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Biomedical subjects

J D Amsterdam

Publications and source records attributed to J D Amsterdam.

At least 19 recordsLinked to original sources
PubMed2001

Acute mood and thyroid stimulating hormone effects of transcranial magnetic stimulation in major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has recently been demonstrated to have antidepressant effects. Some work suggests that rTMS over prefrontal cortex administered to healthy individuals produces acute elevations of mood and serum thyroid-stimulating hormone (TSH). We sought to determine whether single rTMS sessions would produce acute mood and serum TSH elevations in subjects with major depressions. METHODS: Under double-blind conditions et al 14 medication-free subjects with major depression received individual sessions of either active or sham rTMS. rTMS was administered over the left prefrontal cortex at 10 Hz et al 100% of motor threshold, 20 trains over 10 min. Immediately before and after rTMS sessions, subjects' mood was rated with the Profile of Mood States (POMS) and the 6-Item Hamilton Depression Scale, and blood was drawn for later analysis of TSH. Subjects and raters were blind to treatment assignment. RESULTS: The group receiving active stimulation manifested significantly greater improvement on the POMS subscale of Depression (p < or = .0055) and a trend toward greater improvement on the modified Hamilton Rating (.05 < p < or =.1). No hypomania was induced. The change in TSH from pre- to post-rTMS was significantly different between active and sham sessions. CONCLUSIONS: This blinded, placebo-controlled trial documents that individual rTMS sessions can acutely elevate mood and stimulate TSH release in patients experiencing major depressive episodes.

Acute Disease↗
PubMed2000

Venlafaxine monotherapy in women with bipolar II and unipolar major depression.

BACKGROUND: Women with bipolar (BP) disorder have more depressive episodes and drug-induced manic switches compared to men. Current guidelines suggest treating BP type I and type II major depressive episode (MDE) with both a mood-stabilizer and antidepressant. In a post hoc analysis, we examined the safety and efficacy of venlafaxine monotherapy in women with BP II MDE. METHODS: 15 women with BP II MDE (mean+/-SD age: 37+/-12 years) were compared to 17 women with unipolar (UP) MDE (41+/-12 years). Patients were randomized to double-blind treatment with once versus twice daily venlafaxine up to 225 mg for 6 weeks. Efficacy was measured using the HAM-D(21), MADRS and CGI scales. Drug-induced manic switch episodes characterized by agitation, irritability, euphoria or mood lability were assessed at each visit. RESULTS: No episodes of drug-induced hypomania or rapid cycling were observed during 6 weeks of venlafaxine monotherapy. Similar efficacy was observed in BP and UP depressed women (p=ns). LIMITATIONS: This study was retrospective in nature and limited in patient number. Only BP II women were included in this study, and it is possible that efficacy and the manic switch rate might have differed if BP I women were included. CONCLUSION: Short-term venlafaxine monotherapy may be a safe and effective antidepressant treatment in women with BP II MDE.

Adult↗
PubMed2000

Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression.

BACKGROUND: The goal was to examine predictors of relapse during continuation/maintenance treatment of major depression that had remitted following 12 to 14 weeks of fluoxetine therapy. METHOD: The study utilizes data collected in a collaborative clinical trial including patients with DSM-III-R major depression at 5 university-affiliated outpatient psychiatry clinics. Three hundred ninety-five patients who remitted with fluoxetine therapy were randomly assigned to 1 of 4 treatments: fluoxetine for 14 weeks followed by placebo for 36 weeks, fluoxetine for 38 weeks followed by placebo for 12 weeks, fluoxetine for 50 weeks, or placebo for 50 weeks. Cox proportional hazard models were used to identify predictors of time to relapse. RESULTS: In addition to the previously reported longitudinal pattern of response during acute treatment, neurovegetative symptom pattern was a predictor of fluoxetine benefit compared with placebo. Greater chronicity predicted poorer survival, which was not differential by treatment. The most robust advantage of fluoxetine was seen for patients with endogenous vegetative symptoms, chronic depression, and acute treatment response characterized by onset in the third week or later and persistence of response once attained. CONCLUSION: Both nonspecific pattern of response and neurovegetative symptoms characteristic of atypical depression were predictive of lack of fluoxetine efficacy in continuation/ maintenance treatment. These findings have importance for both clinical management and analyses of future maintenance trials.

