Biomedical subjects
Publications and source records attributed to M C Mauri.
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 levels of excitatory amino acids were measured in 38 psychiatric out-patients and in 19 comparison subjects; the patients had DSM-III-R diagnoses of organic mental disorders (N = 3), mood disorders (N = 15), schizophrenia (N = 13), and anxiety disorders (N = 7). The glutamate plasma levels were significantly higher in the patients with mood disorders than in the comparison group.
Quazepam, a recently introduced long-half-life benzodiazepine, seems to have a more specific hypnotic activity and a physiological mechanism of action. The present study evaluated clinical efficacy and eventually rebound symptoms after the treatment with quazepam and triazolam. Sixty-five patients, affected by sleep disorders, were entered into the study. Patients were treated with a placebo for four days and, if no amelioration of insomnia was observed, they were allocated randomly to receive 15 mg of quazepam (32 patients) or 0.5 mg triazolam (33 patients) for eight weeks and finally the placebo for another week. The sleep quality, the sleep efficacy, the unwanted effects and the rebound effects had been assessed by specific evaluation scales. Both of the drugs showed a hypnogenic efficacy but patients treated with quazepam had significantly less night awakenings; at the treatment's interruption, only the patients treated with triazolam had longer awakenings and rebound symptoms. In conclusion, quazepam seems to have a good hypnotic effect without inducing rebound effects. On the contrary, triazolam turned out to be just a hypnoinducent drug with higher risks of rebound effects after withdrawal.
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1. Clinical activity, extrapyramidal side-effects were evaluated in 22 schizophrenic out patients diagnosed according to DSM III and treated with haloperidol decanoate (50-300 mg i.m. monthly dose) for 12 months. 2. BPRS total scores did not show significant fluctuations showing a clinical stability of the patient population. 3. Patients with a duration of illness greater than 10 yrs (Group 2) showed significant (p less than 0.01) higher EPSE total scores compared to those with a duration of illness less than 10 yrs (Group 1). 4. A positive correlation was found between the administered dose and haloperidol plasma levels. 5. Patients from Group 2 reached the steady-state more slowly and showed a lower total L/D ratio compared to those from Group 1. 6. The pharmacokinetic approach seems desirable in order to adjust the dose and avoid schizophrenic relapses.
The research literature on alternative drug treatments to lithium therapy for the prevention of recurrences in bipolar disorders is discussed. In particular, the data on anticonvulsants (carbamazepine and valproic acid), antidepressants (alprazolam), and calcium channel blockers (verapamil) are reviewed and original data on clonazepam (CLN) are reported. In a preliminary study on six patients with bipolar disorders (DSM-III-R) without a history of psychotic features in which lithium prophylaxis was ineffective, contraindicated, or badly tolerated, CLN was administered in combination with low-dose neuroleptics or antidepressants in all but one case. All subjects were followed for 13 to 34 months. There were no relapses during the observation period with CLN dose regimens ranging from 1.5-8 mg/day p.o. Side effects were minimal and mostly consisted of transient sedation.
Twenty elderly chronic schizophrenic inpatients of both sexes, age ranging from 60 to 73 years (mean age 63 +/- 0.81 years), diagnosed according to DSM III-R, were treated with fluphenazine decanoate, 12.5 mg intramuscularly, administered every 21 days for six months. Psychopathological features were assessed by means of the Brief Psychiatric Rating Scale at time 0 and then weekly. At 0, 6, 12, 24, 36, 48, 72h and 7, 14 and 21 days after each administration, extrapyramidal side-effects were evaluated using the Extrapyramidal Side-Effects Scale. Fluphenazine was significantly effective in treating symptoms such as emotional withdrawal, blunted affect, suspiciousness, thought disturbances, but not hallucinations. The most severe extrapyramidal side-effects occurred within the first two days of administration of fluphenazine, with a peak after 36 h, following the first four administrations of the drug, possibly related to early peak plasma concentrations. The severity of these effects was reduced after the fifth injection indicating the occurrence of tolerance mechanisms during long-term fluphenazine administration.
