Fluoxetine In Major Depressive Disorder Research Articles

Predictors of response to pharmacotherapy in children and adolescents with psychiatric disorders: A combined post hoc analysis of four clinical trial data.

The prediction of response to pharmacotherapy has not been sufficiently explored in children and adolescents with psychiatric disorders, which was addressed in this study. Data from four double-blind, placebo-controlled studies (sertraline and fluvoxamine for anxiety disorders, risperidone for autistic disorder, and fluoxetine for major depressive disorder) in children and adolescents funded by the National Institute of Mental Health were used. The response was defined as a score of 1 or 2 on the Clinical Global Impression-Global Improvement (CGI-I) at the endpoint. Logistic regression analysis was performed to evaluate associations between response status and the following variables: sex, diagnosis, treatment allocation, and CGI-Severity of Illness (CGI-S) score at baseline. Moreover, the presence of early improvement (a score of ≤3 in the CGI-I) at Week 1 was added to the independent variables in an additional binary logistic regression analysis, using the data from two studies. A total of 599 patients were included in the analysis. In the binary logistic regression analysis, active drug use (odds ratio [OR]=8.64, P < 0.001) and female sex (OR=1.89, P=0.002) were significantly associated with treatment response. In the second binary logistic regression, the presence of early improvement in the CGI-I (OR=3.47, P=0.009), as well as active drug use (OR=15.05, P < 0.001) and female sex (OR=2.87, P=0.016), were associated with subsequent responses. Allocation to active drugs, female sex, and early improvement may predict treatment response to pharmacotherapy among children and adolescents with psychiatric disorders.

Directly Observed Weekly Fluoxetine for Major Depressive Disorder Among Hemodialysis Patients: A Single-Arm Feasibility Trial

Rationale & ObjectiveMajor depressive disorder (MDD) is common among hemodialysis patients, but treatment can add to their pill burden and may be limited by nonadherence. We sought to investigate the value of directly observed, once-weekly fluoxetine dosing in MDD.Study DesignFeasibility trial of adult hemodialysis patients with untreated MDD. The diagnosis of MDD was determined using the Mini International Neuropsychiatric Interview.Setting & Participants16 patients at 15 hemodialysis facilities in Northeast Ohio.InterventionPatients were initially prescribed 20 mg of fluoxetine once daily for 2 weeks to assess their tolerance. The patients took this daily fluoxetine unobserved at home. They were then transitioned to 90 mg of fluoxetine once weekly for 10 weeks. The patients took this weekly fluoxetine during hemodialysis treatment and were observed by the study staff. The dose was increased to 180 mg once weekly among patients with an inadequate response based on the judgment of the prescribing clinician.OutcomesMini International Neuropsychiatric Interview diagnosis of MDD at the end of the trial and changes in the Patient Health Questionnaire (PHQ-9) scores over 12 weeks.ResultsOne patient withdrew from active treatment after 2 daily doses of 20 mg of fluoxetine because of side effects of stomach cramping, vomiting, dizziness, and lightheadedness but completed the baseline and final assessments. The remaining 15 patients received all scheduled weekly fluoxetine doses during the trial. At 12 weeks, 14 of 16 patients (87.5%) no longer met the criteria for MDD (P < 0.001). Among all participants, the mean PHQ-9 scores decreased from 11.3 to 6.6 (P = 0.002).LimitationsSmall sample size, modestly elevated baseline PHQ-9 scores, no comparison group, and short treatment duration.ConclusionsDirectly observed, once-weekly fluoxetine may be an effective and well-tolerated treatment option for hemodialysis patients. Future research should investigate longer-term health outcomes of weekly fluoxetine in this population and explore the feasibility of implementing this depression treatment model in routine clinical practice.Trial RegistrationThis trial was registered at clinicaltrials.gov as NCT03390933.

Intravenous administration of adenosine triphosphate and phosphocreatine combined with fluoxetine in major depressive disorder: protocol for a randomized, double-blind, placebo-controlled pilot study

