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Biomedical subjects

P Boyer

Publications and source records attributed to P Boyer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sequential improvement of anxiety, depression and anhedonia with sertraline treatment in patients with major depression.

OBJECTIVE: To establish the therapeutic effect profile of sertraline in major depression. It was hypothesized that the antidepressant effect of sertraline showed three phases: Phase 1 where improvements in anxiety are most pronounced; Phase 2 where the greatest improvements are in depressive symptoms; and Phase 3 where the symptoms of anhedonia show the most improvement. To test this hypothesis, an 8-week, open-label study was conducted. METHODS: Patients with a major depressive episode (DSM-IV) and a score > or = 24 on the 17-item HAM-D were enrolled and treated with sertraline 50-150 mg/day. The three symptomatic clusters, anxiety, depression and hedonia, were defined a priori using the Inventory of Depressive Symptomatology-Clinician rated (IDS-C). Periods of interest were: Days 0-7 for anxiety, Days 7-21 for depression and Days 21-56 for anhedonia. Raters were blinded as to the constitution of the clusters and periods. RESULTS: 140 patients were recruited. Improvement in the anxiety cluster of the IDS-C was greatest during Days 0-7, whereas over Days 7-21 most improvement was observed in the depression cluster and the greatest improvement in the hedonic cluster occurred during Days 21-56. CONCLUSION: These preliminary results are consistent with the hypothesis that the therapeutic effects of sertraline occur in a sequential manner. The symptoms of anxiety improved first, followed by depression and then anhedonia.

Adolescent↗
PubMed2000

Is anhedonia a specific dimension in chronic schizophrenia?

This article explores the relationships among anhedonia, depression, and schizophrenic symptomatology in chronic schizophrenia. To explore these relationships, factor analysis methods were used to analyze the latent organization of the variables. The Fawcett Clark Pleasure Capacity Scale-Physical Pleasure (FCPCS-PP) and the abridged version of the Beck Depression Inventory (BDI) were completed by 150 subjects who met research diagnostic criteria for definite chronic schizophrenia. The schizophrenic symptomatology was rated using the Positive and Negative Syndrome Scale (PANSS). Two separate exploratory principal components analyses were completed, followed by varimax rotation. The first was made on the correlation matrix comprising items from both the FCPCS-PP and PANSS and yielded a five-factor solution with virtually no overlap of the significant factor loadings for the items from each scale. The second was made on the correlation matrix comprising items from both the FCPCS-PP and BDI and yielded a two-factor solution with virtually no overlap of the significant factor loadings for the items from each scale. Confirmatory factor analyses corresponding to the two exploratory factor analyses were done to examine the goodness of fit of the five-factor solution versus a four-factor solution and the two-factor solution versus a one-factor solution. The five-factor and the two-factor solutions yielded the best fit to the data relative to the other models tested. The findings support the view that part of anhedonia is a construct that is distinct and separate from depression and schizophrenic symptomatology in chronic schizophrenia.

Adult↗
PubMed2000

Do anxiety and depression have a common pathophysiological mechanism?

OBJECTIVE: To review, examine and propose a common mechanism for anxiety and depression based on modifications observed in neurotransmitter systems (mainly noradrenergic and serotonergic) and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. METHOD: The relevant papers were identified by searches in Medline, Excerpta Medica, PsychLIT and other databases. The primary reports were reviewed and classified into animal and human data concerning: modifications of the monoamine receptors in anxiety and depression, pathophysiology of endocrine factors in anxiety and depression, pathophysiology of the hypothalamic-pituitary-adrenal (HPA) axis and the pathophysiology of the HPA dysregulation in anxiety and in depression. In addition, a proposed model of a neuroendocrine continuum for anxiety and depression, in which anxiety occurs first during the life course and major depressive episodes occur later, was examined. RESULTS: Based on the available literature, increased concentrations of corticotropin-releasing factor (CRF) in the cerebrospinal fluid has been reported in both anxiety and depression. However, release of other peptides or hormones of the HPA axis is regulated differently in the two disorders. Anxiety is characterized by hypocortisolemia, supersuppression after dexamethasone and increased numbers of glucocorticoid receptors, whereas depression is characterized by hypercortisolemia, nonsuppression after dexamethasone and decreased numbers of glucocorticoid receptors. A 'neuroendocrine continuum' model is proposed to explain these differences. A general desensitization of CRF receptors at pituitary, limbic (amygdala) and cortical as well as hippocampal levels could be secondary to the loss of hippocampal inhibition resulting from hippocampal damage linked to repeated stressing events. CONCLUSION: The proposed hypothesis remains to be tested by examination of either the changes in receptors and neurotransmission or the mechanisms underlying the dysregulation of endocrine factors.

