Abstract
Background
Primary orthostatic tremor (POT) is a rare hyperkinetic movement disorder with limited and largely ineffective treatment options. Perampanel has been suggested as a therapy, but has so far only been investigated in small studies with short duration.
Objective
To (1) describe longitudinal perampanel use and its association with key clinical outcomes and baseline characteristics in a well‐defined cohort of POT, and (2) evaluate factors possibly associated with treatment continuation.
Methods
A prospective observational cohort study in POT patients who started perampanel treatment between November 2018 and November 2022, and who completed five self‐report scales prior to treatment start and during clinical follow‐up were included. Scales assessed daily functioning and well‐being, and included the Dutch OT‐questionnaire, Hospital Anxiety and Depression Scale, (instrumental) Activities of Daily Living, and the Short Form‐36.
Results
Thirty one POT patients were included, and followed for 32 months on average. Seventeen patients continued taking perampanel, demonstrating improvements in social functioning, fewer emotional role limitations, better mental health, and reduced pain compared to those who discontinued. Fourteen patients discontinued perampanel due to lack of effect and/or adverse effects, which were also common and persistent in those who continued. Men were more likely to continue treatment. Patients who discontinued had lower baseline functioning and well‐being scores than those continuing, which persisted over time.
Conclusion
In around half of patients, continued use of perampanel is associated with better clinical outcomes, also on the long term, but adverse effects are common and persistent.
Keywords: long‐term follow‐up, Perampanel, primary orthostatic tremor, quality of life, treatment effect
Primary orthostatic tremor (POT) is a rare hyperkinetic movement disorder typically occurring in the sixth decade of life. OT is characterized by a general feeling of unsteadiness and a fast (≥13 Hz) tremor in the legs while standing, as revealed by electromyography (EMG), and in POT this occurs in the absence of signs of neurodegeneration or other neurological disorders. Symptoms typically emerge/exacerbate while standing still, and improve upon walking, leaning or sitting down. 1 The inability to stand still has a severe impact on patients’ quality of life (QoL).2, 3 Currently, there is no cure for OT. Symptomatic management relies primarily on non‐pharmacological interventions, like weight loss and home environment adjustments. Pharmacological therapies are tried in most patients, with clonazepam and gabapentin being used most frequently.1, 4 Treatment response, however, is poor and inconsistent and has shown to diminish over time.1, 5, 6
Perampanel is an anti‐epileptic drug with anti‐glutamatergic activity used to treat focal onset seizures and primary generalized epilepsy. Since the first publication, 7 several observational studies have reported positive effects of perampanel on POT,8, 9, 10, 11 it is currently prescribed off‐label for POT by many practitioners. 4 However, studies so far only assessed the short‐term (maximum duration of 14 months) effectiveness and encompassed a limited amount of patients (total n = 50).4, 7, 8, 9, 10, 11 All studies reported an overall positive effect of perampanel on POT symptoms although a high proportion (±40%) of patients discontinued treatment due to adverse effects and/or lack of effect.7, 8, 9, 10, 11
Following our previous report on the short‐term effectiveness in a cohort of 27 POT patients in the Netherlands, 11 in this study we aimed to (1) describe longitudinal perampanel use and its association with key clinical outcomes and baseline characteristics in a well‐defined cohort of POT, and (2) evaluate factors possibly associated with treatment continuation. The results may help to optimize treatment strategies of POT, provide patients with better information about their therapeutic options, and ultimately reduce the impact of this debilitating disorder.
Methods
Patients
This study included patients followed at the Amsterdam University Medical Centers (Amsterdam UMC) and Dutch OT Patient Support Group who: (1) had a diagnosis of POT as per Movement Disorder Consensus Criteria, 12 (2) started perampanel treatment between November 2018 and November 2022, (3) completed the set of self‐report scales prior to treatment start and at least once during follow‐up, and (4) provided informed consent.
