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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
PubMed2001

Severe depression: is there a best approach?

A major depressive episode can be categorised as severe based on depressive symptoms, scores on depression rating scales, the need for hospitalisation, depressive subtypes, functional capacity, level of suicidality and the impact that the depression has on the patient. Several biological, psychological and social factors, and the presence of comorbid psychiatric or medical illnesses, impact on depression severity. A number of factors are reported to influence outcome in severe depression, including duration of illness before treatment, severity of the index episode, treatment modality used, and dosage and duration of and compliance with treatment. Potential complications of untreated severe depression include suicide, self-mutilation and refusal to eat, and treatment resistance. Several antidepressants have been studied in the treatment of severe depression. These include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline (norepinephrine) reuptake inhibitors, noradrenergic and specific serotonergic antidepressants, serotonin 5-HT(2) receptor antagonists, monoamine oxidase inhibitors, and amfebutamone (bupropion). More recently, atypical antipsychotics have shown some utility in the management of severe and resistant depression. Data on the differential efficacy of TCAs versus SSRIs and the newer antidepressants in severe depression are mixed. Some studies have reported that TCAs are more efficacious than SSRIs; however, more recent studies have shown that TCAs and SSRIs have equivalent efficacy. There are reports that some of the newer antidepressants may be more effective than SSRIs in the treatment of severe depression, although the sample sizes in some of these studies were small. Combination therapy has been reported to be effective. The use of an SSRI-TCA combination, while somewhat controversial, may rapidly reduce depressive symptoms in some patients with severe depression. The combination of an antidepressant and an antipsychotic drug is promising and may be considered for severe depression with psychotic features. Although the role of cognitive behaviour therapy (CBT) in severe depression has not been adequately studied, a trial of CBT may be considered in severely depressed patients whose symptoms respond poorly to an adequate antidepressant trial, who are intolerant of antidepressants, have contraindications to pharmacotherapy, and who refuse medication or other somatic therapy. A combination of CBT and antidepressants may also be beneficial in some patients. Electroconvulsive therapy (ECT) may be indicated in severe psychotic depression, severe melancholic depression, resistant depression, and in patients intolerant of antidepressant medications and those with medical illnesses which contraindicate the use of antidepressants (e.g. renal, cardiac or hepatic disease).

Animals↗
PubMed2001

T3 blood levels and treatment outcome in depression.

OBJECTIVE: We examined the correlation between the basal triiodothyronine resin uptake (T3-RU) levels in depressed subjects and the response to anti-depressant treatment. METHOD: We treated with fluoxetine 235 outpatients meeting DSM-IV criteria for major depression. We measured T3 resin uptake (T3-RU) levels before the onset of treatment. The 17-item Hamilton Rating Scale for Depression (Ham-D-17) was administered before, during and after the eight weeks of treatment to assess changes in depressive symptoms. RESULTS: 16 patients (6.8 percent) had low T3-RU levels (range 16.5-21), and 7 patients (3.0 percent) had high T3-RU levels (range 36-38). No relationship was found between T3-RU levels and clinical improvement, defined as either total Ham-D-17 score change or Ham-D-17 score < or = 7 in the last 3 weeks of treatment, even after adjusting for baseline severity of depression. CONCLUSION: Abnormal T3-RU levels are rather uncommon in outpatient depression and do not correlate with the response to antidepressant treatment or lack thereof.

Adolescent↗
PubMed2001

Efficacy and safety of mirtazapine in major depressive disorder patients after SSRI treatment failure: an open-label trial.

