Health outcomes and cost-effectiveness of treating depression in people with HIV in Sub-Saharan Africa: a model-based analysis.

High prevalence of depression among people living with HIV (PLHIV) impedes antiretroviral therapy (ART) adherence and viral suppression. We estimate the effectiveness and cost-effectiveness of strategies to treat depression among PLHIV in Sub-Saharan Africa (SSA). We developed a microsimulation model of HIV disease and care in Uganda which captured individuals' depression status and the relationship between depression and HIV behaviors. We consider a strategy of screening for depression and providing antidepressant therapy with fluoxetine at ART initiation or re-initiation (if a patient has dropped out). We estimate that over 10 years this strategy would reduce prevalence of depression among PLHIV by 16.0% [95% uncertainty bounds 15.8%, 16.1%] from a baseline prevalence of 28%, increase adherence to ART by 1.0% [1.0%, 1.0%], and decrease rates of loss to followup by 3.7% [3.4%, 4.1%]. This would decrease first-line ART failure rates by 2.5% [2.3%, 2.8%] and increase viral suppression rates by 1.0% [1.0%, 1.0%]. This strategy costs $15/QALY compared to the status quo, and was highly cost-effective over a broad range of sensitivity analyses. We conclude that screening for and treating depression among PLHIV in SSA with fluoxetine would be effective in improving HIV treatment outcomes and would be highly cost-effective.

The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: a study protocol for three multicentre randomised controlled trials.

BACKGROUND: Several small trials have suggested that fluoxetine improves neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials that aim to determine whether routine administration of fluoxetine (20 mg daily) for 6 months after acute stroke improves patients' functional outcome. METHODS/DESIGN: The three trial investigator teams have collaboratively developed a core protocol. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia and New Zealand (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will subsequently provide the most precise estimate of the overall effect of fluoxetine after stroke and establish whether any effects differ between trials and subgroups of patients. The trials include patients ≥18 years old with a clinical diagnosis of stroke, persisting focal neurological deficits at randomisation between 2 and 15 days after stroke onset. Patients are randomised centrally via web-based randomisation systems using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for 6 months. Our primary outcome measure is the modified Rankin scale (mRS) at 6 months. Secondary outcomes include the Stroke Impact Scale, EuroQol (EQ5D-5 L), the vitality subscale of the Short-Form 36, diagnosis of depression, adherence to medication, adverse events and resource use. Outcomes are collected at 6 and 12 months. The methods of collecting these data are tailored to the national setting. If FOCUS, AFFINITY and EFFECTS combined enrol 6000 participants as planned, they would have 90 % power (alpha 5 %) to detect a common odds ratio of 1.16, equivalent to a 3.7 % absolute difference in percentage with mRS 0-2 (44.0 % to 47.7 %). This is based on an ordinal analysis of mRS adjusted for baseline variables included in the minimisation algorithm. DISCUSSION: If fluoxetine is safe and effective in promoting functional recovery, it could be rapidly, widely and affordably implemented in routine clinical practice and reduce the burden of disability due to stroke. FOCUS: ISRCTN83290762 (23/05/2012), AFFINITY: ACTRN12611000774921 (22/07/2011). EFFECTS: ISRCTN13020412 (19/12/2014).

Treatment of depression in older adults beyond fluoxetine.

This review aimed to discuss the importance of the comprehensive treatment of depression among older adults in Brazil. The abuse of selective serotonin reuptake inhibitors, including fluoxetine hydrochloride, as antidepressants has been considered a serious public health problem, particularly among older adults. Despite the consensus on the need for a comprehensive treatment of depression in this population, Brazil is still unprepared. The interface between pharmacotherapy and psychotherapy is limited due to the lack of healthcare services, specialized professionals, and effective healthcare planning. Fluoxetine has been used among older adults as an all-purpose drug for the treatment of depressive disorders because of psychosocial adversities, lack of social support, and limited access to adequate healthcare services for the treatment of this disorder. Preparing health professionals is a sine qua non for the reversal of the age pyramid, but this is not happening yet.

Treatment of depression in older adults beyond fluoxetine / Tratamento de depressão no idoso além do cloridrato de fluoxetina

This review aimed to discuss the importance of the comprehensive treatment of depression among older adults in Brazil. The abuse of selective serotonin reuptake inhibitors, including fluoxetine hydrochloride, as antidepressants has been considered a serious public health problem, particularly among older adults. Despite the consensus on the need for a comprehensive treatment of depression in this population, Brazil is still unprepared. The interface between pharmacotherapy and psychotherapy is limited due to the lack of healthcare services, specialized professionals, and effective healthcare planning. Fluoxetine has been used among older adults as an all-purpose drug for the treatment of depressive disorders because of psychosocial adversities, lack of social support, and limited access to adequate healthcare services for the treatment of this disorder. Preparing health professionals is a sine qua non for the reversal of the age pyramid, but this is not happening yet.

