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Reversible Transvestic Fetishism in a Man With Parkinson's Disease Treated With Selegiline
Abstract
Dopaminergic therapy in patients with Parkinson's disease may change the quality as well as the quantity of sexual interest and behavior. This 72-year-old man had a 37-year history of Parkinson's disease treated with a right thalamotomy and was later treated with levodopa for more than 20 years. Selegiline (5 mg twice daily) was added for motor fluctuations. He developed a frequent impulse to wear women's clothing but did not act on this impulse until his wife died over a year later. He then began to dress in women's clothing an average of once per week. He stated he had never thought of cross-dressing previously. The selegiline was stopped, and his urge to wear women's clothing ceased. Paraphilias are a rare behavioral complication of Parkinson's disease treatment. Other paraphilias have been attributed to dopamine agonists, suggesting that the action of the monoamine oxidase inhibitor responsible for the patient's transvestism in this case was dopamine potentiation. Drug-induced paraphilias and hypersexuality may represent a reversal of the putative premorbid Parkinson's disease personality traits of introversion, cautious behavior, and lack of "novelty-seeking." A biologic basis for transvestism, and paraphilias in general, is not known. Rare clues emerge from cases similar to this one.
... This possibility is supported by the observation that most paraphilic behaviors reportedly ceased after dose reduction of DRTs. 3,7,8,11,12,14,15,[17][18][19]21,[23][24][25] Of note, Nielsen and colleagues 12 showed that these conditions ceased after withdrawal of dopaminergic drugs and resumed soon after DRT reinstatement. However, the use of lower doses of dopaminomimetics did not result in a relapse of paraphilias, suggesting a specific relation of these conditions with high doses of DRTs. ...
... 52,53 The chronic stimulation of dopamine receptors by DRTs has been postulated to lead to receptor hypersensitivity as the basis for these behavioral side effects. 15,51 According to Robinson and Berridge's 54,55 incentive sensitization theory, progressive and persistent neuroadaptations induced in dopamine projections to the accumbens-related circuitry are closely related to compulsive drug use. 54,55 More recently, a positron emission tomography study in PD patients affected by a compulsive medication use showed an increased ventral striatal dopamine release in response to an acute levodopa challenge, thus suggesting a crucial neuronal sensitization of such chronic levodopa use in this particular class of vulnerable individuals. ...
... 56 Conceivably, similarly to DDS, overuse of dopaminergic agents could result in paraphilic behaviors by driving aberrant "novelty seeking" behaviors and excessive risk taking, or promoting disinhibition mechanism P A R A P H I L I A S I N P D in control pathways. 15 Taken together, these data suggest that an excessive load of dopaminergic drugs could overtake the classical features of hypersexuality and lead to the expression of paraphilic disorders. In addition to the accumbal involvement, other dopaminergic pathways may be involved in the genesis of paraphilic behaviors. ...
Paraphilias are intense urges or behaviors involving non-normative sexual interests. The newly approved diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) have established that, although paraphilias should not be regarded as inherently pathological, they ought to be qualified as paraphilic disorders if resulting in distress, impairment, or harm to the affected individual or others. Recent evidence documents that both phenomena can emerge as relatively uncommon iatrogenic consequences in Parkinson's disease (PD) patients. To outline the clinical characteristics of paraphilias and paraphilic disorders in PD patients, we summarized the available evidence on these phenomena. The review encompasses all studies on paraphilias in PD patients identified by a search on the Pubmed and Scopus online databases through May 2014. Twenty-two case reports on a total of 31 PD patients with paraphilias or paraphilic disorders were identified. These phenomena were typically associated with dopaminomimetic treatment (with a mean levodopa-equivalent daily dose of 1,303 ± 823 mg/d) in male patients with motor complications, young age at PD onset, and long disease duration. Paraphilias were highly concomitant with impulse-control disorders or dopamine dysregulation syndrome. Although evidence on paraphilias and paraphilic disorders in PD patients remains anecdotal, available data point to these phenomena as likely sequelae of high-dose dopaminomimetic treatment. Accordingly, the intensity of paraphilic urges is typically attenuated by the reduction of dopaminomimetic doses, sometimes in association with atypical antipsychotics. Failure to recognize paraphilic disorders may significantly impair the relational functioning of the affected PD patients. Practitioners should routinely inquire about paraphilias during their clinical assessment of PD patients. © 2015 International Parkinson and Movement Disorder Society
... Ya desde la década de los 70 se atribuían múltiples efectos secundarios de tipo psi-son apropiadas en el contexto de una enfermedad neurodegenerativa (15) y que se le reconoce como un tipo de TCI. En esta línea es fundamental conocer tales conductas e identificar a pacientes en riesgo de padecerlas para reconocerlas a tiempo, dadas las múltiples repercusiones que pueden poner en riesgo la integridad del paciente, de sus familiares y/o cuidadores e impactar en las relaciones psicosociales, dado que se han reportado casos de divorcio y aislamiento, despidos laborales, crímenes sexuales, robo, trasvestismo, pérdidas económicas (12,16,17), entre otras conductas relacionadas con hipersexualidad, juego patológico y compras compulsivas, potencialmente tratables. ...
... Mientras que la hipersexualidad o conductas sexuales compulsivas se refiere a preocupación por pensamientos sexuales con ideación parafílica intrusiva que dificultan enfocarse en las actividades diarias (5). Tal tipo de conducta es más común en hombres y se ha manifestado con conductas sexuales violentas, trasvestismo, fetichismo, entre otros (16,17). Por su parte el trastorno por atracones de comida se refiere a la necesidad de ingesta de alimentos más allá de la saciedad (31), conducta en la que el paciente puede mostrar pérdida de control en la alimentación, comer rápidamente, sin tener la sensación de saciedad, comer grandes cantidades de alimento sin tener apetito y sensación de enojo o culpa después de comer en exceso (5). ...
... Mientras que el uso de amantadina; un fármaco con acción dopaminérgica comúnmente utilizado en el control de las discinesias en EP, con el desarrollo de TCI, sobre todo de tipo juego patológico (42). Se han reportado múltiples casos de desarrollo de TCI del tipo sexual con el uso de fármacos inhibidores de la enzima MAO-B como selegilina y rasagilina en EP (17,(43)(44)(45). En el estudio DOMINION fue posible detectar de forma retrospectiva factores asociados a mayor probabilidad de presentar TCI, tales como: sexo masculino, inicio de la enfermedad antes de los 65 años, ser soltero, nacionalidad norteamericana, tabaquismo, antecedente personal de depresión, ansiedad, síntomas obsesivo-compulsivos y antecedente familiar de ludopatía (30). ...
La enfermedad de Parkinson (EP) es la segunda enfermedad neurodegenerativa más frecuente a nivel mundial y afecta múltiples sistemas neuronales. La terapia dopaminérgica es la más efectiva para el control de los síntomas motores, sin embargo su administración se asocia al desarrollo de efectos adversos como el trastorno del control de los impulsos (TCI). Este es un trastorno caracterizado por escasa capacidad para controlar conductas como apuestas, atracones de comida, compras compulsivas y conductas sexuales compulsivas, hobbismo, actividades sin propósito e ingesta excesiva de medicamento. Se cree que el TCI se desarrolla por un exceso en los niveles de dopamina del sistema de recompensa, lo que altera la capacidad de toma de decisiones y comprensión de riesgos. El TCI se asocia a pobre calidad de vida del paciente y sus cuidadores, así como conductas delictivas, por lo que es importante su detección y manejo oportunos.
... Less frequent and less well-reported are occurrences of sexual deviancy in conjunction with antiparkinsonian medications. Such incidences include states of hypersexuality [1], transvestic fetishism [4], zoophilia [5,6] and internet pornography [7]. Marital infidelity has also been reported [7]. ...
... Marital infidelity has also been reported [7]. Reported cases indicate that a reduction or change in antiparkinsonian medication may result in diminished or at least partial improvement in abnormal sexual behavior [2,[4][5][6]. We report two cases of aberrant sexual behavior which appears to have arisen de novo in conjunction with selegiline therapy. ...
... Hypersexuality and aberrant sexual behavior in PD have previously been reported [1][2][3][4][5][6]. The actual incidence of pharmacologically induced paraphilias or sexual compulsions in PD patients is difficult to ascertain. ...
