A systematic chart review of pharmacological interventions in patients with clozapine-induced hypersalivation.

OBJECTIVES: To investigate the efficacy and tolerability of medications, such as mouthwash use of 1 % atropine sulfate and tropicamide drops, oral amitriptyline and amisulpride used for clozapine-induced hypersalivation (CIH). METHODS: The medical charts of inpatients with psychotic disorders between 2010 and 2022 were reviewed retrospectively. We detected 161 patients with eligible data who received or commenced clozapine. Primary outcome was defined as the percentage change in the diameter of a wet patch on the pillow (DWP) for improvements in CIH. RESULTS: The frequency of CIH was 42 % (n = 68). The first step medications for CIH were tropicamide drops (49 %), atropine drops (43 %) and amitriptyline (3 %). After the first step, the median DWP significantly decreased by -33 %. During the index hospitalization, in 18 patients with persistent CIH, the median DWP significantly decreased by -42 % with the second step medications which also included amisulpride. There were no reported serious adverse events. The change in DWP was significantly correlated with the duration of clozapine treatment (r = 306) and clozapine serum level at discharge (r = 0.294). A linear regression model showed a link between the change in DWP and reduced Positive and Negative Syndrome Scale scores. CONCLUSIONS: Our findings emphasize that mouthwash use of atropine or tropicamide drops has a satisfying and tolerable effect in treating CIH. Switching medications for CIH seems to be effective when CIH persists despite a first step agent. Controlled follow-up studies are needed to understand the relationship between CIH, clozapine serum levels, illness severity, and functioning.

A diffusion tensor imaging study in schizophrenia patients with clozapine induced obsessive compulsive symptoms.

OBJECTIVE: The aim of this study was to evaluate brain connectivity by diffusion tensor imaging (DTI) in schizophrenia patients with clozapine-induced obsessive compulsive symptoms (OCS). METHODS: Eighteen schizophrenia patients, nine of which had clozapine-induced OCS (Clz-OCS (+)), 9 without OCS (Clz-OCS (-)) and 9 healthy controls were included. Psychopathology was evaluated with Positive and Negative Syndrome Scale and Yale-Brown Obsession and Compulsion Scale in the patient groups. All groups were assesed with neurocognitive tests and DTI. RESULTS: Tract-Based Spatial Statistics based comparison of DTI revealed lower fractional anisotropy in the genu of corpus callosum (CC), right cingulum, left frontal white matter (WM) in the Clz-OCS (+) group, compared to controls. Fractional anisotropy was found to be lower in the bilateral occipital WM and higher in the bilateral medial temporal regions, anterior limb of internal capsule, cingulum, frontoparietal peripheral WM, right external capsule and genu of CC in Clz-OCS (+) patients compared to Clz-OCS (-). CONCLUSIONS: WM integrity in several pathways such as cortico-striato-thalamo-cortical circuitry and orbito-frontal tracts seems to be affected differently in patients with Clz-OCS (+). Different neuroplastic effects of clozapine leading to occurrence of OCS in a subgroup of patients is possible, and needs further evaluation by longitudinal follow-up studies.

High/severe fear of childbirth and related risk factors among pregnant women: is vaginismus a risk factor?

This study aimed to investigate the prevalence of fear of childbirth (FOC) and associated factors including vaginismus in pregnant women with high/severe FOC. In the study, 407 women who were at 24-40 weeks of gestation were included. The Wijma Delivery Expectancy/Experience Questionnaire Version A (WDEQA), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and vaginismus sub-scale of the Golombok Rust inventory of sexual satisfaction (GRISS) were used. 186 (46%) participants had high/severe FOC. Pregnant women with high/severe FOC had a significantly higher fear of pain during sexual intercourse, higher scores in the WDEQA, BDI, BAI, and vaginismus sub-scale of GRISS. Depression and anxiety level, educational level, access to information on delivery during pregnancy, presence of medical disease, and expression of FOC were predictors of high/severe FOC. Assessment of FOC and associated risk factors, including vaginismus, during pregnancy, will enable the identification of risk groups and the creation of support programmes.Impact StatementWhat is already known on this subject? The range of fear of childbirth (FOC) changes from mild anxiety to severe fear. The prevalence and severity of FOC and related risk factors vary in the studies due to cultural factors, differences in the definition of FOC and measurement tools. The relationship between FOC and vaginismus has not been sufficiently investigated.What do the results of this study add? This study aimed to investigate the prevalence of fear of childbirth (FOC) and associated factors including vaginismus in pregnant women with high/severe FOC.What are the implications of these findings for clinical practice and/or further research? This is the first study that evaluates vaginismus as a risk factor for FOC. Assessment of FOC and associated risk factors, including vaginismus, in pregnant women, will enable the identification of risk groups and the creation of support programs for risk reduction.

