Side effects of clozapine in older adults with treatment-resistant schizophrenia compared to younger adults.

OBJECTIVES: To study the differences in side effects of clozapine between older adults aged ≥55 years and younger adults aged 18-55 years with treatment-resistant schizophrenia. METHODS: A retrospective cohort study in a large mental health institute in the Netherlands. All patients diagnosed with treatment-resistant schizophrenia who started with clozapine between 2011 and 2020 (N = 284) were included. We compared the number and type of side effects reported in the electronic patient files as well as the number of treatment discontinuations and the time until discontinuation, both due to side effects, of older adults versus younger adults. RESULTS: In the younger age group (N = 183), the number of reported side effects was significantly higher in the first 3 months of treatment (Mann-Whitney U = 7341.5, p = 0.004) and after those 3 months (Mann-Whitney U = 5668.5, p < 0.001) compared with the number reported in the older age group (N = 101). Sedation, hypersalivation, dizziness, tachycardia, heartburn, nausea, weight gain, and constipation were reported significantly more often in the younger age group, and only extrapyramidal symptoms were reported significantly more often in the older age group. There was no significant difference in the number of treatment discontinuations due to side effects (23% vs. 21.8%, Chi-2 = 0.051, df = 1, p = 0.821) and time until discontinuation due to side effects (b = 0.091, SE = 0.335, p = 0.798) between younger and older adults. CONCLUSIONS: Side effects of clozapine were reported significantly less often in older patients compared with younger patients. Older patients did not discontinue treatment due to side effects more often or earlier than younger patients. Older patients with schizophrenia may not be more vulnerable to side effects than younger adults.

The impact of personality traits on the course of frailty.

OBJECTIVES: Determinants of frailty are generally explored within context of somatic healthcare and/or lifestyle characteristics. To examine the impact of personality traits on change in frailty and the potential role of depression. METHODS: A 2-year follow-up study including 285 patients with a depressive disorder and 116 never-depressed controls. Multiple linear regression analyses were conducted to regress the Big Five personality traits (independent variables) on different frailty measures (dependent variables), including the Frailty Index, Frailty phenotype, gait speed, and handgrip strength. Analyses were adjusted for confounders (with and without depressive disorder) and baseline frailty severity. Interactions between personality traits and depressive disorder were examined. RESULTS: All personality traits were associated with change in at least one frailty marker over time. Over time, a higher level of neuroticism was associated with an accelerated increase of frailty, whereas a higher level of extraversion, agreeableness, conscientiousness and openness were associated with an attenuated increase of frailty. None of the associations were moderated by depression. Additional adjustment for depression decreased the strength of the association of neuroticism, extraversion and conscientiousness with frailty. CONCLUSIONS: Personality traits have impact on frailty trajectories in later life. CLINICAL IMPLICATIONS: Underlying pathways and potential modification by psychotherapy merit further study.

Psychotropic drug treatment for agitated behaviour in dementia: what if the guideline prescribing recommendations are not sufficient? A qualitative study.

BACKGROUND: Agitation is a common challenging behaviour in dementia with a negative influence on patient's quality of life and a high caregiver burden. Treatment is often difficult. Current guidelines recommend restrictive use of psychotropic drug treatment, but guideline recommendations do not always suffice. OBJECTIVE: To explore how physicians decide on psychotropic drug treatment for agitated behaviour in dementia when the guideline prescribing recommendations are not sufficient. METHODS: We conducted five online focus groups with a total of 22 elderly care physicians, five geriatricians and four old-age psychiatrists, in The Netherlands. The focus groups were thematically analysed. RESULTS: We identified five main themes. Transcending these themes, in each of the focus groups physicians stated that there is 'not one size that fits all'. The five themes reflect physicians' considerations when deciding on psychotropic drug treatment outside the guideline prescribing recommendations for agitated behaviour in dementia: (1) 'reanalysis of problem and cause', (2) 'hypothesis of underlying cause and treatment goal', (3) 'considerations regarding drug choice', (4) 'trial and error' and (5) 'last resort: sedation'. CONCLUSION: When guideline prescribing recommendations do not suffice, physicians start with reanalysing potential underlying causes. They try to substantiate and justify medication choices as best as they can with a hypothesis of underlying causes or treatment goal, using other guidelines, and applying personalised psychotropic drug treatment.

