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Biomedical subjects

M Fava

Publications and source records attributed to M Fava.

At least 91 records · Page 5Linked to original sources

Nutrition and depression: the role of folate.

A relationship between folate and neuropsychiatric disorders has been inferred from clinical observation and from the enhanced understanding of the role of folate in critical brain metabolic pathways. Depressive symptoms are the most common neuropsychiatric manifestation of folate deficiency. Conversely, borderline low or deficient serum or red blood cell folate levels have been detected in 15-38% of adults diagnosed with depressive disorders. Recently, low folate levels have been linked to poorer antidepressant response to selective serotonin reuptake inhibitors. Factors contributing to low serum folate levels among depressed patients as well as the circumstances under which folate and its derivatives may have a role in antidepressant pharmacotherapy must be further clarified.

Adult↗

Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study.

OBJECTIVE: The purpose of this study was to evaluate whether the concentration of beta-nucleoside triphosphate is lower in the basal ganglia of depressed subjects. METHOD: In vivo 31P magnetic resonance spectra were acquired from a 45-cm3 region surrounding the basal ganglia of 35 unmedicated depressed subjects and 18 comparison subjects. RESULTS: beta-Nucleoside triphosphate, which arises primarily from beta-ATP, was 16% lower in the depressed subjects than in the comparison subjects. CONCLUSIONS: The low level of beta-nucleoside triphosphate is consistent with an abnormality of high-energy phosphate metabolism in the basal ganglia of subjects with major depression.

Adenosine Triphosphate↗

Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine.

OBJECTIVE: The rate of adverse events following discontinuation of treatment with extended-release venlafaxine was compared with the rate associated with discontinuation of placebo administration. METHOD: The subjects were 20 outpatients with major depressive disorder who had participated in a multicenter, double-blind, placebo-controlled study of the efficacy of the new extended-release formulation of venlafaxine. RESULTS: During the 3 days after discontinuation of treatment with the study drug, seven (78%) of the nine venlafaxine-treated subjects and two (22%) of the nine placebo-treated patients reported the emergence of adverse events, a statistically significant difference. CONCLUSIONS: These results suggest that clinicians discontinuing venlafaxine treatment should consider tapering the medication dose gradually.

Adult↗

Folate, vitamin B12, and homocysteine in major depressive disorder.

OBJECTIVE: The authors examined the relationships between levels of three metabolites (folate, vitamin B12, and homocysteine) and both depressive subtype and response to fluoxetine treatment in depressed patients. METHOD: Fluoxetine, 20 mg/day for 8 weeks, was given to 213 outpatients with major depressive disorder. At baseline, depressive subtypes were assessed, and a blood sample was collected from each patient. Serum metabolite levels were assayed. Response to treatment was determined by percentage change in score on the 17-item Hamilton Depression Rating Scale. RESULTS: Subjects with low folate levels were more likely to have melancholic depression and were significantly less likely to respond to fluoxetine. Homocysteine and B12 levels were not associated with depressive subtype or treatment response. CONCLUSIONS: Overall, the results are consistent with findings linking low folate levels to poorer response to antidepressant treatment. Folate levels might be considered in the evaluation of depressed patients who do not respond to antidepressant treatment.

Adolescent↗

Are dependency and self-criticism risk factors for major depressive disorder?

OBJECTIVE: To determine whether dependent and self-critical personality traits are associated with specific types of life events and whether these traits change with pharmacotherapy. METHOD: Overall, 142 depressed outpatients completing 8 weeks of fluoxetine treatment were administered the Life Experiences Survey (LES) at baseline and the Dysfunctional Attitude Scale (DAS) and Hamilton Depression Rating Scale (HDRS) at baseline and endpoint. RESULTS: The DAS dependency subscale, but not the self-criticism subscale, showed significant correlations with life events regardless of congruency. Baseline HDRS scores were positively correlated with both DAS subscales and total score. The DAS subscales, the total DAS score, and the HDRS all improved significantly with treatment. CONCLUSIONS: These results confirm a growing body of research that has found an association between sociotropic or dependent personality traits and life events.

Adult↗

A cross-sectional study of private psychiatric practices under a single-payer health care system.