While hypersexuality and paraphilia are known side effects of anti-Parkinson medications, it is seldom reported. Furthermore, selegiline is rarely implicated in such behaviors. We report two cases of early onset PD who experienced paraphilia and hypersexuality when selegiline was initiated, and later developing obsessive-compulsive and punding behavior with the addition of dopamine agonists. Social repercussions may prohibit patients and/or their families from volunteering such information. (c) 2006 Elsevier Ltd. All rights reserved.
... Des cas d'exhibitionnisme ont été rapportés [1,6,11,12,18]. Nous relevons également des cas de frotteurisme [4,6], de travestisme-fétichisme [25,27] et de zoophilie [14,16]. Plus grave encore, certains auteurs rapportent des agressions sexuelles avec sadisme [6] et des pédophilies [1,21]. ...
... Les agonistes non dérivés de l'ergot de seigle ont également été impliqués dans les manifestations sexuelles : pramipexole [22,29] et ropinirol [1,11]. Des cas de paraphilie associés à la prise de sélégiline sont également rapportés [25,27]. Enfin, les injections d'apomorphine ont donné lieu à des manifestations sexuelles particulièrement intenses [6,12,17]. ...
... Dans un premier temps, il est préconisé de réaliser un switch en remplaçant la prescription d'un agoniste dopaminergique par le levodopa [20]. De plus, les troubles sexuels régressent régulièrement après une diminution de la posologie des traitements dopaminergiques qu'il s'agisse des agonistes dopaminergiques ou de levodopa [16,18,19,22,25]. ...
In France, a psychiatric report is routine in cases of sexual violence. The expert psychiatrist should be aware of the major mental disorders that could alter or suppress controlled acts by perpetrators of sexual offences. In this context, a neuropsychiatric abnormality may still remain not well known to psychiatrists. This concerns sexual compulsions and paraphilia which are iatrogenic, occurring during dopaminergic treatment. The main case concerns patients suffering from Parkinson's disease, who suddenly present with a severe sexual conduct disorder due to their treatment. We performed a literature review to in order to identify the characteristics of this disorder: clinical picture, risk factors, epidemiological data.
... Des cas d'exhibitionnisme ont été rapportés [1,6,11,12,18]. Nous relevons également des cas de frotteurisme [4,6], de travestisme-fétichisme [25,27] et de zoophilie [14,16]. Plus grave encore, certains auteurs rapportent des agressions sexuelles avec sadisme [6] et des pédophilies [1,21]. ...
... Les agonistes non dérivés de l'ergot de seigle ont également été impliqués dans les manifestations sexuelles : pramipexole [22,29] et ropinirol [1,11]. Des cas de paraphilie associés à la prise de sélégiline sont également rapportés [25,27]. Enfin, les injections d'apomorphine ont donné lieu à des manifestations sexuelles particulièrement intenses [6,12,17]. ...
... Dans un premier temps, il est préconisé de réaliser un switch en remplaçant la prescription d'un agoniste dopaminergique par le levodopa [20]. De plus, les troubles sexuels régressent régulièrement après une diminution de la posologie des traitements dopaminergiques qu'il s'agisse des agonistes dopaminergiques ou de levodopa [16,18,19,22,25]. ...
Parkinson’s disease and sexual violence
In France, a psychiatric report is routine in cases of sexual violence. The expert psychiatrist should be aware of the major mental disorders that could alter or suppress controlled acts by perpetrators of sexual offences. In this context, a neuropsychiatric abnormality may still remain not well known to psychiatrists. This concerns sexual compulsions and paraphilia which are iatrogenic, occurring during dopaminergic treatment. The main case concerns patients suffering from Parkinson’s disease, who suddenly present with a severe sexual conduct disorder due to their treatment. We performed a literature review to in order to identify the characteristics of this disorder: clinical picture, risk factors, epidemiological data.
... Insomnia and psychomotor agitation Courty et al., 1997;Mü ller et al., 2002;Serrano-Duenas, 2002 Heightened aggression: includes irritability, low tolerance of frustration, use of insulting language, angry outbursts, threats of homicide and occasional violence. Uncommon Lawrence et al., 2002 Altered appetite: eating disorders, such as compulsive eating and binge eating are observed during phase, sometimes associated with uncontrollable food cravings Barichella et al., 2003;Macia et al., 2004;Tuite et al., 2005;Nirenberg and Waters, 2006;Giladi et al., 2007;Novakova et al., 2007 Punding: an intense preoccupation with complex, repetitive manipulations of technical equipment, examining and sorting through common objects, hoarding and handling that may be associated with motor restlessness and hyperactivity (''walkabouts'') Friedman, 1994;Fernandez and Friedman, 1999;Kurlan, 2004;Voon, 2004;Kumar 2005;Bonvin et al., 2007;Miyasaki et al., 2007;Kashihara and Inamura, 2008;Weintraub, 2008;Wolters et al., 2008;O'Sullivan et al., 2009 Hypersexuality: increased libido, not necessarily associated with increased erectile frequency, may lead to repeated masturbation and repeated demands for sexual intercourse and be associated with paraphilias Vogel and Schiffer, 1983;Harvey, 1988;Uitti et al., 1989;O'Sullivan and Hughes, 1998;Giovannoni et al., 2000;Riley, 2002;Lawrence et al., 2003;Klos et al., 2005;Shapiro et al., 2006;Solla et al., 2006;Weintraub et al., 2006;Cannas et al., 2007;Giladi et al., 2007;Meco et al., 2008;Doshi and Bhargava (2008) Pathological shopping: compulsive shopping is defined by the presence of repetitive impulsive and excessive buying leading to personal and family distress Lejoyeux et al., 1997;Maia et al., 2003;Lejoyeux et al., 2005 Pathological gambling: gambling is classified as an impulse control disorder according to the DSM IV criteria (Table 3) Does not occur exclusively during periods of hypomania or mania Excessive use of Internet: surfing the Internet becomes such a magnet for some patients to the extent that they are unable to leave the computer, forget to sleep or demand to eat, while in front of the computer. Participating in sporting activities: individuals spend 10-12 h a day, 7 days a week participating in different sports. ...
... Over the years since the first two articles related to levodopa therapy (Ballivet et al., 1973;Gisselmann, 1973), many cases of hypersexuality have been reported with levodopa (Harvey, 1988;Jiménez-Jiménez et al., 1999), levodopa plus bromocriptine (Vogel and Schiffer, 1983), pergolide alone (Kanowský et al., 2002) or in combination with levodopa (Jiménez-Jiménez et al., 2002;Solla et al., 2006;Cannas et al., 2007), and selegiline in association with levodopa (Riley, 2002;Shapiro et al., 2006). Klos et al. (2005) were the first to show clearly the role of DA receptor agonists in the development of hypersexuality. ...
Over the last decade, evidence has emerged linking disorders in the impulsive-compulsive spectrum in Parkinson's disease to dopamine receptor agonist treatment. These disorders include hypersexuality, gambling and, to a minor extent, compulsive shopping and eating, as well as dopamine dysregulation syndrome, characterized by an addictive pattern toward dopamine replacement therapy and stereotyped behaviors, such as punding. These syndromes, which have only recently been recognized and are still underdiagnosed, have deleterious social consequences that warrant interventions at the clinical level and promotion of research at the preclinical level. In this review, we first provide a summary of features of Parkinson's disease and current pharmacological therapies associated with the development of dopamine dysregulation syndrome and impulsive-compulsive disorders. We also examine the dopamine receptors and brain areas important in reward and compulsive behaviors. We then critically examine the neuroadaptations in dopaminergic circuitries and the literature concerning gambling, hypersexuality, and other addictive behaviors in parkinsonian patients. Finally, we focus on suggestions pointing to a role for dopamine D(3) receptors and sensitization phenomena as the main factors which may be the origin of these disorders.
... 22,31 Nevertheless, some patients develop behaviors that are apparently completely out of character. 18,24,32 Although many ICDs share features of "manic" behavior, and medication-induced mania may be part of DDS, 11 diagnostic criteria for pathological gambling, hypersexuality, and compulsive buying stipulate that these behaviors do not occur exclusively during periods of hypomania or mania. ...