Adult↗
PubMed1999

Autoantibody disturbances in affective disorders: a function of age and gender?

BACKGROUND: Numerous investigators have reported increased autoantibodies to a wide variety of native antigens in patients with affective disorders. However, association of autoimmunity with affective subtypes, mood state, psychotropic medications, age, and gender has not been extensively explored. METHODS: The present study assessed 79 bipolar I, 24 bipolar II, and 46 unipolar major depression patients along with 22 healthy, nonpsychiatric controls for the presence of serum antinuclear (ANA), anti-double stranded DNA, antithyroid microsomal, antithyroglobulin, anticardiolipin (ACA) IgM, and ACA IgG antibodies. RESULTS: Consistent with their higher prevalence of autoimmune disease, women exhibited increased levels of ANA and ACA IgM compared to men. ACA IgG antibody titers also increased significantly with age. Contrary to prior reports of general, overall increases in autoantibodies and specific increases in ANA and antithyroid antibodies in depressed patients, we did not see a significant association between any of the autoantibodies and affective subtype, mood state, or psychotropic medications. LIMITATIONS: Affective subgroups were heterogeneous with respect to psychotropic medications, affective state, age, and gender in this retrospective analysis. Subgroup sample size was insufficient to determine whether interactions of these clinical variables may have influenced results. CONCLUSION: These results suggest that gender and age may have more influence on autoantibodies than affective diagnosis, affective state, or medications.

Adult↗
PubMed1999

Blood pressure changes during short-term fluoxetine treatment.

Recent reports of sustained hypertension in some patients receiving venlafaxine have rekindled concerns about antidepressant-induced hypertension. This study examined sitting and standing systolic and diastolic blood pressure, pulse rate, and rate of sustained hypertension in 796 depressed patients (mean +/- SD age, 40 +/- 11 years) taking fluoxetine 20 mg daily for up to 12 weeks. A modest reduction in sitting and standing systolic (p < 0.001) and diastolic (p < 0.001) blood pressure measures were observed in the entire patient sample. Patients with pretreatment diastolic blood pressure < 60 mmHg (N = 32) showed a modest increase in mean diastolic blood pressure (p < 0.001), whereas patients with pretreatment diastolic blood pressure > or = 90 mmHg and < or = 95 mmHg (N = 57) had a modest reduction in mean diastolic blood pressure (p < 0.001). Patients with preexisting, stable cardiovascular disease (including hypertension) (N = 35) showed no significant blood pressure change (p = not significant). Of the patients receiving fluoxetine, 1.7% had sustained hypertension for > or = 3 consecutive clinic visits-a rate significantly lower than that previously reported with venlafaxine (4.8%) (chi2 = 13.3, p < 0.001) and similar to that previously seen with placebo (2.1%). In conclusion, these data demonstrate a low rate of sustained hypertension (1.7%) during short-term fluoxetine treatment.

Adolescent↗
PubMed1999

Changes in weight during a 1-year trial of fluoxetine.

OBJECTIVE: Fluoxetine has been associated with weight loss during acute treatment, but no controlled studies of weight change during long-term treatment with fluoxetine or other selective serotonin reuptake inhibitors have been reported. Weights were assessed for patients whose depressive symptoms had disappeared with acute fluoxetine treatment. Patients were then randomly assigned to continuation treatment with fluoxetine or placebo. METHOD: Patients whose illness had remitted after 12 weeks of treatment with fluoxetine, 20 mg/day, were randomly assigned to receive up to 38 weeks of treatment with fluoxetine or placebo. Weight was assessed at each visit. Change in weight was analyzed during the initial 12 weeks of acute treatment and after 14, 26, and 38 weeks. Relationships between weight change and body mass index and between weight change and appetite change were assessed. RESULTS: During the initial 4 weeks of therapy, a mean absolute weight decrease of 0.4 kg was observed for all patients. Among patients who completed 50 weeks of therapy, the mean absolute weight increase during continuation treatment was similar for both the placebo- and fluoxetine-treated groups. Weight increase was not related to initial body mass index but was related to both poor appetite at study entry and to improvement in appetite after recovery. No patients discontinued therapy because of weight gain. CONCLUSIONS: Acute therapy with fluoxetine is associated with modest weight loss. After remission of depressive symptoms, weight gain for patients taking fluoxetine for longer periods is not different from that for patients taking placebo and is most likely related to recovery from depression.

