Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial.

BACKGROUND: Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes. AIMS: To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia. METHOD: A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods. RESULTS: There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively. CONCLUSIONS: In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.

Economic evaluation of duloxetine versus serotonin selective reuptake inhibitors and venlafaxine XR in treating major depressive disorder in Scotland.

BACKGROUND: Major depressive disorders (MDD) are responsible for substantial direct and indirect health care costs. Despite the availability of numerous treatments, the need for effective pharmacotherapy remains. Duloxetine is a relatively balanced serotonin norepinephrine reuptake inhibitor (SNRI) with favourable clinical and tolerability profile. The cost-effectiveness of duloxetine versus established SSRIs, venlafaxine XR and mirtazapine was estimated in the UK. METHODS: A decision analysis simulating clinical management of MDD was developed to estimate health and economic impacts of alternative treatments over one year. Patients on treatment experience remission, response without remission, no response, relapse or discontinue the initial regimen. Model outcomes were total treatment costs and quality-adjusted life years. Resource utilization data were derived from literature and practising UK psychiatrists and GPs. The robustness of findings with respect to modelling assumptions was assessed in extensive sensitivity analyses. RESULTS: With similar efficacy to venlafaxine XR but lower drug costs, duloxetine is less costly and marginally more effective than venlafaxine XR both in the overall MDD population and in a more severe subgroup. Duloxetine has a low cost-effectiveness ratio in primary care against SSRIs and mirtazapine, and was found cost-saving against mirtazapine in more severe patients. LIMITATIONS: Cost-effectiveness results are sensitive to changes in efficacy parameters and resource use data were collected from physician panel. CONCLUSIONS: Duloxetine represents an important option in the treatment of MDD in the UK that can be recommended on economic grounds. With similar efficacy and different side-effect profile to venlafaxine XR it represents a valuable choice to MDD patients.

Prescribing a sedative antidepressant for patients at work or on sick leave under conditions of routine care.

BACKGROUND: Sedation can be a beneficial effect of medication, but it can also be an unwanted side-effect, especially in patients who have to work. The aim of this study is to analyze whether physicians prescribe sedative antidepressants differently for patients at work vs. those on sick leave. METHODS: A drug utilization study of mirtazapine was conducted for 12 weeks on 594 depressed outpatients from 227 general practitioners or psychiatrists. There were 319 patients working and 275 patients on sick leave. The two groups were compared regarding sociodemographic variables, illness characteristics, mode and course of treatment. RESULTS: As expected, patients on sick leave were sicker than working patients; they were treated by specialists more often and received higher dosages of mirtazapine. Work status had no influence on dosage after controlling for severity of illness, patient sex, and physician specialty. The overall improvement of depression was similar in both patient groups. Under treatment with mirtazapine, 64.5% of patients on sick leave returned to work, while 2.6% of the patients initially at work went on sick leave by the end of the 12 weeks. Sedation as an undesired side-effect was reported in less than 1%. The rate of sedative polypharmacy declined during treatment with mirtazapine. CONCLUSION: The results suggest that in routine treatment physicians do not see a need to adjust prescribing of mirtazapine because of its sedative properties to the working status of the patients. The majority of patients on sick leave returned to work. Mirtazapine can help to reduce sedative polypharmacy.

The cost-effectiveness of mirtazapine versus paroxetine in treating people with depression in primary care.

Currently, there are no data available comparing cost-effectiveness of two antidepressants in the primary care setting in the UK. Alongside a randomized, double-blind, 24-week study of mirtazapine and paroxetine, data were prospectively collected on patients' use of hospital and non-hospital services and days off work. Costs were estimated in each treatment arm from National Health Service (NHS) and societal perspectives, and were compared with selected outcome measures (numbers of 17-item Hamilton Rating Scale for Depression (17-HAMD) responders and changes in Quality of Life in Depression Scale scores between baseline and 24-week endpoint) to explore and compare relative cost-effectiveness. Mirtazapine treatment resulted in a statistically significantly greater improvement in quality of life than paroxetine at endpoint (P=0.021). Although the 17-HAMD response rates were higher for the mirtazapine users at endpoint, the difference (7%) was not statistically significant (P=0.31). However, mean total societal costs per patient were 375 pounds less with mirtazapine (1850 pounds) compared to paroxetine (2225 pounds; P=0.32). Mean total NHS costs per patient were also lower (120 pounds) with mirtazapine (1408 pounds) compared to paroxetine (1528 pounds). The advantage for mirtazapine remained present on all variables analysed after performing sensitivity analyses. The results suggest that mirtazapine may be a cost-effective treatment choice compared to paroxetine for depression in a primary care setting.

