L. Boscati

Plasma and Platelet Amino Acid Concentrations in Patients Affected by Major Depression and under Fluvoxamine Treatment

Plasma and platelet levels of 18 amino acids were measured in 29 outpatients (mean age ± SD 47.41 ± 10.85 years; 14 F, 15 M) affected by major depression (DSM IV) and in 28 healthy volunteers (mean age 42.46 ± 14.19 years; 12 F, 16 M). Plasma and platelet levels of amino acids tended to be higher in depressed patients than in healthy controls. In particular, glutamate, taurine and lysine plasma levels and aspartate, serine and lysine platelet levels were significantly higher. Tryptophan/large neutral amino acids ratio (trp/LNAAs) was significantly lower in depressed patients. Fluvoxamine treatment did not influence plasma and platelet levels of amino acids or trp/LNAAs ratio.

Long-term treatment of chronic schizophrenia with risperidone: a study with plasma levels

Twenty-four chronic schizophrenic outpatients with a mean age of 37.21 years +/- 9.96 SD were treated with risperidone (RSP) at the dosage of 2-9 mg/die (mean 4.46 mg/die +/- 1.30 SD, mean 0.06 mg/kg +/- 0.01 SD) for a year. Clinical evaluation was assessed with the Brief Psychiatric Rating Scale (BPRS), Positive and Negative Symptoms Scale (PANSS), Extrapyramidal Side Effects Rating Scale (EPSE) and a checklist for Anticholinergic Side Effects (ACS) at T0, then after 1 (T1), 2 (T2), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months. RSP and 9-hydroxy-risperidone (9OH-RSP) plasma levels were determined at T12 by the HPLC method. BPRS and PANSS mean values showed a significant improvement during the study. No correlation between RSP dosage (mg/kg) and RSP, 9OH-RSP plasma levels or active moiety resulted. A positive correlation between age and active moiety was observed. A positive correlation between RSP and 9OH-RSP plasma levels was observed. A curvilinear relationship between active moiety and PANSS improvement (%) was observed. Patients with the higher PANSS amelioration showed RSP + 9OH-RSP plasma levels ranging from 15 to 30 ng/mL. RSP seems to be quite an effective drug. It seems, however, difficult to devise appropriate dose schedules and plasma level determination seems to be necessary in some cases.

Clinical outcome and tolerability of sertraline in major depression: A study with plasma levels

Sertraline (SRT) has been shown to be an effective antidepressant in extensive clinical trial programs but data on plasma concentrations regarding clinical outcome and tolerability are lacking. Twenty-one out-patients of both sexes, with mean age of 50.23 years (S.D. = 17.37), affected by major depressive disorder, recurrent (Diagnostic and Statistical Manual of Mental Disorder--IV, DSM-IV), were treated with 25-150 mg of SRT once a day (mean=66.26 mg, S.D.=30.50) for 30 days. Clinical evaluation was assessed at baseline (T0), after 15 days (T15), and then after 30 days (T30). Plasma samples for SRT level determination were collected at T30. Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scale for Depression (HRS-D), and Hamilton Rating Scale for Anxiety (HRS-A) showed a significant improvement during the study (P<.01 vs. T0). The most commonly reported side effects were nausea (19%), cephalalgia (9.5%), dry mouth (9.5%), decreased libido (9.5%), tremor (4.7%), and tachycardia (4.7%). SRT plasma levels ranged from 2.82 to 112.20 ng/ml (mean=40.42 ng/ml, S.D.=26.93). No correlation between SRT plasma levels and clinical improvement or side effects were observed. Drug plasma level determination does not seem be strictly necessary from a clinical point of view but further research seems advisable in patients at risk like elderly and during long-term studies.

Long term efficacy of paroxetine in major depression: A study with plasma levels.

Depressive disorders can be regarded as recurrent and chronic conditions that may reduce the quality of life and work output of patients. Data on the long-term efficacy of paroxetine appear to indicate that it is an effective maintenance treatment. Our aim was to measure paroxetine concentrations in plasma in order to optimize its clinical efficacy and tolerability during long-term treatment. We studied 35 patients aged 23-70 years, suffering from Major Depressive Disorder (recurrent). These patients received 10-50 mg of paroxetine once a day for one year; they were evaluated at baseline, after 2 weeks and then after 1,2,6,9 and 12 months by BPRS, HRS-D and HRS-A rating scales, and at the same time, any side-effects were assessed and samples for paroxetine plasma determination were also collected. Results confirmed the efficacy and tolerability of paroxetine for long-term treatment. We observed a curvilinear relationship between plasma paroxetine levels and improvement on the HRS-D with greater clinical amelioration at plasma levels between 20 and 70 ng/ml.

Predictive Value of Amino Acids in the Treatment of Major Depression with Fluvoxamine

Sixteen outpatients (mean age ± SD 50.18 ± 11.55 years; 11 females and 5 males) affected by major depression without melancholia (DSM-IV) were included in the study. The control group consisted of 11 healthy volunteers (mean age ± SD 39.90 ± 13.39 years; 2 females and 9 males). Patients were treated with fluvoxamine (FVX) 100–300 mg daily. Clinical assessment was performed using the Hamilton Rating Scales for Anxiety and Depression (HRS-A; HRS-D) and the Clinical Global Impression Scale (CGI) at basal time (T₀), after 4 weeks and after 8 weeks (T8). Plasma and platelet amino acid levels were determined at T₀ in all the subjects and also at T8 in depressed patients. A significant clinical improvement was observed in depressed patients according to the HRS-A (p = 0.004), HRS-D (p = 0.008) and CGI (p = 0.002). A negative correlation (r = –0.53, p = 0.049) was found between platelet levels of valine and HRS-D improvement rate. Patients showed significantly higher tyrosine/large neutral amino acids (LNAAs) and lower tryptophan/LNAAs, ratios which could represent an index of good response to a serotonergic drug like FVX.