Dopamine Agonist Treatment Research Articles

Anastrozole as add-on therapy for cabergoline-resistant prolactin-secreting pituitary adenomas: real-life experience in male patients

IntroductionProlactin-secreting adenoma (PRLoma) can present as large and invasive neoplasm, with increased markers of cellular proliferation. First-line approach is Dopamine Agonists (DAs) treatment; however, DA-resistance has been reported, especially in male patients. Estrogens induce lactotroph cell replication and PRL secretion: the use of anti-estrogen treatment in patients with PRLoma have been described in few cases. We reported our experience regarding treatment with the aromatase inhibitor anastrozole (ANA) as add-on therapy for male patients with DA resistant PRLoma.Materials and methodsWe describe four male patients (26, 38, 29 and 19 years old at diagnosis), with PRLoma (median diameter 26 mm, PRL 7730 μg/L). They were resistant to cabergoline (CAB, > 2 mg/week) in terms of PRL secretion and tumor size reduction. ANA 1 mg/day was added to the maximum tolerated dose of CAB for at least 1 year. Magnetic Resonance was performed at baseline, after 6 months of CAB + ANA combination and every 12 months afterward.ResultsPRL levels decreased in all patients after CAB + ANA (mean − 70%, range − 44/− 97%), achieving a normalization of PRL levels in one case. Tumor size decreased in all cases (mean − 47%, range − 24.5/− 68%). No severe adverse effects have been reported, a moderate weight gain has been observed in two cases.ConclusionsAddition of an aromatase inhibitor (ANA) to the dopamine agonist therapy improved the control of prolactin levels and induced tumour regression.

Abstract #1003713: Cabergoline Induced Psychosis During Medical Therapy of Macroprolactinoma

Dopamine agonist (DA) treatment is the mainstay of therapy for prolactinomas and in many tumors can result in significant decreases in tumor size. DA therapy is not without its risks however, with some patients reporting adverse effects such as nausea, lightheadedness, and rarely increased impulsivity or even psychosis. Here we present a case involving a patient with macroprolactinoma on DA therapy with cabergoline (CBG) who developed psychosis requiring discontinuation of CBG, and eventually transsphenoidal surgery (TPS) as well as stereotactic radiotherapy (STRT) to diminish the effects of his giant prolactinoma.

Successful Pregnancies in an Acromegalic Woman After Non-Radical Pituitary Adenomectomy for Somatoprolactinoma

Background: Pregnancy is unusual in patients with acromegaly due to somatotropinomas or somatoprolactinomas. Fertility is impaired because of hormonal hypersecretion, pituitary damage by tumor compression or both. Managing somatoprolactinomas and fertility issues are often challenging. Clinical Case: A 20-year woman with primary amenorrhea and headache was diagnosed with hypogonadotrophic hypogonadism secondary to hyperprolactinemia (2500 µg/L, n<23 µg/L). No other abnormalities were found on the pituitary function screening tests. MRI revealed an intra and suprasellar adenoma (2.5x1.8x1.8 cm) with optic chiasm compression. The onset of menses occurred after 11 months under dopaminergic treatment, and tumor size diminished (1.9x1.5x1.5 cm), bringing on optic chiasm decompression. She remained under dopamine agonist treatment for 6 years, when she realized extremities enlargement and height increase by 3 cm. Acromegaly was confirmed by blood levels of IGF-1 (3.37xULN), GH (8 µg/L, n<8 µg/L), and GH nadir (4.3 µg/L, n<1 µg/L) during OGTT. Then, octreotide LAR was added to cabergoline treatment while waiting for elective surgical treatment. She underwent to transsphenoidal endonasal neurosurgical microscopy approach guided by neuronavigation, with the removal of a large portion of tumor. However, it was not possible to extract the part of invasive adenoma close to right carotid artery due to the risk of vascular and intracavernous cranial nerves injury. Immunohistochemistry analysis of the adenoma was positive only for GH cells with low Ki67 index (<1%). Due to the poor biochemical control (unsuppressed post-OGTT GH, IGF-1 1.66xULN and PRL 301 µg/L) and the presence of a small stable tumor residue, treatment with cabergoline and somatostatin analogues was maintained (3-year octreotide LAR, transitioned to lanreotide in an attempt to achieve a better biochemical response). After 14 years of the initial diagnosis and 5 years post-surgery, the patient expressed the desire to get pregnant and all medications in use were suspended. In the following 3 years, she had two uneventful gestation without complications or worsen of acromegaly; she only breastfed for few months after her first pregnancy. The second one was a twin pregnancy. After one year, the MRI revealed no increase of tumor mass (1.0x0.3x1.0 cm), and PRL levels withing normal range, IGF-1 slightly elevated, but GH not suppressed by OGTT. Cabergoline was reintroduced and the biochemical control of acromegaly was achieved. Conclusion: We reported the very unusual spontaneous conception and normal course of pregnancies in a woman with acromegaly, who was submitted to successful transsphenoidal neurosurgical microscopy approach in which large part of the tumor was removed and the normal pituitary tissue was preserved, allowing fertility restoration.

