Fluoxetine-treated Patients Research Articles

Recovery in Stroke Patients Treated With Fluoxetine Versus Placebo: A Pooled Analysis of 7165 Patients.

Stroke is a major cause of disability and death. Stroke recovery outcomes range from functional impairment to disability. This study was designed to compare the recovery results of stroke patients treated with fluoxetine to those treated with placebo. Seventeen randomized clinical trials were identified by searching PubMed, Cochrane, Scopus, and Web of Science until June 2021. Fluoxetine enhances the National Institutes of Health Stroke Scale (NIHSS) score [mean difference (MD)=-0.67, 95% confidence interval (CI) (-1.19 to -0.15)] and the Fugl-Meyer Motor Scale (FMMS) score [MD=17.36, 95% CI (12.12-22.61)] at the 3-month follow up. However, the NIHSS score showed no significant difference between the 2 groups at 2 weeks [MD=-0.32, 95% CI (-0.72 to 0.07)] or at 6 months [MD=-0.17, 95% CI (-0.47 to 0.14)]. Fluoxetine-treated and placebo-treated patients had the same overall impact on FMMS scores at 1 month (P=0.41). Barthel index showed no significant difference between the 2 arms at 3 months (P=0.21) or 6 months (P=0.68). Fluoxetine-treated patients were at a higher risk of broken bone [risk ratios (RR)=2.30, 95% CI (1.59-3.32)] and hyponatremia [RR=2.12, 95% CI (1.19-3.76)], and at lower risk of new depression [RR=0.72, 95% CI (0.61-0.84)] in comparison with placebo. The efficacy of fluoxetine on the NIHSS and FMMS is likely to take time to emerge and is expected to be transient. The Barthel index score did not differ between the fluoxetine and placebo groups. The use of fluoxetine increased the incidence of hyponatremia and bone fractures while decreasing the risk of new-onset depression.

The Safety and Efficacy of Fluoxetine for the Treatment of Refractory Primary Monosymptomatic Nocturnal Enuresis in Children: A Randomized Placebo-Controlled Trial.

We investigated the efficacy and safety of fluoxetine, a selective serotonin reuptake inhibitor, for treating refractory primary monosymptomatic nocturnal enuresis in children. Children 8-18 years old with severe primary monosymptomatic nocturnal enuresis unresponsive to alarm therapy, desmopressin, and anticholinergics were screened for eligibility. After excluding children with daytime urinary symptoms, constipation, underlying urological, neuropsychiatric, endocrinological, or cardiac conditions, patients were randomly and equally assigned to 10 mg fluoxetine once daily or placebo for 12 weeks. The primary outcome was treatment response according to the International Children's Continence Society terminology. Treatment-related adverse effects and nighttime arousal were secondary outcomes. A total of 150 children were enrolled, of whom 110 (56 in fluoxetine group and 54 in placebo group) with a mean age of 11.8 (SD 2.46) years were finally analyzed. After 4 weeks, 7.1% and 66.1% of the fluoxetine group achieved complete response and partial response (defined as 50%-99% reduction of the number of wet nights), respectively, versus 0% and 16.7% of the placebo group (P < .001). At 12 weeks, complete and partial responses were achieved in 10.7% and 21.4% of the fluoxetine group, respectively (vs 0% and 14.8% of the placebo group, P = .023). Fluoxetine-treated patients had fewer wet nights (4.7 [SD 4.2] fortnightly vs 9.7 [SD 3.5] at 4 weeks, P < .001; 5.7 [SD 4.4] vs 9.9 [SD 3.4] at 8 weeks, P < .001; 7.5 [SD 4.6] vs 9.9 [SD 3.4] at 12 weeks, P = .003). Fluoxetine was associated with improved nighttime arousal (P = .017), and minor and rapidly reversible adverse effects in 5 (8.9%) patients. Fluoxetine is safe treatment for refractory primary monosymptomatic nocturnal enuresis in children with good initial response that declines at 12 weeks.

Electroconvulsive Therapy Versus Fluoxetine in Suicidal Resolution for Patients With Major Depressive Disorder.

