Digest

Do omega‐3s improve depression? Low levels of omega‐3 fatty acids have been recorded in people with depression but trials of supplementation have produced conflicting findings. A meta‐analysis of 10 placebo‐controlled trials lasting at least four weeks and involving a total of 329 participants with depression ratings by HAM‐D score has now shed some light on the problem ( J Clin Psychiatry 2007;68:1056‐61). Most studies reported a positive effect from omega‐3 supplementation. The pooled effect size (standardised mean difference) was 0.61 and was statistically significant, suggesting a modest antidepressant effect. However, there was no dose‐response relationship and some evidence of publication bias and heterogeneity between studies. Better designed studies are needed, the authors conclude. Better timing for Parkinson's disease medication Irregular timing of medication is almost universal among patients with Parkinson's disease, prompting Glasgow neurologists to determine whether timing can be improved with education and whether this improves symptom control ( BMC Neurology 2007;7:20. doi:10.1186/1471‐2377‐7‐20). Patients taking at least one drug for their Parkinson's disease were randomised to no intervention or to education about the continuous dopaminergic hypothesis of symptom control. The intervention included verbal and written information, and tailored guidance on timing doses. Adherence was monitored using electronic containers that recorded the time and date of opening. Thirty‐one patients withdrew from the trial, leaving post‐intervention data for 52 patients. Baseline median timing adherence was 17 and 21 per cent in the control and intervention groups; this was much better for once‐daily drugs (82 per cent) than those taken twice daily (33 per cent) or more frequently. Three months after the intervention, timing adherence was significantly greater after the intervention compared with controls (39 vs 20 per cent). The ‘before and after’ difference in timing adherence was 23 per cent when once‐daily drugs were excluded. However, there were no improvements in symptom scores or quality‐of‐life scores. Zolpidem abuse may be more widespread than thought The ‘Z’ drugs have gradually been replacing benzodiazepines as hypnotics, in part because they are believed to carry a lower risk of dependence. However, the French regulatory authorities now suggest that abuse of zolpidem is a bigger problem than previously acknowledged ( Br J Clin Pharmacol 2007;64:198‐209). Their analysis of published literature suggested that the behavioural effects of zolpidem are generally similar to those of the benzodiazepines, with a history of alcohol or drug abuse as risk factors. The French authorities received 235 spontaneous reports of dependence or abuse between 1993 and 2002, and 159 forged prescriptions were identified between 1995 and 2002. The incidence of both increased over the years. The proportion of addicts in a national French programme who reported using zolpidem increased from less than one per cent in 1998 to 2 per cent in 1999 and 4 per cent since 2001. Whereas supplies were initially obtained solely through prescriptions, street deals accounted for 15‐20 per cent after 2001. Suicide and treatment for depression Recent concern about the risk of suicide associated with antidepressants has highlighted a possible increased risk after starting treatment. Two US studies, based on analyses of claims records, have now provided further information. New depression treatment episodes, including prescriptions for antidepressants and initial psychotherapy visits for depression (total 131 788), were identified in a health care programme for inpatients and outpatients (n=109 256) in Washington State and Idaho ( Am J Psychiatry 2007;164:1029‐34). Fifty‐five per cent of episodes were antidepressant prescriptions by family physicians, 5 per cent were prescriptions by psychiatrists, and 40 per cent were psychotherapy visits. As expected, the incidence of likely or possible suicide attempts was higher among patients treated by psychiatrists (1.1 per cent) and those referred for psychotherapy (0.8 per cent) than those receiving antidepressant prescriptions in primary care (0.3 per cent). However, the relationship between incidence and time was similar in all groups. The incidence was low more than 30 days before the index appointment, greatest in the 30 days preceding the appointment, then decreasing over the next six months. The pattern was similar in adolescents and adults under 25 years old. The second study used records from the Veterans' Health Administration ( Am J Psychiatry 2007;164:1044‐9) to evaluate suicide rates among 226 866 patients first diagnosed with depression in 2003/04. Of these, half received antidepressant monotherapy and 23 per cent received more than one drug; the remainder did not receive medication. Compared with no treatment, the odds ratio for suicide attempt was 0.37 in those treated with an SSRI and 0.29 for a tricyclic antidepressant. The relative risk of a suicide attempt after treatment compared with before was 0.5‐0.6 for any antidepressant therapy. The odds of a suicide attempt were similarly reduced for all age groups (including 18‐25 year olds) before and after treatment, including treatment with an SSRI. Cardiovascular effects of venlafaxine overdose Data from the Scottish Poisons Information Bureau show that the cardiovascular effects of venlafaxine in overdose increase the risk of arrhythmia ( Br J Clin Pharmacol 2007;64:192‐7). This retrospective analysis of 235 patients admitted with venlafaxine overdose (median dose 1500mg, range 919‐2800mg) showed that tachycardia, high blood pressure and mydriasis were common (28‐40 per cent of patients), and QTc prolongation occurred in over 10 per cent two to six hours after ingestion regardless of other drugs ingested. QTc prolongation and heart rate correlated significantly with dose