Sexual Side Effects of Psychiatric Medications in Women: A Clinical

Sexual Side Effects of Psychiatric
Medications in Women: A Clinical Review
Laura L. Post, MD , FAACS
Abstract
S exual side dficts ofpsychiatric medications have been estimated to occur in 60% of male
clients (1) and 30%offemale clients (2). Despite a bodyofliterature relating individual medications
to specific sexual side dficts, fe to studies have satisfactorily addressed the psychotropic-induced
sexual dysfunctions in women. The spectrum ofknoton sexual side dficts resultingfrompsychopharmacologic interventions will be reviewed. GuidelinesJOr appropriately addressing the possibility qf
sexual side effects within a therapeutic relationship.for maximizing reporting ofsexual side dficts,
andfor possible treatment approaches to sexual side dficts will be described.
INTROD UCTION
The pa st tw enty years have shown a dram at ic su rge in t he a pproaches to and
tools of bio logical psychi atry. Concomit ant with th ese adva nces has e me rge d awareness of psychotropic-induced se xua l side effec ts. These side effec ts may con tribu te to
physiologi cal morbidity, to e m ba rras sme n t and sh am e, to non compli an ce, to stressinduced sym ptom exace r ba tion, and, argu ably, to mi stru st of psychi at ric pr actit ioners. R epresen ta t ives of severa l class es of psychiatric medi cations- including bcn zodiaz epines, beta-blockers, lit hi u m , monoamine oxidase inhibit ors, neu rol ep t ics, and
tri- and t etra-cyclic a nt ide pressa n ts- ha ve been report ed to ca use so me form of
se xua l impairm ent.
Kn own sex ua l side effec ts associat ed with psych otropi cs include anorgasmia (3) ,
un satisfyin g or painful or gasm (4), a lte re d libid o or sex ua l willing ness, erecti le
fa ilu re, priapi sm (5), menstrual irregul ariti es, d elayed o r ret ro grad e ejacu la t ion (6) ,
a nd a lte re d sexual se nsa tio n and se ns itivity (7,8) . Yet , th e se xual side effects of
psych o-pharmaceuticals are st ill a mo ng th e most subt le, least discu ssed , a nd poorly
und erstood co nse q ue nce s of modern m edi cal treatm ent s.
The psychiatric lit erature contains num erou s case report s but few well -designed
res earch st ud ies addressing sexu al side effec ts (9). This knowl ed ge ga p may reflect
wides pread e rot ophobic attitud es, skewed fundin g a nd ed uca t ional prio rit ies around
th e import an ce of human se xua lity, or inad equ a t e training of pr escribers in eliciting
se x ua l side effec ts from clients.
Laura L. Post , M.D. , recently co m ple te d he r res ide ncy in Psychi at ry at th e Langley Port er
Psych iatric In stitut e of th e U nivers ity of California in Sa n Fra ncisco.
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JEffERSON J O UR NAL OF PSYCHIATRY
In add it ion, very few of th e ex ist ing st ud ies include fe male subjects (10 ,11,1 2);
thos e that do oft en fail to separat e outcom es by ge nde r, renderin g problematic th e
drawing of conclus ions rel evant to wom en client s. The lack of a tt en tion to incid en ces
a nd ex pe rie nces of psych otropi c-gen e rat ed sexua l side effec ts in wom en may occ ur
for several reason s. First , th e ease of meas ureme n t of ma le se x ua l arou sal (e rec tio n)
an d o rgas m (ejacu la t ion) , a nd th e rel a tive simp licity of male e ndoc rine fun ction s,
m ay have co n t rib u te d to a researc h bias towa rd male sub jects, Second, th e sexua l
e mo t ions, respon ses, a nd beh aviors of wo me n a re fre q ue n t ly constrained by cult ur allybased and se xist cr ite r ia; th e sa me cult ura l se xism m ay reduce t he mo t ivation for th e
co m pre he ns ive exam ina t ion of th e pot ential ac tio ns of psyc hiatric medication s on
fem al e sex ua lity. (T his hyp oth esis is so mewha t s uppor te d by t he dearth of publi sh ed
info rmation on ge nera l fema le sex ua l funct ion) .
Third , th e na rrow d efin iti on s of fe male sexual dysfun ction may result in
incon sist e nt re po rt ing or inap propri at e dat a analysis . For example, qu eryin g lesbi a n
clients a bo ut int ercourse may be irrel evant ; not qu e ryi ng wom en specificall y a bou t
fant as y, a bo u t lubrication, a bo ut ejacula t ion, o r a bo ut th e size , shape , sens itivity, a nd
se nsa tio n of br east s, vagina, a nd clitoris m ay lead to om ission of vit al in fo r ma t ion.
Fi nall y, th e subjectivity inh erent in t he d e termi na tion and describing of sex ua l
impai r m e nt may lead to va ria tions betwe en studi es, introducing difficulty in com piling d at a: t he re is a d iffere nce bet wee n libido and orgasm . Neverthel ess, th e ava ilable
report s do sugges t so me ge neral patt erns of sexual sid e effec ts, in wom en , from
psych ot ropics.
