Treatment Of Impulse Control Disorders Research Articles

Diagnostics and treatment of impulse control disorders, psychosis and delirium: systemic review-based recommendations- guideline "Parkinson's disease" of the German Society of Neurology.

Impulse control disorders (ICD), psychosis and delirium are part of the spectrum of behavioural changes associated with Parkinson's disease (PD). The diagnostic and therapeutic management of these rather complex neuropsychiatric conditions has been updated in the clinical guideline by the German Society of Neurology (DGN). Recommendations are based on a systematic literature reviews, other relevant guidelines and expert opinion. Patients receiving dopamine agonists (DA) therapy should be informed about the symptoms and risks of an ICD and should be routinely screened for ICD symptoms. In the presence of an ICD, DA should be reduced or discontinued and psychotherapeutic treatment may be considered. Non-oral therapies (levodopa/carbidopa intestinal gel infusion or deep brain stimulation) may also be an option for appropriate candidates. Psychosis in PD often has a gradual onset. Cognitive and affective disorders, psychiatric and medical comorbidities as well as polypharmacy are risk factors for a psychosis. Non-pharmacological treatments should be implemented as soon as possible and anti-parkinsonian medications should be adjusted/reduced if feasible. For psychosis associated with PD, quetiapine or clozapine should be used on an as-needed basis and for as short a time as is necessary, with safety monitoring. Delirium in PD may be underdiagnosed due to an overlap with chronic neuropsychiatric features of PD. Although transient by definition, delirium in PD can lead to permanent cognitive decline, motor impairment and increased mortality. Management of delirium includes pharmacological and non-pharmacological interventions. The updated guideline encompasses the evidence-based diagnostic, non-pharmacological and pharmacological management of ICD, psychosis and delirium in PD.

Impulse Control Disorders in Parkinson's Disease: Epidemiology, Pathogenesis and Therapeutic Strategies.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are aberrant behavior such as pathological gambling, hypersexuality, binge eating, and compulsive buying, which typically occur as a result of dopaminergic therapy. Numerous studies have focused on the broad spectrum of ICDs-related behaviors and their tremendous impact on patients and their family members. Recent advances have improved our understanding of ICDs. In this review, we discuss the epidemiology, pathogenesis and treatment of ICDs in the setting of PD.

Decreased risk-taking and loss-chasing after subthalamic nucleus lesion in rats.

The subthalamic nucleus (STN) is known to play a role in the control of impulsivity of action and in impulsivity of choice under certain conditions. In order to assess its influence on decision-making under uncertainty, we have tested here the effects of bilateral STN lesions in rats performing a probability discounting task (PDT) and a "loss-chasing" task, both tasks assessing risky decision under uncertainty, but one in a positive context (probability to obtain a larger reward) and the other in a negative context (risk for a larger loss). The PDT measures the choice between a small certain and a large uncertain reward. Conversely, in the "loss-chasing" task, animals choose between accepting a small certain loss versus risking a larger but uncertain penalty. The results show that STN lesions reduce risk-taking in both the PDT and the loss-chasing task, suggesting that STN inactivation could decrease risky decision-making whatever the nature of the outcome in an ambiguous context. Interestingly, opposite results were found in a small number of animals for which the lesions extended to the area dorsal to the STN (in the zona incerta), such that these animals increased choice of the uncertain option in the PDT. These results confirm the specificity of STN involvement in these processes and may provide explanations for some side-effects reported in patients when STN manipulations extend to the Zona Incerta. They also support the choice of the STN as a target for the treatment of impulse control disorders in Parkinson's disease and in obsessive compulsive disorders.

