Naltrexone Use in Treating Hypersexuality Induced by Dopamine Replacement Therapy: Impact of OPRM1 A/G Polymorphism on Its Effectiveness

Abstract

Hypersexuality is a well-known adverse side effect of dopamine replacement therapy (DRT), and anti-craving drugs could be an effective therapeutic option. Our aim was to update the knowledge on this issue, particularly on the influence of an Opioid Receptor Mu 1 (OPRM1) genetic polymorphism. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We also analyzed a case of iatrogenic hypersexuality that occurred in a patient treated with DRT. An analysis of the OPRM1 gene was performed on said patient. Our search identified 597 publications, of which only 7 were included in the final data synthesis. All seven publications involved naltrexone use. Five of them were case reports. None of the publications mentioned DRT side effects, nor did they report genetic data. Regarding our case report, the introduction of naltrexone corresponded with the resolution of the patient’s hypersexuality. Moreover, the patient carried the A/G genotype, which has been reported to be associated with a stronger response to naltrexone for patients with an alcohol use disorder. Although studies are inconclusive so far, naltrexone could be an interesting therapeutic option for resistant hypersexuality due to DRT. Carrying the A/G genotype could help explain a good response to treatment.

Sexual Disorders and Quality of Life in Parkinson's Disease

“…89,90 In PD, the precise mechanism of compulsive sexual behavior is not clearly known, 91 but both the dopaminergic and serotonergic pathways can contribute to the development and maintenance of compulsive sexual behavior 92 and to the high level of anxiety in this disease. 86,92 In addition, compulsive sexual behavior is commonly associated with depressed mood. 86 It is essential to warn about the risk of pathological behaviors and side effects of the medication, as patients may not be able to immediately report the symptoms they feel voluntarily.…”

“…86,92 In addition, compulsive sexual behavior is commonly associated with depressed mood. 86 It is essential to warn about the risk of pathological behaviors and side effects of the medication, as patients may not be able to immediately report the symptoms they feel voluntarily. 90,93 Thus, in PD, compulsive sexual behavior can be a challenge because there is no approved therapy, and the urgent first step is to reduce or discontinue the use of dopaminergic agonists.…”

“…62 In a recent systematic review, naltrexone was used with promising results in compulsive sexual behavior refractory in PD, but further studies yet are needed with this drug to compulsive sexual behavior. 86…”

Impulse Control Disorders in Parkinson’s Disease: From Bench to Bedside

“…A number of pharmacologically distinct psychotropic agents have been examined as interventions, but consensus treatment recommendations are still absent as these studies have typically employed small sample sizes. Positive results have been observed with naltrexone, an opioid antagonist ( Bosco et al, 2012 ; Verholleman et al, 2020 ); citalopram, a selective serotonin reuptake inhibitor (SSRI) ( Ye et al, 2014 ); atomoxetine, a selective norepinephrine reuptake inhibitor ( Kehagia et al, 2014 ; Rae et al, 2016 ); valproate, an anticonvulsant mood stabilizer ( Hicks et al, 2011 ); clozapine, an atypical antipsychotic ( Rotondo et al, 2010 ); and amantadine, a weak N-methyl-D-aspartate (NMDA) receptor antagonist ( Thomas et al, 2010 ). However, naltrexone ( Papay et al, 2014 ), various SSRIs ( Bosco et al, 2012 ; Jeon and Bortolato, 2020 ), amantadine ( Thomas et al, 2010 ; Weintraub et al, 2010b ), and several atypical antipsychotics and glutamatergic modulators ( Jeon and Bortolato, 2020 ) have also been reported to have no or negative impact on PD + ICD.…”

A Case–Control Study on Behavioral Addictions and Neurocognition: Description of the BANCO and BANCO2 Protocols

“…22 Pharmacological treatments, such as naltrexone, which is known to inhibit dopamine release in the ventral part of the striatum and is used as a treatment to regulate craving in alcohol use disorder, have been used with patients with a compulsive sexual behavior disorder and resulted in improvements in their symptoms. [22][23][24] These arguments are thus in favour of considering compulsive sexual behavior disorder as a BA, which could permit the expansion of alternative treatments and research, thereby providing benefit to patients. 25 The concept of FA emerged during the previous century, but human research has primarily emerged in the last decade.…”