Mirtazapine is associated with less anxiolytic use among elderly depressed patients in long-term care facilities.

BACKGROUND: Depression is a common, treatable disorder among nursing facility residents. OBJECTIVE: The purpose of this study was to examine medication use and cost between two groups of patients: (1) persons treated with mirtazapine, as compared with (2) persons taking other antidepressants. DESIGN: This study was a retrospective chart review of long-term care patients. Consultant pharmacists collected data on patients who were receiving selective serotonin reuptake inhibitors (SSRIs), venlafaxine, nefazodone, or mirtazapine. SETTING: Nursing facilities that were geographically dispersed throughout the United States. PARTICIPANTS: We studied patients greater than 65 years of age with major depressive disorder or a depression-related diagnosis and receiving antidepressant treatment for at least 3 months. Patients with bipolar-induced depression were excluded as well as those receiving tricyclic antidepressants. RESULTS: The two groups were similar in terms of age, but those receiving mirtazapine had lower body weight and body mass index. Patients on mirtazapine were less likely to be taking a sedative/hypnotic (P = 0.006). This was primarily the result of fewer patients in the mirtazapine group taking lorazepam (P = 0.03). There was no difference between the two groups regarding their use of other psychotropic medications, including multiple antidepressants, antipsychotics, anticonvulsants, acetylcholinesterase inhibitors, or appetite stimulants. Monthly medication costs were less for those patients receiving mirtazapine ($82.83) as compared with other antidepressants ($97.03) (P <0.0001). CONCLUSIONS: The results of this study suggest that patients receiving mirtazapine are less likely to be on anxiolytic/hypnotic agents. The findings also suggest that medication costs are less when mirtazapine is used compared with other antidepressants.

Mirtazepine: heir apparent to amitriptyline?

"What's new in therapeutics?" will examine and evaluate drugs that may have a place in hospice, palliative, and long-term care. Mirtazepine will be examined and evaluated. Mirtazepine is a potential alternative anti-depressant with multiple additional benefits. It is an atypical anti-depressant, which has both noradrenergic and specific serotonergic receptor antagonism (NaSSa), and a unique pharmacological profile. Mirtazepine appears to be a "designer drug" for palliative medicine with a number of benefits, but cost may be a drawback.

Economic impact of using mirtazapine compared to amitriptyline and fluoxetine in the treatment of moderate and severe depression in the UK.

This study modelled the economic impact of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in the UK, as well as the costs related to discontinuation of antidepressant treatment. Decision models of the management of moderate and severe depression were developed from clinical trial data, resource use obtained from interviews with general practitioners and psychiatrists, and published literature, and were used to estimate the expected direct National Health Service (NHS) costs of managing a patient with moderate or severe depression. The expected cost of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment, irrespective of the initial treatment, was estimated to be pounds sterling 206 (range pounds sterling 50 to pounds sterling 504) over five months. Using mirtazapine instead of amitriptyline for seven months increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%) and reduces the expected direct NHS cost by pounds sterling 35 per patient (from pounds sterling 448 to pounds sterling 413). Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for an additional cost to the NHS of pounds sterling 27 per patient (from pounds sterling 394 to pounds sterling 420). In conclusion, this study suggests that mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine in the management of moderate and severe depression in the UK.

Mirtazapine. A pharmacoeconomic review of its use in depression.