Rivastigmine for ECT-induced cognitive adverse effects in late life depression (RECALL study): A multicenter, randomized, double blind, placebo-controlled, cross-over trial in patients with depression aged 55 years or older: Rationale, objectives and methods.

Background: Cognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confusion and delirious states are especially troublesome for patients, relatives and clinicians. In particular inter-ictal delirium-like states are worrisome, since they may lead to premature treatment discontinuation. Besides a need for further insight into determinants of cognitive side-effects of ECT, there is a great need for treatment options. Methods and design: The Rivastigmine for ECT-induced Cognitive Adverse effects in Late Life depression (RECALL) study combines a multicenter, prospective cohort study on older patients with depression, treated with ECT, with an embedded randomized, placebo-controlled cross-over trial to examine the effect of rivastigmine on inter-ictal delirium. Patients are recruited in four centers across the Netherlands and Belgium. We aim to include 150 patients into the cohort study, in order to be able to subsequently include 30 patients into the trial. Patients are included in the trial when inter-ictal delirium, assessed by the Confusion Assessment method (CAM), or a drop in Mini Mental State Examination (MMSE) score of ≥4 during ECT, develops. In the cohort study, comprehensive measurements of ECT-related cognitive side-effects-and their putative determinants-are done at baseline and during the ECT-course. The primary outcome of the clinical trial is the effectiveness of rivastigmine on inter-ictal delirium-severity, assessed with a change in the Delirium Rating Scale-Revised-98. Secondary outcomes of the clinical trial are several ECT-characteristics and side-effects of rivastigmine. Discussion: This study is the first clinical trial with a focus on ECT-induced, inter-ictal delirium. The cohort provides the basis for recruitment of patients for the cross-over trial and additionally provides an excellent opportunity to unravel cognitive side-effects of ECT and identify putative determinants. This paper describes the rationale and study protocol. Clinical trial registration: EudraCT 2014-003385-24.

Direct and Indirect Exposure to Trauma, Posttraumatic Stress Disorder Symptoms, and Poor Subjective Sleep Quality in Patients with Substance Use Disorder.

Background: Despite the frequent co-occurrence of posttraumatic stress disorder and substance use disorder, screening for trauma exposure and posttraumatic stress disorder symptoms is not a routine practice in substance use disorder clinics. The aims of this study were to examine the prevalence of exposure to traumatic events, posttraumatic stress disorder symptoms, and subjective sleep quality in substance use disorder inpatients after detoxification. In addition, we analyzed associations of sociodemographics, direct and indirect exposure to traumatic events, and sleep quality with posttraumatic stress disorder symptom severity. Methods: Adults diagnosed with substance use disorder (n = 188; 25% women, mean age 46.6 ± 12.3 years) from 2 inpatient addiction clinics were assessed at approximately 4 days post-admission for age, gender, educational level, self-reported substance use, trauma exposure, general and posttraumatic stress disorder-specific subjective sleep quality, and posttraumatic stress disorder symptom severity. Correlates of posttraumatic stress disorder symptom severity were identified with linear regression analyses. Results: The prevalence of direct trauma exposure was high (89%), 51% of participants screened positive for posttraumatic stress disorder and 87% reported clinically significant poor sleep quality. Younger age, female gender, direct and indirect exposure to more traumatic events, and poor subjective sleep quality were associated with more severe posttraumatic stress disorder symptoms. Conclusion: Nearly all substance use disorder patients admitted for detoxification in our study had been directly or indirectly exposed to 1 or more traumatic events, and many reported posttraumatic stress disorder symptoms and poor sleep quality. Younger and female substance use disorder patients were at higher risk of posttraumatic stress disorder symptoms. Our results emphasize the need for systematic screening for direct and indirect trauma exposure, posttraumatic stress disorder symptoms, and poor sleep quality in patients admitted for clinical substance use disorder treatment.

[Reducing depressive symptoms in patients with dementia]. / Depressieve klachten bij dementie.

This comment is a reflection on the article 'Comparative efficacy of interventions for reducing symptoms of depression in people with dementia: systematic review and network meta-analysis' of Jennifer Watt et al. (BMJ 2021;372:n532). Although 256 RCTs were included, only 10 interventions were more effective than treatment as usual for the treatment of depressive symptoms in persons with dementia. Effective interventions were almost all psychosocial treatments, only acetylcholinesterase inhibitors in combination with cognitive stimulation was more effective than treatment as usual. Only 22 RCTs were aimed at patients with a depressive disorder and no NMA was possible, also because of the heterogeneity between these studies. The authors did not present data about some important transivity assumptions, as for example antidepressant dose, treatment duration or depression severity. The NMA did result in evidence suggesting which psychosocial interventions may be the best choice in dementia patients with depressive symptoms. Conflict of interest and financial support: none declared.

