Delusionality and response to open-label fluvoxamine in body dysmorphic disorder

BACKGROUND: Available data suggest that the delusional variant of body dysmorphic disorder (BDD), a type of delusional disorder, may respond to serotonin reuptake inhibitors (SRIs) and that delusionality (lack of insight) in BDD may improve with SRI treatment. However, this research has been hampered by the lack of a reliable and valid scale to assess delusionality. METHOD: Thirty subjects (21 women, 9 men; mean age = 33.3 +/- 9.0 years) with DSM-IV BDD were prospectively treated with open-label fluvoxamine for 16 weeks. Subjects were assessed at regular intervals with the Brown Assessment of Beliefs Scale (BABS), the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS; a measure of BDD severity), and other instruments. The BABS is a reliable and valid 7-item, semistructured, clinician-administered scale that assesses current delusionality. RESULTS: In this prospective, open-label study, 63% of BDD subjects responded to fluvoxamine. Delusional and nondelusional subjects had similar improvement in BDD symptoms. In addition, insight significantly improved in both delusional and nondelusional subjects. Baseline BABS scores did not contribute significantly to endpoint BDD-YBOCS scores in a regression analysis. CONCLUSION: Degree of delusionality did not predict fluvoxamine response, and delusionality significantly improved. These findings are preliminary and require confirmation in controlled trials. The implications of these findings for other types of delusions requires investigation.     

Fluoxetine versus placebo in posttraumatic stress disorder

BACKGROUND: This study was designed to address the efficacy and tolerability of fluoxetine in patients with posttraumatic stress disorder (PTSD) as diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders and the Clinician-Administered PTSD Scale (CAPS). The patient population included both civilians and combat veterans. METHOD: This was a double-blind, randomized, placebo-controlled study conducted in Europe, Israel, and South Africa, primarily in war-torn countries. Patients were predominantly male (81%) and white (91%), with 48% exposed to a combat-related traumatic episode. Patients were randomly assigned to 12 weeks of acute treatment with fluoxetine, 20 to 80 mg/day (N = 226), or placebo (N = 75). The primary efficacy measurement was the mean change from baseline in the Treatment Outcome PTSD rating scale (TOP-8) total score, which was analyzed using a repeated-measures analysis of variance. Secondary assessments included the CAPS, the Davidson Trauma Scale, the Clinical Global Impressions-Severity of Illness scale (CGI-S), the CGI-Improvement scale (CGI-I), the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Rating Scale for Anxiety (HAM-A), and the Hopkins 90-Item Symptom Checklist-Revised. RESULTS: Fluoxetine was associated with a greater improvement from baseline in total TOP-8 score than was placebo. This difference was statistically significant by week 6 of treatment (p < .001) through the end of the acute phase of the study (week 12; p = .006). Compared with placebo, fluoxetine was also associated with significantly greater improvement in CAPS total score as well as intrusive and hyperarousal subscores and in CGI-S, CGI-I, HAM-A, and MADRS scores (p < .05). The presence of dissociative symptoms at baseline appeared to be a predictor of high placebo response. The mean fluoxetine dose at endpoint was 57 mg. There were no clinically significant safety differences. CONCLUSION: Fluoxetine is effective and well tolerated in the treatment of PTSD. Most PTSD patients will respond satisfactorily at doses in the upper normal range for the usual antidepressant doses of fluoxetine.     

Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial.

OBJECTIVE: This study assesses the efficacy and tolerability of fluoxetine in the acute treatment of child and adolescent obsessive-compulsive disorder (OCD) during a 13-week, double-blind, placebo-controlled study. METHOD: Eligible patients aged 7 to 17 (N = 103) were randomized at a ratio of 2:1 to receive either fluoxetine or placebo. Dosing was initiated at 10 mg daily for 2 weeks, then increased to 20 mg daily. After 4 weeks of treatment, and again after 7 weeks of treatment, non-responders could have their dosage increased by 20 mg daily, for a maximum possible dosage of 60 mg daily. Primary measure of efficacy was improvement in OCD symptoms as measured by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). All analyses were intent-to-treat. RESULTS: Fluoxetine was associated with significantly greater improvement in OCD as assessed by the CY-BOCS (p = .026) and other measures than was placebo. Fluoxetine was well tolerated and had a rate of discontinuation for adverse events similar to that of placebo (p = 1.00). CONCLUSIONS: Fluoxetine 20 to 60 mg daily was effective and well tolerated for treatment of OCD in this pediatric population.     