BackgroundMajor depressive disorder (MDD) is a common psychiatric disorder. With systematic antidepressant treatment, 50–75% of patients have a treatment response but require 4–6 weeks to have their symptoms alleviated. Therefore, researchers anticipate the development of novel fast-acting antidepressants. Previous studies have revealed that the decrease of bio-energetic metabolism may contribute to the occurrence of depression, while our team has found adenosine triphosphate (ATP) and phosphocreatine (PCr) to be fast-acting antidepressants in the depressed-animal model. ATP and PCr have already been widely prescribed clinically as energy supplements for cells. This will be the first clinical attempt of the intravenous administration of ATP and PCr combined with orally administered fluoxetine in MDD.MethodsThis is a single-center, randomized, double-blind, placebo-controlled pilot study. A total of 42 patients will be divided randomly into three groups. Patients will receive an intravenous administration of ATP or PCr or saline twice daily combined with orally administered fluoxetine (20 mg/day) for the first 2 weeks and fluoxetine monotherapy for the following 4 weeks. Follow-up assessment will be completed at week 10. Feasibility outcomes will include percentages of patient eligibility, intention to use medication, willingness to participate, drug adherence, completion of the scheduled assessment, retention, drop-out, etc. Physical examination results, Side Effect Rating Scale, adverse events, results from blood tests, electroencephalogram, and electrocardiograph will be recorded for safety evaluation of the augmentation therapy. The trends of efficacy will be evaluated by the reduction rate of the Hamilton Depression Rating Scale, the mean change of the Clinical Global Impression Scale, and the Patients Health Questionaire-9 items.DiscussionIn our study, ATP and PCr will be given by intravenous infusion. Thus patients will be hospitalized for the initial 2 weeks for safety concern. Hospitalization will be an impact factor for the recruitment, participation, drop-out, efficacy, results, etc. The evaluation of our feasibility outcomes, study setting, safety of augmentation therapy and possible efficacy trends among groups, will facilitate a full-scale trial design and sample size calculation.Trial registrationNCT03138681. Registered on 3 May 2017. First patient: 4 May 2017.

6-Sulfatoxymelatonin predicts treatment response to fluoxetine in major depressive disorder

Background:To date, no biomarker has been able to predict antidepressant response at an early blockade of norepinephrine or serotonin uptake. The transient nocturnal increase in plasma melatonin levels is upregulated by blocking these uptakes. The aim of this study was to test whether fluoxetine increase in urinary 6-sulfatoxymelatonin (aMT6s) is an indicator of serotonin uptake blockade.Methods:A total of 20 women (35–45 years of age) recruited from the community had a diagnosis of major depressive disorder confirmed by the Structured Clinical Interview for DSM-IV. Depressive symptoms were evaluated by the Beck Depression Inventory (BDI). Participants were instructed to take 20 mg of fluoxetine every morning. Every 4 weeks, the dose could be increased by 20 mg until symptom remission. The concentration of aMT6s was evaluated in overnight urine samples collected 1 day before and 1 day after the first fluoxetine dose.Results:An increase in aMT6s correlated to a decrease in BDI score evaluated on day 45 (ρ = −0.67, p = 0.024) was observed.Conclusions:Nocturnal increase in urinary aMT6s after the first day of medication use links the early mechanism of action of fluoxetine to its clinical output 45 days later. Thus, the relationship between urinary aMT6s excretion 1 day before/1 day after is a biomarker for predicting clinical output earlier, reducing illness burden and health care costs.

Glucocorticoid Receptor Genetic Variants and Response to Fluoxetine in Major Depressive Disorder.

Hyperactivity of the hypothalamic pituitary adrenocortical (HPA) axis is one of the main clinical findings in depression. The HPA axis is interrelated with glucocorticoid signaling via glucocorticoid receptors (GCRs). Thus, functional genetic variants on GCRs might influence therapeutic outcomes in depression. The aim of the present study was to investigate the association between three functional polymorphisms (rs41423247, rs6195, and rs6189/rs6190) on GCR and response to fluoxetine in a group of depressed patients. One hundred newly diagnosed patients completed 6 weeks of fluoxetine treatment. Response to treatment was defined as a 50% decrease in the Hamilton Depression Rating Scale score. Variants of rs41423247, rs6195, and rs6189/rs6190 polymorphisms were determined in extracted DNAs using PCR-RFLP method. Regarding rs41423247 polymorphism, carriers of the CG and GG genotype responded significantly better to fluoxetine compared with CC carriers (p=0.008, OR=3.3, 95% CI=1.35-8.07). Moreover, the G allele of rs41423247 polymorphism was strongly associated with response to fluoxetine (p=0.032, OR=2.2, 95% CI=1.09-4.44). There was no significant association between different genotypes and alleles of rs6195, rs6189/rs6190 variants, and response to fluoxetine (p=0.213 and 0.99, respectively). In conclusion, rs41423247 polymorphism might be a predictor for better response to fluoxetine. These findings support the idea that some variants of the GCR might contribute to interindividual variability of response to antidepressants.

