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Depression Resistance to maintenance therapy? Maintenance therapy of depression reduces the risk of relapse and recurrence by about 70 per cent compared with placebo but, say US psychiatrists, uncertainty remains over how long to continue treatment after remission, whether patients with a history of multiple episodes fare worse than those with fewer, and whether treatment should be terminated abruptly or gradually ( J Clin Psychiatry 2008; published online pii:ej06r02932). Their meta‐analysis of 30 randomised trials involving 4890 patients in primary and secondary care confirmed that maintenance therapy reduced the overall risk of relapse by 76 per cent with an SSRI and by 71 per cent with a tricyclic antidepressant. This risk reduction persisted for at least 12 months and was unaffected by treatment beyond three months or, overall, whether treatment ended abruptly or gradually. However, patients with recurrent episodes were at significantly greater risk of relapse than those with a single episode (odds ratios, OR, 0.37 vs 0.12) and were more likely to relapse after abrupt compared with gradual withdrawal (OR 0.32 vs 0.11). The authors say they found no evidence to justify a distinction between continuation (up to six months) and maintenance (more than six months) phases. Maternal remission improves children's symptoms Successful treatment of maternal depression is associated with significant improvements in psychiatric symptoms of their children, a new analysis from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study shows ( Am J Psychiatry 2008;165:1136‐47). STAR*D was designed to compare treatment options for adults with major depression. In one sub‐study involving 123 women and their children aged 7‐17 years, psychiatric symptoms in children were monitored for one year after treatment initiation to determine the impact of maternal remission. In the year following initiation of treatment with citalopram, maternal symptom scores improved most during the first three months then stabilised. Remission was achieved in 57 per cent of mothers – approximately evenly divided between early (less than three months months) and later remission (after treatment with two or more antidepressants). Sixty children had definite psychiatric symptoms at baseline (anxiety, depression, disruptive behaviour disorders). Symptoms improved in children whose mothers achieved early or late remission but not in those whose mothers did not respond to treatment. Children's symptom scores improved during the year after their mothers began treatment, and was most marked in the first six months. There was a correlation between concurrent maternal and children's symptom scores but it accounted for little of the overall change seen in children. There was some evidence, albeit inconclusive, that children's symptoms correlated with maternal symptom scores in the preceding three months. However, the study excluded the possibility that mothers became less depressed following improvement in their children's symptoms. Prescribing varies with ethnicity GP prescribing of antidepressants is low in areas of England with high black and Asian populations, an analysis of Quality and Outcomes Framework (QOF) data suggests ( Br J Psychiatry 2008;193:235‐9). Using data from QOF, the 2001 UK national census and prescribing data for primary care for 8430 GP practices, the authors found marked variation in treatment. The mean volume of antidepressant prescribing was 2471 average daily quantities (similar to defined daily doses) per 1000 STAR‐PUs (age‐ and gender‐standardised prescribing units). However, the figure was below 1833 in a quarter of practices and above 3039 in another quarter. The main variables associated with antidepressant prescribing were chronic disorders (COPD, epilepsy, coronary heart disease, asthma). The strongest predictors of prescribing volume were social deprivation, ethnicity, COPD, asthma and epilepsy. There was a negative correlation between the proportion of Black or Asian patients per practice and prescribing volume, which was independent of social deprivation. It is possible that the prevalence of depression is below average in areas with large ethnic populations but disparities in care cannot be excluded. The authors say the association between chronic respiratory disorders/epilepsy and depression may be greater than is generally recognised. Mirtazapine: any advantage? The alpha 2 ‐receptor, 5‐HT 2 and 5‐HT 3 antagonist mirtazapine may act more quickly than an SSRI but short‐term outcomes in the treatment of depression are otherwise similar, an international panel of psychiatrists has concluded ( J Clin Psychiatry 2008; published online pii:ej07m03599). Their meta‐analysis included 25 randomised trials (in all languages) involving 4842 patients comparing mirtazapine with other antidepressants for the treatment of acute major depression. The duration of follow‐up was 5‐24 weeks. Response was defined as at least 50 per cent reduction in symptom score and remission as a score of 7 or less or 8 or less on the short or long versions of the Hamilton Rating Scale for Depression (HAM‐D) respectively. After two weeks' treatment, mirtazapine was associated with a response rate of 27 per cent and a remission rate of 10 per cent. This was not significantly different from the tricyclics or trazodone but superior to the SSRIs and venlafaxine. At the end of acute phase treatment (usually six weeks), rates of response (61 per cent) and remission (37 per cent) with mirtazapine were not significantly different compared with any other antidepressant, with the exception of a superior remission rate compared with paroxetine. Overall, 25 per cent of patients discontinued treatment with mirtazapine; this was no different from most other antidepressants but significantly more than with sertraline. Ten per cent of patients treated with mirtazapine withdrew due to adverse effects; by this criterion, mirtazapine was slightly better tolerated than amitriptyline and less well tolerated than sertraline. Multiple sclerosis Fluoxetine for MS? Fluoxetine seems an unlikely treatment to prevent progression of multiple sclerosis (MS) but investigators from The Netherlands have shown that it may substantially reduce new enhancing lesions in patients with relapsing‐remitting or relapsing secondary progressive disease ( J Neurol Neurosurg Psychiatry 2008;79: 1027‐31). Their proof‐of‐concept study randomised 40 non‐depressed