Dementia is one of the most disabling disorders afflicting adult and elderly population reaching to epidemic proportions with an estimated 4.6 million new cases worldwide each year [
Dementia is characterized by progressive loss of memory or mental faculties such as language, judgment planning leading to impairment of daily activities, and deficiency in social interaction. While the treatment of dementia is basically directed towards management of cognitive and behavioral symptoms of dementia, partially effective treatments are available for most core symptoms of dementia. The treatment of dementia varies through the course of its illness, because symptoms evolve over time. Various drugs have been utilized for delaying cognitive decline as well as improving the behavioural symptoms associated with dementia. Acetyl cholinesterase inhibitors including Donepezil, Rivastigmine, and Galantamine have been recommended to be used in mild to moderate cases of dementia while Memantine is the only drug recommended for severe cases of dementia. Looking into the morbidity, appropriate utilization of antidementia therapy is highly essential for these patients. On the other hand psychosis, agitation and other behavioral symptoms are reported in patients with dementia causing lot of distress in caregivers. The atypical antipsychotics like Olanzepine, Quetiapine, Risperidone, and Clozapine have become the first line pharmacological treatments for behavioral symptoms in dementia patients. However the increased risk of mortality reported with the use of atypical antipsychotics has resulted in considerable skepticism over their use in the dementia patients.
Published Indian literature [
Drug utilization studies derives its importance in Pharmacoepidemiology from the fact that it is a part of medical audit involving the monitoring and evaluation of various prescriptions of Medical Practitioners to ensure rationality in medical care. In this article, we highlight the present Indian scenario of dementia in relation to its epidemiology, comorbidities and drug utilization in this particular region. Adjuvant supplements of vitamin B12 and folic acid are also being administered by clinicians to improve cognitive function of people. According to consensus guidelines on treatment of dementia before selecting a supplementation strategy, it is recommended that clear goals and target populations be set and checking of vitamin B12 and folic acid levels should be included in the diagnostic workup in patients undergoing assessment for dementia [
In light of this in current practice there seems to be scarcity of data on prior determination of serum vitamin B12 and folic acid status by clinicians before supplementing these vitamins in patients of dementia. Overuse of such multivitamins and folic acid, along with antidementia medications, without checking the serum levels may lead to an overprescribing of these drugs as well as increased economic burden to the patients.
Thus, this study was undertaken in patients presenting with impaired cognition, diagnosed to be suffering from dementia, to provide a glimpse of the drug utilization pattern amongst patients with dementia in a rural based medical teaching hospital in western India.
The study reported here was carried out at a rurally based tertiary care hospital (ShriKrishna Hospital, H.M.Patel Centre Medical Care & Education, Gokalnagar, Karamsad, Gujarat.) in western India. This was a cross sectional, point prevalence, open observational study, carried for a period of six months (July 2013 to December 2013). The study was initiated after the approval from the Ethics Committee of the hospital for the same (Approval No. HREC/FCT/46/APPROVAL/21).
Prospective as well as Retrospective data was collected. Prospective data was collected from outpatient department of hospital from July 2013 to December 2013. The prospective data was collected from the outpatient departments of the neurology, medicine, and psychiatry of the hospital from the prescriptions written by the respective medical professionals, that is, Neurologists (MBBS, MBBS, MD (Internal Medicine), DM (Neurology) [All India Institute of Medical Sciences] Consultant Neurologist), Physicians (MBBS, MD Internal Medicine) and Psychiatrist, (MBBS, MD Psychiatry) after obtaining the informed consent of the patient, while Retrospective data was collected from medical record section, that is, data was obtained from preserved past medication files of the patients visiting the hospital between the years 2008 to June 2013 after seeking permission for the same.
The study criterion included all patients who were diagnosed with dementia on the basis of DSM IV classification of disorders criteria. In addition, all patients also underwent MMSE (Mini Mental State Examination) and FAB (Frontal Assessment Battery) evaluations used for assessing the patients with dementia. MMSE is a brief, structured mental status examination for global cognitive function. The FAB is a brief tool that can be used at the bedside or in a clinic setting to assist in discriminating between dementias mainly between frontotemporal dementia and dementia of Alzheimer’s Type. All the obtained data was entered into a predesigned case record form. Case record form included all the information of patient like demographic details, their education level, socioeconomic class, details of MMSE and FAB scores, and drugs prescribed in dementia as well as various comorbid conditions. All the prescriptions were analyzed to find out the sample characteristics, frequency of different types of dementia, and prescribing pattern in these patients mainly focusing on the antidementia, antipsychotics, and vitamin supplementation.
