Vlado Jukić

QTc and psychopharmacs: are there any differences between monotherapy and polytherapy.

BackgroundSome psychotropic drugs are connected with prolongation of QT interval, increased risk of cardiac arrhythmias and greater incidence of sudden death, especially when used in combination. Concomitant use of antipsychotics and antidepressants is not rare in our clinical practice. The study compares the length of QT interval in patients on monotherapy with an antipsychotic or an antidepressant and patients taking polytherapy (an antipsychotic agent combined with an antidepressant).MethodsSixty-one hospitalized women who met the ICD-10 criteria for schizophrenia, schizoaffective psychosis, delusional disorder and mood disorder were included in the study. The monotherapy group was consisted of thirty-two women treated with an antipsychotic or an antidepressant while the polytherapy group was composed of twenty-nine women treated with an antipsychotic agent plus an antidepressant. Two electrocardiograms (ECGs) were obtained for each patient: the first was carried out before the treatment and the second after two weeks of treatment.Statistical analysis was carried out by SPSS program and included unpaired and paired t test and Fishers exact test.ResultsMean baseline QTc values did not differ between the groups (439 ± 22 ms was the same value found in the both groups; unpaired t test, p > 0.5). Mean QTc intervals after two weeks of treatment were also similar (439 ± 24 ms in the monotherapy group and 440 ± 20 ms in the polytherapy group; unpaired t test, p > 0.5). Fishers exact test did not reveal significant difference in the number of patients with borderline (451–470 ms) or prolonged (> 470 ms) QTc between groups, neither before treatment nor after two weeks of treatment. Twenty two women of the total of sixty one patients (36%) had QTc > 450 ms before applying therapy.ConclusionWe did not find significant QT prolongation in our patients after two weeks of treatment with antipsychotics and/or antidepressants. The QTc interval length did not differ significantly in the monotherapy and the polytherapy group. More than one third of included women exceeded the threshold value of borderline QTc interval (450 ms) before starting treatment. This finding calls for caution when prescribing drugs to female psychiatric patients, especially if they have other health problems.

Association between total serum cholesterol and depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder: a cross-sectional study

Aim To investigate the relationship between total serum cholesterol and levels of depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder (PTSD) without psychiatric comorbidity. Methods A total of 203 male PTSD outpatients were assessed for the presence of depression, aggression, and suicidality using the 17-item Hamilton Depression Rating Scale (HAM-D17), Corrigan Agitated Behavior Scale (CABS), and Scale for Suicide Ideation (SSI), respectively, followed by plasma lipid parameters determination (total cholesterol, high density lipoprotein [HDL]-cholesterol, low density lipoprotein [LDL]-cholesterol, and triglycerides). PTSD severity was assessed using the Clinician-Administered PTSD Scale for DSM-IV, Current and Lifetime Diagnostic Version (CAPS-DX) and the Clinical Global Impressions of Severity Scale (CGI-S), before which Mini-International Neuropsychiatric Interview (MINI) was administered to exclude psychiatric comorbidity and premorbidity. Results After adjustments for PTSD severity, age, body mass index, marital status, educational level, employment status, use of particular antidepressants, and other lipid parameters (LDL- and HDL- cholesterol and triglycerides), higher total cholesterol was significantly associated with lower odds for having higher suicidal ideation (SSI≥20) (odds ratio [OR] 0.09; 95% confidence interval [CI] 0.03-0.23], clinically significant aggression (CABS≥22) (OR 0.28; 95% CI 0.14-0.59), and at least moderate depressive symptoms (HAM-D17≥17) (OR 0.20; 95% CI 0.08-0.48). Association of total cholesterol and HAM-D17 scores was significantly moderated by the severity of PTSD symptoms (P < 0.001). Conclusion Our results indicate that higher total serum cholesterol is associated with lower scores on HAM-D17, CABS, and SSI in patients with chronic PTSD.

Minor physical anomalies in women with recurrent unipolar depression.