Adult↗
PubMed1999

Changes in adverse events reported by patients during 6 months of fluoxetine therapy.

BACKGROUND: Although a period of 6 to 12 months of antidepressant therapy is recommended for most patients with depression, systematic examinations of the course of adverse events over time, the resolution of early-onset events, and the possible emergence of later-onset events are limited. We examined the safety of fluoxetine, 20 mg/day, in a large, prospective, long-term treatment trial, and we report a comparison of early- and late-onset adverse events and the course of adverse events over 26 weeks of treatment. METHOD: Adverse events were recorded at each visit in a uniform format by open-ended questioning, regardless of perceived causality. New or worsened events reported in either the first 4 weeks of treatment (early-reporting interval) or weeks 22 through 26 of treatment (late-reporting interval) were compared. RESULTS: Patients (N = 299) whose depression (DSM-III-R) remitted with 12 weeks of fluoxetine treatment entered continuation therapy, and 174 completed 26 weeks of therapy. All events that occurred in > or =5% of patients early in treatment decreased in frequency over time (p<.05), and no events occurred significantly more frequently during continuation therapy. No previously uncommon adverse events became common during long-term treatment. CONCLUSION: Common adverse events associated with initiating fluoxetine treatment in depressed patients, including nausea, insomnia, nervousness, and somnolence, resolve in the majority of patients and become significantly less frequent with continued treatment over a 6-month period. No adverse events present initially become more frequent late in treatment. Therapy with fluoxetine, 20 mg/day, is well tolerated over 6 months, and most adverse events observed early in treatment resolve.

Anxiety↗
PubMed1998

Rates of flu-like infection in patients with affective illness.

Studies of immunologic profiles of depressed patients are suggestive of chronic viral infection and several investigators have found specific viral protein in some depressed patients. Moreover, several psychotropic drugs have anti-viral activity and can inhibit viral replication. In this preliminary report, we retrospectively examined the rate of reported flu-like episodes before and during psychotropic drug treatment in 236 affectively ill patients: 177 receiving lithium prophylaxis and 59 receiving chronic antidepressant medication. We observed a small but significant reduction in the mean rate of reported flu-like illness during lithium therapy (P < 0.001), with a greater reduction in men vs. women (P < 0.05). We also found a modest reduction in reported flu-like illness during chronic treatment with antidepressants (P = 0.08). Although these observations are preliminary in nature, they complement earlier reports that some psychotropic drugs may have anti-viral activity.

Antiviral Agents↗
PubMed1998

Positive and negative acute phase proteins in affective subtypes.

BACKGROUND: Patients with affective disorders show evidence of increased positive acute phase proteins (e.g., C-reactive protein [CRP], alpha-1-acid glycoprotein, haptoglobin) and decreased negative acute phase proteins (e.g., albumin, transferrin [TFN]). CRP reductions have been reported to be greater in patients who later respond to lithium augmentation, and these patients also demonstrate higher CRP levels on the failed antidepressant, prior to the addition of lithium. However, association of such systemic immune changes with affective subtypes, mood state, psychotropic medications, age and gender has not been extensively explored. METHODS: The present study assessed levels of CRP and TFN in 79 bipolar I, 24 bipolar II, and 46 unipolar depressed outpatients in comparison to 22 healthy controls. RESULTS: Patients on lithium monotherapy were significantly less likely to demonstrate elevated CRP, and a similar trend was noted in those patients taking lithium in combination with an antidepressant. The frequency of elevated CRP levels did not significantly vary for different psychotropic medications, affective subgroups, or mood states. TFN levels were not influenced by diagnosis, affective state or psychotropic medications. LIMITATIONS: Due to the retrospective nature of this analysis, the affective subgroups were heterogeneous with regard to medications and affective state, and differed significantly in age. Due to limitations in subgroup sample size, significant effects of clinical variables may have been masked by interactions of medications, age, affective subtype, and mood state. CONCLUSIONS: The results imply that lithium may play a role in normalizing systemic immune activation associated with depression. Whether such immune changes may be restricted to lithium-responsive subgroups deserves further evaluation.

