Schizophrenia, psychotropic medication, and cataract

OBJECTIVE: To compare the distribution of cataract types between psychiatric patients diagnosed with schizophrenia and the general population not exposed to psychotropic medication, and to compare cataract prevalence between users and nonusers of various psychotropic medications in the general community. DESIGN: Case-control. PARTICIPANTS: A total of 151 (93%) eligible patients from a community mental health service and 3271 (83%) eligible residents from the Melbourne Visual Impairment Project (VIP) were examined. MAIN OUTCOME MEASURES: All patients 40 years of age and older from a community mental health service and residents of nine randomly selected areas of Melbourne were eligible. Best-corrected distance visual acuity was determined using a 4-m logarithm of the minimum angle of resolution (LogMAR) chart. The presence of cataract was determined by photographs or slit-lamp examination using direct and indirect retroillumination. Anterior, cortical, nuclear, and posterior subcapsular cataracts were measured. Participants from the Melbourne VIP were classified as to whether they had taken benzodiazepams, phenothiazines, thioxanthenes, butyrophenols, tricyclic antidepressants, or monoamine oxidase inhibitors for at least 12 months during their lifetime. RESULTS: The distribution of cataract type varied between persons with and without schizophrenia. Anterior subcapsular (ASC) cataract was significantly more prevalent (26%) in participants with schizophrenia from the community mental health service than Melbourne VIP participants (0.2%) not exposed to psychotropic medication (chi-square, 1 degree of freedom = 605.5, P = 0.001). This remained significant after controlling for age (odds ratios = 250, 95% confidence interval = 83.3, 1000). The distribution of the age-related cataract was similar across all groups of psychotropic medication users with the exception of the phenothiazine users. They had less of all types of the age-related cataracts, despite being slightly older than the control group (mean age, 60.0 vs. 58.4, t test = 0.85, P = 0.40). However, only cortical cataract in the phenothiazine group was statistically lower (chi-square, 1 degree of freedom = 3.96, P = 0.047). CONCLUSION: This study has identified the need to investigate whether other newer agents, especially high-potency medications, cause ASC opacities if a certain threshold of exposure to psychotropic medications must be attained to develop cataract, or if schizophrenia itself is associated with cataract formation.

Prescription and over-the-counter pain medication in arthritis: awareness of active ingredients and attitudes to medication borrowing and sharing

Background:
Many Australians with arthritis self-manage their pain with prescription and/or over-the-counter pain medications, containing paracetamol. If taken appropriately, these medications are relatively safe; however, if mismanaged through patients' iinability to understand medication labels and instructions, these medications may cause adverse drug events and/or toxicities.
Aim:
This study explored the prescription and over-the-counter pain medications most commonly used by people with arthritis and the ability of these patients to correctly identify paracetamol as an active ingredient in commonly available preparations. The study also investigated the functional health literacy of these patients and their inclination to borrow and/or share pain medications.
Method:
Adult participants diagnosed with arthritis were invited to complete an anonymous survey which included questions about their prescription and over-the-counter pain medications; their medication borrowing and sharing behaviours; their functional health literacy; and their knowledge about preparations containing paracetamol as an active ingredient.
Results:
Most of the 254 participants used analgesic agents containing paracetamol, as combination tablets (paracetamol 500 mg and codeine 30 mg) or paracetamol-only tablets (paracetamol 665 mg) to self-manage their pain. Respondents with low functional health literacy scores were significantly less likely to identify paracetamol as an active ingredient in both combination and paracetamol-only pharmaceutical products, and were more likely to guess or did not know how to identify that paracetamol was an active ingredient in these products. Almost 30% of the respondents indicated that they had and/or intended to borrow/share their over-the-counter
pain medications whereas less than 10% suggested that they had and/or intended to borrow/share their prescription pain medication.
Conclusion:
Australians with arthritis, especially those with low functional health literacy scores, self-managing their pain with paracetamol-containing products, do not always recognise paracetamol as an active ingredient in combination products, and may risk potential paracetamol-related adverse effects and/or toxicities.

Explaining psychological insulin resistance in adults with non-insulin-treated type 2 diabetes: the roles of diabetes distress and current medication concerns. Results from diabetes MILES-Australia.