Renal effects of long-term lithium therapy, revisited.

OBJECTIVE: The aim of this study was to investigate the effect of lithium treatment on renal function and to determine influencing factors. In addition, the utility of spot urine protein/creatinine ratio in detection of lithium induced nephropathy was also investigated. METHODS: Serum concentrations of lithium, blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), and urinalysis including protein/creatinine ratio were measured in 375 patients using lithium. RESULTS: Patients taking lithium for ≥8 years had higher BUN, creatinine levels, percentage of proteinuria, percentages of stage 2 and 3 chronic kidney disease (CKD); lower urine density and eGFR compared to patients taking lithium <8 years. Urine density was lower in groups with >0.8 and 0.6-0.8 mmol/L lithium level than <0.6 mmol/L. Predictors of CKD were serum level of lithium, dose of lithium, cumulative duration of lithium use, age at onset of illness, and caffeine consumption. CONCLUSIONS: Detrimental effects of lithium on renal functions were detected after lithium use for ≥8 years. Proteinuria measured by spot urine protein/creatinine ratio can be detected even when eGFR is >90 ml/min/1.73 m2 . Spot urine protein/creatinine ratio, which is a cost-effective and practical laboratory test, can be used to monitor lithium-treated patients.

Effect of Clozapine on Proton Magnetic Resonance Spectroscopy Findings in Hippocampus. / Klozapinin Hipokampusta Proton Manyetik Rezonans Spektroskopi Bulgulari Üzerine Etkisi.

OBJECTIVE: The purpose of this study was to investigate the effect of clozapine on proton magnetic resonance spectroscopy (1H-MRS) findings in hippocampus in patients with schizophrenia. In addition, the relationship between the change in 1H-MRS findings and the change in psychopathology and neurocognitive functions was evaluated. METHOD: Patients with schizophrenia (n=16) were assessed with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), a neurocognitive test battery and 1H-MRS at baseline, and twelve weeks after the initiation of clozapine. Healthy controls (n=8) were assessed once with a neurocognitive test battery and 1H-MRS. Bilateral multivoxel and left single voxel NAA/Cr, Cho/Cr, MI/Cr was calculated in the hippocampi. RESULTS: After 12 weeks of clozapine treatment, PANSS and CGI scores decreased; immediate recall, cumulative learning subtests of the Rey Auditory Verbal Learning Test, Category Verbal Fluency Test and Wechsler Memory Scale's visual reproduction delayed subtest scores increased significantly. Compared with healthy controls and patients after clozapine, hippocampi multivoxel and single voxel NAA/Cr, Cho/ Cr, MI/Cr ratios were not different in patients before clozapine. No significant correlations between change in 1H-MRS metabolite ratios and change in psychopathology, neurocognitive functions were detected. CONCLUSION: This study is the first longitudinal study to investigate the effect of clozapine in hippocampus with 1H-MRS. There were no significant changes in 1H-MRS findings in hippocampi after twelve weeks of clozapine treatment. Clozapine's effect in hippocampus should be investigated further in longer follow up studies with larger samples to reach a final conclusion.

Weight Loss Associated with Clozapine: A Case Report. / Klozapin Kullanimina Bagli Kilo Kaybi: Vaka Sunumu.