... 102 There are reports implicating these monoamine oxidase-B inhibitors in ICDs (pathological gambling, hypersexuality, compulsive buying), although usually these patients were already taking other antiparkinsonian medication. 32,[103][104][105] We are aware of only one published report where the ICD (hypersexuality) developed de novo in two PD patients on selegiline monotherapy. 50 ...
In the past decade, impulse control disorders, punding, and dopamine dysregulation syndrome (which we refer to collectively as disinhibitory psychopathologies) have been increasingly recognized in treated patients with Parkinson's disease. Practicing neurologists must understand these problems to limit potential harm. In this article, we summarize current knowledge regarding these behavioral disorders, including phenomenology, epidemiology, pathophysiology, and treatment.
... Rare studies have suggested that MAO-I can induce ICDs. 7,8 The role of amantadine in alleviating or inducing ICDs is unclear due to few published data and conflicting opinions. 9-11 A small randomized, placebo-controlled, cross-over study involving 17 patients demonstrated benefit from amantadine (200 mg/day) for pathological gambling 9 . ...
Impulse control disorders in Parkinson's disease are a group of impulsive behaviors most often associated with dopaminergic treatment. Presently, there is a lack of high quality evidence available to guide their management. This manuscript reviews current management strategies, before concentrating on the concept of dopamine agonist withdrawal syndrome and its implications for the management of impulse control disorders. Further, we focus on controversies, including the role of more recently available anti-parkinsonian drugs, and potential future approaches involving routes of drug delivery, nonpharmacological treatments (such as cognitive behavioral therapy and deep brain stimulation), and other as yet experimental strategies. © 2015 International Parkinson and Movement Disorder Society.
© 2015 International Parkinson and Movement Disorder Society.
... Hypersexuality has also been reported to be triggered by selegiline. 70 After deep brain stimulation (DBS) of the subthalamic nucleus (STN), it is often transient and associated with hypomanic behavior. DBS induced hypersexuality cases have younger onset PD compared to DBS STN patients without hypersexuality. ...
Antiparkinson therapy can be the primary cause of a range of nonmotor symptoms that include a set of complex disinhibitory psychomotor pathologies and are linked by their repetitive, reward or incentive-based natures. These behaviors relate to aberrant or excessive dopamine receptor stimulation and encompass impulse control disorders (ICDs), punding, and the dopamine dysregulation syndrome (DDS). Common ICDs include pathological gambling, hypersexuality, compulsive eating, and compulsive buying. This review focuses on the phenomenology, epidemiology, and methods to identify and rate these disorders. The management of dopaminergic drug-related compulsive behaviors is discussed in the light of the current understanding of the neurobiological substrate of these disorders.
... A number of behavioral phenomena have been associated with chronic use of dopaminergic drugs, mainly relating to L-dopa and dopamine agonists (Table 1), although there have been reports of selegiline-inducing hypomania, compulsive spending and transvestic fetishism. 22,23 Hypersexuality, punding (repetitive purposeless motor acts not distressing to the patient), compulsive gambling and shopping, and other obsessive behaviors may be consequent to drug use in some patients. Reducing dopaminergic therapy can lead to cessation or improvement in symptoms. ...
This review deals with the range of neuropsychiatric problems that may arise from the use of medical and surgical therapies in the treatment of Parkinson's disease. As new approaches emerge, these problems are diversifying. Well-recognized drug-related complications include hallucinations and psychosis and the so-called dopamine-dysregulation syndrome. The etiology of these problems has not been fully established and is not clearly dose related, while the management can be difficult and needs to be tailored to the individual patient. Cholinergic and dopaminergic drugs may both influence cognitive function. The development of pharmacogenetics could improve the therapeutic ratio of medical approaches to PD in the future. The literature relating to the neuropsychiatric issues complicating the surgical treatment of Parkinson's disease is more recent and frequently suffers from methodological problems, lack of a systematic approach, and adequate patient follow-up. The emergence of neuropsychiatric problems in association with surgery has shed new light upon the pathophysiological mechanisms underpinning these symptoms. Depression, hypomania, euphoria, mirth, and hypersexuality have all been described following deep brain stimulation procedures, although most studies have concentrated upon the depressive features. Anxiety has been described only rarely to date. Fortunately, permanent cognitive complications appear to be rare. The optimal management approach for surgically related neuropsychiatric problems is unknown at present. Prospective multicenter studies would contribute significantly to resolving this therapeutic uncertainty.
... De bijdrage van hersendisfunctioneren aan parafiele drang is recent meer in de belangstelling gekomen. De relatie tussen hersenschade en seksuele ontremdheid, die een parafiele vorm aanneemt, als gevolg van de ziekte van Parkinson en de medicamenteuze behandeling ervan (Riley, 2002), en van beschadiging van frontale corticale gebieden (Miller, Cummings, McIntyre, Ebers & Grode, 1986) is meermalen beschreven in gevalsstudies. Op grond van recente neurologische en neuropsychologische vergelijkingen wordt verondersteld dat hersendysfunctioneren op het niveau van de lagere executieve functions, zoals aandachtsfixatie en gedragsinhibitie, en tekorten op het gebied van de verbale vaardigheden een rol spelen bij het ontstaan van seksueel deviante voorkeuren. ...
Het wetenschapsgebied van de seksuologie omvat, historisch gezien, de seksuele stoornissen, waartoe de seksuele disfuncties
en de parafilieën gerekend worden, en de stoornissen van de genderidentiteit. Deze onderverdeling wordt eveneens gehanteerd
in de DSM-IV. In dit hoofdstuk bespreken we deze stoornissen en hanteren daarbij de genoemde indeling.
... In entrambi i casi i comportamenti furono messi in relazione agli alti dosaggi di farmaci ad azione dopaminergica. Riley (2002) (25) ha descritto un caso di travestitismo feticista indotto dall'introduzione in terapia della Selegelina, che è regredito una volta sospeso il farmaco. Visto il valore patogenetico attribuito ai farmaci dopaminoagonisti nel determinare altre parafilie, in questo caso la ragione del comportamento sessuale aberrante è stata ricondotta al potenziamento della dopamina da parte dell'IMAO-B. ...
Le disfunzioni sessuali sono comuni nei pazienti affetti da malattia di Parkinson (1). L ' i n t e resse per questo argomento è aumentato soprattutto negli utimi 10 anni, da quando cioè sono stati introdotti farmaci che possono essere utilizzati in alcuni di questi disturbi. Aspetti fisiologici della sessualità Per quanto riguarda la sessualità umana nel determinare la risposta sessuale interven-gono fattori legati alla cognitività, all'affettività e al soma. La performance sessuale ha un declino con l'invecchiamento; il gradiente del declino dipende dalla attività precedente, dalla salute fisica e da quella mentale. Il benessere psichico, l'integrità delle strutture neuroanatomiche somato-sensoriali e motorie, un normale assetto ormonale ed una normale funzionalità vascolare sono elementi essenziali per determ i n a re la libido e l'abilità ad avere un rapporto sessuale soddisfacente. Dal punto di vista neuroendocrino l'Ossitocina interviene nei processi di attaccamento, nella e rezione, nell'arousal e nel raggiungimento dell'orgasmo, mentre la Prolattina può interf e r i-re con la libido; la Dopamina aumenta i livelli di Ossitocina, mentre inibisce la Pro l a t t i n a . La Dopamina nel suo complesso ha un ruolo fisiologico nel controllo del comportamento sessuale. E' importante per la funzione motoria e per l'arousal generale. A livello dell'accumbens promuove l'arousal e l'attivazione di non specifici patterns motori. II release della Dopamina a livello dei nuclei preottici e paraventricolare potrebbe avere relazione con meccanismi della eiaculazione o con le conseguenze neuroendocrine dell'attività sessuale. Non ci sono sufficienti dati sperimentali su un possibile ruolo della Dopamina nella moti-vazione sessuale. Ci sono evidenze sperimentali che mostrano che la Dopamina non ha importanza nella gratificazione sessuale (2). Le alterazioni della Dopamina potrebbero dare una prima spiegazione dei disturbi della sfera sessuale nella malattia di Parkinson, poichè si tratta di una funzione complessa non possono darne ragione esse sole. I disturbi sessuali e di identità di genere I disturbi sessuali e di identità di genere secondo il DSM IV-R vengono divisi in disfunzioni sessuali, parafilie e disturbi dell'identità di genere. Le disfunzioni sessuali si distinguono in disturbi del desiderio sessuale, dell'eccitazione ses-suale, dell'orgasmo (femminile e maschile, eiaculazione precoce), da dolore sessuale, dovuto a condizioni mediche o da sostanze e non altrimenti specificato.