Anxiety Disorders↗
PubMed1999

Effect of indinavir and higher CD4+ T-cell count on viral load response after 6 months of highly active antiretroviral therapy.

This retrospective, unmasked chart review was undertaken to determine which HIV-infected patients receiving protease inhibitors (PIs) for the first time were most likely to experience a decrease in plasma viral load (PVL) and which factors were associated with a PVL < 500 copies/mL below the detectable limits after 6 months. A total of 308 patients aged > 15 years with a PVL > 500 copies/mL received therapy that included a PI in addition to other antiretroviral therapies (128 patients, saquinavir hard-gel capsule 600 mg TID; 107 patients, indinavir 800 mg TID; and 73 patients, ritonavir 600 mg BID). The choice of drug was at individual clinicians' discretion. Patients were followed for a median of 10 (range, 6 to 21) months. Of the 128 patients who received saquinavir, 45% were switched to another PI (33%, indinavir; 12%, ritonavir). Seventy percent of the 73 patients initially given ritonavir were switched (45%, indinavir; 25%, saquinavir), as were 23% of the 107 patients initially given indinavir (15%, saquinavir; 8%, ritonavir). A total of 34.1% (n = 105) of patients achieved a PVL < 500 copies/mL; in 51.6%, PVL decreased > 0.5 log copies/mL. In this subgroup, both treatment-naive patients and those who were receiving a new combination of antiretroviral therapy when they started PI treatment had a more pronounced decline in PVL (P < 0.001). After adjustment by logistic regression analysis for age, sex, mode of transmission, and duration of highly active antiretroviral therapy (HAART), CD4+ cell count and initial type of PI received were independently associated with PVL < 500 copies/mL. In the present study, the treatment success rate was low (34.1%) compared with rates observed in randomized, controlled trials. A higher CD4+ cell count and use of indinavir at the initiation of HAART are associated with a better viral load response.

Adult↗
PubMed1999

Psychometric properties of the French version of the composite scale of morningness in adults.

The objective of this study was to provide a reliable instrument to measure morningness for upcoming studies in French samples, using the Composite Scale of Morningness (CSM), which has been translated into French. Nursing students (n = 356) completed the questionnaire between February and March 1997. The total score obtained was independent of age and gender, and normally distributed. The reliability was high (Cronbach's alpha = 0.85), and factorial analysis confirmed the unidimensionality of the scale. Evening-type subjects are thought to score under 31, and morning-type subjects are thought to score above 44. As an external validation, morningness was associated, on weekdays and weekends, with early rising times and bedtimes and early peak times of physical and mental performance. In conclusion, we found that the English and the French versions of the Composite Scale of Morningness gave identical results. The scale is reliable and can be used for French-speaking adult samples. Nevertheless, normative data and other external validity criteria are needed.

Adult↗
PubMed1999

A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients.