Resolution of suicidal ideation for patients with major depressive disorder is an important public health challenge. We aimed to determine whether electroconvulsive therapy (ECT) or fluoxetine was more efficacious in resolving suicidal ideation and achieving long-term protective effect against suicidality. The data used in this study were drawn from 2 open-label trials for major depressive disorder patients receiving ECT or fluoxetine for acute treatment, together with continuation medication in the 12-week follow-up. We compared the effects of ECT and fluoxetine on suicidal ideation as scored by the suicide item on the 17-item Hamilton Rating Scale for Depression. The differences between these 2 groups in time to resolution of suicidal ideation (suicide item = 0) in the acute treatment period, and time to relapse of suicidal ideation (suicide item score ≥1 or rehospitalization for suicidality) in the follow-up period were analyzed. Electroconvulsive therapy-treated patients (n = 111) had significantly shorter time to resolution of suicidal ideation than fluoxetine-treated patients (n = 114) during acute treatment. However, there was no statistically significant difference in time to relapse of suicidal ideation between 2 groups in the 12-week follow-up period. Electroconvulsive therapy was superior to fluoxetine in resolving suicidal ideation during acute treatment. Therefore, ECT should be an early consideration for suicidal patients. Electroconvulsive therapy and fluoxetine were equally effective in preventing recurrence of suicidal ideation in the 12-week follow-up period. Routine suicide risk assessments from hospital care to outpatient care are required to identify any signs of suicidal relapse.

1901. Safety, Tolerability, and Efficacy of Fluoxetine as an Antiviral for Enterovirus D68 Associated Acute Flaccid Myelitis: A Retrospective Multicenter Cohort Study

BackgroundMost patients with enterovirus (EV) D68-associated acute flaccid myelitis (AFM) have long-term disability. No effective therapies have been identified. Fluoxetine is the only FDA-approved medication with in vitro antiviral activity against EV-D68. This study retrospectively analyzed the safety, tolerability, and efficacy of fluoxetine for EV-D68-associated AFM.MethodsA multicenter cohort study of US children with AFM in 2015–2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls with AFM. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was summative limb strength score (SLSS; sum of Medical Research Council strength in all four limbs).Results56 patients with AFM from 12 centers met study criteria (Figure 1). Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effects were similar to controls (P = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs. 14.3%, P = 0.001). Fluoxetine-treated patients had similar strength on initial examination compared with untreated controls (mean SLSS 12.9 vs. 14.3, P = 0.313), but more severe paralysis at nadir (mean SLSS 9.25 vs. 12.82, P = 0.023) and latest follow-up (mean SLSS 12.5 vs. 16.4, P = 0.005) (Figure 2). In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% CI: −1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI: +0.7 to +4.4) in controls (P = 0.015). ConclusionFluoxetine was safely administered and relatively well-tolerated. Patients with AFM treated with fluoxetine were more likely to have EV-D68-associated disease and had more severe paralysis at nadir and poorer long-term outcomes. These data do not suggest a positive efficacy signal for fluoxetine as a potential antiviral therapy for AFM.Disclosures All authors: No reported disclosures.

Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis.

To determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68-associated acute flaccid myelitis (AFM). A multicenter cohort study of US patients with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was change in summative limb strength score (SLSS; sum of Medical Research Council strength in all 4 limbs, ranging from 20 [normal strength] to 0 [complete quadriparesis]) between initial examination and latest follow-up, with increased SLSS reflecting improvement and decreased SLSS reflecting worsened strength. Fifty-six patients with AFM from 12 centers met study criteria. Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effect rates were similar to unexposed patients (47% vs 65%, p = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, p < 0.001). Their SLSS was similar at initial examination (mean SLSS 12.9 vs 14.3, p = 0.31) but lower at nadir (mean SLSS 9.25 vs 12.82, p = 0.02) and latest follow-up (mean SLSS 12.5 vs 16.4, p = 0.005) compared with the 28 patients receiving 1 (n = 2) or no (n = 26) doses. In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% confidence interval [CI] -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI +0.7 to +4.4) in untreated patients (p = 0.015). Fluoxetine was well-tolerated. Fluoxetine was preferentially given to patients with AFM with EV-D68 identified and more severe paralysis at nadir, who ultimately had poorer long-term outcomes. This study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes.