... We discuss a man with Parkinson's disease treated with ropinerole who developed a frequent compulsion to cross-dress. P e e r R e v i e w O n l y 3 A 60 year old man presented with an eight year history of Parkinson's disease initially presenting with left sided loss of dexterity. Over many years his motor symptoms had remained stable on co-careldopa 25/100 three times daily, but more recently he had required the addition of ropinerole 4mg three times daily. ...
... The initial search revealed 1,219 articles. After being scanned for relevance, several [7][8][9][10][11][12]49,50,[61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78] were rejected for being case reports, five 46,79-82 were review articles, and 1,181 were irrelevant to the study. Twenty-three articles were studied further, with the majority being rejected for not examining etiological or pathological factors, followed by not using recognized or any specific criteria for HS, with the rest failing to draw conclusions specifically related to HS. ...
Hypersexuality (HS) was one of the earliest examples of an impulse control disorder (ICD) or behavior to be associated with treatment for Parkinson's disease (PD), with an estimated prevalence of approximately 3.5%. Here, we report on a systematic review of the published literature of HS in PD with a view to uncovering evidence as to whether it is distinct from other ICDs. In addition, we report on 7 new cases that had broad neuropsychological testing, including a gambling test, which taps into reward and inhibitory mechanisms. The review uncovered a number of case series and cohorts that comment on the prevalence of HS, but very few made systematic comparisons with other ICDs, although younger onset and male sex are usually noted. A few studies have begun to map out a neuropsychological profile for HS, and our own cases show particular deficits in learning from negative outcomes, but, overall, there are insufficient data to draw firm conclusions. Functional imaging has shown patterns of increased content-specific activation in response to sexual material and this might relate to increased dopamine release. We conclude with a brief survey of the neurobiology of sexuality, which suggests possible avenues for further research and treatment of HS.
... Over an 11-year period of observation, the manifestation of ASB in nine PD patients during dopaminergic therapy, while the literature presents only rare anecdotal reports [1, 2, 4,8,10,14], suggests that the phenomenon is likely to be largely underestimated. Although these types of behaviour are often punishable by law and may at times lead to imprisonment, in our case series, the occurrence of ASB mainly took place in a family setting and no types of legal proceedings were undertaken by relatives, with the exception of one patient. ...
... Other changes in sexual behavior have also been documented in patients with PD. One such case was reversible transvestic fetishism in a patient who had PD for 37 years and was newly treated with selegiline [51]. Hypersexuality is considered a manifestation of enhanced libido and inappropriate frontal inhibition [52]. ...
Degeneration of the dopaminergic system in Parkinson's disease and longstanding exposure to dopaminergic drugs may cause reward system malfunction. This may manifest as addiction to l-dopa and behavioral disturbances associated with the impulse control system. These disturbances include: gambling, excessive spending (shopping), hypersexuality and binge eating. We included one such patient's personal story to emphasize the devastating consequences of these potentially reversible phenomena: the patient describes in his own words how gambling induced by an exposure dopamine agonist therapy significantly worsened his disease-related difficulties.
The prevalence of psychiatric comorbidity in Parkinson's disease (PD) is about 50%.
The authors investigated differences among PD patients treated by deep brain stimulation (DBS), by drugs alone (noDBS), and healthy control subjects.
Samples of 22 subjects in each group were assessed with the Temperament and Character Inventory (TCI) and Hamilton scales for anxiety and depression (Ham-A and Ham-D).
Higher scores emerged on two Novelty-Seeking subscales in PD-DBS patients. Ham-A and Ham-D scores were lower in PD-DBS patients than in PD-noDBS patients and control subjects. Rigidity and non-impulsiveness were lower in PD-DBS than in PD-noDBS patients.
Further studies should investigate whether or not these changes in personality are a consequence of the motor and depression improvement after DBS.
Parkinson disease (PD) is a complex and challenging disorder, characterised by a broad range of neurological and psychiatric symptoms and a variety of pharmacological and surgical therapies, which, combined with premorbid personality traits, can produce a complex, distressing and challenging clinical picture. We present a case report which highlights a particularly challenging range of symptoms (including neurological and psychiatric symptoms), behaviours (including compulsions and pathological gambling) and treatments (including surgical and medical treatments) in one patient with PD.
Parkinson's disease is associated with classical Parkinsonian features that respond to dopaminergic therapy. Neuropsychiatric sequelae include dementia, major depression, dysthymia, anxiety disorders, sleep disorders, and sexual disorders. Panic attacks are particularly common. With treatment, visual hallucinations, paranoid delusions, mania, or delirium may evolve. Psychosis is a key factor in nursing home placement, and depression is the most significant predictor of quality of life. Clozapine may be the safest treatment for psychotic features, but more research is needed to establish the efficacy of antidepressant treatments. Dementia with Lewy bodies, the second most common dementia in the elderly, may present in association with systematized delusions, depression, or RBD. Early evidence suggests the utility of rivastigmine, donepezil, low-dose olanzapine, and quetiapine in treating DLB. Parkinson-plus syndromes generally lack a good response to dopaminergic treatment and evidence additional features, including dysautonomia, cerebellar and pontine features, eye signs, and other movement disorders. MSA is associated with dysautonomia and RBD. SND (MSA-P) is associated with frontal cognitive impairments, but dementia, psychosis, and mood disorders have not been strikingly apparent unless additional pathological findings are present. In SDS (MSA-A), impotence is almost ubiquitous; urinary incontinence is frequent; depression is occasional, and sleep apnea should be treated to avoid sudden death during sleep. OPCA neuropsychiatric correlates await further definition. Progressive supranuclear palsy neuropsychiatric features include apathy, subcortical dementia, pathological emotionality, mild depression and anxiety, and lack of appreciable response to donepezil. CBD usually is recognized by early frontal dementia with ideomotor apraxia, often in the right upper extremity, attended later by poorly responsive unilateral Parkinsonism, with additional signs including cortical reflex myoclonus, limb dystonia, alien limb, oculomotor apraxia when asked to look horizontally, depression, personality changes, and, occasionally, Kluver-Bucy syndrome. The neuropsychiatry of FTDP-17 involves apraxia, executive impairment, personality changes, hyperorality, and occasional psychosis. Future research in these Parkinsonian disorders should target the characterization of neuropsychiatric sequelae and their treatment.
There is a growing consensus among clinicians that sex offenders represent a heterogeneous group of individuals. Assessment and treatment of sex offenders is complicated by phenomenological and etiological differences and the presence of psychopathology, including paraphilias. The authors discusses the most commonly employed psychosocial therapies for sex offenders in general. Pharmacologically based treatments for paraphilic sex offenders are also reviewed.
Neuropsychological and psychopathological modifications induced by dopaminergic drugs in patients with Parkinson's disease (PD) are invariably not taken into sufficient consideration by the neurologist. Among the former, modifications of sexual urges and behaviours are of particular importance with regard to severity and variety of clinical pictures. Although rare, such modifications may assume the connotations of an aberrant sexual behaviour with criminal implications, in line with a diagnosis of paraphilia. The authors report the case of a 51-year-old male PD patient who, after a few years of dopaminergic treatment with pergolide, developed a paraphilic disorder, consistent with DSM-IV TR diagnosis of frotteurism, and delusional jealousy. The patient presented mild motor impairment and lack of or negligible cognitive deterioration, thus providing evidence that these disorders are not typical of advanced PD. Pergolide was reduced and quetiapine, an atypical neuroleptic, was introduced with subsequent subsiding of the paraphilic disorder and improvement of delusional jealousy.
