Therapeutic effects of cannabinoids on Parkinson's disease: an updated systematic review and meta-analysis of randomized controlled trials.

BackgroundAlthough non-motor symptoms of Parkinson’s disease (PD) are serious, effective treatments are still lacking. Acupuncture may have clinical benefits for non-motor symptoms of PD patients, but high-quality evidence supporting this possibility is still limited. Hence, we conducted this meta-analysis to evaluate the effect of acupuncture treatment on non-motor symptoms in patients with PD.MethodsRandomized controlled trials (RCTs) of acupuncture treatment for PD were retrieved from the following electronic databases: Medline (OVID), Embase (OVID), Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, Chonqing VIP (CQVIP), and Wangfang database. Studies evaluating non-motor symptoms of PD were retrieved. Methodological quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions.ResultsA total of 27 RCTs were included, among which 8 outcomes related to non-motor symptoms were evaluated. The results showed that acupuncture combined with medication had benefits for PD-related insomnia relative to medication alone or sham acupuncture [standardized mean difference (SMD) = 0.517; 95% confidence interval (CI) = 0.242–0.793; p = 0.000], and acupuncture treatment had benefits at 8 weeks (SMD = 0.519; 95% CI = 0.181–0.857; p = 0.003). Regarding depression, acupuncture treatment was more effective (SMD = −0.353; 95% CI = −0.669 to −0.037; p = 0.029) within 2 months (SMD = −0.671; 95% CI = −1.332 to −0.011; p = 0.046). Regarding cognition, quality of life, and Unified Parkinson’s Disease Rating Scale (UPDRS) I and II scores, acupuncture treatment was effective [SMD = 0.878, 95% CI = 0.046–1.711, p = 0.039; SMD = −0.690, 95% CI = −1.226 to −0.155, p = 0.011; weighted mean difference (WMD) = −1.536, 95% CI = −2.201 to −0.871, p = 0.000; WMD = −2.071, 95% CI = −3.792 to −0.351, p = 0.018; respectively]. A significant difference was not found in terms of PD-related constipation. Only one study evaluated PD-related fatigue.ConclusionThe results of the analysis suggested that acupuncture treatment could ameliorate the symptoms of depression, quality of life, cognition, total mentation, behavior and mood, and activities of daily living in PD patients. Nevertheless, more prospective, well-designed RCTs with larger sample sizes are required to confirm our findings.

Parkinson's disease (PD) is usually accompanied by rapid eye movement sleep behavior disorder (RBD). A systematic review has concluded that motor manifestations are associated with RBD in PD patients, but whether the same is true of non-motor symptoms is unclear. A systematic review and meta-analysis was conducted by searching studies related to PD and RBD in PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled where appropriate and used to calculate odds ratios (ORs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic. PD patients with RBD were more likely to be male (OR 1.26, 95% CI 1.14-1.40) and older (MD 1.70years, 95% CI 1.24-2.16) than those of patients without RBD. Patients with RBD were at a higher risk of non-motor symptoms such as constipation (OR 1.94, 95% CI 1.57-2.38), hallucination (OR 2.62, 95% CI 2.01-3.41), depression (SMD 0.39, 95% CI 0.25-0.53), and cognitive impairment (SMD - 0.29, 95% CI - 0.42 to - 0.17) based on standardized questionnaire scores. Similarly, PD patients with RBD suffered more severe motor symptoms and required higher doses of levodopa therapy. The available evidence suggests that PD patients with RBD suffer severer non-motor and motor symptoms than those without RBD. A potential explanation is that PD patients with RBD present more diffuse neurodegeneration.

Role of Antimuscarinics Combined With Alpha-blockers in the Management of Urinary Storage Symptoms in Patients With Benign Prostatic Hyperplasia: An Updated Systematic Review and Meta-analysis.

