ANALYSIS OF THE COST-EFFECTIVENESS AND COSTS RATIONALIZATION OF ANTIDEPRESSANTS CONSUMPTION IN LITHUANIA

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LITHUANIAN UNIVERSITY OF HEALTH SCIENCES MEDICAL ACADEMY

Liubov Kavaliauskienė

ANALYSIS OF THE COST-EFFECTIVENESS

AND COSTS RATIONALIZATION

OF ANTIDEPRESSANTS CONSUMPTION

IN LITHUANIA

Doctoral Dissertation Biomedical Sciences, Pharmacy (08B) Kaunas, 2013

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Dissertation prepared in 2008–2012 in Lithuanian University of Health Sciences.

Scientific Supervisor

Prof. Dr. Rimantas Pečiūra (Lithuanian University of Health Sciences Medical Academy, Biomedical Sciences, Pharmacy – 08B).

Consultant

Prof. Dr. Virginija Adomaitienė (Lithuanian University of Health Sci-ences Medical Academy, Biomedical SciSci-ences, Medicine – 06B).

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LIETUVOS SVEIKATOS MOKSLŲ UNIVERSITETAS MEDICINOS AKADEMIJA

Liubov Kavaliauskienė

ANTIDEPRESANTŲ PANAUDOJIMO

LIETUVOJE SĄNAUDŲ EFEKTYVUMO

IR IŠLAIDŲ RACIONALIZAVIMO

ANALIZĖ

Daktaro disertacija Biomedicinos mokslai, farmacija (08B) Kaunas, 2013

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Disertacija rengta 2008–2012 metais Lietuvos sveikatos mokslų universiteto Medicinos akademijoje.

Mokslinis vadovas

prof. dr. Rimantas Pečiūra (Lietuvos sveikatos mokslų universiteto Me-dicinos akademija, biomeMe-dicinos mokslai, farmacija – 08B).

Konsultantė

prof. dr. Virginija Adomaitienė (Lietuvos sveikatos mokslų universiteto Medicinos akademija, biomedicinos mokslai, medicina – 06B).

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ABBREVIATIONS

AD Antidepressants

ANOVA Analysis of variance

ATC Anatomical Therapeutic Chemical classification CHIF Compulsory Health Insurance Fund

CI Confidence Interval

CL Confidence Level

CNS Central Nervous System

CVD Cardiovascular disease

DALY Disability Adjusted Life Year

DDD Defined Daily Dose

EU European Union

EUROSTAT European Union Statistical Office

GDP Gross Domestic Product

HIF Health Insurance Fund

IMS Intercontinental Marketing Services INN International Nonproprietary Names

IOM Institute of Medicine

LTL Litas

MAO Monoamine Oxidase

MoH Ministry of Health

OECD Organization for Economic Cooperation and Development

PDD Prescribed Daily Dose

SPSS Statistical Package for the Social Sciences SSRI Selective Serotonin Reuptake Inhibitor TCA Tricyclic Antidepressant

THIF Territorial Health Insurance Funds

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INTRODUCTION

The prevalence of depression and the high costs associated with its man-agement heightened the interest in pharmacoeconomic evaluation of drug treatment [68]. The economic aspects of treating depression are becoming more frequently evaluated as newer antidepressant medications become available and as healthcare entities attempt to address increasing costs [10]. In recent years, there has been much debate regarding the real cost effec-tiveness of new antidepressants [41].

Depressive disorder is a common condition often unrecognized, misdiag-nosed, undertreated and usually accompanied by a high level of medical morbidity [78]. Since depressive disorder is associated with substantial di-rect and indidi-rect costs, its managed-care systems became a target of special interest for decision-makers susceptible to be frequently affected by cost-containment policies.

Pharmacoeconomic studies are becoming an essential part of medicine registration process, medicine pricing and reimbursement policy. Pharmaco-economic studies analyze various treatment alternatives and thus highlight their pros and cons presenting decision-makers and providers with robust data concerning the “best” (i.e., the most effective, the most cost-beneficial) treatment alternatives for a given condition [8].

According to the World Health Organization (WHO), more than 150 mil-lion individuals suffer from a depressive disorder at any point in time. The prevalence of depressive disorders and the high costs associated with their treatment are increasing the interest in pharmacoeconomic evaluations of antidepressants.

It is important to evaluate the economic and social impact of depression as treatment costs are exorbitant but generally not recorded. In case of eval-uation of this factor, depression treatment would be considered more care-fully and responsibly.

The investigated problem involves medicament depression treatment costs rationalization without any negative impact on the patients’ health condition.

Enhanced care of depression incurs increased healthcare costs. Therefore, in deciding whether to adopt these approaches, decision-makers will have to judge whether the expected benefits can be justified by the required invest-ments. Depression is associated with profound impairments in the quality of life and daily function, and the health benefits that might be expected are comparable to many interventions already funded by healthcare systems.

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These decisions can be made on the basis of a large and robust clinical and economic evidence base.

Pharmacoeconomic methods are means of measuring the related ad-vantages and costs and provide guidance in medicine selection [102].

The aim of the research. To investigate and assess the possibilities of a

more rational use of the public and private funds of the Lithuanian popula-tion in the cases of medicament depression treatment.

The tasks of the research:

1. To perform a comparative analysis of the antidepressant consump-tion in the years 2004 to 2009 in Lithuania.

2. To evaluate depression diagnosis and treatment effectiveness and depression diagnosis dynamics in Lithuania from 2004 to 2009.

3. To perform antidepressant cost analysis from 2004 to 2009 in Lithu-ania.

4. To perform the cost-effectiveness analysis of depression treatment and propose the possible ways for costs rationalization.

Scientific novelty of the research. For the first time, depression relapse

rate was used as a medicament depression treatment effectiveness evalua-tion indicator in assessing the raevalua-tionality of the costs of treatment with anti-depressants.

Pharmacoeconomics in Lithuania is highly relevant and both the provi-sion of medicines and savings on health insurance and people resources can be achieved. The economic side of depression treatment (as well as of im-proper treatment or untimely diagnosis) must also be assessed to calculate how much the state pays for the patients with depression and what preven-tive means must be taken.

Practical and theoretical implementation. The impact of depression on

health economics and the society in Lithuania has not been assessed yet. This disease has a large epidemiological scale, is often misdiagnosed and not properly treated. Depression is associated with the economic and social losses of a certain family and all society [7].

The survey data can be used in practice when dealing with antidepres-sants consumption and the improvement of the effectiveness of evaluation and reimbursement systems in Lithuania.

According to the Ministry of Health, in Lithuania, generic medicine poli-cies were one of the priority areas of pharmaceutical policy during the re-cent years. The suggested treatment effectiveness criteria can be included in the update of the Minister of Health-approved methods of depression treat-ment.

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1. LITERATURE REVIEW

1.1. Consumption and costs of antidepressants in Lithuania

The costs of reimbursable medicines are increasing in all the countries; this becomes a problem even for the wealthy countries. This issue is even more important for such countries as Lithuania which are unable to allocate the funds necessary for the reimbursement of medicines to meet their ever-increasing demand. New technologies, as well as modern and often expen-sive medicines, appear in the Lithuanian market each year, and, of course, the need of the Lithuanian people for treatment is not less than in the West-ern European countries.

