Impulse control disorders in hyperprolactinemic patients on dopamine agonist therapy.

Dopamine agonists (DAs) represent a mainstay of therapy for hyperprolactinemia and prolactinomas. The widespread use of DAs, including bromocriptine, cabergoline and (in some countries) quinagolide, has led to the emergence and recognition of impulse control disorders (ICDs) that may occur in association with DA therapy.Such ICDs include pathological gambling, compulsive shopping, hypersexuality and punding (the performance of repetitive tasks), among others. These manifestations can lead to substantial harms to patients and their families, if left undiagnosed and untreated. Several risk factors that may increase the risk of ICDs have been proposed, including younger age, male gender, smoking and alcohol use and history of depression.The diagnosis of ICDs in hyperprolactinemic patients treated with DAs requires a high index of suspicion and a systematic approach, using available screening questionnaires. However, it should be noted that available test instruments, including questionnaires and computerized tasks, have not been validated specifically in hyperprolactinemic patients. Hyperprolactinemic patients who develop ICDs should be withdrawn from DA therapy or, at a minimum, undergo a DA dose reduction, and considered for psychiatric consultation and cognitive behavioral therapy. However, the role of psychopharmacotherapy in hyperprolactinemic patients with ICDs remains incompletely characterized.Patient counseling regarding the risk of ICDs occurring in association with DA therapy, early detection and prompt intervention may mitigate potential harms associated with ICDs. Additional studies are needed to fully characterize risk factors, underlying mechanisms and identify effective therapies for ICDs in patients with hyperprolactinemia receiving DAs.

Bromocriptine therapy: Review of mechanism of action, safety and tolerability.

Bromocriptine is a sympatholytic dopamine D2 receptor agonist with remarkable bioactivities. It has been used clinically as a prescription drug for more than 30 years to treat hyperprolactinemia associated conditions, Parkinson's disease, acromegaly, prolactinomas and other pituitary hormone dependent adenomas and recently, diabetes mellitus as well as various other disorders. Long-term treatment with bromocriptine has minimal or no harmful effects on renal, hepatic, cardiac or hematologic functions. This review article was planned to study the hypothetical and proposed mechanism of action as well as provide a brief discussion about its safety issues and tolerability. Bromocriptine represents an attractive option with high efficacy and safety profile for hyperprolactinemia-associated conditions, acromegaly, parkinsonism, type 2 diabetes mellitus and various other diseases in a variety of dosage forms for best possible beneficial effects. It appeared to be an effective and safe addition to the pharmacopoeia of drugs for the treatment of a vast variety of diseases as monotherapy or in combination with other drugs.

Incidence of heart valve disease in women treated with the ergot-derived dopamine agonist bromocriptine.

BACKGROUND: Ergot-derived dopamine agonists are thought to induce fibrotic changes in cardiac valve leaflets. We sought to determine the incidence of heart valve disease in women treated with bromocriptine compared with age and sex matched controls from the background population. METHODS: In nationwide Danish registries we identified female patients treated with bromocriptine in the period 1995-2018. Patients were included at date of second redeemed prescription and were matched 1:5 with controls from the background population based on age, sex and year of inclusion by use of incidence density sampling. The outcomes were hospital admission for or outpatient diagnosis of heart valve disease, and death as competing risk. Incidence rates, cumulative incidence curves, and adjusted cox-proportional hazard models adjusted for cardiovascular risk factors were used to assess outcomes in bromocriptine users versus controls. RESULTS: A total of 3035 female bromocriptine users and 15,175 matched controls were included. Median age at inclusion was 32 years (Q1-Q3, 28-37 years). Both bromocriptine users and controls had few comorbidities and low use of concomitant pharmacotherapy. Within 10 years of follow-up, 11 patients (0.34%, 95% CI 0.13-0.55%) and 44 controls (0.29%, 95% CI 0.20-0.37) met the primary endpoint of heart valve disease, p = 0.63. The adjusted cox regression analysis yielded a hazard ratio of 0.96 (95% confidence interval (CI) 0.55-1.69, p = 0.89). CONCLUSIONS: Treatment initiation with ergot-derived dopamine agonist bromocriptine in younger women with few comorbidities, was associated with a low absolute long-term risk of heart valve disease, not significantly different from the risk in age and sex matched population controls. Thus, indicating a low clinical yield of pre-treatment echocardiographic screening in this patient population in accordance with current guidelines.