The data was suitably coded and compiled on a Microsoft Excel sheet and descriptive statistics was used to analyze the data.
A total of 125 prescriptions were analyzed. Looking into the demographics of the patients, mean age of the population was found to be
Depiction of different demographic parameters of study population.
Distribution parameter | No. of patients ( | |
---|---|---|
Retrospective data | Prospective data | |
Gender distribution | ||
Male | 51 (58.61) | 24 (63.15%) |
Female | 36 (41.32%) | 14 (36.82%) |
Age range | 45–94 years | 52–93 years |
Average age |
|
|
Age distribution | ||
Below 65 years | 28 (32.18) | 12 (31.57%) |
Above 65 years | 59 (67.81%) | 26 (68.42%) |
|
||
Total no. of patients | 87 | 38 |
Geriatric population age distribution of dementia patient.
Regarding Gender distribution, males dominated the population of study that is, 60.57% (63.1% in Prospective data while 58.61% in Retrospective data) while females 39.43% (36.82% in Prospective data while 41.32% in Retrospective data) as depicted in Table
Socioeconomic class of the patients depicted that most of them belonged to the lower socioeconomic class, that is, 59.2%. Regarding education of patients in the sample, it was also noted that almost 8.0% of the patients were illiterate. A total of 56.0% of the patients were high school graduates. The percentage of population who were graduates was 24.0% while postgraduates were very less 12.0%, as shown in Tables
Socioeconomic classification of dementia cases.
SR. no. | Socioeconomic class | Retrospective data | Prospective data |
---|---|---|---|
1 | Low | 53 | 21 |
2 | Middle | 23 | 9 |
3 | High | 11 | 8 |
|
|||
Total | 87 | 38 |
Education status of dementia patients.
SR. no. | Patient education | Retrospective data | Prospective data |
---|---|---|---|
1 | Illiterate | 8 | 2 |
2 | High school graduate | 53 | 17 |
3 | Graduate | 20 | 10 |
4 | Post graduate | 6 | 9 |
|
|||
Total | 87 | 38 |
Mini Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) score was conducted to establish the diagnosis of the stage of dementia, to determine the advancement of diseases in dementia patients, and also to predict the mental capacity of patient. In our study the MMSE score ranges from 9–29 out of 30. A total of 40% of the population had a score ranging within 9–14. Approximately 30% of the population had a score within 15–19. The remaining 30% had a score ranging within 20–30. This is shown in Figure
(a) depicts the MMSE score pattern of dementia cases. (b) depicts FAB score pattern of dementia cases.
Out of 125 patients, the commonest type of dementia reported was Alzheimer’s disease found in 65.6% of the cases, (82 patients, Male = 45, Females = 37, Mean age =
Depiction of subtypes of dementia.
SR. no. | Type of dementia | No. of patients |
---|---|---|
1 | Lewy body dementia | 2.4% (3) |
2 | Alzheimer’s disease | 65.6% (82) |
3 | Vascular dementia | 21.6% (27) |
4 | Frontotemporal dementia | 10.4% (13) |
|
||
Total | 125 |
Similarly the distribution of different comorbidities associated with the dementia patients is represented in Figure
Representation of comorbidity distribution of dementia cases.
Patients included in the study were those of who were being treated with the Anticholinestrase drugs like Donepezil, Rivastigmine, Galantamine, Memantine either singly or in combination, and patients who were on concurrent medications like antipsychotics and vitamin B12 and folic acid therapy along with antidementia drugs.
In the given study, a total of 125 patients suffering from dementia were included. Prescription analysis of dementia patients depicts that most popular drug of choice for the given condition was Donepezil (68.49%) in a dose range of 5 to 10 mg, Rivastigmine (13.63%) in a dose range of 1.5 to 3 mg, Donepezil + Memantine (6.43%) and Galantamine (12.83%), respectively, as shown in Figure
Depiction of dose distribution of different antidementia drugs used.