OBJECTIVES: To examine current concerns that in the Canadian single-payer mental health care system, the "rich worried well" (that is, wealthy individuals who are worried yet mentally well) may overuse psychiatric services, while low-income, uninsured mentally ill individuals may remain undertreated. The current study focuses on the mental health care in the Canadian region of Ottawa-Carleton, where a single-payer system provides universal access to mental health services, to assess how psychiatric services are provided by psychiatrists in private practice. METHOD: One hundred and seven private psychiatrists working in the region of Ottawa-Carleton completed a questionnaire which contained questions about the sociodemographic characteristics and background of the psychiatrists themselves and which asked the psychiatrists specific questions about the sociodemographic status, diagnosis, and treatment of each patient seen on November 10, 1994. RESULTS: Approximately 93% of the patients seen met criteria for one or more Axis I disorders, of which mood and anxiety disorders were the most common. Wealthier patients were relatively underrepresented among the patients treated by the private psychiatrists. In addition, we found no significant differences in the distribution of Axis I, Axis II, and Axis III disorders between patients earning below $30,000 per year compared with patients earning above $60,000 per year. CONCLUSIONS: Our results suggest that outpatient psychiatric care delivered by private psychiatrists in a Canadian single-payer system targets primarily individuals with major psychiatric disorders and does not seem to favour "the worried well." Larger epidemiological studies with independent assessments of psychiatric populations are necessary to confirm our findings.

Adolescent↗

Sociodemographic predictors of response to antidepressant treatment.

OBJECTIVE: Our goal was to assess whether sociodemographic variables such as gender, marital status, level of education, and employment status are related to the changes in social functioning that have been reported after drug treatment in outpatients with major depressive disorder. METHOD: Eligible subjects were 166 depressed outpatients participating in a study involving open treatment with fluoxetine 20 mg/day for eight weeks. Diagnosis of major depressive disorder was made with the use of the Structured Clinical Interview for DSM-III-R-Patient Edition (SCID-P), and patients were required to have a seventeen-item Hamilton Rating Scale for Depression (HAM-D-17) score > or = at study entry. All subjects were administered the HAM-d-17 and the Social Adjustment Scale-Self-Report (SAS-SR) before and after treatment with fluoxetine. RESULTS: We found that SAS-SR scores decreased significantly following treatment with fluoxetine from a mean score at baseline of 2.6 +/- 0.7 to a mean score at endpoint of 2.3 +/- 0.6. After adjusting for the degree of change in HAM-D-17 scores, we found a significant relationship between degree of change in SAS-SR and level of education. No statistically significant relationships were observed between SAS-SR change and age, gender, marital status, and employment status. CONCLUSION: The degree of improvement in psychosocial functioning observed in depressed outpatients following antidepressant treatment appears to be related to the level of education at study entry, but not to other sociodemographic variables. Further studies need to investigate the nature of this relationship.

Adult↗

A preliminary study on the efficacy of sertraline and imipramine on anger attacks in atypical depression and dysthymia.

There is clinical and biological evidence suggesting that patients with anger attacks, sudden spells of anger accompanied by intense autonomic activation, may represent a distinct psychopathological subgroup of patients with depressive disorders. We compared the prevalence of anger attacks in 168 outpatients with atypical depression or primary dysthymia with 38 normal subjects and tested the effect of treatment on anger attacks in a double-blind, placebo-controlled trial of sertraline versus imipramine. Patients were randomly assigned to sertraline (n = 56), imipramine (n = 52), or placebo (n = 60) and were administered the Anger Attacks Questionnaire before and after treatment. Depressed outpatients were significantly more likely to report anger attacks than controls. Anger attacks ceased in 53 percent of the patients receiving sertraline, 57 percent of those receiving imipramine, and 37 percent of those in the placebo group. Our findings support previous studies indicating that anger attacks are more prevalent among depressed outpatients than normals. Our results also suggest that sertraline and imipramine may be more effective than placebo in reducing the number of anger attacks following treatment although the differences were not statistically significant. Larger studies are needed to confirm our findings.

1-Naphthylamine↗

[Anger outbursts in unipolar depressive disorders].

Approximately one third of depressed outpatients present with "anger attacks", sudden spells of anger accompanied by symptoms of autonomic activation such as tachycardia, sweating, flushing, and tightness of the chest. These anger attacks are experienced by the patients as uncharacteristic of them and inappropriate to the situations in which they occur. Depressed patients with anger attacks are significantly more anxious and hostile, and they are more likely to meet criteria for borderline, histrionic, narcissistic, and antisocial personality disorders than depressed patients without anger attacks. Treatment studies suggest that antidepressant treatment of anger attacks in depression is helpful and sage. Anger attacks disappear in 53-71% of depressed outpatients treated with antidepressants such as fluoxetine (Prozac), sertraline and imipramine. In addition, the rate of emergence of anger attacks after treatment with fluoxetine (Prozac) (6-7%) is no different from the rates observed after treatment with sertraline (8%) and imipramine (10%), and lower than the rate with placebo (20%). Finally, one can hypothesize that antidepressants that affect serotonergic neurotransmission, known to be involved in the modulation of aggressive behavior in animals and humans, should be particularly effective in this population. Larger placebo-controlled studies, comparing selective serotonin reuptake inhibitors such as fluoxetine with relatively noradrenergic tricyclic antidepressants such as desipramine, may help us understand whether depressed patients with anger attacks show a distinctive responsiveness to drug treatment.