Parkinson's disease polygenic risk score is not associated with impulse control disorders: A longitudinal study

ObjectiveTo examine the relationship between a Parkinson's disease (PD) polygenic risk score (PRS) and impulse control disorders (ICDs) in PD. BackgroundGenome wide association studies (GWAS) have brought forth a PRS associated with increased risk of PD and younger disease onset. ICDs are frequent adverse effects of dopaminergic drugs and are also more frequent in patients with younger disease onset. It is unknown whether ICDs and PD share genetic susceptibility. MethodsWe used data from a multicenter longitudinal cohort of PD patients with annual visits up to 6 years (DIG-PD). At each visit ICDs, defined as compulsive gambling, buying, eating, or sexual behavior were evaluated by movement disorders specialists. We genotyped DNAs using the Megachip assay (Illumina) and calculated a weighted PRS based on 90 SNPs associated with PD. We estimated the association between PRS and prevalence of ICDs at each visit using Poisson generalized estimating equations, adjusted for dopaminergic treatment and other known risk factors for ICDs. ResultsOf 403 patients, 185 developed ICDs. Patients with younger age at onset had a higher prevalence of ICDs (p < 0.001) as well as higher PRS values (p = 0.06). At baseline, there was no association between the PRS and ICDs (overall, p = 0.84). The prevalence of ICDs increased over time similarly across the quartiles of the PRS (overall, p = 0.88; DA users, p = 0.99). ConclusionDespite younger disease onset being associated with both higher PRS and ICD prevalence, our findings are not in favor of common susceptibility genes for PD and ICDs.

Impulse Control Disorders in Parkinson’s Disease

There is an increasing awareness that impulse control disorders (ICDs), including pathologic gambling and compulsive sexual behavior, can occur as a complication of Parkinson’s disease (PD). Anecdotal experience and case reporting have suggested an association between ICDs in PD and the use of dopamine agonists. Lacking established treatments for ICDs in PD, clinical management should initially consist of modifications to or discontinuation of dopamine replacement therapy, particularly dopamine agonists. It is important that PD patients be aware that dopamine agonist use may lead to the development of an ICD, and that clinicians monitor patients as part of routine clinical care. As empirically validated treatments for ICDs are emerging, it will be important to examine their efficacy and tolerability in individuals with co-occurring PD and ICDs.

The Kaplan–Meier method for estimating and comparing proportions in a randomized controlled trial with dropouts

ABSTRACTWe propose a method for estimating and comparing proportions of study participants who reached an event of interest during a randomized controlled trial. Standard methods for estimating this proportion include the intent-to-treat method, which counts the number who reached the event of interest divided by the total number of participants, and the completers-only method, which counts the number who reached the event only among those who completed the entire study. When participants drop out of the study early, however, these methods will either be biased or inefficient. We propose to use the Kaplan–Meier method from survival analysis to estimate the proportion of interest in this non-survival setting. We show through extensive simulation studies that the Kaplan–Meier method has less bias and is more efficient than the standard methods. We demonstrate the performance of all methods for estimating proportions in one sample and for comparing proportions across two samples. Finally, we apply the proposed method to a data-set for estimating and comparing proportions of patients who achieved treatment response during a Parkinson's disease trial for the treatment of impulse control disorders.

The in Vivo Neurochemical Profile of Selectively Bred High-Responder and Low-Responder Rats Reveals Baseline, Cocaine-Evoked, and Novelty-Evoked Differences in Monoaminergic Systems.

