Chanaka Wijeratne

Treatment-Resistant Depression: Critique of Current Approaches

The aim of the present study was to critically appraise current conceptual approaches; demographic, neurobiological and clinical correlates; and management strategies of treatment-resistant depression (TRD), especially in light of recent research findings. To this end, a review of the relevant English-language literature was undertaken using Medline, Embase and Psychinfo. TRD has been defined in conceptually restrictive terms as symptomatic non-response to physical therapies alone, with little systematic study of aetiology made. It is likely that a range of sociodemographic (such as higher socioeconomic status), genetic (such as variation in functional monoamine polymorphisms) and clinical variables (such as signal hyperintensities seen on structural neuroimaging scans) are responsible for non-response in individuals. There is insufficient evidence to suggest that TRD is associated with specific subtypes of depression, physical comorbidity, personality or chronicity. The large-scale Sequenced Treatment Alternatives to Relieve Depression (STAR∗D) and other studies have suggested that a structured psychotherapy such as cognitive behaviour therapy may be as effective as medication in initial drug non-responders. Also conventional alternatives such as the use of older antidepressant classes, pharmacological augmentation or electroconvulsive therapy in established cases of TRD are not as effective as traditionally thought. There is insufficient preliminary evidence to make formal recommendations about the use of novel brain stimulation techniques in TRD. TRD should be re-defined as the failure to reach symptomatic and functional remission after adequate treatment with physical and psychological therapies. Treatment resistance may be more usefully conceived within the context of well-defined cohorts such as patients with specific subtypes of depression. Although neurobiological markers such as gene polymorphisms, which are potentially predictive of medication tolerance and efficacy, may be used in the future, it is likely that sociocultural variables such as beliefs about depression, and evidence-based treatments for it, will also determine treatment resistance.

Reformulation of current recommendations for target serum lithium concentration according to clinical indication, age and physical comorbidity

Background: There have been significant changes in the nature of psychiatric patient populations and patterns of drug prescribing in mood disorders since serum lithium monitoring was introduced. It seems opportune to review current guidelines for target lithium concentration given the decline in lithium monotherapy and increase in the numbers of older people and those with comorbid physical disease administered lithium. Method: A review was made of the literature of lithium monitoring and target serum concentration in mood disorders, older people, and comorbid physical illness. Results: Current guidelines, which generally recommend a target serum concentration of 0.5/0.6 to 1.1/1.2 mmol/L, have a number of limitations. A target lithium level of > 0.8 mmol/L is inappropriate given poor tolerability, and adequate efficacy when combination lithium-antipsychotic therapy is used at this or lower levels. Guidelines have largely failed to match specific clinical indications to serum levels, and to consider comorbid physical illness factors known to be associated with lithium toxicity. Conclusion: For most patients, a target serum lithium concentration range of 0.5–0.8 mmol/L, varying according to clinical indication, age and concurrent physical status, seems most appropriate in enhancing efficacy and minimizing adverse effects. The lower end of this range (0.5–0.6 mmol/L) is recommended for patients 50 years and over; those with diabetes insipidus, renal impairment or thyroid dysfunction; those administered diuretics, angiotensin converting enzyme (ACE) inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 inhibitors; and in the prophylaxis of bipolar depression and management of acute unipolar depression. The higher end of this range (0.7–0.8 mmol/L) is recommended in the management of acute mania and prophylaxis of mania.

Vascular mania: an old concept in danger of sclerosing? A clinical overview

Objective:  To review the evidence for an association between vascular disease and mania, and in this context, to assess the suitability of previously proposed diagnostic criteria.

Separation anxiety in the elderly

Separation anxiety has been studied in children and young adults but little is known about this form of anxiety in older people. This study aimed to examine socio-demographic, psychological and physical health correlates of separation anxiety in the elderly. Eighty-six ambulatory subjects aged 62-87 years were recruited from primary medical care practices to participate in this study. The presence of lifetime DSM-IV affective and anxiety disorders was determined by structured clinical interview. Subjects also completed a battery of self-report questionnaires measuring levels of state and trait anxiety, juvenile and adult separation anxiety. Adult separation anxiety scores were moderately correlated with juvenile separation anxiety scores (r= .52, P < .001), trait anxiety (r = .55, P < .001) and state anxiety scores (r = .66, P < .001), as well as younger age (r = .39, P < .001). Higher adult separation anxiety scores were also associated with a lifetime history of any anxiety disorder (t = 3.74, df = 84, P < .001) or any affective disorder (t = 2.12, df = 84, P < .05). However, adult separation anxiety was not associated with increasing age, being widowed, living alone or poorer physical health. Clinicians working with the elderly need to routinely explore this form of anxiety as it may complicate the pattern of presentation of other anxiety and affective disorders, and require specific forms of intervention.

Hippocampal and amygdala volumes in an older bipolar disorder sample.