Esse comentário tem como objetivo discutir a importância da multidisciplinariedade do tratamento da depressão do idoso no Brasil. O abuso de prescrições de antidepressivos inibidores seletivos da receptação de serotonina, como o cloridrato de fluoxetina, já tem sido apontado como grave problema de saúde pública, especialmente entre idosos. Embora seja consenso a necessidade de multidisciplinariedade no tratamento da depressão nessa população, o Brasil ainda encontra-se despreparado. A interface entre farmacoterapia e psicoterapia encontra-se prejudicada por falta de serviços, de profissionais especializados e de planejamento assistencial efetivo. A fluoxetina tornou-se uma “muleta” para a cura de males causados pelas adversidades psicossociais, falta de suporte social e de acesso a serviços de saúde adequados para o tratamento desse transtorno em idosos. É condição sine qua non haver preparo para a inversão das pirâmides etárias, o que parece não acontecer atualmente.

State Medicaid programs missed $220 million in uncaptured savings as generic fluoxetine came to market, 2001-05.

Patent expiration of brand-name pharmaceuticals creates opportunities for large savings for state Medicaid programs because generic versions of medications frequently represent a lower-cost alternative. State Medicaid programs that quickly recognize the availability of generics and adjust their drug payments in response to falling market prices can obtain the greatest benefit. We examined one such case: the movement to generic fluoxetine following patent expiration for Prozac, a widely prescribed antidepressant and an expensive drug for Medicaid. We found large differences in states' responses to generic availability. States took between two and ten calendar quarters to reach 90 percent use of generic rather than brand-name fluoxetine and four to eight quarters to achieve a 50 percent decrease in reimbursement per pill. We estimated that states failed to realize $220 million in uncaptured savings during 2001-05. By coordinating their efforts, perhaps with federal help, states could gain access in a more timely way to market prices for generic drugs and, hence, take greater advantage of the savings that those drugs offer.

'You've got m@il: fluoxetine coming soon!': accessibility and quality of a prescription drug sold on the web.

BACKGROUND: The increasing phenomenon of online pharmacies has potential for serious public health problems. This study aimed to evaluate the possibility of accessing a prescription drug in the absence of a prescription for an Italian purchaser. METHODS: Fluoxetine pills were ordered from several online pharmacies. The study included website analysis, and the quality of the received product including packaging, chemical and microbiological analyses. RESULTS: Orders could be placed correctly on 61 of the 98 selected websites, and a sales transaction was concluded successfully on 17 websites. Thirteen drug samples were eventually received. In one case it was necessary to fill in a questionnaire before ordering the drugs. All websites displayed aggressive marketing strategies. There was wide variation in terms of domain registration, company base (when declared) and manufacturer's location (mostly India). All pills were delivered in sealed blister packs showing the lot number and manufacturer's details. A leaflet was enclosed in one case only. In three cases we received more pills than ordered, and in one case Viagra pills as a free gift. Pharmacopoeia microbiological requirements were satisfied. Chemical analysis revealed that the active principle was always present, although many samples did not meet the Pharmacopoeia "other impurities" or "total impurities" criteria. Heavy metals and solvents regulated by the Pharmacopoeia did not exceed the set limits; some of the non-regulated ones were also assessed, in some cases with a positive result (e.g. styrene). CONCLUSION: About 20% of purchase attempts resulted in delivery of the drugs, even in the absence of a medical prescription. Traceability was poor and drug quality was generally worse compared to conventional pharmacy-purchased products. Based on all these broad-spectrum results, user safety appears not to be globally guaranteed.

A cost effectiveness analysis of stepped care treatment for bulimia nervosa.

BACKGROUND: The cost effectiveness of various treatment strategies for bulimia nervosa (BN) is unknown. AIMS: To examine the cost effectiveness of stepped care treatment for BN. METHOD: Randomized trial conducted at four clinical centers with intensive measurement of direct medical costs and repeated measurement of subject quality of life and family/significant other time involvement. Two hundred ninety-three women who met DSM-IV criteria for BN received stepped care treatment or cognitive behavioral therapy. Cost effectiveness ratios were compared. RESULTS: The cost per abstinent subject was $12,146 for stepped care, and $20,317 for cognitive behavioral therapy. Quality of life ratings improved significantly with treatment, and family/significant other time burden diminished substantially. DISCUSSION: In this trial, stepped care for BN appeared cost effective in comparison to cognitive behavioral therapy. Treatment was associated with improved quality of life and diminished time costs of illness.

