Clozapine metabolism rate as a possible index of drug-induced granulocytopenia.

A possible relationship between haematological adverse reactions and clozapine (CLZ) metabolism rate was studied. Sixteen chronic schizophrenic outpatients (mean age 34.62 years +/- 7.56 SD) were treated with CLZ, 75-600 mg/daily for 9 weeks. CLZ and norclozapine (NCLZ) plasma levels were determined weekly, contemporarily with blood cell counts. CLZ plasma levels ranged from 25 to 1270 ng/ml (mean 266.27 ng/ml +/- 197.44 SD), while NCLZ plasma levels ranged from 25 to 1280 ng/ml (mean 169.0 ng/ml +/- 127.94 SD). NCLZ/CLZ ratio ranged from 0.13 to 1.72 (mean 0.72 +/- 0.28 SD). Leukocyte count ranged from 5.2 to 18.8 10(9)/l (mean 9.37 10(9)/l +/- 2.94 SD) and neutrophil count ranged from 1.8 to 13.4 10(9)/l (mean 5.73 +/- 2.57 SD). No correlation was found between CLZ dosage and NCLZ plasma levels. Both CLZ and NCLZ plasma levels correlated positively with neutrophil count (CLZ: P = 0.001, r = 0.26; NCLZ: P = 0.01, r = 0.20). The correlation between NCLZ/CLZ plasma level ratio and neutrophil count was significantly negative (P = 0.002, r = 0.25). These preliminary data suggest that the NCLZ/CLZ ratio, as an index of CLZ metabolism, might be a possible risk factor associated with CLZ treatment.

A risk-benefit assessment of sulpiride in the treatment of schizophrenia.

Sulpiride is a substituted benzamide with a selective action on receptors of the dopamine D2-like family, and clinical and pharmacological data suggest that it could be considered to be an atypical antipsychotic. Sulpiride penetrates the blood-brain barrier poorly because of its low lipid solubility. It is mainly excreted unchanged in the urine, and accumulation of the drug could occur in patients with renal dysfunction and possibly in elderly patients with declining glomerular filtration rate. At low dosages (50 to 150 mg/day), sulpiride produces a disinhibiting and antidepressant effect, which is probably related to its action on D2 presynaptic autoreceptors, thus facilitating dopaminergic neurotransmission. Data have confirmed the efficacy of sulpiride in patients with acute or chronic schizophrenia during both short and long term treatment, but long term, placebo-controlled trials are still lacking. It is still doubtful whether sulpiride is more effective than typical antipsychotics for the treatment of negative symptoms. Data from clinical studies are controversial; the majority of authors indicate that sulpiride produces a better recovery rate from negative than from positive symptoms at low doses, but it shows a similar efficacy either on negative and positive symptoms at higher doses. The safety profile of sulpiride is similar to that of typical antipsychotics, although the frequency of adverse effects seems to be globally lower. Extrapyramidal reactions appear generally to be mild. Autonomic effects occur less frequently with sulpiride than with typical antipsychotics, showing no clinically relevant influence on cardiovascular parameters and, on the whole, good tolerability in elderly patients. Sulpiride is known to induce prolactin elevation in both serum and CSF, which may be associated with impotence in men and diminished gonadal function in women; these effects appear to be dosage-dependent. Sulpiride can be considered to be an atypical antipsychotic, considering its action on negative, defective symptoms, its partial activity against positive symptoms, and its low incidence of extrapyramidal adverse effects. Sulpiride could find its specific therapeutic role in elderly patients with schizophrenia, as it shows a good margin of safety between therapeutic dosages and toxic concentrations.

Psychopathological and cognitive features in subclinical hypothyroidism.