Cure and Hormonal Control After Prolactinoma Resection: Case Series and Systematic Review.

ContextSurgical management of prolactinomas is an important treatment for patients intolerant of dopamine agonist therapy. However, predictors of postoperative outcomes remain unclear.ObjectWhile transsphenoidal surgical resection (TSSR) is important second-line therapy in prolactinoma patients, predictors of surgical cure and biochemical remission following TSSR remain sparse.MethodsA retrospective review of prolactinoma patients undergoing TSSR at the USC Pituitary Center from 1995 to 2020 was conducted. Participants were categorized as surgical cure (normalization of serum prolactin without medical treatment), surgical noncure, biochemical control (prolactin normalization with or without adjuvant therapy), and nonbiochemical control. A systematic review of the outcomes of surgically managed prolactinomas was performed.ResultsThe 40 female and 16 male participants had an average age of 35.6 years. Prior treatment included transsphenoidal resection (6, 11%) and dopamine agonist treatment (47, 84%). The 40 macroadenomas and 15 microadenomas exhibited suprasellar extension (24, 43%) and parasellar invasion (20, 36%). Fifteen (27%) were purely intrasellar. Gross total resection was achieved in 25 patients (45%) and subtotal in 26 (46%). Surgical cure was achieved in 25 patients (46%) and biochemical control in 35 (64%). Surgical cure was more likely in smaller, noninvasive tumors, those that were fully resected, and patients with lower preoperative (< 1000 ng/mL) and immediately postoperative (< 7.6 ng/mL) prolactin levels. Ten of 26 patients (38%) undergoing adjuvant therapy achieved biochemical control, which was less likely in men and those with higher preoperative prolactin or invasive tumors.ConclusionSurgical resection of prolactinomas is a safe procedure that, when offered judiciously, can achieve symptom and/or biochemical control in a majority of patients. A variety of predictors may be useful in advising patients on likelihood of postoperative remission.

An Unusual Complication of Cabergoline Treatment of Macroprolactinomas

Dopamine agonist (DA) treatment is the first choice treatment of prolactinomas. Optic chiasm prolapse with secondary visual deterioration is an unusual and rare complication of DA treatment. A 40-year-old man with giant prolactinoma was successfully treated by cabergoline. After 14 months, he presented with a visual impairment with no ophthalmologic anomalies that could explain this worsening. The pituitary magnetic resonance imaging (MRI) revealed an important shrinkage of prolactinoma with a prolapse and a central atrophy of optic chiasm secondary to the adenoma shrinkage. This case highlights the need of regular assessment of visual field all along cabergoline treatment of macroprolactinomas despite initial improvement or even normalization of visual field, to promptly identify an optic chiasm prolapse and avoid the optic chiasm atrophy. J Endocrinol Metab. 2021;11(2):52-55 doi: https://doi.org/10.14740/jem730

An Unusual Complication of Cabergoline Treatment of Macroprolactinomas

Dopamine agonist (DA) treatment is the first choice treatment of prolactinomas. Optic chiasm prolapse with secondary visual deterioration is an unusual and rare complication of DA treatment. A 40-year-old man with giant prolactinoma was successfully treated by cabergoline. After 14 months, he presented with a visual impairment with no ophthalmologic anomalies that could explain this worsening. The pituitary magnetic resonance imaging (MRI) revealed an important shrinkage of prolactinoma with a prolapse and a central atrophy of optic chiasm secondary to the adenoma shrinkage. This case highlights the need of regular assessment of visual field all along cabergoline treatment of macroprolactinomas despite initial improvement or even normalization of visual field, to promptly identify an optic chiasm prolapse and avoid the optic chiasm atrophy. J Endocrinol Metab. 2021;11(2):52-55 doi: https://doi.org/10.14740/jem730

Apoplexy of microprolactinomas during pregnancy: report of five cases and review of the literature.