Cost-effectiveness of adjunctive therapy with atypical antipsychotics for acute treatment of major depressive disorder.

BACKGROUND: While the clinical utility of atypical antipsychotics has been established in patients with major depressive disorder (MDD) who are refractory to antidepressant therapy, their cost-effectiveness is unknown. OBJECTIVE: To examine the cost-effectiveness of aripiprazole, quetiapine, and olanzapine/fluoxetine in adults with MDD who are refractory to antidepressant therapy. METHODS: Using techniques of decision analysis, we estimated expected outcomes and costs over 6 weeks in adults with MDD receiving (1) aripiprazole 2-20 mg/day and antidepressant therapy; (2) quetiapine 150 mg/day or 300 mg/day and antidepressant therapy; (3) the fixed-dose combination of olanzapine 6, 12, or 18 mg/day with fluoxetine 50 mg/day; or (4) antidepressant therapy alone. Cost-effectiveness was assessed in terms of the cost per additional responder at 6 weeks, defined as the ratio of the difference in the cost of MDD-related care over 6 weeks versus antidepressant therapy alone to the difference in the number of patients achieving clinical response by 6 weeks. We estimated the model using data from Phase 3 clinical trials of atypical antipsychotics along with other secondary data sources. RESULTS: With antidepressant therapy alone, the estimated clinical response rate at 6 weeks was 30%. Aripiprazole, quetiapine 150 mg/day, quetiapine 300 mg/day, and olanzapine/fluoxetine were estimated to increase clinical response at 6 weeks to 49%, 34%, 38%, and 45%, respectively. Costs of MDD-related care over 6 weeks were estimated to be $192 for antidepressant therapy, $847 for aripiprazole, $541 for quetiapine 150 mg/day, $672 for quetiapine 300 mg/day plus antidepressant therapy, and $791 for olanzapine/fluoxetine. Costs per additional responder (vs antidepressant therapy) over a 6-week period were estimated to be $3447 for aripiprazole, $8725 for quetiapine 150 mg/day, $6000 for quetiapine 300 mg/day, and $3993 for olanzapine/fluoxetine. CONCLUSIONS: Atypical antipsychotics substantially increase clinical response at 6 weeks. Cost per additional responder is lower for aripiprazole than for quetiapine or olanzapine/fluoxetine.

Cost-effectiveness analysis of pharmacologic treatment of fibromyalgia in Mexico.

OBJECTIVE: To identify, from the Mexican Public Health System perspective, which would be the most cost-effective treatment for patients with Fibromyalgia (FM). MATERIAL AND METHODS: A Markov model including three health states, divided by pain intensity (absence or presence of mild, moderate or severe pain) and considering three-month cycles; costs and effectiveness were estimated for amitriptyline (50mg/day), fluoxetine (80 mg/day), duloxetine (120 mg/day), gabapentin (900 mg/day), pregabalin (450 mg/day), tramadol/acetaminophen (150 mg/1300 mg/día) and amitriptyline/fluoxetine (50mg/80 mg/día) for the treatment of FM. The clinical outcome considered was the annual rate of pain control. Probabilities assigned to the model were collected from published literature. Direct medical costs for FM treatment were retrieved from the 2006 data of the Mexican Institute of Social Security (IMSS) databases and were expressed in 2010 Mexican Pesos. Probabilistic Sensitivity Analyses were conducted. RESULTS: The best pain control rate was obtained with pregabalin (44.8%), followed by gabapentin (38.1%) and duloxetine (34.2%). The lowest treatment costs was for amitriptyline ($ 9047.01), followed by fluoxetine ($ 10,183.89) and amitriptyline/fluoxetine ($ 10,866.01). By comparing pregabalin vs amitriptyline, additional annual cost per patient for pain control would be around $ 50.000 and $ 75.000 and would result cost-effective in 70% and 80% of all cases. CONCLUSIONS: Among all treatment options for FM, pregabalin achieved the highest pain control and was cost-effective in 80% of patients of the Mexican Public Health System.

Cost-effectiveness analysis for antidepressants and cognitive behavioral therapy for major depression in Thailand.