Anger↗

Are neurovegetative symptoms stable in relapsing or recurrent atypical depressive episodes?

Few data exist that assess the presence of reversed and positive neurovegetative symptoms through successive depressive episodes. To assess the stability of depressive symptoms across episodes, we studied 74 outpatients with atypical unipolar major depression, diagnosed by the Structured Clinical Interview for DSM-III-R, before response to fluoxetine treatment and again after relapse on either fluoxetine or placebo. Patients were assessed at baseline with the Atypical Depression Diagnosis Scale and at baseline and during follow-up with the 17-item Hamilton Rating Scale for Depression. Thirty-two (43%) of responders had a relapse or recurrence, 21 (66%) of whom had a predominance of reversed of positive neurovegetative symptoms at baseline. Nine of 10 (90%) patients with reversed symptoms at baseline had the same symptoms when they relapsed; seven of 11 (64%) of those with positive symptoms at baseline had positive symptoms again (kappa 0.557). Overall, five of 21 (24%) had changes in their disturbances in sleep, appetite, or weight when they relapsed. This study supports the relative stability of neurovegetative symptoms in atypical depression across episodes.

Adolescent↗

Prevalence and correlates of anger attacks: a two site study.

Although anger attacks have been described in depressed outpatients, they have not been well studied in other disorders. In Study 1, we examined the prevalence of anger attacks in 50 outpatients with panic disorder. In Study 2, we replicated the initial findings at an independent site and examined the specificity of anger attacks by comparing their occurrence in patients with panic disorder, patients with other non-panic anxiety disorders and patients with a depressive disorder. At both sites, we also explored the relationship between anger attacks and demographic and clinical characteristics, such as gender, presence and severity of depression, and social anxiety measures. In both sites, the prevalence of anger attacks in patients with panic disorder was approximately one-third. However, anger attacks were not unique to panic disorder, with similar rates emerging for patients with other anxiety disorders. Furthermore, patients with depressive diagnoses had twice the prevalence of anger attacks than did anxiety patients. At both sites, those with anger attacks were significantly more depressed and were likely to have either current or past history of major depression. Anger attacks were not associated with social anxiety measures, but were related to cluster B, cluster C and self-defeating personality disorder traits. Our findings support the notion that anger attacks are best conceptualized as an associated feature of depression.

Adolescent↗

Gender differences in Axis I comorbidity among depressed outpatients.

OBJECTIVE: The aim of our study was to assess gender differences in Axis I comorbidity in patients with a primary diagnosis of Major Depressive Disorder (MDD), as well as gender differences in age of onset of MDD. METHODS: The presence of MDD, including age of onset, and of comorbid Axis I disorders were assessed in 396 depressed outpatients. RESULTS: Women were significantly more likely than men to meet criteria for comorbid bulimia nervosa and for simple phobia, while men were significantly more likely than women to meet criteria for lifetime history of alcohol abuse/dependence and other substance abuse/dependence. No other significant gender differences in those comorbid Axis I disorders examined were observed. In addition, the age of onset of the first episode of MDD was significantly lower in women than in men. CONCLUSIONS: Our findings are consistent with those of previous studies showing a greater prevalence of alcohol and substance abuse and dependence in men and of eating disorders in women.

Adolescent↗

TRH stimulation test as a predictor of acute and long-term antidepressant response in major depression.

We assessed the prognostic utility of the TRH stimulation test by examining (a) the relationship between pre-treatment delta TSH and acute response to fluoxetine treatment, and (b) the relationship between the change in delta TSH (delta delta TSH value) after repeated TRH testing at 6 weeks of fluoxetine treatment and long-term outcome during maintenance fluoxetine or placebo therapy. 43 MDD patients were studied with sequential TRH tests at 6-week intervals. Fluoxetine 'responders' were defined as patients with a Hamilton Depression Rating Scale score < or = 7 by week 9 of treatment and who remained in remission at least 3 additional weeks. These subjects were then randomized to one of four fluoxetine/placebo treatment groups and long-term outcome assessed. Overall, there was no difference in the mean pre-treatment delta TSH values between acute fluoxetine responders and nonresponders. Moreover, we observed similar delta delta TSH values in patients who maintained long-term remission compared to those who relapsed during maintenance with either fluoxetine or placebo. In contrast to prior reports of an higher delta delta TSH value in long-term remitters, the present observation of similar mean delta delta TSH values patients with long-term remission compared to those who relapsed suggest a limited prognostic utility for the TRH stimulation test in MDD.

Adult↗

Attention deficit hyperactivity disorder in childhood among adults with major depression.