AIMS: To investigate the contribution of general and diabetes-specific emotional wellbeing and beliefs about medicines in the prediction of insulin therapy appraisals in adults with non-insulin-treated type 2 diabetes. METHODS: The sample included Diabetes MILES-Australia cross-sectional survey participants whose primary diabetes treatment was oral hypoglycaemic agents (N=313; 49% women; mean±SD age: 57±9 years; diabetes duration: 7±6 years). They completed validated measures of beliefs about the 'harm' and 'overuse' of medications in general (BMQ General); 'concerns' about and 'necessity' of current diabetes medications (BMQ Specific); negative insulin therapy appraisals (ITAS); depression (PHQ-9); anxiety (GAD-7), and diabetes distress (DDS-17). Factors associated with ITAS Negative scores were examined using hierarchical multiple regressions. RESULTS: Twenty-two percent of the variance in ITAS Negative scores (52±10), was explained by: number of complications (β=-.15, p=.005), DDS-17 subscale 'emotional burden' (β=.23, p<.001), and 'concerns' about current diabetes treatment (β=.29, p<.001). General beliefs about medications and general emotional wellbeing did not contribute significantly to the model. CONCLUSIONS: Psychological insulin resistance may reflect broader distress about diabetes and concerns about its treatment but not general beliefs about medicines, depression or anxiety. Reducing diabetes distress and current treatment concerns may improve attitudes towards insulin as a potential therapeutic option.

Antidepressant actions of lateral habenula deep brain stimulation differentially correlate with CaMKII/GSK3/AMPK signaling locally and in the infralimbic cortex

High frequency deep brain stimulation (DBS) of the lateral habenula (LHb) reduces symptoms of depression in severely treatment-resistant individuals. Despite the observed therapeutic effects, the molecular underpinnings of DBS are poorly understood. This study investigated the efficacy of high frequency LHb DBS (130Hz; 200μA; 90μs) in an animal model of tricyclic antidepressant resistance. Further, we reported DBS mediated changes in Ca(2+)/calmodulin-dependent protein kinase (CaMKIIα/β), glycogen synthase kinase 3 (GSK3α/β) and AMP-activated protein kinase (AMPK) both locally and in the infralimbic cortex (IL). Protein expressions were then correlated to immobility time during the forced swim test (FST). Antidepressant actions were quantified via FST. Treatment groups comprised of animals treated with adrenocorticotropic hormone alone (ACTH; 100μg/day, 14days, n=7), ACTH with active DBS (n=7), sham DBS (n=8), surgery only (n=8) or control (n=8). Active DBS significantly reduced immobility in ACTH-treated animals (p<0.05). For this group, western blot results demonstrated phosphorylation status of LHb CaMKIIα/β and GSK3α/β significantly correlated to immobility time in the FST. Concurrently, we observed phosphorylation status of CaMKIIα/β, GSK3α/β, and AMPK in the IL to be negatively correlated with antidepressant actions of DBS. These findings suggest that activity dependent phosphorylation of CaMKIIα/β, and GSK3α/β in the LHb together with the downregulation of CaMKIIα/β, GSK3α/β, and AMPK in the IL, contribute to the antidepressant actions of DBS.

Anxiety, depression and fatigue at 5-year review following CNS demyelination

BACKGROUND: Anxiety and depression are common in multiple sclerosis (MS). We evaluated the prevalence and factors associated with anxiety, depression and fatigue at the 5-year review of a longitudinal cohort study following a first clinical diagnosis of CNS demyelination (FCD).

METHODS: Cases with a FCD were recruited soon after diagnosis and followed annually thereafter. A variety of environmental, behavioural and clinical covariates were measured at five-year review. Anxiety and depression were measured using the Hospital Anxiety & Depression Scale (HADS), and fatigue by the Fatigue Severity Scale (FSS).

