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Biomedical subjects

M Fava

Publications and source records attributed to M Fava.

At least 19 recordsLinked to original sources
PubMed2000

Elevated plasma thymopoietin associated with therapeutic nonresponsiveness in major depression.

BACKGROUND: Stress predisposes to major depression, and hyperactivity of the stress-activated hypothalamic-pituitary-adrenal (HPA) axis occurs in this disease. Thymopentin, an active fragment of thymopoietin (TP), reduces endocrine and behavioral responses to experimental stress, possibly by lowering plasma TP (pTP) levels. METHODS: Plasma TP and the HPA hormones arginine vasopressin (pAVP), adrenocorticotropic hormone (pACTH), and plasma cortisol (pCORT) were measured in 21 untreated depressed patients and 21 matched control subjects. Clinical responses to antidepressants were evaluated in 17 depressed patients. RESULTS: Plasma TP was elevated in depression (p < .002), with in 8 out of 21 (38%) depressed patients having significant elevations (p < .03). For 17 patients whose antidepressant responses were evaluated, nonresponsiveness occurred in 6 out of 7 (86%) with elevated pTP (>7.5 pg/mL) versus 3 out of 10 (30%) with normal pTP (p < .05). CONCLUSIONS: The significant association of elevated pTP with nonresponsiveness to antidepressant drugs may signify a distinct pathogenesis for the depression of patients with elevated pTP.

Adrenocorticotropic Hormone↗
PubMed2000

Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study.

BACKGROUND: Previous studies have shown that major depression is frequently accompanied by hypercortisolemia. There is some evidence suggesting that an increase in the glucocorticoid levels may make hippocampal cells more vulnerable to insults caused by hypoxia, hypoglycemia, or excitatory neurotransmitters. Using magnetic resonance imaging (MRI), the hippocampi of patients with major depression were measured and compared with values observed in control subjects. METHODS: Thirty-eight patients with primary unipolar major depression were recruited. Twenty control subjects were matched for age, gender, and years of education. The hippocampal volume was measured from coronal MRI scans in all of the subjects. Patients were also grouped and compared as responders and nonresponders to treatment with fluoxetine of 20 mg/day, for 8 weeks. Hamilton Depression Rating Scale (HDRS) was used to determine the severity of depression. RESULTS: No significant differences were observed between the hippocampal volumes of patients with major depression and control subjects; however, a significant correlation was observed between the left hippocampal volume of men and their HDRS baseline values. In addition, female responders had a statistically significant higher mean right hippocampal volume than nonresponders. CONCLUSIONS: The results of our study indicate no reduction in the volume of the hippocampus in patients with major depression. Nonetheless, the results do suggest that the effects of disease severity, gender, and treatment response may influence hippocampal volume.

Adult↗
PubMed2000

Fenfluramine challenge in unipolar depression with and without anger attacks.

We have previously hypothesized that patients with major depression and anger attacks may have a greater central serotonergic dysregulation than depressed patients without such attacks. We wanted to compare the prolactin response to fenfluramine challenge, as an indirect measure of central serotonergic function, in depressed patients with and without anger attacks. We recruited 37 outpatients (22 men and 15 women; mean age: 39.5+/-10.5) with DSM-III-R major depressive disorder, diagnosed with the SCID-P. Their initial 17-item Hamilton Rating Scale for Depression score was >/=16. Patients were classified as either having or not having anger attacks with the Anger Attacks Questionnaire. All patients received a single-blind placebo challenge followed by a fenfluramine challenge (60 mg orally) the next day. Plasma prolactin measurements were obtained with double antibody radioimmunoassay before and after both placebo and fenfluramine challenges, and fenfluramine and norfenfluramine blood levels after each challenge were determined by gas chromatography. Of the 37 study participants, 17 (46%) were classified as having anger attacks. There were no significant differences in age, gender, fenfluramine, or norfenfluramine blood levels between depressed patients with and without anger attacks. Depressed patients with anger attacks showed a significantly blunted prolactin response to fenfluramine challenge compared to patients without anger attacks. As previous studies have shown blunted prolactin responses to fenfluramine in impulsive aggression among patients with personality disorders, our results support our hypothesis that depressed patients with anger attacks may have a relatively greater serotonergic dysregulation than depressed patients without these attacks.

Adult↗
PubMed2000

Incidence of RET mutations in patients with Hirschsprung's disease.

