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Pharmacological Treatment of
Paraphilias
Abdi Tinwalla, M.D.
Chief of Psychiatry
Wexford Health Sources
Illinois Department of Human Services
Treatment and Detention Facility
Rushville, IL
IL ATSA
March 16, 2017
Rushville TDF
Rushville TDF
The Commitment Process
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Pre-screen: all inmates in DOC with any sexual
offense are reviewed for initial eligibility (qualifying
offense).
Those with qualifying offenses reviewed with some
selected for interview/assessment.
Psychologist recommendation as to whether or not
individual meets the criteria for SVP.
Attorney General files petition in civil court for
probable cause.
The Commitment Process
(cont’d)
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Upon release from DOC, probable cause hearing held in civil
court in county of origin. If successful, order of detention is
issued and individual arrives at facility as pre-trial “detainee”.
Some states house detainees and individuals officially
committed as SVP in separate facilities.
Following finding of probable cause, evaluation process
begins again. State and defense evaluators conduct new
assessments and offer opinion to court regarding SVP criteria.
Once committed, re-evaluation occurs after 6 months, then
every 12 months thereafter
In states with a conditional release component, after
commitment can be placed in the community, following
demonstration of risk reduction.
Treatment of psychiatric illness
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About 10% of the population of Sex offenders
at the TDF suffer from Serious Mental Illness
such as Schizophrenia, severe Depression with
Psychotic features and Bipolar disorder.
Another 20 % suffer from mild to moderate
Depression and Anxiety disorders.
Substance abuse
Antisocial Personality Disorder
These illnesses make them more vulnerable to
commit any kind of offense.
Goals
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Reduce the deviant fantasies, urges and
behavior
Not to impair the non-deviant sexual behavior
Have minimal side effects
Neurobiology of Sexuality
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Highly complex
Substances produce stimulating and inhibiting effects
in CNS, peripheral nervous system and primary and
secondary sexual organs
Meston C.M. and Frohlich P.F. Neurobiology of
sexual function. Arch of general Psychiatry. 57
(2000)1012-1030
Rubinow D.R. and Schmidt P.J (1996) Androgens,
Brain and Behavior. Am J Psychiatry. 153, 974-984
Neurobiology of Sexuality
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2 types of substances
a) hormones such as Testosterone,
Progesterone, Prolactin, Luteinizing hormone
and Follicle Stimulating hormone
b) neurotransmitters and neuro-peptides such
as Serotonin, Gonadotropin Releasing
hormone, nitrous oxide, dopamine, adrenaline,
acetylcholine, histamines
Treatment of Paraphilia and
compulsive sexual behaviors
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1)
2)
3)
4)
Sexual drive consist of:
Subjective desire to engage in sexual activity
Sexual fantasies paraphilic and nonparaphilic
Sexual arousal
Sexual activity and orgasm
Treatment needs to target all these
components of sexual drive
Assumptions
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The suppression of sexual drive will result in a
decrease in sexual fantasies and urges and decrease in
paraphilic behavior
The aim of pharmacological treatment is to reduce or
suppress deviant sexual fantasies, urges, and behavior
while allowing the individual to remain sexually
active in a non-deviant manner.
Another theory views paraphilic behavior either as
Obsessive Compulsive behavior or as Impulsive
behavior. (Urges and behaviors are compulsions and
fantasies are obsessions)
Treatment of Paraphilia
Psychotherapy
 Surgery
 Pharmacotherapy

Psychotherapy
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It is the most common form of treatment
Consist of Cognitive, Behavioral and
Relapse prevention alone or in
combination in individual and group
setting.
Surgical Castration
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Widely used to treat paraphilia with aggressive
behaviors until the onset of pharmacological
treatment with CPA and MPA in 1970s.
Irreversible and intrusive hence restricted to
most severe and treatment resistant cases
It is legal in Texas but rarely used nowadays
because of ethical and legal considerations.
