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Depression and bipolar disorder Mixed outcomes in bipolar disorder Not enough is known about the long‐term efficacy of antidepres‐sants in the treatment of bipolar dis‐order, say US investigators, but they are widely prescribed nonetheless. They conducted a meta‐analysis of seven randomised controlled trials of antidepressant therapy of at least six months' duration in a total of 350 patients ( Acta Psychiatr Scand 2008;118:347–56). The studies were of moderately high methodological quality and lasted eight months to three years. Six studies required trial enrichment (an initial response to treatment of an acute episode before randomisation to long‐term treatment). All but two included a tricyclic antide‐pressant and lithium as mood stabilisers. Drop‐out rates ranged from zero to 69 per cent with a mean of 19 per cent. Compared with a mood stabiliser alone or no treatment, anti‐depressant treatment reduced the risk of new depression by 27 per cent. However, neither antidepres‐sant monotherapy nor a combination of antidepressant plus mood stabiliser were more effective than a mood stabiliser alone in preventing depression. By contrast, long‐term antide‐pressant use was associated with a 72 per cent increase in the risk of mania or hypomania compared with non‐use and more than doubled the risk compared with mood stabiliser alone or no treatment. The combination of antidepressant and mood stabiliser did not significantly increase this risk compared with a mood stabiliser alone. Data from other studies suggested that adding an antidepressant to established mood stabiliser treatment may also increase the risk of mania. The authors estimated a number needed to treat (NNT) of 11 for antidepressant therapy, with or without a mood stabiliser, to reduce the risk of one new depressive episode but it was more likely to increase the risk of mania (number needed to harm (NNH) of seven) compared with a mood stabiliser alone or no treatment. Long‐term benefits of antidepressants – but why? Treatment with an antidepressant or anxiolytic appears to have long‐term benefits ‐ but not necessarily because of the drug's effects, a study by UK and Canadian epidemiologists suggests ( Br J Psychiatry 2008;193:327–31). In 1946, the MRC recruited 5362 babies into the National Survey of Health and Development. The cohort was assessed at age 43 years (n=3156) for symptoms of depression, anxiety and medication use using the Psychiatric Symptom Frequency scale; 204 individuals (7 per cent) then met criteria for a mental disorder. In this subgroup, 45 (22 per cent) were taking an anti‐depressant or an anxiolytic. This study reports 10–year out‐comes for 157 members of the sub‐group still in the cohort, using the General Health Questionnaire. After allowing for propensity for treatment, ie adjusting for risk factors predicting medication use, those who were treated with an antidepressant or anxiolytic at age 43 years were less likely to have a clinical or subclinical mental disorder 10 years later compared with those who received no treatment (odds ratio 0.3). The authors are cautious in attributing these outcomes to drug treatment. They point out that most people had stopped taking medication (of those treated at age 43 years, 24 per cent were still taking medication at age 53 years) and the benefits could be attributed to a greater willingness to seek help. However, they acknowledged that their statistical adjustment for propensity for treatment could not account for many potentially significant variables. Low‐dose paroxetine for older people? Plasma levels of paroxetine can be raised in older people, for whom the recommended dosage is limited to 20–40mg daily. US psychiatrists have now evaluated the shortterm efficacy of low‐dose paroxetine in older people, using a modified‐release formulation ( J Clin Psychiatry 2008;e1–e12 pii:ej06m02996). They randomised 525 patients aged 60 years or over (mean 67 years) with major depression to treatment with modified‐release paroxetine 12.5mg or 25mg daily or placebo. After 10 weeks, the mean Hamilton Rating Scale for Depression (HAM‐D) score (baseline 23) was reduced by 1.8 and 3.3 points with 12.5mg and 25mg paroxetine respectively compared with placebo. The proportion of patients in remission (HAM‐D ≤7) was significantly greater than placebo (28 per cent) with paroxetine 25mg (41 per cent) but not 12.5mg (31 per cent). Response rates (≥50 per cent reduction in HAM‐D score) were significantly greater with both doses (52 and 58 per cent with 12.5mg and 25mg paroxetine vs 40 per cent with placebo; NNT nine for 12.5mg and six for 25mg). Importantly, patients rated paroxetine superior to placebo, with no difference between the doses. Somnolence, influenza and nasopharyngitis were more common