BACKGROUND Brain volumetric magnetic resonance imaging (MRI) studies of adult bipolar disorder samples, compared with healthy controls, have reported conflicting results in hippocampal and amygdala volumes. Among these, few have studied older bipolar samples, which would allow for examination of the effects of greater duration in mood episodes on brain volumes. The aim of this study was to compare hippocampal and amygdala volumes in older bipolar patients with controls. METHODS High-resolution MRI scans were used to determine hippocampal and amygdala volumes that were manually traced using established protocols in 18 euthymic patients with DSM-IV bipolar I disorder (mean age 57 years) and 21 healthy controls (mean age 61 years). Analysis of covariance (ANCOVA) was used to explore group differences while controlling for intracranial volume (ICV), age, sex, and years of education. RESULTS While gray matter, white matter, and cerebrospinal fluid volumes did not differ between the groups, bipolar disorder patients had smaller ICV (t = 2.54, p = 0.015). After correcting for ICV, the bipolar group had smaller hippocampal (left hippocampus F = 13.944, p = 0.001; right hippocampus F = 10.976, p = 0.002; total hippocampus F = 13.566; p = 0.001) and right amygdala (F = 13.317, p = 0.001) volumes. Total hippocampal volume was negatively associated with the duration of depressive (r = -0.636; p = 0.035) and manic (r = -0.659; p = 0.027) episodes, but not lithium use. Amygdala volumes were not associated with the duration of mood episodes. CONCLUSIONS Older bipolar disorder patients had smaller hippocampal and amygdala volumes. That smaller hippocampal volume was associated with the duration of mood episodes may suggest a neuroprogressive course related to the severity of the disorder.

Somatic distress syndromes in later life: the need for paradigm change.

Somatic distress syndromes, which include somatoform disorders and syndromes of chronic fatigue such as neurasthenia but not somatic presentations of anxiety and depression, are one of the common expressions of distress in primary care (Ormel et al . 1994) and general hospital settings (Hemert et al . 1993). They are of considerable importance cross-culturally (Ono et al . 1999), and often lie at the interface of psychiatry and medicine (Hickie, 1999). They are associated with significant disability (Ormel et al . 1994; Andrews, 2000) and health-care utilization (Escobar et al . 1991).

A PILOT STUDY COMPARING PSYCHOLOGICAL AND PHYSICAL MORBIDITY IN CARERS OF ELDERLY PEOPLE WITH DEMENTIA AND THOSE WITH DEPRESSION

A pilot study compared the difficulties faced by co‐resident relatives caring for elderly patients with dementia and those with depression, referred to a psychogeriatric service in London. The mean GHQ‐28 score of 23 dementia carers was significantly higher than that of 17 carers of elderly people with depression. The relatively low level of distress in the latter group of carers may have been related to the majority of the depressed patients suffering minor depression. Behavioural difficulties in the patient, a poor premorbid relationship with patient and dissatisfaction with their social contacts were associated with a significant GHQ‐28 score (over 4) in carers. However, the two groups of carers reported comparable levels of physical health.

Electroconvulsive Therapy and Subdural Hemorrhage

Electroconvulsive therapy (ECT) was used to treat severe depressive illness in two patients, one of whom had undergone recent neurosurgery for subdural hemorrhage (SDH) and another with a concurrent SDH in the absence of raised intracranial pressure. Although the second patient died 1 month after the completion of ECT, in neither case did ECT extend the SDH or lead to other intracranial complications. It would seem that ECT can be performed safely in the presence of SDH without mass effect or after surgical drainage of SDH, although clinicians should proceed cautiously in close collaboration with neurosurgical colleagues, review neuroimaging scans at regular intervals during and after the course of ECT, and use the dose-titration method of treatment with unilateral electrode placement away from the site of the lesion or surgery to minimize adverse effects.

Adaptive ageing surgeons

The surgical workforce is ageing. This will impact on future workforce supply and planning, as well as the professional performance and welfare of surgeons themselves. This paper is a ‘call to arms’ to surgeons to consider the complex problem of advancing years and surgical performance. We aim to promote discussion about the issue of ageing as it relates to surgeons, while exploring ways in which successful ageing in surgeons may be promoted. The task‐specific aspects of surgical practice suggest that it is a physically and cognitively demanding task, reliant on a range of fine motor, sensory, visuospatial, reasoning, memory and processing skills. Many of these skills potentially decline with age, although there is great inter‐individual variation, particularly in cognitive performance. Nevertheless, there is some consensus in the literature that age‐related cognitive changes exist in a proportion of surgeons, and there is an increase in operative mortality rates for certain surgical procedures performed by older and more experienced surgeons. In the absence of mandatory retirement, guidance is needed in regard to individualizing the timing of retirement and encouraging reflective and adaptive practice based on insight into how ones skills and performance may change with age. This may be best facilitated by some form of informed and guided self‐monitoring or ‘self‐screening’. It should be emphasized that self‐screening is not a form of self‐treatment but aims to enhance insight, using a tool kit of resources to promote adaptive ageing. Moreover, self‐screening should not be restricted to cognition, which is only part of the picture of ageing, but extended to emphasize the maintenance of mental and physical wellness, and the acceptance of independent professional treatment and support when required.

Neuropsychiatric effects of Parkinson's disease treatment

Advances in the treatment of Parkinsons disease have led to significant improvement in many of the disabling motor symptoms of the disease, but often at the cost of neuropsychiatric side‐effects. These include psychosis, dopamine dysregulation syndrome, impulse control disorders, mood disorders and Parkinsons disease drug withdrawal syndromes. Such side‐effects can be as disabling and have as much impact on activities of daily living, quality of life, relationships and caregiver burden as motor symptoms. Awareness of these potential side‐effects is important both in terms of obtaining informed consent, and to aid early identification and intervention, as patients may not spontaneously report side‐effects because of lack of insight, or deny them out of shame or embarrassment. The challenge of treatment can be a trade off between the emergence of such side‐effects and the amelioration of parkinsonism, best mastered with an informed dialogue between clinician and patient.