Digest

Abstract 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.uk Multiple 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 associat

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