[The use of mGlu2/3 receptors as a new approach to treat schizophrenia: results of a randomized double-blind trial].

Glutamate neurotransmission has been considered as one of pathogenetic factors of schizophrenia though all antipsychotics widely used in modern psychiatric practice are dopamine antagonists. LY2140023 is a selective agonist for metabotropic glutamate 2/3 (mGlu2/3) receptors with antipsychotic effect. In the present study, we have assessed clinical efficacy of LY2140023 in patients with schizophrenia compared to the control group receiving olanzapine in a randomized double-blind placebo-controlled trial. The statistically significant reduction of positive and negative symptoms measured with the PANSS (p<0.001) was observed for both antipsychotics at week 4 of treatment compared to placebo. The treatment with LY2140023 was safe and well-tolerated; treated patients did not differ from the placebo group by hyperprolactinemia and extrapyramidal symptoms, and weight gain. The results suggest that the agonist for 2/3 (mGlu2/3) receptors has antipsychotic properties and provides a new, alternative to dopamine agonists, method for pharmacotherapy of schizophrenia.

[Parameters of platelet serotonin system in patients with schizophrenia treated with olanzapine: a search for the serotonergic predictors of therapeutic efficacy].

Fifty-nine patients, 21 women and 38 men, with ICD-10 diagnosis of schizophrenia (F20.0), attack-like type, were treated with olanzapine during 28 weeks (8-weeks of acute and 20-weeks of maintenance therapy). Evaluation of clinical symptoms measured by the Positive and Negative Syndromes scale (PANSS) revealed that female patients responded better to therapy as compared to male ones, with PANSS total, PANSS negative and PANSS general psychopathological scores being significantly reduced (p < 0.006) in females after 1 week of the treatment and in males--after 2 weeks. In the female group, a reduction of PANSS total score by 50% in the acute stage of treatment qualified as a very good response was observed in 7 (33%) patients and in the male group--in 1 (2.7%). The between-groups difference was highly significant (p = 0.002). When examined for a rate of 3H-serotonin uptake into platelets, density of sites of 3H-imipramine binding on the whole platelets, platelet serotonin level and levels of high- also low-molecular weight forms of platelet immunoreactive serotonin transporter protein, a significant decrease of the platelet serotonin level, comparing to controls, was detected in the female group before treatment. During the treatment, this parameter gradually increased up to control level. Other parameters did not change significantly for 28-weeks of therapy and did not differ from the control values. There were positive correlations between the levels of platelet serotonin before treatment and subsequent reduction of the PANSS total and positive subscale scores in the female group. In responders with a very good treatment-related response, the serotonin level in the platelets before treatment was higher compared to the values in resistant patients: 5.4 +/- 2.5 and 2.7 +/- 1.3 nmol/10(9) cells, respectively. Relative risk (RR) of unfavorable treatment outcome in patients with initially reduced levels of platelet serotonin was approximately twice lower (RR = 1.83; Cl 95% 1.1-34.9) than that in patients with normal or elevated levels of platelet serotonin. The results suggest that selection of patients with initial higher level of platelet serotonin before olanzapine treatment can reduce the risk of non-responding to therapy by 36%.

[The experience of application of olanzapine: an atypical neuroleptic in acute schizophrenia]. / Opyt primeneniia atipichnogo neiroleptika -- olazapina v ostrom periode shizofrenii.

Thirty adult patients with acute schizophrenia were included into six-week open-labelled, non-comparative trial of olanzapine with free dosing from 5 to 20 mg per day. For assessment of efficacy and safety of the treatment PANSS, BPRS, CGL and ESRS scales were used. The main criterion of improvement was the percentage of reduction of BPRS score to the end of the trial. More than 50% reduction was achieved in 23% of the patients, more than 20%--in 57% of the cases; 20% were non-responders (reduction less than 20%). Changes in the scores of the positive and negative PANSS subscales were significant (p < 0.001) starting from the second week of treatment. There was no correlation in changes in positive and negative scores as well as in changes in negative and ESRS scores. The first signs of the antipsychotic effect (a reduction of tension, suspiciousness and fear) appeared just in the first two weeks of treatment and manifested in the reduction of delusions and hallucinations. Reduction of depression didn't correlate with changes in scores of the positive or negative PANSS subscales. The changes in behavioral and cognitive symptoms were statistically significant starting from the second week of treatment. No clinically significant signs of extrapiramidal syndrome or other side-effects except weight gain were observed during the trial.

[Characteristics of the premanifest period of late schizophrenia with the picture of an involutional paranoid]. / Osobennosti domanifestnogo perioda pozdnei shizofrenii s kartinoi involiutsionnogo paranoida.

Study of the premanifest period in 65 patients with schizophrenia that first manifested in old age by the "involutional paranoid" syndrome demonstrated that most patients presented signs of a torpid (17.5%) or a latent (68%) course of the schizophrenic process already in young or middle age. In only 14.5% of cases the pre-manifest period was characterized by personality accentuation. Analysis of cases of the latent course of the disease has made it possible to distinguish three main variants of its clinical manifestations: hypoparanoid, psychopathy-like and neurosis-like. On the basis of these findings a conclusion can be drawn that most of the cases of schizophrenia manifested in old age by the syndrome of involutional paranoid belong to a group of diseases with an early onset, prolonged torpid or latent course, and with increased progression of the process in advanced age.