According to earlier observations, minor physical anomalies (MPAs) are more prevalent in psychotic disorders, especially in schizophrenia, and represent an indicator of abnormal fetal development. Limited research has been conducted on these structural abnormalities among patients with unipolar depression, with and without psychotic features. We hypothesized that the mean total MPA score would be greater in patients with psychotic depression than depressive patients without psychosis and control subjects. An extended scale of MPAs was used to detect the presence or absence of 51 MPAs in women with recurrent unipolar depression with psychotic symptoms (n=50), women with recurrent unipolar depression without psychotic symptoms (n=50) and healthy female controls (n=50). Women with recurrent depression had significantly more MPAs than controls. With regard to MPAs of specific body regions, depressive patients had significantly higher rates of MPAs in the mouth area than control subjects. Higher rates of MPAs were not significantly related to psychotic features of depression. The study results are indicative of possible early neurodevelopmental disturbance in recurrent unipolar depression.

Treatment-resistant schizophrenia and DAT and SERT polymorphisms.

One fifth to one third of all patients diagnosed with schizophrenia are resistant to drug treatment, which makes it a major clinical challenge. Genetic studies have focused on the association between treatment resistant schizophrenia (TRS) and a number of candidate genes, including serotonin and dopamine system genes. We explored associations between carefully characterized TRS and DAT-VNTR, SERT-PR and SERT-in2 polymorphisms. There were 173 patients enrolled in the study that were clinically evaluated using Positive and Negative Syndrome Scale and Clinical Global Impressions Scales and divided into two groups based on treatment resistance (92 patients in TRS group). Patients with a combination of SERT-in2 ll and DAT 9/10, 9/11, 9/9 and 6/6 genotypes were more likely to have TRS, compared to those with 10/10 or 10/12 genotype (OR=5.1; 95% CI=1.6-16.8). In the group of patients with DAT 10/10 or 10/12 genotype, those who also shared SERT-in2 ls or ss genotype were more likely to have TRS, compared to ll genotype carriers (OR=2.7; 95% CI=1.0-7.0). The model in which interaction between SERT-in2 and DAT polymorphisms is linked to TRS can possibly explain contradictory previous results regarding role of DAT and SERT in TRS, but further research is needed.

Testosterone levels and clinical features of schizophrenia with emphasis on negative symptoms and aggression

Abstract Background: Aggressive behavior and negative symptoms are two features of schizophrenia that may have a hormonal basis. Aim: The aim of this study was to compare testosterone level with clinical features of schizophrenia, focusing on negative symptoms and aggressive behavior. Methods: The study population consisted of 120 male schizophrenic patients (ages 18–40) classified into non-aggressive (n = 60) and aggressive (n = 60) groups. Depending on the type of aggression that was manifested prior to admission, the aggressive group was divided into violent (n = 32) and suicidal (n = 28) subgroups. Psychopathological severity, violence and suicidality were assessed using the Positive and Negative Syndrome Scale (PANSS), Overt Aggression Scale and Columbia Suicide Severity Rating Scale, respectively. Total serum testosterone level was determined on the same morning that symptoms were assessed. Results: In the non-aggressive group, testosterone level was negatively correlated with the score on the negative subscale of PANSS (P = 0.04) and depression (P = 0.013), and positively correlated with excitement (P = 0.027), hostility (P = 0.02) and impulsive behavior (P = 0.008). In the aggressive group, testosterone level had non-significant correlation with these parameters, and with violent or suicidal behavior. Conclusions: The results confirmed that non-aggressive male schizophrenic patients with lower levels of testosterone had a greater severity of negative symptoms. In aggressive patients, there was no correlation between testosterone and clinical features of the disorder or the degree or type of aggression. These findings indicate that therapeutic strategies targeting testosterone could be useful in the treatment of negative symptoms of schizophrenia.

Anxious depression and the stiff-person plus syndrome.

ObjectiveTo present the case of a patient with anxiety and depressive symptoms who developed the clinical picture of stiff-person plus syndrome (SPS-plus). BackgroundBefore the onset of typical SPS symptoms, psychiatric symptoms (like depression and anxiety) may be prominent and as such misleading, resulting in the diagnosis of a psychiatric condition. MethodWe describe the case of a woman who initially presented with anxious depression and remained resistant to treatment with different classes of antidepressants and additional therapy with lithium and atypical antipsychotics. ResultsEvidence of neurologic dysfunction and significantly increased levels of serum autoantibodies for glutamic acid decarboxylase supported the diagnosis of SPS. The patient appeared to benefit from short-term immunosuppressive therapy with methylprednisolone. ConclusionsThe authors believe that anxious depression and SPS-plus seen in this patient are the result of the same underlying autoimmune process, together forming a unique syndrome. Anxious and depressive symptoms in SPS can be explained by alterations in GABAergic neurotransmission.

