"In the midnight hour": a case report of musical hallucinations with multiple etiological factors treated with lamotrigine.

We report the case of JW, a 66-year-old woman who presented with musical hallucinations and multiple etiological factors for these rare phenomena. We discuss these factors and the successful amelioration of her symptoms with lamotrigine.

The clinical effectiveness and cost of repetitive transcranial magnetic stimulation versus electroconvulsive therapy in severe depression: a multicentre pragmatic randomised controlled trial and economic analysis.

OBJECTIVE: To investigate if repetitive transcranial magnetic stimulation (rTMS) was as effective as electroconvulsive therapy (ECT) in treating major depressive episodes and to perform a cost-effectiveness analysis. DESIGN: A single-blind pragmatic multicentre randomised controlled trial (RCT) with 6 months of follow-up to test equivalence of rTMS with ECT. SETTING: The South London and Maudsley NHS Trust and Pembury Hospital in the Invicta Mental Health Trust in Kent. PARTICIPANTS: Right-handed adult patients referred for ECT for treatment of a major depressive episode (DSM-IV) were assessed. During the 2.5-year trial period, 260 patients were referred for ECT, of whom 46 entered the trial. The main reason for not entering the trial was not consenting to ECT while being formally treated under the UK Mental Health Act 1983. INTERVENTIONS: Patients were randomised to receive a 15-day course of rTMS of the left dorsolateral prefrontal cortex (n = 24) or a course of ECT (n = 22). MAIN OUTCOME MEASURES: Patients were assessed before randomisation, at end of treatment and at the 6-month follow-up. Primary outcome measures were the 17-item Hamilton Rating Scale for Depression (HRSD) and proportion of remitters (defined as HRSD score

CBF tomograms with [99mTc-HM-PAO in patients with dementia (Alzheimer type and HIV) and Parkinson's disease--initial results.

We present preliminary data on the utility of functional brain imaging with [99mTc]-d,l-HM-PAO and single photon emission computed tomography (SPECT) in the study of patients with dementia of the Alzheimer type (DAT), HIV-related dementia syndrome, and the "on-off" syndrome of Parkinson's disease. In comparison with a group of age-matched controls, the DAT patients revealed distinctive bilateral temporal and posterior parietal deficits, which correlate with detailed psychometric evaluation. Patients with amnesia as the main symptom (group A) showed bilateral mesial temporal lobe perfusion deficits (p less than 0.02). More severely affected patients (group B) with significant apraxia, aphasia, or agnosia exhibited patterns compatible with bilateral reduced perfusion in the posterior parietal cortex, as well as reduced perfusion to both temporal lobes, different from the patients of the control group (p less than 0.05). SPECT studies of HIV patients with no evidence of intracraneal space occupying pathology showed marked perfusion deficits. Patients with Parkinson's disease and the "on-off" syndrome studied during an "on" phase (under levodopa therapy) and on another occasion after withdrawal of levodopa ("off") demonstrated a significant change in the uptake of [99mTc]-d,l-HM-PAO in the caudate nucleus (lower on "off") and thalamus (higher on "off"). These findings justify the present interest in the functional evaluation of the brain of patients with dementia. [99mTc]-d,l-HM-PAO and regional cerebral blood flow (rCBF)/SPECT appear useful and highlight individual disorders of flow in a variety of neuropsychiatric conditions.

A multicenter double-blind study of controlled-release physostigmine for the treatment of symptoms secondary to Alzheimer's disease. Physostigmine Study Group.

OBJECTIVE: A multicenter trial to evaluate the efficacy of controlled-release physostigmine salicylate, a cholinesterase inhibitor, was conducted in 1,111 mild-to-moderate Alzheimer's disease (AD) subjects. DESIGN: During dose titration, subjects received 18, 24, or 30 mg of physostigmine or placebo daily. After a 2-week washout period, 366 subjects with putative improvement were randomized to receive either placebo or their best dose of physostigmine in a 6-week double-blind trial. Nonresponding patients (439) were randomized to receive in a separate double-blind trial either placebo or their highest tolerated dose of physostigmine. The primary efficacy measures included the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) and a Clinical Global Impression of Change (CGIC). Secondary measures included the Mini-Mental State Examination and two activities-of-daily-living scales. RESULTS: At the end of the 6-week double-blind phase, physostigmine-treated patients scored 1.75 points higher than placebo-treated patients on the ADAS (p = 0.003) and 0.26 points higher on the CGIC (p = 0.012) in the intent-to-treat analysis. There was no significant improvement on the secondary outcome measures. Patients failing to respond to physostigmine during the dose titration phase failed to respond on any of the outcome measures during the double-blind period of re-exposure. Common adverse events included nausea, vomiting, diarrhea, and anorexia. There were no significant changes in liver function tests. CONCLUSION: This study demonstrated statistically significant differences between physostigmine and placebo on both a performance-based cognitive functioning instrument and a clinician's global evaluation. The magnitude of the effect size was small and occurred only in the subset of patients who responded in the initial dose titration study period. Nevertheless, the results suggest that in a subset of patients, physostigmine can induce a degree of cognitive improvement over 6 weeks of treatment.