On September 13, 2005, the Decision No. 994 of the Government ap-proved the procedure for the base price calculation of reimbursable medi-cines, which is valid at the moment. The approved procedure for the base price calculation has the following major differences from the previously valid procedure: first, the prices of a medicines manufacturer, which are used to calculate the base medicines prices in our country, cannot exceed 95 per cent of the average producer prices in Latvia, Estonia, Poland, Czech Republic, Slovakia, and Hungary. Secondly, for the first time, the procedure of the base price calculation determined the basic principles for the base price of the medicine grouping [99].

Reimbursable medicines are mostly intended for the treatment of the pa-tients having chronic diseases. This is especially important for the low-income and socially-supported patients, as well as pensioners.

In 2009, the surcharges for reimbursable medicines and medical devices of the population amounted to 20 per cent of the total costs in Lithuania.

Figure 1.1.1 shows the costs of the Compulsory Health Insurance Fund (CHIF) budget for reimbursable medicines and medical devices, according to Level I of the Anatomical Therapeutic Chemical (ATC) Classification [99].

Based on the data presented above, the costs of the medicines that affect the nervous system form a great part of the CHIF costs and account for 15 per cent of the total cost of reimbursable medicines and medical devices.

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Figure 1.1.1. Compulsory Health Insurance Fund expenses distribution

by ATC classes

According to the the data of the Health Insurance Fund, in 2009, the CHIF budget allocated 653 mln. LTL for reimbursable medicines and medi-cal devices, while another 165 mln. LTL were paid by the patients. The same surcharge rate covered by the population remained in recent years as well which reveals the stability in the distribution of the costs of reimbursa-ble medicines in Lithuania. 20 per cent of all reimbursed medicines expens-es are population-covered expensexpens-es.

In recent years the surcharge paid by the population for the medicines that affect the nervous system amounted to 13 per cent and 14 per cent of the total costs of reimbursable medicines, respectively, which is much less compared to the trends of the total cost distribution in Lithuania.

The surcharge paid by the population for the medicines that affect the nervous system is significantly lower than that for reimbursable medicines and medical devices in general; thus, on the one hand, a bigger part of the costs needs to be covered by the CHIF budget while on the other hand smaller private surcharges for medicines prevents the population from the excess purchase of medicines.

Therefore, the rationalization of the cots for the medicament treatment of depression would largely affect the rationalization of the CHIF budget costs and the antidepressant consumption.

25% 17% 15% 12% 8% 8% 6% 9% C - Cardiology L - Antineoplastic N - Nervous system A - Gastrointestinal tract and metabolism R - Respiratory system Medical Aid devices B - Blood circulation Other

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According to the data of the State Health Insurance Fund under the Min-istry of Health, in 2007, the costs of the CHIF for antidepressants amounted to 15.57 mln. LTL in Lithuania.

99.2 per cent of depression treatment costs represent adult treatment (Figure 1.1.2).

Figure 1.1.2. Compulsory Health Insurance Fund expences for

antidepressants in 2007

According to the IMS Health data, in 2007, the costs of antidepressants in Lithuania reached 25 mln. LTL.

This data suggests that in 2007 the costs of antidepressants from the CHIF budget accounted for 86 per cent of the total cost for medicines in this group while the surcharges/expenses covered by the population accounted for the remaining 14 per cent.

This data correlates with the data of the State Health Insurance Fund un-der the Ministry of Health, and leads to the conclusion that almost all anti-depressants in Lithuania are to be exempt under the passport for the reim-bursed prescriptions and funded by the CHIF. The planned researches of the cost-efficiency and the rationalization of the antidepressant costs should largely affect the state budget.

About 10 per cent of the gross expenditure on health constitutes medi-cines expenditure (Figure 1.1.3).

99,20% 0,80%

Adults Children

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Figure 1.1.3. Health expenditure distribution in Lithuania in 2009

As it is shown in Figure 1.1.4, income and expenditure of the Compulsory Health Insurance Fund budget are constantly growing up. In 2009, the expenditure of Compulsory Health Insurance Fund was lower than the income.

Figure 1.1.4. Compulsory Health Insurance Fund budget from 2004 to 2009 33% 23% 10% 8% 7% 7% 4% 2% 6% Hospitals Physicians/clinical services Pharmaceuticals Other professionals Nursing homes Private insurance administration Equipment/supplies Home care Others 0 500 1000 1500 2000 2500 3000 3500 4000 4500 2004 2005 2006 2007 2008 2009 M ln . LTL Year Income Expenditure

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These values form a constant trend of cost ratio, and the results are well-correlated with other European countries.

1.2. Depression epidemiology, usage of antidepressants and risk factors affecting the rationality of antidepressant consumption

Around 1 in 5 people experience an episode of major depressive illness at some time in their lives, and 70-80 per cent of the victims experience re-lapse [1].

About 30 per cent of patients remain depressed despite the initial antide-pressants therapy [87]. Depression was also associated with an increased mortality risk of 1.81 (1.58-2.07) in a meta-analysis of 25 community sur-veys involving more than 100,000 subjects [14].

In recent years, an increasing number of cases of relapsed depression is recorded which greatly increases the overall number of patients with this disease [42].

Mental health is a key aspect of well-being and quality of life. Marked differences are found between countries when overall mental health is con-sidered [17].

The Second European Quality of Life Survey findings show that the highest scores for good mental health are seen in the Norway, the Nether-lands, Ireland, Germany, Denmark and Sweden. Turkey comes at the bot-tom, at 47, followed by Malta, Romania, Macedonia and Latvia (all between 53 and 55). Lithuania got 58 per cent of the mean mental health index and is not far from the lowest level countries (Figure 1.2.1).

The use of antidepressants has increased in all Western countries during the past 15-20 years. In Finland, the increase between 1990 and 2006 was nearly 8-fold [92], from 7.09 defined daily doses (DDD) expressed for 1,000 inhabitants a day in 1990 to 55.47 DDDs in 2006. Similar trends have been reported elsewhere [75].

The trend of the continuing high level of antidepressant use has led the government to establish very recently a national committee on ‘rationalizing psychotropic medication use in Belgium [34].

Although consumption of antidepressants at the population level has in-creased notably, population-based studies with all psychotropics and antide-pressants in particular suggest that the increased prescribing may not have markedly improved the mental health of the population [1].

When analyzing the trends of consumption of antidepressants, attention is paid to the gender of patients with this disease [103, 104]. It is assessed that generally women suffer from this disease twice as frequently as men [87].

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Figure 1.2.1. Mean mental health index (%) in European countries According to a Eurostat report on the causes of deaths in the EU (2006), depression is relapsed even in 50 per cent of those with depression and those who had been treated. After a repetitive treatment, about 70 per cent of pa-tients fall into depression for the third time, and after three treatments, even 90 per cent do.

Just as there are different types of depression, there are different treat-ments for the different varieties of mood disorders and in this section the main therapeutic approaches will be highlighted. Reactive depression is best treated by helping the individual to understand the personal significance of the upsetting event in their life and getting them to identify their emotional “blind spot”. This is done through a process called psychotherapy, of which there are many varieties. Some of the more severe varieties of this form of depression may need to be treated initially with some sedative medication before psychotherapy can proceed.