Prolactinomas frequently cause amenorrhoea, galactorrhoea and infertility and require dopamine agonist (DA) treatment to normalize prolactin levels and hence, restore ovulation. The vast majority of female patients harbour microprolactinomas in whom DA treatment is usually discontinued at the time of pregnancy diagnosis and surveillance is generally limited as the symptomatic growth is considered very rare. We report five cases of women harbouring a microprolactinoma in whom symptomatic pituitary apoplexy occurred during pregnancy. Only one necessitated surgery during pregnancy, while the others were treated conservatively by reintroducing DAs in three. A systematic literature review found reports of four additional cases among 20 cases of prolactinomas (both macro- and micro-prolactinomas) complicated by apoplexy during pregnancy. During pregnancy, pituitary apoplexy may occur in pre-existing microprolactinomas, causing tumour enlargement and headache, which may be self-limiting but may require intervention by re-initation of dopamine agonists or surgery. Our literature review confirms that this clinical event is rare; nevertheless, physicians managing pregnant patients with microprolactinomas must be aware that symptomatic pituitary apoplexy may incidentally occur in all trimesters of pregnancy and require prompt radiological, endocrine and ophthalmological assessment and treatment.

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

Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by symptoms that impact both motor and non-motor domains. Outside of motor impairments, PD patients are at risk for impulse control disorders (ICDs), which include excessively disabling impulsive and compulsive behaviors. ICD symptoms in PD (PD + ICD) can be broadly conceptualized as a synergistic interaction between dopamine agonist therapy and the many molecular and circuit-level changes intrinsic to PD. Aside from discontinuing dopamine agonist treatment, there remains a lack of consensus on how to best address ICD symptoms in PD. In this review, we explore recent advances in the molecular and neuroanatomical mechanisms underlying ICD symptoms in PD by summarizing a rapidly accumulating body of clinical and preclinical studies, with a special focus on the utility of rodent models in gaining new insights into the neurochemical basis of PD + ICD. We also discuss the relevance of these findings to the broader problem of impulsive and compulsive behaviors that impact a range of neuropsychiatric syndromes.

Outcomes of Transsphenoidal Microsurgery for Prolactinomas - A Contemporary Series of 162 Cases.

Renewed interest in transsphenoidal surgery (TSS) as a therapeutic option for prolactinomas has emerged. This study is aimed at defining the current role of pituitary surgery in the management of prolactinomas. In this retrospective, consecutive single-center study, 162 patients who underwent primary microscopic TSS for prolactinomas between 2006 and 2019 were analyzed regarding surgical indication, previous dopamine-agonist (DA) treatment, early remission rates (3 months postoperatively), surgical complications and pituitary function. Seventy-four microprolactinomas and 88 macroprolactinomas were operated by TSS. 62.3% of the patients had received prior DA treatment. For microprolactinomas, the predominant indication for surgery was patient's wish (41.9%), while indications for macroprolactinomas varied. For enclosed microprolactinomas, the initial remission rate was 92.1%, while for macroprolactinomas, the rate was 70.4%. No significant difference of remission rates was found between DA-pretreated (65.3%) and non-pretreated (72.1%) patients (p=0.373).None of the patients suffered a significant complication. Re-operation for a postoperative cerebrospinal fluid leak was required in one patient (0.6%). Permanent postoperative deterioration of pituitary function was only observed in one of 158 patients with surgery for a prolactinoma (0.6%). Improvement of pituitary function was observed in 8 of 25 patients (32%) with preoperative deficits. Transsphenoidal microsurgery is safe and efficient for treatment of prolactinomas. It is particularly suitable for enclosed prolactinomas. The patient should be well informed of the pros and cons of the treatment options, which include DA medication and TSS, and the patient's preference should be taken into account during decision-making.