Sparing of attentional relative to mnemonic function in a subgroup of patients with dementia of the Alzheimer type.

Patients with dementia of the Alzheimer type (DAT) received two tests of visual selective attention, together with tests of spatial and visual recognition memory and visuospatial conditional learning previously used to show deficits early in the course of DAT. One set of attentional tests compared visual discrimination learning along intra- and extra-dimensional shifts, using a "total change" design. In the 12 DAT patients capable of attempting the extra-dimensional shift (subgroup 1), performance was equivalent to that of controls. This subgroup was also unimpaired at simple and compound discrimination learning and reversal and an intra-dimensional shift. They were as accurate as controls on a visual search task requiring matching of stimuli on two dimensions with variable numbers of alternatives, but were significantly impaired in the tests of recognition memory and learning. By contrast, the other 13 patients showed marked impairments in the attentional tasks. This subgroup was also significantly worse than subgroup 1 in performance on the visual recognition and conditional learning tasks, and showed greater severity on most of the clinical ratings of dementia. The sparing of attentional shifting in patients early in the course of DAT is contrasted with the impairments previously described in patients with Parkinson's disease with only mild or absent memory loss. The implications of this double dissociation of deficits for understanding the neural bases of the cognitive deficits in these two neurodegenerative diseases are discussed and their significance for the staging of DAT is considered.

Arylsulphatase A pseudodeficiency in vascular dementia and Alzheimer's disease.

The carrier rates of a genetic marker for arylsulphatase A pseudodeficiency (ASA-PD) were determined in three series of patients with vascular dementia (VaD) or Alzheimer's disease (AD). In the first community-based sample, the 1524 + 95A-->G mutation, which is known to be associated with ASA-PD, was present in 35% of VaD cases and none of the AD cases. In a second sample of cases drawn from a Dementia Register, the mutation rates were 18% (VaD) and 16% (AD). Brain DNA from a post-mortem sample revealed the ASA-PD mutation in 60% of VaD cases and 34% of AD cases. These rates are higher than previous studies of culturally similar populations and suggest that ASA-PD may be a risk factor for dementia.

99mTc-HMPAO single photon emission tomography in late life depression: a pilot study of regional cerebral blood flow at rest and during a verbal fluency task.

Relative regional cerebral blood flow (rCBF) was measured at rest and during a verbal fluency task in ten elderly patients with major depressive disorder and nine controls. At rest, depressed patients showed significant reductions in the cortico-cerebellar ratios of tracer uptake in the right and left parietal, left temporal and left occipital regions. During the task relative rCBF increased in patients such that these differences disappeared. Relative rCBF did not correlate with severity of depressed mood or endogenous features but did correlate positively with severity of psychotic symptoms. Frontal relative rCBF correlated negatively with somatic symptoms and anxiety.

The use of dexamethasone in elderly patients with antidepressant-resistant depressive illness.

Many depressed patients do not respond to first-line antidepressant treatment. Dexamethasone is a synthetic steroid which may have antidepressant properties. Its use in two elderly patients with resistant depression is reported. Both patients appeared to benefit from the treatment. The possible modes of action of this treatment, and its potential benefits to the elderly, are discussed.

The psychopathology of Basal Ganglia calcification.

Basal ganglia calcification (BGC) was found in 36 of 4122 patients undergoing computed tomography as part of a clinical investigation of their psychiatric illness. The prevalence of BGC increased with age in both men and women. No psychiatric diagnosis was specifically associated with BGC although calcification of the putamen and the caudate was only found in patients with functional disorders. No abnormalities of calcium or phosphate metabolism were found. The results do not support the hypothesis that BGC is an aetiological factor in schizophrenia-like psychoses.

Barriers to the use of electroconvulsive therapy in the elderly: a European survey.

