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Biomedical subjects

A Lucca

Publications and source records attributed to A Lucca.

At least 19 recordsLinked to original sources

Total sleep deprivation combined with lithium and light therapy in the treatment of bipolar depression: replication of main effects and interaction.

The clinical usefulness of total sleep deprivation (TSD) in the treatment of bipolar depression is hampered by a high-rate short-term relapse. Previous literature has suggested that both long-term lithium treatment and light therapy could successfully prevent relapse. We randomized 115 bipolar depressed inpatients to receive three cycles of TSD, alone or in combination with morning light exposure, given at an intensity of 150 or 2500 lux. Forty-nine patients were undergoing long-term treatment with lithium salts (at least 6 months), while 66 patients were taking no psychotropic medication. Mood was self-rated by the Visual Analogue Scale three times a day during treatment. The results showed that both light therapy and ongoing lithium treatment significantly enhanced the effects of TSD on the perceived mood, with no additional benefit when the two treatments were combined. Subjective sleepiness during TSD, as rated by the self-administered Stanford Sleepiness Scale, was significantly reduced by light exposure, and was correlated with the outcome. This study confirms the possibility of obtaining a sustained antidepressant response to TSD in bipolar patients.

Adult↗

Effects of fluvoxamine treatment on the in vivo binding of [F-18]FESP in drug naive depressed patients: a PET study.

This study investigates the effect of chronic treatment with Fluvoxamine, a potent and specific serotonin reuptake sites inhibitor (SSRI), on 5HT(2) serotonin and D(2) dopamine receptors in the brain of drug naive unipolar depressed patients. Drug effect was evaluated in different cortical areas and in the basal ganglia by positron emission tomography (PET) and fluoro-ethyl-spiperone ([(18)F]FESP), an high affinity 5HT(2) serotonin and D(2) dopamine receptors antagonist. Patients underwent a PET study at recruitment and after clinical response to Fluvoxamine treatment. Nine of the 15 patients recruited completed the study. Fluvoxamine treatment significantly improved clinical symptoms and modified [(18)F]FESP binding in the frontal and occipital cortex of all of the nine patients who completed the study; in these regions a mean 31% increase in the in vivo [(18)F]FESP binding was found (P < 0.01). On the contrary, no significant changes in the in vivo [(18)F]FESP binding were found in the basal ganglia where [(18)F]FESP binds mainly to D(2) dopamine receptors. Chronic treatment with Fluvoxamine significantly increases the in vivo binding of [(18)F]FESP in the frontal and occipital cortex of drug naive unipolar depressed patients. The increase of the in vivo binding of [(18)F]FESP may reflect a modification in 5HT(2) binding capacity secondary to changes in cortical serotonin activity.

Adult↗

Simultaneous determination of human plasma levels of four selective serotonin reuptake inhibitors by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatography (HPLC) method with fluorimetric detection, which allows the simultaneous determination of plasma concentrations of four selective serotonin reuptake inhibitors (SSRIs) is presented. Fluvoxamine, paroxetine, sertraline, and fluoxetine were extracted from plasma with ethyl acetate and then derivatized with dansyl chloride. The analytes were separated using Hypersyl ODS C18 (5 microm) 250 x 4.6 mm column (ThermoQuest, Runcorn, UK). For continuous gradient separation, the mobile phase consists of two eluents, acetonitrile and potassium phosphate buffer (10 mmol/L, pH 7.2) at total flow rate of 1.5 mL/min. Detection was carried out at lambda exc = 366 nm and lambda em = 490 nm. The authors found recoveries of 90% to 95% for fluvoxamine, 94% to 100% for paroxetine, 88% to 95% for sertraline, 93% to 100% for fluoxetine, and 97% to 100% for internal standard (nortriptyline). Imprecision of the method ranged from 2.5% to 8.9%. The assay was linear from 10 to 1500 ng/mL for sertraline, and from 5 to 1500 ng/mL for the other drugs. The authors conclude that this method is suitable for monitoring antidepressant therapy. In addition, the authors report the effects of adding paroxetine to fluvoxamine on plasma levels in a group of patients in combined drug therapy.

Adult↗

Faster onset of action of fluvoxamine in combination with pindolol in the treatment of delusional depression: a controlled study.