Relative to bred low-responder (bLR) rats, bred high-responder (bHR) rats have an exaggerated locomotor response to a novel environment, take more risks,are more impulsive, and more likely to exhibit compulsive drug-seeking behaviors. These phenotypic differences in addiction-related behaviors and temperament have previously been associated with differences in neurotransmitter signaling, including the mesolimbic dopamine system. In this study, we applied advanced in vivo microdialysis sampling in the nucleus accumbens of bHRs and bLRs to assess differences in basal and stimulated neurochemical efflux more broadly. We used liquid chromatography-mass spectrometry measurements of dialysate samples to quantify a panel of 17 neurochemicals, including dopamine, norepinephrine, serotonin, histamine, glutamate, GABA, acetylcholine, adenosine, DOPAC, 3-MT, HVA, 5-HIAA, normetanephrine, taurine, serine, aspartate, and glycine. We also applied a stable isotope labeling technique to assess absolute baseline concentrations of dopamine and norepinephrine in the nucleus accumbens. Finally, we investigated the role of norepinephrine tone in the nucleus accumbens on the bHR phenotype. Our findings show that bHRs have elevated basal and cocaine-evoked dopamine and norepinephrine levels in the nucleus accumbens compared to those of bLRs. Furthermore, norepinephrine signaling in the nucleus accumbens appeared to be an important contributor to the bHR phenotype because bilateral perfusion of the α1 adrenergic receptor antagonist terazosin (10 μM) into the nucleus accumbens abolished the response of bHRs to novelty. These findings are the first to demonstrate a role for norepinephrine in the bHR phenotype. They reveal a positive relationship between dopamine and norepinephrine signaling in the nucleus accumbens in mediating the exaggerated response to novelty and point to norepinephrine signaling as a potential target in the treatment of impulse control disorders.

Impulse Control and Related Disorders in Parkinson's Disease.

Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual, and eating behaviors, are a serious and increasingly recognized complication in Parkinson's disease (PD), occurring in up to 20% of PD patients over the course of their illness. Related behaviors include punding (stereotyped, repetitive, purposeless behaviors), dopamine dysregulation syndrome (DDS) (compulsive medication overuse), and hobbyism (e.g., compulsive internet use, artistic endeavors, and writing). These disorders have a significant impact on quality of life and function, strain interpersonal relationships, and worsen caregiver burden, and are associated with significant psychiatric comorbidity. ICDs have been most closely related to the use of dopamine agonists (DAs), while DDS is primarily associated with shorter acting, higher potency dopamine replacement therapy (DRT), such as levodopa. However, in preliminary research ICDs have also been reported to occur with monoamine oxidase inhibitor-B and amantadine treatment, and after deep brain stimulation (DBS) surgery. Other risk factors for ICDs may include sex (e.g., male sex for compulsive sexual behavior, and female sex for compulsive buying behavior); younger age overall at PD onset; a pre-PD history of an ICD; personal or family history of substance abuse, bipolar disorder, or gambling problems; and impulsive personality traits. Dysregulation of the mesocorticolimbic dopamine system is thought to be the major neurobiological substrate for ICDs in PD, but there is preliminary evidence for alterations in opiate and serotonin systems too. The primary treatment of ICDs in PD is discontinuation of the offending treatment, but not all patients can tolerate this due to worsening motor symptoms or DA withdrawal syndrome. While psychiatric medications and psychosocial treatments are frequently used to treat ICDs in the general population, there is limited empirical evidence for their use in PD, so it is critical for patients to be monitored closely for ICDs from disease onset and routine throughout its course. In the future, it may be possible to use a precision medicine approach to decrease the incidence of ICDs in PD by avoiding DA use in patients determined to be at highest risk based on their clinical and neurobiological (e.g., motor presentation, behavioral measures of medication response, genetics, dopamine transporter neuroimaging) profile. Additionally, as empirically validated treatments for ICDs and similar disorders (e.g., substance use disorders) emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.

Management of impulse control disorders in Parkinson's disease

Impulse control disorders (ICDs) have become a widely recognized non-motor complication of Parkinson's disease (PD) in patients taking dopamine replacement therapy (DRT). There are no current evidence-based recommendations for their treatment, other than reducing their dopaminergic medication. This study reviews the current literature of the treatment of ICDs including pharmacological treatments, deep brain stimulation, and psychotherapeutic interventions. Dopamine agonist withdrawal is the most common and effective treatment, but may lead to an aversive withdrawal syndrome or motor symptom degeneration in some individuals. There is insufficient evidence for all other pharmacological treatments in treating ICDs in PD, including amantadine, serotonin selective reuptake inhibitors, antipsychotics, anticonvulsants, and opioid antagonists (e.g. naltrexone). Large randomized control trials need to be performed before these drugs can be routinely used for the treatment of ICDs in PD. Deep brain stimulation remains equivocal because ICD symptoms resolve in some patients after surgery but may appear de novo in others. Cognitive behavioral therapy has been shown to improve ICD symptoms in the only published study, although further research is urgently needed. Further research will allow for the development of evidence-based guidelines for the management of ICDs in PD.

