Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Hormone replacement therapy (menopause) wikipedia , lookup
Testosterone wikipedia , lookup
Sexually dimorphic nucleus wikipedia , lookup
Hyperandrogenism wikipedia , lookup
Hormone replacement therapy (male-to-female) wikipedia , lookup
Kallmann syndrome wikipedia , lookup
Hormone replacement therapy (female-to-male) wikipedia , lookup
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 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) 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 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 Reduce the deviant fantasies, urges and behavior Not to impair the non-deviant sexual behavior Have minimal side effects Neurobiology of Sexuality 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 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 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 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 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 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 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 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 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 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 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 It is the major activator element of sexual desire, fantasies and behavior and controls the frequency, duration, and magnitude of spontaneous erections. In paraphilic patients the levels of testosterone are usually within normal levels suggesting an abnormal response to androgens by the receptors. 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 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 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 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 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 Cyproterone Acetate (CPA) Medroxyprogesterone Acetate (MPA) (Provera) Hormonal agents - CPA 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 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) 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 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 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 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 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 Goserelin (Zoladex injection) 3.6 mg subcutaneous injection into the anterior abdominal wall every 28 days Triptorelin (Trelstar) 3.75 mg injection every 4 weeks and 11.25 mg injection every 12 weeks Nafarelin (Synarel nasal spray) LHRH / GnRH agonist 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 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 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 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 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 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 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 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 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 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) 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 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) The Injection 45 mg is given in the abdominal fat region. 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 Management of Osteopenia and Osteoporosis in Residents on Lupron 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 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 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 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 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