Depression is associated with considerable morbidity and mortality. As depressive disorders carry a high risk of relapse, treatment strategies include the use of a 6-month continuation period after resolution of the acute episode. Tolerability is of major importance when determining compliance and outcome during long-term therapy. Due to the superior tolerability profile of the selective serotonin reuptake inhibitors (SSRIs) over the older tricyclic antidepressants (TCAs), the former may be more suitable for extended therapy. Comparative studies have not shown differences between the SSRIs in terms of efficacy, but side-effect profiles may vary. A multicenter, double-blind, comparative study of sertraline and fluoxetine was carried out in outpatients fulfilling DSM-III-R criteria for major depressive disorder. Patients were randomised to receive sertraline (50-150 mg, n = 118) or fluoxetine (20-60 mg, n = 120) for 24 weeks. Assessments for depression (HAM-D, HAD, CGI-I, CGI-S), anxiety (Covi), sleep (Leeds Sleep Evaluation scale) and quality of life (SIP) were made at study entry and at weeks 2, 4, 8, 12, 18 and 24. All adverse events were recorded to allow evaluation of tolerability. In total, 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group. Side effects were responsible for the premature treatment withdrawal of seven (6%) sertraline patients and 12 (10%) fluoxetine patients. Two-hundred and thirty-four patients were included in an ITT analysis up to last visit (116 sertraline, 118 fluoxetine). At study endpoint, both treatments produced a significant improvement over baseline on all efficacy variables (P < 0.001). Although the magnitude of global changes in depression, anxiety, and quality of life was larger with sertraline than fluoxetine, none of the between-group differences reached statistical significance. However, significant differences in favour of sertraline were observed for individual HAM-D items including item 4 (insomnia onset) (P = 0.04), item 9 (agitation) (P = 0.02), and item 13 (general somatic symptoms) (P = 0.008). In addition, sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest, emotional behaviour and ambulation. Both sertraline and fluoxetine were well tolerated with no significant differences between treatments.

Adolescent↗
PubMed1999

Alpha-synuclein immunoreactivity is present in axonal swellings in neuroaxonal dystrophy and acute traumatic brain injury.

The primary neuroaxonal dystrophies (NAD), which include infantile NAD and Hallervorden-Spatz syndrome (HSS), are characterized by dystrophic terminal axons and axonal swellings. Lewy bodies have been found in some cases. In Parkinson disease (PD) and dementia with Lewy bodies (DLB), Lewy bodies and neurites display prominent alpha-synuclein immunoreactivity. We examined 2 cases of HSS and 4 cases of infantile NAD with alpha-synuclein immunohistochemistry to test the hypothesis that these disorders with similar morphological findings might share a biochemical phenotype. Furthermore, we compared them to 8 cases of secondary or physiologic NAD of various causes and 2 cases of recent traumatic head injury. Alpha-synuclein positive neuronal cytoplasmic inclusions, including Lewy bodies, and neurites were numerous in 1 HSS and 1 infantile NAD case. In addition, axonal spheroids were immunostained in all 6 cases of primary NAD, 5 cases of secondary NAD, and 2 cases of recent head injury. Axonal spheroids were faintly stained in the 3 physiologic NAD cases. Alpha-synuclein positive axonal swellings may suggest a mechanism, such as axonal injury, leading to the neuronal cytoplasmic accumulation of alpha-synuclein in NAD and other disorders.

Acute Disease↗
PubMed1999

Amisulpride versus amineptine and placebo for the treatment of dysthymia.

Amisulpride, a selective antagonist for D2 and D3 dopamine receptors, acts preferentially on presynaptic receptors increasing dopaminergic transmission at low doses. In a multicentre, 3-month, placebo-controlled study, amisulpride (50 mg/day) was compared to amineptine (200 mg/day) in the treatment of primary dysthymia. A total of 323 patients were enrolled. Amisulpride and amineptine were found to be statistically superior to placebo (p < 0.0001) on the Clinical Global Impression (item 2): 63, 64 and 33% responders, respectively; improvement of Montgomery-Asberg Depression Rating Scale and Scale for the Assessment of Negative Symptoms scores following amisulpride or amineptine treatment was twice as high as with placebo (p < 0.0001). The adverse event profile of amisulpride was similar to that of placebo except for endocrine symptoms in female patients; amineptine showed mainly events linked to psychic activation (insomnia, nervousness). Results show that amisulpride can improve symptoms of chronic depression in dysthymia.

Amisulpride↗
PubMed1999

Venlafaxine and paroxetine in treatment-resistant depression. Double-blind, randomised comparison.

