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.

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 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.

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.

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 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.

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.

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.

Use of Bayesian net benefit regression model to examine the impact of generic drug entry on the cost effectiveness of selective serotonin reuptake inhibitors in elderly depressed patients.

INTRODUCTION: Since their invention in the late 1980s and early 1990s, selective serotonin reuptake inhibitors (SSRIs) have become the primary form of pharmaceutical treatment for depression. As the patents of several top-selling SSRIs have expired or are soon to be expired, the SSRI market is expected to witness an increasing share of generic SSRIs. We explored the impact of generic drug entry on the cost effectiveness of SSRIs. METHOD: Using Medicare MarketScan claims data, we compared the cost effectiveness of sertraline, citalopram, escitalopram and fluoxetine with paroxetine in elderly depressed patients, before and after the entry of generic paroxetine. We followed users of SSRIs for 6 months, starting from the date of their first prescription of an SSRI. For each patient, we measured costs (C(i)) as total medical costs and quantified effectiveness (E(i)) as the avoidance of treatment failure, which was defined as having a break exceeding 45 days in the use of antidepressants. We then calculated individual net benefit as lambda x E(i)- C(i) and employed both net benefit and Bayesian net benefit regression models to examine the impact of generic paroxetine on the cost effectiveness of the other four SSRIs compared with paroxetine, while controlling for patients' sociodemographic characteristics, co-morbidities and patterns of medication switch. RESULTS: Deterministic analysis showed that paroxetine was dominated by most SSRIs prior to the availability of generic paroxetine, and that, after the entry of generic paroxetine, citalopram and escitalopram were dominated by paroxetine. Net benefit regression analysis found that, at a number of lambda values ($US1000, $US5000 and $US10,000), sertraline and escitalopram were more cost effective than paroxetine in the pre-generic-entry period but not in the post-entry period, although the difference in net benefit between the two SSRIs and paroxetine was not statistically significant in both periods. The Bayesian net benefit regression analysis reached similar conclusions. At lambda = $US5000, the probability that sertraline, citalopram, escitalopram or fluoxetine was more cost effective than paroxetine was 96.7%, 77.6%, 96.3% and 97.0%, respectively, in the pre-entry period in the pooled analysis. These probabilities reduced to 36.7%, 62.7%, 33.0% and 60.1%, respectively, in the post-entry period. The probabilities became 94.1%, 71.9%, 89.1% and 92.1% in analysis using the pre-entry data as a prior to update the post-entry data rather than using the pooled data. CONCLUSION: Using generic drug entry as an example, our study demonstrated the importance of including the economic life cycle of pharmaceuticals in cost-effectiveness analyses. Additionally, the proposed Bayesian framework not only preserves the advantages of the net benefit regression framework, but more importantly, it introduces the possibility of conducting probabilistic cost-effectiveness analyses with claims data.

Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial.

BACKGROUND: Clinical depression is common, debilitating and treatable; one in four people experience it during their lives. The majority of sufferers are treated in primary care and only half respond well to active treatment. Evidence suggests that folate may be a useful adjunct to antidepressant treatment: 1) patients with depression often have a functional folate deficiency; 2) the severity of such deficiency, indicated by elevated homocysteine, correlates with depression severity, 3) low folate is associated with poor antidepressant response, and 4) folate is required for the synthesis of neurotransmitters implicated in the pathogenesis and treatment of depression. METHODS/DESIGN: The primary objective of this trial is to estimate the effect of folate augmentation in new or continuing treatment of depressive disorder in primary and secondary care. Secondary objectives are to evaluate the cost-effectiveness of folate augmentation of antidepressant treatment, investigate how the response to antidepressant treatment depends on genetic polymorphisms relevant to folate metabolism and antidepressant response, and explore whether baseline folate status can predict response to antidepressant treatment. Seven hundred and thirty patients will be recruited from North East Wales, North West Wales and Swansea. Patients with moderate to severe depression will be referred to the trial by their GP or Psychiatrist. If patients consent they will be assessed for eligibility and baseline measures will be undertaken. Blood samples will be taken to exclude patients with folate and B12 deficiency. Some of the blood taken will be used to measure homocysteine levels and for genetic analysis (with additional consent). Eligible participants will be randomised to receive 5 mg of folic acid or placebo. Patients with B12 deficiency or folate deficiency will be given appropriate treatment and will be monitored in the 'comprehensive cohort study'. Assessments will be at screening, randomisation and 3 subsequent follow-ups. DISCUSSION: If folic acid is shown to improve the efficacy of antidepressants, then it will provide a safe, simple and cheap way of improving the treatment of depression in primary and secondary care. TRIAL REGISTRATION: Current controlled trials ISRCTN37558856.

