Transcript Sexual Dysfunction Related to Psychotropic Drugs

Sexual Dysfunction Related
to Psychotropic Drugs
Dr Maryam Banihashemi
Resident of psychiatry
Roozbeh Hospital
It is not Easy to determine if a Drug
Disrupts Sexual Function or Not:
*Many Diseases Affect Sexual Function
*Sexual Problems may not be Reported
due to Feeling Embarrassed
Actual Rate of Sexual Dysfunction due to Drugs
may be Higher than Reported
The burden of sexual dysfunction is not
only relevant to drug
compliance: sexual functioning
impacts significantly on
quality of life
Psychopharmacological effect of neurotransmitters on the 3 stages
(desire, arousal and orgasm) of the human sexual response
Stage 1: DESIRE
Stage 2: AROUSAL
Stage 3: ORGASM
dopamine (DA) ( + )
dopamine (DA) ( + (
serotonin (5HT) (–)
melanocortin ( + )
melanocortin ( + )
norepinephrine (NE) (+)
testosterone ( + )
testosterone ( + )
dopamine (DA) ( + /–)
estrogen ( + )
estrogen ( + )
nitric oxide (NO) ( + /–)
prolactin (–)
nitric oxide (NO) ( + )
serotonin (5HT) (–)
acetylcholine (Ach) ( + )
norepinephrine (NE) (+)
serotonin (5HT) (–)
Antidepressants
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Major depression is the most common mental
disturbance .
Sexual dysfunction is a potential side effect of
antidepressant drugs .
Antidepressants with strong serotonergic
properties have the highest rate of sexual side
effects .
Other mechanisms
Antidepressant-induced sexual
dysfunction is mainly due to a
sexual inhibitory action
Delayed ejaculation : The most common
Delayed and/or absent orgasm
Reduced and/or lack of sexual desire
Reduced and/or absent sexual arousal
Enhanced sexual functioning : More rarely
Percentage of sexual dysfunction
Class
Drug
Percentage
Class
Drug
Percentage
SSRI
citalopram
79%
SNRI
venlafaxine
80%
escitalopram
37%
duloxetine
42%
fluoxetine
70%
amineptine
7%
fluvoxamine
26%
imipramine
44%
paroxetine
71%
phenelzine
42%
sertraline
80%
moclobemide
4%
mirtazapine
24%
nefazodone
8%
bupropion
10%
agomelatine
4%
Others
TCA
MAOI
Others
TCAs :
• Clomipramine , amitriptyline and imipramine
: higher rates of sexual dysfunction
• Desipramine and nortriptyline : lower rates
of sexual dysfunction
• Clomipramine : Treatment of patients with
premature ejaculation (With daily dosing of
12.5-50 mg )
SSRIs :
• Sertraline and Paroxetine : Difference
in sexual side effects between men and
women
• Delayed ejaculation : Paroxetine ,
Citalopram & Sertraline
• Dapoxetine : Exclusive indication is the
treatment of premature ejaculation
Other antidepressants :
• Venlafaxine has not been shown to be
effective in the treatment of premature
ejaculation
• Bupropion : Improvement in
psychosexual function
• Nefazodone and Trazodone are
associated with a very low incidence of
sexual dysfunction
• …
Case :
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Female/35 yrs
Depression from 9 mo. Ego
Citalopram : 40mg/d
Increased low desire ( 6 mo.)
Delayed orgasm
Treatment of
Antidepressant-Induced Sexual
Dysfunction
1. Wait for a spontaneous
reduction of side effects over time
2. Reduce dose of drug
3. Arrange a temporary drug reduction or a
suspension of drug for 2 days in the week :
“therapeutic vacation” or “drug holiday”
This strategy does not apply to fluoxetine due to
its longer half-life
4. Switch to a different antidepressant
drug with fewer sexual side effects
bupropion, mirtazapine, or
nefazodone
5. Add a symptomatic therapy
-Other antidepressants : Bupropion,Nefazodone or
Mirtazapine
-Partial serotonergic agonists and also partial
alphanoradrenergic antagonist : Buspirone
-Serotonin antagonist : Cyproheptadine
-Alpha-adrenergic antagonist : Yohimbine
-Dopaminergic agonists : Amantadine , Bromocriptine
-Psychostimulant dopamine agonists :
Methylphenidate and dextroamphetamine
-Cholinergic enhancers : Neostigmine, Bethanechol
-Phosphodiesterase inhibitors : Sildenafil, Tadalafil
-Herbal medicines : Ginkgo biloba , Ginseng
Antidote
Sexual
Dysfunction
Dose Range
Neostigmine (Males)
 Libido; Impaired
Ejaculation
7.5-15 mg ½ hr Before
Sexual Activity
Bethanechol Chloride
(Males and Females)
Anorgasmia; Impotence;
Impaired Ejaculation
F: 12.5 mg HS
M: 10-20 mg ½-2 hr before
Sexual Activity or 30-100
mg/d
Cyproheptadine
(Males and Females)
Anorgasmia
F: 4-12 mg 1.5-4 hr before
Sexual Activity or 8
mg/d
M: 8-12 mg 1-2 hr before
Sexual Activity or 16
mg/d
Yohimbine
(Males and Females)
Anorgasmia;  Libido;
Impaired Erection
F: 6.75-10.8 mg 2-4 hr
before Sexual Activity
or 5.4 mg TID
M: 5.4-16.2 mg 1.5-4 hr
before Sexual Activity
or 5.4 mg TID
Amantadine
(Males and Females)
Anorgasmia;  Libido;
Impaired Erection
100-200 mg/d
Side Effects
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F: Irritability; Visual