P.4.035 Clinical improvement and plasmatic concentrations of fluoxetine in major depressive disorder (MDD), obsessive–compulsive disorder (OCD) and generalised anxiety disorder (GAD)

P.4.035 Clinical improvement and plasmatic concentrations of fluoxetine in major depressive disorder (MDD), obsessive–compulsive disorder (OCD) and generalised anxiety disorder (GAD)

The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder

Introduction Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4 weeks of treatment in a sample of patient with MDD. Methods 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. Results Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. Limitations The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. Conclusions Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment.

A randomized, double-blind, and placebo-controlled trial of quetiapine augmentation of fluoxetine in major depressive disorder

The objective of this study was to investigate whether quetiapine, when compared with placebo, can speed the onset of action and improve the quality of response to fluoxetine treatment in patients suffering from major depressive disorder. A total of 114 patients with major depressive disorder were enrolled in an 8-week treatment study. Patients were initiated on a course of fluoxetine treatment and randomized to quetiapine or placebo. Quetiapine was flexibly dosed starting at 25 mg to a maximum of 100 mg daily. Mixed-effects regression showed that quetiapine plus fluoxetine did not achieve 50% reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale, Clinical Global Improvement (CGI)-Severity, and CGI-Improvement scores sooner than the fluoxetine plus placebo group; however both groups improved in all scores over time. Mixed-effects linear regression of insomnia scores showed that the quetiapine plus fluoxetine group improved significantly more rapidly compared with the fluoxetine plus placebo group. The study indicates that quetiapine plus fluoxetine did not achieve a reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale or CGI scores from baseline sooner than the fluoxetine plus placebo group. The combination of quetiapine and fluoxetine, however, improved sleep over fluoxetine alone over the first few weeks of treatment.

Psychic and somatic anxiety symptoms as predictors of response to fluoxetine in major depressive disorder

The purpose of this study was to examine whether the presence/severity of psychic and somatic anxiety symptoms predicted clinical response following a 12-week, flexible-dose (20–60 mg daily), open-label trial of fluoxetine for major depressive disorder (MDD). The presence and severity of psychic and somatic anxiety symptoms were assessed with the use of select subscales of the Symptom Questionnaire and the Hopkins Symptom Checklist among 518 outpatients with MDD. With the use of separate logistic regressions, we tested for the relationship between clinical response, baseline Hamilton Depression Rating Scale (HAM-D-17) scores, and subscale scores at baseline entered separately as independent variables Overall completion, response and remission rates for the trial were 64.2%, 55.4%, and 48.9%, respectively. All subscale scores selected for this analysis significantly predicted treatment response to fluoxetine. The presence/severity of psychic and somatic anxiety symptoms of MDD at baseline predicted an increased likelihood of non-response to fluoxetine in MDD. Studies examining whether specific treatment strategies are more effective than the selective serotonin reuptake inhibitors for MDD patients with high levels of co-morbid psychic and somatic anxiety symptoms are warranted.

Early Symptomatic Worsening During Treatment With Fluoxetine in Major Depressive Disorder

A subset of patients experience worsening of depressed mood after beginning antidepressant treatment, which could represent the natural history of the illness or a treatment-related effect. While patterns of response have been examined as possible predictors of outcome, the clinical correlates and implications of early worsening per se have not been investigated. In a post hoc analysis, we studied the clinical correlates of early worsening in a large sample of outpatients (N = 694) diagnosed with a DSM-III-R-defined major depressive episode and treated with fluoxetine (20 mg/day) for up to 12 weeks. We defined early worsening as an increase of at least 5 points on a modified 17-item Hamilton Rating Scale for Depression (mHAM-D, including reverse vegetative symptoms) compared to the previous visit, and occurring during the acute phase of treatment. The primary analysis compared remission and response at week 12 between those patients with and without worsening. In our sample, 211 patients (30.4%) experienced early worsening of depression. An increase in mHAM-D score at week 2, 3, 4, or 6 was associated with a significantly lower probability of remission and response at both week 8 and week 12, while no significant difference was observed in study discontinuation. Baseline features, including gender, age, mHAM-D score at entry, number of previous depressive episodes, and duration of illness were not associated with the development of early worsening during fluoxetine treatment. Early clinical worsening is common and associated with a decreased likelihood of achieving remission.