BACKGROUND: RET mutations have been reported variously to affect 7% to 41% of Hirschsprung's disease (HSCR) patients depending on familial or sporadic occurrence of the disease, length of aganglionosis and possible association with other disease phenotypes. The authors report a study of the incidence of RET mutations in unselected HSCR patients from two regional centers and correlate their genotypes and phenotypes. METHODS: The records of HSCR patients treated in 2 regional centers with a combined population of 5 million were reviewed, and blood samples were obtained from 57 patients. During the same period, 39 patients with similar demographic data refused or provided insufficient blood for study. DNA was extracted, and the 21 exons of the RET protooncogene were screened for mutations using denaturing gradient gel electrophoresis (DGGE). RESULTS: Of 57 patients, 48 were sporadic, and 9 were familial. Lengths of aganglionosis were total colonic, 4; long, 11; short, 39; ultrashort, 1; unclassified, 2. Associated anomalies were present in 20. Causative mutations were identified in 4 (7%): missense or "silent" in 3 (exons 5, 11, 13) and deletion in 1. The silent mutation of exon 11 recently has been shown to have effects on correct RET mRNA splicing. One mutation occurred in total colonic aganglionosis (25%), 1 in long segment dysganglionosis (9%), and 2 in short segment aganglionosis (5%). Surprisingly, all these mutations occurred in sporadic cases (10%). Five patients (9%) had rare polymorphic alleles at exon 14 (n = 1) and exon 18 (n = 4). Fifty patients (88%) showed common polymorphic alleles (sequence variants) in 1 or more exons (> 4, n = 5). CONCLUSIONS: RET mutation as a primary cause for Hirschsprung's disease in the general surgical population is less frequent than previously thought. This observation is compatible with the hypothesis that HSCR could be a polygenic disease caused by additive subclinical effects of more than one gene, including RET.

Drosophila Proteins↗
PubMed2000

Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression.

BACKGROUND: Major depression with high levels of anxiety (anxious depression) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment. It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors. For this reason, using head-to-head acute treatment comparison, we compared efficacy and tolerability of fluoxetine, sertraline, and paroxetine among depressed patients with high levels of anxiety. METHODS: Patients (N = 108) with DSM-IV major depression and high levels of anxiety (a HAM-D-Anxiety/Somatization Factor score > or =7) were randomized to fluoxetine, sertraline, or paroxetine treatment in a double-blind fashion. Changes in overall depression and anxiety were assessed. RESULTS: Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores. Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores, except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score. There were no significant differences across treatments in percentages of patients with substantial emergence, any worsening, or improvement at endpoint in individual HAM-D Items 9 (agitation), 10 (psychic anxiety), and 11 (somatic anxiety). Overall, all treatments were well tolerated. CONCLUSION: These data showed no significant differences in efficacy and tolerability of fluoxetine, sertraline, and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression. Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression.

Adult↗
PubMed2000

Hormonal markers of stress response following interruption of selective serotonin reuptake inhibitor treatment.

Depressive illness is associated with loss of the usual regulation of stress-responsive hormonal and neurotransmitter systems, and antidepressants have intrinsic effects reducing the activity of these systems. Abrupt interruption of treatment with some antidepressants has been associated with a self-limited syndrome of physical and psychological symptoms distinct from relapse, of which drug half-life appears to be the major determinant. We hypothesized that reactivation of stress-response systems could play a role in this syndrome and studied the effects of treatment interruption in patients successfully treated with the antidepressant fluoxetine, paroxetine or sertraline. During placebo substitution, interruption of paroxetine was associated with statistically significant increases in plasma IGF-1 and heart rate. These data suggest that some activation of physiologic stress-responses may accompany symptom increases during treatment interruption of shorter half-life agents.

Adult↗
PubMed2000

Risk of suicidality in depression with serotonergic antidepressants.

Since depression is a risk factor for suicidal thoughts and behaviors, and since suicidal behaviors are associated with low serotonin activity, are selective serotonin reuptake inhibitors (SSRIs) more effective than other antidepressants in treating suicidality in depressed patients? There is inconclusive evidence for and against this hypothesis. However, all studies suggest that antidepressants are effective treatments of suicidal ideations and behaviors, and SSRIs have been shown to have prophylactic effects in preventing suicidal behaviors. Although some reports suggest that SSRIs might increase suicidal ideations and behaviors, the results of large, double-blind studies do not suggest a causal relationship between pharmacotherapy and the emergence of suicidality. Undertreatment of depression and therapeutic failure are more significant problems with the use of antidepressants in suicidal patients than the risk of using antidepressants in overdose. Prescribing inadequate doses of antidepressants is therefore a source of overlooked risk.