Clinical symptoms of Parkinson disease (PD) included both motor and nonmotor symptoms. Previous studies indicated inconsistent results for the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on motor and depression in PD. The study aimed to assess the therapeutic effect of rTMS with different mode on motor and depression in PD using a meta-analysis. Articles published before July 2019 were searched based on the following databases (PubMed, Web of Science, Medline, Embase, and Google Scholar). The therapeutic effects were assessed by computing the standard mean difference (SMD) and a 95% confidence interval (CI). The present study indicated that rTMS showed significant therapeutic effects on motor in PD (SMD 2.05, 95% CI 1.57-2.53, I = 93.0%, P < .001). Both high-frequency (HF)-rTMS and low-frequency rTMS showed therapeutic effects on motor; stimulation over primary motor cortex (M1), supplementary motor area, dorsal lateral prefrontal cortex (DLPFC) or M1+DLPFC showed therapeutic effects; stimulation during "on" and "off" states showed therapeutic effects; the study showed long-term effect of rTMS on motor in PD. In addition, the study indicated that rTMS showed significant therapeutic effects on depression in PD (SMD 0.80, 95% CI 0.31-1.29, I = 89.1%, P < .001). Stimulation over left DLPFC showed significant therapeutic effects on depression in PD; only HF-rTMS showed therapeutic effects; ages, disease durations, numbers of pulses, and session durations displayed influence on the therapeutic effects of rTMS on depression in PD; the therapeutic effects on depression was long term. However, no significant difference in therapeutic effects on depression were showed between rTMS and oral Fluoxetine (SMD 0.74, 95% CI -0.83 to 2.31, I = 92.5%, P < .001). The rTMS showed significant therapeutic effects on motor in PD. HF-rTMS showed a significant positive antidepressive effect in PD only over DLPFC.

To provide an up-to-date systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating the postoperative outcomes of two lateral osteotomy techniques (external vs. internal) in patients undergoing rhinoplasty. We conducted a comprehensive search in PubMed, Scopus, Web of Science, Embase, and the CENTRAL from their inception until January 2025. Eligible RCTs were assessed for risk of bias using Cochrane's risk of bias tool. The specific outcomes included clinically relevant measures, such as eyelid edema, ecchymosis, and step-off deformity. Standardised mean differences (SMD) and risk ratios (RR) with 95% confidence intervals (CIs) were used to combine the data. STATA software was used for statistical analysis. A total of 13 RCTs involving 1008 patients were included. Five RCTs demonstrated a low risk of bias, six had some concerns, and two exhibited a high risk of bias. The pooled analysis showed no significant difference in eyelid edema between the external and internal osteotomy groups at 2 days (SMD = -0.13, 95% CI [-0.49, 0.22]), 3 days (SMD = -0.14, 95% CI [-0.77, 0.48]), and 7 days (SMD = -0.08, 95% CI [-0.27, 0.12]). Similarly, no significant difference was observed in ecchymosis between the two groups at 2 days (SMD = -0.12, 95% CI [-0.51, 0.27]), 3 days (SMD = -0.21, 95% CI [-1.11, 0.70]), and 7 days (SMD = -0.10, 95% CI [-0.33, 0.12]). The mean score of step-off deformity was significantly higher in the external osteotomy group compared to the internal osteotomy group (SMD = 0.54, 95% CI [0.19, 0.89]), whereas the rate of step-off deformity did not differ significantly between the groups (RR = 0.79, 95% CI [0.43, 1.44]). This updated systematic review and meta-analysis of 13 RCTs involving 1008 patients demonstrated comparable outcomes between external and internal lateral osteotomy in terms of postoperative eyelid edema, ecchymosis, and step-off deformity in patients undergoing rhinoplasty. PROSPERO: CRD420251003922.

Physical exercise interventions are known to improve quality of life, motor and non-motor symptoms in people with Parkinson's disease (PD). However, systematic reviews and meta-analyses on cognitive outcomes are rare. To perform a systematic review and meta-analysis of physical exercise intervention effects compared with passive and active control groups (CGs) on global cognition in people with PD. A literature search was performed for randomized controlled trials (RCTs) on physical exercise interventions in PD using nine databases. We included RCTs reporting global cognition outcomes. A meta-analysis was performed using random-effects models and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Bias was assessed with the revised Cochrane Risk of Bias tool and the certainty of evidence was rated using the GRADE approach. Seventeen studies (ten with passive, seven with active CGs) were included in the systematic review. Exercise interventions varied considerably between studies. The meta-analysis included nine studies with 236 people with PD (seven with passive, two with active CGs). The SMD was 0.33 (95% CI 0.00; 0.65) demonstrating a small effect (p = 0.05) in favor of physical exercise. Compared with passive CGs, physical exercise had a small non-significant effect (SMD = 0.22, 95% CI -0.14;0.58, p = 0.24). Compared with active CGs, physical exercise had a medium significant effect (SMD = 0.72, 95% CI 0.12;1.33, p = 0.02). Physical exercise may increase global cognition in people with PD, but the evidence is very uncertain. Further large-scale RCTs are needed to confirm this finding and to identify the most effective type of physical exercise for improving cognition.