Perampanel was prescribed off‐label. Standard initiation dose was 2 mg of perampanel ante noctem, with dosage and timing adjustments made during regular outpatient consultations based on positive and adverse effects. Management of ancillary anti‐tremor medication was at the discretion of the treating physician, although lowering or even stopping ancillary anti‐tremor medication was generally advised. Deep brain stimulation (DBS) prior to or after treatment start with perampanel was no exclusion criterium.
Data Extraction and Collection
Data were collected at multiple time points: at baseline (within 12 months before treatment initiation), at treatment start and while determining the optimal dosage, and during clinical follow‐up assessments after reaching the optimal dosage. Follow‐up assessments occurred at 0–6 months, 6–12 months after baseline, and annually thereafter.
The following clinical characteristics were collected: gender, age at onset and treatment start, diagnostic delay, disease duration (from symptom onset), co‐medication, and DBS. In addition, the following self‐report scales were used, as previously described11, 13:
Dutch OT‐questionnaire to assess patients’ clinical characteristics and adverse treatment effects;
Hospital Anxiety and Depression Scale (HADS) for evaluating anxiety and depression;
The 36‐Item Short Form Health Survey (SF‐36) for measuring health related QoL;
The activities of daily living (ADL) and the instrumental activities of daily living scale (iADL) for measuring physical disability.
For patients under active clinical care at the OT center of expertise of Amsterdam UMC, additional data was extracted from electronic patient files (EPF).
Self‐reported data from the questionnaires were cross‐checked against information in the EPF. When discrepancies occurred, particularly regarding adverse effects not documented in the EPF, information from both sources was combined. In case of clear conflict, the questionnaire data were considered leading for current medication use, whereas the EPF was leading for previously used medication.
Outcome Measures and Analysis
The following outcome measures were used:
Used anti‐tremor treatment as per OT questionnaire and/or EPF;
Perampanel usage as per OT questionnaire and/or EPF, including dosage of perampanel and time to reach a stable perampanel dose (defined as a dose maintained consistently for more than 6 months);
Reported treatment effect of perampanel as per OT questionnaire and/or EPF, including tolerability, as well as reasons for discontinuation;
Daily functioning and patient well‐being as per HADS, (i) ADL, and (SF‐36).
Analysis of patient characteristics and outcome measures was performed by statistically comparing patients who continued perampanel treatment throughout the follow‐up period with those who discontinued perampanel treatment at any point before end of follow‐up. Additionally, baseline scores on the SF‐36 and HADS were compared to established normative values. All comparisons were conducted using SPSS version 28. Further comparisons of patient characteristics and concomitant use of other tremor medication were made between patients with versus without adverse effects, and patients with versus without treatment benefit.
To determine whether the baseline characteristics gender, age, and disease duration were associated with treatment continuation a generalized linear model (GLM) was used. To evaluate the association of perampanel use with outcome measures for daily functioning and patient well‐being over time, linear mixed models (LMMs) were used. These models included linear fixed effects of time, gender, age, and disease duration, a time‐varying fixed effect of treatment status (dichotomous), and random intercepts at the patient level to account for within subject correlation of the observations. Both the GLM and LMM analyses were conducted using R version 4.4.2.
The analysis account for missing outcome data under the assumption that they are missing at random. Missing covariates were not replaced. Self‐report scales with >3 missing (sub‐)scores were excluded from all analyses.
Results
Patients
A total of 31 patients were included, of which 21 (67.7%) were female. This group includes 27 patients who have been previously described. 11 Of the 31 patients, 30 were treated at our center of expertise. Patients started perampanel treatment at a mean age of 67.6 years (SD = 8.0), and had a mean disease duration of 16.3 year (SD = 15.5) since start of symptoms. Patient characteristics are presented in Table 1. Baseline characteristics according to adverse effects and treatment benefit are provided in Table S1.
TABLE 1.