Generic fluoxetine and choice of antidepressant medication.

OBJECTIVE: In 2002 generic fluoxetine, the first generic product in a relatively expensive medication class, became available at Veterans Affairs medical centers at only 5% of its previous cost. This study examined whether its availability was associated with an increase in use compared with other medications. METHODS: All new starts of 15 antidepressants during fiscal year (FY) 2001 (before generic fluoxetine became available) and FY2003 were identified from administrative records, and the change in proportions of new starts across years was examined. RESULTS: Altogether, 55,673 patients had a new start on antidepressants in FY2001 and 48,002 had a new start in FY2003. The percentage of fluoxetine prescriptions (both branded and generic) rose only 1.2%--from 8.3% in FY2001 to 9.5% in FY2003. CONCLUSIONS: Only a small increase was found in the rate of new starts of fluoxetine in the year after its release as a low-cost generic. There appear to be untapped opportunities to realize savings for antidepressants with appropriate administrative mechanisms and incentives.

[The dilemma of court expertise--commentary on the SSRI-tapering verdict by the Saxonian social court]. / Fragwürdigkeit eines Gerichtsurteils zur Antidepressiva-verordnung bei Jugendlichen.

We comment on a Social Court verdict that sentenced a German health insurance carrier to pay for the tapering of fluoxetine in a case of adolescent depression but not to payment for ongoing SSRI treatment in view of their off-label status. Evidence presented to the competent court, including a statement by the German Association for Child and Adolescent Psychiatry (DGKJP), was inadequately interpreted or else misunderstood. The court abstained from substantiating its own competence, e.g. by means of an external expertise. Even though an earlier verdict by the Federal Social Court was taken into account, there were shortcomings with regard to its realisation. The physician in charge of such a case is confronted with therapeutical and ethical dilemmata, as well as with problems of liability, as the court-ordered discontinuation of pharmacological treatment could conceivably compromise the well-being of the patient. Due to the recent marketing authorisation by the EMEA for the use of fluoxetine in the treatment of depressed children above the age of eight years in Europe, the case may be settled. Yet the implications of juridical intrusions into medical practice and therapy regimes must still be addressed.

Effectiveness and cost-effectiveness of antidepressant treatment in primary health care: a six-month randomised study comparing fluoxetine to imipramine.

BACKGROUND: Over the past decade, studies of the effectiveness of pharmacological treatment for depression have often been based on research designs intended to measure efficacy, and for this reason the results are of limited generalizability. Research is needed comparing the clinical and economic outcomes of antidepressants in day-to-day clinical practice. METHODS: A six-month randomised prospective naturalistic study comparing fluoxetine to imipramine carried out in three primary care health centres. Outcome measures were the Montgomery Asberg Depression Rating Scale (MADRS), direct costs, indirect costs and total costs. Subjects were evaluated at the beginning of treatment and at one, three and six months thereafter. RESULTS: Of the 103 patients, 38.8% (n = 40) were diagnosed with major depressive disorder, 14.6% (n = 15) with dysthymic disorder, and 46.6% (n = 48) with depressive disorder not otherwise specified. Patients with major depressive disorder or dysthymic disorder achieved similar clinical improvement in both treatment groups (mean MADRS ratings decrease in major depressive disorder from baseline to 6 months of 18.3 for imipramine and 18.8 for fluoxetine). For patients with major depressive disorder and dysthymic disorder, the imipramine group had fewer treatment-associated costs (imipramine 469.66 Euro versus fluoxetine 1,585.93 Euro in major depressive disorder, p < 0.05; imipramine 175.39 Euro versus fluoxetine 2,929.36 Euro in dysthymic disorder, p < 0.05). The group with depressive disorder not otherwise specified did not experience statistically significant differences in clinical and costs outcomes between treatment groups. LIMITATIONS: Exclusion criteria, participating physicians may not represent GPs. CONCLUSIONS: In a primary care context, imipramine may represent a more cost-effective treatment option than fluoxetine for treating major depressive disorder or dysthymic disorder. There were no differences in cost-effectiveness in the treatment of depressive disorder not otherwise specified.