Comparison of Effect of Antidepressants on Psychomotor Functions.

Objective:The comparison of the effect of antidepressants on psychomotor functions in patients with endogenous depression.Materials and Methods:This prospective interventional study was carried out at a tertiary care teaching hospital on 95 literate patients with newly diagnosed endogenous depression matching inclusion and exclusion criteria. Patients were prescribed either desvenlafaxine (50 mg) or fluoxetine (40 mg) or sertraline (50 mg). Psychomotor functions were assessed by digit letter substitution, six letter cancellation, choice reaction time, hand steadiness and flicker fusion test at the baseline 1st month and 3rd month. Efficacy of drugs was also measured by Hamilton rating scale for depression. Data were analyzed by using ANOVA and P < 0.05 was considered as statistically significant.Results:A total of 95 patients were enrolled. Fluoxetine, desvenlafaxine, and sertraline were prescribed in 32, 32, and 31 patients, respectively. At the end of 3 months, a significant improvement in psychomotor functions was observed in patients treated with sertraline (P < 0.05), while desvenlafaxine-treated patients did not show any significant change in any of the tests. Surprisingly, fluoxetine-treated patients showed deterioration in all psychomotor tests (P < 0.05). Hamilton rating score improved at the end of 3 months treatment as compared to baseline. Most commonly observed adverse reactions in all three drug groups were nausea (n = 20), dizziness (n = 3), headache (n = 20), and diarrhea (n = 3).Conclusion:Sertraline significantly improves psychomotor function as compared to desvenlafaxine while fluoxetine impairs.

Catechol-O-methyltransferase activity in erythrocytes from patients with eating disorders.

Abnormal feeding has been linked to disruptions in brain dopaminergic activity and recent studies have assessed the role of catechol-O-methyltransferase (COMT) in eating disorders. This is the first study to quantify the soluble catechol-O-methyltransferase (S-COMT) activity in erythrocytes from patients with anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED) and the first study at all to evaluate the COMT on patients with BED. Forty blood samples from patients with AN, BN and BED and healthy controls were drawn to evaluate S-COMT activity in erythrocytes by high-performance liquid chromatography and mass spectrometry. Since several patients were being treated with fluoxetine 20mg, they were included in a different group (BN MED and BED MED). Liver homogenates from rats were used to evaluate baseline S-COMT activity in the presence of fluoxetine by the same in vitro procedures and assays. Erythrocyte S-COMT activity (pmol/mgprt/h) was significantly increased in patients with BN and BED (41.3±6.8 and 41.4±14, respectively) compared to control group (25.3±9.7). In fluoxetine-treated patients with BN, S-COMT activity (15.9±8.8) was decreased compared to the other BN group; however, in BED group, the difference between BED MED and BED was not observed. In patients with AN, no significant difference was found compared to controls. Patients with BN and BED presented higher S-COMT activity in erythrocytes, which is in agreement with previous studies on the literature addressing the high-activity COMT allele, Val158, as risk factor for eating disorders. Although in fluoxetine-treated patients with BN the activity of S-COMT was similar to the controls, this is not explained by a direct interaction between fluoxetine and S-COMT as verified in in vitro assays.

Acute and longer-term safety results from a pooled analysis of duloxetine studies for the treatment of children and adolescents with major depressive disorder.