Patient characteristics.
| Characteristics | Group | Result | n |
|---|---|---|---|
| Amount of females (n) | Total | 21 (67.7%) | 31 |
| Continued | 9 | 17 | |
| Discontinued | 12 | 14 | |
| Age at diagnosis (y) | Total | 62.5 (±12.2) | 31 |
| Continued | 64.0 (±9.8) | 17 | |
| Discontinued | 59.9 (±14.5) | 14 | |
| Age at onset (y) | Total | 54.8 (±14.2) | 30 |
| Continued | 55.5 (±14.4) | 17 | |
| Discontinued | 53.7 (±14.7) | 13 | |
| Diagnostic delay (y) | Total | 9.0 (±8.2) | 30 |
| Continued | 8.9 (±7.0) | 17 | |
| Discontinued | 9.0 (±9.8) | 13 | |
| Age treatment start (y) | Total | 67.6 (±8.0) | 31 |
| Continued | 69.9 (±6.8) | 17 | |
| Discontinued | 66.8 (±9.1) | 14 | |
| Disease duration treatment start (y) a | Total | 16.3 (±15.5) | 31 |
| Continued | 14.9 (±9.0) | 17 | |
| Discontinued | 17.9 (±21.2) | 14 |
Note: Values are given either in absolute numbers (percentage of total) or in mean ± SD.
Abbreviations: n, number of subjects; y, years; C, since symptom onset.
Duration of the disease from diagnosis till inclusion in the study.
Mean follow‐up duration was 32.0 months (range 7.0–45.5). Patients completed a mean of four sets of scales (range 2–6), see Table 1. During follow‐up, 17 patients (54.8%) continued perampanel treatment, of which four temporarily discontinued treatment between follow‐up assessments, ranging from a few days till 2 months. For these 17 patients, the mean follow‐up duration was 32.2 months (range 7.0–45.5). Fourteen patients (45.2%) discontinued treatment after a mean follow‐up of 3.9 months (range 1 week–27 months), of which nine patients ceased treatment before first follow‐up. For these 14 patients, the mean total follow‐up was 31.8 months (range 16.0–42.75).
From four patients (ie, three who continued and one who discontinued treatment) a set of self‐report scales was removed from analyses due to missing data. In addition, most patients had one or more instances of missing outcome data over the course of follow‐up. The overall amount of missing data was very limited and generally restricted to isolated time points, with no systematic pattern in the nature or timing of the missing data.
No significant differences in patient characteristics were found between the patients who continued and discontinued treatment at baseline, although there was a higher proportion of females in the group that discontinued treatment, but this difference was not statistically significant (p = 0.052) (Table 1).
Anti‐Tremor Treatment
Medication
Perampanel starting regimens were as follows: 2 mg once daily (n = 15), 2 mg twice daily (n = 11), 1 mg once daily (n = 2), 4 mg once daily (n = 2), and 1 mg twice daily (n = 1). A stable dose was reached within 1–4.5 months. After reaching a stable dose, four patients (12.9%) made dose adjustments (ie, of which two continued and two discontinued treatment), with three patients lowering and one patient increasing their dosage (Table 2).
TABLE 2.
Anti‐tremor treatment.
| Treatment dosage perampanel | 2 mg once daily | 15 | 9 | 6 |
| 1 mg once daily | 2 | 0 | 2 | |
| 1 mg twice daily | 1 | 1 | 0 | |
| 2 mg twice daily | 11 | 5 | 6 | |
| 4 mg once daily | 2 | 2 | 0 | |
| Dosage change perampanel | Stable dose | 1–4.5 months | 1–4.5 months | 1–3 months |
| Increasing dosage | 1 | 1 | 0 | |
| Lowering dosage | 3 | 1 | 2 | |
| Additional anti‐tremor medication (n) | Baseline |
|
Propranolol: 2 |
Propranolol: 0 |
| Follow‐up |
|
|
|
|
| Deep brain stimulation | Prior to baseline | 3 | 2 | 1 |
| After treatment stop | 2 | 0 | 2 |
Switched from propranolol to clonazepam and topiramate before stopping all additional anti‐tremor medication.
At baseline, 19 patients (61.3%) used at least one anti‐tremor medications. Twelve patients discontinued all anti‐tremor medication before starting perampanel, one lowered the dosage, and two discontinued only one out of two medication. During follow‐up, seven of the 17 patients continuing perampanel and eight of the 14 who discontinued perampanel used other anti‐tremor medications at some point (Table 2).