OBJECTIVE: To determine the cost-effectiveness of fluoxetine and cognitive-behavioral therapy (CBT) for major depression in Thailand. METHODS: A microsimulation model was developed to describe the variation in course of disease between individuals. Model inputs included Thai data on disease parameters and costs while impact measures were derived from a systematic review and meta-analysis of the international literature. Fluoxetine as the cheapest antidepressant drug in Thailand was analyzed for treatment of episodes plus a 6-month continuation phase and for maintenance treatment over 5 years of follow-up. CBT was analyzed for episodic treatment and for 5-year maintenance treatment. Results are presented as cost (Thai bahts) per disability-adjusted life-year (DALY) averted, compared with a "do-nothing" scenario. RESULTS: The cost-effectiveness ratios of all interventions were below 1 time Thailand's gross domestic product of 110,000 bahts per capita. The uncertainty ranges around the cost-effectiveness ratios overlap: maintenance treatment with CBT 11,000 bahts per DALY (8,000-14,000); episodic treatment with CBT 23,000 bahts per DALY (10,000-36,000); episodic plus continuation drug treatment 33,000 bahts per DALY (26,000-44,000); maintenance drug treatment 38,000 bahts per DALY (30,000-48,000); and episodic drug treatment 42,000 bahts per DALY (32,000-57,000). CONCLUSIONS: CBT and generic fluoxetine are cost-effective treatment options for both episodic and maintenance treatment of major depression in Thailand. Maintenance treatment has the greatest potential of health gain.

Economic outcomes of eszopiclone treatment in insomnia and comorbid major depressive disorder.

BACKGROUND: Eszopiclone is effective for the treatment of insomnia in patients with insomnia and comorbid major depressive disorder (MDD). Both conditions impose significant economic burden, with the US societal cost of depression estimated at USD 50 billion annually. AIMS OF THE STUDY: The purpose of this analysis was to examine the costs and benefits of eszopiclone co-administered with fluoxetine (ESZ+FLX) compared to placebo co-administered with fluoxetine (PBO+FLX) in adults meeting the DSM-IV criteria for insomnia and MDD. METHODS: Data from 434 patients enrolled in an 8-week clinical trial who met the economic-subanalysis criteria were examined. The costs of medical care (in 2007 USUSD ) and lost work time were estimated from the Hamilton Depression Scale (HAM-D17) scores using published algorithms. Cost of lost productivity while at work was based on responses to the Work Limitations Questionnaire. The impact of therapy on quality-adjusted life years (QALYs) was estimated by transforming HAM-D17 (base case analysis) or Short Form Health Survey (SF-12) (scenario analyses) responses into health utility scores using published algorithms. Drug costs were estimated based on average wholesale price. RESULTS: The mean 8-week increases in QALYs from baseline were 0.0392 and 0.0334 for the ESZ+FLX and PBO+FLX groups, respectively. Mean per-patient costs were USD 1,279 and USD 1,198 for the respective groups. Thus, co-treatment resulted in net increases of 0.0058 QALYs and USD 81, leading to an incremental cost per QALY gained of approximately USD 14,000. DISCUSSION AND LIMITATIONS: Co-administration of eszopiclone and fluoxetine improved patients' insomnia symptoms and appeared to be a cost-effective treatment strategy for patients with insomnia and comorbid MDD. One limitation of this study is that optimal utility estimation techniques were not available. Utilities were instead derived indirectly using the HAM-D17 (disease-specific, not generic) or SF-12 (generic, but potentially insensitive to important changes in some conditions) instruments. IMPLICATIONS FOR HEALTH CARE PROVISION: Sleep disturbance is predictive of depression relapse, and is the most common residual symptom in patients who have been successfully treated with fluoxetine for depression. Thus, identifying cost-effective strategies for the treatment of insomnia symptoms is important for this patient population. IMPLICATIONS FOR HEALTH POLICIES: Treatment guidelines and drug coverage decisions should be based on clinical evidence, effectiveness, and economic criteria (i.e., whether an effective drug therapy produces sufficient benefits given its costs). This information about the overall value of eszopiclone can be measured as the cost per QALY gained with the use of ESZ+FLX compared with FLX alone. In order to make decisions based on value, payers and policy makers must have access to reliable cost-effectiveness information. IMPLICATIONS FOR FURTHER RESEARCH: The residual efficacy observed in the clinical trial following the discontinuation of co-therapy should be explored further to determine whether intermittent treatment with ESZ+FLX is a cost-effective strategy.

Cost-effectiveness analysis of treatments for premenstrual dysphoric disorder.