UNLABELLED: Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA). The antidepressant efficacy of mirtazapine has been established in randomised, double-blind comparative studies. Mirtazapine has generally shown similar efficacy to other antidepressants. There is evidence for a faster onset of action with mirtazapine than with the selective serotonin (5-hydroxytryptamine; 5-HT) re-uptake inhibitors (SSRIs) on the basis of mean depression rating scale scores. Data from a long term (mean 240 days) clinical trial that was subsequently used in pharmacoeconomic analyses showed that mirtazapine was associated with significantly higher sustained remission rates and rates of discontinuation because of improvement than amitriptyline and placebo. Although differences were not statistically significant, mirtazapine had higher response rates at 6 weeks than the SSRI fluoxetine in an analysis that was also used as the basis of pharmacoeconomic studies. Mirtazapine improved quality of life to a similar extent to fluoxetine, citalopram and paroxetine in unpublished studies of 6 and 8 weeks' duration. Pooled analyses suggest that mirtazapine may be associated with greater improvement than fluoxetine and citalopram in quality of life after 2 and 4 weeks, although confirmation is required. In a decision analytical model of approximately 6 months' duration, mirtazapine was associated with a higher proportion of successfully treated patients and lower total direct costs than amitriptyline. The direct cost per successfully treated patient with mirtazapine was lower than that with amitriptyline by 33,112 Austrian schillings (S; year of costing not stated), 24,212 French francs (FF; 1995/1996 values), 13,851 Swedish kronor (SEK; 1997 values) and 553 Pounds (1997/1998 values) in Austrian, French, Swedish and UK analyses, respectively. Compared with fluoxetine, mirtazapine was associated with higher per-patient costs in all 4 countries but a higher proportion of successfully treated patients. Mirtazapine was more cost effective than fluoxetine: the direct cost per successfully treated patient was lower by S32,046 in Austria, FF25,914 in France, SEK9796 in Sweden and 327 Pounds in the UK. The additional cost of mirtazapine versus fluoxetine for each additional successfully treated patient at 6 months was S11,732, SEK17,229, 750 Pounds and FF3342 in the Austrian, Swedish, UK and French analyses, respectively. Mirtazapine was generally associated with lower indirect costs (for lost productivity of employed patients) than amitriptyline and similar indirect costs to fluoxetine in the analyses. CONCLUSIONS: Available data suggest that mirtazapine is a cost-effective alternative to amitriptyline and fluoxetine for the treatment of depression. Mirtazapine also has similar effects to SSRIs on quality of life with possibly a shorter time to onset of action, although published trial results are required to confirm these preliminary data.

[Treatment of depression and cost efficiency. The cost of a tablet is a poor indicator seen from a socioeconomic perspective]. / Depressionsbehandling och kostnadseffektivitet. Priset per tablett dålig indikator i ett samhällsekonomiskt perspektiv.

Direct costs for treating depression, i.e. the cost of out-patient and in-patient care together with drug costs, have increased by 55 per cent during the period 1987-1997 in Sweden. Drugs incurred the greatest increase, whereas the cost of in-patient care has decreased. Indirect costs, i.e. sick leave, morbidity and premature mortality due to depression, have also increased during this period. Cost-effectiveness calculations comparing mirtazapine with amitriptyline show that it is less expensive to initiate treatment with mirtazapine, both when direct costs are compared and when indirect costs are included. In a comparison between mirtazapine and fluoxetine, initial treatment with fluoxetine is less expensive with respect to direct cost, but these two alternatives are equivalent when indirect costs are taken into consideration. The price of drug is a poor criterion of resource expenditures and of rational pharmacological therapy in the treatment of depression.

Cost-effectiveness of mirtazapine compared to amitriptyline and fluoxetine in the treatment of moderate and severe depression in austria.

This study estimated the cost-effectiveness of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in Austria, as well as the costs related to the discontinuation of antidepressant treatment from the perspective of the Austrian Sick Funds (Gebietskrankenkassen). The economic analyses were based on a meta-analysis of four randomised clinical trials comparing mirtazapine with amitriptyline, and on a six week comparative trial of mirtazapine and fluoxetine which was extrapolated to six months using assumptions derived from the literature. Decision models of the treatment paths and associated resource use attributable to managing moderate and severe depression in Austria were developed from clinical trial data, information on Austrian clinical practice obtained from interviews with an Austrian Delphi panel (comprising psychiatrists and GPs), and from published literature. The models were used to estimate the expected costs to the Gebietskrankenkassen of managing a patient with moderate or severe depression, and the indirect cost per patient to Austrian society due to lost productivity. The expected cost to the Gebietskrankenkassen of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment was estimated to be ATS 4,088 over five months, of which hospitalisations accounted for nearly 69% of the cost. Using mirtazapine instead of amitriptyline for 28 weeks increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%), and reduces the expected cost to the Gebietskrankenkassen by ATS 1,112 per patient (from ATS 31,411 to ATS 30,299). Patients treated with mirtazapine and amitriptyline for 28 weeks are expected to miss 4.76 and 5.01 weeks of work respectively, due to their depression. Hence, the expected indirect cost to Austrian society over this period was estimated to be ATS 58, 787 and ATS 61,851 per patient respectively. Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for a negligible additional cost to the Gebietskrankenkassen of ATS 408 per patient (from ATS 29,205 to ATS 29,613). Patients treated with mirtazapine and fluoxetine for six months are expected to miss 4.53 weeks of work, due to their depression. Hence, the expected indirect cost to Austrian society due to lost productivity was estimated to be ATS 55,900 per patient with either antidepressant. In conclusion, this study suggests that despite the differences in acquisition costs, mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine, supporting the adoption of this treatment in the management of moderate and severe depression in Austria.