Quetiapine Add-On Therapy May Improve Persistent Sleep Disturbances in Patients with PTSD on Stabile Combined SSRI and Benzodiazepine Combination: A One-Group Pretest-Posttest Study.

BACKGROUND: To assess potential benefits of quetiapine for persistent sleep disturbances in patients with posttraumatic stress disorder (PTSD) on stable combined SSRI and benzodiazepine therapy, who previously failed to respond to various benzodiazepine and non-benzodiazepine hypnotic adjuvant treatment as well as to first-generation antipsychotic add-on treatment. SUBJECTS AND METHODS: Fifty-two male PTSD outpatients on stable combination treatment with SSRI and benzodiazepines, with persistent sleep disturbances not responding to prescription of zolpidem, flurazepam, nitrazepam, promazine, and levopromazine, were assessed for sleep disturbances improvements after prescription of quetiapine in the evening. Each patient met both ICD-10 and DSM-IV criteria for PTSD. Psychiatric comorbidity and premorbidity were excluded using the Mini-International Neuropsychiatric Interview (MINI). Improvement on the CAPS recurrent distressing dream item, reduction in the amount of time needed to fall asleep, prolongation of sleep duration, and reduction in average number of arousals per night in the last 7 days before the assessment period were used as efficacy measures. RESULTS: All sleep-related parameters improved significantly at the end of a five-week follow-up: sleep duration increased by one hour (p<0.001), sleep latency decreased by 52.5 minutes (p<0.001), median number of arousals per night decreased from two to one (p<0.001), CAPS recurrent distressing dream item median decreased from five to four (p<0.001), and the number of patients dissatisfied with their sleep quality and quantity decreased from 45 to two (p<0.001). CONCLUSION: Quetiapine prescribed in the evening may be successful therapy for persistent sleep disturbances in patients with PTSD and generally good response to an SSRI and benzodiazepine combination, who previously failed to respond to some of the usual hypnotic medication or addition of first-generation antipsychotics: zolpidem, flurazepam, nitrazepam, promazine, and levopromazine.

Remission Is not Associated with DRD2 rs1800497 and DAT1 rs28363170 Genetic Variants in Male Schizophrenic Patients after 6-months Monotherapy with Olanzapine.

BACKGROUND: Symptomatic remission is an achievable goal in the treatment of schizophrenia. The type of antipsychotic medication and particular genetic variants of the dopaminergic system might be associated with remission. Potential pharmacogenetic markers of the treatment response to antipsychotic medication are missing. This study assessed the possible association between dopamine receptor type 2 (DRD2 rs1800497) and dopamine transporter (DAT1 rs28363170) gene variants with symptomatic remission in schizophrenia. SUBJECTS AND METHODS: Olanzapine (5-20 mg/d) monotherapy was administered for 6 months to 150 male Caucasian subjects with schizophrenia. Remission was evaluated according to "Remission in Schizophrenia Working Group" criteria. Genotyping was performed by PCR-RFLP. RESULTS: Symptomatic remission was found in 31% of patients. DRD2 rs1800497 and DAT1 rs28363170 gene variants were not significantly associated with symptomatic remission. The limitations are a relatively small sample size of patients with schizophrenia (N=150), especially of group with symptomatic remission (N=45). However, the study had moderate but adequate sample sizes for most of the comparisons. Only two dopaminergic polymorphisms were analyzed, and plasma concentration of olanzapine was not determined. CONCLUSION: These results revealed a lack of association between DRD2 rs1800497 and DAT1 rs28363170 genetic variants and symptomatic remission in male patients treated with olanzapine, suggesting that these genetic variants could not be used to predict symptomatic remission to olanzapine monotherapy. Negative results should be further confirmed or rejected in the larger samples, including haplotype analyses, to detect clinically useful and easy obtainable pharmacogenetic markers that might predict therapeutic response or remission in schizophrenia.

Latent Toxoplasma gondii infection is associated with decreased serum triglyceride to high-density lipoprotein cholesterol ratio in male patients with schizophrenia.

