area of antipsychotic-induced sexual
dysfunction: a) erectile, ejaculatory, and orgasmic dysfunction 9,10,11,12,13,14,15,16 b) low sexual desire 11,13,14,15,16 and c) priapism 12. Although fewer studies have been
areas: a) lack of orgasm 11,13,17,18 b) low lubrification 13,19 c) loss of libido14,19 and d) amenorrhea 11. Sexual dysfunctions induced by antipsychotic treatment can be responsible for non-adherence to treatment 20 and non compliance is one of the
main obstacles to an adequate control of the symptoms present in patients with
schizophrenia 21. Moreover, sexual dysfunction is rated as one of the most distressing adverse effects of antipsychotic treatment 22,23 and experienced by patients as significantly more distressing than sedation, or extrapyramidal side
effects 22.
At present, there are three scales available to asses sexual dysfunctions in
patients under antipsychotic treatment: a) the Dickson and Glazer Scale for the
Assessment of Sexual Functioning Inventory (DGSFi) 24; b) the Arizona Sexual Experience Scale (ASEX), 25 c) the Psychotropic-Related Sexual Dysfunction
(PRSexDQ-SALSEX) 26. Unlike the more traditional and lengthy scales for assessing sexual dysfunctions, the ASEX can be completed in approximately 5
minutes 27 and it was designed to be self- or clinician-administered. In addition, the ASEX questionnaire can be used for heterossexual and homossexual populations,
as well as for those without sexual partners 28 .
Antipsychotic-induced sexual dysfunctions are poorly recognized, and not properly
disorder under antipsychotic therapy; b) to investigate the effect of different
antipsychotics on sexual function; and c) to evaluate the accuracy of the ASEX to
identify sexual dysfunction.
2.Methods
A cross-sectional study of sexual function was conducted with 1-year consecutive
outpatients from the Schizophrenia Program of the Universidade Federal de São
Paulo (Proesq), from February 2007 to January 2008. The study was submitted
and approved by the Ethics Committee of the Universidade Federal de São Paulo,
and participants signed a written informed consent to participate. Eligible subjects
recruited were stabilized outpatients who met DSM-IV criteria for schizophrenia
and schizoaffective disorder under antipsychotic therapy for at least 4 weeks. The
patients were currently receiving a fixed dose of a first- or second-generation
antipsychotic (risperidone was analyzed separately since it is an antipsychotic that
frequently causes hyperprolactinaemia), or a combination of first- and
second-generation antipsychotics, or a combination of antipsychotics and antidepressants.
Patients consecutively attending the outpatient clinic were asked to fulfill a
questionnaire comprising information on social and demographic characteristics,
clinical symptoms, pharmacologic treatment, substance use disorders, sexual
function, presence of partner, and time of disease onset, followed by the
application of the ASEX and the DGSFi.
The DGSFi was developed by Ruth Dickson and Willian Glazer in the University of
Calgary, Canada, to assess sexual dysfunctions in patients suffering from
schizophrenia spectrum disorders. It is a computerized assessment, categorical
and qualitative, of sexual functioning and was developed to be easy for the
researcher to obtain detailed information reducing embarrassment and discomfort
for patients. The DGSFi is a computerized self-report questionnaire of sexual
functioning with parallel versions developed for males (32 questions) and females
(41 questions). It is a multiple choice questionnaire aiming to assess sexual activity
frequency, desire, arousal, and orgasm for both solitary and partner sexual
activities and perceptions of medication side effects for the prior 2 weeks 24. A Brazilian version of the DGSFi was adapted and used by Costa et al. 30 to compare the frequency of sexual dysfunction between first-generation
antipsychotic treatment and olanzapine.
The ASEX was developed by McGahuey et al. in the University of Arizona in
response to the need for evaluating psychotropic drug-induced sexual dysfunction.