A systematic review of treatments for Impulse Control Disorders and related behaviours in Parkinson׳s disease

Impulse Control Disorders (ICDs) are a set of behaviours characterised by impulsivity despite known harm. Related to ICDs is the dopamine dysregulation syndrome (DDS), which is characterised by an addiction-like consumption of dopaminergic medication and punding. These behaviours all have an increased prevalence in Parkinson׳s disease (PD). The aim of this review is to identify treatments available for patients suffering from ICDs, DDS and punding in PD. Searches of The Cochrane Controlled Trials Register, Embase, Medline and PsychInfo were conducted, using the entire timescale available. Seven out of the 688 papers retrieved met the inclusion criteria and were considered in this systematic review. One class I study, one class II study, and five class IV studies were identified. All studies demonstrated a positive effect on ICDs in PD. Research in this field is still in its early stages. At present, there is insufficient evidence to recommend any treatment over another. There is a need for more methodologically robust research, using larger, more generalisable samples, randomisation and meaningful follow-up periods. In addition, the use of a validated outcome measures should be implemented in future research efforts.

Naltrexone for impulse control disorders in Parkinson disease: a placebo-controlled study.

Impulse control disorders (ICDs) in Parkinson disease (PD) are common and can be difficult to manage. The objective of this study was to determine the efficacy and tolerability of naltrexone, an opioid antagonist, for the treatment of ICDs in PD. Patients with PD (n = 50) and an ICD were enrolled in an 8-week, randomized (1:1), double-blind, placebo-controlled study of naltrexone 50-100 mg/d (flexible dosing). The primary outcome measure was response based on the Clinical Global Impression-Change score, and the secondary outcome measure was change in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) ICD score. Forty-five patients (90%) completed the study. The Clinical Global Impression-Change response rate difference favoring naltrexone in completers was 19.8% (95% confidence interval [CI] -8.7% to 44.2%). While this difference was not significant (odds ratio=1.6, 95% CI 0.5-5.2, Wald χ2 [df]=0.5 [1], p=0.5), naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD score over time compared with placebo (regression coefficient for interaction term in linear mixed-effects model=-7.37, F[df]=4.3 [1, 49], p=0.04). The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95% CI 9.9-19.9) for naltrexone and 7.5 points (95% CI 2.5-12.6) for placebo. Naltrexone treatment was not efficacious for the treatment of ICDs in PD using a global assessment of response, but findings using a PD-specific ICD rating scale support further evaluation of opioid antagonists for the treatment of ICD symptoms in PD. This study provides Class I evidence that in patients with PD and an ICD, naltrexone does not significantly increase the probability of achieving response. However, the study lacked the precision to exclude an important difference in response rates.

Diagnosis and treatment of impulse control disorders in patients with movement disorders.

Impulse control disorders are a psychiatric condition characterized by the failure to resist an impulsive act or behavior that may be harmful to self or others. In movement disorders, impulse control disorders are associated with dopaminergic treatment, notably dopamine agonists (DAs). Impulse control disorders have been studied extensively in Parkinson's disease, but are also recognized in restless leg syndrome and atypical Parkinsonian syndromes. Epidemiological studies suggest younger age, male sex, greater novelty seeking, impulsivity, depression and premorbid impulse control disorders as the most consistent risk factors. Such patients may warrant special monitoring after starting treatment with a DA. Various individual screening tools are available for people without Parkinson's disease. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease has been developed specifically for Parkinson's disease. The best treatment for impulse control disorders is prevention. However, after the development of impulse control disorders, the mainstay intervention is to reduce or discontinue the offending anti-Parkinsonian medication. In refractory cases, other pharmacological interventions are available, including neuroleptics, antiepileptics, amantadine, antiandrogens, lithium and opioid antagonists. Unfortunately, their use is only supported by case reports, small case series or open-label clinical studies. Prospective, controlled studies are warranted. Ongoing investigations include naltrexone and nicotine.

