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Biomedical subjects

B Lafer

Publications and source records attributed to B Lafer.

At least 19 recordsLinked to original sources
PubMed2004

Treatment emergent affective switch: a controlled study.

OBJECTIVE: To study the clinical features of treatment emergent affective switch (TEAS) in comparison with spontaneous mania. METHODS: Twelve patients with TEAS within a 12-week period (average) of starting standard antidepressant medication were compared with 12 patients with spontaneous mania. RESULTS: Patients with TEAS were older, had longer duration of illness, more previous episodes, higher prevalence of subclinical hypothyroidism, and reported more previous episodes of mania associated with antidepressant use. TEAS was less severe, with a lower incidence of psychotic symptoms, lower Young Mania Rating Scale index score and rarely required hospitalization. The interval from intervention to response and remission was similar in both groups. CONCLUSION: TEAS was less severe, but had similar duration when compared with spontaneous mania. These results cannot directly answer the question of whether there is a causal relationship between antidepressant use and TEAS. While it is also possible that patients with longer duration of illness and higher cycle frequencies are more likely to experience episodes, it is difficult to attribute lesser severity of TEAS episodes to these clinical factors. Our observations are consistent with the suggestion that patients with longer duration of illness and previous history of TEAS may be at a greater risk of switching to mania during the use of antidepressants.

Adolescent↗
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

Double-blind comparison of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia.

The purpose of this study was to compare the efficacy and tolerability of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia. This was an 8-week, multicentre, randomized, double-blind, parallel-group comparison of venlafaxine and amitriptyline. Outpatients with DSM-IV major depression, a minimum score of 20 on the 21-item Hamilton Depression Rating Scale (HAM-D), and depressive symptoms for at least 1 month were eligible. Patients were randomly assigned to venlafaxine or amitriptyline, both drugs titrated to a maximum of 150 mg/day until study day 15. The primary efficacy variables were the final on-therapy scores on the HAM-D, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression severity scales. Data were evaluated on an intent-to-treat basis using the LOCF method. One hundred and 16 patients were randomized, and 115 were evaluated for efficacy. Both drugs showed efficacy in the treatment of depression with or without melancholia. No significant differences were noted between treatments for any efficacy parameter. However, significantly (p < 0.05) more patients in the amitriptyline group had at least one adverse event. These results should support the efficacy and tolerability of venlafaxine in comparison with amitriptyline for treating major depression with or without melancholia.

Adolescent↗
PubMed1998

Analysis of a novel functional polymorphism within the promoter region of the serotonin transporter gene (5-HTT) in Brazilian patients affected by bipolar disorder and schizophrenia.

It has been suggested that the serotonin transporter (5-hydroxytryptamine-transporter or 5-HTT) may be involved in the pathogenesis of affective disorders. Recently, Collier et al. (1996) found that the frequency of the low-activity short variant (s) of the 5-HTT-linked polymorphic region (5-HTTLPR) was higher among patients with affective disorders than in normal controls. However, since the observed level of significance was not high, they suggest that these findings should be replicated in independent samples. We have analyzed 86 unrelated patients (47 with bipolar disorder and 39 with schizophrenia) and 98 normal controls from the Brazilian population for the 5-HTTLPR. Statistical analysis revealed that the genotypes (LL, Ls, ss) as well as the estimated allele frequencies (L,s) did not differ significantly among the three studied groups or between bipolar and normal controls. In addition, although not statistically significant, the genotype ss in our sample was less frequent among our bipolar patients than in our normal controls (12.8% versus 16.3%) which is the opposite of what was found by Collier et al. (24% versus 18%) in the European study. Although it will be important to extend the present analysis in a larger sample, our preliminary results suggest that the 5-HTTLPR does not seem to play a major role in the genetics of bipolar and schizophrenic disorders at least in this group of Brazilian psychiatric patients.