Parkinson's disease (PD) is a multifactorial neurodegenerative disease with a high prevalence worldwide, leading to motor and non-motor symptoms. Moreover, PD presents a progressive aggravation alongside time, the middle and late patients in PD requires the use of a variety of anti-Parkinson's drugs with obvious side effects, which bring serious impact on the quality of life of patients. In recent years, repetitive transcranial magnetic stimulation (rTMS), as a kind of non-invasive neuromodulation therapy, has drawn increasing interest from neurologists, and has been effectively utilized to alleviate both motor and non-motor symptoms of PD. However, the treatment protocols and therapeutic effects of rTMS for PD patients are inconsistent. This meta-analysis aims to systematically evaluate the safety and efficacy of rTMS therapy in patients with PD. We will perform a comprehensive search in the following electronic databases: PubMed/Medline, Web of Science, EMBASE, and Cochrane, without language restrictions, from their inception to September 2024. This review protocol was formulated according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. The Cochrane risk of bias tool is utilized to assess the risk of bias. Finally, the effect size was expressed by a standardized mean difference (SMD) with a 95% confidence interval (CI). A total of 45 randomized controlled trials were included. The results of enrolled studies indicated that both primary and secondary indicators had improved. Subgroup analysis showed that high-frequency rTMS (HF-rTMS) targeting the supplementary motor area (SMD = -0.56; 95%CI = [-0.77, -0.36]; p<0.00001), primary motor cortex (SMD: -1.65; 95%CI=[-2.35, -0.95]; p<0.00001), and dorsolateral prefrontal cortex (DLPFC) (SMD: -0.68; 95%CI=[-1.16, -0.21]; p=0.005) yielded a significant reduction in motor UPDRS-III scores, compared to the sham group. In addition, HF-rTMS over left DLPFC or intermittent theta burst stimulation over left DLPFC may benefit cognition. Furtherly, the subgroup analysis of the Beck Depression Inventory scores indicated HF-rTMS over the left DLPFC was a beneficial treatment for depressive symptoms in PD. The meta-analysis showed that rTMS was effective and safe in the treatment of PD, improving motor function (such as a decrease in UPDRS-III total scores, subscores of UPDRS-III, and FOG-Q scores) in patients with PD and leading to improvement in cognitive function and depression (such as an increase in MocA scores and a decrease BDI scores). Although the results of the subgroup analysis provide a valuable reference for the selection of rTMS for clinical application, further larger multicenter, randomized, placebo-controlled studies with a large number of participants are still required to validate these results.

L-dopa-induced dyskinesias (LIDs) are abnormal involuntary movements (AIM) that develop with long-term L-dopa therapy for Parkinson's disease (PD). In this study, we used these tools to describe the efficacy of nicotine reduced LID in animal models of PD. Studies were identified by electronic searching of six online databases up to September of 2013 to identify preclinical trials involving nicotine for LID in animal model. Data were extracted for AIM compared with LID animals. Pre-specified subgroup analysis was carried out according to method of model, gender, anesthetic used, and species. Combined standardized mean difference (SMD) estimates and 95 % confidence intervals (CIs) were calculated using a random-effects model. Eleven studies involving 181 animals which described the effect of nicotine on LID were included in the meta-analysis. Nicotine was efficacious in reducing total AIM compared with control group (SMD -3.77, 95 % CI -5.30 to -2.23, P < 0.00001). Meanwhile, four studies showed certain effects of nicotine for improving the axial AIM (SMD -2.21, 95 % CI -4.17 to -0.24, P = 0.03); oral AIM and forelimb AIM were obvious improved in six studies in the nicotine group (SMD -3.00, 95 % CI -4.55 to -1.44, P = 0.0002; SMD -2.52, 95 % CI -3.52 to -1.53, P < 0.00001, respectively). We conclude that nicotine appears to have efficacy in animal models of LID. Large randomized clinical trials testing the effect of nicotine in PD patients with LID are warranted.