Add-on treatment of aripiprazole in an adult onychophagia patient

Nail biting (onychophagia) is a common disorder which has not been investigated yet. There are different opinions about to classify onychophagia, but according to DSM-IV-TR it is classified as impulse control disorder not otherwise specified. The knowledge about treatment of onychophagia is limited. There are a few studies about treatment of onychophagia with psychotherapy and a study with pharmacotherapy. Some studies suggest that an atypical antipsychotic aripiprazole may have beneficial effects in the treatment of impulse control disorders. In this study we report a case of onychophagia which has successfully treated with aripiprazole add-on to escitalopram treatment that has never reported before.

Dissociable effects of monoamine reuptake inhibitors on distinct forms of impulsive behavior in rats

RationaleHigh levels of impulsivity are a core symptom of psychiatric disorders such as ADHD, mania, personality disorders and drug addiction. The effectiveness of drugs targeting dopamine (DA), noradrenaline (NA) and/or serotonin (5-HT) in the treatment of impulse control disorders emphasizes the role of monoaminergic neurotransmission in impulsivity. However, impulsive behavior is behaviorally and neurally heterogeneous, and several caveats remain in our understanding of the role of monoamines in impulse control.ObjectivesThis study aims to investigate the role of DA, NA and 5-HT in two main behavioral dimensions of impulsivity.MethodsThe effects of selective DA (GBR12909; 2.5–10 mg/kg), NA (atomoxetine; 0.3–3.0 mg/kg) and 5-HT (citalopram; 0.3–3.0 mg/kg) reuptake inhibitors as well as amphetamine (0.25–1.0 mg/kg) were evaluated on impulsive action in the five-choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed reward task (DRT). In the 5-CSRTT, neuropharmacological challenges were performed under baseline and long intertrial interval (ITI) conditions to enhance impulsive behavior in the task.ResultsAmphetamine and GBR12909 increased impulsive action and perseverative responding and decreased accuracy and response latency in the 5-CSRTT. Atomoxetine increased errors of omission and response latency under baseline conditions in the 5-CSRTT. Under a long ITI, atomoxetine also reduced premature and perseverative responding and increased accuracy. Citalopram improved impulse control in the 5-CSRTT. Amphetamine and GBR12909, but not citalopram or atomoxetine, reduced impulsive choice in the DRT.ConclusionsElevation of DA neurotransmission increases impulsive action and reduces impulsive choice. Increasing NA or 5-HT neurotransmission reduces impulsive action.

Effects of selective dopaminergic compounds on a delay-discounting task

Impulsivity is widely regarded as a multidimensional trait that encompasses two or more distinct patterns of behavior, and dopaminergic systems are implicated in the expression of impulsive behavior in both humans and animal subjects. Impulsive choice, or the tendency to choose rewards associated with relatively little or no delay, has been extensively studied in humans and animal subjects using delay-discounting tasks. Here, delay-discounting procedures were used to assess the effects of receptor-selective dopaminergic agonists, antagonists, and dopamine transporter ligands on choices of immediate versus delayed sucrose pellets. The effects of d-amphetamine, GBR 12909, apomorphine, SKF 81297, sumanirole, pramipexole, ABT-724, SCH 23390, L-741,626, PG01037, and L-745,870 were assessed in 24 Sprague-Dawley rats. The only drugs to affect impulsive choice selectively without altering undelayed choice were the D1-like antagonist, SCH 23390 (0.01 mg/kg), and the D4 partial agonist, ABT-724 (3.2 mg/kg), which both increased impulsive choice. The shared effects of these compounds may be explained by their localization within the prefrontal cortex on different groups of neurons. None of the selective agonists and antagonists tested reduced impulsive choice, so further research is needed to determine if direct dopaminergic agonists or antagonists may be therapeutically useful in the treatment of impulse-control disorders.

