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Biomedical subjects

Maurizio Fava

Publications and source records attributed to Maurizio Fava.

At least 109 records · Page 6Linked to original sources
PubMed2003

Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment.

BACKGROUND: The short (S) allele of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been associated with poorer antidepressant response in major depressive disorder (MDD) and with antidepressant-induced mania. This study investigated a possible association with treatment-emergent insomnia or agitation. METHODS: Thirty-six outpatients with MDD were genotyped at 5HTTLPR and treated with open-label fluoxetine up to 60 mg/day. Treatment-emergent adverse effects were assessed at each study visit. RESULTS: Of nine subjects homozygous for the "S" allele, seven (78%) developed new or worsening insomnia, versus 6 of 27 (22%) non-"S"-homozygous subjects (Fisher's exact p =.005). Similarly, six of nine subjects homozygous for the "S" allele (67%) developed agitation, versus 2 of 27 (7%) of non-"S"-homozygous subjects (Fisher's exact p =.001). CONCLUSIONS: The "S" allele of the 5HTTLPR may identify patients at risk for developing insomnia or agitation with fluoxetine treatment. This preliminary result requires confirmation in larger samples.

Adult↗
PubMed2003

Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD).

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was conceived in response to a National Institute of Mental Health initiative seeking a public health intervention model that could generate externally valid answers to treatment effectiveness questions related to bipolar disorder. STEP-BD, like all effectiveness research, faces many design challenges, including how to do the following: recruit a representative sample of patients for studies of readily available treatments; implement a common intervention strategy across diverse settings; determine outcomes for patients in multiple phases of illness; make provisions for testing as yet undetermined new treatments; integrate adjunctive psychosocial interventions; and avoid biases due to subject drop-out and last-observation-carried-forward data analyses. To meet these challenges, STEP-BD uses a hybrid design to collect longitudinal data as patients make transitions between naturalistic studies and randomized clinical trials. Bipolar patients of every subtype with age >/= 15 years are accessioned into a study registry. All patients receive a systematic assessment battery at entry and are treated by a psychiatrist (trained to deliver care and measure outcomes in patients with bipolar disorder) using a series of model practice procedures consistent with expert recommendations. At every follow-up visit, the treating psychiatrist completes a standardized assessment and assigns an operationalized clinical status based on DSM-IV criteria. Patients have independent evaluations at regular intervals throughout the study and remain under the care of the same treating psychiatrist while making transitions between randomized care studies and the standard care treatment pathways. This article reviews the methodology used for the selection and certification of the clinical treatment centers, training study personnel, the general approach to clinical management, and the sequential treatment strategies offered in the STEP-BD standard and randomized care pathways for bipolar depression and relapse prevention.

Bipolar Disorder↗
PubMed2003

Serum cholesterol and serotonergic function in major depressive disorder.

Studies have revealed a relationship between serum cholesterol levels and serotonergic (5HT) function in healthy young adults. Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy adults, while MDD patients with elevated cholesterol have a poorer prognosis for treatment response. The goal of the present study is to examine (1) the relationship between serum cholesterol levels and central 5HT function by way of the cortisol and prolactin response to the 5HT-selective agonist DL-fenfluramine in MDD patients and (2) differences in 5HT-function between MDD patients who present with and without elevated cholesterol. Fasting serum cholesterol levels were measured in 21 outpatients with MDD. After oral administration of 60 mg of DL-fenfluramine in these patients, cortisol and prolactin responses were measured to test whether cholesterol levels predicted the degree of cortisol or prolactin response. Cortisol and prolactin responses were compared between patients with and without elevated cholesterol levels, defined as >/=200 mg/dl. MDD patients with elevated cholesterol levels were more likely to demonstrate an attenuated cortisol response. There was no relationship between cholesterol levels and cortisol or prolactin response. Excess cholesterol may adversely affect the function of membrane-bound serotonergic structures, and this may explain why MDD patients with elevated cholesterol are more likely to exhibit attenuated neuroendocrine responses, less likely to respond to treatment and more likely to relapse.

Adult↗
PubMed2003

Axis III disorders in treatment-resistant major depressive disorder.