The prevalence of attention deficit hyperactivity disorder (ADHD) with childhood onset and its relationship to course and treatment outcome of major depressive disorder (MDD) in adults was studied in 116 patients (ages 18-65) consecutively enrolled for treatment of MDD. Sixteen percent of the patient were found to meet full or subthreshold criteria for the DSM-III-R diagnosis of childhood ADHD. Twelve percent endorsed persistence of ADHD symptoms into adulthood. Depressed adults meeting criteria for childhood ADHD did not differ significantly from other depressed adults on any measures related to the chronicity or severity of the mood disorder, Axis I comorbidity, or response to acute antidepressant treatment. Our results are clinically important as they suggest that clinicians need to be aware of the possibility that a substantial proportion of patients with MDD may suffer from comorbid ADHD and that treatments need to include the targeting of possible residual ADHD symptoms in addition to those of depression.

Adolescent↗

A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia.

BACKGROUND: Despite the high prevalence of dysthymia and its associated morbidity, few controlled trials have evaluated the efficacy of antidepressant medication for this disorder. A 12-week, double-blind, placebo-controlled, randomized, multicenter trial was performed to evaluate the safety and efficacy of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia. METHODS: A total of 416 outpatients (271 women and 145 men) aged 25 to 65 years with DSM-III-R-defined, early-onset, primary dysthymia without concurrent major depression were randomized to 12 weeks of treatment with sertraline, imipramine, or placebo. RESULTS: Both active treatments resulted in significantly reduced scores on the 17-item Hamilton Rating Scale for Depression (P = .04 and P = .01 for sertraline and imipramine vs placebo, respectively), the Montgomery-Asberg Depression Rating Scale (P = .01 and P = .003 vs placebo, respectively), Hopkins Symptom Checklist (P < .05), and the self-rated version of the Inventory of Depressive Symptoms (P < .05). With the use of a Clinical Global impressions improvement score of 1 or 2 (very much or much improved) to define response, response rates were 59% for sertraline, 64% for imipramine, and 44% for placebo (P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo). A significantly greater proportion of patients receiving imipramine than those receiving sertraline or placebo discontinued treatment because of adverse events (P = .001 and P < .001, respectively). CONCLUSIONS: Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder, with both sertraline and imipramine being more effective than placebo. The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia, which may require prolonged treatment with antidepressant medication.

1-Naphthylamine↗

Dichotic listening before and after fluoxetine treatment for major depression: relations of laterality to therapeutic response.

Despite the wide variance in therapeutic response to antidepressants, there are few clinical or biological predictors of treatment outcome. Studies have suggested the possible value of dichotic listening measures of perceptual asymmetry (PA) as predictors of treatment response. This study examined the relation between outcome of fluoxetine treatment and performance on verbal and nonverbal dichotic tests. As part of a multisite study, 86 outpatients with major depression were tested on dichotic fused-words and complex-tones tests both before and during treatment. Fluoxetine responders differed from nonresponders in having greater right-ear (left-hemisphere) advantage for dichotic words and less left-ear (right-hemisphere) advantage for complex tones. There was no change in PA during fluoxetine treatment, which indicates that PA differences between treatment responders and nonresponders are stable (trait) characteristics. An aggregate, characteristic PA measure was the best predictor of responder status in a logistic regression analysis. Findings from two clinical centers support the hypothesis that a characteristic tendency for relatively greater left-than right-hemispheric activation during dichotic listening is associated with better outcome of fluoxetine treatment.

Acoustic Stimulation↗

Definition and epidemiology of treatment-resistant depression.

Our results suggest that between 29% and 46% of depressed patients fail to respond fully with antidepressant treatment of adequate dose and duration. In particular, although partial response appears to occur in 12% to 15% of the depressed patients studied, nonresponse is observed in 19% to 34% of this population. The prevalence of treatment-resistant depression derived from studies using ITT analysis is likely to be an overestimate of the actual occurrence of the phenomenon, as these rates also reflect the outcome of patients who were treated inadequately or were intolerant to the treatment. On the other hand, data derived from studies using completer analysis are likely to generate under-estimates of the prevalence of this phenomenon, as patients may have dropped out before completion of the study due to lack of efficacy. One could, therefore, guess that the actual rates of treatment resistance in the clinical population of depressed patients probably lie between these two types of estimates. From an epidemiologic point of view, because the prevalence of depression has been estimated to vary from 2.6% to 5.5% in men and from 6.0% to 11.8% in women, one must conclude that treatment-resistant depression is a very common clinical problem that is likely to affect more than one third of depressed patients. In summary, treatment-resistant depression patients can be defined as those who fail to respond to standard doses (i.e., significantly superior to placebo in double-blind studies) of antidepressants administered continuously for at least 6 weeks. Additional requirements of this operational definition are an accurate diagnosis of depressive disorder, patient compliance with the treatment, the use of valid outcome measures, and therapeutic range of antidepressant blood levels for the tricyclic antidepressants. Finally, symptomatic improvement that is equal or greater than 25% and less than 50% qualifies as partial response, and less than 25% symptomatic improvement is complete nonresponse.

Antidepressive Agents↗