Antidepressive Agents↗
PubMed2000

Development of a brief screening instrument: the HANDS.

BACKGROUND: The present study was designed to develop a briefer screening scale of approximately 10 items which maintained the validity of the Zung Self-Rating Depression Scale in a sample similar to that attending National Depression Screening Day (NDSD), as well as a more general audience. METHODS: We first administered 70 items from a variety of existing rating scales to 40 subjects who answered an ad for depressed subjects and 55 who answered an ad for non-depressed subjects, all of whose diagnoses were confirmed by the Structured Clinical Interview for DSM-IV (SCID). Based on the correlation between each item and the diagnostic criterion, we reduced the number of items to 17 which we then administered to another 45 subjects who answered an ad similar to that used for NDSD and also underwent a SCID interview. Based on these results, we arrived at the final 10-item Harvard Department of Psychiatry/NDSD scale (HANDS) with the assistance of the item-response theory. The items are scored for frequency of occurrence of each symptom over the past 2 weeks. Total scores range from 0 to 30. RESULTS: The 10-item scale (HANDS) has good internal consistency and validity: a cutpoint score of 9 or greater gave sensitivity of at least 95% in both studies. Although specificity was lower for all scales in the self-selected population, the HANDS performed at least as well as the 20-item Zung Scale, the 21-item Beck Depression Inventory-II and the 15-item Hopkins Symptom Depression Checklist. CONCLUSION: The 10-item HANDS performs as well as other widely used longer self-report scales and has the advantage of briefer administration time.

Adolescent↗
PubMed2000

Strategies for managing depression refractory to selective serotonin reuptake inhibitor treatment: a survey of clinicians.

OBJECTIVE: To examine treatment practices in cases where selective serotonin reuptake inhibitors (SSRIs) are ineffective. METHODS: We surveyed 801 clinicians (including 630 psychiatrists) attending the Massachusetts General Hospital's annual psychopharmacology review course. Clinicians were presented with a vignette about a patient with depression who had responded partially to an SSRI and were asked to choose among various strategies available to manage this patient. RESULTS: Of those surveyed, 466 clinicians had been in practice a mean of 16.6 years (SD 10.7). Not all clinicians chose to answer every question. Among 455 respondents, 84% (n = 382) chose to increase the dose of the SSRI, 10% (n = 47) chose augmentation or combination, and 7% (n = 31) opted for switching agents. When asked to switch to another agent, 448 responded, of whom 52% (n = 235) chose a newer antidepressant, 34% (n = 152) chose another SSRI, 10% (n = 44) chose a tricyclic antidepressant (TCA), 2% (n = 8) chose a serotonin norepinephrine reuptake inhibitor (SNRI), 1% (n = 5) chose a monoamine oxidase inhibitor (MAOI), and 1% (n = 4) chose an undefined "other" agent. Among 445 respondents, bupropion was the most widely chosen augmenting agent (30%, n = 134), followed by lithium (22%, n = 98). West coast and Canadian clinicians preferred to switch to another SSRI rather than to a newer antidepressant. Canadian clinicians preferred lithium to bupropion as their first-choice augmenting agent, as did clinicians from academic settings. Clinicians from community, individual practice, or group settings favoured bupropion. More experienced clinicians preferred bupropion as a first-choice augmenter, whereas less experienced ones showed a slight preference for lithium. Canadian clinicians were more likely to use MAOIs as second-line agents. CONCLUSIONS: Clinicians in this sample often followed strategies different from those recommended in the literature. Bupropion may have an important role in augmentating treatment with SSRIs.

Antimanic Agents↗
PubMed2000

Interruption of selective serotonin reuptake inhibitor treatment. Double-blind, placebo-controlled trial.

BACKGROUND: Abrupt interruption of therapy with selective serotonin reuptake inhibitors (SSRIs) has been associated with somatic and psychological symptoms. AIMS: Systematically to assess symptoms and effects on daily functioning related to interruption of SSRI therapy. METHOD: Patients treated with fluoxetine, setraline or paroxetine underwent identical five-day periods of treatment interruption and continued active treatment under double-blind, order-randomised conditions, with regular assessment of new symptoms. RESULTS: Placebo substitution for paroxetine was associated with increases in the number and severity of adverse events following the second missed dose, and increases in functional impairment at five days. Placebo substitution for sertraline resulted in less pronounced changes, while interruption of fluoxetine was not associated with any significant increase in symptomatology. CONCLUSIONS: Abrupt interruption of SSRI treatment can result in a syndrome characterised by specific physical and psychological symptoms. Incidence, timing and severity of symptoms vary among SSRIs in a fashion that appears to be related to plasma elimination characteristics.