BACKGROUND: About one-third of patients fail to respond to initial antidepressant therapy, which suggests a need for more effective drugs. AIMS: To compare the efficacy and safety of venlafaxine and paroxetine in 122 patients with non-chronic treatment-resistant depression. METHOD: In-patients or out-patients satisfying DSM-III-R criteria for major depression in evolution for less than eight months, having a baseline HAM-D score > or = 18 and a HAM-D Item 3 score < 3 were eligible. Patients were required to have a history of resistance to two previous antidepressant treatments and a CGI improvement score of 3 at the beginning of treatment. Doses were adjusted to 200-300 mg/day for venlafaxine and 30-40 mg/day for paroxetine. RESULTS: For the observed-case analysis, the response rate was 51.9% for venlafaxine and 32.7% for paroxetine (P = 0.044), and a remission was achieved in 42.3% of venlafaxine-treated and 20.0% of paroxetine-treated patients (P = 0.01). The incidence of adverse effects was comparable between treatment groups. CONCLUSIONS: Venlafaxine showed some evidence of superiority to paroxetine in this difficult-to-treat patient population.

Adult↗
PubMed1999

[Proofs of efficacy].

Several factors are to be taken account in the assessment of the overall efficacy of a new antidepressant. There are rules governing the diagnostic categories, baseline scores and the conditions for the assessment of their course in the context of both placebo-controlled trials and studies versus reference products. As an illustration, two studies of clomipranine versus specific inhibitors of serotonin reuptake are reviewed. The author analyzes various studies conducted on venlafaxine, a new serotoninergic and noradrenergic product.

Antidepressive Agents, Tricyclic↗
PubMed1998

Maternal and perinatal factors related to maternal-infant transmission of HIV-1 in the P2C2 HIV study: the role of EBV shedding. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV-1 Infection (P2C2 HIV) Study Group.

The association of maternal and perinatal factors with mother-infant transmission of HIV-1 was examined in a prospective multicenter cohort of singleton live births to 508 HIV-1-infected women with children of known HIV-1 infection status (91 [18%] HIV-1-infected, 417 [82%] uninfected). From multivariate logistic regression, independent predictors of HIV-1 transmission included maternal CD4 percentage (CD4%) (odds ratio [OR] per 10% increase in CD4% = 0.70; p = .003), ruptured membranes <24 hours (OR = 3.15; p = .02), and maternal bleeding (OR = 2.90; p = .03), whereas maternal zidovudine (ZDV) use was marginally associated (OR = 0.60; p = .08). The associations of maternal urinary cytomegalovirus (CMV) shedding, oropharyngeal Epstein-Barr virus (EBV) shedding, and serology profiles during pregnancy with HIV-1 transmission were examined in the subset of mothers in whom the CMV and EBV measurements were available. Maternal EBV seropositivity, CMV shedding, and CMV seropositivity were 100% (279 of 279), 7% (16 of 229), and 92% (270 of 274), respectively. These rates did not differ between transmitting and nontransmitting mothers. In univariate analyses, maternal EBV shedding was higher among transmitting than nontransmitting mothers (40 of 49 [82%] compared with 154 of 226 [68%]; p = .06) and was independently associated with transmission in multivariate logistic analyses adjusting for CD4%, ruptured membranes, and ZDV use, with an OR of 2.45 (95% confidence interval (CI), 1.03-5.84; p = .04). This permits the conclusion that EBV shedding is associated with maternal-infant HIV-1 transmission, independent of CD4%.

Anti-HIV Agents↗
PubMed1998

Influence of dietary calcium concentration on body size and bone composition in rats during recovery from malnutrition.