SR. no. | Drug prescribed | Percentage | |
---|---|---|---|
1 | Donepezil | Percentage | 58.4 |
5 mg | 68.49 | ||
10 mg | 31.50 | ||
Total |
|
||
|
|||
2 | Rivastigmine | Percentage | 13.63 |
1.5 mg | 41.17 | ||
3 mg | 58.82 | ||
Total |
|
||
|
|||
3 | Donepezil (5 mg) + mementine (5 mg) | 6.43 | |
|
|||
4 | Galantamine (8 mg) | 12.83 | |
|
|||
5 | No. antidementia drug | 8 |
Depiction of antidementia drug prescribing pattern.
Along with antidementia drugs a large number of antipsychotics were prescribed to the dementia patients. Viewing the prescribing pattern, it was revealed that out of 125 patients 78 patients were prescribed at least one anti-psychotic drug. Among this commonest Antipsychotics used were atypical in nature that is, Quetiapine used in 30 (38.46%) cases, Clozapine in 9 (11.53%) cases, Olanzepine in 2 (2.56%) of cases, Older antipsychotic like Haloperidol in 3 (3.84%) of cases, Benzodiazepines like Lorazepam in 18 (23.07%) of cases, Nitrazepam in 1 (1.28%) of the cases, Non Benzodiazepine hypnotics like Zolpidem in 2 (2.56%) cases, Antidepressants like SSRI (Selective Serotonin Reuptake inhibitors) Escitalopram in 8 (10.25%) cases, Fluoxetine in 1 (1.28%) of the case, Sertraline in 2 (2.56%) of cases, Atypical Antidepressants like Tianeptine in 1 (1.28%) of the case while Antiepileptics like Lamotrigine in 1 (1.28%) of the case, respectively, as shown in Figure
Depiction of antipsychotic drug prescribing pattern in dementia cases.
On an average in our study in geriatric group population it was noted that 0.72 antipsychotic drug per prescription was prescribed.
Detailed analysis of the prescriptions under study reveals that there was high prescribing of folic acid and vitamin B12 in the patients without performing test to find out the need for the same in patient. folic acid was prescribed in 69 cases out of 125 (55.2%) while vitamin B12 alone was prescribed in 77 cases (61.6%), folic Acid and vitamin B12 was concurrently prescribed in 46 cases out of 125 (36.8%).
On an average in the study each prescription had
Dementia is a silent epidemic well observed in elderly throughout the world as well as in developing countries like India but they are poorly recognized and treated in developing countries including India [
Our study reports the mean age of patients to be
However regarding Socioeconomic statusmost of them belonged to the lower socioeconomic class which can be one of the important risk factors responsible for dementia. A study by Qian et al. found that individuals with lower socioeconomic status come into memory clinic later when the disease has progressed to dementia, while higher socioeconomic status individuals present earlier when the disease is still in its mild cognitive impairment stage. They concluded that higher socioeconomic status is associated with better cognitive functioning and increased use of cognitive enhancers [
Mini Mental State Examination mean score was
In the present study we found that amongst the types of Dementia Alzheimer’s disease was the most common type in 65.6% of the cases, (Mean age =
A clinic-based study from South India also depicts similar results, in which Alzheimer’s disease was found to be the commonest in 38.3% of the cases, vascular dementia in 25.4% of the cases, followed by frontotemporal dementia (FTD) in 18.7%, diffuse Lewy body disease (DLB) in 8.9%, and mixed dementia in 8.6% of the patients, respectively [
A total of 56.8% of the patient had one or more associated comorbidity. Regarding the comorbidity pattern in dementia patients in the study, we found that hypertension and diabetes mellitus were found to be the most common type of associated comorbidity. These comorbidities were effectively managed with antihypertensive drugs and antidiabetic drugs. Details of same were not a part of the current study. A study reported by Poblador-Plou et al. also found similar results, where the two most frequent comorbidities both for men and women with dementia were hypertension and diabetes. Other comorbidities significantly associated with dementia were Parkinson’s disease, congestive heart failure, cerebrovascular disease, anemia, cardiac arrhythmia, chronic skin ulcers, osteoporosis, thyroid disease, retinal disorders, prostatic hypertrophy, insomnia and anxiety, and neurosis [