Effects of physical exercise interventions on cognitive function in Parkinson's disease: An updated systematic review and meta-analysis of randomized controlled trials

Background:Depression is a major nonmotor symptom of Parkinson’s disease (PD). However, few treatments exist for PD depression. Monoamine oxidase-B inhibitors (MAOB-Is) provide symptomatic relief for the motor symptoms of PD and exert antidepressive effects. The present meta-analysis of randomized controlled trials (RCTs) investigated the effects of MAOB-Is on depressive symptoms in patients with PD.Methods:Articles on PD-management-related RCTs using one of three MAOB-Is approved by the US Food and Drug Administration, that is, selegiline, rasagiline, and safinamide, were identified. The primary outcomes were the benefits of MAOB-Is for depressive symptoms. Subgroup analysis included the effects of MAOB-Is on patients in the early versus middle-to-late stages of PD and the effect of short-term versus long-term treatment.Results:Overall, six studies were included, four of which were conducted on patients with early stage PD. Overall, MAOB-Is significantly reduced the severity of depressive symptoms [standardized mean difference (SMD): −0.14, 95% confidence interval (CI): −0.21 to −0.06, p < 0.001]. Subgroup analysis indicated that the positive effect of MAOB-Is was significant in patients with early stage PD (SMD: −0.20, 95% CI: −0.31 to −0.09, p < 0.001), but not in those with middle-to-late-stage PD (SMD: −0.07, 95% CI: −0.17 to 0.03, p = 0.18). The antidepressive effect was significant for short-term treatment, that is, 90–120 days (SMD: −0.23, 95% CI: −0.35 to −0.10, p < 0.001), but not long-term treatment, that is, 24 weeks to 18 months (SMD: −0.08, 95% CI: −0.18 to 0.01, p = 0.09).Conclusion:In addition to the treatment of PD motor symptoms, MAOB-Is may help reduce the severity of depressive symptoms in PD, especially in patients with early stage PD. Considering the tolerability and simultaneous benefits of MAOB-Is, further RCTs are warranted to confirm their therapeutic effects in moderate-to-severe PD depression.

Objective: Initial randomized controlled trials (RCTs) and recently released systematic reviews have identified resistance training (RT) as a modality to manage motor symptoms and improve physical functioning in individuals with Parkinson's disease (PD), although the effects are inconsistent. Therefore, we conducted an updated meta-analysis to reassess the evidence of the relationship.Methods: We performed a systematic search of studies reporting the effects of RT in PD available through major electronic databases (PubMed, Medline, Embase, Ovid, Cochrane Library, CNKI, Wanfang) through 20 July 2020. Eligible RCTs were screened based on established inclusion criteria. We extracted data on the indicators of leg strength, balance, gait capacity, and quality of life (QoL) of lower limbs. Random and fixed effects models were used for the analysis of standard mean differences (SMD) or mean differences (MD) with their 95% confidence intervals (CI).Results: Thirty-one papers from 25 independent trials compromising 1,239 subjects were selected for eligibility in this systematic review and meta-analysis. Summarized data indicated that the leg strength increased statistically significant in PD patients (SMD = 0.79, 95% CI 0.3, 1.27, P = 0.001), the balance capability was improved statistically significant in PD patients (SMD = 0.34, 95% CI 0.01, 0.66, P = 0.04), and QoL statistically significantly improved (MD = −7.22, 95% CI −12.05, −2.39, P = 0.003). For gait performance, four indicators were measured, the results as follows: fast gait velocity (MD = 0.14, 95% CI 0.06, 0.23, P = 0.001), Timed-up-and-go-test (TUG, MD = −1.17, 95% CI −2.27, −0.08, P = 0.04) and Freezing of Gait Questionnaire (FOG-Q, MD = −1.74, 95% CI −3.18, −0.3, P = 0.02) were improved statistically significant across trials, while there were no statistically significant improvement in stride length (MD = −0.05, 95% CI −0.12, 0.02, P = 0.15) in PD patients.Conclusions: Lower limb RT has positive effects during rehabilitation in individuals with PD in leg strength, QoL, and improve gait performance to a certain extent. RT also could improve balance capacity of patients, although a wide variety of tools were used, and further study is needed to confirm these findings.