OBJECTIVE: The purpose of our study was to assess the influence of different levels of calcium (Ca) in a diet containing 30% protein on the rehabilitated of the body size from protein-energy malnutrition (PEM) and to establish the optimal Ca/protein ratio for attaining a normal body composition. METHODS: Weanling female Wistar rats were fed with protein-free diet up to a weight deficit of 20 +/- 1%. Then they were arranged in groups (TO) and fed diets with 30% protein and 0.0, 0.2, 0.4, 0.6, 0.9 or 1.2% Ca for 28 days (T28). Food and deionized water were given ad libitum. Body weight and length were recorded every 3 days. At T28, the animals were sacrificed to determine femur composition. RESULTS: At T13, weight-for-age (W/A) was within the normal range for rats consuming > or = 0.6% Ca. At T28 all groups showed adequate W/A. Although length-for-age was adequate during rehabilitated period, rate of weight gain improved when Ca was > or = 0.6%. Femur length did not show significant difference between groups. Total femur Ca content and mg Ca/g of dry-weight tissue increased with increments in dietary Ca concentration and tended to plateau with 0.4% Ca. Ca/P ratio reached the highest value with 0.9% Ca. CONCLUSIONS: Our findings indicate that at a dietary protein level of 30% the Ca/protein ratio is a limiting factor in attaining of normal body size; this is achievable when Ca concentration is 1.2% and the Ca/protein ratio is 0.04.

Aging↗
PubMed1998

Anhedonia, alexithymia and locus of control in unipolar major depressive disorders.

The relationship between anhedonia, alexithymia and locus of control was studied in a group of healthy subjects (n = 56) and in a group of unipolar major depressives (n = 59). These dimensions were rated using the Physical Anhedonia Scale (PAS), the Toronto Alexithymia Scale (TAS) and the Internal Powerful others and Chance Scale. The unipolar major depressives were divided into two subgroups using the endogenomorphic subscale of the Hamilton Depression Rating Scale. There are respectively 25 and 17 depressives in the nonendogenomorphic (NENDO) and endogenomorphic (ENDO) subgroups. The unipolar major depressives were significantly more anhedonic, alexithymic and externalized than the controls. In the ENDO group the PAS and TAS Feelings scores were positively correlated suggesting that a third variable of emotional deficit could characterize endogenomorphic depression. In the NENDO group the PAS, TAS Daydreaming, Powerful others and Chance scores were positively correlated. In nonendogenomorphic depression anhedonia could be related to a poverty of imagery and could be interpreted as a consequence of external causes.

Adult↗
PubMed1998

Milnacipran, a new specific serotonin and noradrenaline reuptake inhibitor.

Milnacipran is a new antidepressant which inhibits equipotently the reuptake of serotonin and noradrenaline both in vitro and in vivo with no effect on dopamine reuptake. Microdialysis studies have shown increased extracellular levels of both serotonin and noradrenaline after acute administration. Milnacipran is devoid of interactions at any known neurotransmitter receptor. In particular, and unlike tricyclic antidepressants (TCAs), it has no activity at noradrenergic, muscarinic or histaminergic receptors. Contrary to TCAs, chronic administration of milnacipran does not modify beta-adrenoceptor binding or second messenger function. Milnacipran is active on various animal models of depression such as the forced swimming test in the mouse, learned helplessness in the rat and the olfactory bulbectomized rat model. Milnacipran has a high bioavailability, low plasma protein binding, and is largely eliminated in the urine as the parent drug or as a glucuronide. These features suggest that interactions with other drugs given concurrently are unlikely. Studies in patients with liver dysfunction and in the elderly suggest that dose adjustment is not necessary. In patients with renal impairment, decreased elimination of milnacipran is correlated to the degree of renal impairment allowing an easy dosage adjustment. An intermediate half-life of approximately 8 h is compatible with twice-daily administration. Clinical studies comparing milnacipran, placebo and other antidepressants provide evidence of its efficacy in moderate to severe depression in both hospitalized and outpatient settings. Meta-analyses of the original data of controlled trials comparing milnacipran with imipramine or selective serotonin reuptake inhibitors (SSRIs) show that milnacipran provides antidepressant efficacy similar to that of TCAs and significantly superior to that of SSRIs. An analysis of a database of over 3300 patients shows that both the general and cardiovascular tolerability of milnacipran are superior to those of TCAs with notably less cholinergic side effects. The tolerance of milnacipran was comparable to that of SSRIs with a higher incidence of dysuria with milnacipran but a higher frequency of nausea and anxiety with the SSRIs. Milnacipran represents an interesting new therapeutic option in depression, being as well tolerated as the SSRIs but offering clinical efficacy similar to the TCAs.

Journal Article↗