Relations between clinical characteristics and cognitive deficits among adult patients diagnosed with major depressive disorder.

OBJECTIVE: The present study examined the relations between clinical characteristics and cognitive deficits in adult patients with major depressive disorder (MDD) from a local outpatient psychiatric clinic in Malaysia. METHODS: The present sample included 110 participants aged 20-60 years old. Participants were invited to provide their information on sociodemographic variables (age, gender, and educational level) and clinical characteristics (age at onset of depression and duration of illness) and to complete a series of cognitive performance measures including the Trail Making Tests A (psychomotor speed) and B (executive function), the Digit Symbol Substitution Test (attention), and the Auditory Verbal Learning Test (immediate free recall, acquisition phase, and delayed recall). The Mini International Neuropsychiatric Interview Version 6.0 was used to confirm the diagnosis of MDD and the Montgomery-Åsberg Depression Rating Scale was used to assess illness severity. RESULTS: At the bivariate level, relations of age and educational level to all cognitive deficit domains were significant. At the multivariate level, only educational level and illness severity consistently and significantly predicted all cognitive deficits domains. CONCLUSIONS: Therapeutic modalities should be individualised whilst considering the impacts of cognitive deficits in an attempt to prevent further deterioration in psychosocial functioning of MDD patients.KEY POINTSCognitive deficits are an elemental component of Major Depressive Disorder (MDD) persisting during a current major depressive episode or during remission, altering individuals' ability to process information and changes the way they perceive and interact with the environment.Cognitive deficits in MDD are evident among the upper-middle income groups in South-Eastern Asian countries warranting more local research as such deficits could lead to functional decline and work performance such as absenteeism and presenteeism.Therapeutic modalities should be individualised by taking the impacts of cognitive deficits into consideration to promote psychosocial functioning of MDD patients.

Pharmacometric modeling of drug adverse effects: an application of mixture models in schizophrenia spectrum disorder patients treated with clozapine.

Clozapine has superior efficacy to other antipsychotics yet is underutilized due to its adverse effects, such as neutropenia, weight gain, and tachycardia. The current investigation aimed to introduce a pharmacometric approach to simultaneously model drug adverse effects, with examples from schizophrenia spectrum patients receiving clozapine. The adverse drug effects were represented as a function of time by incorporating a mixture model to describe individual susceptibility to the adverse effects. Applications of the proposed method were presented by analyzing retrospective data from patients' medical records in Psychiatric Clinic, Penang General Hospital. Tachycardia, weight gain, and absolute neutrophils count (ANC) decrease were best described by an offset, a piecewise linear, and a transient surge function, respectively. 42.9% of the patients had all the adverse effects, including weight gain (0.01 kg/m2 increase every week over a baseline of 24.7 kg/m2 until stabilizing at 279 weeks), ANC decrease (20% decrease from 4540 cells/µL week 12-20.8), and tachycardia (14% constant increase over a baseline of 87.9 bpm for a clozapine maintenance dose of 450 mg daily). 32.5% of the patients had only tachycardia, while the remaining 24.6% had none of the adverse effects. A new pharmacometric approach was proposed to describe adverse drug effects with examples of clozapine-induced weight gain, ANC drop, and tachycardia. The current approach described the longitudinal time changes of continuous data while assessing patient susceptibility. Furthermore, the model revealed the possible co-existence of ANC drop and weight gain; thus, neutrophil monitoring might predict future changes in body weight.

A Repeated Time-to-Positive Symptoms Improvement among Malaysian Patients with Schizophrenia Spectrum Disorders Treated with Clozapine.

