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Biomedical subjects

Maurizio Fava

Publications and source records attributed to Maurizio Fava.

At least 55 records · Page 3Linked to original sources
PubMed2006

Brain white-matter hyperintensities and treatment outcome in major depressive disorder.

BACKGROUND: An increased incidence of brain white-matter hyperintensities has been described in major depressive disorder, butthe impact of such hyperintensities on treatment outcome is still controversial. AIMS: To investigate the relationship of brain white-matter hyperintensities with cardiovascular risk factors and with treatment outcome in younger people with major depressive disorder. METHOD: We assessed brain white-matter hyperintensities and cardiovascular risk factors in 84 people with major depressive disorder prior to initiating antidepressant treatment. We also assessed hyperintensities in 35 matched controls. RESULTS: We found no significant difference in the prevalence of white-matter hyperintensities between the depression and the control groups. Left-hemisphere subcortical hyperintensities correlated with lower rates of treatment response. We found no correlation between global hyperintensity measures and clinical outcome. Brain white-matter hyperintensities correlated with hypertension and age and withtotal cardiovascular risk score. CONCLUSIONS: Subcortical white-matter hyperintensities in the left hemisphere (but notin other brain areas) maybe associated with poor response to antidepressant treatment in major depression.

Adolescent↗
PubMed2006

Children of currently depressed mothers: a STAR*D ancillary study.

OBJECTIVE: To assess the current and lifetime prevalence of psychiatric disorders among children of currently depressed mothers and to assess the association of clinical features of maternal depression (i.e., severity, chronicity, and clinical features) with child psychopathology. Mothers were participants in the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) multisite trial, designed to compare effectiveness and acceptability of different treatment options for outpatients with non-psychotic major depressive disorder (MDD). METHOD: Treatment-seeking mothers with a current DSM-IV diagnosis of MDD and with at least 1 child 7 to 17 years old were assessed during a major depressive episode (MDE). For each mother, 1 child was assessed (if a mother had more than 1 child, 1 was randomly selected). Maternal features assessed for this study were history of MDEs, severity of current MDE, comorbid conditions, depressive symptom features, and social functioning. Children were assessed for selected psychiatric diagnoses (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version [K-SADS-PL]), psychopathologic symptoms and social functioning (Child Behavior Checklist), and global functioning (Children's Global Assessment Scale). Data were gathered from December 2001 to April 2004. RESULTS: A large proportion (72%) of mothers were severely depressed (17-item Hamilton Rating Scale for Depression score >/= 22). About a third (34%) of children had a current psychiatric disorder, including disruptive behavior (22%), anxiety (16%), and depressive (10%) disorders. Nearly half (45%) had a lifetime psychiatric disorder, including disruptive behavior (29%), anxiety (20%), and depressive (19%) disorders. Atypical depressive features in the mother were associated with a 3-fold increase in the odds of having a child with depressive (OR = 3.3 [95% CI = 1.2 to 9.5]; p = .02) or anxiety (OR = 2.6 [95% CI = 1.1 to 6.9]; p = .03) disorders. A history of maternal suicide attempts and the presence of comorbid panic disorder with agoraphobia were associated with a 3-fold increase and an 8-fold increase in the odds of depressive disorders in the offspring, respectively. The final model showed significant associations (p </= .05) between the following characteristics of maternal depression and offspring disorders: maternal comorbid panic disorder with agoraphobia and offspring depressive and anxiety disorders, maternal irritable depression and offspring disruptive behavior disorders and any disorder, and maternal substance use disorders and any disorder. CONCLUSIONS: Children of mothers in the midst of a current MDE are at high risk for disruptive behavior and anxiety disorders. The elevated risk of psychopathology among children of depressed mothers may recommend assessment of these children when clinically suggested. Children of depressed mothers with comorbid panic disorder with agoraphobia are at high risk for depressive and anxiety disorders and deserve special attention from clinicians.