1. To evaluate effective and cognitive dysfunctions in subjects with a marginal form of thyroid hypofunction the authors studied a population of female goiter patients, divided in two groups on the basis of thyroid function: euthyroidism and subclinical hypothyroidism (SCH). 2. The SCH patients were treated with levothyroxine (LT4) in order to obtain euthyroidism, as demonstrated by normalization of the hormonal pattern. 3. Both groups were evaluated with a wide range of psychometric tests (Wechsler memory test, scribble test, reaction times) and psychopathological rating scales (Hamilton rating scales for depression and anxiety, brief psychiatric rating scale) at admission and after 3 months. 4. At admission, a significant decrease in logical memory was found in SCH patients; no differences in affectivity ratings were found between the groups. 5. After LT4 treatment, SCH patients showed a significant improvement in some items of memory performance. 6. In conclusion, when interfering factors relating to the perception of disease were excluded by employing euthyroid goiter patients as a comparison group, SCH appeared associated only with memory impairment, while the impairment of affective functions described in previous studies comparing SCH patients with normal controls was not confirmed. A significant improvement of memory skills was induced by LT4 treatment in SCH patients.

Schizophrenic patients before and after HIV infection: a case-control study.

Thirteen HIV positive schizophrenic patients (Group 1), age ranging from 23 to 60 years, diagnosed as schizophrenics (DSM IV), were studied during a four week hospitalization period, due to an acute exacerbation phase. The patients were treated with haloperidol (3-15 mg/die p.o.) and diazepam (2-25 mg/die p.o.). Clinical picture and side-effects were assessed by BPRS, HRS-A, HRS-D, and DOTES, at admission and after 2, 3, 4 weeks of hospitalization period (Time 5, 7, 8, 9). Clinical evaluations were compared to a previous hospitalization period, before seroconversion (Time 0, 2, 3, 4), and to a control group (Group 2) of HIV negative schizophrenic patients (11 pb) followed as well during 2 periods of hospitalization. Our data seem to emphasize that the HIV infection could induce organic alterations in the CNS which might cause psychopathological consequences: significantly more severe depressive symptomatology and a reduction of tolerability to neuroleptics in the seroconverted patients' group.

Depressive symptoms and schizophrenia a psychopharmacological approach.

The frequency of depression was assessed in 43 chronic schizophrenic patients during an acute exacerbation phase of schizophrenia. The dexamethasone suppression test was administered to all patients. Depressive symptomatology showed a prevalence from 16.3% for moderate symptoms to 23.3% for mild ones. Depressive symptoms occurred concurrently with the psychotic picture and resolved as the psychosis remitted. Depressive symptoms were not relative to age, sex, duration of illness, DST cortisol levels, drug dosages and extrapyramidal side effects while basal cortisol levels were negatively correlated with basal Hamilton score.

[Effects of psychopathological components of the onset of Alzheimer's disease]. / Effetti della componente psicopatologica all'esordio della patologia di Alzheimer.

A particular importance can assume, especially during the onset of Alzheimer's disease, the psychiatric symptomatology characterized by depressive mood, auto and hetero-aggressive behaviour, psychomotor agitation, anxiety disorders, sleep disorders, delusions and hallucinations, these pictures showing a prevalence of 30%. 13 patients affected by Alzheimer's disease at the onset, of both sexes, age ranging from 45 to 80 years, were included in the study. The clinical picture was assessed by BDS, GDS, ICS, IADL, BIMC, MMSE, ADAS, a neuropsychological test battery such as Token Test, verbal fluency test for semantic categories, prose memory test, scribble discrimination test, numeric matrix test, Raven test, judgement of line orientation. A computerized test battery by NYU Computerized Test Battery have been also administered. The psychiatric clinical picture has been evaluated by HRS-D and the non cognitive session of ADAS. There was a positive significant (r = 0.85, p = 0.0004) correlation between depressive symptomatology evaluated at HRS-D and deterioration of daily living activities evaluated at the Blessed Dementia Scale (BDS). On the other hand the deterioration of cognitive capacities was not significantly correlated with a worsening of behavioural aspects. In conclusion seems to have a particular importance, at the onset of Alzheimer's disease, the psychopathological component that often seems to be the principal component in the determination of the early deterioration of daily living and behaviour or patients.

[Psychopharmacological therapy in dementia]. / Terapie psicofarmacologiche in corso di patologia demenziale.

The psychopharmacological approach plays an important role in dementia. In this illness several studies have been carried out, using neuroleptics and other drugs such as anxiolytics and hypnotics, lithium, beta-adrenergic blockers, antiepileptics and antidepressants. Results obtained, not always uniform, are still limited pointing out the need of new and more available trials.

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.