To assess acute and longer-term safety of duloxetine in the treatment of children and adolescents with major depressive disorder (MDD), a pooled analysis of data from two completed randomized, double-blind, multicenter, phase 3, placebo- and active-controlled trials was undertaken. In these studies, neither duloxetine (investigational drug) nor fluoxetine (active control) demonstrated a statistically significant improvement compared with placebo on the primary efficacy measure. Patients ages 7-17 years with MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) received duloxetine (n=341), fluoxetine (n=234), or placebo (n=225) for 10 week acute and 26 week extended (duloxetine or fluoxetine only) treatments. Safety measures included treatment-emergent adverse events (TEAEs), the Columbia-Suicide Severity Rating Scale, vital signs, electrocardiograms, laboratory samples, and growth (height and weight) assessments. Significantly more patients discontinued because of adverse events during duloxetine (8.2%) treatment than during placebo (3.1%) treatment (p≤0.05). TEAEs in >10% of duloxetine-treated patients were headache and nausea. No completed suicides or deaths occurred. During acute treatment, 6.6% of duloxetine-, 8.0% of fluoxetine-, and 8.2% of placebo-treated patients had worsening suicidal ideation from baseline. Among patients initially randomized to duloxetine or fluoxetine who had suicidal ideation at study baseline, 81% of duloxetine- and 77% of fluoxetine-treated patients had improvements in suicidal ideation at end-point in the 36-week studies. Suicidal behavior occurred in two fluoxetine-treated patients and one placebo-treated patient during acute treatment, and in seven duloxetine-treated patients and one fluoxetine-treated patient during extended treatment. Duloxetine-treated patients had a mean pulse increase of ∼3 beats per minute, and mean blood pressure (both systolic and diastolic) increases of <2.0 mm Hg at week 36. Weight decrease (≥3.5%) during acute treatment occurred with statistically (p≤0.05) greater frequency for both the duloxetine (11.4%) and fluoxetine (11.5%) groups versus the placebo (5.5%) group; however, mean weight increase occurred for both duloxetine and fluoxetine groups during extended treatment. Results from this pooled analysis of two studies were consistent with the known safety and tolerability profile of duloxetine. Clinical Trial Registry Numbers: NCT00849901 and NCT00849693.

Influence of Sex and Menopausal Status on Response, Remission, and Recurrence in Patients With Recurrent Major Depressive Disorder Treated With Venlafaxine Extended Release or Fluoxetine

To evaluate the effects of sex and menopausal status on acute-, continuation-, and maintenance-phase treatment outcomes in patients with recurrent major depressive disorder (MDD). This was a secondary analysis of data from the Prevention of Recurrent Episodes of Depression With Venlafaxine for Two Years (PREVENT) trial, a multiphase, multicenter, double-blind study in which adult outpatients with recurrent MDD (by DSM-IV criteria) were randomly assigned to 10 weeks of acute-phase venlafaxine extended release (ER) (75-300 mg/d) or fluoxetine (20-60 mg/d). Patients achieving response or remission had 6 months of continuation-phase treatment. Responding or remitting patients in the venlafaxine ER group were randomly assigned to venlafaxine ER or placebo for 2 consecutive 12-month maintenance phases; fluoxetine-treated patients continued receiving fluoxetine. The outcome measures for this analysis were acute- and continuation-phase response and remission rates (as measured by the 17-item Hamilton Depression Rating Scale) and time to depression recurrence in the maintenance phases according to sex and menopausal status at baseline. The intent-to-treat population comprised 781 patients in the venlafaxine ER group (65% women) and 266 patients in the fluoxetine group (61% women); 64% of all women were premenopausal, and 25% were postmenopausal (5% perimenopausal; not analyzed). At acute-phase end, remission rates in the venlafaxine ER vs fluoxetine groups were 44% vs 47% in men, 51% vs 52% in women, 50% vs 52% in premenopausal women, and 52% vs 55% in postmenopausal women. At continuation-phase end, remission rates in the venlafaxine ER vs fluoxetine groups were 71% vs 74% in men, 72% vs 67% in women, 72% vs 69% in premenopausal women and 71% vs 63% in postmenopausal women. Response rates were consistent with these findings. Based on a Cox proportional hazards model, sex was not a significant predictor of recurrence during the first or second maintenance phase (hazard ratio [HR] = 1.233; P = .3712 and HR = 1.103; P = .8075, respectively), and neither was menopausal status at acute-phase baseline (HR = 0.941; P = .8234 and HR = 0.531; P = .2065, respectively). In this study of patients with recurrent MDD, treatment outcomes with venlafaxine ER and fluoxetine did not differ on the basis of sex or menopausal status. Our confidence in these findings is limited by the lack of a placebo arm during the acute and continuation phases and by the small sample sizes for subgroup analyses in the maintenance phases. ClinicalTrials.gov identifier: NCT00046020.