BackgroundFreezing of gait (FOG) is one of the most disabling gait disturbances in Parkinson’s disease (PD), affecting mobility and balance severely, thereby leading to an increased risk of falls.ObjectivesThe purpose of this systematic review and meta-analysis was to investigate the effects of transcranial magnetic stimulation on FOG in PD.MethodsBased on PRISMA guidelines, we searched the databases of MEDLINE (PubMed), Cochrane Library, PEDro, Embase, and Web of Science. Studies of the English language published up to July 2023 were searched. We retrieved for studies of randomized controlled trials (RCTs) of transcranial magnetic stimulation to treat FOG after PD and screened by inclusion and exclusion criteria. Risk of bias was assessed using the Cochrane Collaboration’s tool (Revman5.30). Characteristics of RCTs were extracted. The heterogeneity of the trials was measured by I2 statistic. The effect size was expressed by a standardized mean difference (SMD) with a 95% confidence interval (CI).ResultsA total of 488 articles were screened, after screening sixteen RCTs involved in 408 patients were included in the qualitative analysis, and 15 RCTs were included in meta-analysis. The outcome measures included FOG-Q, walking time, TUG, and UPDRS. Six studies used FOG-Q as outcome measure, six studies used walking time, four studies used TUG, and six studies used UPDRS. Compared with placebo treatment, transcranial magnetic stimulation has positive significant effects in improving gait status with increased walking speed (SMD = −0.41, 95% CI = −0.75 to −0.06, I2 = 7% p = 0.02), FOG-Q scores (SMD = −0.55, 95% CI = −0.89 to −0.21, I2 = 29%, p = 0.002), UPDRS scores (SMD = −1.08, 95% CI = −1.39 to −0.78, I2 = 49%, P < 0.001) and the time of TUG (SMD = −0.56, 95% CI = −0.88 to −0.23, I2 = 25%, p = 0.02) decreased.ConclusionTranscranial magnetic stimulation could significantly improving gait conditions in PD patients with FOG.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, CRD42023434286.

Simple SummaryParkinson’s disease (PD) is a common neurodegenerative disease that manifests as motor dysfunction and nonmotor symptoms (NMSs). Apart from motor symptoms, NMSs include sleep disorders, neuropsychiatric problems, and cognitive impairment, which negatively influence patients’ daily lives and caregivers. Disturbances of the sleep cycle also worsen overall health, causing dysregulation of cortisol and melatonin secretion. Furthermore, bright light therapy (BLT) is a well-known treatment for circadian rhythm sleep disorders, seasonal affective disorders, and dementia-related sleep disturbances under the regulation of circadian rhythm by melatonin, a chronological pacemaker. BLT is also applied to treat depressive symptoms and bipolar disorder through unknown mechanisms. The present study, at first, conducted a literature review, which found that a few non-controlled studies demonstrated improvements in motor symptoms and NMSs in PD. Secondly, the present study performed a meta-analysis of the randomized controlled trials which treated the PD patients with BLT. The results revealed that BLT nonsignificantly alleviated symptoms of depression and sleep disorders in patients with PD. However, the inconsistency between BLT protocols, such as varied timing, dosages, and treatment durations, may render BLT’s efficacy challenging to demonstrate, and future RCTs must be obtained.Sleep disorders and depression are significant nonmotor symptoms (NMSs) of Parkinson disease (PD). However, few effective, evidence-proven medical treatments are available for alleviating these symptoms. Bright light therapy (BLT) is a well-established treatment for circadian rhythm sleep disorders and seasonal affective disorder. The present study conducted a literature review for the effect of BLT on PD, especially a meta-analysis of randomized controlled trials (RCTs). We searched for studies using the PubMed and Cochrane Library databases. The major outcomes were the effects on sleep and depression. The effect on motor symptoms was also analyzed as a secondary outcome. This study was registered with PROSPERO (CRD42020204454). Six studies were included in the literature review only, and the other five RCTs were included in the meta-analysis. Despite the positive effects of BLT on PD patients, which were demonstrated in noncontrolled studies, in the meta-analysis of the RCTs, BLT did not significantly improve the depressive symptoms (standardized mean difference (SMD): −0.15, 95% confidence interval (CI): −0.48 to 0.17, p = 0.36) and excessive daytime sleepiness (EDS) (SMD: −0.12, 95% CI: −0.49 to 0.25, p = 0.53) in PD patients. Regarding motor symptoms, no significant beneficial effects were conferred (SMD: −0.11, 95% CI: −0.44 to 0.21, p = 0.49). In conclusion, BLT did not significantly alleviate depression and sleepiness. The inconsistency between BLT protocols, such as the varied timing, dosages, and treatment durations, may render BLT’s efficacy difficult to demonstrate. The small effect size obtained from the present meta-analysis indicates that future RCTs are necessary, for which BLT protocols are standardized and more patients are enrolled to determine whether a significant therapeutic benefit was conferred.