Antidepressant medications are the mainstay of treatment for endogenous depression and their effectiveness in dealing with this variety of mood dis-order has been clearly demonstrated. Depressions which are particularly severe or have been shown to be resistant to antidepressant medication will require electro-convulsive therapy (ECT). This treatment remains the single most effective therapy for patients with severe biological depressions.

Patients, who have relapsed endogenous or unipolar depression with a particularly disruptive effect on their lives, may require ongoing antidepres-sant medication or the mood stabilizer, Lithii carbonas, to prevent relapses rather than start treatment each time depression re-emerges.

0 10 20 30 40 50 60 70 T ur ke y R om an ia L atv ia B u lg ar ia L ith u an ia Ita ly P or tug al G reece S lo ve ni a C zech R ep u b li c H ung ar y F inl an d B el gi um D en m ar k Ir el an d No rwa y 47 53 54 54 55 56 57 58 58 58 59 59 60 60 60 60 60 61 62 62 63 63 65 66 66 67 67 67 67 67 70 %

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Depressions have a marked effect on many facets of the patient’s life and that of their families [55].

Controlled comparisons of the available antidepressants have usually led to the conclusion that they are roughly equivalent medicines. Although this may be true for groups of patients, individual patients may for uncertain reasons fare better on one medicine than on another. European studies show that patients depressed enough to be hospitalized respond better to classic tricyclics than to monotherapy with SSRIs. Meta-analyses of outpatient studies also show greater efficacy of tricyclics in comparison with SSRIs inpatients who complete trials. The greater tolerability of the SSRIs, howev-er, makes them the preferred agent for most patients. At high doses (> 225 mg), venlafaxine also shows greater efficacy than the SSRIs. Thus finding the right medicine and the right dose for the individual patient must be ac-complished empirically.

The past history of the patient’s medicines experience is the most valua-ble guide. At times, such a history may lead to the exclusion of tricyclics, as in the case of patients who have responded well in the past to MAO inhibi-tors.

Tricyclics and the second- and third-generation agents differ mainly in the degree of sedation they produce (greater with amitriptyline, doxepin, trazodone, and mirtazapine) and their antimuscarinic effects (greatest with amitriptyline and doxepin). SSRIs are generally free of sedative effects and remarkably safe in overdose. Combined with the ease of once-a-day dosing, these qualities may explain why they have become the most widely pre-scribed antidepressants.

No special indications for particular types of depression have been found for the selective serotonin reuptake inhibitors or other newer antidepres-sants. The popularity of these medicines, despite their higher cost, is due principally to their greater acceptance by patients [18].

Adverse effects of various ADs are summarized in Table 1.2.1. Most common unwanted effects are minor, but they seriously affect the patient compliance; the more seriously depressed the patient is, the more likely it is that unwanted effects will be tolerated [18].

Table 1.2.2 illustrates the priority of ADs selection in Lithuania [24]. It explains that amitriptyline should be the first choice medication for treat-ment of depression disorders for adults when patients are not contraindicat-ed for TCAs.

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Table 1.2.1. Adverse effects of antidepressants

Antidepressants Adverse effects

Tricyclics Sedation (sleepiness, additive effects with other sedative medicines)

Sympathomimetic (tremor, insomnia)

Antimuscarinic (blurred vision, constipation, urinary hesitancy, con-fusion)

Cardiovascular (orthostatic hypotension, conduction defects, ar-rhythmias)

Psychiatric (aggravation of psychosis, withdrawal syndrome) Neurologic (seizures)

Metabolic-endocrine (weight gain, sexual disturbances)

MAO inhibitors Sleep disturbances, weight gain, postural hypotension, sexual

dis-turbances (phenelzine)

Mirtazapine Somnolence, increased appetite, weight gain, dizziness

Venlafaxine Nausea, somnolence, sweating, dizziness, sexual disturbances,

hy-pertension, anxiety

Bupropion Dizziness, dry mouth, sweating, tremor, aggravation of psychosis,

potential for seizures at high doses Fluoxetine and

other SSRIs

Gastrointestinal symptoms, decreased libido, sexual dysfunction, anxiety (acutely), insomnia, tremor.

Table 1.2.2. Priority of ADs selection for treatment of depressive disorders

First Choice Second Choice

TCA Amitriptyline SSRI* Fluoxetine Citalopram + Escitalopram + Paroxetine Sertraline + Fluvoxamine Other Mirtazapine *+ Reboxetine* Bupropion Venlafaxine Tianeptine+ SSRI Fluoxetine Citalopram Paroxetine Sertraline Fluvoxamine Other Mirtazapine Reboxetine Bupropion Venlafaxine Tianeptine

* For children and patients who are con-traindicated for TCA.

+ Elderly patients (> 65 years)

Factors affecting rationality of antidepressants use

Political factors

In Lithuania, mental health services are provided by four sectors: residen-tial psychiatric hospitals, mental health centers, non-governmental organiza-tions and the private sector.

Since 2007, the right to diagnose depression for the first time and to pre-scribe the treatment has been provided to family doctors in Lithuania.

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While treating the starting or acute depression, the effect of medicament preparations should be observed already after 4 weeks, and the improvement of the course of disease after 8 weeks.

Lithuania is currently running the following legislation and programs: • Mental Healthcare Act (adopted in 1995, i.e. one of the first in the Central and Eastern Europe),

• The Law on the Patients’ Rights and Compensation, • National Suicide Prevention Program,

• National Mental Health Protection Program.

Specialists point out that although the legislation and programs do exist, the lack of a common strategy in the field of the mental healthcare can be observed. The mental health services are only partially combined with pre-vention programs, social care and protection, education, employment and housing. There is no mechanism to ensure the service quality. Some institu-tions of the mental healthcare have an internal audit, but such an audit is not performed at the national level.

The availability of medicines is ensured by the mechanism for the medi-cine reimbursement, the pharmacies working 24 hours a day, the receptions of the psychiatric hospitals and the doctors on duty.

The mechanism that ensures that people with mental health problems possess the right to complain about the treatment is legally valid, but in practice it is poorly operating. The patients and their families really do not know what authorities they should address their complaints to [84].

Economic factors

According to the data of the State Health Insurance Fund (HIF) under the Ministry of Health (MoH), in the first quarter of 2009, 82 per cent of all the reimbursable prescription medicines were sold at the level of the prices of generic medicines (without the evaluation of the surcharges paid by the pa-tient).

• The highest costs for the reimbursement are associated with the origi-nal patented medicines which makes 52 per cent of the total reimbursement budget.

• 35 per cent of the prescriptions are issued for the original unpatented medicines which together with generic medicines (47 per cent of all the pre-scriptions) represent 48 per cent of the total costs.

As long as the reimbursable price is based on the cheapest medicines at the same International Nonproprietary Names (INN) Group, there is no dif-ference for the Health Insurance Fund whether to reimburse an original un-patented medicine or a generic medicine. For this reason, 82 per cent of all

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the prescriptions are paid at a price determined in accordance with the cheapest level of generics. 18 per cent of all the prescriptions issued for the original patented medicines (having no equivalent among generics) corre-spond to 52 per cent of the reimbursable costs.