Hallucinations; Reversal
of Antibulimic Effects of
Fluoxetine; Sedation
M: Sedation
F: Insomnia; Nausea;
Shakiness
M: Anxiety; Insomnia;
Urinary Frequency;
Nausea; Fatigue; Sweating
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Antidote
Sexual
Dysfunction
Dose Range
Trazodone
(Males and Females)
Anorgasmia;
Impotence
Ginko Biloba
(Males and Females)
 Libido; Anorgasmia;
Impaired Erection
40-60 mg BID;
Increased to 120 mg
BID
gastrointestinal
disturbances;
headache; CNS
Activation; Increased
Bruising
Sildenafil
(Males and Females)
 Libido; Anorgasmia;
Impaired Erection;
Impotence
25-100 mg 1 hr before
Sexual Activity
Headache; Flushing of
the Face; Upset
Stomach; Nasal
Congestion; Priapism;
Visual Problems
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Side Effects
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Ginko Biloba
Mechanism of Action of Ginko Biloba for Reversing
Antidepressant-Induced Sexual Dysfunction
*Enhanced Vascular Flow to the Genitals through Inhibition
of Platelet-Activating Factor
*A Direct Effect of the Extract on Prostaglandins, which
Enhance Erectile Function
*Serotonin and Norepinephrine Receptor-Induced Effects on
the Brain
Ginkgo Biloba was Found to be 84% Effective in Alleviating
Antidepressant-Induced Sexual Dysfunction
 Women (n = 33) more Responsive than Men (n = 30)
 Relative Success Rates: 91% versus 76%.
Pharmacological Treatment for Sexual Pain
Disorders
Includes Treatment of Underlying Cause :
* Estrogen for Vaginal Atrophy or Antifungal
for Vulvovaginal Candidiasis
* TCA ,Other Antidepressants, anticonvulsants,
and Topical Agents for Vulvar Vestibulitis
Vulvodynia
(burning pain during sex)
Testosterone Cream, with use of
biofeedback, and with Low Doses of some
Antidepressants which also Treat Nerve Pain
(eg. Venlefaxine).
Surgery has not been Successful.
Antipsychotics
*The mechanism of action leading to sexual dysfunction is more
complex
*Hyperprolactinemia is caused by blockage of dopamine D2
receptors in the hypothalamic infundibular system (which can
inhibit sexual function)
*There have also been reported cases of sexual dysfunction with
normal prolactin levels : in these cases, the sexual dysfunction
was probably associated with other physical (e. g., diabetes) or
psychological (e. g., quality of partner relationship) factors
Sexual dysfunction (SD) and antipsychotics
Haloperidol
High rates of SD, more than 70 %. No significant difference in SD compared to risperidone.
Haloperidol tends to elevate prolactin levels .
Risperidone
High rates (60–70 %) of SD similar to those for haloperidol, other typical antipsychotics and
clozapine . Significantly higher levels of SD compared to quetiapine and olanzapine . Commonly
reported SD included decreased libido,
erectile dysfunction, ejaculatory problems, impaired orgasm, menstrual irregularities and
decreased vaginal lubrication . Risperidone tends to elevate prolactin levels .
High levels of prolactin induced by risperidone, tend to decline over a period of years and that
prolactin levels did not correlate significantly with sexual dysfunction.
Olanzapine
High SD rates ( > 50 %) similar to haloperidol or other typical antipsychotics reported in some
studies .
Switching from typical antipsychotics or risperidone to olanzapine may improve sexual
functioning in men and women . Olanzapine causes a transient increase in prolactin, which
returns to normal after a few weeks in most but not all patients .
Quetiapine
Prevalence of sexual dysfunction induced by quetiapine varies between 50 % and 60 %, and is
therefore similar or lower to that of risperidone . Quetiapine is not associated with increased
prolactin .
Aripiprazole
Lower SD for aripiprazole as compared with other antipsychotics. Aripiprazole seems to reduce
rates of SD in patients previously treated with
other antipsychotics . Switch from other antipsychotics or add aripiprazole seems to normalize
prolactin levels
Clozapine
High rates of SD but significantly lower as compared with olanzapine, risperidone, and typical
antipsychotics .
Treatment of sexual dysfunction induced by
antipsychotics
1. A thorough clinical evaluation, to
exclude comorbid conditions (physical and
psychiatric) or sexual dysfunction
secondary to alcohol or illicit drug use or
other prescribed medication. The
assessment should include measurement
of serum prolactin in patients presenting
with side effects suggestive of
hyperprolactinemia .
2.Modification of risk factors
(where possible, avoid use of other drugs associated
with sexual dysfunction, smoking cessation, abstinence
from alcohol and illicit drugs, maintaining normal
blood sugar levels in diabetic patients, treatment of
hypertension and hypercholesterolemia).
Thanks for your attention