This double-blind, controlled study was undertaken to investigate whether the addition of pindolol could improve the therapeutic response to fluvoxamine of depressed patients with psychotic features. After a 1-week placebo run-in period, 72 patients received fluvoxamine 300 mg/day in combination with placebo or pindolol 7.5 mg/day. At study completion, 28 (80%) of 35 patients treated with fluvoxamine plus placebo and 29 (80.5%) of 36 patients treated with fluvoxamine plus pindolol were categorized as responders (reduction of their score on the 21-item Hamilton Rating Scale for Depression to 8 or less and on the Dimension for the Delusional Experience Rating Scale to 0). In the third and fourth weeks, the response rates were significantly superior in the fluvoxamine plus pindolol group (p = 0.0001, p = 0.023, respectively). Treatment response seemed to be unrelated to the demographic and the clinical characteristics recorded. No significant difference was found comparing plasma levels of fluvoxamine between groups, thus excluding a pharmacokinetic interaction. Other than mild nausea and sedation in a few patients, treatments were well tolerated. No medically significant adverse events occurred. Depressed patients with psychotic features who were administered pindolol experienced a more rapid improvement during fluvoxamine treatment. Thus, the combination of fluvoxamine with pindolol may be a useful pharmacologic strategy in the treatment of this disorder. A rapid clinical response in such patients is of relevance in clinical practice as well as in economic fields, given the direct and indirect costs of depression.

Adolescent↗

Plasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression.

We have studied fasting plasma tryptophan (TRP) levels and tryptophan/large neutral amino acid (TRP/LNAA) ratios in 12 patients with obsessive-compulsive disorder (OCD) and 12 patients with OCD and a coexisting current diagnosis of major depressive disorder (OCD-MDD). Assessments were made at baseline and after 6 weeks of treatment with fluvoxamine. OCD-MDD patients had significantly lower baseline TRP levels and TRP/LNAA ratios than OCD patients. After 6 weeks of fluvoxamine treatment, OCD-MDD patients had significant increases in plasma TRP and TRP/LNAA ratio, whereas OCD patients had non-significant decreases. Our data suggest that a major depressive syndrome could be a state variable affecting the changes in plasma TRP and TRP/LNAA ratio in OCD patients.

Adult↗

Sleep deprivation hastens the antidepressant action of fluoxetine.

Among ten bipolar depressed patients admitted to our psychiatric ward, five patients were treated with fluoxetine alone and five subjects were treated with fluoxetine in association with total sleep deprivation (TSD) in order to evaluate the effect of the interaction between the administration of the serotonergic antidepressant compound fluoxetine and repeated cycles of TSD. Patients treated with fluoxetine plus repeated TSD showed a faster amelioration of depressive symptomatology compared with the other group. We discuss our findings hypothesizing an enhancement in dopaminergic and possibly in serotonergic transmission due to repeated TSD adding to the increase in serotonergic transmission due to fluoxetine medication.

Adult↗

Tryptophan depletion in obsessive-compulsive patients.

Twelve patients with obsessive-compulsive disorder were studied after the administration of a mixture of amino acids devoid of tryptophan (TRP) or a mixture containing all the essential amino acids, in a double-blind, crossover design. The TRP-free mixture caused a marked depletion of plasma TRP. After TRP decrease, mean ratings of obsessions and compulsions, measured by Visual Analogue Scales (VAS) ratings, did not worsen. In contrast with other reports in literature, TRP depletion also failed to alter mood in our subjects.

Adult↗

Decrease in plasma phenylalanine and tyrosine after phenylalanine-tyrosine free amino acid solutions in man.

After an overnight fast, 5 male healthy subjects ingested increasing amounts of a solution containing a fixed proportion of seven essential amino acids (L-isoleucine, 13.3%; L-leucine, 21.0%; L-lysine, 15.2%; L-methionine, 21.0%; L-threonine, 9.5%; L-tryptophan, 4.8% and L-valine, 15.2%) and lacking phenylalanine and tyrosine. The solutions caused a rapid fall in plasma phenylalanine and tyrosine which was proportional to the total amount of amino acids ingested. Following the highest dose administered (31.5 g) plasma phenylalanine and tyrosine fell to a minimum of, respectively, 12.7% and 29.8% the initial levels and remained markedly reduced at 6 hours after treatment. The decrease of tyrosine and phenylalanine levels was associated with a decrease of systolic and diastolic arterial pressure.

Adult↗

Predictive value of tryptophan/large neutral amino acids ratio to antidepressant response.

The molar ratio of total plasma tryptophan to the sum of other large neutral amino acids (viz., valine, isoleucine, leucine, tyrosine, phenylalanine), thought to reflect brain serotonin formation, was estimated in 69 patients with major depression before and after 1 week of treatment with different serotonin reuptake inhibitors, fluvoxamine (n = 28), fluoxetine (n = 10), citalopram (n = 7), mixed serotonin-noradrenaline reuptake inhibitor amitriptyline (n = 11), clomipramine (n = 8) and the preferentially noradrenaline reuptake inhibitor, nortriptyline (n = 5). A significant difference among 'good', 'intermediate' and 'poor' responders for the percentual variation of tryptophan/large neutral amino acids ratio after 1 week of therapy was found, while pretreatment values of tryptophan/large neutral amino acids ratio, basal Hamilton Depression Rating Scale scores and its percentual variation after 1 week of therapy did not show any significant differences. These results suggest that the percentual variation of tryptophan/large neutral amino acids ratio could be a useful tool in predicting drug response.

Adult↗

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Electric Countershock↗

Neutral amino acid availability in two major psychiatric disorders.