A number of naturalistic studies have found that medical co-morbidity conveys a worse long-term prognosis in the treatment of major depressive disorder (MDD). The purpose of this study was to test whether the presence of co-morbid medical conditions can predict clinical response in patients with treatment-resistant MDD (TRD) treated with open-label nortriptyline (NT). Ninety-two patients with TRD entered a 6-week open trial of NT. The presence of co-morbid medical disorders was assessed during the screen visit. The degree of medical co-morbidity during the screen visit was then quantified with the use of the Cumulative Illness Rating Scale-Geriatric Version (CIRS(G)). We tested whether CIRS(G) scores predicted clinical response or depression severity at endpoint. CIRS scores at baseline did not significantly predict treatment response. The results of this study fail to confirm the relationship between co-morbid medical conditions and poor outcome in the treatment of MDD for patients with TRD. Patients with TRD and co-morbid medical conditions can be expected to respond to antidepressants as well as their counterparts without concurrent axis III co-morbidity. The CIRS(G) scores for this TRD sample were lower than those reported for geriatric depression, or for depressed patients with severe medical illness, common in medical and surgical wards and in most specialty clinics of large academic centers. Thus, the present results cannot be generalized to such populations.

Adult↗
PubMed2003

Somatic symptoms in treatment-resistant depression.

The purpose of this work was to study the prevalence of somatic symptoms in patients with treatment-resistant depression (TRD) and their impact on the response to antidepressant treatment. Somatic symptoms were assessed during the screen visit with the Symptom Questionnaire (SQ) somatic symptom (SQ-SS) and somatic well-being sub-scales (SQ-SWB) in 40 patients with TRD enrolled in a 6-week open trial of nortriptyline. A logistic regression was used to test whether SQ-SS or SQ-SWB scores predicted clinical response to nortriptyline. Ninety-five percent of patients reported at least one somatic symptom. Higher SQ-SS scores during the screen visit predicted poorer response to nortriptyline. There was a trend for lower SQ-SWB scores to predict poor response to nortriptyline. None of the patients with SQ-SS scores above the mean for the sample responded to nortriptyline. The overwhelming majority of patients with TRD presented with somatic symptoms. In addition, a greater number of somatic symptoms during the screen visit placed patients at risk for further treatment resistance.

Adult↗
PubMed2003

Diagnosis and definition of treatment-resistant depression.

Treatment-resistant depression (TRD) typically refers to inadequate response to at least one antidepressant trial of adequate doses and duration. TRD is a relatively common occurrence in clinical practice, with up to 50% to 60% of the patients not achieving adequate response following antidepressant treatment. A diagnostic re-evaluation is essential to the proper management of these patients. In particular, the potential role of several contributing factors, such as medical and psychiatric comorbidity, needs to be taken into account. An accurate and systematic assessment of TRD is a challenge to both clinicians and researchers, with the use of clinician-rated or self-rated instruments being perhaps quite helpful. It is apparent that there may be varying degrees of treatment resistance. Some staging methods to assess levels of treatment resistance in depression are being developed, but need to be tested empirically.

Antidepressive Agents↗
PubMed2003

Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial.

CONTEXT: Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. OBJECTIVE: To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. DESIGN, SETTING, AND PATIENTS: Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. INTERVENTION: Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). RESULTS: Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration. CONCLUSION: In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.

Adult↗
PubMed2003

Early-onset depression and the emotional and behavioral characteristics of offspring.

We compared the emotional and behavioral characteristics of offspring of parents with early-onset depression and the offspring of parents with late-onset depression. Forty-three parents who met criteria for major depressive disorder (MDD) completed the Achenbach Child Behavior Checklist-Parent Report Version (CBCL) for a birth child (n=43, age range 6-17 years). Parents were classified as having either early SD onset (<19 years) or late-onset (> or = 19 years) MDD based on responses gathered during the SCID-P interview. Unpaired t-tests were used to compare the two offspring groups on CBCL clinical and competency scales. Chi-square analyses and unpaired t-tests were used to compare the two parent groups on demographic and clinical features. Offspring of parents with early-onset depression scored significantly higher on the majority of the CBCL clinical scale scores when compared with offspring of parents with late-onset depression, rated as exhibiting higher levels of the characteristics measured: withdrawn, anxious/depressed, social problems, thought problems, attention problems, delinquent behavior, and aggressive behavior. Additionally, this group had a significantly higher total T score (a global measure of psychopathology) and significantly lower social functioning. Children of parents with early-onset depression may be at higher risk for behavioral and emotional problems than offspring of parents with late-onset depression. This finding may be significant in uncovering sources of vulnerability and formulating intervention strategies for offspring of depressed parents.