SUMMARY OF PSYCH OTROPI C-IND UC ED SEXUAL DYSFUNCTI O NS IN
WO~IE N
In fema le pat ients, several psychopharmacologi c agent s have been implicat ed as
causative of sexual side effe cts. Alprazolam (13), amoxapine (14) , clo m ipram ine
(15,16, 17), dia ze pa m ( 18), flu phenazine ( 19), fluraz e pam (20) , imipramin e (21 ,22),
MAGIs (2 1,23,24,25,26), thio rid a zin e (27) , a nd t rifl uoroperazine (27) hav e all been
spec ifica lly rep o rt ed to inhibit orgas m . Fenflu ra m in e has bee n repor ted to enha nce
o rgasm (28).
H oweve r, th e story is not so st raightforward. Desip ra m ine has been rep ort ed to
ca use anorgasmia (29) and not to cause anorgasmia (22) . Fluox etin e has bee n
reported to in hib it orgasm (30,3 1,26) and to e nha nce orgasm (32) . Sim ila rly,
t ra zod one has bee n re ported to inc rease (33) and d ecrease (34) libido.
PERSPECTI VES ON PHARMACOSEXO LOGY
T he re la t ionship betwee n psychiatric medi cations and resultant se xua l dysfun ction is complex. Animal mode ls suggest that sexual fun ction is dep end ent upon
ce n t rally-act ing do pa mi ne agonis ts and is inhibi ted by th e se ro tone rgic syste m (35).
In hu m an males, decr eases in libido have been attribut ed to anti-dopam inergic
a nd se ro to nergic effec ts (36), as well as to limbic fluctu a ti on s a nd to d ecreased levels
of e ndoge no us o pioids a nd test ost e ron e (37). Hu ma n male e rec tion , m edi at ed
SEX UAL SIDE EFFE CTS OF PSYCHIATRIC MEDI CATIONS IN WOM EN
77
principally by autonomic neurons, may be diminish ed: a ) by int erferen ce wit h central
dopamin ergic output (38) ; b) by int erferen ce with bet a- adren ergic ac t ivity or by
e n ha nce me n t of a lp haj -ad rc ne rg ic transmission (39); c) by int erferen ce with th e
choline rg ic spinal refl ex es necessary for erec t io n; or d ) by int errupt ion of th e
neuronal-hem atological fillin g of the co rpo ra.
Human male ejac ula t ion, m ediat ed by alph a I-a d re ne rg ic rece p to rs, may be
a n ta go nize d by alpha I-a d re ne rgic blo ckad e. Hum an m al e o rgas m [which is no t
neces sarily id entical with ej ac u la tion], thought to be ce n t ra l in or igin, may be
e lim ina te d by seroton ergic age n t s (40). Cl early, th e se ro to ne rg ic agon ism, th e
dopaminergic a nd cholin ergic blo ck ade , and alpha I-ad re ne rg ic e ffec ts res ult ing from
som e psychiat ric medications might a Ite r sexual fun ction in m a le cli ent s (41) .
Though anatomic analogi es m ay be mad e between mal e a nd fe male libid o,
between male erection and femal e lubrication /labi al swelling , between m al e ejaculation and femal e ejaculation , and between male and femal e orgasm , th e neu rop hysiology of femal e sexuality-animal or human-is less co m ple te ly und erstood th an the
male counterpart. Conclusions about effe cts, on wom en , of a n t i-do pam ine rgic ,
a n ti-a lpha r-ad re nc rgic, anticholinergic, and seroton ergic e ffec ts remain th eoret ica l
a nd sp eculative.
C LINICAL DISCUSSION AND G UIDELINES
Psychotropic-induced sexu al sid e e ffec ts m ay be am eli orat ed with bioch e m icall yinform ed int erventions. Neverth el ess, ad equat e id entification and treat m e n t of
psychotropi c-induced se x ua l side e ffec ts require a n inform ed , di scernin g, and sensitiv e psychiatric pra ctition er, since m any pati ents will not s po n ta neo usly rep o r t su ch
co nce rns. What follow a re so me s ugges t ions for a pp ro p r ia te ly a dd ressing th e possibility of se x ua l sid e effec ts within a th erapeutic rel ati on ship, for max imi zing r epo rt ing
of se x ua l sid e e ffec ts, and for a p p ro ac hing treatm ent o f se x ual side e ffec ts.