In order to rationalize the medicament treatment of depression in Lithua-nia, it is necessary to encourage the user to choose generic medicines when-ever possible thus saving the money of the state and the patient.

Three pharmaceutical categories taking the highest positions in terms of the costs – C (the medicines that affect the cardiovascular system), N (the medicines that affect the nervous system) and L (the antineoplastic and im-munomodulation agents) – make up 60 per cent of the total cost of the Health Insurance Funds for reimbursable medicines.

As much as 27 per cent of the total cost is composed of ethical unpatent-ed munpatent-edicines within Category N (the munpatent-edicines that affect the nervous sys-tem); the rationalization of this segment of costs is necessary to save the funds designed for the medicament treatment of depression.

In the case of Categories C and N, more than 50 per cent of funds are de-signed for the reimbursement of medicines when the reimbursable cost is determined based on the cheapest generics.

According to the IMS Health data, the penetration of generic medicines in the Baltic countries in the second quarter of 2009 year amounted to 22–26 per cent in terms of value and to 24–25 per cent in terms of quantities.

Compared with the other Baltic countries, the share of generic medicines is the highest in Lithuania.

As it has been mentioned above, as much as 60 per cent of the costs of the Health Insurance Fund for reimbursable medicines involve only three categories of medicines (according to the ATC Classification), one of which is the Medicines that affect the nervous system.

In terms of costs of their consumption, antidepressants can be divided in-to relatively expensive (in terms of money) and relatively cheap ones.

A group of expensive medicines usually consists of the ethical medicines by pharmaceutical companies. A group of the relatively cheap medicines consists of the so-called generic medicines.

According to the IMS Health data, during the period of 2004 to 2009, the market share of generic medicines was decreasing. When comparing the value, the market share of generic medicines remains more or less stable. If compared with the data of 2008, in 2009, the costs of antidepressants de-creased (it amounted to 26.75 and 23.92 mln. LTL respectively) while the trend of the cost growth ceased. It happened after generic medicines – the selective sertraline reuptake inhibitors (SSRI) – entered the market. This

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data suggests that the penetration of generic medicines in the market has a direct impact on the reduction in the costs for the treatment of depression.

In 2009, the costs of antidepressants decreased and the trend of the cost growth ceased. It is probable that it happened after generic medicines – the selective sertraline reuptake inhibitors (SSRI) – entered the market.

The entry of a generic equivalent of a patented medicine into the market caused the significant reduction of expenses of patients as well as the state for these medicines.

Dramatic changes in pharmaceutical markets make it imperative for ge-neric medicine producers to work with governments in order to create the best conditions for developing, manufacturing and marketing their medi-cines [82].

The European Generic Medicines Association study concludes that these traditional instruments — reference-pricing systems, prescribing budgets, generic substitution, patient co-payments, information campaigns — can indeed be effective in stimulating generic up-take but that they must be de-signed to stimulate competition. The EU report on the competition in the pharmaceutical sector research states that in order to develop a generic med-icines market, supply-side measures need to be supplemented by demand-side policies thus creating incentives for physicians, pharmacists and pa-tients to use generic medicines. Indeed, this report demonstrates that de-mand-side policies are critical to a sustainable generic medicines market.

The study clearly identifies the importance of a high-volume share of the market for generic medicines in order for the EU generic medicines industry to compete effectively: the ability of the generic medicines industry to de-liver competitive prices can only be achieved and sustained if it is assured a high volume of the pharmaceutical market. The high volume according to the European Generic Medicines Association is dependent on the demand-side policies.

According to the European Research Centre for Pharmaceutical Care and Pharmacoeconomics, the experience of European countries shows that there is no single approach towards developing a generic medicines market. For instance, the demand for generic medicines in mature markets is driven by generic substitution by pharmacists in Denmark and the Netherlands, a fa-vorable attitude of physicians towards generic medicines in Poland or phy-sician budgets in Germany and the United Kingdom. Also, the development of a generic medicines market needs to be actively sustained by a generic medicines policy. Consequently, countries that promoted generic medicines for 10-15 years (e.g. Denmark, Germany, the Netherlands) naturally have a more mature generic medicines market than the countries that only recently

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implemented measures to stimulate the use of generic medicines (e.g. Aus-tria, Belgium, Portugal).

Countries have drawn on supply-side policies relating to pricing and re-imbursement to develop their generic medicines market. Limiting the policy to supply-side measures only, as is the case of Austria, is insufficient in real-izing the full potential of a generic medicines market. To develop a generic medicines market, supply-side measures need to be supplemented by de-mand-side policies in order to create incentives for physicians, pharmacists and patients to use generic medicines. Furthermore, generic medicines poli-cy grew incrementally in countries over time and reflects demographic, cul-tural, economic and institutional constraints. Therefore, there is no reference set of policy measures that countries can adopt to promote their generic medicines market [94].

The ability of the generic medicines industry to deliver competitive pric-es can only be achieved and sustained if it is ensured a high volume of the pharmaceutical market. This high volume is dependent on demand-side pol-icies. On the one hand, countries with mature generic medicines markets have in place incentives for physicians, pharmacists and/or patients to de-mand generic medicines [81]. On the other hand, there are few incentives to stimulate generic medicines consumption in countries with developing ge-neric medicines markets. In Italy and Spain, the limited volume of gege-neric medicines consumption in combination with low medicine prices has un-dermined the economic viability of the generic medicines market [69].

Countries do not fully recognize the role that patients play in generic medicines consumption. Generally, few policy measures are in place that either incite patients to demand generic medicines or penalize patients for not demanding generic medicines. The extent to which patients contribute to the cost of medicines is likely to play a role in the use of generic medicines [50].

Several countries including Belgium, Italy, Portugal, Spain and the Unit-ed Kingdom launchUnit-ed advertising campaigns to inform patients of generic medicines. In Belgium, the campaign was short-lived and had limited expo-sure. In Portugal, pro-generic-medicine media campaigns aimed at physi-cians and pharmacists in addition to patients appear to have contributed to the increasing demand for generic medicines. No formal evaluations of the impact of advertising campaigns on generic medicines consumption exist [22].

Countries need to incite patients to demand generic medicines or penalize patients who do not demand generic medicines. This may take the form of financial incentives that reduce co-payment on generic medicines or impose higher co-payment on originator medicines.

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Furthermore, countries can increase patient awareness of generic medi-cines by means of advertising campaigns. Initiatives that attempt to influ-ence consumption patterns by personally contacting patients can also be en-visaged [20].

In many cases, the data of the survey conducted in the Pharmaceutical sector by the offices of the Directorate-General (DG) for Competition of the European Commission disclose the interference of medicinal companies in the procedures of national government authorities (rather than in the proce-dures of patent offices). The companies producing patented medicines inter-vened when the companies providers of generic medicines were applying for the permission to sell their products and expressed dissatisfaction due to their status of pricing and reimbursement. The companies producers of pa-tented medicines argued that generic medicines are less safe, less effective, and (or) of lower quality. They also claimed that the marketing permissions and (or) the granting of pricing or reimbursement status could violate their patent rights although the authorities providing the marketing permissions might disregard this claim. The intervention of the companies producers of patented medicines was often associated with several medicines from which a high turnover could be received.