Adult↗
PubMed2006

Efficacy and safety of sildenafil in men with serotonergic antidepressant-associated erectile dysfunction: results from a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of short-term treatment with sildenafil citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile dysfunction (ED). METHOD: Men (aged>or=18 years) with major depressive disorder (MDD; DSM-IV criteria) in remission and taking SRIs who experienced SRI-associated ED were enrolled in this multicenter, 6-week, randomized, flexible-dose, double-blind, placebo-controlled trial. The primary study measures were questions 3 (Q3: frequency of penetration) and 4 (Q4: frequency of maintained erections after penetration) of the International Index of Erectile Function (IIEF) questionnaire. Secondary study measures were all other questions and domains of the IIEF, the Erectile Dysfunction Index of Treatment Satisfaction (EDITS), a global efficacy questionnaire (GEQ), and a patient-maintained event log of sexual activity. RESULTS: Patients receiving sildenafil (N=71) versus placebo (N=71) reported significantly higher mean+/-SE scores on Q3 (3.9+/-0.2 vs. 3.1+/-0.2, p=.003) and Q4 (3.7+/-0.2 vs. 2.8+/-0.2, p<.001) of the IIEF and significantly higher scores on all domains of the IIEF. Patients receiving sildenafil also reported significantly improved scores on all questions of the EDITS questionnaire (p<.02) and the GEQ (p<.0001) and an increased number of successful sexual intercourse attempts per week (p<.0001) compared with patients receiving placebo. All patients remained in MDD remission (score<or=10 on the Hamilton Rating Scale for Depression). Adverse events in patients taking sildenafil (vs. placebo) were headache (9% vs. 9%), dyspepsia (9% vs. 1%), anxiety (6% vs. 4%), and abnormal vision (3% vs. 0%). CONCLUSIONS: Short-term (6-week) administration of sildenafil was well tolerated and significantly improved erectile function and overall sexual satisfaction in men with ED associated with SRI therapy for MDD. Sildenafil may be successfully used to treat SRI-associated ED without interruption of antidepressant therapy.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

Serum prolactin levels among outpatients with major depressive disorder during the acute phase of treatment with fluoxetine.

OBJECTIVE: To determine changes in serum prolactin levels in outpatients with DSM-IV-diagnosed major depressive disorder (MDD) following a 12-week open-label trial of fluoxetine. METHOD: 87 outpatients enrolled in the trial had serum prolactin levels determined at baseline and during their final visit (week 12 or discontinuation visit). In addition, serum testosterone levels were measured in 44 of the 46 men during these 2 visits. Hyperprolactinemia was defined as a serum prolactin level greater than 16.5 ng/mL or 18.9 ng/mL for men and women, respectively. The study was conducted from September 1997 to March 2002. RESULTS: Of 80 patients with normal prolactin levels at baseline, 10 (12.5%) developed hyper-prolactinemia following fluoxetine treatment. Specifically, 2 (4.5%) of 44 men and 8 (22.2%) of 36 women with normal prolactin levels at baseline developed hyperprolactinemia following treatment with fluoxetine (p = .0174 for between-gender difference). In addition, there was a significant increase in mean +/- SD serum prolactin levels following treatment with fluoxetine in all patients with normal baseline prolactin levels (6.4 +/- 3.4 to 10.0 +/- 7.0 ng/mL, p = .002). There were no significant changes from baseline in testosterone levels in men following fluoxetine treatment (448.4 +/- 139.6 to 439.5 +/- 142.1 ng/dL, p > .05; normal above 245 ng/dL), while none of the 44 men developed low testosterone levels following fluoxetine treatment. CONCLUSION: 4.5% of men and 22.2% of women with MDD developed new onset hyper-prolactinemia following fluoxetine treatment.

Adult↗
PubMed2006

A cross-sectional study of the prevalence of cognitive and physical symptoms during long-term antidepressant treatment.

