|Year : 2023 | Volume
| Issue : 5 | Page : 293-298
Cost-minimization analysis of escitalopram, fluoxetine, and amitriptyline in the treatment of depression
Harshit Hemant Salian1, MV Raghav2, Vikram Singh Rawat3, A Divakar4
1 Department of Psychiatry, AIIMS, Vijaypur, Jammu, India
2 Department of Pharmacology, AIIMS, Jodhpur, Rajasthan, India
3 Department of Psychiatry, AIIMS, Rishikesh, Uttarakhand, India
4 Department of Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
|Date of Submission||17-Dec-2022|
|Date of Decision||13-Jul-2023|
|Date of Acceptance||29-Aug-2023|
|Date of Web Publication||02-Nov-2023|
M V Raghav
Department of Pharmacology, Bangalore Medical College and Research Institute, Fort, K R Road, Chamarajpet, Bengaluru - 560 002, Karnataka
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Escitalopram, fluoxetine, and amitriptyline are the drugs commonly used in the treatment of depression. The pharmacoeconomic evaluation of these drugs becomes relevant as they are prescribed for a long period of time, and depression causes a significant economic burden. The cost-minimization study would contribute to bringing down the annual treatment costs, leading to better medication adherence and ultimately better patient outcomes.
MATERIALS AND METHODS: All drug prices are mentioned in Indian National Rupee (INR). All expenses are based on 2022 pricing. No cost discounting was used because all expenditures were calculated over a year. We considered hypothetical scenarios where the patient was prescribed the lowest possible dose for depression, an equivalent antidepressant dose, a defined daily dose, and the maximum acceptable therapeutic dose for depression.
RESULTS: Annual average treatment costs of amitriptyline, escitalopram, and fluoxetine in patients with depression at baseline with equivalent dosing as mono-drug therapy were 2765.53, 2914.78, and 1422.72 rupees (INR), respectively. Savings were high when the patient was shifted to fluoxetine from either escitalopram or amitriptyline. The savings from switching to fluoxetine were 50.66% and 56.42% from escitalopram and amitriptyline, respectively.
CONCLUSION: The choice of an antidepressant depends on multiple aspects, among which the cost of treatment plays a crucial role. Among the drugs compared, fluoxetine seems to offer greater value for money. The study emphasizes that selective serotonin reuptake inhibitors are the most commonly prescribed antidepressants not only because of their favorable pharmacological profile but also because of their affordability.
Keywords: Depression, National List of Essential Medicines, National Pharmaceutical Pricing Authority, pharmacoeconomic study
|How to cite this article:|
Salian HH, Raghav M V, Rawat VS, Divakar A. Cost-minimization analysis of escitalopram, fluoxetine, and amitriptyline in the treatment of depression. Indian J Pharmacol 2023;55:293-8
|How to cite this URL:|
Salian HH, Raghav M V, Rawat VS, Divakar A. Cost-minimization analysis of escitalopram, fluoxetine, and amitriptyline in the treatment of depression. Indian J Pharmacol [serial online] 2023 [cited 2023 Nov 28];55:293-8. Available from: https://www.ijp-online.com/text.asp?2023/55/5/293/389241
| » Introduction|| |
Depression is a common chronic medical condition that impacts one's thoughts, mood, and physical well-being. Low mood, low energy, pessimism, sleeplessness, and an inability to appreciate life are some of its symptoms. The three main types of treatment for managing depression are antidepressants, electroconvulsive therapy, and psychosocial therapies. In general, selective serotonin reuptake inhibitors (SSRIs) are regarded as first-line antidepressants due to their favorable efficacy and safety profiles. Tricyclic antidepressants (TCAs) such as amitriptyline and atypical antidepressants such as mirtazapine, bupropion, and venlafaxine are alternate therapeutic options.
According to a cohort study in Canada by Tanner et al., depression can make the patient and the family suffer mentally, physically, and economically. Among individuals who were depressed, comorbidities were 43% more common. Patients with depression had greater rates of deliberate self-harm, overall death from all causes, and suicide mortality than the nondepressive population. The hospitalization rate, doctor visits, doctor-assisted psychotherapy, and prescription medication use were all greater in the depressive cohort than in the nondepressive group. Patients with depression had average health-care expenses that were 3.5 times greater than those without depression. By ensuring optimal costs for prompt and continued treatment, the economic burden caused by depression can be overcome.
Pharmacoeconomics is defined as the application of economics to optimize benefits for patients, health-care payers, and society through data-driven decision-making by balancing the costs and benefits of interventions toward the utilization of scarce resources. Cost-minimization analysis, cost–benefit analysis, cost-effectiveness analysis, and cost–utility analysis are the four major types of pharmacoeconomic approaches. A cost-minimization analysis is performed to choose the least expensive alternative therapeutic option with almost equal health-care outcomes.