A postal survey was carried out to determine the clinical and legal guidelines governing the use of electroconvulsive therapy (ECT) in the countries of the wider Europe. Respondents from 23 of the 33 countries returned completed questionnaires. Considerable variation was found in the availability of ECT, the frequency of its use and associated legal procedures. However, there was a broad consensus with regard to the clinical indications. Access to the treatment was most frequently limited by financial or other resource constraints, political or legal restrictions.

Impedance cardiography: non-invasive cardiac output measurement after burn injury.

The election of blood from the heart produces changes in transthoracic impedance. It has been proposed that the cardiac output may be determined from these changes. The cardiac output was measured by impedance cardiography and by the thermal dilution method before and after full thickness burn injury to the skin of the anaesthetized rat. The values obtained by the impedance method showed a good correlation with simultaneous thermal dilution cardiac output measurements (r=+0.67 pre-burn, and +0.76 post-burn). Impedance cardiography confirmed the early post-burn reduction in cardiac output reported by other workers using invasive techniques. Good agreement between the two methods was also obtained when the cardiac output of burn injured animals was altered by fluid infusion. This non-invasive technique of cardiac output monitoring may therefore have an important place in the investigation of cardiac function after trauma and burn injury.

A pill in the sandwich: covert medication in food and drink.

The covert administration of medicines in food and drink has been condemned by some and condoned by others. We used questionnaires to ascertain the views of people caring for patients with dementia in institutions and in the community. In 24 (71%) of 34 residential, nursing and inpatient units in south-east England, the respondent said that medicines were sometimes given in this way. It was often done secretly and without discussion, probably for fear of professional retribution. Few institutions had a formal policy on the matter. Of 50 people caring for demented patients in the community, 48 (96%) thought the practice sometimes justifiable, but 47 believed that doctors should consult with carers before deciding. Even if, as most carers and some authorities believe, covert medication can be justified, the poor recording and secrecy surrounding the practice in institutions are cause for concern.

An evaluation of the multidisciplinary approach to psychiatric diagnosis in elderly people.

OBJECTIVE: To determine the accuracy of psychiatric diagnoses made by two community psychogeriatric teams operating a multidisciplinary assessment procedure. DESIGN: Comparison of team diagnosis with independent formal assessment and consensus diagnosis by research psychiatrists. SETTING: Two community psychogeriatric teams with similar operational policies in an inner London health district. SUBJECTS: 100 people aged 65-90 (70 women) newly referred to the teams. MAIN OUTCOME MEASURES: Concordance between team and research diagnoses. RESULTS: Agreement between team and research diagnoses ranged from 90% to 99% for the specific psychiatric disorders studied. There was no significant difference between medical and non-medical team members in their diagnostic performance compared with the research psychiatrists. Increased diagnostic accuracy by team members was associated with longer experience of team working, regardless of the team members' professional background. CONCLUSIONS: The multidisciplinary approach to the assessment of referrals to these community teams for the elderly is not associated with misdiagnosis of psychiatric disorder.

CPR in the nursing home: fool's errand or looming dilemma?

BACKGROUND: The indications for CPR (cardiopulmonary resuscitation) have expanded greatly since the technique was introduced and theoretically it can be attempted on all prior to death. Policy initiatives (such as the British Medical Association/Royal College of Nursing guidelines) have attempted to provide a clinical rationale for the withholding of inappropriate CPR. Traditionally a care home was felt to be an inappropriate environment to attempt CPR but increased use of advance directives may bring the issue to the fore in this setting. AIMS: We elicited the views of managers of care homes regarding resuscitation strategies in hypothetical situations and in actual practice. METHOD: A purpose designed questionnaire in two parts was compiled, gathering factual information and employing a Likert scale to gauge opinion about this issue. The survey was conducted among 187 continuing care homes in South London the subjects being the care managers of the homes surveyed. RESULTS AND CONCLUSION: Responses were obtained from 86 care homes. Care managers would resuscitate 66% of cases of witnessed cardiac arrest but few efforts were reported. Policies in assigning 'Do not resuscitate' orders were referred to by only 9% of homes but 80% of facilities would welcome them, yet 50% would exclude the patient from this discussion. Clear policy guidelines are required for continuing care homes, and advance statements about CPR as part of residents care plans could reduce inappropriate resuscitative efforts and hospital transfers.

A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression.