Adolescent↗
PubMed2003

S-adenosyl-methionine in depression: a comprehensive review of the literature.

As many as 29% to 46% of patients with major depressive disorder (MDD) show only partial or no response to an adequate course of an antidepressant. The current practice is to increase the dose, switch to another antidepressant, or to combine the initial antidepressant with an antidepressant of a different class or a non-antidepressant agent. A growing number of studies have also been directed toward exploring the potential use of augmenting traditional antidepressants with nonpharmaceutic supplements, or even using such supplements as monotherapy for depression. S-adenosyl-methionine (SAMe) is one such compound. Compared with many other nonpharmaceutic supplements, SAMe has been extensively studied, and impressive literature extending back three decades suggests the antidepressant efficacy of SAMe. In the present work, the authors summarize the literature, focusing on the potential role of SAMe and its precursors in the pathophysiology of MDD, followed by a review of studies examining the use of SAMe for the treatment of MDD. Finally, the authors propose a model that would explain the actions of SAMe in the central nervous system.

Antidepressive Agents↗
PubMed2003

Background and rationale for the sequenced treatment alternatives to relieve depression (STAR*D) study.

Sequenced Treatment Alternatives to Relieve Depression (STAR*D) attempts to fill in major clinical information gaps and to evaluate the theoretical principles and clinical beliefs that currently guide pharmacotherapy of major depressive disorder. The study is conducted in representative participant groups and settings using clinical management tools that easily can be applied in daily practice. Outcomes include clinical outcomes and health care utilization and cost estimates. Research findings should be immediately applicable to, and easily implemented in, the daily primary and specialty care practices. This article provides the overall rationale for STAR*D and details the rationale for key design, measurement, and analytic features of the study.

Antidepressive Agents↗
PubMed2003

Switching to bupropion in fluoxetine-resistant major depressive disorder.

Up to 50% of patients with major depressive disorder (MDD) fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as an initial treatment. Switching to bupropion, for depressed patients not responding to SSRIs, is a popular strategy among clinicians. This study assesses the efficacy of bupropion SR in the management of MDD resistant to a prospective trial of fluoxetine. Twenty-nine patients with MDD refractory to an 8- to 12-week open-trial of fluoxetine were enrolled in an 8-week open-trial of bupropion SR. Both a completer analysis (n = 20) and a modified intent-to-treat analysis (n = 26) were performed to evaluate bupropion SR response rates. Using a completer analysis, seven patients (35.0%) were classified as responders, five (25.0%) partial responders, and eight (40.0%) nonresponders. A modified intent to treat analysis resulted in nine (34.6%) patients classified as responders, eight (30.8%) partial responders, and nine (34.6%) nonresponders. The overall proportion of remitters was 6/20 (30.0%) using a completer analysis and 6/26 (23.1%) using an MITT analysis. Approximately 60% of patients with MDD resistant to a prospective trial of fluoxetine experienced a full or partial response to bupropion SR. Bupropion SR should be considered as a potential treatment for patients who remain depressed despite treatment with SSRIs

Adult↗
PubMed2003

Lithium augmentation of nortriptyline for subjects resistant to multiple antidepressants.