Bromocriptine for the treatment of peripartum cardiomyopathy: a multicentre randomized study.

AIMS: An anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental and first clinical observations suggested beneficial effects of the prolactin release inhibitor bromocriptine in PPCM. METHODS AND RESULTS: In this multicentre trial, 63 PPCM patients with left ventricular ejection fraction (LVEF) ≤35% were randomly assigned to short-term (1W: bromocriptine, 2.5 mg, 7 days) or long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for 6 weeks) in addition to standard heart failure therapy. Primary end point was LVEF change (delta) from baseline to 6 months assessed by magnetic resonance imaging. Bromocriptine was well tolerated. Left ventricular ejection fraction increased from 28 ± 10% to 49 ± 12% with a delta-LVEF of + 21 ± 11% in the 1W-group, and from 27 ± 10% to 51 ± 10% with a delta-LVEF of + 24 ± 11% in the 8W-group (delta-LVEF: P = 0.381). Full-recovery (LVEF ≥ 50%) was present in 52% of the 1W- and in 68% of the 8W-group with no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6 months tended to be lower. No patient in the study needed heart transplantation, LV assist device or died. CONCLUSION: Bromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, study number: NCT00998556.

Analysis of bromocriptine treatment in pregnant pituitary prolactinoma patients.

OBJECTIVE: To investigate the therapeutic effects and duration of bromocriptine treatment during pregnancy in patients with pituitary prolactinoma. MATERIALS AND METHODS: A retrospective analysis of the clinical data of 230 female pituitary prolactinoma patients at the Beijing Union Medical College Hospital neurosurgery clinic from January 2001 to May 2014 was conducted. When confirmed pregnant, patients in the control group immediately stopped taking bromocriptine, but patients in the treatment group continued to take the same dose of bromocriptine. RESULTS: The embryos stop rate in the control group was 16.7%, significantly higher than the rate in the natural population (p < 0.05), while the rate in the treatment group (0.9%) not statistically different from that of the natural population (p > 0.05). There was no significant difference in the embryonic malformation rate between the two study groups compared to the normal pregnancy group (p > 0.05). CONCLUSION: Pregnant pituitary prolactinoma patients should not stop bromocriptine treatment, but should instead continue with the same dose for four months. For patients with macroadenoma, bromocriptine should be taken during the entire pregnancy. Blood prolactin, progesterone, human chorionic gonadotropin (hCG), and visual dysfunction should be monitored every two weeks during treatment. Patients should be treated with progesterone and hCG if the blood levels become too low. If regular monitoring shows that prolactin has increased too fast and/or visual dysfunction worsened, the dose of bromocriptine should be in- creased. The authors have found that bromocriptine treatment during pregnancy significantly reduces the embryo stop rate without in- creasing the embryo deformity rate; therefore, bromocriptine treatment is safe and necessary during pregnancy of pituitary prolactinoma patients.

Role of bromocriptine in multi-spectral manifestations of traumatic brain injury.

PURPOSE: Despite the prevalence and cost of traumatic brain injury related disabilities, there is paucity in the literature on modern approaches to pharmacotherapy. Medications may promote recovery by enhancing some neurological functions without impacting others. Herein we discussed the role of bromocriptine in neurorehabilitation for patients with traumatic brain injury. METHODS: A cohort comprising of 36 selective nonsurgical cases of traumatic brain injury in minimally conscious state were enrolled in the study. After hemodynamic stability, bromocriptine was given at paediatric dose of 3.75 mg/d and adult dose of 7.5 mg/d. It was administered through a naso-gastric (NG) feeding tube in the patients with minimally conscious state, then changed to oral route after proper swallowing and good gag reflex were ensured in the patient. The drug was slowly reduced over three weeks after neurological improvement in the patients. Positive result was determined by improved GCS score of 2 and motor power by at least 1 British Medical Council (BMC) motor score. Improvement of deficits was evaluated in terms of fluency of speech for aphasia, task switching, digit span double tasking and trail-making test for cognition and attention, and functional independence measure score for motor functioning and self-independence. RESULTS: Accelerated arousal was seen in 47.0% of cases (8/17) in 4-40 days. In 41.2% of cases (7/17), Glasgow outcome score (GOS) was improved to 4/5 in 90 days. Improvement in hemiparesis by at least 1 BMC score was seen in 55.6% of cases (5/9) in 40 days. Aphasia was improved in 80% of cases (4/5) in 7-30 days. Moderate improvement in cognitive impairment was seen in 66.7% of cases (2/3) in 14-20 days. Improvement in memory was observed in 50% of cases (1/2) in over 30 days. No cases were withdrawn from the study because of adverse reactions of the drug. There was no mortality in the study group. CONCLUSION: Bromocriptine improves neurological sequelae of traumatic brain injury as well as the overall outcome in the patients. If medication is given to promote recovery and treat its associated disabilities, clinicians should thoroughly outline the goals and closely monitor adverse effects.