Tolerability of lithium: A naturalistic discontinuation study in older inpatients (≥60 years).

OBJECTIVES: Lithium is one of the most effective treatment options in both bipolar disorder and treatment-resistant depression. The use of lithium in older patients declined during the last decades, probably resulting in undertreatment of older patients. To investigate how well lithium is tolerated in old age, we aimed to determine the frequency, reasons, and possible predictors of discontinuation due to adverse effects in a cohort of inpatients ≥60 years who had started with lithium. METHODS: We performed a retrospective cohort study based on chart reviews. Participants were in treatment at Parnassia Group at The Hague, The Netherlands. After inclusion (between January 2010 and December 2016), participants were followed until April 2017, when we performed data extraction and analysis. RESULTS: In our sample of 135 patients (median age 69 years, median follow-up duration 18 months), 49 (36.3%) participants discontinued lithium. Only a minority (11 [8.1%]) of the participants discontinued solely due to adverse effects. The majority discontinued lithium due to psychiatric (18, 5%) reasons (most commonly mentioned within this subgroup: lack of effectiveness and noncompliance) or a combination of reasons (7.4%). None of the factors we studied (age, gender, Charlson Comorbidity Index, polypharmacy, renal function, and neurological history) were significantly associated with discontinuation due to adverse effects. CONCLUSIONS: The frequency of lithium discontinuation in our cohort was in range with frequencies reported in younger patients. Older age itself should not be a reason to withhold lithium treatment.

Predicting rehospitalisation in older inpatients with a psychotic disorder.

OBJECTIVE: The objective of this study was to predict rehospitalisation in a psychiatric clinic in older inpatients with a psychotic disorder. METHODS/DESIGN: In this prospective, observational study, all eligible inpatients aged 55 years and over with a primary psychotic disorder, admitted to a specialised ward for older psychotic patients in a large psychiatric inpatient clinic in the Netherlands, were asked to participate. Whether or not patients were rehospitalised and time to rehospitalisation were assessed 1 year after discharge from the ward. We recorded age, gender, living arrangement, psychiatric diagnosis, severity of psychotic symptoms, duration of index episode, age of onset of psychotic disorder, number of previous admissions, involuntary admission and use of depot medication at discharge. All patients underwent a neuropsychological assessment. RESULTS: Of the 90 patients that were included, 32 (35.6%) had been readmitted within 1 year after discharge. None of the demographic or clinical variables predicted rehospitalisation or the time to rehospitalisation. CONCLUSION: Factors that predict rehospitalisationin younger adult patients with schizophrenia may not predict rehospitalisationin older patients with a psychotic disorder, of which the majority suffered from schizophrenia. We expect that other factors than those investigated may be of greater importance to predict rehospitalisation, as for example social support and coping mechanisms.

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine: A Pragmatic Randomized Controlled Trial (CYSCE Trial).

PURPOSE/BACKGROUND: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine. METHODS/PROCEDURES: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks. FINDINGS/RESULTS: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087). IMPLICATIONS/CONCLUSIONS: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression.

Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia.

Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10-5 and c.2702T > G [p.V901G], MAF 2.51 × 10-3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05-13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10-8), viability (P = 8.9 × 10-7), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10-4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10-5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia.

Leucocyte telomere length is no molecular marker of physical frailty in late-life depression.

BACKGROUND: Although average life-expectancy is still increasing worldwide, ageing processes markedly differ between individuals, which has stimulated the search for biomarkers of biological ageing. OBJECTIVES: Firstly, to explore the cross-sectional and longitudinal association between leucocyte telomere length (LTL) as molecular marker of ageing and the physical frailty phenotype (PFP) as a clinical marker of ageing and secondly, to examine whether these associations are moderated by the presence of a depressive disorder, as depression can be considered a condition of accelerated ageing. METHODS: Among 378 depressed older patients (according to DSM-IV criteria) and 132 non-depressed older persons participating in the Netherlands Study of Depression in Older persons, we have assessed the physical frailty phenotype and LTL. The PFP was defined according to Fried's criteria and its components were reassessed at two-year follow-up. RESULTS: LTL was neither associated with the PFP at baseline by Spearman rank correlation tests, nor did it predict change in frailty parameters over a two-year follow-up using regression analyses adjusted for potential confounders. CONCLUSION: LTL is not associated with frailty; neither in non-depressed nor in depressed older persons. As LTL and physical frailty appear to represent different aspects of ageing, they may complement each other in future studies.