Parkinson's disease is primarily considered a motor disease characterized by rest tremor, rigidity, bradykinesia and postural disturbances. However, neuropsychiatric complications, including mood and anxiety disorders, fatigue, apathy, psychosis, cognitive impairment, dementia, sleep disorders and addictions, frequently complicate the course of the illness. The pathophysiologic features of these complications are multifaceted and include neuropathophysiologic changes of a degenerative disease, exposure to antiparkinsonian treatments and emotional reactions to having a disabling chronic illness. Changes in mental status have profound implications for the well-being of patients with Parkinson's disease and of their caregivers. Treatment is often efficacious but becomes a challenge in advanced stages of Parkinson's disease. In this article, we review the key clinical features of neuropsychiatric complications in Parkinson's disease as well as what is known about their epidemiologic characteristics, risk factors, pathophysiologic features and management.
Dopamine replacement therapy (DRT) is the most effective treatment for Parkinson's disease (PD); it provides substantial benefit for most patients, extends independence, and increases survival. A few patients with PD, however, take increasing quantities of medication far beyond those required to treat their motor disabilities. These patients demand rapid drug escalation and continue to request more DRT despite the emergence of increasingly severe drug-induced motor complications and harmful behavioural consequences. In this article we detail the features of compulsive DRT-seeking and intake in PD, in relation to theories of compulsive drug use.
Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.
Prevalence of psychiatric disorders in patients suffering from Parkinson's disease varies from 12 to 90%. The most common disorder in the natural evolution of Parkinson's disease is depression. However, episodes of psychosis and hypomania are related to treatment with L-dopa and dopaminergic agents. Other recognized, although less frequent, psychiatric disorders are hypersexuality and development of certain addictive behaviors, which is compulsive gambling and overdosing of anti-Parkinson agents.
A case is presented of a male patient diagnosed with Parkinson's Disease at an early age who was treated with L-dopa and a combination of dopaminergic agents. During the course of his evolution he manifested symptoms of hypersexuality and pathological gambling which were unrelated to psychotic or mood changes.
A number of hospital admissions were needed into order to detect a pattern of abusive consumption of L-dopa as the main factor behind his behavior changes. The possibility of overdosage of L-dopa and dopaminergic drugs should be considered when there is pathological gambling conduct and/or hypersexuality, without psychotic or accompanying affective symptoms, in a male who develops Parkinson's disease at an early age and who undergoes treatment with these drugs and manifests motor fluctuations and dyskinesias. Early detection of the presence of these alterations, included within those described as "dopaminergic dysregulation syndrome", would allow for an early intervention on the cause behind them and would hence avoid the possible medical and social complications.
Treatment of Parkinson's disease has traditionally focused on the management of motor disability while behavioural disturbances have received less attention. Recently, impulse control disorders and aberrant repetitive behaviours have surged to clinical relevance as they occur during dopamine replacement treatment (mainly with dopamine agonists) and worsen patient and caregiver quality of life. Patients are unable to adequately estimate the negative consequences of their actions and are prone to entertain compulsive reward-seeking activities. This review aims to summarize current evidence on the epidemiology of behavioural disturbances in Parkinson's disease, recent insights into their neurobiological basis and to discuss strategies for management and prevention. Studies from 1990 through to December 2008 were retrieved via searches of the Cochrane Database of Systematic Reviews and PubMed. The mechanisms underlying the development of behavioural disturbances in Parkinson's disease are debated but current evidence points to specific risk factors: male sex, young age at onset, underlying personality traits characterized by high impulsivity and novelty seeking, and personal or family history of addictive disorders. Specifically, in predisposed individuals dopamine replacement therapy leads to overstimulation of dopamine receptors within the mesocorticolimbic pathways and in turn to the development of addictive behaviours, such as impulse control disorders and compulsive medication intake. Since these disturbances affect individuals who have often unremarkable psychiatric history and no cognitive impairment, their identification and management is complex. Compulsive medication intake (described as 'hedonistic homeostatic dysregulation' or 'dopamine dysregulation syndrome') is commonly associated with fluctuations in advanced disease, while impulse control disorders frequently occur in early Parkinson's disease and within normal-range medication dosages. Management primarily requires reduction of dopaminergic therapy but psychosocial support is often required. Use of selective serotonin reuptake inhibitors in the dose used for obsessive compulsive disorders may help, while benefit from atypical antipsychotics is limited in most cases. Deep brain stimulation should be considered with caution in these subjects. Prevention is based on the identification of at-risk individuals and active monitoring. Given the social and potentially medical-legal consequences of these behaviours, we encourage treating physicians to discuss risks with patients before treatment is initiated.
Do patients with restless legs syndrome (RLS) report gambling or other abnormal behaviors as previously reported in Parkinson disease.
This survey study was sent to 261 idiopathic RLS patients, and it included the Gambling Symptoms Assessment Scale, Altman Self-Rating Mania Scale, and questions pertaining to sexual activity and novelty-seeking behaviors.
Ninety-nine patients responded to the survey, and 77 were actively taking 1 or more dopaminergic medications. Of the 70 respondents who answered the gambling questions, 5 (7%) noted a change in gambling, with 4 (6%; 95% confidence interval, 2%-14%) stating that increased urges and time spent gambling occurred specifically after the use of dopaminergic medications (2 on pramipexole, 1 on ropinirole, and 1 on levodopa and pramipexole). Increased sexual desire was reported by 4 (5%) of the 77 respondents, 3 (4%; 95% confidence interval, 1%-11%) reported that this occurred specifically after the use of dopaminergic medications (1 on pramipexole, 1 on ropinirole, and 1 on levodopa). One patient reported both an increase in gambling and sexual habits.
This exploratory survey study revealed the development of gambling and/or increased sexuality in patients with RLS. These data raise the possibility that, as in Parkinson disease, RLS patients should be cautioned about potential behaviors that may occur with the use of dopaminergic medications. Further prospective studies are needed to assess the relationship between these medications and compulsive behaviors associated with the treatment of RLS.
Sexual dysfunction is a common, poorly recognized, poorly discussed (often because of cultural perceptions and sensitivities), bothersome and neglected aspect of the range of non-motor symptoms of Parkinson's disease (PD). The spectrum of sexual dysfunction in PD ranges from hyposexuality-based disturbances to hypersexuality-dominated behaviors in the context of drug-induced impulse control disorder. The pathophysiological mechanisms underlying PD-related sexual dysfunction, specifically for hyposexual disorders, are thus heterogeneous and still not fully understood. However, central and peripheral neural mechanisms secondary to the hallmark pathological alterations of the disease (alpha-synuclein deposition and nigrostriatal degeneration) and to the associated network and neurotransmitter dysfunctions, together with the effects of dopaminergic therapies, seem to play an important role in the development of sexual disturbances. In this chapter, we therefore review the neuroanatomical and neurophysiological basis of sexual function in humans, and we provide insights on the pathophysiological mechanisms of hyposexuality and hypersexuality in PD.
Résumé
Après un bref rappel de la physiopathologie de la maladie de Parkinson et des principaux médicaments utilisés dans cette affection, les auteurs décrivent les données récentes de pharmacovigilance concernant les médicaments antiparkinsoniens ainsi que les actualités sur les syndromes parkinsoniens médicamenteux. Les accès soudains de sommeil, décrits pour la première fois en 1999, sont favorisés par l’ancienneté de la maladie, la dose des médicaments dopaminergiques, l’existence d’une somnolence diurne ou encore une atteinte sous-jacente du système nerveux autonome. Ils peuvent avoir de graves conséquences, allant, par exemple, jusqu’à des accidents de la circulation. Les valvulopathies cardiaques sous pergolide, décrites depuis fin 2002, justifient la prescription du pergolide comme agoniste de dernière intention. Les médicaments dopaminergiques (lévodopa ou agonistes) peuvent déterminer des comportements d’hypersexualité ou favoriser le jeu pathologique. Enfin, dans la longue liste des médicaments susceptibles de déterminer un syndrome parkinsonien, on discute actuellement de l’imputabilité des antidépresseurs sérotoninergiques, de l’acide valproïque et de la trimétazidine. Finalement, ces observations de pharmacovigilance permettent de mieux préciser le rôle physiologique de la dopamine au niveau central : la dopamine, à côté de ses effets moteurs endocriniens ou sur les fonctions supérieures, participe également à la régulation du cycle veille-sommeil. La dopamine doit également être considérée comme le médiateur privilégié du plaisir et des régulations hédoniques. Elle intervient ainsi dans le comportement sexuel. Enfin, cette revue souligne l’importance de la notification spontanée dans la détection des nouveaux effets indésirables.