BACKGROUND: Effectiveness of repetitive transcranial magnetic stimulation (rTMS) for major depression is unclear. The authors performed a randomized controlled trial comparing real and sham adjunctive rTMS with 4-month follow-up. METHOD: Fifty-nine patients with major depression were randomly assigned to a 10-day course of either real (n=29) or sham (n=30) rTMS of the left dorsolateral prefrontal cortex (DLPFC). Primary outcome measures were the 17-item Hamilton Depression Rating Scale (HAMD) and proportions of patients meeting criteria for response (50% reduction in HAMD) and remission (HAMD8) after treatment. Secondary outcomes included mood self-ratings on Beck Depression Inventory-II and visual analogue mood scales, Brief Psychiatric Rating Scale (BPRS) score, and both self-reported and observer-rated cognitive changes. Patients had 6-week and 4-month follow-ups. RESULTS: Overall, Hamilton Depression Rating Scale (HAMD) scores were modestly reduced in both groups but with no significant groupxtime interaction (p=0.09) or group main effect (p=0.85); the mean difference in HAMD change scores was -0.3 (95% CI -3.4 to 2.8). At end-of-treatment time-point, 32% of the real group were responders compared with 10% of the sham group (p=0.06); 25% of the real group met the remission criterion compared with 10% of the sham group (p=0.2); the mean difference in HAMD change scores was 2.9 (95% CI -0.7 to 6.5). There were no significant differences between the two groups on any secondary outcome measures. Blinding was difficult to maintain for both patients and raters. CONCLUSIONS: Adjunctive rTMS of the left DLPFC could not be shown to be more effective than sham rTMS for treating depression.

The birth of a specialty: the first ten thousand patients of an old age psychiatry service.

BACKGROUND: Old age psychiatry as a clinical specialty emerged in the 1970s and modern, open-access multidisciplinary services started in the mid-1980s in South London. There are few accounts of referrals to old age psychiatry services and no quantitative accounts of the referral patterns to such teams. We report on the first 10,000 patients newly referred to the first such service in the world. METHODS: Observational study on routinely gathered data on age, gender, referral source, discipline of team member involved, diagnosis and duration of contact. Data validation was by iterative feedback to clinicians. RESULTS: Ten thousand patients were referred between December 1983 and March 2000. Missing data rates were low. The overall referral rate was 21.0 per 1000 population over 65 per annum, with the highest rate in those 85+ years old, in whom there was a marked rise over time. The rise in referral rate compensated for a decline in the population over 65 so that the numbers of referrals rose. Although there was a rise in the rate of referral of people with an organic diagnosis over time, this was not statistically significant. Organic patients constituted 50-60% of referrals but had shorter contact times than functional ones. Cause for concern included a low rate of referral from care homes, and a high proportion of possibly inappropriate referrals from medical and general psychiatry services. We were pleased to see no excess of such referrals from open-access sources, confirming earlier work. CONCLUSIONS: Descriptive data on referrals and workload of the first open-access multidisciplinary old age psychiatry service have generated cause for both celebration and concern.

The routine use of investigations in elderly psychiatric patients.

The use of investigations was studied in all new admissions (n = 167) to a psychiatric unit for the elderly over an 18-month period. Twenty per cent of the tests revealed abnormalities confirming the relatively high prevalence of physical pathology in this population. However, only 4% of the investigations requested influenced further management. It is suggested that full blood count, serum folate, urea and electrolytes and urine culture should be performed routinely, but that other investigations might be ordered selectively.

Jobst et al's "Detection in life of confirmed Alzheimer's disease using a simple measurement of medial temporal lobe atrophy by computed tomography".

"The medial temporal lobe of the brain is important for normal cognitive function, notably for memory, and is the region with the most extensive pathological change in Alzheimer's disease (AD). We wanted to find out if atrophy of the medial temporal lobe could be detected in life in patients in whom a diagnosis of AD was subsequently established histopathologically. The minimum width of the medial temporal lobe, measured by temporal-lobe-oriented computed tomography (CT) about one year before death, in 44 patients with a histopathological diagnosis of AD (cases) was nearly half (0.56 of the median) that in 75 controls of the same age with no clinical evidence of dementia (95% confidence interval 0.51-0.61). There was little overlap between the distributions of measurements in cases and controls. A cut-off (< 0.79 MoM) selected to yield a 5% false-positive rate gave an expected detection rate of 92%. A cut-off selected to yield a false-positive rate of 1% (< 0.70 MoM) yielded a 79% detection rate. 20 of the 44 patients with histopathologically diagnosed AD had been scanned more than once before death, and the test (cut-off < 0.79 MoM) was positive in all 20 more than a year before and in 9/10 more than 2 years before death. In 10 subjects with dementia but with histopathology excluding AD, the mean minimum width of the medial temporal lobe was significantly greater than that in the cases with AD, but was not significantly different from that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)