Initially, the scale was tested to assess sexual dysfunction among selective
serotonin reuptake inhibitor (SSRI)-treated subjects 25 and end-stage renal disease
31. Byerly et al. tested the psychometric properties of ASEX in patients with
schizophrenia and schizoaffective disorder and demonstrated that ASEX
represents an easy-to-administer tool for assessing sexual dysfunction in this
erection/vaginal lubrification, ability to reach orgasm, and satisfaction with orgasm
over the past week 25. Items are rated on a 6-point scale ranging from
1(hyperfunction) through to 6 (hypofunction), providing a total score range between
5 and 30. A total score > 18, or a score ≥ 5 (very difficult) on any single item or any
three items with individual scores ≥ 4 is indicative of clinically significant sexual
dysfunction.
3.Results
The sociodemographic and clinical characteristics of the sample can be seen in
Table I. The sample was comprised of 137 patients, with an excess of males
(61.3%). The mean age of the sample was 37±10.3 years. Most patients were
Caucasians (62.0%), with a mean of 11.6 ± 4.1 years of schooling. Most patients
were unemployed (78.1%).Most patients were single (82.6% men and 78.4%
women), and only few patients (2.9%) were married (3.5% of men and 2% of
women), or had a stable partner (9.3% of men and 3.9% of women). The mean
duration of illness was 14.4 ± 9 years, with no difference between sexes. Patients
on second-generation antipsychotics (without risperidone) corresponded to 46.7%
(n=64) of the sample and patients on first-generation antipsychotics corresponded
to 16.1% (n=22). Risperidone was used by 14 patients (10.2%). Combination of
antipsychotics was taken by 13 patients (9.5%) and combined antipsychotics and
All the patients (n=137) filled both questionnaires (ASEX and DGSFi). The internal
consistency of the ASEX was estimated by means of the Cronbach’s coefficient
(=0.81), and mean Pearson’s correlation for the five ASEX items was 0.47. Table
II displays the distribution of the ASEX scores against the DGSFi scores. As it can
be seen in Table II, sensitivity was 80.8% (95% CI= 70-88.5), specificity was
88.1%(95% CI= 76.5-94.7), predictive positive value (PPV) was 90% (95%
CI=79.9-95.5), and negative predictive value (NPV) was 77.6% (95%
CI=65.5-86.5). The misclassification rate was 9.5%. As it can be seen in Figure 1 the
comparison between the ASEX and the DGSFi scores resulted in an area under
the curve value of 0.93 ± 0.021 (95%CI= 0.88-0.97, p=0.0001). The ASEX cut-off
point for sexual dysfunction was found to be 14/15.
Table III displays the distribution of penile erection or vaginal lubrification
dysfunction according to type of treatment. The highest percentage of dysfunction
occurred for patients under the combination of antipsychotics (61.5%), followed by
combined antipsychotics and antidepressants (50%). Patients under
second-generation antipsychotics presented a higher probability of dysfunction (28.1%)
than those under first-generation antipsychotics (13.6%), the difference being
statistically significant (Fisher’s exact test, p=0.00108).
For the ASEX items sexual drive, arousal, and satisfaction, there were no statistical
Table IV displays the distribution of sexual dysfunction between genders across
the pharmacological interventions. Sexual dysfunction measured by ASEX was
higher in females (79.2%) than in males (33.3%), and the difference was
statistically significant (chi-square = 27.41, d.f.=1, p<0,001). The mean ASEX
scores for females (19.53 ± 5,69) was higher than those found for males (13.71 ±
5.78), and this difference was statistically significant (t=5.77, d.f.=1, p< 0,001).
Females were more likely to have higher difficulty in sexual drive than males when
using medications, the difference being statistically significant (Fisher’s exact test,
p=0.0131). Moreover, females had higher probability of dysfunction in reaching
orgasm than males when under pharmacological interventions, the difference
being statistically significant (Fisher’s exact test, p=0.0225). The distribution of
sexual dysfunction by gender in the ASEX scores can be seen in Table V. Sexual
functions as sexual drive (χ2=19.38, d.f=1, p<0.001), sexual arousal (χ2= 14.29,
d.f.=1, p<0.001), orgasm (χ2=26.17, d.f=1, p<0.001) and satisfaction with orgasm
(χ2=12.26, d.f=1, p<0.001) occurred in higher frequency in females than in males,
and these differences were all statistically significant.