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.

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).

Duration of therapy and health care costs of fluoxetine, paroxetine, and sertraline in 6 health plans.

BACKGROUND: Previous studies comparing fluoxetine, paroxetine, and sertraline, the 3 most common selective serotonin reuptake inhibitors (SSRIs), in naturalistic settings have produced conflicting results. With this study, we provide new evidence as to the similarities and differences among these SSRI therapies with respect to the duration of use and health care costs. METHOD: Data from 6 health maintenance organizations were used to identify patients with new-onset major depression. number of days with filled prescriptions, and total health care and depression-related costs. The sample consisted of 1771 patients given initial prescriptions for sertraline (N = 386), fluoxetine (N = 840), or paroxetine (N = 545) in the period from July 1, 1994, to March 31, 1997. Analyses included Cox proportional hazards models (for duration of initial therapy) and ordinary least squares regression (for cost). RESULTS: Patients who initiated therapy with fluoxetine were more likely to have a later interruption of therapy than patients who initiated therapy with sertraline (p = .03) and paroxetine (p = .001). Total 1-year costs did not differ statistically between the treatment groups, but 1-year depression-related costs were significantly lower for patients who initiated therapy with sertraline or paroxetine than for those who initiated therapy with fluoxetine ($332 less for sertraline, 95% confidence interval [CI] = $125 to $562; $339 less for paroxetine, 95% CI = $144 to $416). LIMITATIONS: A limitation of this observational study, as well as of observational studies in general, is that unobserved characteristics of the patients may lead to biased estimates of the impact of treatment on adherence or cost, even with controls for observed characteristics. CONCLUSION: We found no significant differences in total health care costs among the 3 SSRIs, but noted significant differences in depression-related costs (the costs of fluoxetine are greater than those of sertraline and paroxetine). Importantly, there was no relationship between treatment interruption and increased health care or depression-related costs, in contrast to the findings of some, but not all, prior studies.

Cost-effectiveness of newer antidepressants compared with tricyclic antidepressants in managed care settings.

BACKGROUND: Our aim was to determine the cost-effectiveness of newer antidepressants compared with tricyclic antidepressants in managed care organization settings. METHOD: We employed cost-utility analysis based on a clinical decision analysis model derived from published medical literature and physician judgment. The model, which represents ideal primary care practice, compares treatment with nefazodone to treatment with either imipramine or fluoxetine or to a step approach involving initial treatment with imipramine followed by nefazodone for treatment failures. The outcome measures were lifetime medical costs, quality-adjusted life years (QALYs), and costs per QALY gained. RESULTS: The base case analysis found that nefazodone treatment had $16,669 in medical costs, compared with $15,348 for imipramine, $16,061 for the imipramine step approach, and $16,998 for fluoxetine. QALYs were greatest for nefazodone (14.64), compared with 14.32 for imipramine, 14.40 for the step approach, and 14.58 for fluoxetine. The cost-effectiveness ratio comparing nefazodone with imipramine was $4065 per QALY gained. The cost-effectiveness ratio comparing nefazodone with the step approach was $2555 per QALY gained. There were only minor differences in costs and outcomes between nefazodone and fluoxetine, with nefazodone resulting in $329 fewer costs and 0.06 more QALYs. The cost-effectiveness ratios comparing fluoxetine with imipramine and with the step approach were $6346 per QALY gained and $5206 per QALY gained, respectively. In the sensitivity analyses, the cost-effectiveness ratios comparing nefazodone and imipramine ranged from $2572 to $5841 per QALY gained. The model was most sensitive to assumptions about treatment compliance rates. CONCLUSION: The findings suggest that nefazodone is a cost- effective treatment compared with imipramine or fluoxetine treatment for major depression. Fluoxetine is cost-effective compared with imipramine treatment, but is estimated to have slightly more medical costs and less effectiveness compared with nefazodone. The basic findings and conclusions do not change even after modifying key model parameters.