BACKGROUND: Antidepressant therapies have been associated with a variety of side effects of both physical and psychological nature. Until recently, however, the majority of the studies focusing on side effects of antidepressants have not routinely included assessment of cognitive side effects. The purpose of the present work is to examine cross-sectionally the prevalence of cognitive and physical side effects of antidepressants during long-term treatment of depression. METHOD: Patients at least 18 years of age who were deemed responders to antidepressant therapy following at least 3 months of treatment for major depressive disorder (MDD) (diagnosed according to DSM-IV criteria) and whose MDD was considered to be in partial or full remission were eligible for inclusion in this study. Eligible patients were enrolled between January 2003 and December 2004. Study participants were administered the Harvard Department of Psychiatry/National Depression Screening Day (HANDS) scale, the Epworth Sleepiness Scale, the Brief Fatigue Inventory, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), and a study-specific questionnaire inquiring about the emergence of specific side effects such as apathy, fatigue, and inattentiveness. RESULTS: 117 MDD patients (mean +/- SD age: 43.4 +/- 12.6 years; women: N = 78 [66.7%]) met criteria for response according to the HANDS (score < 9). Cognitive symptoms (apathy, inattentiveness, forgetfulness, word-finding difficulty, and mental slowing) were each reported on both the CPFQ and the study-specific questionnaire by more than 30% of the responders on antidepressants. The physical symptoms of fatigue and sleepiness/sedation were reported by over 40% of the responders on both the CPFQ and the study-specific questionnaire. A significant, positive relationship was found between the CPFQ and the severity of residual depressive symptoms as measured by the HANDS total score (F = 15.3, p = .0002). CONCLUSION: Physical and cognitive symptoms are frequently reported by MDD patients who have responded to antidepressants and are treated in the long term with these agents. It is likely that these symptoms are both side effects of the antidepressants as well as residual symptoms of MDD.

Adult↗
PubMed2006

Prospective studies of adverse events related to antidepressant discontinuation.

The value of a prospective assessment of discontinuation-emergent symptoms proximal to the termination of antidepressant treatment cannot be overstated. Though varying in frequency and intensity, nearly all classes of antidepressants have been linked with discontinuation reactions and the associated psychological, physical, and somatic discomfort. Spontaneous reports have been typically used to gauge the risks of discontinuation reactions. Judging from a number of prospective studies, spontaneous reports very likely underestimate the occurrence of discontinuation reactions. This probability suggests that systematic inquiry must urgently become a part of the assessment in antidepressant discontinuation studies. Insight into the number and type of events that may occur following antidepressant discontinuation may be gleaned from instruments such as the Discontinuation-Emergent Signs and Symptoms Scale. This article takes a comprehensive view of a number of studies dealing with discontinuation-related adverse events. It discusses key issues in the analysis of incidence rates of antidepressant discontinuation-emergent adverse events such as the obvious bias of both clinicians' and patients' being aware of the treatment discontinuation. This article also looks at early prospective studies of antidepressant discontinuation reactions based on spontaneous reports and discusses, while making the case for, prospective studies based on systematic inquiry.

Antidepressive Agents↗
PubMed2006

Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research.

OBJECTIVE: Currently, no evidence-based guidelines exist for the management of serotonin reuptake inhibitor (SRI) discontinuation syndrome. This article summarizes recommendations with respect to future research as well as clinical management recommendations for SRI discontinuation syndrome. PARTICIPANTS: In April 2004, a panel of physicians convened in New York City to discuss recommendations for clinical management of and additional research on SRI discontinuation syndrome. EVIDENCE: Previous guidance for management of SRI discontinuation syndrome was proposed in 1997 in a consensus meeting also chaired by Alan F. Schatzberg. A literature search of the PubMed database was conducted to identify articles on SRI discontinuation syndrome that have been published since 1997. CONSENSUS PROCESS: The 2004 panel reviewed important preclinical and clinical studies, discussed prospective investigation of this syndrome in clinical trials, and suggested the establishment of a research network to collect data in naturalistic settings. The panel also reviewed the management recommendations published in 1997 and subsequently updated the recommendations, taking into account the latest clinical data as well as the personal experience of its members with patients. CONCLUSIONS: Additional preclinical and clinical studies are necessary to further elucidate the underlying biological mechanisms of SRI discontinuation syndrome and to identify the patient populations and agents that are most affected by this phenomenon. Management strategies include gradual tapering of doses and should emphasize clinical monitoring and patient education.

Antidepressive Agents↗
PubMed2005

Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part I).