1. Evidence suggests catecholamines and indoleamines may play a role in the pathogenesis of several psychiatric disorders. These neurotransmitters (i.e. dopamine, norepinephrine and serotonin) are synthesized within the human brain from their precursors, the aromatic large neutral amino acids tyrosine and tryptophan. Other large neutral amino acids, namely valine, isoleucine, leucine and phenylalanine affect precursor availability by competing with tryptophan and tyrosine for the transport system across the blood brain barrier. 2. The authors evaluated the brain availability of L-tryptophan and tyrosine in a sample of psychiatric patients with a diagnosis of major depression and schizophrenia. 3. The present results suggest a possible usefulness of Tryptophan/Large Neutral Amino Acids ratio in distinguishing major depression from schizophrenia, while Tyrosine/Large Neutral Amino Acids ratio shows a very limited usefulness. The absolute need of powerful and accurate statistical analysis to evaluate the power of a biological test clearly stands out from the present study.

Adolescent↗

Plasma tryptophan to large neutral amino acids ratio and therapeutic response to a selective serotonin uptake inhibitor.

The molar ratio of total plasma tryptophan (Trp) to the sum of the other large neutral amino acids (LNAAs), thought to reflect brain serotonin (5-HT) formation, was estimated in 47 patients with major depression (unipolar and bipolar) before and after 6 weeks of treatment with a serotonin uptake inhibitor, fluvoxamine. We found a significant difference between responders (n = 39) and nonresponders (n = 8) for the pre- and in-treatment plasma Trp to LNAAs ratios. In contrast, there were no differences between the two groups for the mean plasma steady-state fluvoxamine levels. These findings suggest that a specific plasma amino acid profile may be a useful indicator of good clinical response to a selective 5-HT uptake inhibitor.

Adult↗

Serine and glycine metabolism in schizophrenic patients.

1. The brain glycine is almost exclusively derived from serine via serine-hydroxymethyltransferase. 17 males schizophrenic inpatients and 10 males healthy volunteers were submitted to the serine tolerance test. 2. Plasma serine and glycine concentration were evaluated before and after 1, 2, 3, 4 hours of an oral load with L-serine to test the interconversion between the two amino acids. 3. The authors did not find any significant difference between schizophrenic patients and control group and concluded that the enzyme serine-hydroxymethyltransferase is not deficient in the conversion of serine to glycine in schizophrenic patients as suggested by other authors.

Adult↗

Plasma tryptophan levels and plasma tryptophan/neutral amino acids ratio in patients with mood disorder, patients with obsessive-compulsive disorder, and normal subjects.

Fasting plasma tryptophan (TRP) levels and ratios of total plasma tryptophan to the sum of five large neutral amino acids (LNAAs)--tyrosine, phenylalanine, leucine, isoleucine, and valine--that compete with tryptophan for passage across the blood-brain barrier were found to be significantly lower in a group of 28 patients with major depression compared with 29 normal subjects and 21 patients with obsessive-compulsive disorder (OCD). The OCD group was divided in two subgroups: patients with OCD alone and patients with a co-diagnosis of major depression. Since it has been considered that these biological parameters reflect brain tryptophan and serotonin levels, our results suggest their importance in relation to the presence or absence of depressive symptoms. The values of the other LNAAs and their sum did not differ significantly among the groups.

Adolescent↗

Amino acid patterns in schizophrenia: some new findings.

Blood concentrations of various amino acids were measured in schizophrenic patients and control subjects. Significantly higher blood concentrations of glycine, glutamate, and serine were found in the schizophrenic patients. Glycine was abnormally elevated in subjects with paranoid or undifferentiated schizophrenia, but not in disorganized patients. Since glutamate, glycine, and serine play a complex role in the regulation of N-methyl-D-aspartate (NMDA) receptors, which are important in the control of normal cognitive processes, we hypothesized that the elevated levels of these amino acids might disrupt the normal functioning of NMDA receptors and might be involved in the pathophysiology of schizophrenia.

Adolescent↗

Effect of lithium treatment on the GH-clonidine test in affective disorders.

The effects of short-term lithium (Li) administration on alpha 2-adrenoceptor sensitivity was studied in 10 healthy volunteers and in 15 patients with normothymic, phasic depressive disorders. The GH-clonidine test was used to examine alpha 2-adrenoceptor sensitivity, administered before and after Li treatment (600 mg/day for 7 days in controls and for 15 days in patients). Before treatment, the GH response to clonidine in the patients was blunted, and afterwards it tended to increase in the patients and it was significantly decreased in the controls. The difference between the response in the two groups was significant and was correlated both with the diagnosis and the pretreatment GH response to the stimulus. The opposing pattern of the response in patients and controls to Li administration suggests that the drug exerts a modulatory effect on alpha 2-adrenoceptor sensitivity, with up or down regulation inversely correlated with pretreatment status.

Adolescent↗