Clozapine is one of the second generation antipsychotics most commonly associated with serious metabolic side effects including weight gain. Unexpectedly, weight loss can also be seen as a rare side effect of clozapine. The mechanism underlying clozapine induced weight loss is not clearly understood. Several factors including certain brain areas, neurotransmitters, neuropeptides and genetic variants were identified to play a role in weight loss associated with clozapine. In some patients who were reported to have a significant weight loss (13.5-50% of body weight) with clozapine, weight loss might not be associated with any underlying physical disorder. Weight loss may be due to the patients' engagement in diet and exercise after clinical improvement, pharmacodynamic effects of clozapine, or other medical problems such as gastrointestinal tract hypomotility caused by clozapine. Some case reports suggested that clozapine-associated weight loss might be a sign of poor response to clozapine. Clinicians should keep in mind the fact that a specific group of patients may lose weight during clozapine treatment. In this case report, possible causes of weight loss due to clozapine use is discussed. We also discussed the possible relationship between clozapine dose and weight loss which has not drawn attention in previous case reports.

Longitudinal Analysis of Female Authorship of Psychiatry Articles in Turkey.

INTRODUCTION: The number of women with careers in medicine and with academic positions at medical schools has increased substantially since the 1980s; however, women remain underrepresented in medical academia, which may be because of the fewer research publications authored by women. This study aimed to determine the gender distribution among Turkish authors of psychiatry articles published in international scientific journals during a 30-year period. METHODS: The ISI Web of Science database was searched for all psychiatry publications between 1980 and 2009 using the search term Turkey. All articles were classified according to publication period (1980-1989, 1990-1999, 2000-2004, and 2005-2009), gender of the first and last authors, first author title, total number of authors, and type of article. RESULTS: In all, 1961 articles meet the study criteria. The first author of 36.5% of the articles and 34.9% of last authors were women. The percentage of female first and last authors did not differ according to publication period (p=0.57). CONCLUSION: To the best of our knowledge this is the first study to examine gender and authorship of psychiatric research in Turkey. In total, 33% of academic positions in Turkish university psychiatry departments were occupied by women, which is comparable to the percentage of female first authors of psychiatric research papers from Turkey. It could be concluded that women academics in psychiatry departments from state universities are as reproductive as their male counterparts, but there is still a "gender gap" in psychiatry field in our country.

Effect of clozapine on white matter integrity in patients with schizophrenia: a diffusion tensor imaging study.

Several diffusion tensor imaging (DTI) studies have reported disturbed white matter integrity in various brain regions in patients with schizophrenia, whereas only a few studied the effect of antipsychotics on DTI measures. The aim of this study was to investigate the effect of 12 weeks of clozapine treatment on DTI findings in patients with schizophrenia, and to compare the findings with those in unaffected controls. The study included 16 patients with schizophrenia who were assessed with the Positive and Negative Syndrome Scale, a neurocognitive test battery, and DTI at baseline and 12 weeks after the initiation of clozapine treatment. Eight unaffected controls were assessed once with the neurocognitive test battery and DTI. Voxel-wise analysis of DTI data was performed via tract-based spatial statistics (TBSS). Compared with the control group, the patient group exhibited lower fractional anisotropy (FA) in 16 brain regions, including the bilateral superior longitudinal fasciculi, inferior fronto-occipital fasciculi, superior and inferior parietal lobules, cingulate bundles, cerebellum, middle cerebellar peduncles, and left inferior longitudinal fasciculus, whereas the patients had higher FA in six regions, including the right parahippocampus, left anterior thalamic radiation, and right posterior limb of the internal capsule before clozapine treatment. After 12 weeks of treatment with clozapine, white matter FA was increased in widespread brain regions. In two of the regions where FA had initially been lower in patients compared with controls (left inferior fronto-occipital fasciculus and superior parietal lobule), clozapine appeared to increase FA. An improvement in semantic fluency was correlated with the increase in FA value in the left inferior fronto-occipital fasciculus. An increase in FA following 12 weeks of treatment with clozapine suggests that this treatment alters white matter microstructural integrity in patients with schizophrenia previously treated with typical and/or atypical antipsychotics and, in some locations, reverses a previous deficit.