Huzursuz Bacaklar Sendromunda Dopamin Agonisti Tedavisi ile İlişkili Davranış Değişiklikleri: Retrospektif Bir Çalışma

Objective: Restless legs syndrome (RLS) is a neurological sensorimotor disease. Behavioral changes are little-known concern during the treatment and follow-up of RLS. The aim of the study is to highlight the behavioral changes associated with dopamine agonist treatment in the follow-up of RLS, such as dopamine dysregulation syndrome (DDS) and impulse control disorder (ICD). Material and Methods: We analyzed clinical data from RLS patients' files from the previous 15 years retrospectively. The patients receiving dopaminergic monotherapy for RLS, who came to follow-up on a regular basis and whose last examination was within the last 6 months were chosen. The average age of patients without behavioral changes was 48.60±9.21 years. Results: Of the patients' complaints, legs were affected in 90.90%, arms and legs together were affected in 9.09%. Dopamine agonist-related changes were observed in 6 female patients. Mean age of these patients was 40.16±9.23 years old. They showed behavioral abnormalities such as uncontrolled drug use, shopping curiosity, hypersexuality, smoking, and space decoration. One patient presented with manic episode together with DDS. The average age of RLS patients who experienced behavioral changes was younger. Average dose at which behavior changes were observed was unclear since 4 of 6 patients with behavioral changes developed DDS. Despite using a regular-low dose agonist, the other two female patients showed ICD without DDS. Conclusion: With dopaminergic treatment, behavioral changes that may cause problems in family and social life can develop. When prescribing dopaminergic medications, it is important to ask if the patient has any behavioral changes and pay close attention in a busy polyclinic.

Identification of risk factors for impulse-control disorder symptoms in patients with Parkinson’s disease

Parkinson’s disease (PD) is one of the motoric neurodegenerative disorders that has the fastest-growing prevalence, disability, and death rate compared to other neurological disorders. Globally, from 1990 to 2015, the number of individuals with PD increased by 118%, up to around 6.2 million. There are several motor symptoms and non-motor symptoms that occur in Parkinson’s disease. One of the non-motor symptoms that occur is Impulse-Control Disorder (ICD). In PD, there are 4 main symptoms of ICD that often occur such as pathological gambling, binge-eating, compulsive buying, and compulsive sexual behaviour. ICD is often discovered when the treatment of PD begins, so this research focused on the incidence of ICD as a result of the treatment of PD. The purpose of this study is to identify risk factors for the type and number of ICD symptoms that occur in patients with PD. Both binary and multiclass classification tree methods were implemented to identify risk factors associated with the incidence of ICD for PD patients. Imbalance data problems that arose were handled with Synthetic Minority Over-sampling Technique (SMOTE). The results obtained show that the STAI-Trait total score is a risk factor that always appears for each type of, and the number of type of, ICD symptoms that appear. Moreover, risk factors that only appear in several symptoms are the length of education taken, STAI-State total score, age, duration of PD, SCOPA-AUT total score, MOCA total score, and MDS-UPDRS 3 total score. While, risk factors that only appear for a particular symptom are family history of PD, DAT binding ratio, and dopamine agonist treatment.

Long-term Outcome of Microscopic Transsphenoidal Surgery for Prolactinomas as an Alternative to Dopamine Agonists.

BackgroundAlthough long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy.MethodsIn this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA).ResultsThe median age and median follow-up period were 31 (16–73) years and 139.1 (12.2–319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality.ConclusionTSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA.

Use of dopamine agonists to target angiogenesis in women with endometriosis.

Endometriosis requires medical management during a woman's reproductive years. Most treatments aim to create a hypoestrogenic milieu, but for patients wishing to conceive, drugs that allow normal ovarian function are needed. Targeting angiogenesis, a hallmark of the disease, using dopamine agonists (DAs) is a promising strategy for endometriosis treatment. Herein, we review experimental and clinical data that investigate this concept. In experimental models of endometriosis, DAs (bromocriptine, cabergoline, quinagolide) downregulate proangiogenic and upregulate antiangiogenic pathways in inflammatory, endothelial and endometrial cells, blocking cellular proliferation and reducing lesion size. Impaired secretion of vascular endothelial growth factor (VEGF) and inactivation of its receptor type-2 are key events. VEGF inhibition also reduces nerve fiber density in lesions. In humans, quinagolide shows similar effects on lesions, and DAs reduce pain and endometrioma size. Moreover, a 20-fold downregulation of Serpin-1, the gene that encodes for plasminogen activator inhibitor 1 (PAI-1), has been observed after DAs treatment. Pentoxifylline, a PAI-1, increases pregnancy rates in women with endometriosis. Thus, the data support the use of DAs in the medical management of endometriosis to reduce lesion size and pain while maintaining ovulation. A combined approach of DAs and pentoxifylline is perhaps a smart way of targeting the disease from a completely different angle than current medical treatments.