Placebo-controlled study of pimozide augmentation of fluoxetine in body dysmorphic disorder

OBJECTIVE: Although body dysmorphic disorder often responds to serotonin reuptake inhibitors (SRIs), most patients do not respond or respond only partially. However, placebo-controlled studies of augmentation of SRIs have not been done. Furthermore, although 40%-50% of patients are delusional, studies of antipsychotic medications have not been done. METHOD: Twenty-eight patients with body dysmorphic disorder or its delusional variant participated in an 8-week, placebo-controlled, double-blind, parallel-group study of pimozide augmentation of fluoxetine. RESULTS: Pimozide was not more effective than placebo: two (18.2%) of 11 subjects responded to pimozide and three (17.6%) of 17 subjects responded to placebo. There was no significant effect of baseline delusionality on endpoint severity of body dysmorphic disorder. Delusionality did not decrease significantly more with pimozide than placebo. CONCLUSIONS: Pimozide augmentation of fluoxetine treatment for body dysmorphic disorder was not more effective than placebo, even in more delusional patients. Further studies of augmentation for SRIs are needed.     

Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled,randomized clinical trial

BACKGROUND: This report presents results from the acute treatment phase of a clinical trial designed to confirm efficacy of a fixed dose of 20 mg of fluoxetine in children and adolescents with major depressive disorder (MDD). METHOD: After a 3-week screening period, 122 children and 97 adolescents with MDD ( ) were randomly assigned to placebo or fluoxetine. After a 1-week placebo lead-in, fluoxetine-treated patients received fluoxetine 10 mg/day for 1 week, then fluoxetine 20 mg/day for 8 weeks. RESULTS: Fluoxetine was associated with greater mean improvement in Children's Depression Rating Scale-Revised (CDRS-R) score than placebo after 1 week ( <.05) and throughout the study period. Significantly more fluoxetine-treated patients (41%) met the prospectively defined criteria for remission than did placebo-treated patients (20%) ( <.01). More fluoxetine- (65%) than placebo-treated (53%) patients met the prospectively defined response criterion of > or =30% decrease in CDRS-R score, but this difference was not significant ( =.093). Significantly more fluoxetine-than placebo-treated patients completed acute treatment ( =.001). There were no significant differences between treatment groups in discontinuations due to adverse events ( =.408). CONCLUSION: Fluoxetine 20 mg daily appears to be well tolerated and effective for acute treatment of MDD in child and adolescent outpatients. Fluoxetine is the only antidepressant that has demonstrated efficacy in two placebo-controlled, randomized clinical trials of pediatric depression.     

Delusional versus nondelusional body dysmorphic disorder: clinical features and course of illness

DSM-IV's classification of body dysmorphic disorder (BDD) is controversial. Whereas BDD is classified as a somatoform disorder, its delusional variant is classified as a psychotic disorder. However, the relationship between these BDD variants has received little investigation. In this study, we compared BDD's delusional and nondelusional variants in 191 subjects using reliable and valid measures that assessed a variety of domains. Subjects with delusional BDD were similar to those with nondelusional BDD in terms of most variables, including most demographic features, BDD characteristics, most measures of functional impairment and quality of life, comorbidity, and family history. Delusional and nondelusional subjects also had a similar probability of remitting from BDD over 1 year of prospective follow-up. However, delusional subjects had significantly lower educational attainment, were more likely to have attempted suicide, had poorer social functioning on several measures, were more likely to have drug abuse or dependence, were less likely to currently be receiving mental health treatment, and had more severe BDD symptoms. However, when controlling for BDD symptom severity, the two groups differed only in terms of educational attainment. These findings indicate that BDD's delusional and nondelusional forms have many more similarities than differences, although on several measures delusional subjects evidenced greater morbidity, which appeared accounted for by their more severe BDD symptoms. Thus, these findings offer some support for the hypothesis that these two BDD variants may constitute the same disorder. Additional studies are needed to examine this issue, which may have relevance for other disorders with both delusional and nondelusional variants in DSM.     