Obsessive-Compulsive Disorder, Impulse Control Disorders and Drug Addiction

The basic concepts underlying compulsive, impulsive and addictive behaviours overlap, which may help explain why laymen use these expressions interchangeably. Although there has been a large research effort to better characterize and disentangle these behaviours, clinicians and scientists are still unable to clearly differentiate them. Accordingly, obsessive-compulsive disorder (OCD), impulse control disorders (ICD) and substance-related disorders (SUD) overlap on different levels, including phenomenology, co-morbidity, neurocircuitry, neurocognition, neurochemistry and family history. In this review we summarize these issues with particular emphasis on the role of the opioid system in the pathophysiology and treatment of OCD, ICD and SUD. We postulate that with progression and chronicity of OCD, the proportion of the OCD-related behaviours (e.g. checking, washing, ordering and hoarding, among others) that are driven by impulsive 'rash' processes increase as involvement of more ventral striatal circuits becomes prominent. In contrast, as SUD and ICD progress, the proportion of the SUD- and ICD-related behaviours that are driven by compulsive 'habitual' processes increase as involvement of more dorsal striatal circuits become prominent. We are not arguing that, with time, ICD becomes OCD or vice versa. Instead, we are proposing that these disorders may acquire qualities of the other with time. In other words, while patients with ICD/SUD may develop 'compulsive impulsions', patients with OCD may exhibit 'impulsive compulsions'. There are many potential implications of our model. Theoretically, OCD patients exhibiting impulsive or addictive features could be managed with drugs that address the quality of the underlying drives and the involvement of neural systems. For example, agents for the reduction or prevention of relapse of addiction (e.g. heavy drinking), which modulate the cortico-mesolimbic dopamine system through the opioid (e.g. buprenorphine and naltrexone), glutamate (e.g. topiramate), serotonin (e.g. ondansetron) or γ-aminobutyric acid (e.g. baclofen and topiramate) systems, may prove to show some benefit in certain forms of OCD. Based on the available evidence, we suggest that the treatment of patients with these disorders must account for alterations in the underlying motivations and neurobiology of the condition. We provide an initial guide to the specific treatments that future clinical trials might consider in patients with OCD. For example, it might be wise to test naltrexone in patients with co-morbid SUD and ICD, topiramate in patients with co-morbid ICD and eating disorders, and baclofen in patients with co-morbid Tourette's syndrome. These trials could also include scales aimed at assessing underlying impulsivity (e.g. Barratt Impulsiveness Scale) to check whether this construct might predict response to drugs acting on the reward system.

Amantadine use associated with impulse control disorders in Parkinson disease in cross‐sectional study

A recent controlled clinical trial suggested a role for amantadine as a treatment for pathological gambling in patients with Parkinson disease (PD). Analyzing data from a large cross-sectional study of impulse control disorders (ICDs) in PD, amantadine use (n = 728), vs no amantadine use (n = 2,357), was positively associated with a diagnosis of any ICD (17.6% vs 12.4%, p < 0.001) and compulsive gambling specifically (7.4% vs 4.2%, p < 0.001). This amantadine association remained after controlling for covariates of amantadine use, including both dopamine agonist use and levodopa dosage. Further research, including larger clinical trials, is needed to assess the role of amantadine in the development and treatment of ICDs in PD.