The effect of selective serotonin reuptake inhibitor treatment of panic disorder on emergency room and laboratory resource utilization.

BACKGROUND: While it has been well documented that patients with untreated panic disorder frequently utilize emergency room (ER) and laboratory services, no published data evaluate whether selective serotonin reuptake inhibitor (SSRI) treatment of patients with panic disorder is associated with decreased use of these services in the managed care organization setting. METHOD: A medical and pharmacy claims database representing individuals from several managed care organizations was used to analyze ER and laboratory resource utilization and cost for 120 patients with panic disorder (ICD-9-CM criteria) who received SSRI treatment. RESULTS: SSRI treatment was associated with a reduction in the mean number of ER and laboratory visits and costs in the 6-month period following therapy initiation compared with the 6-month period prior to therapy initiation (sertraline: visits, -79.5%; costs, -85.2%; p < .05; fluoxetine: visits, -25.0%; costs, -69.5%; p = NS; and paroxetine: visits, -8.6%; costs, -30.8%; p = NS). CONCLUSION: The results of the current study suggest that appropriate treatment of panic disorder may decrease unnecessary resource utilization for the medical symptoms associated with panic disorder.

Fluoxetine tenth anniversary update: the progress continues.

This tenth anniversary review/update of fluoxetine concentrates on the past 5 years of its clinical application. The mechanism of action of fluoxetine; its metabolism; its efficacy in patients with various diagnostic subgroups of depression, patients with coincident medical disease, children and adolescents with depression, patients with eating disorders, and patients with obsessive-compulsive disorder (OCD); its long-term (maintenance) efficacy; its side effects and toxicity; and pharmacoeconomic considerations are reviewed. Pharmacotherapy is currently the only proven method for treating major depressive disorder that is applicable to all levels of severity of major depressive illness. Since its introduction 10 years ago, fluoxetine has been available to psychiatrists, primary care physicians, and other nonpsychiatric physicians as full-dose effective pharmacotherapy for patients with depression. Fluoxetine has been widely prescribed by physicians knowledgeable in pharmacology and in the treatment of depression because of its proven efficacy (ie, equal to that of tricyclic antidepressants [TCAs]), its ease of administration (with full therapeutic dosing usually starting from day 1), its generally benign side-effect profile, its remarkable safety in over-dose, and its proven effectiveness in the most common depressed patient population--anxious, agitated, depressed patients--as well as in patients with various subtypes and severities of depression. In more recent years it has also proved effective in the treatment of bulimia, an entity for which only limited or inadequate treatment options had been previously available. In OCD, fluoxetine, with its more acceptable side-effect profile and greater ease of dosing, presents a favorable alternative to previous drug therapy and is useful in treating both obsessions and compulsions. Fluoxetine is currently recognized among clinicians as efficacious in treating anxiety disorders and is being used successfully in special depressed populations such as patients with medical comorbidity, elderly patients, adolescents, and children. Rapid discontinuation or missed doses of short-half-life selective serotonin reuptake inhibitors, TCAs, and heterocyclic antidepressants are associated with withdrawal symptoms of a somatic and psychological nature, which cannot only be disruptive, but can also be suggestive of relapse or recurrence of depression. In striking contrast to these short-half-life antidepressants, fluoxetine is rarely associated with such sequelae on sudden discontinuation or missed doses. This preventive effect against withdrawal symptoms on discontinuation of fluoxetine is attributed to the unique extended half-life of this antidepressant. Current studies show that the overall increased effectiveness of fluoxetine in treating depression compensates for its higher cost, compared with older drugs, by reducing the need for physician contact because of increased compliance and less need of titration, and by reducing premature patient discontinuation, thereby yielding fewer relapses, less recurrence, and less reutilization of mental health services.