4.Discussion
The ASEX questionnaire proved to be an accurate instrument to identify sexual
dysfunction when compared to the validity of the DGSFi questionnaire. Sensitivity
and specificity were fairly high at a c.o. p. = 14/15. It is a friendly self-administered
individuals without stable sexual partners 27,28. The frequency of sexual
dysfunctions was very high, a finding consistent with previous studies conducted in
different countries 6,11,15,32,33,34,35. Females had a much higher rate (79.2%) than
males (33.3%). Indeed, females reported high frequencies of sexual dysfunctions
in all stages of sexual activities (sexual drive, arousal, vaginal lubrification, ability to
reach orgasm and satisfaction with orgasm). This difference between genders can
be attributed to biopsychossocial factors, in special: sexual hormones (estrogens x
androgens), sexual education (repressing x permissive), environment (controlling x
stimulant) 36.
Patients under second-generation antipsychotics had a higher probability of
dysfunction (28.1%) than those under first-generation antipsychotics (13.6%).
Antipsychotic medications were associated to disturbance on penile erection and
vaginal lubrication reported in ASEX questionnaire and had scores ranging
progressively for first-generation antipsychotics (13.6%), second-generation
antipsychotics without risperidone (28.1%), risperidone (21.4%), combination of
antipsychotics (61.5%), or combination of antipsychotics and antidepressants
(50%).
Although new second-generation antipsychotics were expected to be associated
with a lower incidence of sexual dysfunction as compared with first-generation
fact that the causes for sexual dysfunction of antipsychotics were exclusively
secondary to hyperprolactinemia, is that clozapine produced little or no change on
serum prolactin concentration 46, but high rates of sexual side effects in a
prospective drug monitoring program 47. Because of the scarcity of comparative
studies, conflicting data and methodological issues, the interpretation of the
findings of antipsychotics leading to sexual dysfunctions are inconclusive 2.
In our study, the pharmacological interventions were different between genders:
women under long-term treatment with antipsychotics, especially with
combinations of antipsychotics or antipsychotics and antidepressants, had
significantly more sexual dysfunction in the items related to sexual drive (p=0.0131)
and orgasm (p=0.0225); men had no significant difference between the items when
analyzed separately. This difference may be explained because women are clearly
more sensitive than men to the effects of antipsychotics on prolactin 48,49,50. In a 6-week study, 63% of treated men, compared with 98% of
haloperidol-treated women had a prolactin level above the upper limit of normal 48. There are few systematic data available regarding the frequency of impaired sexual interest
or function with antipsychotic treatment, and almost all studies are cross-sectional
51. Although less research on this subject has been conducted in women than in
men with schizophrenia, there is evidence that sexual and hormonal dysfunction is
also commom in antipsychotic-treated women. In addition, 33% of women
complained of change in quality of orgasm in a cross-sectional study 52. One study comparing sexual side effects in patients treated with haloperidol and clozapine
sexual desire in 28-33% of women 47. Another study examining sexual function in women treated with typical antipsychotics found a similar proportion (22%),
reporting decreased ability to achieve orgasm with antipsychotic treatment 17.
There is a need of sexual dysfunction studies including women. Many clinical
studies have tended to enlist few women or have excluded them altogether 53. Women may underreport the frequency of sexual side effects because they are
embarassed to discuss this topic. There is a naturalistic study of galactorrhea
incidence in women treated with typical antipsychotics, 20 of 28 women who
developed galactorrhea failed to spontaneously report this side effect on general
inquiry by treating physician about medication side effects 54, so it is important to
develop scales that let women confortable to discuss sexuality.
This study had some limitations that should be considered when interpreting the
data. First, all patients were recruited with ages ranging from 20 to 66 years. The
sexual dysfunction worsens with age since 39% of 40-year-olds have some degree
of erectile dysfunction (5% are completely impotent), but by the age of 70, two
thirds have some degree of erectile dysfunction and complete impotence triples to
15% 55. Second, in this study there were no exclusion criteria such as comorbid depressive syndrome or diabetes, treatment with antidepressants, use of alcohol or
cigarette smoking, and thyroid problems. This is not a longitudinal study, and there
were no measurements of the effects of the illness on sexual functioning prior to
medication treatment. Since this is a croos-sectional study, sexual dysfunction was
drug-induced or other causative factors. Because of the small sample size it was
not possible to draw conclusions regarding cause and effects and possible
relationship of antipsychotic doses. However, it is known that the side effects of
certain drugs are drug-dependent 42.