with paroxetine. Schizophrenia NICE implementation is patchy A survey of mental health trusts by the National Collaborating Centre for Mental Health (NCCMH) has found that implementation of the NICE guideline on schizophrenia management is patchy ( Psychiatric Bull 2008;32:383–7). The NICE 2002 clinical guideline is not compulsory but Trusts are expected to heed its recommendations. NCCMH's analysis of 209 responses to its survey (a 47 per cent response rate) revealed poor provision of cognitive behavioural therapy and incomplete care plans. Nearly 40 per cent of Trusts did not meet the standard for offering clozapine for treatment‐resistant schizophrenia and one‐third failed on providing written information. Successes included use of depot medication and documenting response and adverse effects and avoiding polypharmacy, each achieved by a mean of more than 90 per cent of respondents. The survey demonstrated the importance of corporate commitment and leadership, with commissioner support, for guideline implementation. The authors comment that commissioners should be put under pressure to improve support for NICE guidance. Extrapyramidal effects of atypicals When atypical antipsychotics were introduced it was hoped they would cause fewer complications than the first‐generation agents. Now, Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) investigators have found that the risk of extrapyramidal effects with the newer drugs may be no better than their predecessors ( Br J Psychiatry 2008;193:279–88). CATIE compared olanzapine, quetiapine, risperidone and ziprasidone with the first‐generation antipsychotic perphenazine in a total of 1443 patients over an 18 month period. Eight cases of acute dystonia occurred, three of which were associated with ziprasidone, two with risperidone and one each with quetiapine, olanzapine and perphenazine. There was no difference between treatments in the incidence of new‐onset parkinsonism, with 12–month event rates of 37–44 per cent, though resulting treatment discontinuation was less frequent with quetiapine and ziprasidone and patients taking risperidone were given more antiparkinsonian medication. Rates were also similar for new akathisia (26–35 per cent for atypicals, 35 per cent for perphenazine) and new tardive dyskinesia (1.1–4.5 per cent versus 3.3 per cent respectively). Nevertheless, treatment discontinuation due to extrapyramidal effects was greatest with perphenazine, possibly because more patients in this treatment arm had some extrapyramidal symptoms at baseline. Patient groups National Phobics Society becomes Anxiety UK The UK's largest anxiety disorders charity has rebranded to Anxiety UK, to better reflect the range and scope of their work. ‘Anxiety UK does much more than support sufferers of phobias, and our old name was misleading in this respect,’ says Nicky Lidbetter, CEO of Anxiety UK. ‘We offer advice, treatment and therapies to sufferers of all anxiety conditions from panic disorder, to post traumatic stress disorder, to generalised anxiety. We will, of course, continue to help those suffering from phobias, as anxiety is at the core of all these conditions.’ Anxiety UK offers advice and support through its telephone helpline, and a range of innovative online services. The charity also offers reduced cost therapies to members, allowing thousands of anxiety sufferers to receive treatment they would otherwise be unable to afford, and much faster than through the NHS. The new Anxiety UK logo represents a wave, symbolising both the overwhelming feelings which can be suffered by those with anxiety, and also the soothing nature of the support offered by Anxiety UK. For more information go to www.anxietyuk.org.ukMultiple sclerosis Dose‐ranging trial of fampridine Fampridine, a potassium‐channel blocker, appears to restore function in demyelinated nerves and is under investigation for the treatment of multiple sclerosis. Serious adverse effects, including seizures, have been associated with high plasma levels, prompting the development of a sustained‐release formulation. In a randomised trial involving 206 patients with multiple sclerosis, 15 weeks' treatment with sustained release fampridine 10mg, 15mg or 20mg twice daily did not significantly improve performance in a test of timed walking ( Neurology 2008; 71:1134–41). However, the two lower doses were associated with improved lower extremity strength compared with placebo and 37 per cent of patients in all treatment arms demonstrated consistent improvement in walking speed compared with 8.5 per cent assigned to placebo. Compared with other patients, this group of consistent responders had greater improvements in physician and patient‐assessed global impression of change though no pretreatment parameters predicted this response. Adverse effects at the 10mg