Introduction
Parkinson’s disease (PD) is the second most frequent neurodegenerative disease Neuropathological hallmarks are progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra, causing striatal dopamine deficiency, and intracellular inclusions containing aggregates of alpha-synuclein.1, 2 PD is clinically defined by the presence of bradykinesia and at least one additional cardinal motor feature (rigidity or rest tremor). In addition, most patients with PD also experience non-motor symptoms (NMS), adding to the overall burden of parkinsonian morbidity. 3, 4, 5 PD was the first neurodegenerative disease for which highly efficacious treatments became available. Dopamine replacement with oral levodopa is still the gold standard of symptomatic therapy. The treatment of Parkinson’s disease (PD) with dopaminergic therapy, especially in the early stages, is usually associated with significant improvements in motor disability, and the first few years of pharmacotherapy are often referred to as the ‘honeymoon period’ because patients generally enjoy sustained symptomatic relief with minimal side effects. Satisfactory management of Parkinson’s disease is a challenge that requires a tailored approach for each individual. Dopaminergic treatment continues to benefit patients as PD progresses, but within a few years of starting therapy, whether with levodopa alone or levodopa and a dopamine agonist, the majority of patients begin to notice a decline in the duration of benefit of each dose. This is referred to as ‘end of dose deterioration’ or ‘wearing-off.Qualit. Polypharmacy in Parkinsons disease treatment leads to Adverse Drug Reactions which might impair the quality of life.6, 7, 8, 9 Mostly levodopa is used in parkinson disease treatment and addition of other agents like pramipexole, ropinirole, amantadine, trihexyphenydil etc helps in improvement of symptoms and quality of life of patients.10, 11, 12, 13 So safety of antiparkinson’s drugs and quality of life effects of antiparkinsonian drugs are important parameter to explore.There are few studies conducted in India regarding safety and quality of life effects of Antiparkinson’s drugs in Parkinson disease and none in West-Bengal. Hence this study is taken up in our tertiary care Hospital.
Aims & Objectives
To study Antiparkinson’s drug-effects on quality of life of parkinson disease patients and their safety and tolerability.
Materials and Methods
Study site
Department of Clinical & Experimental Pharmacology, Calcutta School of Tropical Medicine, Kolkata
Study period
The study commenced after obtaining approval from institutional ethics committee, and completed in 24 months.
Subject enrolment: 6 months
Follow up: 12 months
Data analysis and report writing: 4 months
Sample size: 111 sample size was found
Study population: All consecutive criteria-eligible, consenting patients attending the
Neurology OPD of Medical College, Kolkata and the private clinic of the one practising Neurologist.
Inclusion criteria
Adult subjects of either sex, idiopathic parkinsonism (Parkinson’s disease) duly diagnosed, attending Neurology Clinic regularly, willing to take part in the study, and having consented, likely to cooperate for periodic follow-up and other protocol-specified formalities were included .
Study technique
Patients were enrolled from Neuromedicine OPD of Medical College and Hospital, Kolkata as well as from private clinics of one Neurologist in Howrah, West Bengal according to inclusion and exclusion criteria after taking the informed consent. Patient’s data were filled in the Case report form at baseline and then followed up for 3 visits (1month, 3 month and 6 month).The basic demographic details recorded. Quality of life evaluated by Parkinson Disease Questionnaire – 39 at baseline and follow up periods. Safety of antiparkinson medications was analysed by monitoring suspected adverse drug reactions by using Suspected ADR Reporting Form of Indian Pharmacoepia commission (Version 1.3). Causality of such reactions were assessed using WHO UMC Causality Assessment Scale, Naranjo’s Algorithm. Severity of the reactions were assessed using Hartwig and Seigel’s Severity Assessment Scale.
Statistical analysis
Data collected and then statistically analyzed.
Descriptive data represented as mean or percentages.
Demographic and categorical data where possible, analyzed with parametric or non-parametric tests using [Mean± SD, Median, Fisher exact test, Friedman’s ANOVA test, Wilcoxon matched pair signed rank test].
Data analysed by using WPS Excel and Graph pad prism 9 software.
Result
Total Idiopathic Parkinson disease patient were 111 in our study
Table 1
Descriptivestatistics of demography
|
Demography |
Age(YR) |
Wt(KG) |
|
Mean±sd |
61.85±7.20 |
59.47±6.34 |
|
Median |
62 |
59 |
This Table 1 shows Descriptive statistics of Demography in which mean age was 61.85yr, Median age was 62yr and Mean weight was 59.47kg, Median was 59kg
Employment status
epicts employment status of Idiopathic parkinson disease patients. A total of 56(50.5%) were found to be in the Unemployed group.
Comorbidities
epicts Comorbidities among Idiopathic parkinson disease patient. Most common comorbidities were Hypertension 8(33.3%) and Diabetes Melitus type 2 8(33.3%).
Statistical analysis by Friedman’s ANOVA shows PDQ39 score was significant in different groups P< 0.001
Quality of life
epicts quality of life improvement by PDQ 39 score from baseline to subsequent follow ups
Safety & tolerability
epicts suspected drugscausing ADRs and their causality assessment by WHO-UMC scale and Naranjo causality assessment scale among Idiopathic parkinson disease patients. WHO-UMC Scale AND Naranjo causality assesment scale both revealed 36.4% ADRs were Probable category and 63.6% were possible category.
This table 6 shows Hartwig’s severity scale, according to it 11 (100%) ADRs were in level 1 of mild intensity.
The antiparkinson’s drugs are well tolerated as having less ADRs.
Pharmacotherapy
Syndopa found to be most commonly used in parkinson’s disease.