Deep Brain Stimulation
Five of the 31 patients had DBS at some point during the study. Three patients had DBS prior to the baseline assessment, with two patients continuing perampanel during follow‐up. Two patients underwent DBS surgery after discontinuing perampanel.
Reported Treatment Effect Perampanel
Seventeen out of 31 patients (54.8%) reported a positive outcome overall: ie, tremor reduction and/or increased standing time. These patients continued treatment, in some patients (n = 10) even despite adverse effects. The remaining 14 patients discontinued perampanel because of: lack of effect (n = 5), adverse effects (n = 5), or both (n = 4). Three of the five patients who discontinued perampanel because of lack of effect also experienced adverse effects, although this was not the reason for discontinuation. The five patients who experienced adverse effects also reported therapeutic benefit, although the benefit did not outweigh the adverse effects.
In total 22 patients reported adverse treatment effects (1 adverse effect in n = 7; 2 in n = 6; 3 in n = 7; 5 in n = 2). Despite dosage adjustments after treatment initiation, adverse effects persisted in varying degrees during follow‐up. Most commonly reported adverse effects were dizziness (n = 5), sleepiness (n = 4), and tiredness (n = 4) (Table 3).
TABLE 3.
Adverse effects.
| Characteristics | Total | Continued | Discontinued | |
|---|---|---|---|---|
| Adverse effects | Dizziness | 5 | 2 | 3 |
| Sleepiness | 4 | 2 | 2 | |
| Tiredness | 4 | 3 | 1 | |
| Increase tremor | 2 | 0 | 2 | |
| Nightmare | 2 | 0 | 2 | |
| Skin rash | 2 | 0 | 2 | |
| Blurry vision | 1 | 1 | 0 | |
| Nausea | 3 | 1 | 2 | |
| Insomnia | 3 | 1 | 2 | |
| Number of adverse effects | 1 adverse effect | 7 | 5 | 2 |
| 2 adverse effects | 6 | 1 | 5 | |
| 3 adverse effects | 7 | 4 | 3 | |
| 5 adverse effects | 2 | 0 | 2 |
Abbreviations: EMG, electromyography; n.k., not known.
The result of the GLM to evaluate factors possibly associated with treatment continuation indicates that gender is a significant factor, with men being less likely to discontinue treatment compared to women. The odds of discontinuation were approximately 74% lower for men than for women.
Daily Functioning and Patient Well‐Being
Baseline Group Differences
At baseline, patients who discontinued perampanel had lower daily functioning and patient well‐being compared to patients who continued perampanel, aside from the SF‐36 sub‐score “health‐change” (Fig. 1). Significant difference were found in the SF‐36 sub‐scores “social functioning” (p = 0.017), “emotional well‐being” (p = 0.009), “energy/fatigue” (p = 0.026), “pain” (p = 0.022), and HADS depression score (p = 0.008).
Figure 1.
SF‐36 baseline scores (A) are shown for patients who continued and who discontinued, as well as normative values for age matched groups. Depression (B) and anxiety (C) baseline scores are shown for patients who continued, and for those who discontinued. Both the threshold for potential or suspected depression or anxiety (ie, >7), and norm values for both women and men are shown.
Comparison Baseline to Normative Data
When compared to age‐related normal values, patients who discontinued perampanel had significantly lower SF‐36 baseline scores across all domains, except for the sub‐scores “emotional well‐being” and “health progression.” Mean HADS depression (7.3 ± 3.4, n = 14; p = 0.013, 95% CI of 0.63–5.54) and anxiety (7.4 ± 5.1, n = 14; p = 0.046, 95% CI of 0.06–6.00) score were above the threshold for potential or suspected depression or anxiety (ie, >7) and significantly higher than the mean values in the general population (depression/anxiety: 4.8/4.4 for males and 4.7/5.0 for females) (Fig. 1). 14 In total, 57.1% (8 out of 14 patients) had potential or suspected depression, and 50.0% (7 out of 14 patients) had potential or suspected anxiety.