Escitalopram, fluoxetine, and amitriptyline are drugs commonly used to treat depression. Escitalopram, fluoxetine, and amitriptyline were enlisted as medicines used in depressive disorders under 23.2.1 of the National List of Essential Medicines (NLEMs) 2022, Government of India. Fluoxetine and escitalopram belong to a class called SSRIs, which are the approved first-line drugs for the treatment of depression. Amitriptyline, which is a TCA, would be an alternative that is equally efficacious but not used as a first-line medication.,,
The pharmacoeconomic evaluation of these drugs becomes relevant as they are commonly prescribed for a long time, and depression causes a significant economic burden. Although cost-variation studies are present, the cost-minimization study of these drugs is currently unavailable. The cost-minimization study would reduce the annual treatment costs, leading to better medication adherence and, ultimately, better patient outcomes.
The primary objective was to compare the costs of three antidepressants (escitalopram, fluoxetine, and amitriptyline) assuming they had similar efficacy. The secondary objective was to objectively measure the percentage cost saved after switch from one drug to another.
| » Materials and Methods|| |
The current study is a pharmacoeconomic evaluation of antidepressant therapy in the International Classification of Diseases-10-diagnosed cases of depression – three antidepressants were included, escitalopram, fluoxetine, and amitriptyline. It flows model-based pharmacoeconomic evaluation design. All data used in calculation of costs were used from publicly available databases.
It follows a model-based pharmacoeconomic evaluation design using the cost-minimization principle and using four hypothetical scenarios. Cost-minimization analysis compares the expenses of different strategies and compares them. When comparing the treatments, it is assumed that the counterparts are equally effective, allowing just the cost differences to be considered. In order to compare costs, it is assumed that the intervention with the lower cost would be used.
We limited our study to the dosage forms mentioned in the NLEM 2022, as these were the most common formulations to be used. All drug prices are mentioned in Indian Rupee (INR). Only the direct costs of the drugs are considered. The maximum price was obtained from the National Pharmaceutical Pricing Authority (NPPA) pricing list of April 18, 2022. The NPPA mentions the ceiling price at which drugs can be sold, which we assumed was the maximum price. The minimum price was obtained from Jan Aushadhi, a government of India-sponsored generic drug program. The lowest and highest costs were used to calculate the average yearly cost of therapy. All the prices used for calculation are summarized in [Table 1]. We only included preparations with escitalopram, fluoxetine, and amitriptyline as a single active ingredient, and combination preparations were excluded.
|Table 1: Ceiling, minimum, and average prices of escitalopram, fluoxetine, and amitriptyline in INR|
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There were three significant stages in the model.
- Computing the cost: In this study, the payer's point of view was adopted on the presumption that the patient would directly pay for the medication. We, therefore, assume that patients taking any of the three drugs have a similar frequency of doctor visits because all three medications are common oral antidepressant agents, well tolerated, and have similar treatment efficacy and gastrointestinal adverse reactions, which can be alleviated by starting at a low dose and gradually increasing the dose. We thus assume that the expenses associated with treating depression, such as those associated with doctor visits, diagnostic tests, inspections, and hospitalization, may be accounted to be equal and excluded from our analysis. All expenses are based on 2022 pricing. No cost discounting was used because all expenditures were calculated over a year
- Base-case identification: The treatment of depression does not include an exhaustive dosage regimen. Hence, a scenario-based approach was sought
- Sensitivity analysis: A number of distinct clinical scenarios were put together after discourse with psychiatrists treating depression patients with the goal to demonstrate potential clinical situations and to analyze the difference in annual average treatment costs because physicians' compliance with drug instruction recommendations with regard to the initiation and monitoring of drug dosage in treating depression was unknown.
Titration of the doses according to the patient's response is also assumed to be the same, and onset of response by each drug is also assumed to be the same. There are no specific medication dosing guidelines for the treatment of depression as to how dose escalation has to be done and when to switch drugs. However, the course of treatment is determined by the patient's clinical state and medication response as assessed by the treating psychiatrist. We looked at model cases which included the following:,,,,,
- The patient was given the lowest antidepressant dose that could be prescribed for depression
- An equivalent dose of an antidepressant as mentioned in a 2015 Japan study
- A defined daily dose (DDD) of these medications as described by the World Health Organization (WHO): anatomic and therapeutic classification of drugs
- Maximum acceptable therapeutic dose for depression. [Table 2] lists the dosages used for computation.
|Table 2: Hypothetical case scenarios used for cost-minimization analysis between escitalopram, fluoxetine, and amitriptyline|
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The doses used for calculation are mentioned in [Table 2].