BACKGROUND: Previous studies suggested a complex association between Toxoplasma gondii (TG) infection and host lipid metabolism. Both TG infection and metabolic disturbances are very common in patients with schizophrenia, but this relationship is not clear. METHODS: In this cross-sectional study, we evaluated the association between TG seropositivity, serum lipid levels, body mass index (BMI) and metabolic syndrome (MetS) in 210 male inpatients with schizophrenia. RESULTS: In our sample of schizophrenia patients, with the mean age of 43.90 ±â€¯12.70 years, the rate of TG seropositivity was 52.38% and the prevalence of MetS was 17%. Patients with the TG antibodies had lower serum triglyceride levels and body weight compared to TG seronegative patients, despite having more frequently received antipsychotics (clozapine, olanzapine risperidone and quetiapine), which are well known to induce weight gain and metabolic abnormalities. However, the only significant change in metabolic parameters, observed in TG seropositive patients with schizophrenia, was decreased serum triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio. No associations were observed between TG seropositivity and serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose levels, waist circumference, BMI and the rate of MetS. CONCLUSION: This is the first report of the association between TG infection and decreased serum triglyceride to HDL-C ratio in a sample of carefully selected men with chronic schizophrenia.

Nicotine dependence in Croatian male inpatients with schizophrenia.

BACKGROUND: Patients with schizophrenia have the highest known rates of cigarette smoking, but less is known about their smoking behavior and the differences across geographical regions, including Croatia. The aim of this study was to compare patterns of nicotine dependence between patients with schizophrenia and healthy individuals, and to determine the relationship between clinical presentation and the severity of smoking. METHODS: This cross-sectional study included 182 recently hospitalized male inpatients and 280 healthy males, who were daily smokers. All participants have fulfilled the Fagerstrom Test for Nicotine Dependence (FTND). Patients were also evaluated by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Patients had higher FTND total score (p = 0.010), smoked their first cigarette earlier in the morning (p = 0.000), consumed higher number of cigarettes (p = 0.000), while healthy subjects had more difficulties to refrain from smoking in places where it is forbidden (p = 0.000) and smoked more even when they were sick (p = 0.000). While severe dependence was more prevalent in the patient group, light dependence was more frequent in control subjects (p = 0.04). Smoking behavior was not associated with either PANSS total score or any of its subscales and items. CONCLUSIONS: Smokers with schizophrenia differ from healthy smokers in both smoking behavior and level of dependence. Longitudinal studies are needed to shed more light on the complex relationship between smoking and psychopathology in schizophrenia.

Monoamine oxidase and agitation in psychiatric patients.

Subjects with schizophrenia or conduct disorder display a lifelong pattern of antisocial, aggressive and violent behavior and agitation. Monoamine oxidase (MAO) is an enzyme involved in the degradation of various monoamine neurotransmitters and neuromodulators and therefore has a role in various psychiatric and neurodegenerative disorders and pathological behaviors. Platelet MAO-B activity has been associated with psychopathy- and aggression-related personality traits, while variants of the MAOA and MAOB genes have been associated with diverse clinical phenotypes, including aggressiveness, antisocial problems and violent delinquency. The aim of the study was to evaluate the association of platelet MAO-B activity, MAOB rs1799836 polymorphism and MAOA uVNTR polymorphism with severe agitation in 363 subjects with schizophrenia and conduct disorder. The results demonstrated significant association of severe agitation and smoking, but not diagnosis or age, with platelet MAO-B activity. Higher platelet MAO-B activity was found in subjects with severe agitation compared to non-agitated subjects. Platelet MAO-B activity was not associated with MAOB rs1799836 polymorphism. These results suggested the association between increased platelet MAO-B activity and severe agitation. No significant association was found between severe agitation and MAOA uVNTR or MAOB rs1799836 polymorphism, revealing that these individual polymorphisms in MAO genes are not related to severe agitation in subjects with schizophrenia and conduct disorder. As our study included 363 homogenous Caucasian male subjects, our data showing this negative genetic association will be a useful addition to future meta-analyses.

Antipsychotics: to combine or not to combine?

Antipsychotic monotherapy is strongly recommended in the treatment of schizophrenia. However, antipsychotic polypharmacy (APP) is common in clinical practice, and appears to be related to illness severity and duration, treatment-refractoriness, hospitalization status, duration of hospitalization, geographic region and age. Given the high number of different antipsychotic combinations reported in the literature and prescribed in clinical practice, there are perhaps more differences than similarities between such combinations. While the majority of combinations increase side-effect burden, limited evidence suggests benefits of certain combinations.Until more data are available, APP should be reserved for difficult-to treat patients, with careful consideration of pharmacodynamics properties and doses of each drug, as well as close monitoring.