Biomedical subjects

Arun V Ravindran

Publications and source records attributed to Arun V Ravindran.

6 recordsLinked to original sources

PubMed2005

Effect of valproate on plasma levels of interleukin-6 in healthy male humans.

Valproate exerts many biochemical and physiological effects and may have a modulating effect on the immune system. The present study aimed to determine whether there is a treatment effect of valproate on plasma levels of the pro-inflammatory cytokine, interleukin (IL)-6, in healthy male humans. Plasma levels of IL-6 were measured in 10 healthy male humans before and after 7 days of treatment with 1000 mg per day of valproate (i.e. 500 mg in the morning and 500 mg in the evening). All the healthy subjects had no past or current psychiatric disorder. They reported to the outpatient clinic at 09.00 h for baseline sampling. Subsequently, they were commenced on valproate 1000 mg per day for 7 days. They took the last dose of valproate at 22.00 h on the day 7, and post-treatment blood sampling for plasma levels of IL-6 was carried out on day 8. An additional blood sample was also taken from each subject at the same time to measure plasma levels of valproic acid for drug compliance. We found a significant increase in plasma levels of IL-6 after the 7 days of valproate treatment in healthy male subjects. Furthermore, there was a significant positive correlation between the changes in plasma IL-6 and blood levels of valproic acid. The findings of this study are consistent with previous studies on subjects with epilepsy, suggesting a modulating effect of valproate on the pro-inflammatory cytokine IL-6 in humans. However, studies with a larger number of participants and employing a double-blind, placebo-control group are required to confirm the findings, and also the levels of other cytokines should be measured to generalize the effect to the immune system.

Adult↗

PubMed2003

Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study.

This multinational, randomized, double-blind study was specifically designed to prospectively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice. A total of 345 patients with major depressive episode (DSM-IV) received mirtazapine (30-45 mg/d) or sertraline (50-150 mg/d) for 8 weeks. Mirtazapine was administered in the newly developed fast dissolving, orally disintegrating tablet formulation. Assessments were performed at baseline and on days 4, 7, 10, 14, 28, 42, and 56. The primary efficacy variable (mean absolute change from baseline in the Hamilton Depression Rating Scale [HAMD] total score [17 items]) showed that mirtazapine was significantly (P < 0.05) more effective than sertraline at all assessments during the first 2 weeks of the study. After this time, HAMD total scores were similar in both groups. These findings were supported by analysis of the HAMD response rate (ie, > or =50% reduction in HAMD total score from baseline), HAMD remission rate (HAMD total score of < or =7), and the Montgomery-Asberg Depression Rating Scale (MADRS). Both treatments were well tolerated. In addition, mirtazapine had a greater effect than sertraline on sexual functioning. In conclusion, this first prospective onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect than sertraline. The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient.

Adolescent↗

PubMed2002

Does fluoxetine influence major depression by modifying five-factor personality traits?

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of depression, though response to them is difficult to predict. The aims of this study were two-fold: (1) to determine the differences in personality profile between patients with major depression and healthy control subjects and (2) to assess the effect of treatment with fluoxetine on personality domain scores and determine whether any of the personality traits can predict the outcome of antidepressant treatment. METHODS: The study included 53 patients with major depression and 53 healthy controls. The NEO-Five-Factor Inventory (NEO-FFI) was administered to all subjects before and after 24 weeks of treatment with fluoxetine. RESULTS: The patients in an episode of major depression had a significantly different personality profile compared to healthy controls at baseline and the severity of their illness correlated with higher scores in the Neuroticism domain. Treatment with fluoxetine was associated with a reversal of high Neuroticism scores and low Extraversion scores in the whole sample and in a subgroup of responders but not in non-responders. Among the FFI personality domains, Agreeableness was a better predictor of treatment outcome than baseline HAMD-17 scores. LIMITATIONS: There was no placebo group, which would have permitted the evaluation of the effect of non-drug factors in treatment outcome and changes in personality domain scores. The sample size was only moderate. CONCLUSIONS: The results suggest that (a) significant differences exist between the personality profiles of depressed patients and healthy control subjects and (b) responders to treatment with fluoxetine show significant changes in personality profile. These changes may be attributed to improvement of depressive symptoms.

Adult↗

PubMed2002

Stress, coping, uplifts, and quality of life in subtypes of depression: a conceptual frame and emerging data.