In recent years, levodopa-induced behavioral changes have received increased attention in the medical literature and in clinical practice. The spectrum of these symptoms includes non-motor fluctuations with neuropsychiatric symptoms, compulsive behaviors such as punding, dopamine dysregulation syndrome, and impulse control disorders, psychosis and hallucinations, as well as hypomania and mania. Despite knowledge of the clinical features associated with these behaviors, many of them are probably underdiagnosed. Although the mechanisms underlying behavioral symptoms are still incompletely understood, recent data from imaging and pathological studies have increased our understanding and guided new treatment strategies. Appropriate management remains challenging, because reduction of levodopa (l-dopa) and dopaminergic treatment is often recommended; however, doses required for control of motor symptoms may still induce behavioral changes. Newer modes of delivery of dopaminergic treatment, deep brain stimulation, and nondopaminergic agents may either provide alternatives for treatment of these behavioral problems or permit treatment of parkinsonism with less risk of these behavioral disorders. © 2014 International Parkinson and Movement Disorder Society.
© 2014 International Parkinson and Movement Disorder Society.
Sexual dysfunctions (SDs) are one of the most neglected nonmotor symptoms in Parkinson's disease (PD). A number of reasons including social and cultural factors might explain, at least partially, why SD is still one of the most underrecognized aspects of the condition after 200 years since the very first description by James Parkinson. SD has not been extensively investigated, however, a number of studies have shown a high prevalence of decreased libido, orgasmic dysfunction in both men and women with PD, and erectile dysfunction in male subjects. Moreover, SD in PD also comprises the increasingly recognized hypersexuality that is often associated with PD treatment. Taken together, SD in PD includes a remarkable range of symptoms and conditions that often require a multidisciplinary approach regarding assessment, investigation, and treatment.
The word “transvestism” generally means cross-dressing, regardless of its purpose. In popular language, it is also associated with acting in a manner or style associated with the other sex. In sexuology, the term transvestism, from the Latin “trans” (across, over) and “vestitus” (dress, and dressed, clothed) was introduced by Magnus Hirschfeld in 1910 in his book The Transvestites: The erotic drive to cross dressing. Though the term transvestism is just about a hundred years old, there have been references to transvestic behavior/cross-dressing in the Bible (J Forensic Leg Med 16:109–114, 2009) and in the writings of Herodotus and Hippocrates. They described some Scythian males wearing female clothes, and ascribed their cross-dressing to depression (so-called Melancholia Scythorum). Some Roman Emperors, e.g., Caligula, Heliogabalus (aka Elagabalus, possibly transgendered) and Nero, cross-dressed (Transvestism: a handbook with case studies for psychologists, psychiatrists and counselors, New York, 1979).
Sexual health in general and issues of geriatric sexuality in particular are neglected by laymen and health care professionals alike. Contrary to popular beliefs, elderly persons continue to have sexual desire and sexual activities. Sexual problems are more frequently found in elderly. This review describes briefly about the various causes of sexual dysfunction, assessment and management of sexual problems in elderly.
Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.
Definition, Prevalence, Incidence, and PhenomenologyCare for Persons with ParaphiliaPsychotherapeutic InterventionsBiomedical InterventionsEffectiveness of InterventionsParaphilia-Related DisordersSummary and Conclusions
Treatment of Parkinson’s disease has traditionally focused on the management of motor disability while behavioural disturbances have received less attention. Recently, impulse control disorders and aberrant repetitive behaviours have surged to clinical relevance as they occur during dopamine replacement treatment (mainly with dopamine agonists) and worsen patient and caregiver quality of life. Patients are unable to adequately estimate the negative consequences of their actions and are prone to entertain compulsive reward-seeking activities.
This review aims to summarize current evidence on the epidemiology of behavioural disturbances in Parkinson’s disease, recent insights into their neurobiological basis and to discuss strategies for management and prevention. Studies from 1990 through to December 2008 were retrieved via searches of the Cochrane Database of Systematic Reviews and PubMed.
The mechanisms underlying the development of behavioural disturbances in Parkinson’s disease are debated but current evidence points to specific risk factors: male sex, young age at onset, underlying personality traits characterized by high impulsivity and novelty seeking, and personal or family history of addictive disorders. Specifically, in predisposed individuals dopamine replacement therapy leads to overstimulation of dopamine receptors within the mesocorticolimbic pathways and in turn to the development of addictive behaviours, such as impulse control disorders and compulsive medication intake. Since these disturbances affect individuals who have often unremarkable psychiatric history and no cognitive impairment, their identification and management is complex. Compulsive medication intake (described as ‘hedonistic homeostatic dysregulation’ or ‘dopamine dysregulation syndrome’) is commonly associated with fluctuations in advanced disease, while impulse control disorders frequently occur in early Parkinson’s disease and within normal-range medication dosages.
Management primarily requires reduction of dopaminergic therapy but psychosocial support is often required. Use of selective serotonin reuptake inhibitors in the dose used for obsessive compulsive disorders may help, while benefit from atypical antipsychotics is limited in most cases. Deep brain stimulation should be considered with caution in these subjects. Prevention is based on the identification of at-risk individuals and active monitoring. Given the social and potentially medical-legal consequences of these behaviours, we encourage treating physicians to discuss risks with patients before treatment is initiated.
Les dysfonctions sexuelles chez les patients parkinsoniens sont caractérisées par une diminution des performances sexuelles ; cependant, des troubles du comportement sexuel, en particulier l’hypersexualité, sont fréquemment décrits. Les comportements sexuels compulsifs ou des paraphilies peuvent aussi exister. Les facteurs de risque les plus souvent rencontrés sont l’existence d’un traitement agoniste dopaminergique et/ou des antécédents de comportement compulsif sexuel. Les troubles du comportement sexuel ont été décrits avec tous les agonistes dopaminergiques, parfois avec la L-DOPA, mais aussi avec la sélégiline. Ces modifications comportementales peuvent également se présenter après stimulation des noyaux de la base. Certains cas d’hypersexualité ou certaines paraphilies actives ont parfois des conséquences pénales. Par honte et pudeur, les patients ou leur famille parlent difficilement de ces problèmes ; un interrogatoire précis sur la sexualité des patients doit donc faire partie de l’anamnèse et des informations claires sur les conséquences sexuelles doivent être fournies au patient ainsi qu’à sa famille. Des modifications thérapeutiques sont nécessaires avec diminution ou changement du traitement antiparkinsonien, instauration d’un traitement neuroleptique atypique, voire même antiandrogénique.
This chapter discusses the adverse effects and interactions of drugs that affect autonomic functions or the extrapyramidal system. Ephedrine is used to treat vasovagal episodes and has been reported to cause coronary artery spasm and myocardial infarction in these circumstances. Ephedrine and pseudoephedrine can also produce neuropsychiatric adverse effects. Two men with Parkinson's disease aged 66 and 78 years, developed abnormal respiration (tachypnea and irregularity in the depth of breathing) attributed to levodopa. Moreover, hiccups, an unusual form of dyskinesia, have also been associated with levodopa. Daytime sleepiness and nocturnal wakefulness can both occur in relation to dopaminergic drug therapy. Intrathoracic fibrosis is a rare but well recognized complication of the use of dopaminergic ergoline derivatives, such as pergolide. Entacapone is associated with more frequent dyskinesia, nausea, and diarrhea. When parasympathicolytic or anticholinergic agents are used to dilate the pupils, it is important to recognize systemic anticholinergic intoxication, because the outcome can be fatal without treatment.
Compulsive sexual behavior, otherwise known as sexual addiction, is an emerging psychiatric disorder that has significant medical and psychiatric consequences. Until recently, very little empirical data existed to explain the biological, psychological, and social risk factors that contribute to this condition. In addition, clinical issues, such as the natural course and best practices on treating sexual addictions, have not been formalized. Despite this absence, the number of patients and communities requesting assistance with this problem remains significant. This article will review the clinical features of compulsive sexual behavior and will summarize the current evidence for psychological and pharmacological treatment.
Sexual dysfunction is one of the more disabling and poorly investigated aspects of PD. Several variables should be considered when evaluating sexual dysfunction in a disease in which physical, psychological, neurobiological and pharmacological features merge and are not easily distinguishable. Although sexual dysfunction is common in Parkinson's disease, the development of hypersexuality and aberrant sexual behaviour, probably due to dopamine replacement therapy, calls into question the role of dopamine in sexual behaviour. This paper reviews studies that have investigated sexual behaviour and dysfunction in PD patients, paying particular attention to the effect of dopamine replacement therapy.