Surgical Castration
Study
Follow
up perio
Langeluddeke 20 years
1963
Cornu 1973 5 years
Bremer 1959 5-10 years
Sturup 1968 30 years
1972
N
Pre rate Post rate
1036
84
2.3
127
216
900
76.8
58
4.1
2.9
2.2
Pharmacotherapy
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Psychotropic medications such as SSRIs, mood
stabilizers such as Lithium and Antipsychotics such
as Haldol
Anti Androgens
1)Androgen receptor blockers - Flutamide
Bicalutamide and Nilutamide
2) Hormonal agent – Cyproterone Acetate (CPA)
and Medroxyprogesterone Acetate (MPA)
(Provera)
3) GnRH / LHRH agonist - Leuprolide (Lupron,
Eligard, and Viadur), Triptorelin (Trelstar),
Goserelin (Zoladex), and Nafarelin (Synarel)
4) GnRH antagonist – Cetrorelix and Abarelix
SSRIs

Possible mechanisms include:
a) general inhibition of sexual activity
b) reduction of impulsive behavior
c) reduction of obsessive compulsive behavior
d) improvement of depressive symptoms
e) indirect reduction of serum testosterone
levels
SSRIs
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Reduce sexual fantasies, desire, masturbation, and
sexual deviant behavior in patients with various
paraphilias
No double blind studies have been reported
The combination of SSRI with psychotherapy is more
effective than psychotherapy alone
SSRIs used include Paxil, Prozac, Luvox, Zoloft, and
Celexa and no different in treatment outcome was
found for the different SSRIs
SSRIs are helpful in patients with compulsive sexual
symptoms, co morbid affective symptoms
SSRIs
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In an open, uncontrolled, retrospective study
conducted by Strohm and Berner from Germany in
2001, 16 male outpatients were treated for different
paraphilias.
High rate of comorbid psychiatric disorders
Mean treatment duration was 23 months (2-78
months)
9 with Fluoxetine, 4 with Citalopram, 2 with
Sertraline and 1 with Paroxetine
All patients received supportive psychotherapy.
Marked reduction in paraphilic fantasies and
masturbation with high overall treatment satisfaction
SSRIs
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Improvement can be seen in 2-4 weeks and
maximum effect seen in 2-3 months
Same dosage as for mood disorders although
some patients with OCD symptoms may need
higher doses.
Anti androgen and hormonal agents have
limited use in adolescence due to potential side
effects
If retardation of ejaculation leads to increased
recruitment of paraphilic fantasies to reach
orgasm, the dosage can be reduced to target
paraphilic symptoms.
Testosterone
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90-95 % of the testosterone is produced in the
testes and 5-10 % is produced in the adrenal
gland.
Acts on intracellular androgen receptors in the
target organ which includes the prostate and
the limbic and hypothalamic system in the
brain and the penis.
Plays a crucial role in the development and
maintenance of secondary sexual
characteristics and in regulation of sexuality,
aggression, emotion and cognition.
Testosterone
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It is the major activator element of sexual desire,
fantasies and behavior and controls the frequency,
duration, and magnitude of spontaneous erections.
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In paraphilic patients the levels of testosterone are
usually within normal levels suggesting an
abnormal response to androgens by the receptors.
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Hence the anti-androgen therapy for sex offender
is based on the complete reduction of testosterone
and suppression at the receptor level
Hypothalmic Pituitary Axis
GnRH (aka LH-RH) is a decapeptide
synthesized in the hypothalamus and
secreted directly into the hypophysioportal
circulation
The secretion is pulsatile and stimulates
the release of Follicle Stimulating
Hormone (FSH) and Luteinizing Hormone
(LH) from the pituitary
LH and FSH drives the productions of
Testosterone from the testes
The continuous application (instead of the
pulsatile physiological application) of
long acting GnRH agonist suppresses
reversibly the release of LH and FSH
which leads to decrease in the level of
testosterone to castration levels
Anti Androgens Treatments
1)Androgen receptor blockers - Flutamide
Bicalutamide and Nilutamide
2) Hormonal agent – Cyproterone Acetate (CPA)
and Medroxyprogesterone Acetate (MPA)
(Provera)
3) GnRH / LHRH agonist - Leuprolide (Lupron,
Eligard, and Viadur), Triptorelin (Trelstar),
Goserelin (Zoladex), and Nafarelin (Synarel)
4) GnRH antagonist – Cetrorelix and Abarelix
Androgen Receptor blockers
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Act by inhibiting the action of testosterone at
the receptor site.
Flutamide, Casodex, and Nilutamide have
been used in the US for the treatment of
prostrate cancer.
Also used to suppress the initial testosterone
surge seen in GnRH agonist treatment of
Paraphilia.
Androgen Receptor Blockers
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Flutamide given 250 mg orally three times a
day.
Side effects include breast tenderness and
swelling, diarrhea, decrease libido and sex
drive, nausea, tiredness, blurred visions and
liver enzymes elevation.