The calculations were based on the following assumptions:
- SSRIs are usually prescribed as a single dose in the morning to avoid sleep disturbances. TCAs can be given as a single dose at night or twice daily, with a higher dose at night
- We calculated the prices of drugs for 1 year of antidepressant therapy.
| » Results|| |
Annual average treatment costs of escitalopram, fluoxetine, and amitriptyline in patients with depression with equivalent dosing as mono-drug therapy were 2765.53, 2914.79, and 1422.72 rupees (INR), respectively. For the DDD of escitalopram, fluoxetine, and amitriptyline in patients with depression, the prices were 1935.77, 1823.18, and 899.73 rupees (INR), respectively. Further drug prices are summarized in [Table 3].
|Table 3: Prices in INR of annual treatment with escitalopram, fluoxetine, and amitriptyline as mono-drug therapy in four hypothetical scenarios|
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The annual treatment cost, percentage cost difference, and percentage savings in the annual cost of escitalopram, fluoxetine, and amitriptyline in patients with depression are summarized in [Table 4] and [Figure 1], [Figure 2], [Figure 3]. Compared to escitalopram, amitriptyline had a lesser annual average treatment cost in scenarios 1 and 3, whereas amitriptyline and escitalopram were almost similar in prices in scenarios 2 and 4. When fluoxetine was compared with either of the two drugs, unanimously, in all four scenarios, fluoxetine was the cheaper alternative. The findings were that if a patient switched to fluoxetine from escitalopram, he would save 50.66% on treatment annually. Similarly, if the patient switched to fluoxetine from amitriptyline, 37.99% cost could be cut down every year. Hence, savings were high when the patient was shifted to fluoxetine from either escitalopram or amitriptyline.
|Table 4: Comparison of annual treatment cost in INR (₹) of escitalopram, fluoxetine, and amitriptyline in patients with depression|
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|Figure 1: The annual treatment cost, percentage cost difference, and percentage savings in the annual cost of escitalopram and amitriptyline in patients with depression|
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|Figure 2: The annual treatment cost, percentage cost difference, and percentage savings in the annual cost of amitriptyline and fluoxetine in patients with depression|
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|Figure 3: The annual treatment cost, percentage cost difference, and percentage savings in the annual cost of escitalopram and fluoxetine in patients with depression|
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| » Discussion|| |
Economic evaluation is the comparative analysis of various projects' costs and effects using economic theories and methods. In terms of health policy, there is an increasing need to identify medical treatment solutions that are efficient but less expensive as more governments try to contain the growth in health expenditure.
To obtain good value for money, a pharmacoeconomic method is frequently employed to assess the health benefits of medication therapies. [Table 5] summarizes various pharmacoeconomic models available. In a nation like India, where the inclusion of a drug on the NLEMs, the inclusion and exclusion of a drug from the NPPA, and the pricing of new drugs, patent medicines, and other drugs are crucial, the economic appraisal of medical products is very crucial. Drugs in NLEM are readily available across the country and at most government health facilities.
|Table 5: Methods of evaluating subgroups using various pharmacoeconomic designs|
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The selection of an antidepressant is primarily governed by the indication. Not every illness responds to antidepressants in a similar manner. It is hard to prove that one antidepressant regularly outperforms another in treating MDD. As a result, selecting an antidepressant for the treatment of depression mostly depends on pragmatic factors such as cost, availability, side effects, potential drug interactions, the patient treatment response history (or lack thereof), and patient preference. The choice of an antidepressant may also be influenced by additional elements such as the patient's age, gender, and health.
We employed the cost-minimization analysis approach on the assumption that the major clinical outcomes and side effects of the three drugs are practically equal. Since it can be challenging to adequately evaluate research variables in economic evaluation and since each pharmacological therapy may have a varied cost of care depending on the population or medical institution, it is crucial to consider how fundamental assumptions may affect study outcomes. As a result, we created four scenarios to reflect the real-life cost profile.
The indirect cost associated with the antidepressant therapy was not considered because this study was done from the payer's point of view. The payments for doctor visits, medications, diagnostics, checkups, hospitalizations, transportation, and other expenses are considered direct medical costs. Because we expected that other expenses would be the same in the three treatment groups, we only calculated the medication cost in this study and no other expenditures.