Efficacy of venlafaxine extended release in patients with major depressive disorder and comorbid generalized anxiety disorder

BACKGROUND: A subset of patients with comorbid major depressive disorder and generalized anxiety disorder (GAD) was examined from a double-blind. placebo-controlled study comparing the efficacy and safety of venlafaxine extended release (XR) and fluoxetine. METHOD: From a total of 368 patients, 92 patients meeting DSM-IV criteria for major depressive disorder who also had comorbid GAD were identified. The comparison group comprised 276 evaluable noncomorbid patients. Patients received venlafaxine XR (75-225 mg/day), fluoxetine (20-60 mg/day), or placebo for 12 weeks. Efficacy evaluations included Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions (CGI) scale. RESULTS: By the final assessment at week 12, comorbid patients in the venlafaxine XR group, but not in the fluoxetine group, showed a significantly greater decrease than those in the placebo group in the primary efficacy variables of mean HAM-D and HAM-A total scores (p < .05, pairwise comparison). In comorbid patients, significant pairwise differences were noted between venlafaxine XR and placebo at week 12 for the secondary variables of HAM-D anxiety-somatization and retardation factors, HAM-D depressed mood item. HAM-A psychic anxiety factor, the Hospital Anxiety and Depression scale (HAD) anxiety subscale score, and the Covi Anxiety Scale score. Fluoxetine was significantly different from placebo only on the HAD depression subscale score. Response, defined as > or = 50% decrease in symptoms score, was achieved in 66% and 59% of the comorbid patients for HAM-D and HAM-A, respectively, in the venlafaxine XR group at week 12. This response was higher than that seen with fluoxetine (52% and 45%) or placebo (36% and 24%). Onset of efficacy appeared to be slower in comorbid than in noncomorbid patients. CONCLUSION: This is the first evidence from a controlled study of the effectiveness of pharmacotherapy in patients with comorbid major depressive disorder and GAD. The delayed improvement in comorbid patients compared with noncomorbid patients suggests that a longer treatment period may be necessary in comorbid patients.     

An open-label study of citalopram in body dysmorphic disorder

BACKGROUND: Body dysmorphic disorder (BDD), a preoccupation with an imagined or slight defect in appearance, is a relatively common and impairing disorder. While available data suggest that serotonin reuptake inhibitors are effective for BDD, investigation of this disorder's response to pharmacotherapy is limited, and there are no published reports on the efficacy of the selective serotonin reuptake inhibitor citalopram. In addition, there are no published reports on change in quality of life and multiple domains of psychosocial functioning with pharmacologic treatment for patients with BDD. METHOD: Fifteen subjects with DSM-IV BDD or its delusional variant were prospectively treated in a 12-week open-label trial of citalopram. Subjects were assessed at regular intervals with the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS; the primary outcome measure), the Clinical Global Impressions scale (CGI), the Brown Assessment of Beliefs Scale, measures of quality of life and multiple domains of psychosocial functioning, and other scales. Data were collected from Dec. 28, 1999, to March 1, 2001. RESULTS: On the BDD-YBOCS, scores decreased from a mean +/- SD of 30.7 +/- 4.9 at baseline to 15.3 +/- 10.6 at endpoint (p <.001), and 73.3% (N = 11) of subjects were responders. On the CGI, 40.0% of patients (N = 6) were very much improved, and 26.7% (N = 4) were much improved. Psychosocial functioning and mental health-related quality of life also significantly (p <.05) improved. The mean dose of citalopram was 51.3 +/- 16.9 mg/day, and the mean time to response was 4.6 +/- 2.6 weeks. Citalopram was generally well tolerated. CONCLUSION: Citalopram appears safe and effective for BDD. Psychosocial functioning and quality of life also significantly improved with citalopram.     