Androgen Receptor Blockers
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Bicalutamide (Casodex) 50 mg or 150 mg
Orally once a day.
Side effects include breast tenderness, hot
flashes, itching and dry skin, decreased libido
and erection difficulty, weakness and nausea.
Androgen Receptor Blockers
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Nilutamide 300 mg for 30 days then dose
reduced to 150 mg per day.
Side effects include allergic reactions, short of
breath, cough, chest pain, fever, liver damage,
hot flashes, dizziness, nausea, constipation,
decreased libido and impotence.
Hormonal agents
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Cyproterone Acetate (CPA)
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Medroxyprogesterone Acetate (MPA)
(Provera)
Hormonal agents - CPA
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First introduced in the 1970s
Cyproterone Acetate (CPA) not approved by
FDA in US.
It blocks the intracellular uptake of
testosterone competitive inhibition at the
androgen receptors.
Erections, ejaculation and sperm production is
decreased.
It has a strong progestational action and leads
to decreased levels of LH and FSH (unlike
flutamide).
Hormonal agents - CPA
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The antiandrogen properties are dose
dependent
Oral dose is 50-200 mg per day, injectable
dose is 200-400 mg every 1-2 weeks.
Doses over 150 mg a day are required for full
therapeutic effect however it can lead to
feminization (gynecomastia)
Possible side effect include liver dysfunction
and feminization, depression, weight gain and
thromboembolic phenomenon, which limit its
use
Medroxyprogesterone Acetate
(MPA, Provera)
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Primary action is by enhancing the removal of
testosterone by the liver and decreasing its plasma
levels and through blocking the release of LH and
FSH from the pituitary.
The anti androgen effect is dose dependent.
Can be given orally (50 mg – 300 mg daily) but the
absorption is erratic or IM (300-400 mg every week)
Side effects include weight gain decrease sperm
production, gall bladder and gastrointestinal
dysfunction, gynecomastia thromboembolism, liver
damage, and muscular cramps
MPA
Oregon Depo-Provera study
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Retrospective study of 275 inmates in the first
4 years of the Oregon depo-Provera Program
(2000-2004)
134 inmates were judged appropriate for MPA
79 (59%) did receive MPA and 55 (41%) did
not receive it
Outcome data regarding new offense
committed, VOP, and rearrests were collected
from the supervising officer.
Oregon Depo-Provera study results
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Comparison of those who received MPA with
those who were recommended but did not
receive it - they were less likely to commit
new offenses and none of these offenses were
sexual in nature, were also less likely to
commit parole violations, less likely to return
to prison, and were more likely to do well.
Comparison of those who received MPA and
those who were not recommended to receive it
– they committed fewer new offenses, had
fewer parole violations and were less likely to
have had to return to prison.
Oregon Depo-Provera study
Limitations
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Data were collected retrospectively
Some outcome measures were qualitative
Some of the data relied on the memory of the
supervising officers
Absence of dosage and side effects
Lack of objective measures of sexual drive such a
PPG and testosterone level
How long they were on MPA and what other
treatment they received
What other cognitive and behavioral therapies they
received.
LHRH / GnRH agonist
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Leuprolide
1)Lupron 3.75 and 7.5 mg monthly injection, 22.5 mg 3 month injection
and 30 mg 4 month injection,, and Viadur implant)
2) Eligard 7.5 mg monthly, 22.5 mg every 3 months, 30 mg every 4
months, and 45 mg every 6 months given subcutaneously
3) Viadur Implant 72 mg of Leuprolide subcutaneous implant in the upper
arm every 12 months
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Goserelin (Zoladex injection) 3.6 mg subcutaneous injection
into the anterior abdominal wall every 28 days
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Triptorelin (Trelstar) 3.75 mg injection every 4 weeks and
11.25 mg injection every 12 weeks
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Nafarelin (Synarel nasal spray)
LHRH / GnRH agonist
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It can cause an initial transient increase in the level
of testosterone and hence used with flutamide
(Eulexin 250 mg TID) or Bicalutamide (Casodex 50
mg PO QD) to reduce sexual arousal
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LHRH agonist are more effective in some studies
than CPA or MPA on reducing the effect of
testosterone in tissues suggesting a direct effect on
the central nervous system in supressing sexual
deviant behavior.
LHRH / GnRH agonist
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Some of the studies show that there is a abolishment
of abnormal and normal sexual arousal.
Also these agents are associated with decreasing the
bone mineral density.