A distinctive personality type, characterized by introversion, inflexibility, and low novelty seeking, has been suggested
to be associated with Parkinson's disease. To test the hypothesis that Parkinson's disease is associated with a specific dopamine-related
personality type, the personality structures of 61 unmedicated Parkinson's disease patients and 45 healthy controls were examined.
Additionally, in 47 Parkinson's disease patients, the dopaminergic function in the brain was directly measured with 6-[18F]fluoro-l-dopa (18F-dopa) positron emission tomography (PET) with MRI coregistration. The novelty-seeking personality score, supposedly associated
with the parkinsonian personality, was slightly lower in the Parkinson's disease group compared with controls, but it did
not have a significant relationship with 18F-dopa uptake in any of the brain regions studied (r = −0.12 to 0.11, P > 0.15). The harm-avoidance personality score, associated with anxiety and depression, was clearly increased in patients
with Parkinson's disease and it had a paradoxical, highly significant positive correlation with the 18F-dopa uptake in the right caudate nucleus (r = 0.53, P = 0.04, Bonferroni corrected for 220 comparisons). Although the results of this study are not in disagreement with the concept
of low-novelty-seeking personality type in Parkinson's disease, the personality type does not seem to be dopamine dependent.
The correlation between the personality trait of harm avoidance and 18F-dopa may reflect a specific feedback circuitry of neurotransmitters that is associated with negative emotionality in Parkinson's
disease.
Animal studies have shown that prenatal exposure to the anticonvulsant drugs phenobarbital and phenytoin alters steroid hormone levels which consequently leads to disturbed sexual differentiation. In this study, possible sequelae of prenatal exposure to these anticonvulsants on gender development in humans were investigated. A follow-up study was carried out in phenobarbital- and phenytoin-exposed subjects and control subjects matched for age, sex, and the mothers' ages. Subjects were born in the Academic Medical Center between 1957 and 1972. Out of 243 exposed and 222 control subjects who were asked to volunteer, 147 exposed subjects (72 male, 75 female) and equal numbers of their matched control subjects participated in the follow-up study. They were interviewed and were asked to fill out questionnaires on gender role behavior, gender development, and sexual orientation. As a group, exposed and control subjects did not differ with respect to gender role behavior, although higher numbers of prenatally anticonvulsant-exposed subjects reported current or past cross-gender behavior and/or gender dysphoria. Three prenatally anticonvulsant-exposed subjects were transsexuals and had undergone sex reassignment surgery, a remarkably high rate given the rarity of transsexualism. In addition, two exposed males had exclusively homosexual experiences, whereas none of the control males reported exclusive homosexual behavior. The groups did not differ in attainment of pubertal psychosexual milestones.
• We investigated the antidepressant efficacy of l-deprenyl (selegiline), a selective monoamine oxidase B inhibitor (MAOI), in a six-week open trial of 17 patients with atypical depression. Such patients have previously been shown to benefit from nonselective MAOIs such as phenelzine sulfate. Ten patients (59%) responded to l-deprenyl, but nine required dosages above the 10 to 20 mg/day used in previous investigations. l-Deprenyl was superior to six weeks of placebo administered to diagnostically similar patients in a separate double-blind study. In contrast with previous findings with phenelzine, responders to l-deprenyl differed from nonresponders by having lower baseline anxiety ratings. Even at high dosages, there appeared to be fewer side effects with l-deprenyl than with nonselective MAOIs.
We describe 12 patients with Parkinson's disease and pathologic gambling. This association has apparently never been reported. The patients were selected from a Parkinson's disease unit of 250 patients. They met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for pathologic gambling. All patients underwent a neurologic, psychiatric, and psychologic examination, specifically noting the presence or absence of psychopathology in the spectrum of impulse control disorder and the nature of the gambling. Ten patients started gambling after the onset of Parkinson's disease and treatment with levodopa. The pathologic behavior was exclusively present or was markedly increased in “on” periods in 11 patients. All patients had motor fluctuations at the time of the study. Slot machines were the preferred source of gambling for 10 patients, similar to the Spanish gambling population. That the gambling behavior appears more often in the “on” periods of motor fluctuations and that it begins after the onset of Parkinson's disease in most patients and worsens with levodopa therapy suggest that it could be related to the dopaminergic tone in patients with Parkinson's disease and motor fluctuations (that is, it could represent a behavioral manifestation of pharmacologic treatment).
The selective monoamine oxidase (MAO) B inhibitor (-)deprenyl failed to produce any greater benefit than placebo in a limited double-blind trial conducted in depressive patients. Its relative freedom from the so-called cheese effect was confirmed, however, in drug-treated patients challenged IV with tyramine. There is evidence to suggest that this cheese effect, a facilitated tyramine-induced hypertensive response, is pharmacologically distinct from MAO inhibition proper. Thus, it is conceivable that its central counterpart, an enhanced noradrenaline release due to the access of traces of tyramine to the CNS, is a prerequisite for any therapeutic benifit obtainable with the MAO-inhibitory drugs in general.
In a clinical trial the effect of L-deprenil, a selective irreversible inhibitor of monoamine oxidase (M.A.O.) "type B" in potentiating the anti-kinetic properties of levodopa has been investigated in 223 patients. Both drugs were given orally, levodopa as 'Madopar' (levodopa plus the peripherally acting decarboxylase inhibitor, benserazide) 250 mg three times daily and L-deprenil 5 mg once or twice daily. The addition of L-deprenil to madopar therapy resulted in a statistically significant (P less than 0-01-0-001) reduction in patients' functional disability on average within 60 min after a single oral dose and lasting for 1 to 3 days. Dyskinesia occurred in 16 patients, psychosis in 14, orthostatic hypotension in 5, and nausea in 8. Reduction of the L-deprenil dose to 5 mg in these patients eliminated some of the side-effects. Two-thirds of the patients with side-effects had suffered from parkinsonism for between 7 and 15 years. 14% of the patients failed to respond to madopar-deprenil therapy. It is suggested that L-deprenil may act through inhibition of brain M.A.O. as well as by a psychostimulant effect similar to that of amphetamine which occurs through the release of dopamine. Both mechanisms would make more dopamine available at dopamine receptor sites.
Little is known of the metabolism of deprenyl either in man or animals. However, by analogy with that of the not dissimilar MAO inhibitor, pargyline (N-methyl-N-propynylbenzylamine), which is metabolized in mammals to benzylamine. The authors therefore sought to identify these compounds in human urine after the administration of therapeutically-active doses of (-)-deprenyl. Virtually all administered (-)-deprenyl appeared to be metabolized via methamphetamine by an as yet unknown enzymatic mechanism. A careful search for unmetabolized deprenyl proved negative.
A case of transvestism in a 24-year-old manic-depressive man is described. The behavior had been maintained for 2 years and disappeared soon after lithium treatment was begun. It has not returned during the first year on lithium. Dynamic and behavioral explanations for this unusual therapeutic response are considered. The dynamic explanation involves the assumption that the transvestism was perpetuated by mood-dependent motives that were eliminated by lithium. The behavioral explanation involves the assumption that the manic state itself became an intermittent reinforcer for the transvestism, and the lithium, by eliminating the mania, created a relatively permanent extinction period.
To the Editor.
—Selegiline is known to produce a variety of behavioral side effects, including hallucinations, nightmares, and sleep disturbance. A sensation of increased energy may occur at doses greater than 10 mg/d.1 Hypomania has been reported in a patient who received selegiline 5 mg twice daily immediately following adrenalstriatal transplantation, and it was attributed to the interaction between the two therapies.2 We read with interest the letter by Boyson3 regarding psychiatric effects of selegiline, and we want to share our experience with two patients in support of the occurrence of manic episodes as an adverse response to selegiline treatment.
Report of Cases.
—Case 1.