Bipolar Disorder↗
PubMed1997

Changes in regional cerebral blood flow following light treatment for seasonal affective disorder: responders versus nonresponders.

BACKGROUND: Several brain imaging studies of antidepressant pharmacologic treatment utilizing single photon emission computed tomography (SPECT) have reported a normalization of deficits in cerebral blood flow (CBF) associated with recovery; other studies report no change, or a reduction in CBF following successful treatment. There have been no published SPECT studies of seasonal affective disorder (SAD) assessing response to light treatment in relation to changes in regional CBF (rCBF). In this study, we sought to test the hypothesis that increases in rCBF would be observed in SAD patients who responded to light treatment. METHODS: Ten depressed patients with SAD underwent functional brain imaging studies with 99mTc-hexamethylpropyleneamine oxime SPECT before and after light treatment. RESULTS: Relative increases in rCBF were observed in all brain regions compared to cerebellum in treatment responders, whereas nonresponders showed no change or decreases in rCBF relative to cerebellum. Significant differences in mean percentage change in rCBF between responders (n = 5) and nonresponders (n = 5) were detected in frontal and cingulate cortex, and thalamus. CONCLUSIONS: These findings provide preliminary support for the hypothesis that an increase in rCBF is associated with recovery from depression in SAD.

Adult↗
PubMed1997

A quantitative magnetic resonance imaging study of cerebral and cerebellar gray matter volume in primary unipolar major depression: relationship to treatment response and clinical severity.

The authors investigated whether there were differences in cerebral and cerebellar gray and white matter volumes in depressed patients compared to controls, and whether this was associated with treatment response to fluoxetine. Brain magnetic resonance images were obtained from 38 unipolar depressed patients and 20 age, gender, and educationally matched comparison subjects. Patients were divided into groups of "responders" and "nonresponders" based on change in 17-item Hamilton Depression Rating Scale (HDRS) after an 8-week standardized trial of fluoxetine, 20 mg/day. There were no group mean differences in cerebral or cerebellar tissue volumes between patients and controls, or responders and nonresponders. For nonresponders to fluoxetine treatment, cerebral and cerebellar gray matter volume, and total cerebellar tissue volume decreased as baseline HDRS increased. The results suggest an association between gray matter volume and severity of illness in nonresponders to fluoxetine treatment.

Adult↗
PubMed1997

Basal ganglia choline levels in depression and response to fluoxetine treatment: an in vivo proton magnetic resonance spectroscopy study.

We have investigated proton magnetic resonance spectra of the basal ganglia in 41 medication-free outpatients with major depression, prior to starting an 8-week standardized trial of open-label fluoxetine, and 22 matched comparison subjects. Upon completing the trial, depressed subjects were classified as treatment responders (n = 18) or nonresponders (n = 23), based on changes in the Hamilton Depression Rating Scale. Depressed subjects had a lower area ratio of the choline resonance to the creatine resonance (Cho/Cr) than comparison subjects. This statistically significant difference between the depressed subjects and comparison subjects was more pronounced in the treatment responders than in the nonresponders. There were no differences in the relative volumes of gray matter or white matter in the voxel used for proton spectroscopy in depressed subjects relative to comparison subjects. These results are consistent with an alteration in the metabolism of cytosolic choline compounds in the basal ganglia of depressed subjects and, in particular, those who are responsive to fluoxetine.

Adult↗
PubMed1997

Major depression and the basal ganglia.

In the last decade, major changes in our understanding of basal ganglia functions have occurred. Traditionally the basal ganglia were considered to be involved only in the modulation of movement. Recent research has suggested that the basal ganglia also take part in complex fronto-subcortical networks that have an important role in cognition reward, and mood regulation. The authors review recent findings that implicate basal ganglia abnormalities in the pathophysiology of mood disorders and discuss their potential implications for future developments in the pharmacotherapy of depressive disorder.

Antidepressive Agents↗
PubMed1997

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↗
PubMed1996

Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients.