Associations between age and the course of major depressive disorder: a 2-year longitudinal cohort study.

BACKGROUND: Although there is some evidence that older people might have a poorer course of major depressive disorder (MDD) than younger or middle-aged people, and that age-related course differences might affect the optimisation of MDD treatment, large-scale studies with a broad age range, including consistent course assessments, are needed to properly address this issue. Therefore, we aimed to longitudinally examine whether older age was associated with a poorer naturalistic course trajectory of MDD than that of younger ages and to establish which prognostic-clinical, social, and health-factors could explain this potentially poorer course. METHODS: For this longitudinal cohort study, we used baseline and 2-year follow-up data from the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Study of Depression in Older Persons (NESDO) cohorts. People aged between 18 and 88 years, with an MDD diagnosis at baseline, and a valid clinical assessment at 2-year follow-up were included. The primary outcome was the 2-year course of MDD, which was assessed by use of four indicators: having a depression diagnosis (MDD or dysthymia) after 2 years, having a chronic symptom course (depressive symptoms present during 80% or more of the 2-year follow-up period), time to remission, and depression severity change. We used multivariate analyses to examine associations between continuous age and these MDD course indicators. We also examined whether prognostic clinical (eg, comorbid anxiety), social (loneliness and social support), and health (body-mass index, pain, and chronic diseases) factors contributed to the differences in the course of MDD between age groups. FINDINGS: Between 2004-2012, baseline and 2-year follow-up data were obtained for 1042 participants from the NESDA and NESDO cohorts, of whom 690 (66%) were women. Older age was significantly associated with a worse 2-year MDD course for all four indicators (MDD diagnosis: odds ratio [OR] 1·08, 95% CI 1·00-1·17; chronic symptom course: OR 1·24, 1·13-1·35; time to remission: hazard ratio [HR] 0·91, 0·87-0·96; and depression severity change: regression coefficient 1·06, p<0·0001; all per 10-year increase). The course of MDD worsened linearly with age, and people aged 70 years or older had the worst outcomes compared with those of the reference group of people aged 18-29 years (MDD diagnosis: OR 2·02, 95% CI 1·18-3·45; chronic symptom course: OR 3·19, 1·74-5·84; time to remission: HR 0·60, 0·44-0·83; and depression severity change: -12·64 [SD 10·85] in those aged 18-29 years and -5·57 [11·14] in those aged 70 years or older). These results were slightly reduced, but remained mostly significant when adjusting for prognostic clinical, social, and health factors. INTERPRETATION: Older age was found to be a consistent and important risk factor for a poorer MDD course, which could not be explained by a range of well established risk factors. Further investigation of potential underlying mechanisms-including the effect of cognitive impairment, for example-is needed to prevent the negative consequences of a long-term MDD burden in older people. FUNDING: Netherlands Organisation for Health Research and Development, Fonds NutsOhra, Stichting tot Steun VCVGZ, NARSAD The Brain and Behaviour Research Fund, and European Union's 7th Framework Programme.

A Six-Year Prospective Study of the Prognosis and Predictors in Patients With Late-Life Depression.

OBJECTIVES: To examine the six-year prognosis of patients with late-life depression and to identify prognostic factors of an unfavorable course. DESIGN AND SETTING: The Netherlands Study of Depression in Older Persons (NESDO) is a multisite naturalistic prospective cohort study with six-year follow-up. PARTICIPANTS: Three hundred seventy-eight clinically depressed patients (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision criteria) and 132 nondepressed comparisons were included at baseline between 2007 and 2010. MEASUREMENTS: Depression was measured by the Inventory of Depressive Symptomatology at 6-month intervals and a diagnostic interview at 2- and 6-year follow-up. Multinomial regression and mixed model analyses were both used to identify depression-related clinical, health, and psychosocial prognostic factors of an unfavorable course. RESULTS: Among depressed patients at baseline, 46.8% were lost to follow-up; 15.9% had an unfavorable course, i.e., chronic or recurrent; 24.6% had partial remission; and 12.7% had full remission at six-year follow-up. The relative risk of mortality in depressed patients was 2.5 (95% confidence interval 1.26-4.81) versus nondepressed comparisons. An unfavorable course of depression was associated with a younger age at depression onset; higher symptom severity of depression, pain, and neuroticism; and loneliness at baseline. Additionally, partial remission was associated with chronic diseases and loneliness at baseline when compared with full remission. CONCLUSIONS: The long-term prognosis of late-life depression is poor with regard to mortality and course of depression. Chronic diseases, loneliness, and pain may be used as putative targets for optimizing prevention and treatment strategies for relapse and chronicity.