There may be some role of administration of small
doses of testosterone (25-50 mg per month) to
prevent bone loss and ameliorate the erectile
dysfunction while supressing the paraphilic
behaviors.
Leuprolide
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Common side effects include pain at the site
on injection, headaches, hot flashes, joint pain
and mood fluctuations.
Can produce hypogonadism and atrophy of the
testicles leading to loss of fertility and libido.
Osteoporosis is a long term side effect of
Lupron.
Other possible side effects include skin
reactions, dizziness, numbness, muscle pain,
swelling, dehydration, flu like symptoms,
diarrhea, weight changes
Lupron Study 2005 Schober et al
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Five men age ranging from 36-58 with diagnosis of pedophilia
Conducted over a 2-year period in a medical research center in
NW Pennsylvania
Subjects received weekly Cognitive-Behavioral therapy for 24
months and Lupron (LA) depot injection 7.5 mg at baseline
and 22.5 mg at months 1, 4, 7, and 10. Flutamide 250 mg TID
for 2 weeks
After 1 year of therapy, LA was discontinued and replaced
with saline for 1 year
At baseline, 1 month after LA and then at 3 months interval
subjects underwent ABEL, PPG and Polygraph and lab
studies.
Lupron Study 2005 Results
Schober et al
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Testosterone levels fell to a mean of 18.8 ng/dl at 4
months.
Interest preference as measured by ABEL and PPG
did not change while the subjects were on LA
therapy.
Decrease in penile circumference and testicular size
Even with the suppression of testosterone, low levels
of interest and arousal persisted
Evidence of deception at baseline and on placebo
suggesting that self-report alone is a not a reliable
measure of outcome.
GnRH antagonist
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They provide rapid suppression of testosterone
level and do not cause any testosterone surge
Cetrorelix: needs to be given subcutaneously
every 12 hours which limits its clinical use
Abarelix: approved with marketing restrictions
for safety reasons. The physician needs to be
enrolled in the Plenaxis Plus Program. The
dose is 100 mg IM injection in the buttock on
day 1, 15, 29, and every 4 weeks thereafter
GnRH antagonist
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1)
2)
3)
4)
5)
Abarelix was compared with Leuprolide plus bicalutamide
Abarelix was more effective in avoiding the testosterone
surge
Reduced testosterone levels more rapidly to castration level
(day 8)
No significant difference between the two groups in
achieving castrations levels of testosterone
Safety profile were comparable for the two groups
Abarelix causes a sustained suppression of FSH while in the
combination of leuprolide and bicalutamide the FSH level
returned to baseline.
Algorithm for Pharmacotherapy
Protocol for the use of medications
to decrease sexual arousal at TDF
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Discussion regarding medications during the initial
psychiatrist interview
Group therapy is the cornerstone of sex offender
treatment and medications are used as adjunct therapy
Medications may be contraindicated in some cases
(Pituitary pathology, thromboembolic disorder and
Osteoporosis)
Medications may be stopped at any point during the
treatment if requested by the patient or if clinically
indicated.
Informed Consent
Lupron Protocol
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Patient given information regarding Lupron
Patient signs an informed consent for treatment
(yearly)
CMP, CBC, testosterone, FSH, LH, TSH level,
CXR, EKG, UA, bone scan, and PPG prior to
first dose.
Test dose of Lupron
Flutamide or Casodex offered at least 1 day
prior to starting Lupron
Lupron Protocol (contd)
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Initial dose of Lupron is 3.75 mg Intramuscular once a month
6 weeks later, testosterone level is checked
Dose can be increase to 7.5 mg based on testosterone level and
clinical response
PPG repeated after 6 months of treatment
Testosterone level, CBC and CMP must be checked every year
at the least or as clinically indicated
Repeat the Bone scan on a yearly basis or as clinically
indicated
Patients stable on Lupron can be given IM injection of 30 mg
once every 4 months
Eligard Protocol
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Patient given information regarding Eligard
Patient signs an informed consent for treatment
(yearly)
CMP, CBC, testosterone, FSH, LH, TSH level,
CXR, EKG, UA, bone scan, and PPG prior to
first dose.
Flutamide or Casodex offered at least 1 day
prior to starting Lupron
Eligard Protocol (contd)
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The Injection 45 mg is given in the abdominal fat region.