Pharmacological lactation suppression with D2 receptor agonists and risk of postpartum psychosis: A systematic review.

BACKGROUND: It has been suggested that D2 receptor agonists commonly used postpartum for the physiological suppression of lactation, such as bromocriptine and cabergoline, may increase the risk of illness onset or relapse in women where there is a predisposition for or history of schizophrenia, bipolar disorder or postpartum psychosis. This is based on two lines of reasoning: current models of psychosis assume episodes are triggered by dysregulation of brain dopaminergic activity and treated by medications that universally have D2 receptor antagonist properties; and limited research suggesting these agents may be associated with psychotic episodes in vulnerable individuals outside of the postpartum period. AIM: The aim of this study was to examine whether D2 agonists trigger psychosis in previously well mothers, or psychotic relapse or exacerbation of symptoms in mothers with known psychotic illnesses, when used to suppress lactation during the early postpartum period. MATERIALS AND METHODS: A systematic review of the literature was undertaken of electronic databases, including: MEDLINE, EMBASE and PsychINFO from 1950 to 2015 using keywords. RESULTS: Eight case reports, three case series and a pharmacovigilance survey were identified. CONCLUSION: Whilst D2 receptor agonists appear to increase the risk of triggering psychosis in previously well mothers and those previously diagnosed with schizophrenia, bipolar disorder and postpartum psychosis, bromocriptine appears to pose a much greater risk than cabergoline. When considering the use of pharmacological agents to suppress lactation, physicians should carefully screen patients for a history of psychosis and consider alternatives to moderate this risk.

Efficacy and Safety of Bromocriptine-QR in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Bromocriptine-QR (quick release) is a novel treatment for type 2 diabetes. The objective of this study is to assess the efficacy and safety of bromocriptine-QR in adults with type 2 diabetes mellitus based on randomized controlled trials published in peer-reviewed journals or as abstracts. We performed a comprehensive literature search of MEDLINE, Pubmed, Web of Science, EMBASE, and the Cochrane Library up to May 2015. Randomized controlled trials of bromocriptine-QR therapy in type 2 diabetes mellitus were eligible. Two reviewers independently assessed the eligibility of trials based on predefined inclusion criteria. Information was collected concerning basic study data, patient characteristics, efficacy and safety outcomes, and methodological quality. Bromocriptine-QR add-on therapy lowered hemoglobin A1c compared with placebo (weighted mean difference, - 6.52 mmol/mol; 95% CI, - 8.07 to - 4.97 mmol/mol). Bromocriptine-QR exhibited an increase in achieving an HbA1c level ≤ 53 mmol/mol (≤ 7.0%) (32.0 vs. 9.5%; odds ratio, 4.57; 95% CI, 2.42-8.62). Fasting plasma glucose was reduced with bromocriptine-QR compared with placebo (weighted mean difference,-1.04 mmol/l; 95% CI,-1.49 to-0.59 mmol/l). Moreover, bromocriptine-QR had neutral effects on postprandial glycemia, Body Mass Index (BMI), and lipid profile. Bromocriptine-QR had more gastrointestinal side effects of nausea and vomiting. Bromocriptine-QR had no increased risk of hypoglycemia, hypotension, or cardiovascular effects. Bromocriptine-QR therapy offers an alternative option to currently available antidiabetic agents for type 2 diabetes mellitus adults. Neither hypoglycemia nor other metabolic changes occur with this drug. More data for long-term efficacy and safety are needed for further observation.

Severe adverse effects of bromocriptine in lactation inhibition: a pharmacovigilance survey.