Patients who continued perampanel had significantly lower SF‐36 baseline scores for the sub‐scores “energy/fatigue” (p = 0.016, 95% CI of −19.63 to −2.30), “social functioning” (p = <0.001, 95% CI of −26.43 to −6.14), “physical functioning” (p = <0.001, 95% CI of −22.82 to −2.94), and “physical role limitation” (p = <0.001, 95% CI of −56.43 to −17.06) compared to age‐related normal values. Mean HADS depression (4.2 ± 4.0, n = 17) and anxiety (4.4 ± 4.3, n = 17) score were below the threshold for potential or suspected depression or anxiety (ie, >7), and mean values in the general population, although not significantly different. 14 In total, 17.7% (3 out of 17 patients) had potential or suspected depression, and 17.7% (3 out of 17 patients) had potential or suspected anxiety.
Effect of Perampanel Use on Outcome Measures
Perampanel use was associated with significant higher scores for the SF‐36 sub‐scores “emotional role limitation” (β = 26.60, p = 0.00456, 95% CI of −47.32 to −9.21), “social functioning” (β = 11.99, p = 0.04244, 95% CI of −25.00 to −0.98), “emotional well‐being” (β = 9.14, p = 0.01230, 95% CI of −16.63 to −2.39), and “pain” (β = 11.67, p = 0.02271, 95% CI of −23.47 to −2.10) (see Table S2).
Additionally, all patients showed a significant improvement over time in the SF‐36 sub‐score for “physical role limitation” (β = 0.52, p = 0.0351, 95% CI of 0.06–1.01), with other domains remaining unchanged. Disease duration was significantly associated with both ADL and the SF‐36 sub‐score for “pain,” with longer disease duration being associated with lower ADL (β = −0.00, p = 0.0147, 95% CI of −0.0037–0.0006) and pain (β = −0.08, p = 0.04861, 95% CI of −0.14 to −0.01) scores. Furthermore, while marginally non‐significant, a longer disease duration appeared to be related to lower SF‐36 sub‐scores for “physical functioning,” and men tended to have higher SF‐36 sub‐scores for “energy/fatigue” compared to women.
Substantial (unexplained) between‐subject variability remained after adjustment for age, gender, and disease duration. This variability is captured by the random intercepts in the mixed models (see Table S2.), and indicates that mixed models were indeed needed.
Discussion
This is the first study assessing the long‐term effectiveness and tolerability of perampanel for POT by comparing patients who continued treatment throughout the follow‐up period with those who discontinued before the end of follow‐up period. In a considerable proportion (around half) of patients, perampanel is an effective therapy for POT, with minimal dose adjustments made, and sustained association with better clinical outcomes. Adverse effects of perampanel were common and typically appear early after treatment start and persist to varying degrees throughout follow‐up. However, they often do not outweigh the beneficial effect of perampanel on POT. A substantial proportion of patients discontinued perampanel shortly after initiating treatment due to lack of effect and/or adverse effects. Gender was related to treatment continuation, with men being more likely to remain on perampanel. Additionally, no meaningful baseline differences were observed between patients with and without adverse effects or treatment benefit, and concomitant use of other tremor medications was similar across groups (Tables S1 and S3.).
The 54.8% continuation rate and a 71% incidence of adverse effects, with dizziness being the most commonly reported adverse effect, align with previous results in POT patients.4, 8, 11 In epilepsy, continuation rates of perampanel are higher than in POT during the first 6–12 months (approximately 66–77%), as POT patients generally seem to stop within the first year and less often during later follow‐up.15, 16 After 24–36 months, similar continuation rates are observed in both epilepsy and POT patients (±55%). Despite using higher doses, fewer epilepsy patients report adverse effects, though commonly reported adverse effects align with our findings and do not overlap with the symptomatology of POT. Moreover, some studies reported higher adverse effect rates (>60%). 17 The higher rate of adverse effects observed in POT patients compared to those reported in epilepsy studies may partly be related to the higher mean age of the POT population. Age is known to influence tolerability of antiseizure medications, including perampanel (Fan et al, 2023). However, within our cohort, mean age was comparable between patients who experienced adverse effects (71.5 ± 8.0 years) and those who did not (76.6 ± 6.6 years), suggesting that age alone does not account for the observed differences in tolerability. Research on perampanel in essential tremor is limited, showing initial effect, similar continuation rates and (dose related) adverse effects, and, in one open‐label trial (n = 50) a non‐sustained therapeutic effect on the long‐term.18, 19, 20 We did not observe a clear loss of efficacy after 12 months.