In the cases when the patent-related issues reached a trial, the claims of the companies producers of patented medicines were satisfied only in 2 per cent of all the cases, which suggests that the arguments presented against the generic medicines could not be justified.

Due to the intervention and litigation of the companies producers of pa-tented medicines and because of the intervention in the administrative pro-ceedings concerning generic medicines, the market entry of generic medi-cines may be delayed. The detailed examination of the data related to the sample medicines reveals that in the cases of the intervention the market permissions were issued on average four months later.

According to the data of the offices of the DG for Competition of the Eu-ropean Commission, the companies producers of patented medicines spent an average 23 per cent of their turnover on the marketing and advertising of their medicines. While implementing their business strategies, the compa-nies producers of patented medicines not only advertise their medicines to doctors and other healthcare professionals but also seem to take the actions and to call into question the quality of generic medicines.

The mainstream economic theory generally assumes that the characteris-tics of the medicines are obvious for the consumer who can choose between any given medicine on the basis of prices and preferences. This simplistic presentation of medicine qualities is discussed by many researchers in so-cio-economics. The Lithuanian authorities legally defined the generic

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medi-cines as identical in essence to the original medimedi-cines but a myriad of small differences remain in its presentation.

Generic medicines are chemically equivalent and bioequivalent to origi-nator brands, but can be significantly cheaper because they are allowed to enter the market after the patent expiry of the originator brand. In this way, generic manufacturers do not incur Research and Development costs and are able to offer a significant price advantage over the originator brand. As a result, health insurance is keen to promote the use of generics among pa-tients as well as encourage generic competition by using a variety of poli-cies with a view to maximizing savings on the medicines bill. Given the emphasis on healthcare cost containment and the pursuit of efficiency in resource allocation, generic policies and their perceived and actual effec-tiveness have been at the center of attention for many years in the majority of countries.

Policies encouraging the use of generics within healthcare systems have been at the center of attention over the past decade for a number of reasons. First, as healthcare costs as a proportion of GDP have continued to rise over the past decade, governments and health insurers have been trying to con-tain their rate of growth as well as improve the efficiency in the use of scarce resources. Second, the implementation of generic policies necessi-tates policy action both on the supply- as well as the demand-side of healthcare economies. Consequently, multiple actors and stakeholders are involved, incentivized or affected by such policies. Among them are physi-cians, who need to be convinced to prescribe generics, pharmacists, who, in order to dispense generics need an appropriate incentive structure on mar-gins, and patients, who are at times skeptical about whether generics provide the same quality of care as originator brands. Given the multiplicity of ac-tors and stakeholders, different policy measures and incentives need to be made available to each of these making generic policy a complex policy area which has, on several occasions, taken a long time to deliver low prices for off-patent medicines, high levels of penetration, and, by implication, high savings to health insurance. Third, despite the emphasis on generic pol-icies, there is little knowledge of their actual effectiveness in different envi-ronments, whether they indeed result in sustainable price reductions and whether they diffuse fast in different environments [44].

In the Second European Brain Policy Forum, the 12 brain diseases that are most costly for Europe were determined. According to the data from 2004, the affective disorders required 106 billion Euros. In the second place, diseases caused by various addictions could be found, followed by the dis-orders of dementia, psychosis and anxiety. Depression is the costliest brain disease, for which Europe currently allocates 118 billion Euros.

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The costs allocated to depression consist of the direct and indirect costs. The direct costs are associated with the working of the healthcare staff in the case of the people already having depression, i.e. when a patient comes to a specialist, e.g. at a clinic, or hospital emergency department. Also, the direct costs include the loss of work or activity measured in the duration of the days of unemployment. The burden of the indirect costs of depression falls mainly on the surroundings of the patient – the family members, employers, and, during the period of the acute disease, the colleagues who must partial-ly take over his/her work. The journal “Medicine” states that 90 per cent of the costs of depression treatment consist of the indirect expenses that relate to the quality of life [86].

The treatment costs and the rational use of funds has become an integral part of the health system solutions. European countries use different meth-odologies for this assessment. Methmeth-odologies are different as well as health systems and their financing. Taking into account the comparable domestic economic and social conditions, the Baltic countries (Lithuania, Latvia and Estonia) have decided to apply the same recommendations for the phar-macoeconomic analysis of medicines. According to the order by the Minis-ter of Health of the Republic of Lithuania on the approval of the recommen-dations for the pharmacoeconomic analysis, these recommenrecommen-dations are to be referred to during the assessment of any medicine that is requested to be included in the list of medicines reimbursable from the budget of the Man-datory Health Insurance Fund as well as in the methods of disease diagnosis and outpatient treatment.

While the medical science and technology have advanced at an extraor-dinary pace, the healthcare provision system has floundered. As currently structured, the healthcare structure does not make the best use of its re-sources [13].

Healthcare delivery has been relatively untouched by the revolution in in-formation technology that has been transforming nearly every other aspect of society. The Institute of Medicine (IOM) in the United States of America Committee believes that information technology must play a central role in the redesign of the healthcare system if a substantial improvement in quality and safety is to be achieved over the coming decade.

In the absence of a national commitment and financial support to build a national health information infrastructure, progress on quality and safety improvement will be painfully slow.

Social factors

Mental health problems have been estimated to account for approximate-ly 20 per cent of the total burden of ill health across Europe. Unipolar

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de-pressive disorders accounted for the highest proportion of total Disability Adjusted Life Years (DALY) in Austria (9.8 per cent of the total), Belgium (9.7 per cent), Cyprus (6.9 per cent), Denmark (8.1 per cent), Finland (10.8 per cent), France (10.3 per cent), Ireland (8.3 per cent), Italy (6.8 per cent), the Netherlands (7.8 per cent), Norway (8.9 per cent), Slovenia (9 per cent), Spain (5.6 per cent) and Sweden (9.7 per cent). In Finland and Sweden, the most prevalent cause of death after Cardiovascular disease (CVD) was Alz-heimer’s disease and other dementia. Mental health problems affect a great many people; one in four experiences a significant episode of mental illness during their lifetime. Data from the Global Burden of Disease Study indi-cates that four of the six leading causes of years lived with disability are attributable to mental health problems: depression, schizophrenia, bipolar disorders and alcohol-use disorders. Depressive disorders are most common, making up nearly one third of all mental health problems. One recent at-tempt to address this deficit was a systematic review of all available epide-miological studies on a variety of mental disorders affecting individuals aged between 18 and 65 conducted at a community level across the EU27, plus Norway, Iceland and Switzerland (Table 1.2.3).

Table 1.2.3. European prevalence rates of mental disorders and an

estimat-ed number of individuals affectestimat-ed annually

Diagnosis

12-month prevalence median and range (per

cent)

Number of EU indi-viduals affected in any

one year (mln.)