OBJECTIVE: To assess the nature and conditions of the occurrence of adverse drug reactions (ADRs) of bromocriptine, which is used to inhibit lactation. DESIGN: Observational study. SETTING: Cases from the French pharmacovigilance database and the marketing authorisation holders. SAMPLE: Serious ADRs reported between 1994 and 2010 in association with bromocriptine used for lactation inhibition in France. METHODS: Each case was checked to confirm the bromocriptine indication, the seriousness of the ADR, the modalities of bromocriptine use, and to identify possible associated predisposing factors. MAIN OUTCOME MEASURES: Number and description of serious ADRs, with a particular focus on misuse and associated predisposing factors. RESULTS: Among 105 serious ADRs, including two fatal cases, the most frequent were cardiovascular (70.5%), neurological (14.3%), and psychiatric (8.6%) disorders. Cardiovascular disorders primarily consisted of ischaemic manifestations (n = 47): acute ischaemic stroke (n = 18, one death), myocardial infarction (n = 11, one death), and reversible postpartum cerebral angiopathy (n = 10). Misuse was identified in 52 cases (70.3%) of cardiovascular disorders, and mostly consisted of bromocriptine continuation despite the occurrence of first symptoms suggesting an ADR or the absence of a progressive titration of bromocriptine. About half of these women had cardiovascular predisposing factors, mainly tobacco smoking, overweight or obesity, or a history of hypertension or pre-eclampsia. CONCLUSIONS: This survey, together with published data, provides further evidence that serious ADRs still occur after bromocriptine use in lactation inhibition, and that most of these ADRs could have been avoided. The use of bromocriptine should therefore be limited to cases where no other options are available to inhibit lactation.

Transient psychosis in women on clomiphene, bromocriptine, domperidone and related endocrine drugs.

BACKGROUND: There have been reports of transient psychosis in women medicated for gynecologic conditions. OBJECTIVE: The aim of this paper was to explore this literature. METHOD: The PubMed and Google Scholar databases were searched for relevant case reports Results: The following reports were found: psychosis induced by gonadotropin-releasing hormone in the treatment of endometriosis, by clomiphene treatment for infertility, by bromocriptine treatment for milk suppression and by the withdrawal of domperidone prescribed as a galactologue as well as by the withdrawal of estrogen replacement therapy. CONCLUSION: In susceptible women, psychotic symptoms can result from treatments that reduce estrogen levels, such as leuprolide acetate or clomiphene, or treatments that increase dopamine levels (bromocriptine). Psychosis can also be caused indirectly when estrogen treatment is discontinued or dopamine antagonism (e.g. domperidone) withdrawn. Estrogen-reducing and dopamine-increasing treatments used in gynecology need to be carefully monitored.

Inhibiting the onset of lactation. Is cabergoline an alternative to bromocriptine?

In late 2014, following a review by the French Health Products Agency (ANSM) and the European Pharmacovigilance Risk Assessment Committee (PRAC), the European Commission restricted the indications for bromocriptine in lactation inhibition to situations in which breastfeeding must be stopped for medical reasons. Some healthcare professionals have asked us whether bromocriptine can be replaced with cabergoline, an option that is already used in practice and authorised in some European countries.

Choosing not to take bromocriptine.

In a survey of women not wishing to breastfeed, conducted in a French maternity hospital, 89% of those who received balanced information chose not to take bromocriptine to prevent puerperal lactation.

Endoscopic transsphenoidal treatment of a prolactinoma patient with brain and optic chiasmal herniations.

Bromocriptine has been the most widely used and effective agent to treat macroprolactinoma, and chiasmal herniation in a macroprolactinoma patient following the treatment with bromocriptine is a well-recognized complication. However, herniation of the inferior mesial frontal lobe into the sella has been rarely reported. The present clinical report is the second radiographic demonstration of herniation of the inferior mesial frontal lobe into the sella. After the treatment with transsphenoidal endoscopic chiasmopexy, the patient's visual disturbance improved dramatically. We suggest that transsphenoidal endoscopic chiasmopexy is an effective treatment option for the prolactinoma patient with brain and chiasmal herniations following the treatment with bromocriptine.

["Mid-stimulation psychosis" in the course of in vitro fertilization procedure with the use of clomiphene citrate and bromocriptine - case study]. / Przypadek "psychozy okolostymulacyjnej" w przebiegu procedury zaplodnienia pozaustrojowego z zastosowaniem cytrynianu klomifenu oraz bromokryptyny.