Lifestyle factors and the course of depression in older adults: A NESDO study.

OBJECTIVES: To investigate whether lifestyle indicators including physical exercise, sleep duration, alcohol use, body mass index, smoking status, and a composite lifestyle index are associated with the depression course in older adults. METHODS: Data of 283 older adults were used from the Netherlands Study of Depression in Older Persons. Depressive disorders at baseline were assessed with the Composite International Diagnostic Interview. The depression course at 2-year follow-up was assessed with the Inventory of Depressive Symptoms (IDS, score 0-84) every 6 months; physical exercise with the International Physical Activity Questionnaire; alcohol use with the Alcohol Use Disorders Identification Test; body mass index by anthropometry; and sleep duration and smoking status by interview questions. A composite lifestyle index was calculated by summing scores assigned to each lifestyle factor, with a higher score indicating healthier behavior. RESULTS: Of all participants, 61.1% had chronic depression (all IDS scores 14-84), 20.1% had intermittent depression (1 IDS score ≤ 14), and 18.7% remitted depression (last 2 IDS scores ≤14). None of the investigated lifestyle indicators, nor the composite lifestyle index was associated with depression course, after adjustment for covariates. CONCLUSIONS: Lifestyle factors do not predict the course of depression at 2-year follow-up in older adults.

Limited Evidence for Risk Factors for Proarrhythmia and Sudden Cardiac Death in Patients Using Antidepressants: Dutch Consensus on ECG Monitoring.

Currently, there is a lack of international and national guidelines or consensus documents with specific recommendations for electrocardiogram (ECG) screening and monitoring during antidepressant treatment. To make a proper estimation of the risk of cardiac arrhythmias and sudden (cardiac) death during antidepressant use, both the drug and patient-specific factors should be taken into account; however, solid evidence on how this should be done in clinical practice is lacking. Available recommendations on the management of QT(c) prolongation (with antidepressant treatment) emphasize that special attention should be given to high-risk patients; however, clinicians are in need of more concrete suggestions about how to select patients for ECG screening and monitoring. Based on a review of the literature, a Dutch multidisciplinary expert panel aimed to formulate specific guidelines to identify patients at risk for cardiac arrhythmias and sudden death by developing a consensus statement regarding ECG screening before, and monitoring during, antidepressant use. We first reviewed the literature to identify the relative risks of various risk factors on cardiac arrhythmia and sudden (cardiac) death during antidepressant use. These relative contributions of risk factors could not be determined since no systematic reviews or meta-analyses quantitatively addressed this topic. Because evidence was insufficient, additional expert opinion was used to formulate recommendations. This resulted in readily applicable recommendations for clinical practice for selection of high-risk patients for ECG screening and monitoring. ECG screening and monitoring is recommended before and following the start of QTc-prolonging antidepressants in the presence of vulnerability to QTc prolongation or two or more risk factors (age > 65 years, female sex, concomitant use of a QTc-prolonging drug or concomitant use of a drug that influences the metabolism of a QTc-prolonging drug, cardiac disease, excessive dosing and specific electrolyte disturbances).

Electroconvulsive Therapy for Agitation and Aggression in Dementia: A Systematic Review.

OBJECTIVES: Many patients with dementia develop agitation or aggression in the course of their disease. In some severe cases, behavioral, environmental, and pharmacological interventions are not sufficient to alleviate these potentially life-threatening symptoms. It has been suggested that in those cases, electroconvulsive therapy (ECT) could be an option. This review summarizes the scientific literature on ECT for agitation and aggression in dementia. METHODS: We performed a systematic review in accordance with PRISMA guidelines. A search was conducted in Ovid MEDLINE, EMBASE, and PsycINFO. Two reviewers extracted the following data from the retrieved articles: number of patients and their age, gender, diagnoses, types of problem behavior, treatments tried before ECT, specifications of the ECT treatment, use of rating scales, treatment results, follow-up data, and adverse effects. RESULTS: The initial search yielded 264 articles, 17 of which fulfilled the inclusion criteria. Of these studies, one was a prospective cohort study, one was a case-control study, and the others were retrospective chart reviews, case series, or case reports. Clinically significant improvement was observed in the majority (88%) of the 122 patients described, often early in the treatment course. Adverse effects were most commonly mild, transient, or not reported. CONCLUSIONS: The reviewed articles suggest that ECT could be an effective treatment for severe and treatment-refractory agitation and aggression in dementia, with few adverse consequences. Nevertheless, because of the substantial risk of selection bias, the designs of the studies reviewed, and their small number, further prospective studies are needed to substantiate these preliminary positive results.