This study also only considers a single monotherapy for a year; however, in the real-world scenario, due to the complexity of mental health disorders (comorbid anxiety, sleep disturbances, obsessive–compulsive disorder, or switch in bipolar disorder), patients frequently switch medications, which can have an impact on the cost. Minimum and ceiling prices were considered based on prices available on government portals. However, the prices of these drugs may not reflect the real-world scenario. Further research is required to comprehend the annual expenditures on antidepressant therapy and support resource allocation decisions.,
Our study has a notable strength in that it is the first cost-minimization evaluation comparing various antidepressant therapies undertaken based on findings from previous studies and data available in the public domain. Our study included antidepressants commonly used for the treatment of depression, which makes it relevant in a real-world scenario.
| » Conclusion|| |
The choice of an antidepressant depends on aspects such as efficacy, patient illness profile, adverse drug reactions, availability, drug interactions, and cost of treatment, which play a crucial role in a developing economy like India. The study emphasizes that SSRIs are the most commonly prescribed antidepressants not only because of their favorable pharmacological profile but also because of their affordability. In the future, more research can be taken up and include sensitivity analysis for better interpretation of results.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Cui R. Editorial: A systematic review of depression. Curr Neuropharmacol 2015;13:480.
Gautam S, Jain A, Gautam M, Vahia VN, Grover S. Clinical practice guidelines for the management of depression. Indian J Psychiatry 2017;59:S34-50.
Tanner JA, Hensel J, Davies PE, Brown LC, Dechairo BM, Mulsant BH. Economic burden of depression and associated resource use in Manitoba, Canada. Can J Psychiatry 2020;65:338-46.
Tonin FS, Aznar-Lou I, Pontinha VM, Pontarolo R, Fernandez-Llimos F. Principles of pharmacoeconomic analysis: The case of pharmacist-led interventions. Pharm Pract (Granada) 2021;19:2302.
Reeder CE. Overview of pharmacoeconomics and pharmaceutical outcomes evaluations. Am J Health Syst Pharm 1995;52:S5-8.
McIntosh E, Luengo-Fernandez R. Economic evaluation. Part 1: Introduction to the concepts of economic evaluation in health care. J Fam Plann Reprod Health Care 2006;32:107-12.
Szoke-Kovacs Z, More C, Szoke-Kovacs R, Mathe E, Frecska E. Selective inhibition of the serotonin transporter in the treatment of depression: Sertraline, fluoxetine and citalopram. Neuropsychopharmacol Hung 2020;22:4-15.
Landy K, Rosani A, Estevez R. Escitalopram. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022.
Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al.
Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. Lancet 2018;391:1357-66.
Higgins AM, Harris AH. Health economic methods: Cost-minimization, cost-effectiveness, cost-utility, and cost-benefit evaluations. Crit Care Clin 2012;28:11-24, v.
National Pharmaceutical Pricing Authority List, Ministry of Chemical and Fertilisers, Government of India. Available from: https://www.nppaindia.nic.in/en/
. [Last accessed on 2022 Apr 18].
Jan Aushadhi – Pharmaceuticals and Medical Devices Bureau of India (PMBI), Under Department of Pharmaceuticals, Government of India. Available from: https://www.janaushadhi.gov.in/index.aspx
. [Last accessed on 2022 Apr 22].
Gu S, Tang Z, Shi L, Sawhney M, Hu H, Dong H. Cost-minimization analysis of metformin and acarbose in treatment of type 2 diabetes. Value Health Reg Issues 2015;6:84-8.
Hayasaka Y, Purgato M, Magni LR, Ogawa Y, Takeshima N, Cipriani A, et al.
Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials. J Affect Disord 2015;180:179-84.
World Collaborating Centre for Drug Statistics Methodology – ATC/DDD Codes, World Health Organization. Available from: https://www.whocc.no/atc_ddd_index
. [Last accessed on 2022 Apr 22]
Stahl SM. Stahl's Essential Psychopharmacology: Prescriber's Guide. Prescriber's Guide: Stahl's Essential Psychopharmacology. 7th
ed. Cambridge: Cambridge University Press; 2020. p. 96, 796 and 913.
Gu SY, Xu XC, Shi LZ. Cost Minimization Analysis of Clinical Option Scenarios for Metformin and Acarbose in the Treatment of type 2 Diabetes: Based on Direct and Indirect Treatment Comparison Results: ISPOR 6th
Asia-Pacific Conference. Available from: https://www.ispor.org/research_pdfs/47/pdffiles/PDB27.pdf
. [Last accessed on 2022 Apr 22].
Chinese Group for Pharmacoeconomic Evaluations Guidelines. China guidelines for pharmacoeconomic evaluations. China J Pharm Econ 2011;3:7-48.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]