AIM: A few cases of psychosis induced by clomiphene citrate have been described so far. However, data on the prevalence of psychotic symptoms among women treated for infertility are inconclusive. Still a little is known about possible psychiatric complications of medications used in assisted reproduction techniques (ART). We present a case of a patient who developed transient psychotic symptoms in the course of the in vitro fertilization procedures. To our kiiowledge, this is the first case of 'mid-stimulation psychosis', which has been observed during ART using clomiphene.citrate and bromocriptine. The aim of this study is to describe the determinants ofpharmacotherapy undertaken in ART,.which can result in the development of psychotic symptoms. METHODS: The Case presentation. CONCLUSIONS: The use of clomiphene citrate for ovulation induction in combination with bromocriptine used for chronic hyperprolactinemia is a likely mechanism that might have triggered psychotic symptoms in the case presented. However, combination therapy with clomiphen citrate and.bromocriptine may be the pharmacological model of hyper-dopaminergia followed by chaotic changes in serum estrogen levels and might lead to an increased sensitivity of dopamine receptors. The above therapeutic schema may increase susceptibility to the development of psychotic symptoms in treated women. This impact should be considered in the case of any psychotic complications in patients undergoing assisted reproduction techniques

Young female with acromegaloid features and pituitary macroadenoma: what is your diagnosis?

Pseudoacromegaly is a extremely rare condition previously described and characterized by acromegaloid changes, tissue overgrowth, without elevations in insulin-like growth factor or growth hormone as seen in Acromegaly. We present the case of a young female seen initially with acromegaloid features and a pituitary microadenoma. After work-up the patient was diagnosed as insulin-mediated pseudoacromegaly. Only a few cases of pseudoacromegaly has been reported and should always be considered when evaluating patients for acromegaloid features with negative biochemical and hormonal levels.

Efficacy and Safety of Bromocriptine-QR as an Adjunctive Therapy on Glycemic Control in Subjects with Uncontrolled Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

Introduction: There has been an increasing awareness of the effects of combining bromocriptine-QR with other medications for diabetes mellitus type 2. This study aimed to assess the efficacy and safety of bromocriptine-QR as an adjunctive therapy for patients with uncontrolled type 2 diabetes mellitus. Methodology: This systematic review is registered at the International Prospective Register of Systematic Reviews (CRD42022360326). Literature search was done via MEDLINE, NCBI, Google Scholar, Science Direct, Europe PMC and Cochrane Library databases. We included randomized controlled trials with participants 18 years old and above with uncontrolled type 2 diabetes mellitus. The primary outcome of interest is the efficacy and safety of bromocriptine-QR as an adjunctive therapy for glycemic control. Case reports, case series, reviews and animal studies were excluded. The risk of bias was reviewed using the Cochrane Risk of Bias tool. Meta-analysis was performed using Review Manager 5.4 and presented as a weighted mean difference and 95% confidence interval for changes from the baseline level. Results: Nine studies were included in the systematic review with a total of 2709 participants. The baseline HbA1c in the bromocriptine-QR group was 7.42% and 7.51% in the control group. The bromocriptine-QR group was favoured, outperforming the control group in terms of reducing hemoglobin A1c(HbA1c), with a statistically significant difference (weighted mean difference -0.6%; 95% CI [-0.83,-0.36]; p<0.00001). The most common side effects were nausea (33.75% vs 6.92%), fatigue (13.11% vs 5.94%), and headache (11.17% vs 6.87%). Conclusion: Administration of bromocriptine-QR at a dose range of 1.6 to 4.8 mg/day as an adjunctive therapy reduced HbA1c and FBG in patients with uncontrolled type 2 diabetes mellitus (T2DM). However, there were also statistically greater odds of the occurrence of adverse events such as nausea, vomiting, and headache compared to controls.

The effects of bromocriptine on VEGF, kidney function and ovarian hyperstimulation syndrome in in vitro fertilization patients: a pilot study.

The aim of this study was to evaluate the effects of bromocriptine on vascular endothelial growth factor (VEGF) levels in serum, kidney function and ovarian hyperstimulation syndrome in women undergoing in vitro fertilization. Twenty-eight women were randomly divided into two groups and were administered daily oral capsules for 14 days, starting on the day of human chorionic gonadotropin (hCG) administration. Group A received 2.0 mg of folic acid, whereas Group B was given 2.5 mg of bromocriptine. Physical exams, pelvic ultrasounds and laboratory evaluations were performed on the day of hCG administration and again 7 days later. No differences in ovarian hyperstimulation syndrome, urine volume, creatinine clearance, urine sodium concentration or serum VEGF levels were found between the two groups. Thus, these results indicate that bromocriptine does not affect blood levels of VEGF, kidney function or the incidence of ovarian hyperstimulation syndrome in high-risk patients subjected to in vitro fertilization.