Acute-Phase Proteins↗
PubMed1998

Bone density measurement in major depression.

1. Disturbances in cortisol secretory patterns and excessive secretion of cortisol after a variety of neuroendocrine stimulation tests indicate excessive activity of the hypothalamic-pituitary-adrenocortical axis in depression. 2. Peripheral indicators of hypercortisolemia have also been observed (e.g. enlarged adrenal glands, glucocorticoid insensitivity and insulin intolerance). 3. Excessive cortisol production may also result in altered bone metabolism and bone architecture, and a recent study by Michelson et al. (1996) found slightly lower bone density in depressed women with hypercortisoluria versus healthy controls. 4. In this study, the authors examined bone mineral density (BMD) using dual energy radiographic absorptometry (DEXA) technique in 6 depressed patients (3 with and 3 without hypercortisoluria) with a mean (+/- SD) age of 41 +/- 13 years, and in 5 healthy, controls with mean age 38 +/- 4 years). 5. DEXA images of the lumbar vertebrae (L1 to L4) for BMD were acquired over a 5-minute interval. 6. Overall, the authors observed no difference in mean BMD values between patients and controls, nor were differences observed between patients with and without hypercortisoluria.

Absorptiometry, Photon↗
PubMed1998

A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression.

We report results from a multicenter, placebo-controlled, randomized, double-blind comparison of the efficacy and tolerability of paroxetine and fluoxetine in outpatients with major depression. Across five U.S. sites, 128 outpatients (mean age: 41.3 +/- 12.6; 63 men and 65 women) with moderate to moderately severe major depression without a history of mania or hypomania were recruited between 1993 and 1994. All 128 patients completed a 1-week placebo washout period, and were then randomized to 12 weeks of double-blind treatment with paroxetine up to 50 mg/day (n = 55), fluoxetine up to 80 mg/day (n = 54), or placebo (n = 19). Subjects were evaluated weekly for the first 4 weeks, then at weeks 6, 9, and 12 with the 21-item HAMD and the Covi Anxiety Scale. There were no significant differences among the three treatment groups in baseline and endpoint depression and anxiety severity, as well as in the degree of depression and anxiety improvement. There were no statistically significant differences in rates or mean numbers of adverse events between paroxetine-treated patients and fluoxetine-treated patients. In summary, our results, although limited by the lack of a significant difference from placebo in treatment outcome, suggest that the SSRIs paroxetine and fluoxetine have comparable antidepressant and antianxiety efficacies among depressed outpatients, as well as similar safety and tolerability profiles.

Adult↗
PubMed1998

Efficacy and safety of fluoxetine in treating bipolar II major depressive episode.