BACKGROUND: Premenstrual syndrome (PMS) is reported to affect between 13% and 31% of women. Between 3% and 8% of women are reported to meet criteria for the more severe form of PMS, premenstrual dysphoric disorder (PMDD). Although PMDD has received increased attention in recent years, the cost effectiveness of treatments for PMDD remains unknown. OBJECTIVE: To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE). METHODS: A decision-analytic model was used to evaluate both direct costs (medication and physician visits) and clinical outcomes (treatment success, failure and discontinuation). Medication costs were based on average wholesale prices of branded products; physician visit costs were obtained from a claims database study of PMDD patients and the Agency for Healthcare Research and Quality. Clinical outcome probabilities were derived from published clinical trials in PMDD. The incremental cost-effectiveness ratio (ICER) was calculated using the difference in costs and percentage of successfully treated patients at 6 months. Deterministic and probabilistic sensitivity analyses were used to assess the impact of uncertainty in parameter estimates. Threshold values where a change in the cost-effective strategy occurred were identified using a net benefit framework. RESULTS: Starting therapy with DRSP/EE dominated both sertraline and paroxetine, but not fluoxetine. The estimated ICER of initiating treatment with fluoxetine relative to DRSP/EE was $US4385 per treatment success (year 2007 values). Cost-effectiveness acceptability curves revealed that for ceiling ratios>or=$US3450 per treatment success, fluoxetine had the highest probability (>or=0.37) of being the most cost-effective treatment, relative to the other options. The cost-effectiveness acceptability frontier further indicated that DRSP/EE remained the option with the highest expected net monetary benefit for ceiling values

Relative cost-effectiveness of treatments for adolescent depression: 36-week results from the TADS randomized trial.

OBJECTIVE: The cost-effectiveness of three active interventions for major depression in adolescents was compared after 36 weeks of treatment in the Treatment of Adolescents with Depression Study. METHOD: Outpatients aged 12 to 18 years with a primary diagnosis of major depression participated in a randomized controlled trial conducted at 13 U.S. academic and community clinics from 2000 to 2004. Three hundred twenty-seven participants randomized to 1 of 3 active treatment arms, fluoxetine alone (n = 109), cognitive-behavioral therapy (n = 111) alone, or their combination (n = 107), were evaluated for a 3-month acute treatment and a 6-month continuation/maintenance treatment period. Costs of services received for the 36 weeks were estimated and examined in relation to the number of depression-free days and quality-adjusted life-years. Cost-effectiveness acceptability curves were also generated. Sensitivity analyses were conducted to assess treatment differences on the quality-adjusted life-years and cost-effectiveness measures. RESULTS: Cognitive-behavioral therapy was the most costly treatment component (mean $1,787 [in monotherapy] and $1,833 [in combination therapy], median $1,923 [for both]). Reflecting higher direct and indirect costs associated with psychiatric hospital use, the costs of services received outside Treatment of Adolescents with Depression Study in fluoxetine-treated patients (mean $5,382, median $2,341) were significantly higher than those in participants treated with cognitive-behavioral therapy (mean $3,102, median $1,373) or combination (mean $2,705, median $927). Accordingly, cost-effectiveness acceptability curves indicate that combination treatment is highly likely (>90%) to be more cost-effective than fluoxetine alone at 36 weeks. Cognitive-behavioral therapy is not likely to be more cost-effective than fluoxetine. CONCLUSIONS: These findings support the use of combination treatment in adolescents with depression over monotherapy.

Randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of selective serotonin reuptake inhibitors plus supportive care, versus supportive care alone, for mild to moderate depression with somatic symptoms in primary care: the THREAD (THREshold for AntiDepressant response) study.