patients with MS (mean disease duration 11 years; mean two exacerbations in last two years) to placebo or fluoxetine 20mg daily for 24 weeks. Brain gadolinium‐enhancing lesions were assessed by MRI at 4, 8, 16 and 24 weeks The cumulative number of enhancing lesions over 24 weeks was lower among patients taking fluoxetine (mean 1.84 vs 5.16 with placebo); mean cumulative lesion volume was also lower (124 vs 398mm 3 ) and the proportion of patients with no new lesions was greater with fluoxetine (32 vs 21 per cent). However, none of these differences was statistically significant. Fluoxetine was associated with significantly fewer scans showing new enhancing lesions (25 vs 41 per cent). Fluoxetine appeared to have no effect during the first eight weeks of treatment but restricting analysis to the last 16 weeks revealed stronger evidence of a reduction in number and volume of lesions and fewer new lesions. Fluoxetine may reduce major histocompatibility complex antigen expression by astrocytes secondary to increasing intracellular cAMP signalling through enhanced serotonin function. The authors say their findings provide sufficient evidence for further studies with fluoxetine. Parkinson's disease Does levodopa cause fat wasting? People with Parkinson's disease may suffer significant weight loss due to loss of body fat. This is not completely explained by motor symptom effects and may be related to drug treatment: there are theoretical grounds for believing that levodopa, which accumulates in fat cells, may promote lipolysis. Investigators from Germany have now reported in vitro and in vivo studies of the effects of levo‐dopa/benserazide on fat metabolism ( Eur J Clin Pharmacol 2008;64:86370). In 10 patients with Parkinson's disease, direct sampling of adipose tissue revealed no increase in lipolytic activity after treatment – in fact, levodopa attenuated lipolysis by adipocytes, while reducing glucose uptake by skeletal muscle cells. Levodopa – at least, when administered with benserazide – is therefore unlikely to contribute to fat loss in patients with Parkinson's disease, the authors conclude, but they raise the possibility that it may promote glucose intolerance. Dementia Stopping antipsychotics As efforts continue to cut the use of antipsychotic drugs as part of the management of dementia in nursing home residents, evidence is emerging that their use is not only risky for the individuals involved but also unnecessary for many. A study from Norway reveals how stopping the use of haloperidol, risperidone and olanzapine made no difference to behavioural or psychological symptoms in most elderly home residents ( Int J Geriatr Psychiatry 2008;23:889‐95). Fifty‐five residents with dementia (mean age 84 years) who had been taking an antipsychotic for a mean of 17 months were randomised to continue or abruptly stop treatment. After four weeks, 23 of the 27 assigned to stop treatment had not renewed use of an antipsychotic. Overall, total symptom scores (Neuropsychiatric Inventory) decreased from 8.3 to 7.3 over four weeks, with no difference between the groups in individual or total scores. Residents whose symptom scores were stable or improved had previously been treated with lower doses of antipsychotics than those whose scores deteriorated. At follow‐up after three months, 67 per cent of those who had stopped treatment were taking antipsychotics again. The authors comment that this probably reflects a reversion to traditional management by local clinicians. Switching to memantine NICE guidance on cholinesterase inhibitors for moderate to severe Alzheimer's disease includes recommendations for stopping treatment but no advice on what to do next. It also specifically excludes using memantine outside clinical trials. Scandinavian investigators have reported a small non‐blinded study of 46 patients with moderate to severe Alzheimer's disease (mean Mini‐Mental State Examination (MMSE) score 13) in whom clinicians or carers judged donepezil treatment was failing ( Int J Geriatr Psychiatry 2008;23:979‐81). After a two‐week run‐in, they were switched to memantine either abruptly or after dose reduction over a further two weeks. More patients in the abrupt (46 per cent) than the gradual discontinuation (32 per cent) group had treatment‐related adverse events; however, this difference was not considered clinically significant. Patient status was judged improved or stabilised in 74 per cent by Clinical Global Impression (CGI) scores and 53 per cent by MMSE score. Schizophrenia Aripiprazole and weight loss Aripiprazole may offer an alternative for people with schizophrenia who are overweight during treatment with another atypical antipsychotic, a study from The Netherlands suggests ( Acta Psychiatr Scand 2008; 118:246‐50).Of 298 overweight people attending a mental health centre, 53 agreed to treatment with aripiprazole (mean BMI 31kg per m 2 ). Aripiprazole was phased in as current antipsychotic treatment (mostly clozapine or olanzapine) was discontinued. Over 12 months, 11 per cent of patients were lost to follow up, 34 per cent discontinued aripiprazole and 55 per cent continued aripiprazole – about half in combination with another antipsychotic. Significant predictors of weight loss were taking aripiprazole for 12 months and stopping clozapine or olanzapine. Mean weight loss after 12 months' treatment with aripiprazole was 3.6kg whereas those who discontinued treatment gained an average of 4kg. Aripiprazole was associated with weight loss as both monotherapy (mean 3.0kg) or in combination (4.4kg). In patients on combination therapy with aripiprazole, the final mean clozapine dose was 28 per cent lower than at baseline. Epilepsy AEDs linked with bone loss in men A US cross‐sectional study has found that certain antiepileptic drugs (AEDs) are associated with loss of bone mass at the hip in men ( Neurology 2008;71:723‐30). Of the 4222 participants in the Osteoporotic Fractures in Men Study, 100 were taking a nonenzyme‐inducing AED, eg valproate, gabapentin, and 62 were taking an enzyme‐inducing AED, eg carbamazepine, phenytoin. Their mean age was 73‐74 years. After extensive adjustment for potential confounders, the rate of total hip bone loss was significantly increased in men taking non‐enzyme‐inducing agents compared with non‐AED users (0.53 per cent annually vs 0.35 per cent). The increase in bone loss with enzyme‐inducing AEDs (0.46 per cent) was not significantly different to that in non‐ED users. Copyright © 2008 Wiley Interface Ltd