twice daily dosage of fampridine were comparable with those associated with placebo, indicating this may be the best dose for further evaluation. Anorexia and nutrition Olanzapine for anorexia nervosa Olanzapine is potentially useful for the treatment of anorexia nervosa, say Canadian researchers ( Am J Psychiatry 2008;165:1281–8). It causes greatest weight gain in those with lowest body mass and it may reduce symptoms of obsession and depression. Of 147 patients referred for possible inclusion in this trial, 71 did not meet eligibility criteria and 63 otherwise eligible patients refused to participate. Thirty‐four women (mean baseline BMI 16kg per m2) were randomised to usual day hospital treatment (supervised meals and group therapy) plus placebo or olanzapine 2.5–10mg daily. After 10 weeks' treatment, both groups had gained weight but the rate of gain was significantly greater with olanzapine and more patients reached the target body mass index of 18.5kg per m2 (88 vs 56 per cent). There were no differences in depression and anxiety scores but olanzapine was associated with greater improvement in obsession scores and fewer obsessions and compulsions. Vitamin deficiency unrecognised Two studies have revealed that vitamin deficiency is common among patients with long‐term illnesses. A US study has shown that the prevalence of hypovitaminosis D is greater among community‐dwelling with Parkinson's disease (55 per cent) than in patients with Alzheimer's disease (41 per cent) or matched controls (36 per cent) (Arch Neurol 2008;65:1348–52). The authors noted that this may increase the risk of osteoporosis and fragility fractures. In the UK, vitamin D deficiency was identified in 15 of 17 male psychiatric inpatients ( Psychiatric Bull 2008;32:390–3). Supplementation with calcium and vitamin D improved serum vitamin D levels but not to within the recommended range. This study was prompted by several cases of TB within 18 months: low vitamin D levels may be associated with activation of latent TB. Psychiatric adverse effects Effects of glucocorticoids in children French clinical pharmacologists have reminded clinicians of the risk of adverse psychiatric effects associated with high‐dose corticosteroids in children ( Br J Clin Pharmacol 2008;66:566–7). Their review of 455 reports in the national pharmacovigilance scheme between 1985 and 2007 found that 95 involved under–18s (21 per cent), with a total of 136 adverse reactions (ADRs). The mean age of those involved was six years, with over half under that age. About one‐third of cases involved dose errors or high doses and a quarter involved off‐label prescribing. The ADRs included agitation or excitation (43 per cent of ADRs), sleep disturbances (18 per cent), psychotic symptoms (8 per cent) and mania (8 per cent). Oral administration accounted for 70 per cent of reports but inhaled and IV administration were also implicated. Eighty‐six per cent of patients recovered when the steroid was withdrawn. The authors warn that ADRs to corticosteroids can be difficult to recognise but, because it is estimated that only 5–10 per cent of ADRs are reported to the French scheme, the risk is difficult to quantify from these data. Neuropathic pain Analgesic effects of botulinum toxin A Case reports have suggested that botulinum toxin type A (BTX‐A) may relieve chronic neuropathic pain. French neurologists have now reported the first randomised double‐blind trial of this treatment ( Ann Neurol 2008;64:274–84). Twenty‐nine consecutive patients with postherpetic neuralgia or post‐traumatic neuropathies, with daily pain of at least six months' duration and mechanical allodynia, were randomised to receive intradermal injections of BTX‐A 1.5cm apart (mean 20 injections, dose range 20–190 units) or of placebo over the affected area. Over the next 24 weeks, BTX‐A was associated with improved weekly pain scores compared with placebo. After 12 weeks, 40 per cent of patients given BTX‐A rated themselves as improved or very improved compared with 14 per cent assigned to placebo; 53 per cent said they were unchanged or worse after BTX‐A compared with 78 per cent with placebo. The NNT for 50 per cent pain relief with BTX‐A was estimated to be four at four weeks and three at 12 weeks. The area and intensity of allodynia to brush and cold stimuli was also reduced by BTX‐A without affecting thresholds of perception to non‐painful stimuli. The response to BTX‐A tended to be better in patients with more preserved thermal sensation. BTX‐A was also associated with a reduction in pain paroxysms and improvements in some aspects of quality of life, including sleep quality, general activity and mood. Most patients said the injections of BTX‐A and placebo were painful but this was related to the injection site. Copyright © 2008 Wiley Interface Ltd