Hopelessness as a Predictor of Non-Response to Fluoxetine in Major Depressive Disorder

The purpose of this study was to study hopelessness as a predictor of response to fluoxetine in outpatients with Major Depressive Disorder (MDD). The degree of hopelessness was assessed during the baseline visit with the use of the Beck Hopelessness Scale (BHS) in 312 patients with MDD (56.1% women; 39.8 +/- 10.3 years of age) who entered an 8-week, 20-mg, fixed-dose, open trial of fluoxetine. With the use of a logistic regression we tested whether BHS scores at baseline predicted clinical response, controlling for the severity of depression as reflected by the total score on the 17-item Hamilton Depression Rating Scale (HAM-D-17). With the use of a multiple regression we also tested whether BHS scores at baseline predicted HAM-D-17 scores at endpoint, controlling for HAM-D-17 scores at baseline. After controlling for depression severity at baseline, a greater degree of hopelessness was found to significantly increase the risk of non-response to fluoxetine (p = 0.0413), as well as the risk of greater endpoint depression severity (p = 0.0305). Hopelessness appeared to be associated with poorer response to treatment with fluoxetine in MDD, and this was independent of depression severity. Similar studies involving treatment with higher doses of fluoxetine and for greater duration as well as a placebo comparator arm are needed to further explore the relationship between hopelessness, placebo response and drug response.

Long-Term Weight Gain in Patients Treated With Open-Label Olanzapine in Combination With Fluoxetine for Major Depressive Disorder

Patients with major depressive disorder (MDD) treated with olanzapine in combination with fluoxetine (OFC) demonstrate robust improvement in their depressive symptoms. Treatment with olanzapine may impact a patient's weight; thus, long-term weight gain and potential predictors (e.g., age and gender) and correlates (e.g., cholesterol and glucose levels) of weight gain were investigated in OFC-treated patients with MDD. Outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria for MDD were included (N = 549) in the current analyses of this 76-week, open-label study (February 2000 to July 2002). Maximum, endpoint, and potentially clinically significant (PCS; > or = 7% increase from baseline) weight gain; time to PCS weight gain; and predictors and correlates of weight change were assessed. Patients were treated once daily with oral olanzapine (6, 12, or 18 mg) plus fluoxetine (25, 50, or 75 mg) capsules. Statistical significance for all tests was based upon p < or = .05. Mean baseline-to-endpoint weight change was 5.6 +/- 6.6 kg (12.3 +/- 14.6 lb). Weight gain plateaued by 52 weeks. Fifty-six percent of patients met criteria for PCS weight gain by 76 weeks, and the median time to PCS weight gain was 16 weeks. Low baseline body mass index (BMI), female gender, younger age, and increased fluoxetine dose were predictors of weight gain; olanzapine dose was not. Patients with early (< or = 6 weeks) rapid PCS weight gain were 4.6 times more likely to gain substantial (> or = 15%) weight long-term (weeks 7-76). Changes to endpoint in total cholesterol and systolic blood pressure values were positively correlated with weight change. Long-term (76 weeks) OFC treatment may lead to a large percentage (56%) of patients meeting criteria for PCS weight gain (> or = 7%). The risk of weight gain may be significantly increased for OFC-treated patients who have a low BMI or who are female, younger, or taking high-dose fluoxetine. It is important that prescribers balance the risk of weight gain with the benefit of treatment for individual patients with depression.

Controlled Double-Blind Trial of Phenytoin vs. Fluoxetine in Major Depressive Disorder

Phenytoin was the first non-sedative anticonvulsant introduced and is still the anticonvulsant most widely used worldwide in neurology. Given the efficacy of the anticonvulsant lamotrigine in the depressed phase of bipolar disorder, a critical theoretical question is whether other anticonvulsants used in treating bipolar disorder might be similarly effective. We therefore undertook a controlled trial of phenytoin versus fluoxetine in major depressive disorder. Data were collected from July 2001 to July 2003. Thirty-three subjects entered the study. All patients met DSM-IV criteria for major depressive disorder and scored a minimum of 18 on the 24-item Hamilton Rating Scale for Depression (HAM-D) at baseline. After a 3-day washout of any previous medications, patients were randomly assigned to fluoxetine or phenytoin in identical capsules. Each capsule contained phenytoin 100 mg or fluoxetine 7 mg plus cornstarch. Patients started with 1 tablet daily and increased every other day until they were taking 1 tablet 3 times daily with meals. Blood phenytoin levels were taken after 1 week, 3 weeks, and 6 weeks, and dosage was adjusted to achieve blood levels of 10 to 20 microg/mL, to a maximum dose of 4 capsules per day or a minimum dose of 2 capsules per day. Fluoxetine patients were assigned dummy blood phenytoin levels by the control psychiatrist such that the treating physician would raise the number of capsules to at least 3 per day (20 mg of fluoxetine). Thirty-three patients entered the study, and 28 (N = 14 in each treatment group) completed at least 3 weeks and were included in the data analysis. Patients who dropped out after week 3 (3 patients) were included in the study as last value carried forward. There was no difference between treatment groups in overall rate of response or speed of response. The absence of a placebo arm in our study allows for the possibility that neither treatment was more effective than placebo. However, the exclusion of past fluoxetine nonresponders and the minimum HAM-D score at baseline of 18 make this possibility unlikely.