The objective of the present work was to study the interrelationship between white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle including serum folate, vitamin B12, and homocysteine levels in a relatively young sample of outpatients with major depressive disorder (MDD), and to compare the severity of white matter hyperintensities in MDD patients and healthy volunteers. Fifty MDD outpatients (34% women, age 40.6+/-10.3 years), free of psychotropic medications for at least 2 weeks before enrollment, underwent magnetic resonance imaging (MRI) scans of the brain to detect T2 WMHs and also had (1) serum folate, vitamin B12, homocysteine and cholesterol levels measured, and (2) cardiovascular risk factors assessed during the same study visit. Thirty-five healthy comparison subjects (40% women, age 39.2+/-9.8 years) also underwent brain MRI scans. Hypofolatemia, hypertension and age independently predicted a greater severity of total brain WMHs. Separately, the same factors also predicted a greater severity of subcortical WMHs. Hypofolatemic and hypertensive patients had more severe WMHs than normal controls. In light of the adverse impact of WMHs on a number of health-related outcomes later in life, hypofolatemia and hypertension may represent modifiable risk factors to prevent the occurrence of such adverse outcomes.

Adolescent↗
PubMed2005

Anger attacks in major depressive disorder and serum levels of homocysteine.

BACKGROUND: Increased levels of homocysteine have been associated with anger and depression separately. We investigated the association of anger attacks in major depressive disorder (MDD) with serum levels of homocysteine. METHODS: Homocysteine serum levels were measured in 192 outpatients with nonpsychotic MDD, mean age 39.9 +/- 10.7 (range 19-65), 53% women, at baseline of an open-trial antidepressant treatment. We used the Massachusetts General Hospital Anger Attacks Questionnaire to evaluate anger attacks, the Structured Clinical Interview for DSM-III-R Axis I Disorders-Patient Edition (SCID-I/P) to diagnose MDD and the 17-item Hamilton Rating Scale for Depression to measure depression severity. RESULTS: In the multiple regression analysis split by anger attacks adjusted for parameters of depression, creatinine, vitamin B(12), folate, age, smoking, and alcohol consumption, serum levels of homocysteine were positively correlated with length of current major depressive episode (t value, 3.01; 95% confidence interval [CI], .09 to .43; p = .004) and HAM-D-17 scores (t value, 2.48; 95% CI, .07 to 0.64; p = .016) in patients with anger attacks but not in those without anger attacks. CONCLUSIONS: Anger attacks in MDD may moderate the relationship of homocysteine serum levels with the severity and length of the depressive episode. Future studies are warranted to confirm and clarify the nature of this moderating effect.

Adult↗
PubMed2005

Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II).

The objective of this study was to investigate the relative impact of brain white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle metabolism (including serum folate, vitamin B12 and homocysteine levels) on the outcome of antidepressant treatment in non-elderly subjects with major depressive disorder (MDD). Fifty MDD subjects were administered brain magnetic resonance imaging (MRI) scans at 1.5 T to detect T2 WMHs. The severity of brain WMHs was classified with the Fazekas scale (range=0-3). We assessed cardiovascular risk factors in all MDD subjects (age, gender, smoking, diabetes, family history, hypertension, cholesterol). MDD patients also had serum folate, vitamin B12 and homocysteine levels measured. All MDD subjects received treatment with fluoxetine 20 mg/day for 8 weeks. In a logistic regression, the severity of subcortical WMHs and the presence of hypofolatemia were independent predictors of lack of clinical response to antidepressant treatment. Separately, hypofolatemia also predicted lack of remission to antidepressant treatment. These associations were independent of the presence of smoking, diabetes, family history, hypercholesterolemia, hyperhomocysteinemia and low B12 levels. Although preliminary, the results of the present work suggest that subcortical brain WMHs and hypofolatemia may have an independent negative impact on the likelihood of responding to antidepressant treatment in non-geriatric subjects with MDD.

Adolescent↗
PubMed2005

An evaluation of the quick inventory of depressive symptomatology and the hamilton rating scale for depression: a sequenced treatment alternatives to relieve depression trial report.

BACKGROUND: Nine DSM-IV-TR criterion symptom domains are evaluated to diagnose major depressive disorder (MDD). The Quick Inventory of Depressive Symptomatology (QIDS) provides an efficient assessment of these domains and is available as a clinician rating (QIDS-C16), a self-report (QIDS-SR16), and in an automated, interactive voice response (IVR) (QIDS-IVR16) telephone system. This report compares the performance of these three versions of the QIDS and the 17-item Hamilton Rating Scale for Depression (HRSD17). METHODS: Data were acquired at baseline and exit from the first treatment step (citalopram) in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Outpatients with nonpsychotic MDD who completed all four ratings within +/-2 days were identified from the first 1500 STAR*D subjects. Both item response theory and classical test theory analyses were conducted. RESULTS: The three methods for obtaining QIDS data produced consistent findings regarding relationships between the nine symptom domains and overall depression, demonstrating interchangeability among the three methods. The HRSD17, while generally satisfactory, rarely utilized the full range of item scores, and evidence suggested multidimensional measurement properties. CONCLUSIONS: In nonpsychotic MDD outpatients without overt cognitive impairment, clinician assessment of depression severity using either the QIDS-C16 or HRSD17 may be successfully replaced by either the self-report or IVR version of the QIDS.