Adding dopamine agonists (Ropinirole, Pramipexole), Anticholinergic (Trihexyphenydil), NMDA inhibitors (Amantadine) etc also improve quality of life etc
This Figure 1 shows age wise distribution of Idiopathic parkinson disease patients.A total of 70(63%) Idiopathic parkinson disease patients were in age group< 65 years and a total of 41(37%) Idiopathic parkinson disease patients were in age group ≥ 65 years.
.
Table 2
Employment status of idiopathic parkinson disease patients
|
Employed |
Unemployed |
Self Employed |
|
30(27%) |
56(50.5%) |
25(22.5%) |
Table 3
Comorbidities among idiopathic parkinson disease patients
|
Hypertension |
Diabetes Melitus Type 2 |
Hypothyroidism |
Dyslipidemia |
Smoker |
|
8 (33.3%) |
8(33.3%) |
4(16.7%) |
3(12.5%) |
1(4.2%) |
Table 4
PDQ39 at baseline and follow ups
|
Score |
Baseline (Mean±sd) |
1st Follow Up (Mean±sd) |
2nd Follow up (Mean±sd) |
3rd Follow up (Mean±sd) |
Friedman’s ANOVA |
|
PDQ 39 |
180.7±6.35 |
#183.6±4.65 |
#188±4.26 |
#192.3±2.76 |
P<0.001 |
Table 5
ADRs in idiopathic parkinsonism patients
Table 6
|
Severity |
Level |
Number of ADRs |
Total (%) |
|
Mild |
1 |
11 |
100% |
|
2 |
0 |
||
|
Moderate |
3 |
0 |
0 |
|
4 |
0 |
||
|
Severe |
5 |
0 |
0 |
|
6 |
0 |
||
|
7 |
0 |
This Figure 2 shows gender wise distribution of Idiopathic parkinson disease patients.A total of 89(80.2%) Idiopathic parkinson disease patients were found in males and a total of 22(19.8%) Idiopathic parkinson disease patients were found in females
This Table 2 depicts employment status of Idiopathic parkinson disease patients. A total of 56(50.5%) were found to be in the Unemployed group.
This Table 3 depicts Comorbidities among Idiopathic parkinson disease patient. Most common comorbidities were Hypertension 8(33.3%) and Diabetes Melitus type 28(33.3%).
This Table 4 shows Statistical analysis of PDQ39 at baseline and follow ups.
Mean PDQ39 score was 180.7, 183.6, 188, 192.3 at baseline, 1st follow up, 2nd follow up, 3rd follow up respectively.
Statistical analysis by Friedman’s ANOVA shows PDQ39 score was significant in different groups P< 0.001.
Total Adrs- 11
This Table 5 depicts suspected drugs causing ADRs and their causality assessment by WHO-UMC scale and Naranjo causality assessment scale among Idiopathic parkinson disease patients. WHO-UMC Scale AND Naranjo causality assesment scale both revealed 36.4% ADRs were Probable category and 63.6% were possible category
This Table 6 shows Hartwig’s severity scale, according to it 11 (100%) ADRs were in level 1 of mild intensity.
Discussion
Present study was designed to assess safety and tolerability, quality of life in parkinson’s disease patients.
Demographic characteristics of Idiopathic Parkinson disease
Figure 1 shows most of the patients (63%) were in the age group <65 years followed by age group ≥65 years (37%).In our study, mean age found to be 61.85± 7.20 which is nearly corroborated with Shah J et al 14 in that study mean age was 61.88±11.93 and Samii A et al 15 where mean age was 60 yrs.
FIGURE 2 reveals males constituted the majority i.e. 89 of all IPD patient (80.2%) while females comprised 22 cases (19.8%) of IPD patients. In Shah J et al Study 14 ,PD in male : female was 2.007:1 which is similar to our study I.e,M:F -1.7:1
Multiple studies have indicated that male to female ratios for incidence rates vary from 1.37 to 3.7.
Quality of life
shows distribution of PDQ 39 score among different visits.It also reveals improvement of quality of life from baseline to further follow up visits.
Quality of life is an important measure for parkinson’s disease, in terms of physical and mental health outcomes. Quality of life in our study was measured by using PDQ39 Score 16, 17.
In our study, we evaluated Quality of life by using PDQ39 questionaire. Mean PDQ39 score was found to be 180.7 at baseline that was found to be improved in follow ups.
In Jugal Saha et al study 14, Mean total PDQ 39 score was 130.45 nearly approximate to our study .Higher the score better is the quality of life.
Safety & tolerability
Antiparkinson Drugs are usually well tolerated and adverse events range from mild to moderate found in a study by Federico carbone et al.6 Another study by Thaha F et al7 also revealed that majority of ADRs in their study were mild in intensity. In our study we assessed safety and tolerability to anti Parkinson’s drugs and adverse drug reactions from patients complain, Physical examinations by Neurologists. All the ADRs were mild in intensity as no drug withdrawal or no drug modification needed to treat the ADRs.
Causality assessment of ADRs by WHO-UMC and Naranjo scales
HO-UMC scale shows7 cases (63.6%) in possible category and 4 cases (36.4%) in probable category, Naranjo scale shows 7 cases (63.6%) in possible category and 4 cases (36.4%) in probable category.
Thaha F et al study6, 7 revealed 72.5% ADRs were found to be possible category and 27.5% were found to be in Unlikely category.
Limitation
We were able to follow the patients only for 6 months due to the COVID 19 pandemic and associated lockdown all over the country. So, study duration was very short to evaluate the outcomes. Our study was a Time- bound study, so a limited sample size of 111 was collected.