The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine

The objective of the present study was to examine the relationship between serum folate, vitamin B12, and homocysteine levels and the timing of clinical improvement to fluoxetine in major depressive disorder (MDD) patients. A total of 110 outpatients with MDD who responded to an 8-wk trial of fluoxetine had serum folate, B12, and homocysteine measurements at baseline (prior to fluoxetine initiation). Onset of clinical improvement was defined as a 30% decrease in Hamilton Depression Scale scores that led to a 50% decrease by week 8. Patients with low folate levels (<or=2.5 ng/ml) were more likely to experience a later onset of clinical improvement than eufolatemic patients ( p =0.0028). B12 and homocysteine level status did not predict time to clinical improvement ( p >0.05). In conclusion, low serum folate levels were found to be associated with a delayed onset of clinical improvement during treatment with fluoxetine in MDD by, on average, 1.5 wk.

Safety of Subchronic Treatment with Fluoxetine for Major Depressive Disorder in Children and Adolescents

Safety of Subchronic Treatment with Fluoxetine for Major Depressive Disorder in Children and Adolescents

Safety of Subchronic Treatment with Fluoxetine for Major Depressive Disorder in Children and Adolescents

The aim of this study was to assess the safety of subchronic fluoxetine treatment for major depressive disorder (MDD) in children and adolescents. Patients received up to 19 weeks of treatment with fluoxetine, 10 mg-60 mg daily. Safety was evaluated through the reporting of concomitant medications, vital signs, routine laboratory testing, electrocardiograms (ECGs), and adverse event data. Ninety-six patients, aged 9-17 years, completed 19 weeks of treatment with fluoxetine (n = 49) or placebo (n = 47). There were statistically significant differences between the fluoxetine and placebo groups in mean change from baseline for alkaline phosphatase and total cholesterol levels (p < 0.001, and p < 0.014, respectively), but there were no statistically significant differences between the incidence of abnormal laboratory values for these 2 analytes. Fluoxetine-treated patients gained statistically significantly less height (fluoxetine: 1.0 cm +/- 2.4; placebo: 2.1 cm +/- 2.6; p = 0.004) and weight (fluoxetine: 1.2 kg +/- 2.7; placebo: 2.3 kg +/- 2.6; p = 0.008) than placebo-treated patients during the 19 weeks of treatment. There was no difference in the rate of reported suicide-related events between fluoxetine and placebo. Fluoxetine was found to be safe and well tolerated in this study of children and adolescents with MDD. Clarification and determination of the clinical significance of the growth-rate reduction seen during fluoxetine treatment requires further investigation. During treatment with fluoxetine, the growth of child and adolescent patients should be monitored.

Association Study of Serotonin 1B Receptor (A-161T) Genetic Polymorphism and Suicidal Behaviors and Response to Fluoxetine in Major Depressive Disorder

Serotonin 1B receptors (5-HT1B) are autoreceptors involved in the local inhibitory control of serotonin release, and have been suggested to play a role in the pathogenesis of major depressive disorder (MDD) and the antidepressant effects of the selective serotonin reuptake inhibitors in patients. We genotyped the 5-HT1B A-161T polymorphism in 160 patients with MDD and 160 normal controls. We then tested the hypothesis that the allelic variant, A-161T, of the 5-HT1B gene confers susceptibility to MDD or is associated with suicide attempt. We also examined the association of this polymorphism with therapeutic response in 116 of the MDD patients who received fluoxetine treatment for 4 weeks. No significant difference was found in the A-161T genetic polymorphism between MDD patients and controls. The genotype distribution between patients with and without suicide attempt, or between fluoxetine treatment responders and nonresponders were also similar. Our findings suggest that 5-HT1B A-161T genetic polymorphism does not play a major role in the susceptibility to MDD, nor is it related to suicidal attempt or the therapeutic response to fluoxetine in MDD.