Adult↗
PubMed2005

Adjunctive atomoxetine for residual fatigue in major depressive disorder.

OBJECTIVE: To assess the effectiveness and safety of atomoxetine as an adjunctive medication for residual fatigue in a naturalistic treatment setting. METHODS: A retrospective chart review was conducted to identify major depressive disorder (MDD) patients who had experienced significant symptom improvement (either partial response or remission) following treatment with conventional antidepressants but who were continuing to complain of fatigue. Fourteen such patients (42.2+/-13.4 years of age, five women, baseline HDRS 6.2+/-2.4) with a 17-item Hamilton Depression Rating Scale (HDRS17)<11 who received adjunctive atomoxetine for fatigue were included in the report. Antidepressants augmented were the selective serotonin reuptake inhibitors (SSRIs) (n=11; 78.6%), mirtazapine (n=2, 14.3%), and amitriptyline (n=1, 7.1%). RESULTS: Twelve (85.7%) patients (nine remitters, three partial responders) received at least 4 weeks of atomoxetine treatment. The remaining two (partial responders) discontinued atomoxetine within 1-3 days due to increased anxiety. The brief fatigue inventory (BFI) and Clinical Global Impressions Scale (CGI) were administered when atomoxetine was first prescribed, and following 4-10 weeks of treatment (mean of 5.4+/-1.8 weeks). There was a significant decrease in BFI scores (41.9+/-14.9 versus 24.3+/-13.4, p=0.0015), and HDRS-17 scores (6.2+/-2.4 versus 3.5+/-2.8, p=0.0466), but not CGI-S scores (1.3+/-1.4-1.0+/-0.0, p=0.08) following treatment with atomoxetine. 5/12 (41.6%) patients had a 50% or greater decrease in BFI scores. All 12 patients were remitters at follow-up. The mean atomoxetine dose was 42.8+/-10.6 mg. Side effects included insomnia (n=6), increased anxiety (n=3), nausea (n=1) and dry mouth (n=1). CONCLUSIONS: Although preliminary, these results suggest a possible augmentation role for atomoxetine when used in conjunction with conventional antidepressants for residual fatigue in MDD. Prospective as well as controlled studies are necessary to further explore the role of atomoxetine augmentation in MDD.

Adrenergic Uptake Inhibitors↗
PubMed2005

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 ( 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.

Adolescent↗
PubMed2005

Comorbid psychiatric disorders in depressed outpatients: demographic and clinical features.

BACKGROUND: This study evaluated the clinical and sociodemographic features associated with various degrees of concurrent comorbidity in adult outpatients with nonpsychotic major depressive disorder (MDD). METHODS: Outpatients enrolled in the STAR*D trial completed the Psychiatric Diagnostic Screening Questionnaire (PDSQ). An a priori 90% specificity threshold was set for PDSQ responses to ascertain the presence of 11 different concurrent DSM-IV Axis I disorders. RESULTS: Of 1376 outpatients, 38.2% had no concurrent comorbidities, while 25.6% suffered one, 16.1% suffered two, and 20.2% suffered three or more comorbid conditions. Altogether, 29.3% met threshold for social anxiety disorder, 20.8% for generalized anxiety disorder, 18.8% for posttraumatic stress disorder, 12.4% for bulimia, 11.9% for alcohol abuse/dependence, 13.4% for obsessive-compulsive disorder, 11.1% for panic disorder, 9.4% for agoraphobia, 7.3% for drug abuse/dependence, 3.7% for hypochondriasis, and 2.2% for somatoform disorder. Those with more concurrent Axis I conditions had earlier ages at first onset of MDD, longer histories of MDD, greater depressive symptom severity, more general medical comorbidity (even though they were younger than those with fewer comorbid conditions), poorer physical and mental function, health perceptions, and life satisfaction; and were more likely to be seen in primary care settings. LIMITATIONS: Participants had to meet entry criteria for STAR*D. Ascertainment of comorbid conditions was not based on a structured interview. CONCLUSIONS: Concurrent Axis I conditions (most often anxiety disorders) are very common with MDD. Greater numbers of concurrent comorbid conditions were associated with increased severity, morbidity, and chronicity of their MDD.