Increased prevalence of impulse control disorder symptoms in endocrine diseases treated with dopamine agonists: a cross-sectional study

IntroductionImpulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions.Materials and methodsA cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s disease (QUIP).ResultsCompared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%, p < 0.01), any ICD (46% vs. 24%, p < 0.01), any related behavior (31% vs. 17%, p < 0.05), compulsive sexual behavior (27% vs. 14%, p < 0.04), and punding (20% vs. 7%, p < 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior [odds ratio (OR) 2.43] and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82).DiscussionDespite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions.

Bipolar Spectrum disorders in Parkinson's disease: a systematic evaluation.

Psychiatric disorders are very common in patients affected by Parkinson's disease (PD). However, comorbidity with Bipolar Spectrum disorders is understudied. The aim of this study is to explore the clinical correlates of PD associated with Bipolar Spectrum disorders. One hundred PD patients were screened for psychiatric comorbidities, cognitive profile, motor, and non-motor symptoms. The sample was divided into three groups: PD-patients with Bipolar Spectrum disorders (bipolar disorder type I, type II, and spontaneous or induced hypomania; N=32), PD-patients with others psychiatric comorbidities (N=39), PD-patients without psychiatric comorbidities (N=29). Clinical features were compared among the groups using analysis of variance and chi-square test. A logistic regression was performed to evaluate the association between Bipolar Spectrum disorders and early onset of PD (≤50years) controlling for lifetime antipsychotic use. In comparison with PD patients with and without other psychiatric comorbidity, subjects affected by Bipolar Spectrum disorders were younger, showed more frequently an early onset PD, reported more involuntary movements and a higher rate of impulse control disorders and compulsive behaviors. No differences were observed in indexes of exposure to dopamine agonist treatments. The early onset of PD was predicted by Bipolar Spectrum comorbidity, independently from lifetime antipsychotic use. Bipolar Spectrum disorders are common in early onset PD. The presence of bipolar comorbidity could identify a particular subtype of PD, showing higher rates of neurological and psychiatric complications and deserving further investigation.

Contributing Factors and Evolution of Impulse Control Disorder in the Luxembourg Parkinson Cohort.

Background: To establish the frequency of impulse control disorder (ICD) in Parkinson's disease (PD).Methods: Within the Luxembourg Parkinson's Study, PD patients were evaluated for ICD presence (score ≥ 1 on MDS-UPDRS I item 1.6), use of dopamine agonists (DA) and other medications.Results: 470 patients were enrolled. Among 217 patients without DA use, 6.9% scored positive for ICD, vs. 15.4% among 253 patients with DA use (p = 0.005). The regression analysis showed that age at PD diagnosis had only a minor impact on ICD occurrence, while there was no influence by gender or co-medications. The longitudinal study over 2 years in 156 patients demonstrated increasing ICD frequency in DA users (p = 0.005).Conclusion: This large and non-interventional study confirms that PD patients with DA treatment show higher frequency of ICD than patients without DA use. It newly demonstrates that ICD can develop independently from age, gender, or co-medications.

