Benjamin Spencer

Depression and kidney transplantation.

While kidney transplantation offers several advantages in terms of improved clinical outcomes and quality of life compared to dialysis modalities, depressive symptoms are still present in approximately 25% of patients, rates comparable to that of the hemodialysis population. Correlates of depressive symptoms include marital status, income, kidney function, history of affective illness, malnutrition, and inflammation. Depressive symptoms are also associated with poor outcomes following kidney transplantation including nonadherence to immunosuppressant medication, graft failure, and all-cause mortality. Efforts to detect and treat depression should be a priority if one is to improve treatment adherence, quality of life, and outcomes in transplant recipients.

Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility Trial

BACKGROUND AND OBJECTIVES Depression is common in patients on hemodialysis, but data on the benefits and risks of antidepressants in this setting are limited. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of sertraline over 6 months in patients on hemodialysis with depression to determine study feasibility, safety, and effectiveness. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients on hemodialysis at five United Kingdom renal centers completed the Beck Depression Inventory II. Those scoring ≥16 and not already on treatment for depression were invited to undergo diagnostic interview to confirm major depressive disorder. Eligible patients with major depressive disorder were randomized to receive the study medication-either sertraline or placebo. Outcomes included recruitment and dropout rates, change in the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory II, and qualitative information to guide design of a large-scale trial. RESULTS In total, 709 patients were screened and enrolled between April of 2013 and October of 2014; 231 (32.6%) had Beck Depression Inventory II scores ≥16, and 68 (29%) of these were already receiving treatment for depression. Sixty-three underwent diagnostic interview, 37 were diagnosed with major depressive disorder, and 30 were randomized; 21 completed the trial: eight of 15 on sertraline and 13 of 15 on placebo (P=0.05). Dropouts due to adverse and serious adverse events were greater in the sertraline group. All occurred in the first 3 months. Over 6 months, depression scores improved in both groups. Beck Depression Inventory II score fell from 29.1±8.4 to 17.3±12.4 (P<0.001), and Montgomery-Asberg Depression Rating Scale score fell from 24.5±4.1 to 10.3±5.8 (P<0.001). There were no differences between sertraline and placebo groups. CONCLUSIONS Although small, this is the largest randomized trial to date of antidepressant medication in patients on hemodialysis. Our results highlight recruitment issues. No benefit was observed, but trial size and the substantial dropout render consideration of benefit inconclusive. A definitive trial could use shorter follow-up and include depressed patients already taking antidepressants.

Still Sad after Successful Renal Transplantation: Are We Failing to Recognise Depression? An Audit of Depression Screening in Renal Graft Recipients

Background: Depression is common in chronic physical illness, including renal graft recipients. There is evidence that depression is an independent marker of poorer prognosis in dialysis patients. In the UK, screening is advocated by the National Institute for Health and Clinical Excellence guidelines, and validated screening tools exist, such as the Beck Depression Inventory (BDI). Methods: We audited our renal graft recipient outpatient clinic to see if screening was being undertaken by our clinicians, and to confirm the rates of depressive symptoms in our population as reported by the BDI. Results: In a sample of 58 transplant patients, we found that the screening rate for depression was poor, particularly by nephrologists (n = 8, 13.8%). In addition, 13 (22.4%) of our patients had significant depressive symptoms (BDI score ≧16). Following univariate analysis, we found that the most important predictor of current significant depressive symptoms was a past history of depression. Conclusions: Despite the limitations of our small audit, our results confirm that depression is under-screened in renal graft recipients, even in those with a known history of depression. We recommend increased awareness of depression and implementation of regular screening in an outpatient setting; in this regard, the BDI may have utility.

Systematic review on the prevalence of lack of capacity in medical and psychiatric settings

DMC for treatment (DMC-T) is an important consideration for clinicians working in all clinical settings. The authors set out to synthesise the evidence in this area. However, I have concerns over their methods. The authors treat DMC as a generic ability, rather than one that is by definition specific to the decision in hand as per the Mental Capacity Act 2005, as they have included studies assessing DMC for research (DMC-R) along with those assessing DMC-T in their meta-analysis. Decisions around treatment versus participation in research on treatment involve different considerations. Research decisions can be particularly complex due to the need to appreciate that the primary purpose of the research is not to guide individual care (the ‘therapeutic misconception’) 2 among other non-treatment related issues. DMC-T is not synonymous with DMC-R and should be analysed and presented separately. Studies on DMC are highly nuanced by the specific population studied and the specific decision for which DMC is being assessed. They are particularly vulnerable to selection bias given that clinical factors that may impact on recruitment into a research study (ie severity of illness) can be expected to affect DMC. This includes the potential ‘catch 22’ of research participants being required to have DMC-R in order to consent to a study on DMC. 3 The authors perform a sub-analysis to take into account clinical setting (inpatients/outpatients); however, they also need to consider these factors among others, such as diagnosis, separately. Their meta-analyses included all studies non-discriminately ignoring the heterogeneity and inherent biases within, rather than being grouped by the factors above and crucially the specific decision for which DMC is being assessed. Therefore I do not understand what their summary data and analysis represents other than a reflection of the complexity and heterogeneity of studies in this field. ■

Opening Pandora’s box in the UK: a hypothetical pharmacogenetic test for clozapine

Clozapine is a uniquely efficacious antipsychotic drug in treatment-resistant schizophrenia. Its use is restricted due to adverse effects including a rare but dangerous reduction in neutrophils (agranulocytosis) and the mandatory hematological monitoring this entails in many countries. We review the statistical, ethical and legal issues arising from a hypothetical pharmacogenetic test for clozapine, using the UK as an exemplary case for consideration. Our key findings include: a consideration of the probabilistic results that a pharmacogenetic test may return; the impact on drug licensing; and the potential for pharmacogenetic tests for clozapine being used without consent under the UKs legal framework. We make recommendations regarding regulatory changes applicable to the special case of pharmacogenetic testing in clozapine treatment.