Sexual Functioning in Patients With Recurrent Major Depressive Disorder Enrolled in the PREVENT Study

The incidence of treatment-emergent sexual dysfunction in the acute and continuation phases of the prevention of recurrent episodes of depression with venlafaxine ER for two years (PREVENT) study was assessed. Adult outpatients with recurrent major depressive disorder were randomly assigned to receive venlafaxine extended release (ER; 75-300 mg/day) or fluoxetine (20-60 mg/day). Sexual dysfunction was assessed using items from the 17-item Hamilton Rating Scale for Depression (HAM-D(17)) and the Inventory of Depressive Symptomatology-Self-Report (IDS-SR). The baseline rates of sexual dysfunction based on the HAM-D(17) and IDS-SR items were 57.9% and 48.8%, respectively. The rates of new-onset sexual dysfunction for the venlafaxine ER-treated (44.8%, HAM-D(17); 38.4%, IDS-SR) and fluoxetine-treated patients (52.9%, HAM-D(17); 50.0%, IDS-SR) were similar; approximately 80% of the cases resolved during treatment. Treatment response was associated with lower rates of new-onset sexual dysfunction compared with nonresponse. The patients who remitted were the least likely to experience sexual dysfunction during antidepressant treatment.

Psychological and pharmacological interventions for depression in patients with diabetes mellitus and depression

Depression occurs frequently in patients with diabetes mellitus and is associated with a poor prognosis. To determine the effects of psychological and pharmacological interventions for depression in patients with diabetes and depression. Electronic databases were searched for records to December 2011. We searched CENTRAL in The Cochrane Library, MEDLINE, EMBASE, PsycINFO, ISRCTN Register and clinicaltrials.gov. We examined reference lists of included RCTs and contacted authors. We included randomised controlled trials (RCTs) investigating psychological and pharmacological interventions for depression in adults with diabetes and depression. Primary outcomes were depression and glycaemic control. Secondary outcomes were adherence to diabetic treatment regimens, diabetes complications, death from any cause, healthcare costs and health-related quality of life (HRQoL). Two review authors independently examined the identified publications for inclusion and extracted data from included studies. Random-effects model meta-analyses were performed to compute overall estimates of treatment outcomes. The database search identified 3963 references. Nineteen trials with 1592 participants were included. Psychological intervention studies (eight trials, 1122 participants, duration of therapy three weeks to 12 months, follow-up after treatment zero to six months) showed beneficial effects on short (i.e. end of treatment), medium (i.e. one to six months after treatment) and long-term (i.e. more than six months after treatment) depression severity (range of standardised mean differences (SMD) -1.47 to -0.14; eight trials). However, between-study heterogeneity was substantial and meta-analyses were not conducted. Short-term depression remission rates (OR 2.88; 95% confidence intervals (CI) 1.58 to 5.25; P = 0.0006; 647 participants; four trials) and medium-term depression remission rates (OR 2.49; 95% CI 1.44 to 4.32; P = 0.001; 296 participants; two trials) were increased in psychological interventions compared to usual care. Evidence regarding glycaemic control in psychological intervention trials was heterogeneous and inconclusive. QoL did not improve significantly based on the results of three psychological intervention trials compared to usual care. Healthcare costs and adherence to diabetes and depression medication were examined in only one study and reliable conclusions cannot be drawn. Diabetes complications and death from any cause have not been investigated in the included psychological intervention trials.With regards to the comparison of pharmacological interventions versus placebo (eight trials; 377 participants; duration of intervention three weeks to six months, no follow-up after treatment) there was a moderate beneficial effect of antidepressant medication on short-term depression severity (all studies: SMD -0.61; 95% CI -0.94 to -0.27; P = 0.0004; 306 participants; seven trials; selective serotonin reuptake inhibitors (SSRI): SMD -0.39; 95% CI -0.64 to -0.13; P = 0.003; 241 participants; five trials). Short-term depression remission was increased in antidepressant trials (OR 2.50; 95% CI 1.21 to 5.15; P = 0.01; 136 participants; three trials). Glycaemic control improved in the short term (mean difference (MD) for glycosylated haemoglobin A1c (HbA1c) -0.4%; 95% CI -0.6 to -0.1; P = 0.002; 238 participants; five trials). HRQoL and adherence were investigated in only one trial each showing no statistically significant differences. Medium- and long-term depression and glycaemic control outcomes as well as healthcare costs, diabetes complications and mortality have not been examined in pharmacological intervention trials. The comparison of pharmacological interventions versus other pharmacological interventions (three trials, 93 participants, duration of intervention 12 weeks, no follow-up after treatment) did not result in significant differences between the examined pharmacological agents, except for a significantly ameliorated glycaemic control in fluoxetine-treated patients (MD for HbA1c -1.0%; 95% CI -1.9 to -0.2; 40 participants) compared to citalopram in one trial. Psychological and pharmacological interventions have a moderate and clinically significant effect on depression outcomes in diabetes patients. Glycaemic control improved moderately in pharmacological trials, while the evidence is inconclusive for psychological interventions. Adherence to diabetic treatment regimens, diabetes complications, death from any cause, health economics and QoL have not been investigated sufficiently. Overall, the evidence is sparse and inconclusive due to several low-quality trials with substantial risk of bias and the heterogeneity of examined populations and interventions.