Adult↗
PubMed2000

Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current "next-step" practices.

BACKGROUND: Many patients treated for major depression require more than one antidepressant trial to achieve or sustain response. However, the literature provides few treatment algorithms or effectiveness studies that empirically support "next-step" options available to clinicians. We conducted a survey of psychiatrists and other medical specialists who treat depression to ascertain what clinicians actually do when faced with patients who suboptimally respond to an adequate course of selective serotonin reuptake inhibitor (SSRI) therapy. METHOD: Attendees at a psychopharmacology course (N = 801) were queried about their top choices for antidepressant-treatment nonresponders: a minimal responder after 4 weeks of adequate SSRI treatment, a partial responder after 8 weeks of adequate SSRI therapy, a nonresponder after 8 weeks of adequate SSRI therapy, and a relapser on long-term SSRI maintenance therapy. Choices included raising the dose, augmenting or combining with another agent, switching to a second SSRI. or switching to a non-SSRI agent. RESULTS: 432 (54%) of the surveys were returned. Raising the dose was the most frequently reported next-step strategy for a patient with minimal response after 4 weeks of adequate SSRI therapy, partial response after 8 weeks of adequate SSRI therapy, and relapse on long-term SSRI therapy. Switching to a non-SSRI agent was the most frequently chosen option for nonresponders to an adequate trial of SSRI therapy. CONCLUSION: Our findings suggest that clinicians select different next-step strategies when patients are nonresponders versus when patients are partial responders or relapsers.

Antidepressive Agents↗
PubMed2000

New approaches to the treatment of refractory depression.

Although the majority of patients with depression respond well to their initial pharmacologic treatment, as many as 30% to 45% fail to achieve an adequate response. In addition to the more traditional lithium and thyroid hormone augmentation strategies, a number of new pharmacotherapeutic approaches are currently being used to help manage refractory depression, including the addition of another agent or a switch to another antidepressant. Augmentation and switching strategies are often selected in order to obtain a different neurochemical effect (e.g., adding a relatively noradrenergic agent to a relatively serotonergic antidepressant). In particular, several studies have suggested that depressed patients refractory to treatment with selective serotonin reuptake inhibitors (SSRIs) may show a good response to newer agents that have a pharmacologic profile distinct from the SSRIs. Furthermore, preliminary studies have shown that the addition of SSRIs to either noradrenergic drugs such as the tricyclic antidepressants (TCAs) or dopaminergic agents may be efficacious, even though concerns about drug-drug interactions and tricyclic cardiac toxicity have limited the use of TCA-SSRI combinations. The introduction of reboxetine, a relatively selective norepinephrine reuptake inhibitor, may increase the use of the latter therapeutic approach because of its improved safety profile compared with the TCAs. The review of treatment options for refractory depression that follows will outline the advantages, disadvantages, and level of support for a number of new treatment strategies.

Antidepressive Agents↗
PubMed2000

Management of nonresponse and intolerance: switching strategies.

Approximately 29% to 46% of depressed patients show only partial or no response to treatment with antidepressants, with intolerance a frequent cause of treatment failure or discontinuation. Clinicians frequently switch to other antidepressants patients who have failed to tolerate or to respond to antidepressant treatment. The switching strategy involves substitution of another agent for the agent that has either caused intolerable side effects or has failed to induce a response. Fredman and colleagues have recently surveyed 402 psychiatrists from various parts of the country and asked them what steps they would take for patients who fail to respond to 8 weeks or more of an adequate dose of a selective serotonin reuptake inhibitor (SSRI). Interestingly, switching to a non-SSRI agent was the most popular choice indicated by psychiatrists (44% of respondents), with dual-acting agents and bupropion being the next most commonly chosen agents. Even though there are no controlled trials of switching strategies in the literature to date, clinicians often choose this course of action. This article will review some of the currently available studies on switching strategies.

Antidepressive Agents↗
PubMed1999

Patterns of axis I comorbidity in early-onset versus late-onset major depressive disorder.