Adolescent depression: a placebo-controlled fluoxetine treatment study and follow-up

Forty patients aged 13 to 18 years participated in a placebo-controlled double-blind study of fluoxetine. Fifteen subjects in each group completed the eight week study. Approximately two-thirds of the patients showed marked or moderate clinical global improvement with both fluoxetine and placebo. Fluoxetine was superior to placebo on all clinical measures except for sleep disorder, but the differences were not statistically significant. Thirty-two of the patients and their parents were interviewed after a mean follow-up interval of 24 months (range: 8-46 months). Mean age at follow-up was 18 years (range: 15-22 years). Both groups had shown further improvement at follow-up but there were no significant group differences. Independent of the study, 19 patients (59%) had received intervening treatment following study termination and nine patients (28%) were still in treatment. Adolescent depression appears to respond to treatment but both mood disturbance and psychosocial adaptation problems persist, requiring active follow-through.     

Delusional versus nondelusional body dysmorphic disorder

This study assessed demographic and clinical features in 65 subjects with body dysmorphic disorder (BDD) and compared the 39 (60%) with the delusional form (receiving an additional diagnosis of delusional disorder, somatic type) with those who did not meet delusionality criteria. Delusional and nondelusional patients did not statistically differ on most demographic and clinical variables. Delusional patients, however, had significantly more severe BDD symptoms at both baseline and follow-up assessments than those of nondelusional patients. Furthermore, poorer insight was significantly associated with more severe BDD symptoms at both baseline and follow-up. Overall improvement in BDD symptom severity was similar for the 2 groups. Our results support other studies in the view that BDD and its delusional variant have more similarities than differences and that the delusional variant may be simply a more severe form of BDD. Implications for the diagnostic classification of BDD and future research directions are discussed.     

Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder.

OBJECTIVE: The authors compared the efficacy and side effects of fluoxetine and placebo in elderly outpatients with dysthymic disorder. METHODS: Patients were randomly assigned to fluoxetine (20 mg-60 mg/day) or placebo for 12 weeks in a double-blind trial. RESULTS: Of 90 randomized patients, 71 completed the trial. In the intent-to-treat sample, random regression analyses of the Hamilton Rating Scale for Depression (Ham-D; 24-item) and Cornell Dysthymia Rating Scale (CDRS) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group. Analysis of percentage change in Ham-D scores yielded no effect for treatment group, but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group, favoring fluoxetine over placebo. In the intent-to-treat sample, response rates were 27.3% for fluoxetine and 19.6% for placebo. In the completer sample, response rates were 37.5% for fluoxetine and 23.1% for placebo. CONCLUSION: Fluoxetine had limited efficacy in elderly dysthymic patients. The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults, and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients. Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder, and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance.     

Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group

BACKGROUND: We conducted a randomized, double-blind, placebo-controlled study of the efficacy and safety of once-daily venlafaxine extended release (XR) and fluoxetine in outpatients with major depression and concomitant anxiety. METHOD: Patients who met DSM-IV criteria for major depressive disorder and satisfied eligibility criteria were randomly assigned to once-daily venlafaxine XR, fluoxetine, or placebo for 12 weeks. Efficacy was assessed with the Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions scale. RESULTS: Among 359 outpatients, venlafaxine XR and fluoxetine were significantly superior (p < .05) to placebo on the HAM-D total score beginning at week 2 and continuing to the end of the study. Venlafaxine XR but not fluoxetine was significantly better than placebo at week 2 on the HAM-D depressed mood item. At week 12, the HAM-D response rate was 43% on placebo, 67% on venlafaxine XR, and 62% on fluoxetine (p < .05). The HAM-D remission rate was significantly higher (p < .05) at weeks 3, 4, 6, 8, 12, and final evaluation with venlafaxine XR and at weeks 8, 12, and final evaluation with fluoxetine than with placebo. The HAM-A response rate was significantly higher (p < .05) with venlafaxine XR than with fluoxetine at week 12. The incidence of discontinuation for adverse events was 5% with placebo, 10% with venlafaxine XR, and 7% with fluoxetine. CONCLUSION: Once-daily venlafaxine XR is effective and well tolerated for the treatment of major depression and concomitant anxiety and provides evidence for superiority over fluoxetine.     

Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study

BACKGROUND: Although case reports and open studies have reported augmentation with buspirone to be beneficial in the treatment of depression refractory to treatment with a selective serotonin reuptake inhibitor (SSRI), a recently published randomized, placebo-controlled, double-blind study failed to show superiority of buspirone over placebo in this respect. METHOD: One hundred two outpatients who fulfilled DSM-IV criteria for a major depressive episode and who had failed to respond to a minimum of 6 weeks of treatment with either fluoxetine or citalopram were included in this double-blind, randomized, placebo-controlled study. After a single-blind placebo wash-in period of 2 weeks while continuing their SSRI, the patients were randomly assigned to adjunctive treatment with either buspirone, 10 to 30 mg b.i.d., or placebo for 6 weeks. Patients were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impressions scale (CGI), and visual analogue scales. RESULTS: After the first week of double-blind treatment, there was a significantly greater reduction in MADRS score (p = .034) in the buspirone group as compared with placebo. At endpoint, there was no significant difference between treatment groups as a whole, although patients with initially high MADRS scores (> 30) showed a significantly greater reduction in MADRS score (p = .026) in the buspirone group as compared with placebo. CONCLUSION: Patients with severe depressive symptoms may benefit from augmentation with buspirone. It cannot be excluded that augmentation with buspirone may speed up the antidepressive response of patients refractory to treatment with fluoxetine or citalopram.     

Fluoxetine for the treatment of childhood anxiety disorders

OBJECTIVE: To assess the efficacy and tolerability of fluoxetine for the acute treatment of children and adolescents with generalized anxiety disorder, separation anxiety disorder, and/or social phobia. METHOD: Anxious youths (7-17 years old) who had significant functional impairment were randomized to fluoxetine (20 mg/day) (n = 37) or placebo (n = 37) for 12 weeks. RESULTS: Fluoxetine was effective in reducing the anxiety symptoms and improving functioning in all measures. Using intent-to-treat analysis, 61% of patients taking fluoxetine and 35% taking placebo showed much to very much improvement. Despite this improvement, a substantial group of patients remained symptomatic. Fluoxetine was well tolerated except for mild and transient headaches and gastrointestinal side effects. Youths with social phobia and generalized anxiety disorder responded better to fluoxetine than placebo, but only social phobia moderated the clinical and functional response. Severity of the anxiety at intake and positive family history for anxiety predicted poorer functioning at the end of the study. CONCLUSIONS: Fluoxetine is useful and well tolerated for the acute treatment of anxious youths. Investigations regarding the optimization of treatment to obtain full anxiety remission and the length of treatment necessary to prevent recurrences are warranted.     

Fluoxetine in children and adolescents with OCD: a placebo-controlled trial

OBJECTIVE: To examine the safety and efficacy of fluoxetine in child and adolescent obsessive-compulsive disorder (OCD). METHOD: Between 1991 and 1998, 43 patients were randomly assigned to fluoxetine or placebo for 8 weeks. Dosing was fixed for the first 6 weeks (up to 60 mg/day) and then could be increased to 80 mg/day. Responders entered an 8-week maintenance phase. The primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impression-Improvement (CGI-I) scale. Analyses were done on the intent-to-treat sample. RESULTS: Fluoxetine patients (n = 21) had significantly lower CY-BOCS scores than placebo patients (n = 22) after 16 (but not 8) weeks. Fluoxetine responders (n = 11) had significantly lower CY-BOCS scores than placebo responders (n = 7) after an additional 8 weeks of treatment. After 16 weeks, 57% of fluoxetine (versus 27% of placebo) patients were much or very much improved on the CGI-I scale (p <.05). No patient terminated the study because of adverse medication effects. CONCLUSION: Fluoxetine was well tolerated and effective for the treatment of child and adolescent OCD, but fluoxetine's full effect took more than 8 weeks to develop.     