Depressive disorders are frequently associated with alcohol abuse. Though many studies have been carried out to clarify the role of antidepressant drugs in the management of alcoholic patients, the data are controversial. The present placebo-controlled study was planned to assess the antidepressant and attenuating drinking-behaviour efficacy of viloxazine (400 mg per os daily) versus a placebo in 30 dysthymic patients affected by alcohol dependence. The results significantly favour viloxazine treatment in alleviating depression and in reducing alcohol abuse. All patients showed baseline haematochemical evidence of liver dysfunction that did not change significantly during the treatment.
A naturalistic study was performed on 44 schizophrenic outpatients diagnosed according to DSM III-R and presenting neuroleptic-induced extrapyramidal side-effects. All patients had been treated continuously for the previous 10-12 weeks with haloperidol (HL) combined with orphenadrine (ORD). The dosages of HL and ORD remained unchanged for at least four weeks before the evaluations. All patients were assessed for depressive features (HRS-D), extrapyramidal (EPSE) and anticholinergic (ACS check list) side-effects. The plasma levels of ORD and its metabolite tofenacine (TOF) were determined by gas chromatography. There was a positive relationship between HRS-D and EPSE total scores, while there was a negative relationship between age and EPSE total scores. No relationship between the administered dose and plasma levels of ORD was found. The HL daily dose (mg/kg), ORD plasma levels and the TOF/ORD plasma level ratio seem to influence significantly the severity of residual extrapyramidal side-effects.
The aim of this multicenter study was to compare trazodone (TRA) with two reference drugs, amitriptyline (AMI) and mianserin (MIA), under double-blind conditions, in an elderly population, to ascertain age-related patterns for efficacy and tolerability. One hundred six elderly depressed inpatients, ranging in age from 60 to 83 years, diagnosed as having major depression according to DSM-III, were treated with 75 mg AMI (37 patients), 60 mg MIA (33 patients) or 150 mg TRA (36 patients) p.o.t.i.d. for 5 weeks. There were no differences in the clinical outcome among the three groups of patients at the end of the trial, with a significant amelioration (p less than 0.01) for the Hamilton Rating Scale for Depression (HRS-D) and the Geriatric Depression Scale (GDS). TRA showed a lower overall prevalence of side effects than AMI or MIA, particularly for anticholinergic (p = 0.03 vs. AMI) and cardiovascular (p = 0.05 vs. MIA) effects. For these data GDS seems to be most reliable in detecting changes in elderly depressive symptomatology; moreover a comparable therapeutic response (among the three drugs) but a better tolerance for atypical antidepressants, particularly TRA, make advisable the use of the latter drug in the elderly population.
Seventy five elderly depressed in-patients, ages ranging from 60 to 83 years, diagnosed as Major Depression according to DSM III were treated, under double-blind conditions, with 75 mg Amitriptyline (AMI) (26 patients), 60 mg Mianserin (MIA) (24 patients) or 150 mg Trazodone (TRZ) (25 patients) p.o. for 5 weeks. There were no differences in the clinical outcome between the three groups of patients at the end of the trial, with a significant amelioration (P less than 0.01) at the Hamilton Rating Scale for Depression and Geriatric Depression Scale. TRZ showed a significantly lower incidence of side effects compared to MIA and AMI. Atypical antidepressants, including TRZ, seem more suitable for treating elderly depression than the first generation antidepressants on the basis of risk/benefit ratio considerations.