Treatment-Related Adverse Events and Outcome in a Clinical Trial of Fluoxetine for Major Depressive Disorder

Treatment-Related Adverse Events and Outcome in a Clinical Trial of Fluoxetine for Major Depressive Disorder

Adverse events and treatment discontinuations in clinical trials of fluoxetine in major depressive disorder: An updated meta-analysis

Background: A 1993 meta-analysis of US Investigational New Drug clinical trials of fluoxetine reinforced this agent's more favorable adverse-event profile compared with tricyclic antidepressants (TCAs). Objectives: The present meta-analysis sought to provide a reanalysis of updated adverse-event and discontinuation data for fluoxetine 20 to 80 mg/d compared with TCAs and placebo in the treatment of major depressive disorder (MDD) in adults. A subanalysis to assess the safety profile of the most commonly used effective dose of fluoxetine in MDD (20 mg) was also conducted. Methods: Data were obtained from 25 double-blind clinical trials involving 4016 patients with MDD randomized to treatment with fluoxetine 20 to 80 mg/d, TCAs, or placebo. The subanalysis included data from 6 trials involving 1258 patients treated with fixed 20-mg doses of fluoxetine or placebo. Spontaneously reported treatment-emergent adverse events, reasons for discontinuation, and events leading to discontinuation were compared between groups. Results: The age of the 4016 randomized patients ranged from 12 to 90 years, with a mean age of 46 years. Most patients were white (92%), and 62% were female. The age of the 1258 patients in the 20-mg fixed-dose population ranged from 18 to 90 years, with a mean age of 54 years; as in the total population, most of these patients were white (92%), and 57% were female. The adverse-event profiles of fluoxetine and TCAs in these trials were consistent with the typical profiles of selective serotonin reuptake inhibitors and TCAs. At a dose of 20 mg/d, fluoxetine-treated patients had a discontinuation rate due to adverse events that was not statistically significantly different from that in placebo recipients. Discontinuation rates due to lack of efficacy were not significantly different between fluoxetine and TCAs. However, significantly more TCA-treated patients discontinued therapy because of adverse events and significantly fewer completed treatment compared with fluoxetine-treated patients (both, P < 0.001). The most common events (≥2%) leading to discontinuation were asthenia, dizziness, insomnia, nausea, nervousness, somnolence, and tremor in fluoxetine-treated patients and abnormal vision, agitation, constipation, dizzines, dry mouth, headache, nausea, nervousness, rash, somnolence, sweating, and tremor in TCA-treated patients. Conclusions: Data from this large series of clinical trials confirm that fluoxetine is well tolerated in the acute treatment of MDD in adults, especially at a dosage of 20 mg/d, and is better tolerated than the recommended doses of TCAs.

Evaluation of an Information Exchange Program for Primary Care Patients with Depression

A challenge in treating depression in the primary care setting is to improve its detection and maximize benefits associated with available therapies. This multicenter, prospective study was undertaken to evaluate the impact of an information exchange program on patients treated with fluoxetine for major depressive disorder (MDD) diagnosed and managed in the primary care setting. The five-item Mental Health scale from the SF-36 Health Survey was used to screen for major depressive disorder (MDD). Patients with MDD based on Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSMIV) were randomly assigned at the physician level to an intervention group (fluoxetine therapy plus the ProPartnersTM [Hastings Health Care Group, Pennington, NJ] program) or a control group (fluoxetine therapy and usual care). Enrolled patients completed surveys at baseline, 3, 6, and 12 months. The surveys measured disease severity, health-related quality of life (QOL), and satisfaction with care. Of the 18,728 patients screened, 2,820 (15.1%) screened positively (Mental Health Inventory [MHI] score ≤ 52). Of those who screened positive, 68% met DSM IV criteria for MDD. Two hundred twelve patients met all eligibility criteria and were enrolled in the study (131 intervention, 81 control). Baseline QOL scores were significantly lower than U.S. population norms confirming the substantial QOL burden associated with MDD. Over a median follow-up period of 5.8 months, QOL in physical and mental health domains improved in both groups, confirming the known benefits of antidepressant therapy. The intervention patients exhibited better disease severity scores at end point than the control patients (p < 0.05) as measured by the Beck Depression Inventory. A substantial number of patients seeking medical care in the primary care setting experience depression symptoms. Strategies that facilitate communication between patients with MDD and their primary care providers may improve recognition, treatment, and overall patient outcomes associated with MDD. This study provided useful information on the potential benefits of patient-oriented information exchange programs in the primary care setting.