Present study reveals that Donepezil (58.4%) was found to be the most prescribed antidementia drug in patients with mild to moderate dementia. Apart from Donepezil, Rivastigmine (13.63%) was found to be the second most popular choice of drug for dementia patients, Galantamine was preferred for 12.4% of the population, and combination of choline-esterase inhibitor, that is, Donepezil and Memantine was used in 6.43%. An audit involving Indian geriatric population which was performed by Prasad et al. on clinical practice of medications in dementia, his analysis concluded that the commonest antidementia drug used and alone prescribed was Donepezil (52%), while Rivastigmine alone was used in a single patient, Memantine alone was prescribed in 18% of cases, Galantamine alone was used in three patients only, whereas, Rivastigmine in six patients. A total of 12% were not prescribed any anti-dementia drug [
The 3 mg dose of Rivastigmine was more popular because generally patient were visiting in early stages, with mild to moderate dementia, most patients with severe dementia in India would be staying at their own homes with adequate care by children accepting the disease and trying alternative medicines as compared to allopathic leading to low frequency of visits in outpatient departments of respective units and this seems to be highlighted in our study. Hence Rivastigmine higher doses were not documented or not seen in the current study while most studies from the west would include patients under proper, adequate hospice care and hence would have high doses of drugs like Donepezil and Rivastigmine. Moreover population in the current study belongs predominantly to lower and middle socioeconomic class. Dose titrations of Donepezil and Rivastigmine were not reflected in this study because this study is a point prevalence study, so here patients were not serially evaluated but only assessed once. Moreover, the current study was not powered to study the doses in details, as that would have required a high number of patients which would have required a multicentre study. At the same time Rivastigmine happens to be more expensive as compared to Donepezil. Low prescribing of Galantamine can also be explained in similar lines. So considering the cost effectiveness issues in Indian clinical scenario this study favors more of Donepezil prescribing. Thus, here, we only intended to study the different category of drugs utilized.
Our study highlights that on an average each prescription had
Regarding the antipsychotic drugs used for behavioral symptoms
Our study found that Quetiapine, an atypical antipsychotic, was the most common antipsychotic used for behavioral and psychotic symptoms in 38.46% of cases in a dose range of 25 mg to 100 mg per day. In study reported by Prasad et al. [
Results of the Phase 1 outcomes from the clinical antipsychotics Trial of Intervention Effectiveness study for Alzheimer’s disease (CATIE-AD) suggest that antipsychotics may be more effective for particular symptoms like anger, agitation, aggression, and paranoid ideas. They do not appear to improve the functioning, care needs or quality of life [
Detailed analysis of the prescriptions under the current study reveals that there is high prescribing of vitamin B9, that is, folic acid and vitamin B12 in the patients without performing blood levels of the same and to find out the need for the same in patient. This is a judicious point to focus upon since literature supporting the use and benefits of same in dementia is still controversial. A study by Ford et al. reported that daily supplementation of vitamins B12, B6, and folic acid does not benefit cognitive function in older men, nor does it reduce the risk of cognitive impairment or dementia [
Comorbidities in these patients were effectively managed with antihypertensive drugs and antidiabetic drugs and moreover we did not intend to study details of various drugs prescribed in varied comorbid condition in this study.
Keeping in mind the limitations of the current study, nonetheless this investigation has thrown up valuable results that will surely help fine tune the clinical prescription approach in dementia patients. Alzheimer’s disease as other lifelong diseases needs to be more understood and analyzed in terms of its prescribing since it can have a major socioeconomic impact on its patients and caregivers particularly in developing countries like India. The audit highlights the need to study drug utilization pattern in dementia patients residing in developing countries, in terms of both pharmacovigilance and pharmacoeconomics and also strengthens the need to evaluate the rational use of vitamins and folic acid in these patients.
The authors declare that there is no conflict of interests regarding the publication of this paper.