Unwell in hospital but not incapable: cross- sectional study on the dissociation of decision- making capacity for treatment and research in in-patients with schizophrenia and related psychoses.

Background Consent to research with decision-making capacity for research (DMC-R) is normally a requirement for study participation. Although the symptoms of schizophrenia and related psychoses are known to affect decision-making capacity for treatment (DMC-T), we know little about their effect on DMC-R. Aims We aimed to determine if DMC-R differs from DMC-T in proportion and associated symptoms in an in-patient sample of people with schizophrenia and related psychoses. Method Cross-sectional study of psychiatric in-patients admitted for assessment and/or treatment of schizophrenia and related psychoses. We measured DMC-R and DMC-T using ‘expert judgement’ clinical assessment guided by the MacArthur Competence Assessment Tool for Clinical Research, the MacArthur Competence Assessment Tool for Treatment and the legal framework of the Mental Capacity Act (2005), in addition to symptoms of psychosis. Results There were 84 participants in the study. Half the participants had DMC-R (51%, 95% CI 40–62%) and a third had DMC-T (31%, 95% CI 21–43%) and this difference was statistically significant (P < 0.01). Thought disorder was most associated with lacking DMC-R (odds ratio 5.72, 95% CI 2.01–16.31, P = 0.001), whereas lack of insight was most associated with lacking DMC-T (odds ratio 26.34, 95% CI 3.60–192.66, P = 0.001). With the exception of improved education status and better DMC-R, there was no effect of sociodemographic variables on either DMC-R or DMC-T. Conclusions We have shown that even when severely unwell, people with schizophrenia and related psychoses in in-patient settings commonly retain DMC-R despite lacking DMC-T. Furthermore, different symptoms have different effects on decision-making abilities for different decisions. We should not view in-patient psychiatric settings as a research ‘no-go area’ and, where appropriate, should recruit in these settings. Declaration of interest None.

Diversity or disarray? A systematic review of decision-making capacity for treatment and research in schizophrenia and other non-affective psychoses.

BACKGROUND Valid consent for treatment or research participation requires that an individual has decision-making capacity (DMC), which is the ability to make a specific decision. There is evidence that the psychopathology of schizophrenia can compromise DMC. The objective of this review was to examine the presence or absence of DMC in schizophrenia and the socio-demographic/psychopathological factors associated. METHODS We searched three databases Embase, Ovid MEDLINE(R), and PsycINFO for studies reporting data on the proportion of DMC for treatment and research (DMC-T and DMC-R), and/or socio-demographic/psychopathological associations with ability to make such decisions, in people with schizophrenia and related illnesses. RESULTS A total of 40 studies were identified. While high levels of heterogeneity limited direct comparison, meta-analysis of inpatient data showed that DMC-T was present in 48% of people. Insight was strongly associated with DMC-T. Neurocognitive deficits were strongly associated with lack of DMC-R and to a lesser extent DMC-T. With the exception of years of education, there was no evidence for an association with socio-demographic factors. CONCLUSIONS Insight and neurocognitive deficits are most closely associated with DMC in schizophrenia. The lack of an association with socio-demographic factors dispels common misperceptions regarding DMC and characteristics such as age. Although our results reveal a wide spectrum of DMC-T and DMC-R in schizophrenia, this could be partly due to the complexity of the DMC construct and the heterogeneity of existing studies. To facilitate systematic review research, there is a need for improvement within research study design and increased consistency of concepts and tools.

Postdialysis recovery time is extended in patients with greater self-reported depression screening questionnaire scores

Introduction: Most patients take time to recover after a hemodialysis (HD) session. It has been suggested that recovery time is associated with intradialytic hypotension and rapid solute clearances. Other studies have reported a linkage to depression. We investigated the association between recovery time and intradialytic hypotension and depression.

Capacity in vacuo: an audit of decision-making capacity assessments in a liaison psychiatry service

Aims and method We aimed to audit the documentation of decision-making capacity (DMC) assessments by our liaison psychiatry service against the legal criteria set out in the Mental Capacity Act 2005. We audited 3 months split over a 2-year period occurring before, during and after an educational intervention to staff. Results There were 21 assessments of DMC in month 1 (6.9% of all referrals), 27 (9.7%) in month 16, and 24 (6.6%) in month 21. Only during the intervention (month 16) did any meet our gold-standard (n = 2). Severity of consequences of the decision (odds ratio (OR) 24.4) and not agreeing to the intervention (OR = 21.8) were highly likely to result in lacking DMC. Clinical implications Our audit demonstrated that DMC assessments were infrequent and poorly documented, with no effect of our legally focused educational intervention demonstrated. Our findings of factors associated with the outcome of the assessment of DMC confirm the anecdotal beliefs in this area. Clinicians and service leads need to carefully consider how to make the legal model of DMC more meaningful to clinicians when striving to improve documentation of DMC assessments.