OBJECTIVES: To determine (1) the effectiveness and cost-effectiveness of selective serotonin reuptake inhibitor (SSRI) treatment plus supportive care, versus supportive care alone, for mild to moderate depression in patients with somatic symptoms in primary care; and (2) the impact of the initial severity of depression on effectiveness and relative costs. To investigate the impact of demographic and social variables. DESIGN: The study was a parallel group, open-label, pragmatic randomised controlled trial. SETTING: The study took place in a UK primary care setting. Patients were referred by 177 GPs from 115 practices around three academic centres. PARTICIPANTS: Patients diagnosed with new episodes of depression and potentially in need of treatment. In total, 602 patients were referred to the study team, of whom 220 were randomised. INTERVENTIONS: GPs were asked to provide supportive care to all participants in follow-up consultations 2, 4, 8 and 12 weeks after the baseline assessment, to prescribe an SSRI of their choice to patients in the SSRI plus supportive care arm and to continue treatment for at least 4 months after recovery. They could switch antidepressants during treatment if necessary. They were asked to refrain from prescribing an antidepressant to those in the supportive care alone arm during the first 12 weeks but could prescribe to these patients if treatment became necessary. MAIN OUTCOME MEASURES: The primary outcome measure was Hamilton Depression Rating Scale (HDRS) score at 12-week follow-up. Secondary outcome measures were scores on HDRS at 26-week follow-up, Beck Depression Inventory, Medical Outcomes Study Short Form-36 (SF-36), Medical Interview Satisfaction Scale (MISS), modified Client Service Receipt Inventory and medical record data. RESULTS: SSRIs were received by 87% of patients in the SSRI plus supportive care arm and 20% in the supportive care alone arm. Longitudinal analyses demonstrated statistically significant differences in favour of the SSRI plus supportive care arm in terms of lower HDRS scores and higher scores on the SF-36 and MISS. Significant mean differences in HDRS score adjusted for baseline were found at both follow-up points when analysed separately but were relatively small. The numbers needed to treat for remission (to HDRS > 8) were 6 [95% confidence interval (CI) 4 to 26)] at 12 weeks and 6 (95% CI 3 to 31) at 26 weeks, and for significant improvement (HDRS reduction > or = 50%) were 7 (95% CI 4 to 83) and 5 (95% CI 3 to 13) respectively. Incremental cost-effectiveness ratios and cost-effectiveness planes suggested that adding an SSRI to supportive care was probably cost-effective. The cost-effectiveness acceptability curve for utility suggested that adding an SSRI to supportive care was cost-effective at the values of 20,000 pounds-30,000 pounds per quality-adjusted life-year. A poorer outcome on the HDRS was significantly related to greater severity at baseline, a higher physical symptom score and being unemployed. CONCLUSIONS: Treatment with an SSRI plus supportive care is more effective than supportive care alone for patients with mild to moderate depression, at least for those with symptoms persisting for 8 weeks and an HRDS score of > or = 12. The additional benefit is relatively small, and may be at least in part a placebo effect, but is probably cost-effective at the level used by the National Institute for Health and Clinical Excellence to make judgements about recommending treatments within the National Health Service. However, further research is required.

The unlicensed lives of antidepressants in India: generic drugs, unqualified practitioners, and floating prescriptions.

Antidepressant uses have been rising rapidly over the past decades. Two main theories have been advanced to explain this. One claims that socio-economic change causes a global rise of depressive illness. The other holds that European and North American corporations are aggressively marketing antidepressants to expand their global reach. Both theories assume that multinational capitalism drives rising depression rates. Based on ethnographic data from India, this article shows that antidepressants are increasingly used in this country as well, but for reasons than have been little explored yet. Taking fluoxetine (Prozac) as the main example, it is argued that the spread of antidepressants in India is ;unlicensed' by Euro-American corporations in at least three ways: (i) drug marketing is driven by Indian generic producers; (ii) fluoxetine is given by practitioners who have no license to do so; and (iii) knowledge of fluoxetine is spread through unlicensed ;floating' prescriptions that patients take from one prescriber to another.

Fluoxetine and imipramine: are there differences in cost-utility for depression in primary care?

RATIONALE: Depressive disorders generate severe personal burden and high economic costs. Cost-utility analyses of the different therapeutical options are crucial to policy-makers and clinicians. Previous cost-utility studies, comparing selective serotonin reuptake inhibitors and tricyclic antidepressants, have used modelling techniques or have not included indirect costs in the economic analyses. OBJECTIVE: To determine the cost-utility of fluoxetine compared with imipramine for treating depressive disorders in primary care. METHODS: A 6-month randomized prospective naturalistic study comparing fluoxetine with imipramine was conducted in three primary care centres in Spain. One hundred and three patients requiring antidepressant treatment for a DSM-IV depressive disorder were included in the study. Patients were randomized either to fluoxetine (53 patients) or to imipramine (50 patients) treatment. Patients were treated with antidepressants according to their general practitioner's usual clinical practice. Outcome measures were the quality of life tariff of the European Quality of Life Questionnaire: EuroQoL-5D (five domains), direct costs, indirect costs and total costs. Subjects were evaluated at the beginning of treatment and after 1, 3 and 6 months. Incremental cost-utility ratios (ICUR) were obtained. To address uncertainty in the ICUR's sampling distribution, non-parametric bootstrapping was carried out. RESULTS: Taking into account adjusted total costs and incremental quality of life gained, imipramine dominated fluoxetine with 81.5% of the bootstrap replications in the dominance quadrant. CONCLUSION: Imipramine seems to be a better cost-utility antidepressant option for treating depressive disorders in primary care.