A case of iatrogenic severe mitral regurgitation.

Bromocriptine and cabergoline, ergot derived dopamine receptor agonists used to treat Parkinson's disease and prolactinomas, have been associated with increased risk of cardiac valve disease. Here we present a case of iatrogenic symptomatic severe mitral regurgitation due to these drugs.

[Efficacy and safety of ropinirole in the treatment of Parkinson's disease: a multi-center, randomized, double-blind and bromocriptine-controlled trial].

OBJECTIVE: To explore the efficacy and safety of ropinirole in the treatment of Parkinson's disease. METHODS: From November 2005 to April 2007, a total of 221 subjects from 7 hospitals of Beijing, Lanzhou and Wuhan participated in a 12-week multi-center, randomized, bromocriptine-controlled, double-blind, double-dummy and parallel-group trial. The efficacy of ropinirole was assessed with the unified Parkinson's disease rating scale (UPDRS) score, "off" time according to the patient's diary and the overall evolution of clinical efficacy. The safety was assessed on the basis of adverse events, blood pressure, pulse, laboratory measurement and electrocardiographic recordings. And the statistical analyses were performed with t, paired t, χ(2) and covariance tests. RESULTS: In the intent-to-treat population, the average UPDRSIII score decreased to (11 ± 9) in ropinirole group and (11 ± 10) in bromocriptine group while the UPDRSIIscore decreased to (4 ± 4) and (3 ± 5) respectively at Week 12 versus baseline. It showed that ropinirole was non-inferior to bromocriptine. The "off" time at Week 12 [(3.0 ± 1.2)h, (3.8 ± 1.6)h] versus baseline [(4.2 ± 2.0)h, (4.4 ± 1.7)h] decreased (t = 10.772, t = 5.746, P = 0.000) in ropinirole and bromocriptine groups. Ropinirole offered a better overall improvement rate (q = 7.241, P = 0.007). The adverse events occurring at a ratio of over 5% caused by ropinirole included orthostatic hypotension, nausea, dizziness, upper abdominal discomfort, insomnia and palpitation. No significant difference existed in the frequency of adverse events between two groups. CONCLUSIONS: Ropinirole is both effective and safe in the treatment of Chinese patients with Parkinson's disease.

Dopamine agonists versus levodopa monotherapy in early Parkinson's disease for the potential risks of motor complications: A network meta-analysis.

BACKGROUND: Compared with levodopa, dopamine agonists (DAs) as initial treatment are associated with lower incidences of motor complications in early Parkinson's disease (PD). There is no strong evidence that a given DA is more potent in lower incidences of motor complications than another. OBJECTIVE: We performed a network meta-analysis of levodopa versus DAs as monotherapy in early PD to access the risk of motor complications. METHODS: Databases were searched up to June 2022 for eligible RCTs. Levodopa and four DAs (pramipexole, ropinirole, bromocriptine and pergolide) were investigated. The incidences of motor complications and efficacy, tolerability and safety outcomes were analyzed. RESULTS: Nine RCTs (2112 patients) were included in the current study. The surface under the cumulative ranking curve (SUCRA) indicated that levodopa ranked first in the incidence of dyskinesia (0.988), followed by pergolide, pramipexole, ropinirole, and bromocriptine (0.704, 0.408, 0.240, 0.160). Pramipexole was least prone to wearing-off (0.109) and on-off fluctuation (0.041). Levodopa performed best in improvements of UPDRS-II, UPDRS-III, and UPDRS-II + III (0.925, 0.952, 0.934). Bromocriptine ranked first in total withdrawals and withdrawals due to adverse events (0.736, 0.751). Four DAs showed different adverse events profiles. CONCLUSION: In the two non-ergot DAs, ropinirole is associated with a lower risk of dyskinesia while pramipexole is associated with lower risks of wearing-off and on-off fluctuations. Our research may facilitate head-to-head research, larger sample sizes, long following-up time RCTs to confirm the findings of this network meta-analysis.