A randomized double-blind clinical trial on analgesic efficacy of fluoxetine for persistent somatoform pain disorder

Objectives

To verify the efficacy and safety of fluoxetine in treating patients with persistent somatoform pain disorder (PSPD).

Methods

In this 8-week, randomized double-blind placebo-controlled study, 80 patients with an ICD-10 diagnosis of PSPD were randomly assigned to receive 20 mg fluoxetine or a placebo. Several psychological scales including Medical Outcomes Study Pain Measures (MOSPM), Hamilton Depression Scale-17 items (HAMD₁₇) and Treatment Emergent Symptom Scale (TESS) were used to assess analgesic efficacy and safety of fluoxetine, and the possible analgesic mechanism of fluoxetine was preliminarily analyzed. All data were analyzed by SPSS11.5 with t-test, one-way ANOVA and a mixed-effects model repeated measures analysis. Intent-to-treat (ITT) analysis was performed and the last observation carry forward (LOCF) was used for missing values.

Results

There was a significant difference of MOSPM total score between the fluoxetine and placebo group after 2 weeks of treatment. The analgesic effect of fluoxetine was related with treatment time, and depressive patients showed a better analgesic effect than non-depressive patients. An adverse effect of fluoxetine was scarcely found.

Conclusions

Fluoxetine has a better analgesic effect than a placebo in treating persistent somatoform pain disorder, and is considered a safe treatment; its analgesic effect may be related to an antidepressant effect.     

The Can-SAD study: a randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder

OBJECTIVE: Light therapy and antidepressants have shown comparable efficacy in separate studies of seasonal affective disorder treatment, but few studies have directly compared the two treatments. This study compared the effectiveness of light therapy and an antidepressant within a single trial. METHOD: This double-blind, randomized, controlled trial was conducted in four Canadian centers over three winter seasons. Patients met DSM-IV criteria for major depressive disorder with a seasonal (winter) pattern and had scores > or = 23 on the 24-item Hamilton Depression Rating Scale. After a baseline observation week, eligible patients were randomly assigned to 8 weeks of double-blind treatment with either 1) 10,000-lux light treatment and a placebo capsule, or 2) 100-lux light treatment (placebo light) and fluoxetine, 20 mg/day. Light treatment was applied for 30 minutes/day in the morning with a fluorescent white-light box; placebo light boxes used neutral density filters. RESULTS: A total of 96 patients were randomly assigned to a treatment condition. Intent-to-treat analysis showed overall improvement with time, with no differences between treatments. There were also no differences between the light and fluoxetine treatment groups in clinical response rates (67% for each group) or remission rates (50% and 54%, respectively). Post hoc testing found that light-treated patients had greater improvement at 1 week but not at other time points. Fluoxetine was associated with greater treatment-emergent adverse events (agitation, sleep disturbance, palpitations), but both treatments were generally well-tolerated with no differences in overall number of adverse effects. CONCLUSIONS: Light treatment showed earlier response onset and lower rate of some adverse events relative to fluoxetine, but there were no other significant differences in outcome between light therapy and antidepressant medication. Although limited by lack of a double-placebo condition, this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and suggests that other clinical factors, including patient preference, should guide selection of first-line treatment.     