Cost effectiveness of venlafaxine compared with generic fluoxetine or generic amitriptyline in major depressive disorder in the UK.

OBJECTIVE: To estimate the cost effectiveness of venlafaxine compared with generic fluoxetine and generic amitriptyline used in major depressive disorder in primary care in the UK. METHODS: A decision-tree model for the treatment of major depressive disorder was constructed using a Delphi panel. The tree was populated with clinical success rates from a pooled analysis of fluoxetine compared with venlafaxine and a clinical trial of amitriptyline compared with venlafaxine using remission as the key endpoint. Where there was insufficient data from clinical trials, the Delphi panel was used. Costs within the tree were taken from contemporary UK sources. Six-monthly costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were then estimated. RESULTS: Treatment costs for 6 months were pound1530 for venlafaxine, pound1539 for fluoxetine and pound1558 for amitriptyline (year of costing 2006). Cost effectiveness as assessed by incremental cost per QALY ratio at 8 weeks was pound20 600 for venlafaxine compared with fluoxetine, with fluoxetine dominating (being less costly and more effective than) amitriptyline. To test the robustness of the model a Rank Order Stability Assessment was performed that showed that even if fluoxetine and/or amitriptyline were given away free, a scenario starting with venlafaxine would still be the least costly treatment over a 6-month period. CONCLUSION: In this model, venlafaxine was shown to be a cost-effective alternative to generic fluoxetine and amitriptyline when used as a first-line therapy. Thus, cost of therapy should not be a barrier to use of venlafaxine as a first-line option in treating major depressive disorder in primary care in the UK.

Cost-effectiveness and cost-utility of cognitive therapy, rational emotive behavioral therapy, and fluoxetine (Prozac) in treating depression: a randomized clinical trial.

Cost-effectiveness and cost-utility of cognitive therapy (CT), rational emotive behavioral therapy (REBT), and fluoxetine (Prozac) for major depressive disorder (MDD) were compared in a randomized clinical trial with a Romanian sample of 170 clients. Each intervention was offered for 14 weeks, plus three booster sessions. Beck Depression Inventory (BDI) scores were obtained prior to intervention, 7 and 14 weeks following the start of intervention, and 6 months following completion of intervention. CT, REBT, and fluoxetine did not differ significantly in changes in the BDI, depression-free days (DFDs), or Quality-Adjusted Life Years (QALYs). Average BDI scores decreased from 31.1 before treatment to 9.7 six months following completion of treatment. Due to lower costs, both psychotherapies were more cost-effective, and had better cost-utility, than pharmacotherapy: median $26.44/DFD gained/month for CT and $23.77/DFD gained/month for REBT versus $34.93/DFD gained/month for pharmacotherapy, median $/QALYs=$1,638, $1,734, and $2,287 for CT, REBT, and fluoxetine (Prozac), respectively.

[Consumption of antidepressants in Chile from 1992 to 2004]. / Consumo de antidepresivos en Chile entre 1992 y 2004.

BACKGROUND: Data from the Ministry of Health show that in Chile in 2004, 17% of the population had some form of depression, and mood disorders are the tenth cause of disability-adjusted life years (DALY) loss. AIM: To determine consumption of antidepressants (ADs) in Chile from 1992 to 2004. MATERIAL AND METHODS: National sales data were obtained from the company IMS Health Chile and converted into defined daily doses (DDDs) per 1,000 inhabitants per day. Available ADs were classified in four pharmacological groups (i.e., serotonin-norepinephrine reuptake inhibitors, SNRLs; selective-serotonin reuptake inhibitors, SSRLs; tricyclic antidepressants, TCAs; and others). Total economic burden of ADs utilization and cost per DDDs were also calculated. Trends over time were analyzed using Pearson-R2. RESULTS: Total ADs consumption in Chile measured by DDDs per 1,000 inhabitants per day (DHD) increased linearly (y =0.901x + 1.9129; R2 =0.9296; p <0.001) from 2.5 in 1992 to 11.7 in 2004 (total growth of 470.2%). SSRLs were the drug class with higher consumption, and fluoxetine the most commonly consumed antidepressant. SSRLs were the drugs that dominated the market representing 79% of the total drug consumption throughout the years. Total economic burden of ADs in Chile (total cost of DDDs consumed) increased from US$65.4 million in 2001 to US$74.6 million in 2004 (14% increase). Average cost per DDD of all AD increased linearly, however not significantly from US$ 0.94 in 2001 to US$ 1.04 in 2004 (y =0.0362x + 0.8784; R2 =0.7382; p =0,262). CONCLUSIONS: DDDs per 1,000 inhabitants per day increased linearly over 470% from 1992-2004. SSRLs were the most commonly consumed drugs in Chile. Future research should evaluate the cost-effectiveness of antidepressants in Chile, comparing the results with drug utilization, and determining if unnecessary expenditures have been paid out.