This is the first study that investigated specific aspects of daily functioning and well‐being in POT patients using perampanel. Use of perampanel is associated with improved social functioning, reduced emotional role limitations, enhanced mental health, and decreased pain. However, it should be noted that patients who continued perampanel had already higher scores for social functioning, mental health, and pain at baseline. Potentially suggesting that patients in better condition may be more likely to benefit from perampanel use. Additionally, several findings were marginally non‐significant (see Table S2), which may still hold clinical relevance given the wide confidence intervals, likely due to the small sample size in this study. Patients continuing treatment reported tremor reduction and increased standing time, suggesting perampanel may reduce disease severity. Disease severity is known to affect mental health and emotional role limitations. In chronic conditions, particularly those affecting physical functioning, greater disease severity is often linked to worse mental health outcomes. 21 Additionally, improvements in social functioning may be linked to reduced emotional role limitations and better mental health. 22
Continuation of perampanel appears to be influenced by gender, with men being significantly more likely to continue treatment compared to women. This trend is unlikely to be explained by baseline gender distribution, as the percentage of women included in this study aligns with previous literature.1, 4 Although this gender effect has not been previously observed in OT patients, similar findings have been reported in epilepsy. 23 Gender differences in clinical efficacy and tolerability of antiepileptic drugs are well‐established, with men generally showing higher continuation rates, also in perampanel.24, 25, 26, 27 While reported treatment efficacy plays a critical role in continuation rates, adverse effects are the primary reason for discontinuation of perampanel, with women more frequently discontinuing due to these effects.23, 25, 27
Our findings on daily functioning and well‐being align with previous literature. 3 Notably, patients who discontinued treatment had lower baseline SF‐36 and HADS scores than those who continued. However, it remains unclear whether disease severity influenced treatment continuation, as this was not directly assessed in our study. While prior research suggests that QoL in OT remains stable over time despite its progressive nature, 13 findings from other movement disorders show that greater disease severity is often linked to reduced QoL.3, 28, 29 Further research is needed to better understand its role in QoL and treatment outcomes in POT. Additionally, we observed a link between longer disease duration and increased pain, an association not previously reported in POT. Although leg pain has been mentioned in POT, it remains unclear whether this pain worsens with disease progression or how it affects daily functioning.6, 30
Compared to the wider OT literature, our study of perampanel adds to a field largely consisting of small open‐label cohorts and case reports. Clonazepam is reported as the most effective and widely used first‐line therapy in literature, with the systematic review showing clinically relevant improvement in approximately 40–50% of patients. 4 Gabapentin has more limited evidence, supported primarily by a small double‐blind crossover trial demonstrating an improvement in all four patients, and by several small observational studies reporting variable benefit around 30%.1, 4 In contrast, evidence for perampanel remains exploratory. Yet observed response rates effect is around 70%, and around 50% when considering only those who continue treatment, which, compared to existing therapies, is higher. 4 Nonetheless, the small and heterogeneous samples available for perampanel preclude firm conclusions regarding its relative effectiveness or the identification of patient subgroups with differential response or tolerability.