Schizophrenic patients have a certain level of sexual life that cannot be ignored by
physicians. When patients are stable, they want to maintain their sexual life.
Because of the high rates of sexual dysfunction, psychiatrists should pay more
attention and ask specific questions about their patients’ sexual life in routine
clinical practice. Structured scales can be useful to diminish the embarrassment
and discomfort for patients and physicians when this issue is raised. Controlled
studies should directly inquire about sexual side effects and investigate how such
side effects alter medication compliance and quality of life. The development of
reliable and valid detailed side effect rating scales for use in research trials and in
clinical encounters, such as the ASEX and DGSFi, should help to further elucidate
data on sexual side effects 53. A study showed that the prevalence of sexual dysfunction associated with quetiapine or risperidone was 11.7% based on
spontaneous reports, but increased to 32% when assessed using a
semi-structured interview 34. Thus, use of structured scales can yield a higher incidence of sexual dysfunction. There is a need of studies on multifactorial etiology of sexual
dysfunction. Studies need to account for individual variation in what constitutes
normal sexual functioning and confounding factors that can affect sexual
functioning 2. These include differences between genders, alcohol and tobacco
psychiatric symptoms. Sexual dysfunctions are different between males and
females with schizophrenia and further research on this area should be conducted
to clarify this complex subject. This study showed that the combination of
medications (two or more kinds of antipsychotics and antipsychotics and
antidepressants) leads to high rates of sexual dysfunctions; therefore, trying to use
antipsychotic in monoterapy or lower doses, whenever possible, would be of great
benefit to the patient in terms of achieving a healthier sexual life. Since sexual
dysfunction has high prevalence in patients with schizophrenia spectrum,
psychiatrists’ awareness and sensitivity regarding this important side effect and
choosing the correct treatment would contribute to a better quality of life for these
patients.
Acknowledgments
The authors thank Anna Maria Niccolai Costa for her assistence throughout the
Table 1 - The sociodemographic and clinical characteristics of the schizophrenia spectrum outpatients
Male Female Total P Value
Gender (n e %) 84 (61.3%) 53 (38.7%) 137 <0.001
Age, years (mean, SD) 36.7 (SD=9.6) 37.5 (SD=11.4) 37.0 (SD=10.3) 0.663* t
Marital Status (n e %)
Married 3 (3.5%) 1 (2.0%) 4 (2.9%) 0.144† f
Stable Partner 8 (9.3%) 2 (3.9%) 10 (7.3%)
Single 69 (82.6%) 42 (78.4%) 111 (81.0%)
Widow - 2 (3.9%) 2 (1.5%)
Divorced 4 (4.7%) 6 (11.8%) 10 (7.3%)
Race/Ethnicity (n e %)
Caucasians 55 (65.5%) 30 (56.6%) 85 (62.0%) 0.673‡ q
Asians 10 (11.9%) 11 (20.8%) 21 (15.3%)
Africans 2 (2.4%) 2 (3.8%) 4 (2.9%)
Mestizos 9 (10.7%) 5 (9.4%) 14 (10.2%)
Others 8 (9.5%) 5 (9.4%) 13 (9.5%)