Clozapine remains the drug of choice for resistant schizophrenia. However, its dose-response relationship is still controversial. The current investigation aimed to develop a repeated time-to-positive symptoms improvement following the onset of clozapine treatment in Malaysian schizophrenia spectrum disorder patients. Data from patients' medical records in the Psychiatric Clinic, Penang General Hospital, were retrospectively analyzed. Several parametric survival models were evaluated using nonlinear mixed-effect modeling software (NONMEM 7.3.0). Kaplan-Meier-visual predictive check (KM-VPC) and sampling-importance resampling (SIR) methods were used to validate the final model. A total of 116 patients were included in the study, with a mean follow-up of 306 weeks. Weibull hazard function best fitted the data. The hazard of positive symptoms improvement decreased 4% for every one-year increase in age over the median of 41 years (adjusted hazard ratio (aHR), 0.96; 95% confidence intervals (95% CI), (0.93-0.98)). However, patients receiving a second atypical antipsychotic agent had four-folds higher hazard (aHR, 4.01; 95% CI, (1.97-7.17)). The hazard increased 2% (aHR, 1.02; 95% CI, (1.01-1.03)) for every 1 g increase in the clozapine six months cumulative dose over the median of 34 g. The developed model provides essential information on the hazard of positive symptoms improvement after the first clozapine dose administration, including modifiable predictors of high clinical importance.

Anxiety Disorders in Family Caregivers of Breast Cancer Patients Receiving Oncologic Treatment in Malaysia

Background: Anxiety is recognized as a normal psychological reaction of those caring for cancer patients. However, anxiety disorders in caregivers may interfere with their care-giving role and require further clinical attention. Objectives: To determine the prevalence and associated factors of anxiety disorders among caregivers of breast cancer patients receiving oncologic treatment in Kuala Lumpur Hospital. Methodology: A cross-sectional study was conducted on 130 caregiver-patient dyads, recruited by non-random sampling at Kuala Lumpur Hospital. Data were collected in 2 stages: 1) the caregivers were screened for psychological distress using the Depression, Anxiety, Stress, Scale (DASS-21) while other related factors for the patients and their caregivers were obtained; 2) the identified distressed caregivers (n=64) were then administered the Mini International Neuropsychiatric Interview (MINI) to diagnose anxiety disorders. Results: A total of 11.5% (n=15) of the caregivers reported suffering from anxiety disorders. Bivariate analysis found duration of caregiving (OR=3.31; CI=2.21-11.93), shared caregiving (OR=4.07; CI=1.34-12.36), and patients' treatment type (OR=3.42; CI=1.92-12.76) were significantly associated with anxiety disorders (p value <0.05), with shared caregiving and patient's treatment type remaining significant using logistic regression (p value < 0.05, R2 = 0.255). Conclusions: Every one in ten of the caregivers in this study had a diagnosable anxiety disorder, associated with certain care-giving factors and patients' treatment. This should alert clinicians to such risk and indicates psychological support needs for family caregivers.

Clinical depression while caring for loved ones with breast cancer.

INTRODUCTION: The period of the cancer patients undergoing treatment is also the most stressful time for their family caregivers. This study aimed to determine the rates of major depressive disorder and dysthymia; and their associated factors in the caregivers during this time. METHODS: One hundred and thirty caregiver-patient dyads attending the oncology centre for breast cancer treatment participated in this cross-sectional study. While the data on the patients' socio-demographic and illness characteristics were obtained from their medical record, the caregivers completed three self-report measures: 1) socio-demography and the caregiving factor questionnaire, 2) Multi-dimensional Perceived Social Support (MSPSS) and 3) Depression, Anxiety and Stress Scale (DASS-21). Subsequently, those with "probable depression" identified from the DASS-21 score were interviewed using The Mini-International Neuropsychiatric Interview (MINI) to obtain the diagnoses of depressive disorders. RESULTS: Twenty-three of the 130 caregivers (17.69%) were diagnosed to have depressive disorders, where 12.31% (n=16) had major depressive disorder and 5.38% (n=7) had dysthymic disorder. Factors associated with depression include ethnicity, duration of caregiving, the patients' functional status and the caregivers' education level. Logistic regression analysis showed that the patients' functional status (p<0.05, OR=0.23, CI=0.06-0.86) and the caregivers' education level (p<0.05, CI=9.30, CI=1.82-47.57) were significantly associated with depression in the caregivers attending to breast cancer patients on oncology treatment. CONCLUSIONS: A significant proportion of family caregivers were clinically depressed while caring for their loved ones. Depression in this population is a complex interplay between the patients' factors and the caregivers' factors.