[A review on augmentation of clozapine treatment]. / Klozapin tedavisini güçlendirme: bir gözden geçirme.

Clozapine is one of the most effective pharmacological agents in the treatment of treatment-resistant patients with schizophrenia, schizoaffective and bipolar disorder. Nevertheless, there is still an important proportion of patients who do not respond to clozapine treatment given at a sufficient dose and duration. Some patients cannot tolerate the dosage necessary for an adequate treatment. Case reports, series, various open and controlled trials suggest that there are effective strategies of augmenting clozapine treatment in such cases. In this article, strategies of clozapine augmentation are reviewed in the light of findings related with the efficacy, safety and pharmacokinetic/dynamic interaction profiles of such combinations used for augmentation. To our knowledge, there is only one study in the current literature reviewing this subject. Augmenting strategies are reviewed through the combination of clozapine with the serotonin reuptake inhibitors (SSRI), typical and atypical antipsychotics, mood stabilizers, NMDA agonists and electroconvulsive treatment (ECT).

Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms.

Previous studies have suggested decreased N-methyl-D-aspartate (NMDA)-type glutamate receptor function may contribute to increased negative symptoms in patients with schizophrenia. Consistent with this hypothesis, glycine, a co-agonist at NMDA receptors, has been reported to improve negative symptoms associated with the illness. This study was performed to determine if plasma levels of glycine or its ratio to serine, a precursor of glycine, are decreased in patients with schizophrenia compared to normal control subjects or patients with major depression. We also tested the hypothesis that these amino acids were correlated with negative symptoms in subjects with schizophrenia. Plasma levels of glycine, serine, and their ratio, were compared in 144 patients with schizophrenia, 44 patients with major depression, and 49 normal control subjects. All subjects were medication-free. Psychopathology was evaluated using the Brief Psychiatric Rating Scale (BPRS). Plasma glycine levels and glycine/serine ratios were decreased in patients with schizophrenia relative to control subjects and patients with major depression. By contrast, serine levels were increased in patients with schizophrenia compared to normal subjects but not compared to major depression. Patients with major depression also had increased plasma serine levels and decreased glycine/serine ratios compared to normal controls, but glycine levels were not different from those of normal controls. In subjects with schizophrenia, glycine levels predicted the Withdrawal-Retardation score (BPRS), whereas no such correlation was found in subjects with major depression. These results provide additional evidence that decreased availability of glycine may be related to the pathophysiology of negative symptoms. The decreases in plasma glycine levels support the evidence for an abnormality in the glutamatergic system in schizophrenia, and provide additional support for efforts to improve negative symptoms by augmentation of antipsychotic drugs with agonists at the glycine site of the NMDA receptor.

Reexamination of the characteristics of the deficit schizophrenia patients.

The aim of this study was to reexamine and compare the characteristics of the deficit and nondeficit schizophrenic patients. This cross-sectional study consisted of 62 in- and out-patients, 18-65 years of age, diagnosed with schizophrenia according to DSM-IV. The sociodemographic variables, premorbid adjustment, clinical course and general functioning level in the past five years were evaluated by utilizing the appropriate sections of Comprehensive Assessment of Symptoms and History (CASH). In addition, GAF, the Schedule for the Deficit Syndrome (SDS), Positive and Negative Syndrome Scale (PANSS), Montgomery Asberg Depression Scale (MADRS), the Neurological Evaluation Scale (NES) and the Simpson Angus Extrapyramidal Side Effects (EPS) Rating Scale, Trail A and B, Verbal Fluency, Stroop, Block Design and Finger Tapper tests were administered. Using the SDS, 19 patients (30.6 %) were categorized as deficit; 43 (69.4 %) were categorized as nondeficit. The deficit patients were worse on the Functioning During Past Five Years score of CASH. The PANSS and MADRS mean scores were not significantly different between the two groups, except a higher level of negative symptoms observed in the deficit group. NES scores were also significantly higher in the deficit group. However, sociodemographic and other clinical variables, neurocognitive measures and EPS symptoms did not show any significant difference between the two groups. Our findings suggest that the deficit schizophrenia is a distinct subgroup comprised of patients who have more negative symptoms, neurological impairment and poor functioning which may have a common underlying pathology.

The Turkish version of the Auditory Consonant Trigram Test as a measure of working memory: a normative study.

The following study was conducted to adapt the Auditory Consonant Trigram Test (ACT) to Turkish, acquire a new and larger set of normative data, and finally investigate the reliability and validity of the adapted version. The data were collected from a sample of 236 healthy individuals. To test the validity of the Turkish version of ACT, the normative results of ACT were first compared with those obtained from the Digit Span Test (DST) backwards section. Secondly, the ACT performance of 53 schizophrenic patients was compared with that of a matched group selected from the normative sample. Age and education variables influenced performance, whereas gender did not in the normal sample. The ACT and DST backwards scores were positively correlated. As expected, the ACT performance was worse in schizophrenic patients compared to controls. The internal consistency of the adapted version of ACT was found to be at a reliable level (alpha=0.8535). The Turkish version of ACT can be considered to be a reliable and valid measure of working memory.