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

• Published in: Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova Vol. 105; no. 3; p. 27
• Main Authors: Brusov, O S, Faktor, M I, Zlobina, G P, Dupin, A M, Katasonov, A B, Kartseva, N K, Beniashvili, A G, Zharkova, N B, Rubashkina, V V, Morozova, M A
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 2005
• Subjects: Adult; Age Factors; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - therapeutic use; Benzodiazepines - administration & dosage; Benzodiazepines - therapeutic use; Blood Platelets - metabolism; Data Interpretation, Statistical; Female; Humans; Male; Middle Aged; Schizophrenia - blood; Schizophrenia - diagnosis; Schizophrenia - drug therapy; Serotonin - blood; Serotonin - metabolism; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - therapeutic use; Sex Factors; Time Factors
• ISSN: 1997-7298

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%.