This study examined choline augmentation of lithium for rapid-cycling bipolar disorder. Choline bitartrate was given openly to 6 consecutive lithium-treated outpatients with rapid-cycling bipolar disorder. Five patients also underwent brain proton magnetic resonance spectroscopy. Five of 6 rapid-cycling patients had a substantial reduction in manic symptoms, and 4 patients had a marked reduction in all mood symptoms during choline therapy. The patients who responded to choline all exhibited a substantial rise in the basal ganglia concentration of choline-containing compounds. Choline was well tolerated in all cases. Choline, in the presence of lithium, was a safe and effective treatment for 4 of 6 rapid-cycling patients in our series. A hypothesis is suggested to explain both lithium refractoriness in patients with bipolar disorder and the action of choline in mania, which involves the interaction between phosphatidylinositol and phosphatidylcholine second-messenger systems.

Adult↗
PubMed1996

Regional cerebral blood flow changes after light therapy in seasonal affective disorder.

There is considerable evidence to indicate that depressive disorders may be associated with changes in regional cerebral blood flow (rCBF), and that successful treatment may reverse these changes. We studied patients with seasonal affective disorder (SAD) using 99Tcm-hexamethylpropylene amine oxime (99TCm-HMPAO) single photon emission tomography (SPET) to examine the effect of light therapy on rCBF. Ten depressed patients (8 females, 2 males) with a mean (+/- S.D.) age of 33.5 +/- 11.3 years underwent 99TCm-HMPAO SPET studies before and after light therapy. The treatment response was evaluated using the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version (SIGH-SAD). A patient was considered responsive to light therapy if the post-treatment SIGH-SAD score was reduced by 60% or more in comparison to the pre-treatment score (responders, n = 5; non-responders, n = 5). Pre- and post-treatment SIGH-SAD scores and SPET data were compared in each patient. An improvement in depressive symptoms after light therapy was associated with an increase in rCBF in the frontal and cingulate regions as well as the thalamus. Such changes were not seen in non-responsive subjects.

Adult↗
PubMed1995

Influence of phototherapy treatment duration for seasonal affective disorder: outcome at one vs. two weeks.

Most previous phototherapy research has been conducted on trials of 1 week duration. This study compares response to phototherapy at weeks 1 and 2. All subjects (n = 26) were between 18 and 65 years and met Diagnostic and Statistical Manual of Mental Disorders, 3rd ed, revised, (DSM III-R) criteria for major depression, recurrent, seasonal pattern and had a Hamilton Depression Rating Scale score (HAM-D) > or = 20. A rater blinded to treatment schedule and study hypothesis repeated the HAM-D-31 1 and 2 weeks after baseline to assess treatment response to bright light. Response rates at week 1 defined by 50% reduction in HAM-D-31 and HAM-D-31 score < 8 were 62% and 27%, respectively. At week 2, however, 65% had a 50% reduction in HAM-D-31 and 62% had a HAM-D-31 < score 8 (chi-square = 6, p = 0.01). Four patients (15%) who were nonresponders at week 1 responded after 2 weeks. The results show a statistically different outcome after 2 weeks of treatment and suggest the necessity of longer trials of phototherapy.

Adolescent↗
PubMed1995

Variability of brain lithium levels during maintenance treatment: a magnetic resonance spectroscopy study.

In vivo magnetic resonance spectroscopy (MRS) was used to determine the relationship between serum and brain lithium levels in bipolar patients (n=25). Over the broad range of serum lithium levels observed, the correlation (r=.68) with brain lithium levels was high. This correlation was much weaker (r=.39) when limited to only those patients with serum lithium levels in the range of 0.6-1.0 mmol/l. This variability may account for failure of lithium prophylaxis in some patients who have serum lithium levels in the therapeutic range.

Adult↗
PubMed1994

Phototherapy for seasonal affective disorder: a blind comparison of three different schedules.