Alcohol dependence 2.4 (0.1–6.6) 7.2

Illicit substance dependence 0.5 (0.1–2.2) 2.0

Psychotic disorders 0.8 (0.2–2.6) 3.7 Major depression 6.9 (3.1–10.0) 18.4 Bipolar disorder 0.9 (0.2–1.1) 2.4 Panic disorder 1.8 (0.7–3.1) 5.3 Agoraphobia 1.3 (0.1–10.5) 4.0 Social phobia 2.3 (0.6–7.9) 6.7

General anxiety disorder 1.7 (0.2–4.3) 5.9

Specific phobias 6.4 (0.8–11.1) 18.5

Obsessive compulsive disorder 0.7 (0.1–2.3) 2.7

Somatoform disorders 6.3 (1.1–11.0) 18.9

Eating disorders 0.4 (0.2–0.7) 1.2

Any mental disorder 27.0 82.7

The review identified 24 country-specific and 3 cross-national studies; one striking finding being that no population-based data at all was available

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from 12 countries (Cyprus, Estonia, Greece, Ireland, Latvia, Lithuania, Lux-embourg, Malta, Poland, Portugal, Slovakia and Slovenia), representing 54.8 mln. inhabitants (17.5 per cent) in the age range under scrutiny. By using this data, the study estimated that 82.7 mln. people (27 per cent of the population) across Europe (including Iceland, Norway and Switzerland) are affected by a mental disorder during any 12-month period [63].

It is estimated that up to 6 per cent of males and 12 per cent of females experience at least one episode of clinical depression during their lifetimes. An episode of depression can be mild to severe, or it can be chronic (dys-thymia), lasting for at least two years. An estimated 70 to 80 per cent of pa-tients with depression can be treated successfully, and usually feel better within weeks of beginning treatment. As depression is biochemical in na-ture, antidepressant medications are successful as a first-line defense in its treatment.

Patients with a depressive disorder are treated in outpatient settings by general practitioners (or family doctors, GPs) or by specialists for psychia-try. GPs play a key role as they are often the first healthcare providers for the recognition, diagnosis, referral, and treatment of depression. Depression is rather common in primary care: it is estimated to affect about 10 per cent of all primary care attendees [28], [95], [115]. Recent studies in Germany show that 11.5 per cent of the adult population suffer from affective disor-ders, 8.3 per cent of the population have experienced a major depression during the past 12 months, and that every fourth patient in general practice fulfills the criteria for depression.

According to recent data of the United States of America and Canada [11], [49], [120], the German study of Wittchen and colleagues revealed that only a half of depressed patients ever contacted a healthcare institution, and only one third of these patients ever received intervention [118]. Another problem relates to delayed referrals to specialists or psychiatric hospitals [77], [97]. Reasons for this situation in primary care are various, and a range of patient, doctor and organizational factors contribute to this problem [35], [52], [95], [110].

In addition to GPs, specialists such as psychiatrists, psychotherapists or neuropsychiatrists have an important function in outpatient care. Depressive disorders are the most significant and frequent illnesses treated by these specialists [58]. However, there is empirical evidence of underdiagnoses and undertreatment, even by psychiatrists [47].

The fact that guideline-oriented treatment leads to distinct improvement in the treatment of depression was established in international studies [53]. Unfortunately, such guidelines [27], [40] are still underused in practice. The adherence to a multi-level care model between general practitioners and

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specialists also brings about evident improvement in the treatment of de-pression [118], [45]. Moreover, the efficacy of specific quality management programs in reducing deficits in the diagnosis and treatment of depression has been shown [45], [48].

In Sweden, only 1 of 5 patients is treated with antidepressants. The sui-cide risk for the patients with depression treated with antidepressants is 141/ 100,000 patients per year while the risk of the untreated patients with de-pression is 259/ 100,000 patients per year, i.e. 1.8 times higher than in the case of those treated with antidepressants [29].

In conclusion, because depression is underdiagnosed and undertreated, screening in a primary care setting should be routine, especially when there are comorbidities [107].

The analysis of the mental health rates in Lithuania reveals that in the long-term last period perspective (during the period of the years 2007 through 2011), the incidence and prevalence of mental disorders has been increasing (Figure 1.2.2). This dynamics correlates with the growing num-bers of depression diagnosis and especially with the dynamics of relapsed depression cases in Lithuania.

In addition, the remission itself is not easy to achieve. Only 1 out of 3 pa-tients are lucky to achieve the remission with the first medication pre-scribed, and the successive antidepressants further decrease this likelihood.

A recent research reveals that the increase in the likelihood of achieving remission can be determined by the fast response to the treatment, i.e. if the medicine starts to work within the first two weeks. Unfortunately, the onset of an action of the most common conventional antidepressant is 3-4 weeks [112].

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Figure 1.2.2. Incidence and prevalence of depression in Lithuania

from 2007 to 2011

The International guidelines for mild depression offers to prescribe psy-chotherapy; only Canada and the U.S. also refer to certain cases which should be treated with antidepressants [71].

All the guidelines advise to treat the average depression with an antide-pressant or psychotherapy, or with an antideantide-pressant and psychotherapy [51].

Antidepressants should always be prescribed for the treatment of severe depression, which also can be combined with other means of treatment.

In order to improve the mental health of the Lithuanian population, more attention should be provided to the institution of a family doctor. According to the data of the Department of Statistics under the Government of the Re-public of Lithuania, the number of family doctors working in the primary healthcare facilities reached 1,792 in 2006, and was 2.6 times bigger than compared to 2000 when the figure merely reached 692. In 2008, family doc-tors provided their services to 76 per cent of the residents while temporary teams worked with 24 per cent of the population [122]. This indicates that the institution of a family doctor is a particularly important part of healthcare. Family doctors are the closest to the people; the patients’ health status is often dependent only on the expertise and knowledge of a family doctor. In providing efficient primary healthcare services of high quality, it may be possible to determine the risk factors in time, to identify the disease

1.000 2.000 3.000 4.000 5.000 6.000 2007 2008 2009 2010 2011 250 259 267 269 292 4.864 4.955 4.956 5.082 5.124 C as es pe r 100 t h ou sa n d in h ab ita n ts Incidence Prevalence

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early, to prevent the disease complications and exacerbations, to reduce the number of the addresses to specialists as well as the necessity of hospitaliza-tion [30].

Technological factors

Health insurance has been implemented in Lithuania since July 1997 while the pharmacoeconomic assessment of the reimbursement of the medi-cations designed for the outpatient treatment has been carried out from the budget of the Mandatory Health Insurance Fund since August 1, 1997. The centralized purchases of medical devices and a part of medicines was launched in 1998 by the State Health Insurance Fund.

The Division for the Medical Technology Assessment of the State Health Insurance Fund was formed in April 1999. Medical technology assessment is a very broad term that includes technical measures applied in medicine as well as the installation of scientific innovations; it can also be treated as medical service assessment. Medical service assessment intended for medi-cal technology better quality, is associated with a number of institutions: the Health Committee of the Lithuanian Parliament (the Seimas), the Ministry of Health, the State Health Insurance Fund, other health authorities, health professionals and their associations, patients, their associations, the suppli-ers of medical devices or medicines. The State Health Insurance Fund per-forms the analysis of the costs of healthcare services and presents sugges-tions on ways to modify the order of payment for various services (e.g. for the emergency medicament treatment or primary healthcare). Together with the MoH and individual experts in different fields, the services are detailed, and the prices are set (e.g. for tuberculosis, psychiatry, intensive care).

