Digest

Abstract Augmentation in treatment‐resistant depression Faith in antidepressants seems to be fading. ‘Expectations with regard to efficacy may be higher than the reality of clinical practice’ write US psychiatrists, reviewing the evidence for augmenting antidepressant therapy with atypical antipsychotics in treatment‐resistant depression ( Acta Psychiatr Scand 2008;117:253–9). Response rates of 60–70 per cent in clinical trials mask the fact that many people continue to have significant functional impairment; few achieve remission and the STAR*D trial showed that most who do relapse within a year. Augmentation of antidepressant therapy is therefore an attractive proposition. The potential of atypical antipsychotics appears to lie in their complex effects on serotonin receptors in addition to many other possible actions on dopamine, noradrenaline and NMDA function. Reviewing controlled trials of atypicals in patients for whom at least one adequate trial of antidepressant therapy failed, the authors note that initial experience was encouraging. For example, adding olanzapine after failure of fluoxetine achieved remission (defined as HAM‐D score ≤7) in 60 per cent of patients compared with 20 per cent who continued fluoxetine and 25 per cent taking olanzapine alone. Subsequent larger trials had mixed results, partly due to methodological problems. Experience with risperidone followed a similar pattern. There has been greater consistency with augmentation using quetiapine, in combination with SSRIs or SNRIs, and favourable but less robust evidence for ziprasidone. Evidence for aripiprazole is limited to small, short‐term trials. The authors conclude there is adequate evidence only for augmentation with olanzapine (despite the inconsistency of the trials) and quetiapine. They caution that the adverse effects of atypicals pose such problems that augmentation is not an option early in the course of treatment. More trials are needed to clarify their role. Aromatherapy for behaviour problems in dementia The adverse effects of atypical antipsychotics in patients with dementia – which include an increased risk of stroke in the elderly – have greatly limited their role in the management of behaviour problems. One alternative proposed by NICE is aromatherapy, prompting UK researchers to assess the supporting evidence ( Int J Geriatr Psychiatry 2008; 23:337–46). Their literature search identified 11 prospective randomised trials of aromatherapy as a treatment for behavioural and psychological symptoms in a total of 298 patients with dementia. In fact, so few publications met their search criteria that they included in their analysis all the randomised trials they found. There were important methodological failings, including lack of statistical power in eight trials (fewer than 25 participants); mixed assessment methods, some of which were qualitative; and inadequate blinding. Lavender was the oil most frequently assessed; others included lemon balm, tea tree and sweet orange, and some used mixtures of several oils. Only one trial involved individualisation of treatment (oils being selected according to the characteristics of the patient) and there was little assessment of adverse effects. Meta‐analysis of these trials was not possible. The authors conclude that, although aromatherapy is potentially useful for behaviour problems in dementia, standards of weighing risk and benefit are not being applied to aromatherapy in the same way as they are to antipsychotics. While this probably reflects the popular belief that this is a safe intervention, there is no adequate evidence to support such a view. Nurse supplementary prescribing in an acute unit Supplementary prescribing – the ‘voluntary partnership between an independent prescribing doctor and a supplementary prescribing nurse’ – was introduced several years ago but uptake has been limited by organisational barriers, lack of awareness and lack of confidence among clinicians. Initiatives have largely been led by nurses and the impact on psychiatrists has provoked little comment. The team at Wrexham Hospital has now described its experience implementing a supplementary prescribing scheme in an acute inpatient setting ( Psychiatr Bull 2008;32:136–9). They used a five‐step model in which a nurse consultant is responsible for the first 72 hours of care, after which a treatment plan is agreed with a psychiatrist. This incorporates the clinical management plan, the document that formally delegates prescribing authority and sets out guidance for assessment and prescribing. Patient review and ward rounds are the responsibility of the nurse consultant; the psychiatrist provides advice at management review meetings and is on call for urgent consultation. Care management plans implemented to date include switching antipsychotics, adding hypnotics, anxiolytics or antidepressants, initiating and titrating clozapine and other antipsychotics. Acknowledging the issues of delegation and distributing responsibility is the key to success, say the authors. Stopping antipsychotics in dementia Despite concerns about the safety of antipsychotics in people with dementia, some use has persisted. UK specialists recently reported a placebo‐controlled trial of discontinuation in 165 patients with severe behaviour disorders associated with Alzheimer's disease to determine whether continued use of antipsychotics was associated with accelerated cognitive decline (DART‐AD trial, PLoS Med 2008;5:e76. doi:10.1371/journal.pmed.0050076). Patients were randomised to switch to placebo or continue treatment for 12 months. Of these, 22 per cent did not begin their randomised treatment and a further 26 patients were lost to follow‐up, leaving 102 for analysis. An additional 47 did not complete 12 months' follow up, nearly half of whom died. At six months, the Severe Impairment Battery (SIB) score deteriorated in both groups with no difference between them. There was also no difference in overall neuropsychiatric symptoms scores in continued treatment and placebo groups though there was a trend for a beneficial effect of antipsychotics in patients with worse symptoms, and a trend favouring placebo in assessment of parkinsonism. There was a significant difference between placebo and continued treatment in verbal fluency assessment, favouring placebo. Only 55 patients remained in the study at 12 months and, although SIB score favoured placebo, the difference was not statistically significant. However, there was a significant difference in neuropsychiatric symptom score at 12 months, favouring continued treatment, with some evidence to suggest patients with more severe symptoms benefit most. For most patients, stopping an antipsychotic makes no difference and may even improve functional and cognitive status, the authors conclude. The possible benefits of continuing treatment for patients with severe neuropsychiatric symptoms must be weighed against the risks of adverse effects. Two new studies have investigated the effects of olanzapine and quetiapine on cognitive function in patients with dementia and behavioural disorders. In a six‐week placebo‐controlled trial of 40 patients with Alzheimer's disease, quetiapine did not improve psychotic symptoms and did not affect scores of cognitive or motor function ( Int J Ger Psychiatr 2008;23:393–400). A pooled analysis of three placebo‐controlled trials of olanzapine found no significant effect on cognitive function overall compared with placebo; the authors acknowledged that negative effects could not be excluded in some patients with worse cognitive function or whose behavioural problems remain uncontrolled ( Int J Geriatr Psychiatry 2008;23:364–9). Automating MS treatment decisions Computerised assessment of interferon beta treatment can predict clinical outcomes for patients with relapsing‐remitting multiple sclerosis, say Spanish investigators ( BMC Neurology 2008;8:3. doi:10.1186/1471‐2377–8–3). They developed software to implement the recommendations of the Canadian Multiple Sclerosis Working Group for assessing patients and optimising treatment. The software utilises clinical assessments of attacks, progression and MRI to formulate a risk report stating whether treatment should continue or change. Such an approach would avoid ‘subjective’ assessment, they suggest. Using a retrospective sample of 55 patients initially treated with interferon beta 1a 30mg per week, and subsequent clinical outcomes as a comparator, the software had a sensitivity of 74 per cent, a specificity of 84 per cent and a positive predictive value of 77 per cent for treatment optimisation for up to five years based on the first year's outcomes. It performed better at predicting progression than relapse. Kinetics explain poor sumatriptan response Oral sumatriptan does not relieve headache in almost one‐third of patients with migraine, Italian pharmacologists say, prompting them to compare the drug's pharmacokinetics in responders and non‐responders ( Eur J Clin Pharmacol 2008;64:489–95). Defining responders as those showing an improvement from moderate/severe

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