As many as 45% of patients with major depressive episode also meet DSM-IV criteria for bipolar II (BP II) disorder. Although some clinicians advocate using a mood stabilizer in treating BP II depression, antidepressant monotherapy has been less well studied in this disorder. As part of a prospective, placebo-controlled, relapse-prevention study in 839 patients, the efficacy and safety of short- and long-term fluoxetine treatment in patients with BP II major depression compared with patients with unipolar (UP) major depression was retrospectively examined. Eighty-nine BP II patients (mean age, 41+/-11 years) were compared with 89 age- and gender-matched UP patients and with 661 unmatched UP patients (mean age, 39+/-11 years). All received short-term fluoxetine therapy at 20 mg daily for up to 12 weeks. Complete remission was defined as a final Hamilton Rating Scale for Depression score < or = 7 by week 9 that was then maintained for 3 additional weeks. Remitted patients were then randomly assigned to receive double-blind treatment with one of the following: (1) fluoxetine 20 mg daily for 52 weeks; (2) fluoxetine for 38 weeks, then placebo for 14 weeks; (3) fluoxetine for 14 weeks, then placebo for 38 weeks; or (4) placebo for 52 weeks. Antidepressant efficacy was similar in BP and UP patients during short-term therapy. Discontinuation for lack of efficacy was lower in BP II (5%) than in UP (12%) patients (p = not significant [NS]), whereas dropouts for adverse events were similar in BP II (11%) and UP (9%) patients. During long-term relapse-prevention therapy, relapse rates were similar in BP II and UP patients (p = NS). During short-term fluoxetine therapy, three BP II (3.8%) versus no matched UP (p = NS) and 0.3% unmatched UP (p = 0.01) patients had a "manic switch." During long-term fluoxetine therapy, one (2%) BP II and three (1%) unmatched UP patients (one taking placebo) had a manic switch (p = NS). In conclusion, fluoxetine may be a safe and effective antidepressant monotherapy for the short-term treatment of BP II depression with a relatively low manic switch rate. Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder.

Adolescent↗
PubMed1998

Optimal length of continuation therapy in depression: a prospective assessment during long-term fluoxetine treatment.

OBJECTIVE: The purpose of this study was to determine prospectively the optimal length of therapy in a long-term, placebo-controlled continuation study of patients who responded to acute fluoxetine treatment for major depression (defined by DSM-III-R). METHOD: The study was conducted at five outpatient psychiatric clinics in the United States. Patients who met criteria for remission after 12 or 14 weeks of open-label acute fluoxetine therapy, 20 mg/day (N=395 of 839 patients), were randomly assigned to one of four arms of a double-blind treatment study (50 weeks of placebo, 14 weeks of fluoxetine and then 36 weeks of placebo, 38 weeks of fluoxetine and then 12 weeks of placebo, or 50 weeks of fluoxetine). Relapse rate was the primary outcome measure. Both Kaplan-Meier estimates and observed relapse rates were assessed in three fixed 12-week intervals after double-blind transfers from fluoxetine to placebo at the start of the double-blind period and after 14 and 38 weeks of continued fluoxetine treatment. RESULTS: Relapse rates (Kaplan-Meier estimates) were lower among the patients who continued to take fluoxetine compared with those transferred to placebo in both the first interval, after 24 total weeks of treatment (fluoxetine, 26.4%; placebo, 48.6%), and the second interval, after 38 total weeks of treatment (fluoxetine, 9.0%; placebo, 23.2%). In the third interval, after 62 total weeks of treatment, rates were not significantly different between the groups (fluoxetine, 10.7%; placebo, 16.2%). CONCLUSIONS: Patients treated with fluoxetine for 12 weeks whose depressive symptoms remit should continue treatment with fluoxetine for at least an additional 26 weeks to minimize the risk of relapse.

Adult↗
PubMed1998

Selective serotonin reuptake inhibitor efficacy in severe and melancholic depression.

Depression with melancholic features appears to be a discrete affective syndrome characterised by profound psychomotor, cognitive and mood disturbances that are qualitatively different from other forms of depression. Some investigators have hypothesised that melancholia may have a neurological basis with psychomotor disturbances associated with selective alterations in dopamine neurotransmission and disturbances in basal ganglia function. A number of studies have examined the role of selective serotonin reuptake inhibitors (SSRIs) in the treatment of melancholia. Although relatively few prospective trials have focused on melancholic depression, several retrospective meta-analyses and trials in populations that are likely to include a high proportion of melancholic patients have provided a wealth of data. While some early studies suggested that SSRIs might be less effective in the treatment of melancholia, the results of these may have been biased and confounded by several side-effects of tricyclic antidepressants (TCAs), which might contribute to their apparent efficacy. It appears, however, that the SSRIs may vary among themselves in their apparent efficacy in melancholia. In this regard, sertraline may be more efficacious than other SSRIs and similar to TCAs in the treatment of patients with melancholia. Several studies have suggested that the presence of melancholic features may predict a good response to sertraline, and it has been hypothesised that this may be the result of the relatively potent dopaminergic activity of sertraline, compared with other SSRIs.