A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease

OBJECTIVE: To examine the efficacy of fluoxetine in the treatment of depression in patients with probable Alzheimer's disease (AD). METHODS: This double-blind, parallel-design study included a consecutive series of 41 AD subjects meeting DSM-IV criteria for major or minor depression who were randomized to receive fluoxetine (up to 40 mg/day) or identical-appearing placebo. All patients received biweekly evaluations consisting of the Hamilton Depression Scale (HAM-D) and the Clinical Global Impression as primary efficacy measures, and the Mini-Mental State Exam, Hamilton Rating Scale for Anxiety, and the Functional Independence Measure as secondary efficacy measures. RESULTS: Complete remission of depression was found in 47% of subjects treated with fluoxetine and in 33% of subjects treated with placebo. Both the fluoxetine and the placebo groups showed a significant decline in HAM-D scores over time, but the magnitude of mood improvement was similar for both groups. Fluoxetine was well tolerated, and most side effects were mild. CONCLUSION: Fluoxetine treatment for depression in AD did not differ significantly from treatment with placebo. Our study also confirms the presence of a placebo effect in the treatment of depression in AD.     

Early fluoxetine treatment of post-stroke depression

Objective: Poststroke depression is a frequent psychiatric complication after stroke that may have strong negative impact on rehabilitation therapy and functional recovery. This study was conducted to show the efficacy and safety of early treatment with the selective serotonin reuptake inhibitor fluoxetine in post-stroke depressed patients. Methods: This double-blind, randomized placebo-controlled study was of patients within two weeks after stroke. Moderate to severe depressed patients (determined by Hamilton Depression Scale (HDS) > 15, the Beck Depression Inventory (BDI) and the Clinical Global Impression (CGI) Scale) were randomized to receive either 20 mg/d fluoxetine or placebo for 3 months. Beside the psychiatric assessment, patients were evaluated by use of the Scandinavian Stroke Scale (SSS), the Mini-Mental-State-Examination (MMSE) and the Barthel-Index (BI). An open-label long-term follow up was done 18 months after the initial assessment. Results: 54 depressed patients of an inpatient population of 242 consecutive stroke patients aged 25 to 85 years entered the trial within the first two weeks post-stroke. 50 patients completed the trial per-protocol. The initial severity of depression was comparable in the two groups (mean baseline HDS score 32.8 in the fluoxetine vs. 30.3 in the placebo group), as were neurological symptom severity and demographic parameters. Significant improvement was seen in both groups within 4 weeks of treatment, whereas no advantages of fluoxetine could be observed at this time. This indicates a high degree of spontaneous recovery during early rehabilitation therapy. BDI scores of patients treated with fluoxetine further decreased until the follow-up at 12 weeks, whereas the scores increased again in the placebo group. This depressive relapse of the placebo patients after the end of most rehabilitation efforts was evident at a long-term follow-up 18 months after inclusion, when patients who had been treated with fluoxetine were significantly less depressed. No side effects of fluoxetine treatment were detected. Conclusions: The advantages of fluoxetine were obvious at the follow-up 18 months after inclusion, but could not be demonstrated within the first three months of controlled treatment. The multitude of therapeutic efforts that take place in the early phase of rehabilitation might have facilitated spontaneous recovery from depression and might have hindered benefits of antidepressant treatment to become obvious. Fluoxetine treatment was well tolerated and safe. Received: 5 February 2002, Received in revised form: 8 October 2002, Accepted: 28 October 2002 Correspondence to Stefan Fruehwald, MD     

Psychosis in body dysmorphic disorder

Body dysmorphic disorder (BDD) has both psychotic and nonpsychotic variants, which are classified as separate disorders in DSM-IV (delusional disorder and a somatoform disorder). Despite their separate classification, available evidence indicates that BDD's delusional and nondelusional forms have many similarities (although the delusional variant appears more severe), suggesting that they may actually be the same disorder, characterized by a spectrum of insight. And contrary to what might be expected, BDD's delusional form, although classified as a psychotic disorder, appears to respond to serotonin-reuptake inhibitors alone. These and other data suggest that a dimensional view of psychosis (in particular, delusions) in these disorders may be more accurate than DSM's current categorical view. A dimensional model might also facilitate more consistent and accurate classification of other disorders that are likely characterized by a spectrum of insight, such as obsessive compulsive disorder, hypochondriasis, and anorexia nervosa. Further research is needed to better understand these classification issues, which likely have treatment implications.