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Biomedical subjects

M Fava

Publications and source records attributed to M Fava.

At least 37 records · Page 2Linked to original sources
PubMed2000

Anemia and macrocytosis in the prediction of serum folate and vitamin B12 status, and treatment outcome in major depression.

BACKGROUND: Folate and B12 deficiencies may result in macrocytic anemia, and are common in major depression; hypofolatemia may result in poorer antidepressant response. We wished to determine whether anemia or macrocytosis predict hypofolatemia, low B12, or refractoriness to antidepressants. METHODS: After obtaining serum folate, B12, and hematological indices, 213 depressed adults were treated with fluoxetine 20 mg/day. Amelioration of depressive symptoms was measured. RESULTS: Neither macrocytosis nor anemia predicted low serum folate/B12, or antidepressant refractoriness. Among 39 patients with hypofolatemia, none had macrocytosis; 28% had low HCT; 41% had low RBC. Among 25 patients with low B12, none had macrocytosis; 24% had low HCT; 28% had low RBC. Among non-responders, 3% had macrocytosis; 24% had low HCT; 25% had low RBC. CONCLUSION: Anemia and macrocytosis should not be used to predict folate or B12 deficiencies, or refractoriness to antidepressants. Measurement of folate and B12 should be considered when evaluating treatment refractoriness.

Adult↗
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

Docosahexanoic acid and omega-3 fatty acids in depression.

Geographic areas where consumption of DHA is high are associated with decreased rates of depression. DHA deficiency states, such as alcoholism and the postpartum period, also are linked with depression. Individuals with major depression have marked depletions in omega-3 FAs (especially DHA) in erythrocyte phospholipids compared with controls. These data suggest that DHA may be associated with depression, and the limited data available on supplementation with DHA or other omega-3 FAs seem to support the hypothesis that DHA may have psychotropic effects. Overall, the use of EFAs is promising, particularly in view of the many illnesses potentially treatable with these substances; however, larger, carefully designed studies are needed to establish whether DHA is an effective and safe antidepressant, mood stabilizer, or antipsychotic. A few preliminary trials of DHA are in progress, but no studies comparing DHA against placebo or against an established antidepressant have been carried out. Studies to address this issue are being developed at the Massachusetts General Hospital. Studies likely will require escalating doses of DHA, eventually reaching high levels so as to ensure that patients will avoid a potentially ineffective subclinical dose. Careful monitoring of dietary intake among subjects also will necessary because a high intake of omega-3-rich foods may confound results. Finally, large-scale, placebo-controlled, double-blind trials comparing the efficacy and safety of DHA against standard antidepressants are required before psychiatrists can recommend DHA therapy as effective and safe for the treatment of depression and other mood disorders. Given the popularity of self-medication by patients who already are taking marketed antidepressants, studies examining the use of DHA as an augmentor to standard antidepressants may answer whether DHA can occupy a niche as an augmenting agent for patients who have made a partial response or have not responded to conventional antidepressants. Considering that natural medications generally seem best for treating mild to moderate illness, the role of DHA as a therapy for minor and subsyndromal depression also should be considered. It is hoped that studies of these types will help to clarify some of the knowledge gaps outlined in this article.

Clinical Trials as Topic↗
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

Massive pulmonary embolism: treatment with the hydrolyser thrombectomy catheter.

PURPOSE: To assess the efficacy of clot removal with use of the Hydrolyser thrombectomy catheter in acute massive pulmonary embolism (PE). MATERIALS AND METHODS: Eleven patients (eight women, three men) with a mean age of 61 (range, 37-79) years with acute massive PE underwent percutaneous mechanical thrombectomy (PMT) with use of the Hydrolyser. In four patients with no contraindication, fibrinolysis was performed with use of urokinase at low doses after thrombectomy. RESULTS: Ten patients (90.91%) recovered from massive PE and were discharged within 11 days. The Urokinase Pulmonary Embolism Trial angiographic severity indexes (mean +/- SD) were 14.7 +/- 2.6 and 7.5 +/- 2.7, respectively, before and after thrombectomy (P < .001). Partial arterial pressures of O2 increased from 72.8 mm Hg +/- 16.4 to 93.5 mm Hg +/- 5.6 (P < .005). Pulmonary artery pressure decreased from 45.5 mm Hg +/- 14.2 to 29.5 mm Hg +/- 13.6 after thrombectomy (P < .0001). Calculated by semiquantitative computed analysis, PMT with use of the Hydrolyser removed 74.06% of thrombus +/- 13.46%. One patient developed self-limited hemoptysis immediately after thrombectomy. One patient died during the procedure secondary to PE. CONCLUSION: PMT with use of the Hydrolyser is effective and safe in massive PE, resulting in improved hemodynamics and blood oxygenation and decreased pulmonary artery pressure. It offers an alternative to fibrinolysis and surgical thrombectomy.

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

Pramipexole augmentation in the treatment of unipolar and bipolar depression: a retrospective chart review.