After the presentation of psychiatry services in greater detail and the in-troduction of the new payment fees, the costs of psychiatry increased by 16 per cent; on the other hand, the costs of services provided within this profile of disease treatment are allocated more appropriately, and the HIF is aware of what services and for what quantity of them are to be paid. This data fa-cilitates the performance of an expert analysis. The HIF, together with the MoH, advises healthcare facilities on the installation of new medical tech-nologies and carries out their assessment [130].

In accordance with the Public Procurement Act and other regulations, the HIF exercised the centralized procurement of various medical devices and some medicines. All the devices centrally procured by the HIF are approved for the use in Lithuania. Under the established conditions of competition, foreign producers are required to provide international quality certificates. At the moment, virtually all of the medical devices centrally procured by the HIF are manufactured in the Western countries. The need for medical

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de-vices (pacemakers, blood clotting factors, etc.) designed for the emergency medical aid is fully satisfied. Due to financial difficulties, the need of the medical devices used for the planned medical aid is not fully satisfied be-cause the queues are formed for some of these devices (e.g. patients need to wait for the planned joint replacement surgery for about two years). The patient receives a centrally procured medical device for free, i.e. he/she does not have to pay any surcharges. The list of the centrally procured medical devices approved by the Order No. 67 as of February 4, 2000 by the MoH, includes the devices of 22 names for which 37 mln. LTL is allocated.

Currently, the following scheme for the access of a new device to the list of the centrally procured devices is formed: the supplier’s proposal, recom-mendations of healthcare professionals as well as patients’ requests, are pre-sented, the analysis of the experience of other countries, the potential as-sessment of costs and the financial capability of the Fund are carried out, and the decision by the Mandatory Health Insurance Council is also neces-sary.

According to the State Patient Fund, the benefit of the centralized pro-curement is that the allocated considerable resources tend to attract more suppliers and increase their competition; this in its turn leads to a greater supply of goods, a better quality and lower prices. More medical devices or medications can be procured for the same budget.

Logical model of antidepressants utilization and its interaction with ex-ternal factors

Antidepressants as a means (tools) used in cases of mental health prob-lems application affecting factors model can be constructed by the interac-tions of three functional systems (Figure 1.2.3).

In the social-economic models of the system, the following entities are involved: the population (patients), professionals (doctors and pharmacists), cultural development entities that affect the patients’ behavior (family, school, work environment, the community), social and health policy-making institutions (public policy and management bodies, specialized depart-ments), monitoring and control models (epidemiological observations, re-source accounting: Statistics Department in Lithuania, Institute of Hygiene at the Ministry of Health of Lithuania, the Health Insurance Fund of Minis-try of Health and others).

Besides, in the economic-financial models of the system, medicines price reimbursement mechanism ensuring institutions and bodies (Compulsory Health Insurance Fund, Health Insurance Fund) and generic penetration providers (Ministry of Health of Lithuania, generic medicines companies) also operate.

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The functioning of innovation-financial models is ensured by such sub-jects as scientific research institutions (universities, laboratories) as well as ethical pharmaceutical companies introducing new medicines and new me-dicament treatments by initiating new meme-dicament treatment policies and setting new trends in pharmacotherapy.

Figure 1.2.3. Logical model for antidepressant use affecting factors According to the rational antidepressants consumption evaluation in Lithuania carried out in the PEST analysis, it was found that the technologi-cal and policy factors (legislation, modern antidepressants registration in Lithuania, medicines reimbursement system regulation) do not ensure a ra-tional use of certain medicines. The basic risk factors of efficient and ration-al use of antidepressants consist of sociration-al and economic factors (heration-althcare professionals’ qualification, patients’ behavior, relatively slow penetration of generic medicines into the market) (Table 1.2.4).

S

O

C

IA

L

-

E

C

O

NO

MIC

MODELS

EC

ON

O

M

IC

-F

IN

A

N

C

IA

L

M

OD

ELS

IN

NO

VAT

IV

E-FIB

NA

N

C

IA

L

M

O

D

E

L

S

Physicians Patients Pharmacists Social and health policy makers Universities Laboratories Drug reimbursement system

Generic Drug Policy Monitoring and control models Cultural development entities Ethical pharmaceutical industry

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Table 1.2.4. Evaluation of the risk factors of rational antidepressants

con-sumption evaluation

High risk Medium risk Low risk

Family doctors

quali-fication Generic medicines politics

Medicines reimbursement sys-tem

Patients’ behavior

Inefficient use of pharmacist competence in health activi-ties

The legal regulation of antide-pressants use

Information system database

management

According to the results of the situational analysis, there are numbers of factors associated with the depression diagnosis, treatment and antidepres-sants use and its costs in the healthcare industry that need to be improved. According to this survey, certain tasks were selected, the result of which had to be the definition of certain logical models of continuous failure as well as the adjustment of the current model of depression treatment in order to ra-tionalize the use of antidepressants and increase the depression treatment costs effectiveness in Lithuania.

1.3. Costs of antidepressants management

Pharmacoeconomic analysis of medicines involves the application of an-alytical methods in order to link the costs of the medicament treatment or other interventions with the treatment results as well as to address the issues of the rational allocation of resources for the healthcare.

The application of the pharmacoeconomic methods helps to avoid errors while including new medications into the list of the reimbursed medicines and to use the funds allocated to medicines more rationally. The pharmaco-economic analysis should justify that the ratio between the price and the efficiency of the proposed medication is optimal, i.e. that it is safe; moreo-ver, a comparative analysis of any other medicines for the treatment of the same disease should be performed. If this analysis reveals that a more ex-pensive medicine is less effective and less safe, it cannot be reimbursed.

Although different healthcare systems exist in various countries, they all address virtually the same challenges: how to improve the quality and ac-cessibility of healthcare services while maintaining a stable funding at the same time. The constantly rising costs for the reimbursement of medicines obliges the state authorities involved in the medicine reimbursement system

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to seek different measures to help reduce the growth in the medicines spend-ing.

In Lithuania, as well as in other EU countries, there is a problem that the cost of medicines is growing faster than the costs in other sectors of the health system. Therefore, it is necessary to prevent the increase in the costs of medicines through the application of various cost control techniques. The effective cost control is determined not only by rational allocation of the budget funds but also by other measures that help to reduce the growth in the costs of medicines.

According to the Minister of Health of Lithuania, the measures of the medicines cost control can be divided into the following groups: the regula-tory measures of the medicines supply and demand control and other measures such as the generic medicines policy, the development of the par-allel import of medicines and the installation of information technologies within the system of the medicine reimbursement.

The measures of the medicines supply control include: the measures to reduce the prices of medicines, the application of contracts concerning the prices of medicines and the scope of sales, the reference pricing application in the pricing of medicines and the application of the science of health eco-nomics in making the decisions on the reimbursement of medicines.