BACKGROUND: Depressive illness is associated with several functional disturbances, including increased stress perception and reliance on emotion focused coping styles, reduced perception of uplifting events, and impairment of several aspects of quality of life. Inasmuch as different subtypes of depression may be accompanied by differing neuroendocrine profiles, it was of interest to establish whether they could also be distinguished from one another on the basis of functional behavioral indices. METHODS: Major stressors, day-to-day stressors and uplift perception, coping styles, and quality of life were assessed in control participants, as well as in acute or chronically (dysthymia) depressed patients exhibiting either typical or atypical features, and in treatment resistant major depressive patients. RESULTS: Relative to controls, the depressive groups had higher perceptions of day-to-day stressors (hassles), reduced perception of uplifting events, excessive reliance on emotion-focused coping strategies, and diminished quality of life. Among depressed patients the hassles, coping styles and some elements of quality of life were related to symptom severity, as well as treatment-resistance. LIMITATIONS: Data concerning stress, coping and quality of life were collected retrospectively, and the number of subjects in each condition was small. Hence, the relationship of the outcome measures to depression need to be considered cautiously. CONCLUSIONS: Quality of life represents a functional index of the behavioral and cognitive impact of depression. This outcome measure is sensitive to differences as a function of depressive characteristics, and may prove to be a useful assessment tool in evaluating treatment efficacy.

Acute Disease↗

PubMed2002

Sertraline and fluoxetine treatment of obsessive-compulsive disorder: results of a double-blind, 6-month treatment study.

The purpose of this study was to evaluate the comparative efficacy and tolerability of sertraline and fluoxetine in the treatment of obsessive-compulsive disorder (OCD). Outpatients meeting DSM-IV criteria for OCD, with a Yale-Brown Obsessive-Compulsive (Y-BOCS) total score >or= 17, an NIMH Global Obsessive-Compulsive (NIMH-OC) scale score >or= 7, and a CGI-Severity score >or= 4 were randomized to 24 weeks of double-blind treatment with sertraline (N = 77) or fluoxetine (N = 73). Primary efficacy measures consisted of the Y-BOCS, the NIMH-OC scale, and the CGI-Severity (CGI-S) and Improvement (CGI-I) scales. Equivalent and significant (p < 0.001) improvement was found at week 24 in Y-BOCS and NIMH-OC scale scores for sertraline and fluoxetine. After 12 weeks, 49.2% of patients on sertraline were rated on the CGI-S scale as being mildly ill or not ill compared to 24.6% on fluoxetine (p < 0.01). A Cox analysis found patients on sertraline to have a statistically nonsignificant 42% greater likelihood of achieving a response by week 12 (CGI-I, much or very much improved; 95% CI, 0.85, 2.38; p = 0.18). Sertraline treatment also resulted in a higher proportion of remissions than fluoxetine (defined as a CGI-I <or= 2 and a Y-BOCS score <or= 11), both at week 12 (20% vs. 8%; chi2, 3.95; df 1; p = 0.047) and week 24 (36% vs. 22%; chi2, 3.18; df, 1; p = 0.075). Both medications were well-tolerated and demonstrated significant efficacy in the treatment of outpatients with moderate to severe OCD with the subjects treated with sertraline showing a greater likelihood of remission as well as an earlier improvement on some but not all efficacy measures

Adolescent↗

PubMed2002

Effects of short-term administration of valproate on serotonin-1A and dopamine receptor function in healthy human subjects.

OBJECTIVE: To examine the effects of short-term valproate treatment on human brain serotonin and dopamine function by means of challenge tests with ipsapirone, a partial agonist at 5-HT1A receptors, and apomorphine, a dopamine receptor agonist. DESIGN: Experimental challenge-rechallenge, within-subjects repeated measures, before and at the end of 14 days of treatment with valproate at a dosage of 625 mg/d (reached gradually over the first 5 days). PARTICIPANTS: Eight healthy male volunteers (mean age 38 years) selected for good physical and mental health who were nonsmokers. OUTCOME MEASURES: Pharmacological probes were used to evaluate the effects of valproate. In the ipsapirone challenge, changes in adrenocorticotropic hormone (ACTH), cortisol and body temperature were measured, and in the apomorphine challenge, growth hormone (GH) and prolactin were the dependent variables. RESULTS: Valproate treatment did not significantly alter the ACTH, cortisol or body temperature responses to ipsapirone (20 mg by mouth), which reached equivalent plasma levels at each challenge. Similarly, valproate treatment did not alter the GH or prolactin responses to apomorphine (5 micrograms/kg subcutaneously). CONCLUSIONS: These results suggest that short-term treatment with valproate at a dose of 625 mg/d does not alter hypothalamic or pituitary 5-HT1A or dopamine receptor responses to challenges with ipsapirone and apomorphine, respectively.

Adrenocorticotropic Hormone↗