OBJECTIVE: To assess the effectiveness and safety of pramipexole as an adjunctive medication in refractory bipolar and unipolar depression in a naturalistic setting. METHODS: Retrospective chart review by psychiatrists on staff at a university hospital identified all patients who had received pramipexole. Response was based on moderate to marked improvement in the Clinical Global Impression-Improvement (CGI-I) scale. RESULTS: Pramipexole (mean dose 0.70 mg/d, mean duration 24.4 weeks) was effective in 6/12 (50.0%) of patients with bipolar depression, and 8/20 (40%) of patients with unipolar depression, mean duration of follow-up of 24.4 weeks. One case of transient hypomania was noted. Eight patients discontinued pramipexole due to lack of response and four due to side effects. CONCLUSIONS: Pramipexole, used as an adjunct to antidepressants or mood stabilizers, appeared to be effective and safe in the treatment of unipolar and bipolar depression. These uncontrolled, retrospective, naturalistic pilot data require confirmation by controlled research before conclusions can be made.

Adult↗
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

Timing of onset of antidepressant response with fluoxetine treatment.

OBJECTIVE: The purpose of this study was to assess the time until onset of antidepressant response with fluoxetine treatment. METHOD: The authors evaluated 182 outpatients with major depression who had a sustained acute response to fluoxetine treatment. The outpatients received 8 weeks of treatment with 20 mg/day of fluoxetine and were assessed biweekly with the 17-item Hamilton Depression Rating Scale. The onset of response was defined as a 30% decrease in score on the Hamilton depression scale that persisted and led to a 50% decrease by week 8. The Kaplan-Meier product limit and Cox regression analysis were used to model the relationship between relevant variables and time until onset of response. RESULTS: The authors found that at weeks 2, 4, and 6, the probabilities of having an onset of response (for responders) were 55.5%, 24.7%, and 9.3%, respectively. The cumulative probabilities of onset of response at each time point were 55.5%, 80.2%, and 89.5%. Neither demographics nor clinical characteristics of depression predicted time until initial response. CONCLUSIONS: These data suggest that more than half of eventual responders to fluoxetine treatment at 8 weeks start to respond by week 2; over 75% start to respond by week 4. Conversely, the lack of onset of response at 4-6 weeks was associated with about a 73%-88% chance that patients would not have an onset of response by 8 weeks.

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

The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder.

BACKGROUND: A simple, once-weekly dosing regimen could be a convenient alternative for many patients during long-term treatment of depression. Such a strategy might also be effective for improving medication compliance and the outcome of continuation treatment. The safety and effectiveness of a new formulation of enteric-coated fluoxetine (90 mg) given once weekly was tested during the continuation treatment of major depressive disorder. METHOD: Patients meeting DSM-IV criteria for major depressive disorder with modified 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores > or = 18 and Clinical Global Impressions-Severity of Illness scale (CGI-S) scores > or = 4 were treated 13 weeks with open-label 20 mg/day of fluoxetine in a multicenter U.S. study. Responders (N = 501) were randomly assigned to receive 20 mg of fluoxetine daily, placebo, or 90 mg of enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. The primary efficacy measure was the percentage of patients who relapsed. Time to relapse was tested over the 25-week continuation period using log-rank analyses of the Kaplan-Meier estimates of relapse rates. Additional analyses of efficacy included comparison of change from baseline to endpoint for the HAM-D-17, CGI-S, and HAM-D-28 subscales by last observation carried forward (LOCF). Safety measures included comparison of treatment-emergent adverse events, both spontaneous and solicited (using the Association for Methodology of Documentation in Psychiatry-Module 5), vital signs, and laboratory measures. RESULTS: Relapse rates for patients assigned to fluoxetine, either 20 mg daily or 90 mg weekly, were significantly lower than for placebo by log-rank analysis and LOCF analyses of secondary efficacy measures. Efficacy did not significantly differ between the 2 active drug groups by these measures. Enteric-coated fluoxetine at a once-weekly dose of 90 mg was well tolerated, and its safety profile was similar to that of daily 20 mg of fluoxetine. CONCLUSION: The formulation of enteric-coated fluoxetine taken once weekly is effective, safe, and well tolerated for continuation treatment of depression in patients who responded to acute treatment with 20 mg/day of fluoxetine. Monitoring during long-term treatment for evidence of sustained remission is important regardless of dosing regimen.

Adolescent↗
PubMed2000

Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment.

BACKGROUND: The effects of extended selective serotonin reuptake inhibitor (SSRI) treatment on weight are not well characterized. Also unknown is whether different agents have differential effects. To examine these questions, we assessed weight changes in patients randomly assigned to long-term treatment with fluoxetine, sertraline, or paroxetine. METHOD: Patients (N = 284) with major depressive disorder (DSM-IV) were randomly assigned to double-blind treatment with fluoxetine (N = 92), sertraline, (N = 96), or paroxetine (N = 96) for a total of 26 to 32 weeks. The mean percent change in weight was compared for each group, as was the number of patients who had > or = 7% weight increase from baseline. RESULTS: Patients (fluoxetine, N = 44; sertraline, N = 48; paroxetine, N = 47) who completed the trial were included in these analyses. Paroxetine-treated patients experienced a significant weight increase, fluoxetine-treated patients had a modest but nonsignificant weight decrease, and patients treated with sertraline had a modest but nonsignificant weight increase. The number of patients whose weight increased > 7% from baseline was significantly greater for paroxetine-treated compared with either fluoxetine-treated or sertraline-treated patients. CONCLUSION: Risk of weight gain during extended SSRI treatment differs depending on which SSRI is used.

Adult↗
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↗