Adult↗
PubMed2005

The relationship between early changes in the HAMD-17 anxiety/somatization factor items and treatment outcome among depressed outpatients.

The 17-item Hamilton Rating Scale for Depression (HAMD-17) Anxiety/Somatization factor includes six items: Anxiety (psychic), Anxiety (somatic), Somatic Symptoms (gastrointestinal), Somatic Symptoms (general), Hypochondriasis and Insight. This study examines the relationship between early changes (defined as those observed between baseline and week 1) in these HAMD-17 Anxiety/Somatization Factor items and treatment outcome among major depressive disorder (MDD) patients who participated in a study comparing the antidepressant efficacy of a standardized extract of hypericum with both placebo and fluoxetine. Following a 1-week, single-blind washout, patients with MDD diagnosed by the Structured Clinical Interview for DSM-IV (SCID) were randomized to 12 weeks of double-blind treatment with hypericum extract (900 mg/day), fluoxetine (20 mg/day) or placebo. The relationship between early changes in HAMD-17 anxiety/somatization factor items and treatment outcome was assessed separately for patients who received study treatment (hypericum or fluoxetine) versus placebo with a logistic regression method. One hundred and thirty-five patients (female 57%, mean age=37.3+/-11.0 years; mean baseline HAMD-17=19.7+/-3.2 years) were randomized to double-blind treatment and were included in the intent-to-treat (ITT) analyses. After adjusting for baseline HAMD-17 scores and for multiple comparisons with the Bonferroni correction, patients who remitted (HAMD-17 score <8) after study treatment had significantly greater early improvement in Somatic Symptoms (General) scores than non-remitters. No other significant differences in early changes were noted for the remaining items between remitters versus non-remitters who received active treatment. For patients treated with placebo, early change was not predictive of remission for any of the items after Bonferroni correction. In conclusion, the presence of early improvement on the HAMD-17 item concerning fatigue and general somatic symptoms is significantly predictive of achieving remission at endpoint with active study treatment but not with placebo.

Adolescent↗
PubMed2005

Empirical testing of two models for staging antidepressant treatment resistance.

BACKGROUND: An increasing amount of attention has been paid to treatment resistant depression. Although it is quite common to observe nonremission to not just one but consecutive antidepressant treatments during a major depressive episode, a relationship between the likelihood of achieving remission and one's degree of resistance is not clearly known at this time. This study was undertaken to empirically test 2 recent models for staging treatment resistance. MATERIALS AND METHODS: Psychiatrists from 2 academic sites reviewed charts of patients on their caseloads. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scales were used to measure severity of depression and response to treatment, and 2 treatment-resistant staging scores were classified for each patient using the Massachusetts General Hospital staging method (MGH-S) and the Thase and Rush staging method (TR-S). RESULTS: Out of the 115 patient records reviewed, 58 (49.6%) patients remitted at some point during treatment. There was a significant positive correlation between the 2 staging scores, and logistic regression results indicated that greater MGH-S scores, but not TR-S scores, predicted nonremission. CONCLUSIONS: This study suggests that the hierarchical manner in which the field has typically gauged levels of treatment resistance may not be strongly supported by empirical evidence. This study suggests that the MGH staging model may offer some advantages over the staging method by Thase and Rush, as it generates a continuous score that considers both number of trials and intensity/optimization of each trial.

Adult↗
PubMed2005

A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder.

OBJECTIVE: This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo and fluoxetine. METHOD: After a 1-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate. RESULTS: One hundred thirty-five patients (57% women; mean age, 37.3 +/- 11.0; mean HAMD-17, 19.7 +/- 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean +/- SD, 10.2 +/- 6.6) compared with the fluoxetine group (n = 47; 13.3 +/- 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 +/- 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). Overall, St John's wort appeared to be safe and well tolerated. CONCLUSION: St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25%) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo.

Adolescent↗