Effect of Valproate and Antidepressant Drugs on Clozapine Metabolism in Patients With Psychotic Mood Disorders

BACKGROUND: The aim of the present study was to appraise retrospectively the influence of valproate (VPA) and antidepressants (ADs) on the steady-state plasma concentrations of clozapine (CLZ), the prototype of various second-generation antipsychotics, norclozapine (NCLZ, its main metabolite), and their ratio (NCLZ:CLZ). METHODS: Sixty-seven psychotic patients with a prevalent diagnosis of bipolar disorder were studied. We then analyzed data altogether and subdivided them into 4 groups, according to pharmacological treatments: #1 CLZ (n = 21), #2 CLZ plus ADs (n = 13), #3 CLZ plus VPA (n = 16), and #4 CLZ plus ADs plus VPA (n = 17). RESULTS: First, significant positive between CLZ and NCLZ plasma levels (in nanograms/milliliter) and the drug daily dosages (in milligrams/kilogram of body weight) (n = 67) were observed (Spearman: rCLZ = 0.49; rNCLZ = 0.61; P < 0.001). We then normalized by given doses CLZ and NCLZ plasma levels, natural log transformed them, and performed analysis of variance factor analyses followed by pairwise comparisons, performed on the 4 groups and the 3 CLZ parameters. We identified significant drug effects on (1) CLZ plasma levels, significantly higher in group #2 versus group #1, and (2) NCLZ:CLZ ratio, lower in group #2 versus groups #1 and #3. Significant drug × gender interactions were observed in group #3, showing higher NCLZ levels and NCLZ:CLZ ratios in men compared with women. CONCLUSIONS: Despite its inherent limitations, this observational study confirms the significant increase in plasma CLZ concentrations and reduction in NCLZ:CLZ ratio when this drug was coadministered with ADs (group #2), an effect apparently counteracted by VPA (group #4). The drug × gender interactions in patients taking both CLZ and VPA (group #3) warrant further prospective study

Validity and reliability of the Structured Clinical Interview for the Trauma and Loss Spectrum (SCI-TALS)

Background. DSM-IV identifies three stress response disorders (acute stress Disorder (ASD), post-traumatic stress Disorder (PTSD) and adjustment disorders (AD)) that derive from specific life events. An additional condition of complicated grief (CG), well described in the literature, is triggered by bereavement. This paper reports on the reliability and validity of the Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS) developed to assess the spectrum of stress response. The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising clinical and subsyndromal manifestations. Methods. Study participants, enrolled at 6 Italian Departments of Psychiatry located at six sites, included consecutive patients with PTSD, 44 with CG and a comparative group of 48 unselected controls. Results. We showed good reliability and validity of the SCI-TALS. Domain scores were significantly higher in participants with PTSD or CG compared to controls. There were high correlations between specific SCI-TALS domains and corresponding scores on established measures of similar constructs. Participants endorsing grief and loss events reported similar scores on all instruments, except those with CG who scored significantly higher on the domain of grief reactions. Conclusion. These findings provide strong support for the internal consistency, the discriminant validity and the reliability of the SCI-TALS. These results also support the existence of a specific grief-related condition and the proposal that different forms of stress response have similar manifestations

Leadership and early strategic response to the SARS-CoV-2 pandemic at a COVID-19 designated hospital in South Africa

While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA).While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SAgovernment announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes

Mood disorders in subjects with bruxing behavior

Objective. An investigation was conducted on 105 subjects to assess the existence of an association between mood psychopathology and bruxism. Methods. Validated clinical criteria were used to diagnose bruxism and a self-report validated questionnaire (MOODS-SR) was filled out by each patient for an evaluation of depression and mania symptoms of mood spectrum. Results. Prevalence of mood psychopathology, as identified by MOODS-SR score &gt;= 60, was significantly higher in bruxers (11/38, 28.9% vs. 6/67, 8.9%; P = 0.007). Significant differences between bruxers and non-bruxers also emerged in total MOODS-SR (P = 0.001) scores and in total scores of domains evaluating manic (P = 0.001) and depressive symptoms (P = 0.007). Conclusions. Support to the existence of an association between bruxism and mood disorders has been provided. Further studies are strongly needed to clarify mechanisms underlying the described association. (C) 2005 Elsevier Ltd. All rights reserved

Significance of REM sleep dysregulation in depression: State of the art (In press.)

Disturbances of sleep are typical for most depressed patients and belong to the core symptoms of the disorder. Since the 1960ies polysomnographic sleep research has demonstrated that besides disturbances of sleep continuity, depression is associated with altered sleep architecture, i.e. a decrease in slow wave sleep (SWS) production and disturbed REM sleep regulation. Shortened REM latency (i.e. the interval between sleep onset and the occurrence of the first REM period), increased REM sleep duration and increased REM density (i.e. the frequency of rapid eye movements per REM period) have been considered as biological markers of depression which might predict relapse and recurrence. High risk studies including healthy relatives of patients with depression demonstrate that REM sleep alterations may precede the clinical expression of depression and may thus be useful in identifying subjects at high risk for the illness. Several models have been developed to explain REM sleep abnormalities in depression, like the cholinergic-aminergic imbalance model or chronobiologically inspired theories, which are reviewed in this overview. Moreover, REM sleep alterations have been recently considered not only as biological "scars" but as true endophenotypes of depression. This review discusses the genetic, neurochemical and neurobiological factors that have been implicated to play a role in the complex relationships between REM sleep and depression. We hypothesize on the one hand that REM sleep dysregulation in depression may be linked to a genetic predisposition/vulnerability to develop the illness; on the other hand it is conceivable that REM sleep disinhibition in itself is a part of a maladaptive stress reaction with increased allostatic load. We also discuss whether the REM sleep changes in depression may contribute themselves to the development of central symptoms of depression such as cognitive distortions including negative self-esteem and the overnight consolidation of negatively toned emotional memories