The authors investigated the outcome of an alternating time schedule versus two fixed schedules (either morning or evening) of bright light treatment for seasonal affective disorder. The subjects were 31 patients who met DSM-III-R criteria for major depression with a seasonal pattern. No statistically significant difference was observed among patients in the three groups for response criteria after 1 week of treatment. These results support the use of more flexible phototherapy schedules.

Adolescent↗
PubMed1994

A double-blind trial of bupropion versus desipramine for bipolar depression.

BACKGROUND: Although treatment of bipolar depression is a frequent clinical problem, double-blind studies of the treatment of bipolar depression are scarce. Some case series and uncontrolled data suggest antidepressants may differ in their propensity to induce mania or their efficacy for bipolar depression. METHOD: The authors conducted a prospective double-blind trial to assess efficacy and rate of treatment-emergent mood elevation in depressed bipolar patients when bupropion or desipramine was added to an ongoing therapeutic regimen of lithium or an anticonvulsant. Results were assessed after 8 weeks of acute treatment and during maintenance treatment up to 1 year. RESULTS: No difference was found for acute efficacy between the two drugs. Mania/hypomania was observed in 5 of 10 desipramine-treated patients, but only 1 of 9 bupropion-treated patients. The occurrence of hypomania or mania was correlated with treatment group (Kendall's tau correlation = 0.42; Z = -2.5, p < .012). CONCLUSION: These pilot findings suggest that bupropion is less likely to induce mood elevation than desipramine. For treatment of bipolar depression, bupropion and desipramine appear to have similar antidepressant efficacy.

Adult↗
PubMed1994

Side effects induced by bright light treatment for seasonal affective disorder.

BACKGROUND: Bright light treatment has become an accepted treatment for seasonal affective disorder (SAD), but there have been few studies about adverse effects from using this treatment. We conducted a study to examine the frequency of adverse effects of bright light treatment for SAD. METHOD: Thirty patients meeting DSM-III-R criteria for major depression, recurrent, with seasonal pattern as determined by the Structured Clinical Interview for DSM-III-R were administered a structured interview, the 42-item Systematic Assessment for Treatment Emergent Events, to assess side effects from bright light treatment. RESULTS: Side effects were limited and mild. They remitted with time or decreased light. No patient discontinued treatment. One patient developed mild hypomania and 3 became agitated. Sleep disturbance occurred in 62% of patients (5 of 8) using evening light. Visual side effects occurred in 26% of patients (8 of 30). CONCLUSION: Except for one case of mild hypomania, no other clinically significant treatment-emergent adverse effects developed. Hypomania is an uncommon, but clinically important side effect. Mild visual complaints were common and remitted promptly. In this group of patients with SAD, bright light treatment was well tolerated and resulted in a limited number of adverse effects, none of which compromised treatment. The absence of a control group limits the specificity of these side effects to bright light treatment.

Adolescent↗
PubMed1993

The influence of DST and TRH test administration on depression assessments: a controlled study.

Significant antidepressant effects have been reported after administration of dexamethasone and thyrotropin-releasing hormone (TRH). The purpose of this study was to evaluate whether or not the administration of the dexamethasone suppression test (DST) and TRH test in depressed patients, just before their entering clinical trials, has any impact on their symptoms. The Hamilton Rating Scale for Depression was administered to 166 subjects at screen visit, 1 week later (baseline visit), and 1 week after beginning treatment with fluoxetine 20 mg/day (week-1). Between screen and baseline visits, 62 patients were administered the DST alone, 6 underwent the TRH test alone, and 26 received both the DST and the TRH test. Seventy-two patients were not administered either test. No statistically significant differences in depression scores were found at screen, baseline and week-1 visits between patients who underwent neuroendocrine tests and those who did not. Our data suggest that the administration of neuroendocrine tests such as the DST and the TRH test does not have a statistically significant effect on depressive symptoms and, therefore, does not interfere with study results and interpretation.

Adolescent↗