BackgroundBrain-derived neurotrophic factor (BDNF) is essential for regulating neuronal proliferation and survival in neurodegenerative diseases, including Parkinson’s disease (PD). However, Studies on BDNF levels in peripheral blood and cerebrospinal fluid (CSF) have inconsistent results. Therefore, this study aimed to examine BDNF levels in patients with PD and to explore their correlation with non-motor symptoms.MethodsFour databases (PubMed, Embase, Cochrane Library, and CNKI) were searched for eligible studies. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using Stata version 14.0, applying either a fixed-effect or a random-effects model based on heterogeneity. Furthermore, subgroup analysis, meta-regression, and sensitivity analysis were employed to identify and analyze sources of heterogeneity. Publication bias was assessed using funnel plots and Egger’s test.ResultsA comprehensive systematic review and meta-analysis was conducted, encompassing 48 articles. A total of 38 studies, covering 2,589 patients with PD and 2,422 healthy controls, were analyzed, revealing significantly lower peripheral blood BDNF levels in PD patients compared to healthy controls (SMD = −1.037; 95% CI [−1.412, −0.662]; P < 0.001), with substantial heterogeneity (I2 = 97.0%; P < 0.001). This result may be more applicable to serum samples and the Asian population according to subgroup analysis. PD patients with depression showed no significant difference in serum BDNF levels compared to those without depression (SMD = −0.511; 95% CI [−1.692, 0.671]; P = 0.397). A significant association was found between decreased serum BDNF concentrations and cognitive impairment in PD (SMD = −1.035; 95% CI [−1.340, −0.730]; P < 0.001). Moreover, negative correlations were observed between lower serum BDNF levels and autonomic dysfunction, rapid eye movement sleep behavior disorder (RBD), and restless legs syndrome (RLS), respectively. However, CSF BDNF levels showed no statistically significant difference between PD patients and controls (SMD = −0.398; 95% CI [−2.499, 1.703]; P = 0.711).ConclusionReduced expression of BDNF is associated with both PD and its non-motor symptoms. Further research is needed to explore the potential of BDNF as a biomarker for non-motor symptoms of PD, particularly for cognitive impairment.

Motor fluctuations and OFF episodes are common complications of long-term levodopa therapy in Parkinson's disease (PD) and significantly impair quality of life. Apomorphine, a short-acting dopamine agonist, is available in multiple formulations for on-demand symptom relief; however, comparative evidence across administration routes remains limited. To evaluate the efficacy and safety of apomorphine across various routes of administration in patients with PD. Systematic review and meta-analysis of randomized controlled trials and randomized crossover trials. A comprehensive search of PubMed, Scopus, Web of Science, CENTRAL, and Embase was conducted from inception to December 28, 2025. Eligible studies included randomized controlled or crossover trials assessing apomorphine versus placebo in PD. Primary outcomes were motor improvement measured by Unified Parkinson's Disease Rating Scale III (UPDRS-III) or Movement Disorder Society-UPDRS-III (MDS-UPDRS-III) and OFF time. Safety outcomes included treatment-related adverse events. Risk of bias was assessed using the Cochrane RoB 2 tool. Pooled analyses were conducted using standardized mean differences (SMD), mean differences (MD), and risk ratios (RR) with 95% confidence intervals (CIs). Thirteen studies involving 557 patients were included. Apomorphine significantly improved motor symptoms across multiple administration routes. Intermittent subcutaneous (SC) injection showed the greatest efficacy (SMD: -2.19, 95% CI: (-3.32, -1.05), p < 0.0001). The inhalation and sublingual routes also showed significant improvement (SMD: -1.11, 95% CI: (-1.52, -0.7), p < 0.0001, I 2 = 0%), (SMD: -1.69, 95% CI: (-1.99, -1.38), p < 0.0001, I 2 = 0%) respectively. Intermittent SC injections also significantly reduced OFF time (MD = -1.62 h; 95% CI = (-2.59, -0.65); p < 0.00001). Adverse events were more frequent with apomorphine (RR 1.50, 95% CI = 1.09-2.06), particularly nausea, vomiting, dyskinesia, somnolence, yawning, and rhinorrhea. Apomorphine is an effective on-demand therapy for reducing motor symptoms and OFF time in PD, particularly when administered as intermittent SC injection. Although associated with increased mild-to-moderate adverse events, treatment choice should be individualized. PROSPERO (CRD42024548330).