—A 62-year-old woman with Parkinson's disease of several years' duration was being treated with carbidopa/levodopa, bromocriptine, trihexyphenadyl, and nortriptyline. Selegiline was added to treat wearing-off phenomena, beginning with 5 mg daily and increasing to 5 mg twice daily. Within 7
Clinical evidence suggests that deprenyl may slow progression of Parkinson's disease, although mechanisms underlying this putative neuroprotective action remain poorly understood. To address this issue, we studied deprenyl in 12 parkinsonian patients using a single-blind, placebo-controlled, crossover design. After 1 month, deprenyl (10 mg/d) decreased the optimal levodopa requirement by 24% (oral) and 16% (intravenous). Levodopa-induced dyskinesias were prolonged by 430%, and antiparkinsonian action by 44%. Mood improved by 47%. One month after withdrawing deprenyl, effects on dyskinesias and mood had yet to return to baseline. There was no change in activities of circulating glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, and catalase, nor in levels of lipid peroxide and vitamin E. Deprenyl also failed to modify CSF levels of total glutathione and activities of glutathione peroxidase or superoxide dismutase. These effects on levodopa pharmacodynamics and mood complicate the interpretation of available investigations of deprenyl's neuroprotective action and increase the risk of adverse effects of levodopa.
To the Editor.
—The exciting news that selegiline (deprenyl, Eldepryl) may retard the progression of early Parkinson's disease,1,2 accompanied by the observation that few significant adverse effects were observed in these studies, has led physicians to treat many of their Parkinson's disease patients with this drug. This report concerns adverse psychiatric effects seen in my referral population of patients with Parkinson's disease. Over the last year, we have started selegiline therapy in approximately 60 patients, almost all of whom were both on multiple other antiparkinsonian medications and known to me for some time prior to this treatment. I have not included adverse effects that could be ameliorated by reduction of the dose of carbidopa/levodopa.Apparent adverse effects in the younger population were most common in physically small patients, especially women. Five otherwise healthy women in their 40s and 50s developed adverse effects, although only two of these had a
Thirteen parkinsonian patients drawn from two large parkinsonism clinics experienced hypersexuality as a consequence of anti-parkinsonian therapy. The cases include only those whose sexual behavior on treatment became a concern to the patient's family or a social agency. The majority of patients were men and had a relatively early onset of parkinsonian symptomatology. There was no relation between functional improvement and increased sexuality. Most patients showed some element of dose dependency between antiparkinsonian drugs and the hypersexual behavior. Prior sexual profile included from no sexual outlet to hypersexuality. Neither the prior history of psychiatric illness nor brain damage predisposed to such response on treatment, and in most patients, it was not a part of hypomania or a more diffuse psychiatric disturbance. We propose that hypersexuality on antiparkinsonian drugs is consequent to inhibition of prolactin secretion.
A synthetic ovarian hormone, diethylstilbestrol, was used to reduce the desire to cross-dress in a 65-year-old, gender-dysphoric transvestite. Antiandrogens may be of use in treating patients refractory or inaccessible to other clinical approaches.
The author presents a case report of a 46-year-old man with generalized anxiety disorder and transvestic fetishism who responded to treatment with buspirone. The patient stopped cross-dressing while taking buspirone, but alprazolam had no effect on the frequency of cross-dressing. The author discusses the implications of using buspirone in the treatment of both inhibited sexual desire and transvestic fetishism.
We investigated the antidepressant efficacy of l-deprenyl (selegiline), a selective monoamine oxidase B inhibitor (MAOI), in a six-week open trial of 17 patients with atypical depression. Such patients have previously been shown to benefit from nonselective MAOIs such as phenelzine sulfate. Ten patients (59%) responded to l-deprenyl, but nine required dosages above the 10 to 20 mg/day used in previous investigations. l-Deprenyl was superior to six weeks of placebo administered to diagnostically similar patients in a separate double-blind study. In contrast with previous findings with pheneizine, responders to l-deprenyl differed from nonresponders by having lower baseline anxiety ratings. Even at high dosages, there appeared to be fewer side effects with l-deprenyl than with nonselective MAOIs.
Hypersexuality induced by dopaminergic drug treatment in parkinsonian patients is a rarely reported side-effect. A case history is presented where it occurred together with hyperkinesias while the patient was treated with L-dopa and bromocriptine. An addictive misuse of these drugs complicate the guidance of this patient. Approximately three years after the beginning of hypersexuality he developed several paranoid-hallucinatory psychoses which subsided each time upon dose reduction.
The use of dopaminergic drugs may be associated with unmasking of a latent sexual deviation in parkinsonian patients.
This article reports a survey of childhood experiences and family dynamics reported by a sample of 85 cross-dressing males drawn from the readership of a magazine for transvestites. The sample had a higher percentage of only children and eldest children compared to a national sample and also a much closer relationship with their mothers than with their fathers. Their identification as nuclear or marginal transvestites or transsexuals is related to the quality of the reported relationship with the mother, to the factors they identify as associated with their cross-dressing, and to their sexual orientation. Covert cross-dressers account for over three fourths of the subjects, but those who were overt (their cross-dressing openly encouraged by female family members) show significantly different patterns and distributions on several variables. A constellation of family and parental relationships is proposed--drawn in part from the insights of object relations and family systems theory--which may contribute to the development of transvestism.
We treated 17 narcolepsy patients in a placebo-controlled, double-blind, crossover trial with 10-, 20-, 30-, and 40-mg daily doses of selegiline, a monoamine oxidase inhibitor widely used in Parkinson's disease. There was a dose-dependent as well as a statistically and clinically significant improvement in narcoleptic symptoms and polygraphic measures. At 40 mg, there was a 36% reduction in the number of daytime sleep episodes and a 34% reduction in their duration (compared with placebo, mean values). The number of excessive sleepiness episodes decreased by 43%, and the duration decreased by 47%. The number of cataplectic attacks was reduced by 89%. On the multiple sleep latency test, the REM sleep latency increased from 5.0 to 13.3 minutes, and the number of sleep-onset REM periods decreased from 3.1 to 0.6. Sleep (S1) latency was not changed. No intolerable adverse events occurred. The effective dose range was 20 to 40 mg, requiring a low-tyramine diet, which was easy to maintain. In conclusion, selegiline alleviates both main symptoms of narcolepsy--the abnormal sleep tendency and cataplexy. Thus, treatment with selegiline makes it possible to avoid polypharmacy and to use a potent stimulant without known addiction risk.
Studies suggest that Parkinson's disease (PD) is associated with a particular group of personality characteristics. With relative uniformity, PD patients are described as industrious, rigidly moral, stoic, serious, and nonimpulsive. In this controlled study, we used a recently developed personality questionnaire, Cloningers's Tridimensional Personality Questionnaire, to test the hypothesis that these personality traits are behavioural manifestations of damaged dopaminergic pleasure and reward systems. We found significantly less (p < 0.01) of a group of traits called "novelty seeking" in PD patients compared with matched medical controls. Patients with low novelty seeking are described as being reflective, rigid, stoic, slow-tempered, frugal, orderly, and persistent, characteristics similar to those in the clinical description of PD patients. We review evidence supporting the claim that novelty seeking is dopamine-dependent, and suggest that damage to the mesolimbic dopaminergic system causes the described personality profile of PD patients.
The relative benefits of selegeline hydrochloride (2 x 5 mg, 2 x 10 mg selegeline) were studied in 30 narcoleptic patients using a randomized, double-blind, placebo-controlled design. Patients were randomly assigned to three groups (placebo and 2 x 5 mg and 2 x 10 mg selegeline). After a 2-week washout period for previous anticataplectic and stimulant medication, the study started with a 2-day period of placebo intake for each group, continued by 14 days of medication, ending with a 2-day placebo period. Outcome was measured by comparison of four polysomnographies and four multiple sleep latency tests (MSLTs) performed during the initial and the final placebo and medication period. Each MSLT day included acoustic and visual vigilance tests. Blood pressure and pulse rate were monitored daily. Patients reported daily about mood, concentration, subjective sleep time, nocturnal awakenings, nocturnal wake times, number of naps, and occurrence of symptoms of the narcoleptic tetrad. Selegeline caused dose-dependent REM suppression during nighttime sleep and naps and increase of sleep and REM latency. Under selegeline, daytime sleepiness improved significantly and the number of sleep attacks and naps as well as the frequency of cataplexy were reduced. Selegeline at a dose of a least 20 mg/day is a potent drug for the treatment of all narcoleptic symptoms.