Mean years of schooling 11.8 (SD=4.1) 11.4 (SD=4.0) 11.6 (SD= 4.1) 0.632* t
Employment Status
Unemployed 65 (77.4%) 43 (81.1%) 108 (78.8%) 0.601‡ q
Employed or Studying 19 (22.6%) 10 (18.9%) 29 (21.2%)
Illness Duration (years, mean, SD) 14.4 (SD=9.1) 14.0 (SD=8.8) 14.4 (SD=9.0) 0.779* t
Medications
First Generation 11 (13.1%) 11 (20.8%) 22 (16.1%) 0.062‡ q
First + Second Generation 5 (6.0%) 8 (15.1%) 13 (9.5%)
Risperidone 10 (11.9%) 4 (7.5%) 14 (10.2%)
Antipsychotics + Antidepressants 12 (14.3%) 12 (22.6%) 24 (17.5%)
Number of admissions 3.6 (SD=11.3) 2.2 (SD=2.3) 2.4 (SD=3.5) 0.468§ u
Sexual Dysfunction 28(33.3%) 42(79.2%) P<0.001‡ q
* Student’s
t test
† Fisher’s exact test
‡ Chi-square test
Table 2 - The validity coefficients comparing the ASEX scores against the DGSFi scores
DGSFi
dysfunction
DGSFi
No dysfunction
Total
ASEX
dysfunction
63 7 70 PPV=90.0
(C.I.=79.9-95.5)
ASEX
No dysfunction
15 52 67 NPV=77.6
(C.I.=65.5-86.5)
Total 78 59 N=137
Sensitivity=80.8
(C.I.=70-88.5)
Specificity=88.1
(C.I.=76.5-94.7)
Table 3 - The distribution of sexual dysfunction given by the ASEX questionnaire according to the pharmacological treatment
Penis erec/Vaginal lub (male and female) Medication
No Dysfunction
N %
With Dysfunction
N %
First-Generation Antipsychotics 19(86.4%) 3(13.6%)
Second-Generation Antipsychotics 46(71.9%) 18(28.1%)
Risperidone 11(78.6%) 3(21.4%)
Combination of antipsychotics 5(38.5%) 8(61.5%)
Antipsychotics and Antidepressants 12(50%) 12(50%)
Table 4 - The ASEX gender sexual distribution across pharmacological interventions in an outpatient sample of patients of the schizophrenia spectrum
Second
Generation
First
Generation
Risper. First+Second Generation
Antipsyc+Antidep
Female n=18 n=11 n=4 n=8 n=12 p-Value*
Male n=46 n=11 n=10 n=5 n=12
Sexual Drive
Female 12 (66.7%) 6 (54.6%) - 8 (100.0%) 8 (66.7%) 0.0131
Male 13 (28.3%) 2 (18.2%) 3 (30.0%) 1 (20.0%) 3 (25.0%) 0.9821
Arousal
Female 11 (61.1%) 5 (45.5%) 1 (25.0%) 6 (75.0%) 8 (66.7%) 0.4585
Male 13 (28.3%) 1 (9.1%) 4 (40.0%) 1 (20.0%) 3 (25.0%) 0.6044
Penis erec /Vaginal lubr
Female 6 (33.3%) 3 (27.3%) 1 (25.0%) 5 (62.5%) 9 (75.0%) 0.0802
Male 12 (26.1%) - 2 (20.0%) 3 (60.0%) 3 (25.0%) 0.1041
Orgasm
Female 12 (66.7%) 5 (45.5%) 1 (25.0%) 8 (100.0%) 10 (83.3%) 0.0225
Male 13 (28.3%) 2 (18.2%) 3 (30.0%) 1 (20.0%) 1 (8.3%) 0.6664
Satisfaction
Female 10 (55.6%) 3 (27.3%) 1 (25.0%) 5 (62.5%) 6 (50.0%) 0.4573
Male 10 (21.7%) - 4 (40.0%) - 2 (16.7%) 0.1578
Table 5 -The ASEX gender distribution of sexual dysfunction in an outpatient sample of patients of the schizophrenia spectrum
Male Female Total P value
n % n % n %
Sexual Drive 22 26.2 34 64.2 56 40.9 <0.001
Sexual Arousal 22 26.2 31 58.5 53 38.7 <0.001
Penis erection/
Vaginal
lubrification
20 23.8 24 45.3 44 32.1 0.009
Orgasm 20 23.8 36 67.9 56 40.9 <0.001
Satisfaction
Figure 1: The ROC curve and 95% confidence interval, comparing the ASEX and the DGSFi scores.
asextot
0 20 40 60 80 100
100
80
60
40
20
0
100-Specificity
S
en
si
tiv
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