Decreased ventral striatal activity with impulse control disorders in Parkinson's disease

A range of impulse control disorders (ICDs) are reported to occur in Parkinson's disease (PD). However, alterations in brain activity at rest and during risk taking occurring with ICDs in PD are not well understood. We used both arterial spin labeling perfusion functional magnetic resonance imaging (fMRI) to directly quantify resting cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) fMRI to measure neural responses to risk taking during performance on the Balloon Analogue Risk Task (BART). Eighteen PD patients, either with a diagnosis of one or more ICDs (N = 9) or no lifetime ICD history (N = 9), participated. BOLD fMRI data demonstrated that PD patients without an ICD activate the mesocorticolimbic pathway during risk taking. Compared with non-ICD patients, ICD patients demonstrated significantly diminished BOLD activity in the right ventral striatum during risk taking and significantly reduced resting CBF in the right ventral striatum. ICDs in PD are associated with reduced right ventral striatal activity at rest and diminished striatal activation during risk taking, suggesting that a common neural mechanism may underlie ICDs in individuals with PD and those without PD. Thus, treatments for ICDs in non-PD patients warrant consideration in PD patients with ICDs.

Dopamine and impulse control disorders in Parkinson's disease.

There is an increasing awareness that impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, can occur as a complication of Parkinson's disease (PD). In addition, other impulsive or compulsive disorders have been reported to occur, including dopamine dysregulation syndrome (DDS) and punding. Case reporting and prospective studies have reported an association between ICDs and the use of dopamine agonists (DAs), particularly at greater dosages, whereas dopamine dysregulation syndrome has been associated with greater dosages of levodopa or short-acting DAs. Data suggest that risk factors for an ICD may include male sex, younger age or younger age at PD onset, a pre-PD history of ICD symptoms, personal or family history of substance abuse or bipolar disorder, and a personality style characterized by impulsiveness. Although psychiatric medications are used clinically in the treatment of ICDs, there is no empiric evidence supporting their use in PD. Therefore, management for clinically significant ICD symptoms should consist of modifications to dopamine replacement therapy, particularly DAs, and there is emerging evidence that such management is associated with an overall improvement in ICD symptomatology. It is important that PD patients be aware that DA use may lead to the development of an ICD, and that clinicians monitor patients as part of routine clinical care. As empirically validated treatments for ICDs are emerging, it will be important to examine their efficacy and tolerability in individuals with cooccurring PD and ICDs.

Pathological Hypersexuality Induced by Dopamine Replacement Therapy in a Patient with Progressive Supranuclear Palsy