OBJECTIVE: To evaluate the efficacy and safety of mirtazapine in depressed outpatients who have shown nonresponse or intolerance to selective serotonin reuptake inhibitor (SSRI) therapy. METHOD: In this open-label, 8-week study, the efficacy and safety of mirtazapine among 103 outpatients with DSM-IV major depressive disorder who had failed previous therapy with an SSRI (fluoxetine, paroxetine, or sertraline) were evaluated. The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression (HAM-D-17), and safety assessments included reported adverse events, routine laboratory assessments, physical examinations, and assessments of vital signs. A 4-day washout period followed by mirtazapine treatment was compared with an immediate switch from the SSRI to mirtazapine. RESULTS: Based on mean HAM-D-17 scores at endpoint and response rates of 48% based on the criterion of > or = 50% reduction in HAM-D-17 score, mirtazapine was found to be an effective treatment for a substantial proportion of patients for whom an SSRI was ineffective and/or poorly tolerated. Mirtazapine was well tolerated, with sedation and appetite increase/weight gain the most commonly reported adverse events. In addition, no difference in efficacy, safety, or tolerability was observed for patients undergoing an immediate switch from an SSRI (after having been tapered to the minimal effective dose) to mirtazapine, compared with those undergoing the imposition of a 4-day drug-free washout. CONCLUSION: These results suggest that an immediate switch to mirtazapine may be a valid therapeutic option among patients who cannot tolerate or do not respond to SSRIs.

Adult↗
PubMed2001

Augmentation and combination strategies in treatment-resistant depression.

A substantial proportion of depressed patients show only partial or no response to antidepressants, and even among responders to antidepressant treatment, residual symptoms are rather common. When depressions do not respond adequately to treatment with an antidepressant, clinicians may choose to keep the same antidepressant and add another "augmenting" compound. Such augmentation strategies involve the use of a pharmacologic agent that is not considered to be a standard antidepressant but may boost or enhance the effect of an antidepressant. Alternatively, clinicians may choose combination strategies, in which they combine the antidepressant that did not produce adequate response with another antidepressant, typically of a different class. There are only a few controlled clinical trials of these 2 strategies among patients with treatment-resistant depression or among patients who have only partially benefited from antidepressant treatment. Most of the time, clinicians' decisions are, therefore, guided by anecdotal reports, case series, and by some relatively smaller, uncontrolled clinical trials. These augmentation and combination strategies appear to be relatively safe and effective approaches to treatment-resistant depressions, although there is a relative paucity of controlled studies to support their efficacy. These strategies typically aim at obtaining a different neurochemical effect than the one obtained with the antidepressant that has not produced adequate response. While drug-drug interactions may limit the use of some of these strategies, the potential loss of partial benefit from the failed drug inherent in switching may increase the acceptability of augmentation and combination strategies among partial responders. Further studies are clearly needed to evaluate the comparative efficacy and tolerability of these different approaches in treatment-resistant depressions.

Antidepressive Agents↗
PubMed2001

A survey of prescribing preferences in the treatment of refractory depression: recent trends.

The objective of this study was to gather data from a large group of clinicians on antidepressant prescribing practices in the treatment of refractory depression. Eight hundred and thirty-five clinicians about to attend the annual Massachusetts General Hospital psychopharmacology review course were asked to respond to a brief questionnaire regarding a hypothetical clinical case vignette. The case was of a patient who suffered from a new onset, unipolar, nonpsychotic, severe major depressive episode. Three hundred and four (36%) clinicians agreed to participate and filled out our questionnaire. Of the respondents, 260 (85.5%) indicated their preference for an initial treatment that combined medication and psychotherapy, as opposed to either modality alone. Furthermore, given this patient's nonresponse to two adequate selective serotonin reuptake inhibitor (SSRI) trials and one atypical antidepressant trial over an 8-month period, 39.8% of respondents indicated venlafaxine monotherapy as their next choice, whereas combining antidepressants (20.1%) and augmentation (18.4%) were the second and third most preferred treatment choices at this time point. Further on in the course of treatment, with the patient not having responded to any interventions during a 16-month period, 80.9% of survey respondents indicated electroconvulsant therapy (ECT) as their next preference. Among 304 clinicians surveyed, a combination of therapy and medication is the most preferred choice for treating severely depressed outpatients with new onset depression. Switching to venlafaxine, using two antidepressants together, and augmentation of an antidepressant regimen with a second agent accounted for 78.3% of respondents' preferences when faced with treating a depressed patient who had not responded to two adequate SSRI trials and one adequate atypical antidepressant trial. Of the respondents, 80.9% indicated ECT as a treatment preference after 16 months of multiple failed medication trials and nonresponse to psychotherapy. Further research is necessary to elucidate the factors that influence clinicians' reasoning for selecting one strategy over another.

Antidepressive Agents↗
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

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↗