When a pati ent ex pe rie nces a se x ual dy sfuncti on r elat ed to a psych iatric
m edication , the initial priorit y is to d et ermin e wh ether th e dysfunct ion is me d icationinduced. This may be don e, with so me ce rtain ty, by retracing sym p to m d evelop m e n t
in r elation to m edication dosing , in the a bse nce of ot he r prescribed or ove r- t hecou n te r m edications and in th e absence of co nc om ita n t e m o t io na l st ress. If an
e t iolog ica l con nect ion betwe en psychiatric m edication a nd se x ua l side e ffec t appears
likely, then the next st ep is to as se ss the ex te n t of di scomfort ex pe rie nce d by t he
patient, since the pati ent who is substantially both ered by th e dysfuncti o n will
participate most cooperatively in treating th e sid e e ffec t. Th e sim ples t trea t m en t
approach to psychotropic-indu ced se x ua l sid e effec ts is to ma ke only a psych olog ical
int ervention. In cert ain in st ances, suc h an ac t io n might be indicat ed ; anorgasmia
induced by MAGIs has been report ed to r emit naturall y (42) . An ad d it iona l psychological int ervention mi ght be re ferral to co u ples or individu al se x t herapy or
psychoth erapy, wh en rel evant. Howev er, se x ual side effec ts mu st be m onit ored , and
this minimalistic strat egy must be full y ex pla ine d to th e cli ent.
Another approach might be to r educe the dose of th e p u ta t ively offend ing
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JEFFERSON JOUR AI. OF PSYCHIATRY
psychiatric m edi cation . If dose re d uc t ion fa ils to a llev ia te th e sexual sympt om s, or if
th e primary psychiatric sym pto ms return, th en th e clinician mig ht consider dru g
substit u t io n from a different che m ica l class.
C ombination th erap y, with two psych ot ropi c agen ts be lieved to produce a n tagonisti c sex ual side effec ts, mi ght minimize t he sexual side effect of eac h while
maximizin g th e syne rg istic psych iatric effect. For instance , th e coupling oftrazod onewhich has been rep ort ed to increase libido in wo me n-and fluoxetine-which has
been report ed to decrease libido in wom en-mi ght prove useful.
The se lec t ive utilization of psych opharm acolo gic age nts no t associat ed with
se xual dysfuncti on may redu ce th e incid ence of suc h ia troge nic morbidit y. Sp ecifica lly, no publish ed report exis ts , as of this wr it ing, link ing buproprion or bu spi ron e
wit h sex ual side effects . In fact, bu sp ir on e has bee n report ed to reverse ge ne ra lized
sex ual dysfun cti on rel at ed to a nxie ty (43).
Prescription of a m edi cation used in treat m ent of e ndoge no us sexu al dysfun ction mi ght ass ist in returning th e patien t 's sex ual fu nct ion to baseline. Yohimbine
(44), naltrex on e, a nd a pomor phine ca n each a lleged ly e licit penile e rec tions (45); it is
unknown what influence th ey would exe r t up on wome n.
Addition of a second me d ica tion, aim ed a t addressing th e psych otropic-ind uced
sex ual dysfun ct io n, may have benefit. Seve ral reports have impli ed that libid o has
been e n hanced by t he cho line rgic age n t betha nechol (46,47) and by th e dopamine
ago nist bromocrip ti ne (48) . Several m ixed-gend e r reports have sugges te d t ha t
a no rgas m ia induced by MAGIs (49), fluoxet in e (50), a nd m ulticyclic antid epressants
(29,26,5 1) m ig h t be reduced by th e se ro to nin a n tago nist cyproheptad ine. How ever, it
is impo r tan t to keep in m ind t hat , j ust as primary psychiatric medications ca n e licit
sid e effects, so can adju nct ive medications. Cyproheptadine has been associat ed wit h
anticho linergic crisis in co njunction with treatm e nt of t ricyclic-induced a no rgasm ia
(29) .
A hel pful ove ra rc hing stra tegy is to develop a solid, mutually trusting clini cal
re lat io ns hip wit h each pa ti ent a nd to ro u t ine ly obtain a com plet e se xua l history
before prescribing a ny psych ot ropi c me dica tio ns. Not only does t he sexual inform at ion gat hered es tablish a baseline against which to det ect future cha nges in th e
patient 's sexua l fun ction, bu t direct ly bringing th e cli ent 's sexual histo ry into th e
pati ent -practit ioner in teraction a lso increases t he likel ihood th at th e client will fee l
welcom ed to discuss subjectively perceived changes in sexual fun cti on whic h may
a r ise. As ki ng abo ut specific practices, abou t partn e rs and relationships, and ab out th e
importance of sex ua lity in t he client's overall funct ioning will be more useful t han
simply querying broad ly abo ut sex ua l orientation, partn ership st atus, age a t pubert y,
or history of orgasm.
Practiti oners' co m for t di scussing issues of client sexu ality, practit ion ers' sexual
knowledge, and practitioners' sex-positive attitud es are a ll responsibl e fo r o btaining
thorough sexual histories a nd fo r eliciting, following up on , a nd for ed uca ting a bo u t
psychotro pic-ind uce d sexual side effe cts. Sex-positive at titudes will a lso permit
clinic ian- researc he rs to add to psychi a t ry 's un d e rstan d ing of t he possibl e insidi ou s
outcomes of prescr ibe d m ed ica t ions. In the lo ng run, psychiatric client s will ben efit
SEX UAL SIDE EFFECTS OF PSYCHIATRI C MEDICATIONS IN WOME
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directly from sex-positive attitud es , from op enness to a nd e m pa t hy toward clients'
sexual conce rn s, and from application of the mo st co m ple te ava ilable d at a about
sexual side e ffec ts .
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