Back to table of contents Previous article Next article LETTERFull AccessPathological Hypersexuality Induced by Dopamine Replacement Therapy in a Patient with Progressive Supranuclear PalsyYang Yeol Kim M.D.Hye Yoon Park M.D.,Jong Min Kim M.D., Ph.D.,Ki Woong Kim M.D., Ph.D.,Yang Yeol Kim M.D.Search for more papers by this authorHye Yoon Park M.D.Search for more papers by this author,Jong Min Kim M.D., Ph.D.Search for more papers by this author,Ki Woong Kim M.D., Ph.D.Search for more papers by this author,Published Online:1 Oct 2008AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor : The pathogenesis of pathological hypersexuality is still in controversy. To our knowledge, this is the first report of pathological hypersexuality induced by two different dopamine receptor agonists in a single patient with progressive supranuclear palsy. In this case, dopamine D2 receptor agonism, perhaps specifically D3 receptor subclass agonism, might have played a key role in the development of pathological hypersexuality induced by dopamine replacement therapy. Case Report An 83-year-old man with progressive supranuclear palsy was being treated with Sinemet (carbidopa/ L -dopa 25 mg/100 mg, 125 mg t.i.d.) for 8 months. Due to nausea, Sinemet was replaced by low dose madopar ( L -dopa/benserazid 100 mg/25 mg, 62.5 mg t.i.d.) and bromocriptine (2.5 mg t.i.d.). For the following 2 months, pathological hypersexuality (sexually suggestive remarks, touching, kissing, disrobing, exposing genitalia, facial flushing, penile erection, public masturbation) slowly developed. At this point, his serum testosterone level was normal (2.3 ng/ml), whereas serum prolactin level was suppressed to 1.3 ng/ml. His pathological hypersexuality completely disappeared 2 weeks after discontinuation of bromocriptine. After 4 weeks, pramipexole (0.125 mg b.i.d.), another dopamine receptor agonist, was added instead of bromocriptine since his motor performance deteriorated. After 1 week of pramipexole, all the hypersexual symptoms reemerged. At this point, his serum prolactin level was 2.2 ng/ml.His pathological hypersexuality completely disappeared again just by discontinuing pramipexole. Then we titrated madopar up to 125 mg t.i.d. instead of adding other dopamine receptor agonist. After 3 weeks, his motor performance improved with partial reemergence of hypersexual symptoms (penile erection, facial flushing, sexually suggestive remarks, touching). However, the severity of the reemerged symptoms was much more tolerable than those induced by dopamine receptor agonist. At this point, his serum prolactin level was not suppressed (13.3 ng/ml).Comments This case confirmed an earlier observation 1 through rechallenging two different kinds of dopamine receptor agonists alternatively in a single patient, and illustrated several characteristics of dopamine replacement therapy-induced pathological hypersexuality. First, dopamine receptor agonists may be more likely to induce pathological hypersexuality than L -dopa since pathological hypersexuality induced by combination therapy of either bromocriptine or pramipexole with L -dopa was much more severe than that induced by L -dopa monotherapy. Second, dopamine replacement therapy-induced pathological hypersexuality may be mediated by D2 receptor agonism since pramipexole has no affinity for D1 receptor classes. 2 Third, dopamine receptor agonist-induced pathological hypersexuality may perhaps be mediated by the excessive stimulation of the D3 receptor subclass since pramipexole binds preferentially to D3 receptors with high affinity. 2 Fourth, the difference in the risk of pathological hypersexuality between dopamine receptor agonists and L -dopa may be attributed to their differential suppression of prolactin secretion since serum prolactin was abruptly suppressed when bromocriptine or pramipexole was added to L -dopa. Inhibitory effect of dopamine receptor agonists on prolactin secretion was suggested as a main pathogenic mechanism of hypersexuality. 3Department of NeuropsychiatryDepartment of NeurologyDepartment of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnamsi, Gyeonggido, KoreaReferences1 . Klos KJ, Bower JH, Josephs KA, et al: Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson’s disease and multiple system atrophy. Parkinsonism Relat Disord 2005; 11:381–386Google Scholar2 . Foley P, Gerlach M, Double KL, et al: Dopamine receptor agonists in the therapy of Parkinson’s disease. J Neural Transm 2004; 111:1375–1446Google Scholar3 . Uitti RJ, Tanner CM, Rajput AH, et al: Hypersexuality with antiparkinsonian therapy. Clin Neuropharmacol 1989; 12:375–383Google Scholar FiguresReferencesCited byDetailsCited byEffect of Dopaminergic Therapy on Impulse Control Disorders in Patients With a Prolactinoma26 September 2022 | Cognitive and Behavioral Neurology, Vol. Publish Ahead of PrintAnnales d'Endocrinologie, Vol. 78Journal of the Neurological Sciences, Vol. 374Diagnosis and treatment of impulse control disorders in patients with movement disorders12 February 2013 | Therapeutic Advances in Neurological Disorders, Vol. 6, No. 3Impulse Control Disorders Associated With Dopaminergic Medication in Patients With Pituitary AdenomasClinical Neuropharmacology, Vol. 34, No. 5Impulsive-compulsive spectrum behaviors in pathologically confirmed progressive supranuclear palsy8 March 2010 | Movement Disorders, Vol. 25, No. 5Current awareness: Pharmacoepidemiology and drug safety26 June 2009 | Pharmacoepidemiology and Drug Safety, Vol. 18, No. 7 Volume 20Issue 4 Fall, 2008Pages 496-497 Metrics PDF download History Published online 1 October 2008 Published in print 1 October 2008