Poststroke Treatment With Selective Serotonin Reuptake Inhibitors

Numerous studies failed to translate promising experimental data into clinically effective neuroprotective or neurorestorative therapies for acute ischemic stroke since the introduction of recombinant-tissue plasminogen activator in 1996. Amid gloomy pessimism, the results of the fluoxetine for motor recovery after acute ischemic stroke (FLAME) trial in 2011 ignited hope and restored optimism.1 FLAME was a double-blind, placebo-controlled trial examining the effects of treatment with the selective serotonin reuptake inhibitor (SSRI), fluoxetine, in patients 5 to 10 days after an acute ischemic stroke. Motor improvement to 90 days poststroke, measured as a change in Fugl-Meyer Motor Scale score, was significantly greater in the fluoxetine-treated patients who also had less disability at day 90, defined as modified Rankin Scale score ≤2. Despite some criticisms regarding the limitations of the study and the generalization of its conclusions, the message from FLAME was tempting and appealing. Only a few of acute stroke patients can access and benefit from the currently available reperfusion therapies because of the limited therapeutic time window, …

Gray Matter Volumes in Obsessive-Compulsive Disorder Before and After Fluoxetine or Cognitive-Behavior Therapy: A Randomized Clinical Trial

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n=38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n=36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n=26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n=13), whereas no significant GM volume changes were observed in CBT-treated patients (n=13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action.

Amisulpride vs. fluoxetine treatment of Chronic Fatigue Syndrome: A pilot study

Different pharmacologic agents have been evaluated in the treatment of Chronic Fatigue Syndrome (CFS), albeit with moderate efficacy. Among the compounds thought to present with potential to be efficacious in CFS patients stands out low-dose amisulpride, a substituted benzamide that has been shown to be an useful treatment for conditions which exhibit some overlap with CFS such as dysthymia and somatoform disorders. We thus recruited forty non-depressed CFS patients that were randomized to receive either amisulpride 25 mg bid, or fluoxetine 20 mg uid; all subjects were un-blinded to the treatment regimen. At the time of enrollment in the study and after twelve weeks of treatment, enrolled subjects completed the Krupp Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and a visual analog scale focused on pain and bodily discomfort. Moreover, all subjects were evaluated by a clinician, blinded to the treatment regimen, using the Clinical Global Impression Severity Scale. Our data revealed a significant improvement both in self-report, and observer-based measures for the amisulpride-treated, but not for the fluoxetine-treated patients. Amisulpride-treated subjects also presented with a significant reduction of somatic complaints, while the amisulpride effect on anxiety and mood levels was not significant. Both drugs were equally well tolerated. Summing up, we showed a positive symptomatic effect of amisulpride, compared to SSRI treatment, in a group of non-depressed CSF patients on self-report and on observer-based measures of fatigue and somatic complaints. If confirmed by larger, blinded studies, amisulpride thus could represent an effective approach to this difficult-to-treat condition.