Abstract #300087: Morbid Obesity Due to Prolactinoma and Significant Weight Loss After Dopamine Agonist Treatment

Abstract #300087: Morbid Obesity Due to Prolactinoma and Significant Weight Loss After Dopamine Agonist Treatment

The long noncoding RNA-H19/miRNA-93a/ATG7 axis regulates the sensitivity of pituitary adenomas to dopamine agonists

Dopamine agonists (DAs), such as cabergoline and bromocriptine, are the first-line clinical treatment for prolactinomas. Our previous study demonstrated that long noncoding RNA H19 expression is frequently downregulated in human primary pituitary adenomas and is negatively correlated with tumor progression. However, the significance and mechanism of H19 in the DA treatment of prolactinomas are still unknown. In this study, we reported that H19 had a synergistic effect with DA treatment on prolactinomas in vitro and in vivo. Mechanistically, H19 promoted ATG7 expression in pituitary tumor cells by inhibiting miR-93a expression. In addition, a potential binding site between miR-93 and H19 was confirmed, and low expression of miR-93 was previously found in DA-resistant prolactinomas. Furthermore, we showed that miR-93a regulates ATG7 expression by targeting ATG7 mRNA. In conclusion, our study has identified the role of the H19-miR-93-ATG7 axis in DA treatment of prolactinomas, which may be a potential therapeutic target for human prolactinomas.

Predictors of the Response to Dopaminergic Therapy in Patients With Prolactinoma.

Withdrawal of dopamine agonist (DA) therapy in patients with prolactinoma who are controlled by a small dose of medication is recommended by several guidelines. So far, the likelihood of reaching withdrawal conditions based on baseline characteristics remains uncertain. We retrospectively examined early clinical, radiological, or biochemical features that may predict the likelihood of reaching withdrawal conditions in prolactinoma patients. Data were obtained in a single academic medical center in the United States from patients seen between 2000 and 2018. Using multiple logistic regression, we compared patients who reached withdrawal conditions with those who did not. Of 213 patients, 78 (36.6%) reached withdrawal conditions after at least 2 years of DA treatment. Initial maximal tumor diameter was significantly smaller in those who reached withdrawal conditions than in those who did not. Percent prolactin change at the first check from initiation of DA therapy and parasellar invasiveness were predictors of reaching withdrawal conditions. With constant independent variables, there was a 7% increase in odds for reaching withdrawal conditions for every 1% decrease in percent prolactin change at first check after DA therapy start (P = 0.0000). Parasellar invasion decreased the odds of reaching withdrawal conditions by 84% (P = 0.0000). DA remains a potential life-long treatment modality for most prolactinoma patients. Patients with parasellar invasiveness and low prolactin percent change from baseline to first prolactin check are more likely to require long-term treatment.

Jeu d’argent problématique et responsabilité pénale

ObjectivesIn total, 14% to 30 % of individuals with gambling disorder engage in illegal acts to finance such behavior. This clinical situation could be explained by higher gambling severity, associated substance use disorder, antisocial personality disorder and economic factors (debts, financial problems). The present work focuses, more broadly, on criminal responsibility of problematic gamblers. MethodsWe will discuss this question through different typical situations that medical experts of criminal responsibility may have to face. We will address each of the following cases: 1) isolated problematic gambling; 2) problematic gambling associated with antisocial personality disorder; 3) problematic gambling associated with a manic episode; 4) problematic gambling associated with substance use disorders; and 5) problematic gambling associated wiht dopamine agonist treatment. ResultsIsolated problematic gambling, (not associated with any psychiatric or addictive disorder): it seems consensual that individuals committing infractions in this case are criminally responsible. However, impeded ability to action control and possible sentence attenuation could be discussed in case of severe gambling disorder. Problematic gambling associated with antisocial personality disorder: if the penal offence reports solely to personality disorder, criminal responsibility would be attributed. However, if illegal or violent acting is directly linked to co-cocurrent delusional symptoms, it could be a cause of criminal non-responsibility. Problematic gambling associated with manic episode: manic episode related offence could lead to negation of criminal responsibility, while a hypomanic episode may provide grounds for sentence reduction. Problematic gambling associated with substance use disorders: in France, addiction is not considered to remove nor to impede a person's ability to understand or control his actions and is excluded from criminal non-responsibility causes. However, substance induced delusional or confusional episodes could abolish a subject's discernment or his ability to control his actions yielding to penal non-responsibility. Problematic gambling associated with dopamine agonist treatment: Criminal responsibility for dopamine agonist induced gambling related illegal acts is still controversial. Nevertheless, people committing an infraction linked to associated dementia or dopamine agonist induced mania should be considered as criminally non-responsible. ConclusionsSome clinical dimensions such as craving intensity, compulsivity, disorder's severity, volitional control might be forensic targets to assess criminal responsibility.