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PPG repeated after 6 months of treatment
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Testosterone level, CBC and CMP must be checked every year
at the least or as clinically indicated
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Repeat the Bone scan on a yearly basis or as clinically
indicated
Management of Osteopenia and
Osteoporosis in Residents on Lupron
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Bone scan done prior to Lupron treatment
Patients with osteopenia are counseled regarding the
risk/benefits of using Lupron in the setting of osteopenia
Patient can be started on calcium with vitamin D and Fosamax
depending on the severity.
Bone scan is done more frequently (6 months)
Patients with osteoporosis are encouraged not to proceed with
Lupron. Referred to internist for evaluation of Osteoporosis
Patients counseled on lifestyle changes ( smoking cessation
and exercise and diet)
If the bone scan is normal, then it should be repeated on a
yearly basis as long as the patient remains on Lupron
Lupron Case Study
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Mr. X. is a 35 year old white male committed
to the TDF in 1999.
History of physical and emotional abuse by his
parent
History of sexual abuse by his older nephew
when he was 6 years old (oral and anal sex at
knifepoint daily for 2 years)
Lupron Case Study
•
•
•
Removed from his home at age 13 after he
molested his 7 year old nephew at
knifepoint
Sexually involved with his teenage sister
and two of her friends.
Series of placements in foster homes and
group homes where he often molested
younger children.
Lupron Case Study
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In one of the group homes, he gave a 13 year old girl
large quantity of alcohol, took her to the park and
vaginally raped her and left her unconscious.
At the age of 22, he was charged with sexually
assaulting a 8 year old girl.
While on probation for his crimes, he violated the
probation by touching a 20 year old woman between
her legs in a public park.
Lupron Case Study
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While in the TDF, he was having fantasies of raping
the STAs and the therapists. His fantasies consisted
of pulling the STA in the shower and raping and
choking her so she couldn’t yell.
He was masturbating 4-5 times and day and reported
that his sex drive was very high before he was started
on Lupron.
Recently he was charged with murder of a 6 month
old girl who died from internal bleeding after she
was raped by him.
PPG data
Seg
March 01
April 02
Sept 03
lupron
July 05
April 06
lupron
Baseline
Insig
Insig
Insig
Insig
Insig
Female viol
Low
Insig
Low
Insig
insig
Male infant
Mod
High
Insig
Mod
Insig
Female
infant
Low
High
Insig
Insig
Mod
Male
preschool
coercive
Insig
Mod
Insig
Insig
Insig
Female
preschool
Coercive
Low
High
Insig
High
Insig
Male
preschool
persuasive
Low
Low
Insig
Insig
insig
Female
preschool
persuasive
Mod
High
Insig
Mod
insig
Male gram
coercive
Low
Low
Insig
High
Insig
Fem gram
coercive
Mod
Mod
Insig
Insig
insig
Male gram
persuasive
Low
Mod
Insig
Low
Insig
Fem gram
persuasive
Mod
Mod
Insig
Low
Low
Male teen
coercive
Insig
Low
Mod
Insig
Insig
Fem teen
coercive
Low
Mod
Insig
High
low
Male teen
persuasive
Low
Low
Insig
Insig
low
Fem teen
persuasive
Low
High
Insig
Insig
insig
Male adult
coercive
Low
Insig
Insig
Mod
Low
Fem adult
coercive
Insig
Low
Insig
High
Insig
Male adult
persuasive
Insig
Low
Low
Mod
insig
Fem adult
persuasive
Low
Low
Insig
N/A
N/A
Fem adult
normal
N/A
N/A
N/A
Insig
Insig
Female
challenge
Mod
High
Insig
Low
N/A
Fem adult
exhibition
Low
Mod
Insig
Insig
N/A
Child
violent
N/A
N/A
N/A
N/A
insig
Male
challenge
N/A
N/A
N/A
N/A
insig
References
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Hill et al. (2003) Differential Pharmacological Treatment of
Paraphilias and Sex Offenders. International Journal of
Offender Therapy and Comparative Criminology, 47(4), 407421
Bradford et al. (2001) The Neurobiology,
Neuropharmacology, and Pharmacological Treatment of
Paraphilias and Compulsive Sexual Behavior. Can. J.
Psychiatry 2001;46:26-34
Briken et al. (2003) Pharmacotherapy of Paraphilias with
Long-Acting Agonists of Luteinizing Hormone-Release
Hormone: A Systematic Review. J. Clin. Psychiatry
2003;64;890-897
Dangerous Sex Offenders: A Task Force Report of the
American Psychiatric Association