Is There a Role for Antidepressants in the Treatment of Bipolar II Depression?

Is There a Role for Antidepressants in the Treatment of Bipolar II Depression?

Relative Cost-Effectiveness of Treatments for Adolescent Depression: 36-Week Results From the TADS Randomized Trial

ObjectiveThe 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. MethodOutpatients 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. ResultsCognitive-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. ConclusionsThese findings support the use of combination treatment in adolescents with depression over monotherapy. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(7):711–720

An Integrated Analysis of Olanzapine/Fluoxetine Combination in Clinical Trials of Treatment-Resistant Depression

To evaluate the efficacy of olanzapine/fluoxetine combination (OFC) versus olanzapine or fluoxetine monotherapy across all clinical trials of treatment-resistant depression sponsored by Eli Lilly and Company. Efficacy and safety data from 1146 patients with a history of nonresponse during the current depressive episode who subsequently exhibited nonresponse during a 6- to 8-week antidepressant open-label lead-in phase and were randomly assigned to OFC (N = 462), fluoxetine (N = 342), or olanzapine (N = 342) for double-blind treatment were analyzed. All patients had a diagnosis of major depressive disorder as defined by DSM-III or DSM-IV criteria. The dates in which the trials were conducted ranged from May 1997 to July 2005. After 8 weeks, OFC patients demonstrated significantly greater Montgomery-Asberg Depression Rating Scale improvement (mean change = -13.0) than fluoxetine (-8.6, p < .001) or olanzapine (-8.2, p < .001) patients, via a mixed-effects model repeated-measures analysis. Remission rates were 25.5% for OFC, 17.3% (p = .006) for fluoxetine, and 14.0% (p < .001) for olanzapine. Adverse events in >or= 10% of OFC patients were weight gain, increased appetite, dry mouth, somnolence, fatigue, headache, and peripheral edema. Random glucose mean change (mg/dL) was +7.92 for the OFC group, +1.62 for the fluoxetine group (p = .020), and +9.91 for the olanzapine group (p = .485). Random cholesterol mean change (mg/dL) was +12.4 for OFC, +2.3 for fluoxetine (p < .001), and +3.1 for olanzapine (p < .001); incidence of treatment-emergent increase from normal to high cholesterol (baseline < 200 mg/dL and >or= 240 subsequently) was significantly higher for the OFC group (10.2%) than for the fluoxetine group (3.1%, p = .017) but not the olanzapine group (8.0%, p = .569). Mean weight change (kg) was +4.42 for OFC, -0.15 for fluoxetine (p < .001), and +4.63 for olanzapine (p = .381), with 40.4% of OFC patients gaining >or= 7% body weight (vs. olanzapine: 42.9%, p = .515; fluoxetine: 2.3%, p < .001). Results of this analysis showed that OFC-treated patients experienced significantly improved depressive symptoms compared with olanzapine- or fluoxetine-treated patients following failure of 2 or more antidepressants within the current depressive episode. Safety results for OFC were generally consistent with those for its component monotherapies. The total cholesterol increase associated with OFC was more pronounced than with olanzapine alone.

Placebo-controlled, randomized trial of fluoxetine in the treatment of aggression in male intimate partner abusers

The objective was to determine the efficacy of treating aggressive behavior in men, with a history of intimate partner abuse, with fluoxetine. Twenty-six men with a history of intimate-partner-abusing behavior entered a randomized, placebo-controlled trial of fluoxetine (20-60 mg by mouth per day). The primary outcome measure was the Aggression score from the overt aggression scale-modified (OAS-M). Fluoxetine-treated patients (n=13) did not differ from placebo-treated patients (n=13) on any key demographic or behavioral variables. Although a significant 'pre-post' reduction in OAS-M Aggression score was noted in all patients, no drug-placebo differences for OAS-M Aggression scores were seen in any analysis. Despite the small sample, these results do not support the hypothesis that treatment with an SSRI is associated with a reduction in aggressive behavior among men with a history of intimate partner abuse.