BACKGROUND: This study of a large clinical sample of depressed patients examined whether childhood onset as compared with adult onset Major Depressive Disorder (MDD) would confer a greater risk for Axis I comorbidity and whether childhood onset MDD would also differ from adult onset MDD in the pattern of comorbid disorders. METHODS: We examined lifetime co-occurrence of Axis I disorders among 381 adult outpatients with MDD by Structured Clinical Interview for DSM-III-R-Patient Edition (SCID-P). Subjects were divided into childhood onset (n = 47), adolescent onset (n = 101) and adult onset (n = 233) MDD groups. RESULTS: We found that the two early-onset groups exhibited significantly increased rates of Axis I comorbidity. The childhood onset group accounted for a disproportionately high percentage of depressed adults with two or more comorbid Axis I disorders. Social and simple phobias and alcohol abuse/dependence were significantly more prevalent among individuals with childhood onset MDD than among individuals with adult onset MDD. Alcohol abuse/dependence, but not anxiety disorders, was significantly more prevalent among adolescent onset than adult onset MDD groups. Panic, generalized anxiety, obsessive-compulsive and somatoform disorders were equally distributed across MDD onset groups. Comorbid disorders were much more likely to have followed onset of MDD among individuals with childhood compared with adult onset, except for social phobia which more frequently preceded the depression. The relative ordering among the comorbid conditions with respect to whether they followed or preceded MDD did not vary notably across the three age of onset groups. CONCLUSIONS: We conclude that early-onset MDD is associated with an increased density of Axis I comorbidity that seems to be limited to specific disorders.

Adult↗
PubMed1999

Dysfunctional attitudes and poor problem solving skills predict hopelessness in major depression.

BACKGROUND: Hopelessness is a significant predictor of suicidality, but not all depressed patients feel hopeless. If clinicians can predict hopelessness, they may be able to identify those patients at risk of suicide and focus interventions on factors associated with hopelessness. In this study, we examined potential predictors of hopelessness in a sample of depressed outpatients. METHODS: In this study, we examined potential demographic, diagnostic, and symptom predictors of hopelessness in a sample of 138 medication-free outpatients (73 women and 65 men) with a primary diagnosis of major depression. The significance of predictors was evaluated in both simple and multiple regression analyses. RESULTS: Consistent with previous studies, we found no significant associations between demographic and diagnostic variables and greater hopelessness. Hopelessness was significantly associated with greater depression severity, poor problem solving abilities as assessed by the Problem Solving Inventory, and each of two measures of dysfunctional cognitions (the Dysfunctional Attitudes Scale and the Cognitions Questionnaire). In a stepwise multiple regression equation, however, only dysfunctional cognitions and poor problem solving offered non-redundant prediction of hopelessness scores, and accounted for 20% of the variance in these scores. LIMITATIONS: This study is based on depressed patients entering into an outpatient treatment protocol. All analyses were correlational in nature, and no causal links can be concluded. CONCLUSIONS: Our findings, identifying clinical correlates of hopelessness, provide clinicians with potential additional targets for assessment and treatment of suicidal risk. In particular, clinical attention to dysfunctional attitudes and problem solving skills may be important for further reduction of hopelessness and perhaps suicidal risk.

Adult↗
PubMed1999

The prevalence of sleep-related eating disorder in psychiatric and non-psychiatric populations.

BACKGROUND: Sleep-related eating disorder is a little-described syndrome combining features of sleep disorders and eating disorders. The behaviour consists of partial arousals from sleep followed by rapid ingestion of food, commonly with at least partial amnesia for the episode the following day. The aim of this study was to provide an estimate of the prevalence of sleep-related eating disorder. METHODS: The Inventory of Nocturnal Eating, a self-report questionnaire addressing nocturnal eating and sleep disturbance, was administered to out-patients (N = 126) and in-patients (N = 24) with eating disorders, obese subjects (N = 126) in a trial of an anorexic agent, depressed subjects (N = 207) in an antidepressant trial, and an unselected group (N = 217) of college students. Sleep-related eating disorder was operationally defined as nocturnal eating with a self-reported reduced level of awareness, occurring at least once per week. RESULTS: Almost 5.0% (33/700) of the sample described symptoms consistent with sleep-related eating disorder. The in-patient eating disorders group had nearly twice the prevalence (16.7%) of the out-patient eating disorder sample (8.7%), which had nearly twice the prevalence of the next highest group, the student sample (4.6%). Subjects with sleep-related eating disorder endorsed more symptoms consistent with sleep disorders and had higher levels of depression and dissociation than those without nocturnal eating. CONCLUSIONS: Sleep-related eating disorder is more common than is generally recognized, especially in those with a daytime eating disorder. Sleep disorder symptoms are often associated with sleep-related eating disorder, as are depression and dissociation. Evaluation of individuals with eating disorders should include assessment for sleep-related eating.

Adult↗