Vascular risk factors in older patients with depression: outcome of electroconvulsive therapy versus medication.

OBJECTIVE: Research suggests that in depression, vascular burden predicts a lower efficacy for medication (MED) and a more favourable outcome for electroconvulsive therapy (ECT). Therefore, we investigated the influence of the following vascular risk factors (VRF): hypercholesterolemia, hypertension, smoking, diabetes mellitus, cardiovascular disease, and cerebral vascular accident/transient ischemic attack, on remission from major depression after ECT versus MED. METHODS: The study sample consisted of 81 inpatients with a DSM-IV unipolar major depression diagnosis (mean age 72.2 years, SD = 7.6, mean Montgomery-Åsberg Depression Rating Scale score 32.9, SD = 6.2) participating in a randomized controlled trial comparing nortriptyline versus venlafaxine and 43 inpatients (mean age 73.7 years, SD = 7.5, mean Montgomery-Åsberg Depression Rating Scale score 30.6, SD = 7.1) from an randomized controlled trial comparing brief pulse versus ultrabrief pulse ECT. The presence of VRF was established from the medical records. The remission rate of patients with VRF was compared with those of patients without VRF. RESULTS: The remission rate was 58% (19/33) in the ECT group with ≥1 VRF and 32% (23/73) in the MED group with ≥1 VRF (χ2  = 6.456, p = 0.011). Comparing patients with no VRF versus ≥1 VRF, the remission rate decreased from 80 to 58% (χ2  = 1.652, p = 0.276) in ECT patients and from 38 to 32% (χ2  = 0.119, p = 0.707) in MED patients. Applying different cut-offs for the number of VRFs yielded the same trends. Logistic regression revealed no interaction between VRF and treatment condition. CONCLUSION: The superior efficacy of ECT over pharmacotherapy in major depression in older age was independent of the presence of VRF. Copyright © 2017 John Wiley & Sons, Ltd.

Management of Depression in Older Adults: A Review.

IMPORTANCE: Depression in older adults is a common psychiatric disorder affecting their health-related quality of life. Major depression occurs in 2% of adults aged 55 years or older, and its prevalence rises with increasing age. In addition, 10% to 15% of older adults have clinically significant depressive symptoms, even in the absence of major depression. OBSERVATIONS: Depression presents with the same symptoms in older adults as it does in younger populations. In contrast to younger patients, older adults with depression more commonly have several concurrent medical disorders and cognitive impairment. Depression occurring in older patients is often undetected or inadequately treated. Antidepressants are the best-studied treatment option, but psychotherapy, exercise therapy, and electroconvulsive therapy may also be effective. Psychotherapy is recommended for patients with mild to moderate severity depression. Many older patients need the same doses of antidepressant medication that are used for younger adult patients. Although antidepressants may effectively treat depression in older adults, they tend to pose greater risk for adverse events because of multiple medical comorbidities and drug-drug interactions in case of polypharmacy. High-quality evidence does not support the use of pharmacologic treatment of depression in patients with dementia. Polypharmacy in older patients can be minimized by using the Screening Tool of Older Persons Prescriptions and Screening Tool to Alert doctors to Right Treatment (STOPP/START) criteria, a valid and reliable screening tool that enables physicians to avoid potentially inappropriate medications, undertreatment, or errors of omissions in older people. Antidepressants can be gradually tapered over a period of several weeks, but discontinuation of antidepressants may be associated with relapse or recurrence of depression, so the patient should be closely observed. CONCLUSIONS AND RELEVANCE: Major depression in older adults is common and can be effectively treated with antidepressants and electroconvulsive therapy. Psychological therapies and exercise may also be effective for mild-moderate depression, for patients who prefer nonpharmacological treatment, or for patients who are too frail for drug treatments.