Effects of the Antidepressant Duloxetine on Body Weight

To assess the effect of duloxetine, an inhibitor of serotonin and norepinephrine reup-take, on body weight of patients with major depressive disorder (MDD). Body weight data were obtained from all 10 phase II and III registration studies of duloxetine in the treatment of MDD, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), performed by Eli Lilly and Company between February 1999 and July 2003. Both acute (8-9 weeks) and long-term (26, 34, and 52 weeks) studies were analyzed. In the acute placebo-controlled studies, duloxetine-treated patients had a mean change of -0.5 kg compared with a change of 0.2 kg for placebo-treated patients (p < .001); no consistent relationship between duloxetine dose and weight change was observed. In placebo-controlled studies including an active comparator arm, similar acute mean weight changes were seen in duloxetine-treated and fluoxetine-treated patients (-0.7 kg vs. -0.6 kg) and in duloxetine-treated and paroxetine-treated patients (-0.3 kg vs. -0.2 kg). During longer-term treatment (34 weeks), mean weight change in patients treated with duloxetine 40 mg b.i.d. was not significantly different from that seen in placebo-treated patients (0.7 kg vs. 0.1 kg), while patients treated with the higher duloxetine dose of 60 mg b.i.d. or with paroxetine gained significantly (p ≤?.05) more weight than placebo-treated patients (0.9 kg, 1.0 kg, and 0.1 kg, respectively). In a 52-week open-label study, duloxetine-treated patients had a mean weight gain of 1.1 kg at endpoint (p < .001). Duloxetine-treated patients experienced weight loss after short-term treatment, followed by modest weight gain on longer-term treatment. The size of the weight changes observed suggests that the antidepressant duloxetine has minimal effects on weight for the majority of patients.

Fluoxetine monotherapy of bipolar type II and bipolar NOS major depression: a double-blind, placebo-substitution, continuation study

Current guidelines for the treatment of bipolar type II (BP II) major depressive episode (MDE) recommend using either mood stabilizer monotherapy or the combination of a mood stabilizer with a selective serotonin reuptake inhibitor (SSRI). These guidelines are the result of concern over SSRI-induced manic switch episodes. We previously showed that fluoxetine monotherapy may be effective as an initial treatment for BP II and BP NOS MDE with a low manic switch rate. We now present the results of a double-blind, placebo-substitution continuation study of fluoxetine monotherapy in BP II and BP NOS patients who have recovered from their MDE. This was a two-phase study. In study phase I, patients received open-label fluoxetine monotherapy 20 mg daily for up to 8 weeks. Responders with a final 17-item Hamilton Rating Scale for Depression (HAM-D) score < or =9 were enrolled into study phase II which consisted of double-blind, placebo-substitution continuation therapy with fluoxetine 20 mg daily for up to 6 months. Outcome measures included the 17-item HAM-D and Young Mania Rating (YMR) scales. Changes in YMR scores were assessed using generalized estimating equation analysis. Relapse was assessed using Kaplan-Meier survival analysis and Fisher's exact test. In study phase II, 43% of fluoxetine-treated patients and 100% of placebo-treated patients relapsed during continuation therapy (P=0.08). The mean increase in YMR score in study phase II was slightly higher in the fluoxetine-treated patients (3.0+/-1.8) versus placebo-treated patients (0.2+/-0.4) (P=0.01). However, this difference was not clinically meaningful. No hypomanic switch episodes were observed during study phase II. Despite the limited sample size resulting in insufficient power to detect statistical significance in relapse rates or change in YMR scores between treatment conditions, these preliminary data appear to support previous observations demonstrating that initial and continuation fluoxetine monotherapy may be safe and effective for some patients with BP II or BP NOS MDE with a low manic switch rate. Larger-scale studies are needed to confirm these findings.