RESULTS: Of the 236 cases, 40.2% had clinical anxiety (median HADS-A: 6.0), 16.0% had clinical depression (median HADS-D: 3.0), and 41.3% had clinical fatigue (median FSS: 4.56). The co-occurrence of all three symptoms was 3.76 times greater than expectation. Younger age, higher disability, concussion or other disease diagnosis were independently associated with a higher anxiety score; male sex, higher disability, being unemployed, less physical activity, and antidepressant and/or anxiolytic-sedative medication use were independently associated with a higher depression score. Higher disability, immunomodulatory medication use, other disease diagnosis and anxiolytic-sedative medication use were independently associated with having fatigue, while female sex, higher BMI, having had a concussion, being unemployed and higher disability were associated with a higher fatigue score.

CONCLUSION: These results support previous findings of the commonality of anxiety, depression and fatigue in established MS and extend this to post-FCD and early MS cases. The clustering of the three symptoms indicates that they may share common antecedents.

Quality of life in outpatients with depression in China

BACKGROUND: Quality of life (QOL) is an important outcome measure for patients with depression, but QOL research involving large samples of patients has been uncommon. The purpose of this study was to evaluate the QOL of Chinese outpatients with depression and its determinants. METHODS: Using a cross-sectional survey design, data were collected continuously from 19,984 outpatients; 19,950 usable questionnaires were obtained. Along with the QOL index (WHOQOL-BREF), the questionnaire also included participants' sociodemographic characteristics, outpatient visits, and medication use information. RESULTS: Less than 5% of depressed patients reported "good" or "very good" QOL, while less than 3% were satisfied with their general health. The overall score was low (54.12); four QOL domain (physical health, psychological, social relationships, and environment) scores (range, 35.03-40.10) were significantly lower than in other community population surveys. QOL scores were significantly lower among first-visit than non-first-visit patients. Medication users reported significantly higher QOL scores than non-users, with NaSSA more effective than SSRIs, followed by other types, SNRIs, and no medication, in that order. LIMITATIONS: Since this was an observational, cross-sectional survey with continuous outpatient data collection method instead of random sampling, generalization of the results is limited, and causality cannot be determined. However, the "natural" observational design, large sample size, and similarity in findings with other studies reveal the "real world" QOL of depressed outpatients in mainland China. CONCLUSIONS: Depressed patients had a low QOL, and the scores of first-visit patients with severe symptoms were significantly lower than non-first-visit patients. Though medication can improve patients' QOL, different types of medications have different impacts.

Stress, dopamine, inflammation and energy regulation: Examining the nature of antidepressant-resistance and response

This thesis investigated the nature of treatment-resistant depression and novel antidepressants utilizing a preclinical model of antidepressant-resistance. Chronic disruption of the stress response impaired response to antidepressants and altered dopamine signaling in this model. Inflammatory profile and energy regulation were identified as potential biomarkers for response to ketamine and lithium.

Antidepressant mechanisms of deep brain stimulation for treatment resistant depression

Deep brain stimulation to clinically relevant brain targets all produced therapeutic responses in an animal model of antidepressant resistance. Such effects were achieved by modulating cellular stress, impaired synaptic plasticity, dysregulated dopamine transmission and energy metabolism. The implication of these findings underscore the need for using appropriate animal models to gain valuable insight on the neurobiological state of the organism in health and disease.

Stressors and coping resources of Australian kidney transplant recipients related to medication taking: a qualitative study

AIM: To understand the stressors related to life post-kidney transplantation, with a focus on medication adherence, and the coping resources people use to deal with these stressors. BACKGROUND: Although kidney transplantation offers enhanced quality and years of life for patients, the management of a kidney transplant post-surgery is a complex process. DESIGN: A descriptive exploratory study. METHOD: Participants were recruited from five kidney transplant units in Victoria, Australia. From March to May 2014, patients who had either maintained their kidney transplant for ≥ 8 months or had experienced a kidney graft loss due to medication non-adherence were interviewed. All audio-recordings of interviews were transcribed verbatim and underwent Ritchie and Spencer's framework analysis. RESULTS: Participants consisted of fifteen men and ten women aged 26 - 72 years old. All identified themes were categorised into: 1) Causes of distress and 2) Coping resources. Post-kidney transplantation, causes of distress included the regimented routine necessary for graft maintenance, and the everlasting fear of potential graft rejection, contracting infections and developing cancer. Coping resources utilised to manage the stressors were firstly, a shift in perspective about how easy it was to manage a kidney transplant than to be dialysis-dependent and secondly, receiving external help from fellow patients, family members and healthcare professionals in addition to utilising electronic reminders. CONCLUSION: An individual well-equipped with coping resources is able to deal with stressors better. It is recommended that changes, such as providing regular reminders about the lifestyle benefits of kidney transplantation, creating opportunities for patients to share their experiences and promoting the utilisation of a reminder alarm to take medications, will reduce the stress of managing a kidney transplant.

Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects

Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg(-1)) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P<0.05). NAc DBS effectively improved FST mobility in ACTH-treated animals (P<0.05). No improvement in mobility was observed for sham control animals (P>0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation.

Comparison of medication policies to guide nursing practice across seven Victorian health services

Objectives The objective of this paper is to review and compare the content of medication management policies across seven Australian health services located in the state of Victoria. Methods The medication management policies for health professionals involved in administering medications were obtained from seven health services under one jurisdiction. Analysis focused on policy content, including the health service requirements and regulations governing practice. Results and Conclusions The policies of the seven health services contained standard information about staff authorisation, controlled medications and poisons, labelling injections and infusions, patient self-administration, documentation and managing medication errors. However, policy related to individual health professional responsibilities, single- and double-checking medications, telephone orders and expected staff competencies varied across the seven health services. Some inconsistencies in health professionals' responsibilities among medication management policies were identified. What is known about the topic? Medication errors are recognised as the single most preventable cause of patient harm in hospitals and occur most frequently during administration. Medication management is a complex process involving several management and treatment decisions. Policies are developed to assist health professionals to safely manage medications and standardise practice; however, co-occurring activities and interruptions increase the risk of medication errors. What does this paper add? In the present policy analysis, we identified some variation in the content of medication management policies across seven Victorian health services. Policies varied in relation to medications that require single- and double-checking, as well as by whom, nurse-initiated medications, administration rights, telephone orders and competencies required to check medications. What are the implications for practitioners? Variation in medication management policies across organisations is highlighted and raises concerns regarding consistency in governance and practice related to medication management. Lack of practice standardisation has previously been implicated in medication errors. Lack of intrajurisdictional concordance should be addressed to increase consistency. Inconsistency in expectations between healthcare services may lead to confusion about expectations among health professionals moving from one healthcare service to another, and possibly lead to increased risk of medication errors.

Covert dose reduction is a distinct type of medication non-adherence observed across all care settings in inflammatory bowel disease.

BACKGROUND: Non-adherence by dose omission is common and deleterious to outcomes in Inflammatory Bowel Disease (IBD), but covert dose reduction (CDR) remains unexplored. AIMS: To determine frequency and attitudinal predictors of overall medication non-adherence and of covert dose reduction as separate entities. METHODS: A cross sectional questionnaire was undertaken involving IBD patients in three different geographical regions and care settings. Demographics, medication adherence by dose omission, and rate of patient initiated dose reduction of conventional meds without practitioner knowledge (CDR) were assessed, along with attitudes toward IBD medication. RESULTS: Of 473 respondents (mean age 50.3 years, 60.2% female) frequency of non-adherence was 21.9%, and CDR 26.9% (p<0.001). By logistic regression, significant independent predictors of non-adherence were dissatisfaction with the patient-doctor relationship (p<0.001), depression (p=0.001), anxiety (p=0.047), and negative views regarding medication efficacy (p<0.001) or safety (p=0.017). Independent predictors of covert dose reduction included regular complementary medicine (CAM) use (p<0.001), experiencing more informative (p<0.001) and comfortable (p=0.006) consultations with alternative practitioners, disbelieving doctor delivered information (p=0.021) and safety concerns regarding conventional medication (p<0.001). Neither the frequency of non-adherence (p=0.569) nor CDR (p=0.914) differed between cohorts by different treatment settings. CONCLUSIONS: Covert dose reduction of IBD medication is more common than omission of medication doses, predicted by different factors to usual non-adherence, and has not been previously reported in IBD. The strongest predictor of CDR is regular CAM use.