Pharmacoeconomics of antidepressants in moderate-to-severe depressive disorder in Colombia / Farmacoeconomía de antidepresivos en trastornos de depresión moderada e intensa en Colombia

OBJECTIVE: To compare three antidepressant drugs from different classes used in treating moderate-to-severe major depressive disorder (MDD) in Colombian adults. METHODS: Based on expert input, a decision-tree model was adapted for Colombia to analyze data over 6 months from the government-payer perspective. The cost-effectiveness of amitriptyline, fluoxetine, and venlafaxine was determined. The clinical outcome was remission of depression (a score <7 on the Hamilton Depression [HAM-D] scale or <12 on the Montgomery-Åsberg Depression Rating Scale [MADRS]) after 8 weeks of treatment. Clinical data were obtained from the literature and costs from standard Colombian price lists. One-way and multivariate sensitivity analyses tested model robustness. RESULTS: Costs per patient (in 2007 US$) for treatment were: venlafaxine, $1 618; fluoxetine, $1 207; and amitriptyline, $1 068. Overall remission rates were 73.1 percent, 64.1 percent, and 71.3 percent, respectively. Amitriptyline dominated fluoxetine (i.e., it had lower costs and higher outcomes). The incremental cost-effectiveness ratio (ICER) of venlafaxine over amitriptyline was US$ 31 595. The acquisition price of venlafaxine was the model's cost driver, comprising 53.4 percent of the total cost/patient treated, compared with 18.5 percent and 24.8 percent for fluoxetine and amitriptyline, respectively. For the others, hospitalization comprised the major cost (72.1 percent and 65.2 percent, respectively). Probabilistic (Monte Carlo) sensitivity analysis confirmed the original findings of the pharmacoeconomic model. CONCLUSIONS: Amitriptyline is cost-effective in comparison to fluoxetine and venlafaxine in Colombia. However, the cost of venlafaxine was estimated for the brand-name product, as generics were not currently available. These cost-effectiveness results can be substantially affected by the presence of generics or drug cost regulations.

OBJETIVO: Comparar tres medicamentos antidepresivos de diferentes clases empleados para tratar trastornos depresivos mayores moderados e intensos en adultos colombianos. MÉTODOS: A partir de los aportes de expertos se adaptó un modelo de árbol de decisión para Colombia a fin de analizar los datos de seis meses desde la perspectiva del gobierno como pagador de los servicios. Se determinó la relación costo-efectividad de la amitriptilina, la fluoxetina y la venlafaxina. El desenlace clínico fue la remisión de la depresión (una puntuación <7 en la escala de depresión de Hamilton o <12 en la escala de valoración de la depresión de Montgomery-Åsberg) después de 8 semanas de tratamiento. Los datos clínicos se obtuvieron de la literatura especializada y los costos, de las listas habituales de precios de Colombia. Se realizaron análisis de sensibilidad simples y multifactoriales para probar la robustez de los modelos. RESULTADOS: Los costos del tratamiento por paciente (en dólares estadounidenses de 2007) fueron: US$ 1 618 para la venlafaxina, US$ 1 207 para la fluoxetina y US$ 1 068 para la amitriptilina. Las tasas de remisión general fueron 73,1 por ciento, 64,1 por ciento y 71,3 por ciento, respectivamente. La amitriptilina tuvo un menor costo y una mayor remisión que la fluoxetina. La razón de rentabilidad incremental de la venlafaxina sobre la amitriptilina fue de US$ 31 595. El inductor de costos (cost driver) del modelo fue el valor de adquisición de la venlafaxina, que representó 53,4 por ciento del total del costo por paciente tratado, en comparación con la fluoxetina (18,5 por ciento) y la amitriptilina (24,8 por ciento). En los otros casos, la hospitalización representó el mayor costo (72,1 por ciento y 65,2 por ciento, respectivamente). El análisis de sensibilidad probabilístico (Monte Carlo) confirmó los resultados preliminares del modelo farmacoeconómico. CONCLUSIONES: En Colombia, la amitriptilina es más efectiva en función del...