Cost-Utility Analysis of Depot Atypical Antipsychotics for Chronic Schizophrenia in Croatia

OBJECTIVES As a nation with a developing economy, Croatia is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. We conducted a pharmacoeconomic analysis to determine the cost-effectiveness of atypical depots in Croatia. METHODS A 1-year decision-analytic framework modeled drug use. We determined the average direct cost to the Croatian Institute for Health Insurance of using depot formulations of paliperidone palmitate long-acting injectable (PP-LAI), risperidone LAI (RIS-LAI), or olanzapine LAI (OLZ-LAI). An expert panel plus literature-derived clinical rates populated the core model, along with costs adjusted to 2012 by using the Croatian consumer price index. Clinical outcomes included quality-adjusted life-years, hospitalization rates, emergency room treatment rates, and relapse days. Robustness of results was examined with one-way sensitivity analyses on important inputs; overall, all inputs were varied over 10,000 simulations in a Monte Carlo analysis. RESULTS Costs (quality-adjusted life-years) per patient were €5061 (0.817) for PP-LAI, €5168 (0.807) for RIS-LAI, and €6410 (0.812) for OLZ-LAI. PP-LAI had the fewest relapse days, emergency room visits, and hospitalizations. Results were sensitive against RIS-LAI with respect to drug costs and adherence rates, but were generally robust overall, dominating OLZ-LAI in 77.3% and RIS-LAI in 56.8% of the simulations. CONCLUSIONS PP-LAI dominated the other drugs because it had the lowest cost and best clinical outcomes. Compared with depots of olanzapine and risperidone and oral olanzapine, PP-LAI was the cost-effective atypical LAI for treating chronic schizophrenia in Croatia. Using depot paliperidone in place of either olanzapine or risperidone would reduce the overall costs of caring for these patients.

The relationship between depressive syndrome and suicidal risk in patients with acute schizophrenia.

Aim To determine the relationship between scores on five factors of the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression scale for Schizophrenia (CDSS) and scores on the InterSePT Scale for Suicidal Thinking (ISST) in patients with acute schizophrenia. Methods Data were collected on sociodemographic and clinical characteristics of 180 drug-treated in-patients with acute schizophrenia. Their symptoms were assessed with PANSS, CDSS, and ISST and correlations between the scores were calculated. Statistically significant correlations were included in the logistic regression analysis to identify predictors of suicidal risk. Results CDSS (P < 0.001) score and negative (P < 0.001), disorganized (P = 0.041), emotional (P < 0.001), and total score on PANSS (P < 0.001) showed a significant positive correlation with ISST. Stepwise logistic regression analysis revealed that CDSS scores (odds ratio [OR] 5.18; confidence interval [CI] 1.58-16.95), and disorganized (0.90; 0.81-0.99) and emotional (1.15; 1.01-1.30) factors of PANSS were predictors of suicidal risk. Conclusion Our results suggested a considerable association between depressive syndrome as assessed by the PANSS emotional factor and CDSS score and suicidal risk in patients with acute schizophrenia.

Role of substance abuse in requirement of physical restraint of psychiatric patients in emergency setting.

Background The practice of physical restraint in psychiatric emergency practice is rather frequent. Patients with substance abuse more often present aggressive behavior requiring physical restraint in such settings. The legal frame for such practice in our country is defined in the Law for the protection of persons with mental disturbances. Patients admitted to a psychiatric emergency ward were analyzed prospectively according to their need of physical restraint.

An Unusual Case of Infertility: Urethral Coitus Due to Cribriform Hymen

Urethral coitus is a rare type of sexual practice, usually due to vaginal agenesis or hymeneal anomalies. We report a case of urethral coitus in a healthy couple who were evaluated for infertility. The female partner had cribriform hymen and dilated urethral orifice but did not report any problems except infertility and her genital anatomy was normal. The male partner reported concerns over his penile size but was otherwise healthy. After incision of hymen, they were able to have vaginal coitus and successfully conceived. While urethral coitus is rare, it should be suspected in women presenting with infertility and a dilated urethral orifice.