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1. The knowledge of the pharmacokinetic profile of fluphenazine decanoate (FPZ-D) suggested it was suitable for treatment of schizophrenic patients not just during the maintenance phase of the disease but also during acute relapses. 2. 27 acute schizophrenic in-patients (diagnosed according to the DSM III) were treated with FPZ-D, 25 mg i.m. with repeated administrations (after 2, 4, 30 days). 3. FPZ-D proved effective in all cases, already after the second day and particularly on Brief Psychiatric Rating Scale items such as delusion, hallucinations, hostility. 4. Extrapyramidal side-effects, appeared in about 40% of the patients. 5. The use of the drug both in the acute phase and maintenance schizophrenia therapy is envisaged, overcoming the problems deriving from the rejection by patients of any therapeutic tool and consequently the therapeutic "milieu".
Pharmacokinetics parameters describing the time course of concentrations of mianserin (MIA) in plasma and brain and the relationship between plasma and brain concentrations were studied after acute and chronic administration of increasing doses of MIA in adult mice. There was a linear relationship between the area under the curve (AUC), the maximum concentration (Cmax) and doses, in plasma and brain, both during acute and chronic experiments (p less than 0.05). A five-fold variation in plasma and brain terminal half-life (t 1/2) after chronic administration of the drug was observed, possibly due to a reduction in plasma drug clearance (CL). The values of Cmax and AUC in plasma and brain showed an increase of respectively about three and twelve times after chronic treatment. A very good correlation was observed between plasma and brain Cmax in both acute and chronic experiments; brain Cmax was 10.2 (+/- 0.16) times higher than plasma Cmax after acute administration and 12.08 (+/- 1.33) times higher after chronic administration.
Clonazepam (CLN), a benzodiazepine originally used as an anti-epileptic, was tested in schizophrenia in a double blind comparison in combination with haloperidol (HL). Twenty-four schizophrenic inpatients, diagnosed according to DSM III were treated with HL and CLN (Group 1) or HL and placebo (Group 2) for 4 weeks. The Brief Psychiatric Rating Scale (BPRS) and the Extrapyramidal Side Effect Scale (EPSE) were used for assessing psychopathological features and extrapyramidal side-effects before treatment and then weekly. No differences in specific schizophrenic symptoms were detected between the two groups, but in Group 1 an early significant BPRS amelioration was noticed compared to Group 2. Moreover, the excitement item improved significantly in Group 1 only, from the second week. Less severe EPSE scores were observed in Group 1 in comparison to Group 2. In conclusion the combination of CLN and HL seems to be preferred to HL alone in cases of psychotic excitement and in order to reduce the severity of extrapyramidal side-effects.
Authors studied 42 depressed patients of both sexes suffering from Major Depression and Dysthimic Disorder, treated with viloxazine for 4 weeks. All patients were divided into two groups on the basis of their age (Group 1 mean age 45 +/- 2.2 and Group 2 mean age 68.3 +/- 1.12). Viloxazine was effective in different depressive situations, regardless of the age of the patient or the therapeutic context, even if in Group 2 the out-patients did significantly better (p less than 0.01) than the hospitalized ones. Mean steady-state plasma levels and level/dose ratios were significantly higher (p less than 0.05) in elderly patients than in younger ones. No correlation between viloxazine plasma levels-clinical efficacy and side-effects was found even though patients suffering from Major Depression showed a trend to a better response with plasma levels below 5 gamma/ml. The satisfactory antidepressant activity and the good tolerability of viloxazine in elderly depressed patients make this drug particularly suitable for using in ambulant geriatric depressed patients.
From many decades efficacy of lithium salts, as mood stabilizers, has been largely recognized, but their tolerability, in particular during intermediate or long-term treatments is still discussed. The most frequently described side effects can affect several organs. Aim of the study was to evaluate lithium carbonate tolerability after a "brief" (1 month-4 years), "intermediate" (5-9 years) and "longterm" (10-21 years) treatment of patients affected by Bipolar Disorders (BD). 27 patients (14 males, 13 females), aged from 20 to 78 years (mean 49.03 years +/- 14.61 SD), affected by BD, type I, according to DSM IV criteria were included into the study. Our data suggest a good tolerability of lithium salts without significant differences among the three different periods of treatment.