Lithium augmentation, the most studied augmentation strategy for depression, has not been evaluated in patients with a history of non-response to multiple antidepressants. The objective of this study was to assess the efficacy of lithium augmentation for patients with a history of treatment resistant depression who also failed a prospective trial of nortriptyline. We enrolled 92 subjects with treatment resistant depression. Treatment resistance was defined by at least one, but no more than five, adequate trials of antidepressants during the current episode. Subjects were treated with nortriptyline (NT) for 6 weeks. Those subjects who tolerated NT for 6 weeks and whose depression did not respond (n=35) were randomized to receive either lithium (n=18) or placebo (N=17) augmentation of nortriptyline for an additional 6 weeks. Response was defined as an equal to or greater than 50% decrease in HAM-D-17 scores. After 6 weeks of double-blind augmentation, 12.5 % of subjects responded to lithium and 20.0% to placebo. Our results revealed no significant difference between lithium and placebo augmentation. While lithium augmentation seems to be useful in depression refractory to a single medication in some studies, our data suggest limited usefulness of this option for patients refractory to multiple treatments. More definitive data await the outcome of the NIMH Sequential Treatment Alternatives to Relieve Depression (STAR*D) study.

Adolescent↗
PubMed2003

A pilot, open study of sertraline in outpatients with treatment-resistant depression (TRD) or with a history of TRD who responded but later relapsed.

While most depressed patients are prescribed a selective serotonin reuptake inhibitor (SSRI) as an initial treatment, the use of SSRIs as a second or third-line treatment for depression is not as prevalent. This trial assessed the efficacy of sertraline for patients with treatment-resistant depression (TRD) or patients with a history of TRD who responded but later relapsed. Twelve patients with TRD who had not responded to a number of antidepressant trials (n=7), or had responded but subsequently suffered a relapse (n=5), were enrolled in an 8-week, open trial of sertraline. Both a completer analysis (n=6) and an intent-to-treat (ITT) analysis (n=12) were performed to evaluate sertraline response rates. Using a completer analysis, four patients (66.6%) were classified as responders; one (16.7%) as a partial responder and one (16.7%) as a non-responder. An ITT analysis resulted in five (41.7%) patients being classified as responders; one (8.3%) as a partial responder and six (50%) as non-responders. Of the four responders in the completer analysis, three (50%) achieved remission. Of the five responders in the ITT analysis, four (33.3%) achieved remission. Overall, two of seven (28.6%) non-responders and three of five (60.0%) relapsers responded to sertraline. The present results suggest the potential utility of sertraline for patients with TRD, or those with a history of TRD who responded but later relapsed, and warrant larger, placebo-controlled studies to further explore the potential role of sertraline for such patients.

Adult↗
PubMed2003

Switching to reboxetine: an efficacy and safety study in patients with major depressive disorder unresponsive to fluoxetine.

The aim of the present study was to evaluate the efficacy and safety of an immediate switch to reboxetine, a selective noradrenaline reuptake inhibitor (selective NRI), in patients with depression unresponsive to the selective serotonin reuptake inhibitor (SSRI) fluoxetine. The study included 128 adult outpatients with DSM-IV major depressive disorder (MDD) who had not responded to at least 6 to 12 weeks of fluoxetine treatment, with at least 3 weeks of treatment on a minimum dose of 40 mg/d. Patients were switched, without a washout period, to reboxetine 4 mg twice daily, with the possibility of increasing the dose to 10 mg/d (given in divided doses) after 4 weeks of treatment. Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales. Safety was evaluated by recording spontaneously reported adverse events.A statistically significant (P < 0.001) improvement in the mean total HAM-D-17 score was seen from baseline by week 1 of treatment with reboxetine, and the improvement continue to week 8. CGI-I and CGI-S scores were similarly improved. The switch to reboxetine was well tolerated; the most common treatment-emergent adverse events were insomnia, headache, dry mouth, diaphoresis, and constipation, all of which were mild to moderate in severity and decreased in frequency as the study progressed.Immediate switching to reboxetine appears to be a safe and effective treatment for patients with depression who have failed to respond to an adequate dose of fluoxetine.

Adolescent↗
PubMed2003

Serum cholesterol in treatment-resistant depression.