The regulatory measures for the medicines demand are the measures ap-plied to doctors issuing prescriptions for reimbursable medicines (the in-crease in the economic awareness of doctors), to the structuring of the nega-tive and posinega-tive lists of the reimbursed medicines, to the medicines pre-scription procedures, to the determination of the medicines budgets and to the surcharges to medicines.

In addition to these measures, a number of control mechanisms are em-ployed (licensing, centralized purchases of medications, structuring of the list of medicines, the revenue analysis of pharmaceutical companies and the regulation of the medicines-issuing entities). The methods of payment for services must reduce the motivation of the service provider to prescribe the expensive or unnecessary medicines. It is exercised by determining the methods of disease treatment by providing audits of medicines prescription, by determining bonuses for the ability to stay within the medicines budget, by determining the surcharges imposed on the population for reimbursable medicines.

The nature of the performance and the reasonable measure used for the assessment of the quality of life (standard or prepared for the assessment of a particular disease) must be indicated. The methods of the health perfor-mance ratio are also recommended to apply by the Minister of Health of Lithuania.

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A significant amount of funds is allotted to the treatment of patients with various forms of depression. Not only is the money spent by the mentioned patients or their family members on buying antidepressants but also the ex-penses incurred by the state (insurance, social funds) have already been cal-culated for a long time. Depression impairs or disrupts the working capacity of an ill individual for a long time, complicates the live of his/ her family members and requires additional funds for social care services.

Two groups of expenses are related with depression – direct and indirect ones. Their importance not only to patient but also to the society is undenia-ble. It is normal to pay the greatest attention to the direct expenses related with treatment; however, it is just the tip of the iceberg if compared with depression-related indirect costs which include the loss of working capacity caused by the disease and the related increase of mortality [39].

Pharmacological aspects of depression treatment have already been as-sessed for a long time. For example, in 2004, the total expenses of treatment of patients with various depression forms were estimated to be 118 billion Euros in Europe or on average 253 Euros per capita per year [100]. Re-searches showed that the direct costs of depression treatment accounted for only a small proportion – about 13 per cent – of the total amount of disease-related costs. The annual spending on depression in the United States of America is 43.7 billion dollars, in England and Wales – about 3.4 billion Pounds. While analyzing the costs of the disease, all researches showed that the expenses on medicines accounted for only a small part of the direct costs (10-12 per cent) and only for 1-2 per cent of the total cost of the disease [73].

The growing treatment costs encourage to study and assess whether the treatment is reasonable. While assessing the rationality of treatment of this disease, the need for medicines, psychological support of the patient and cooperation of his/ her relatives and that of the treating doctor is considered.

Relapses of depression after a successful response to antidepressant med-ication have been reported in a number of recent studies of ongoing treat-ment. During routine pharmacotherapy for depression, it is unknown how common it is for psychiatrists eventually to find a need to raise medication dosages after achieving a marked remission according to WHO. Evidence suggests that relapse rates in depression may range from 20 per centto as high as 44 per cent depending on the length of treatment with the main-tained use of selective serotonin reuptake inhibitors (SSRIs) [100]. In con-trast, with tricyclic antidepressants (TCAs), the relapse during an ongoing treatment to maintain remission from depression appears relatively rare [73].

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The costs of depression treatment increase in Lithuania due to the degree of depression relapse; they accounted for 6.95 mln. Euros of direct expenses in 2009.

The growing number of depression relapse in Lithuania shows the need to analyze the rationality of treatment of first-time depression.

1.4. Cost-effectiveness in depression treatment

Pharmacoeconomics has been defined as “the description and analysis of the costs of medicines therapy to healthcare systems and society” [119]. Pharmacoeconomic research identifies, measures, and compares the costs (i.e., resources consumed) and consequences (i.e., clinical, economic, hu-manistic) of pharmaceutical medicines and services. Within this framework the research methods related to cost-minimization, cost-effectiveness, cost– benefit, cost-of-illness, cost-utility, cost-consequences, and decision analy-sis as well as quality-of-life and other humanistic assessments are included [64].

By definition, pharmacoeconomic evaluations include any study de-signed to assess the costs (i.e., resources consumed) and consequences (clin-ical, humanistic) of alternative therapies. This includes such methodologies as cost-benefit, cost-utility, and cost-effectiveness [15] (Table 1.4.1).

Table 1.4.1. Pharmacoeconomic methodologies Pharmacoeconomic methodologies

Methodology Cost

measurement unit Outcome unit

Cost-benefit Currency unit Currency unit

Cost-effectiveness Currency unit Natural units (life-years gained, mg/dL

blood glucose, mm Hg blood pressure)

Cost-minimization Currency unit

Assume to be equivalent in comparative groups

Cost-utility Currency unit Quality-adjusted life-year or other utilities

Cost-effectiveness analysis is a technique designed to assist a decision-maker in identifying a preferred choice among possible alternatives. Gener-ally, cost-effectiveness is defined as a series of analytical and mathematical procedures that aid in the selection of a course of action from various alter-native approaches. Cost-effectiveness analysis has been applied to health matters where the program’s inputs can be readily measured in currency

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units, but the program’s outputs are more appropriately stated in terms of health improvement created (e.g., life-years extended, clinical cures) [89].

Pharmacoeconomic research is the process of identifying, measuring, and comparing the costs, risks and benefits of programs, services or therapies and determining which alternative procedures the best health outcome for the resource invested. For most pharmacists this translates into weighing the cost of providing a pharmacy medicine or service against the consequences realized by using the medicine or service in order to determine which alter-native yields the optimal outcome [111].

In a series of recent studies, the quality and cost-effectiveness of care for severely depressed patients treated under different payment systems by gen-eral medical clinicians and mental healthcare professionals (psychiatrists, psychologists and master-level therapists) were examined. The conclusion was that the overall quality of care for depression is less than optimal, and the cost-effectiveness of care as currently delivered is low. Among seriously depressed patients, many do not receive appropriate care even in the mental health specialty sector but instead receive care for some problem other than depression or receive treatments that are ineffective for depression. Such mistakes are a waste of resources: the healthcare system could get far higher returns for the money it spends when treating depressed patients by spend-ing a little more to improve the quality of care – that is, by appropriately treating more of the depressed patients who are already receiving some care anyway. This potential for improving the cost-effectiveness of care is espe-cially great for depressed patients who visit general medical providers such as internists or family doctors [39].

In the aim to evaluate the pharmacoeconomic benefits of treating depres-sion and to compare the available therapies by reviewing the current aca-demic writings on economic analyses of depression, a PubMed search of the English-language literature relating to economic analyses of depression was conducted. The key search terms included depression, antidepressants, eco-nomics, pharmacoecoeco-nomics, outcomes and costs. Additional literature was collected from the reference lists of articles found as a result of the MED-LINE search. Table 1.4.2 shows the results of the review and meta-analysis of various pharmacoeconomic studies. According to this, new antisants in most cases show better tolerability and cost-effectiveness of depres-sion treatment [14].

ANALYSIS OF THE COST-EFFECTIVENESS AND COSTS RATIONALIZATION OF ANTIDEPRESSANTS CONSUMPTION IN LITHUANIA

Liubov Kavaliauskienė