Our study has several limitations. The relatively small sample size and large number of outcome measures limited the complexity of the statistical analyses, allowing only the use of relatively simple models with respect to the number of included patient characteristics and their possible time‐varying nature and functional form. Consequently, it remains challenging to perform additional comparisons to reliably identify which patients are more likely to experience treatment benefit and/or adverse effects. Additionally, not all patients completed the same amount of questionnaires over time, limiting the available and accuracy of follow‐up data. This complicates comparisons of baseline changes upon follow‐up between both groups. The absence of a control group and the unblinded nature of the study limit the ability to draw definitive conclusions regarding treatment efficacy, as placebo effects and observer bias cannot be excluded. There is also potential reporting bias regarding patient‐reported medication use and its effects, which may have affected data accuracy. However, by collecting data from both EPF and questionnaires, the risk of this bias was reduced as the information could be cross‐checked for consistency. Another possible source of bias that we could not reliably model due to limited sample size was the concurrent use of other medications or DBS, as changes in these treatments could have influenced the outcomes. Nevertheless, given the minimal changes in anti‐tremor medication during follow‐up, this effect is likely small. Lastly, we did not account for disease severity in our analyses due to the absence of data, thereby limiting interpretation of our findings.
This study suggests that perampanel is significantly associated with improved daily functioning and patient well‐being in around half of POT patients. A notable response rate given that other medications for POT generally show a lower effectiveness. 4 Still, a substantial proportion of patients discontinue treatment, with men being more likely to continue treatment. Adverse effects are common, often persisting throughout follow‐up. In absence of experimental data on the efficacy of off‐label perampanel use in patients with POT, our study provides important insight in key patient characteristics and clinical outcomes associated with perampanel use over a long follow‐up period. Although our findings suggest which patients may benefit from or tolerate perampanel, the small sample size precludes firm conclusions, and initiating perampanel treatment should be guided by shared decision‐making, as current guidelines offer no specific recommendations for its use in OT. Further research should assess perampanel in larger cohorts of OT patients, including evaluation of both treatment benefit and adverse effects. Strategies for managing adverse effects to optimize treatment outcomes in OT patients should be explored.
Author Roles
(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique.
W.B.: 1A, 1B,1C, 2A, 2B, 3A.
B.S.: 1A,1B, 3B.
J.H.: 2A, 3B.
R.B.: 1A, 3B.
A.R.: 1A, 2C, 3B.
Disclosures
Ethical Compliance Statement: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Written informed consent was obtained for the data outside of standard patient care. A waiver of informed consent was obtained from the local medical ethical committee for the data that is part of standard patient care.
Funding sources and conflict of interests: All authors report no declarations of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.
Financial Disclosure for the Previous 12 Months: B.S. and J.H. have no financial disclosures for the previous 12 months to report. W.A.B. received a grant from Stichting HET REMMERT ADRIAAN LAAN Fonds paid to the institution. The funding source had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. R.M.A.d.B. has not received any funding related to the current research. The author received research grants from Medtronic, Bial, ZonMw, AMC Foundation, ROMO Foundation, and Stichting ParkinsonFonds, all paid to the institution. A.F.v.R. has not received any funding related to the current research. The author received a research grant from Stichting De Merel, paid to the institution.
Financial Disclosures and Conflicts of Interest
Author disclosures are available in the Supporting Information.
Supporting information
Table S1. Patient characteristics by treatment benefit and adverse effects.
Table S2. LMM outcomes.
Table S3. Anti tremor treatment by treatment benefit and adverse effects.
Data S1. Coi_disclosure All.
Acknowledgments
We thank Jelle Hellemons and Esther V. van der Woude for their help with the collection of the self‐report scales. The manuscript was edited using AI tools to improve grammar and overall readability. The authors carefully reviewed the revised text to ensure that the content, interpretations, and conclusions remain accurate and reflect original work.
Relevant conflicts of interest/financial disclosures: None.
Contributor Information
Wietske A. Babeliowsky, Email: w.a.babeliowsky@amsterdamumc.nl.
Bart Swinnen, Email: bart.swinnen@uzleuven.be.
Jeroen Hoogland, Email: j.hoogland@amsterdamumc.nl.
Rob M.A. de Bie, Email: r.m.debie@amsterdamumc.nl.
Anne‐Fleur van Rootselaar, Email: a.f.vanrootselaar@amsterdamumc.nl.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1. Patient characteristics by treatment benefit and adverse effects.
Table S2. LMM outcomes.
Table S3. Anti tremor treatment by treatment benefit and adverse effects.
Data S1. Coi_disclosure All.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.