OBJECTIVE: Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy controls. A previous study by our group reported that depressed patients with elevated cholesterol levels (>or=200 mg/dl) were significantly more likely to be nonresponders to fluoxetine treatment than depressed patients with nonelevated cholesterol levels. However, very little is known regarding cholesterol in patients with treatment-resistant depression (TRD). The purpose of this study was to compare cholesterol levels at baseline between depressed patients with and without TRD and to test whether cholesterol levels at baseline can predict clinical response in patients with TRD treated with open-label nortriptyline (NT). METHODS: Ninety-two patients with TRD entered a 6-week open trial of NT. Baseline cholesterol levels were randomly collected for 59 of these patients. Controlling for age and gender, we compared baseline cholesterol and triglyceride levels for 35 patients with TRD who did not respond to NT with 205 non-TRD patients who responded to an 8-week open trial of fluoxetine. Furthermore, with the use of logistic regression, we tested whether baseline cholesterol levels predicted clinical response to NT in the patients with TRD. RESULTS: Patients with TRD had higher triglyceride levels at baseline compared with depressed patients without TRD. Cholesterol defined as a dichotomous variable being elevated if equal to or greater than 200 mg/dl, predicted poor response to a 6-week open trial of NT in patients with TRD. CONCLUSIONS: The results of this study confirm the relationship between hypercholesterolemia and poor outcome in the treatment of MDD for patients with TRD.

Adolescent↗
PubMed2003

The impact of medical comorbidity on acute treatment in major depressive disorder.

OBJECTIVE: The authors investigated the impact of medical comorbidity on the acute phase of antidepressant treatment in subjects with major depressive disorder. METHOD: A total of 384 outpatients meeting DSM-III-R criteria for major depressive disorder enrolled in 8-week open treatment with fluoxetine, 20 mg/day. The authors used the Cumulative Illness Rating Scale to measure the burden of medical comorbidity and the 17-item Hamilton Rating Scale for Depression to assess changes in depressive symptoms. The outcome measures were response to treatment (>/=50% reduction in score) and clinical remission (score </=7 at the end of the trial). RESULTS: Compared to responders to fluoxetine, nonresponders had significantly higher Cumulative Illness Rating Scale scores and a greater number of Cumulative Illness Rating Scale categories were endorsed. Compared to subjects who achieved remission with antidepressant treatment, those who did not achieve remission had significantly higher Cumulative Illness Rating Scale scores and a greater number of Cumulative Illness Rating Scale categories were endorsed (i.e., more organs were affected by medical illness). The final Hamilton depression scale score was directly correlated with the total Cumulative Illness Rating Scale score and the number of Cumulative Illness Rating Scale categories endorsed. CONCLUSIONS: The total burden of medical illness and the number of organ systems affected by medical illness had a significantly negative predictive value for clinical outcome in the acute phase of treatment in major depressive disorder.

Adult↗
PubMed2003

When should a trial of fluoxetine for major depression be declared failed?

OBJECTIVE: Although the newer antidepressants are widely used, little is known about how long it takes to see their full effect. The authors sought to determine how many weeks a fluoxetine trial with no improvement should continue before treatment is changed. METHOD: The data involved 840 patients in a 12-week open trial of fluoxetine, 20 mg/day, followed by a blinded, placebo-controlled discontinuation study. Outcomes at 4, 6, 8, 10, and 12 weeks were classified as nonresponse, partial response, response, and remission and were based on Hamilton Depression Rating Scale scores. The rate of remission at week 12 was calculated for each group of patients without remission at the earlier time points. The time to relapse during weeks 13-26 of the discontinuation study was examined in patients taking placebo and fluoxetine in relation to status at week 6. RESULTS: Patients unimproved at week 6 had a remission rate at week 12 of 31%-41%. For patients with remission at week 12, level of improvement at week 6 did not affect prognosis in weeks 13-26. Of the unimproved patients at week 8, 23% had remissions by week 12. The week 12 remission rate for unimproved patients at week 4 was clearly high enough to justify continued treatment; the rate for unimproved patients at week 10 was too low. CONCLUSIONS: These data suggest that nonresponse to fluoxetine should not be declared until 8 weeks of treatment have elapsed. Practitioners should discuss trial length with patients at the beginning of treatment.

Adolescent↗