Aging↗
PubMed1998

Once- versus twice-daily venlafaxine therapy in major depression: a randomized, double-blind study.

BACKGROUND: Psychotropic drug dosing regimens are often based on the pharmacokinetic elimination half-life of the compound. This implies that the pharmacokinetic half-life of the drug may be the critical or sole determinant of pharmacodynamic half-life. In the present study, we examined the safety and efficacy of once- versus twice-daily dosing regimens of the immediate-release formulation of venlafaxine, a serotonin and norepinephrine reuptake site blocker with a short elimination half-life. METHOD: Forty-eight patients with a diagnosis of DSM-IV major depressive episode were randomly assigned to once-daily (N = 25) versus twice-daily (N = 23) venlafaxine. Venlafaxine was started at 37.5 mg daily with specified increments up to 225 mg daily. Efficacy was rated using the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions scale (CGI). RESULTS: Twenty-one patients in each group completed 6 weeks of treatment. We observed a significant reduction in mean weekly HAM-D and MADRS scores at weeks 1 through 6 for both dosing groups (p < .001). There were no statistically significant differences in mean HAM-D or MADRS scores between dosing groups at any time point. There was, however, a nonsignificant trend for a more rapid reduction in the mean HAM-D score at week 2 (p < .06) and in the mean MADRS score at week 1 (p < .07) and week 2 (p < .09) in the b.i.d. dosing group. Similarly, there was a significant decrease in the CGI score at week 2 (p < .02) in the b.i.d. dosing group. The rate of adverse events was similar between treatment groups; the most common adverse events were transient nausea and headaches. CONCLUSION: These results indicate that the immediate-release formulation of venlafaxine may be safe and effective in some patients when used in a once-daily dose regimen. Moreover, the present results suggest that the short elimination half-life of immediate-release venlafaxine should not be the sole determinant for multiple daily dosing and that antidepressant activity may be more profoundly influenced by a drug's pharmacodynamic half-life than by its pharmacokinetic half-life.

Adult↗
PubMed1997

Breast enlargement during chronic antidepressant therapy.

Recent reports of mammoplasia during selective serotonin re-uptake inhibitor (SSRI) therapy suggested that this side effect may be more common than previously reported. We examined 59 women receiving > or = 2 months treatment with an SSRI or venlafaxine for changes in breast size in relation to menopausal status, weight gain and duration of drug therapy. Serum prolactin, estradiol and beta-hCG were also measured before and during treatment in a subgroup of patients. Twenty-three out of 59 patients (39%) reported some degree of mammoplasia. Significantly more SSRI vs. venlafaxine patients reported mammoplasia (p < 0.01). Eighty-four percent with mammoplasia had weight gain vs. 30% without mammoplasia (p < 0.001). The rate of mammoplasia was unrelated to age, menopausal status or duration of treatment. Serum prolactin increased during treatment in the paroxetine subgroup (p < 0.03). In conclusion, antidepressant-induced mammoplasia may be more common than previously expected.

Breast↗
PubMed1997

HMPAO SPECT brain imaging in treatment-resistant depression.

1. There is little published research on brain function in treatment-resistant depression (TRD). This study examined regional cerebral blood flow using 99mTechnetium-hexamethylpropanolamine oxime (HMPAO) single photon emission computed tomography in 8 patients with a history of TRD, 13 depressed patients without TRD (non-TRD) and 16 normal controls. 2. Relative HMPAO activity in selected brain regions revealed a significant increase in hippocampus-amygdala activity in TRD patients compared to non-TRD patients and healthy controls. The mean value of relative HMPAO activity did not differ in any other brain region, nor were there any differences in right-left symmetry among the subject groups. 3. The observation of increased hippocampus-amygdala HMPAO activity in TRD patients suggests that functional abnormalities in limbic circuitry may play a role in the pathophysiology of treatment-resistance.

Adult↗