ingested. No fatalities were recorded. Although only three patients developed arrhythmia, the authors concluded that the sympathomimetic effects of venlafaxine overdose pose an unexpectedly high risk of cardiovascular effects. Do adverse effects determine atypicals choice? A year‐long trial of three atypical antipsychotics has confirmed similar efficacy but revealed different adverse effect profiles ( Am J Psychiatry 2007;164:1050‐60 and 1061‐71). The US trial randomised 400 patients with schizophrenia to treatment with olanzapine (mean dose 11.7mg daily), risperidone (2.4mg daily) or quetiapine (506mg daily). Though patients were required to be in their first episode of psychotic illness, the duration of illness ranged from 0.4 to 166 months. The incidence of the primary endpoint (the percentage of patients withdrawing from treatment before 52 weeks) was 71 per cent with quetiapine and risperidone, and 68 per cent with olanzapine. Ten per cent discontinued because of adverse effects and 10 per cent due to patients' decisions; there were no differences between the groups. Symptoms improved in all groups, with olanzapine showing significantly greater benefit against positive symptoms after 52 weeks. The commonest adverse events associated with olanzapine were drowsiness (53 per cent), weight gain (51 per cent) and insomnia (38 per cent). For risperidone, they were drowsiness, menstrual irregularities and weight gain (50, 47 and 41 per cent). For quetiapine, they were drowsiness, increased sleep and weight gain (58, 42 and 40 per cent). Weight gain was greater, and more rapid, with olanzapine. A second analysis of this study included a subgroup of 244 patients who underwent neurocognitive assessment. All three drugs were associated with improved performance across a range of tests at 12 weeks, with continuing improvement to 52 weeks. The degree of cognitive change was modest but correlated with improved social and occupational functioning. Risperidone and cognitive function in children A pooled analysis of trials of risperidone in children with disruptive behaviour disorders and below average IQ scores has concluded that long‐term treatment may not harm cognitive function ( Biol Psychiatry 2007;62:226‐34). In two six‐week trials, there was no difference in measures of attention or verbal learning in children treated with risperidone 0.020.06mg per kg per day compared with placebo. In three non‐blinded trials lasting 48‐52 weeks, cognitive function improved compared with baseline. Somnolence was the commonest adverse event, reported in 46 per cent of children in short‐term trials ( vs 12 per cent with placebo) and 33 per cent in one‐year trials. Metabolic syndrome and antipsychotics Two studies have recently investigated the prevalence of metabolic syndrome in patients taking antipsychotic medication. In the North‐East of England, a case‐control study compared the prevalence of metabolic syndrome (International Diabetes Federation criteria) and cardiovascular risk factors in 90 people living in the community and taking an antipsychotic, with 92 age‐ and sex‐matched controls ( Br J Psychiatry 2007;191:23‐9). BMI, waist‐to‐hip ratio, total cholesterol, LDL‐cholesterol, serum triglycerides fasting blood glucose, HbA 1c and serum insulin were all significantly higher in those treated with an antipsychotic. Serum insulin was significantly higher in those taking atypical antipsychotics compared with all other groups. The prevalence of metabolic syndrome was 33 per cent in those treated with an antipsychotic compared with 12 per cent in controls. Significantly more of those treated with an antipsychotic were at high cardiovascular risk (18 vs 1.5 per cent); only one‐third of these individuals were taking a lipid‐lowering agent. Follow‐up of this patient cohort for 18 months ( BMC Psychiatry 2007;7:8. doi:10.1186/1471‐244V‐7 28) revealed that most patients did not receive further monitoring or management of their metabolic function in the community even though health professionals had been informed of patients' health status. A survey of 5434 people in Finland produced different results ( J Clin Psychiatry 2007;68:1045‐55). The prevalence of metabolic syndrome (by US ATP III criteria) was 25‐41 per cent among 118 people diagnosed with a psychotic disorder compared with 30 per cent in others. High potency antipsychotics were more frequently associated with metabolic syndrome (52 per cent) than low potency (39 per cent) or atypical agents (23 per cent). Are atypicals less cost effective? Atypical antipsychotics appear to be less cost effective than older agents in routine practice, say UK health economists in the first study of its kind to have non‐commercial funding ( Br J Psychiatry 2007; 191:14‐22). Using data collected prospectively from NHS patients who were being considered for a change in antipsychotic treatment, older antipsychotics were associated with lower direct costs than atypicals. The contribution of drug costs were low for both groups, with hospital costs accounting for most expenditure. Older agents were associated with a slight gain in quality‐adjusted life years (QALYs). Coenzyme Q10 ineffective for Parkinson's disease The antioxidant coenzyme Q10 does not improve activities of daily living or motor symptoms in patients with Parkinso's disease, German neurologists have reported ( Arch Neurol 2007;64:938‐44). Their double‐blind trial randomised 131 patients without motor fluctuations and on stable treatment to placebo or coenzyme Q10 100mg three times daily. After three months, motor function and activities of daily living improved similarly in each group; there were also no differences in other measures of disease severity or according to levodopa use. Coenzyme Q10 was well tolerated, with no significant increase in adverse effects compared with placebo. Cardiovascular events not related to triptan overuse An analysis of a French health insurance database has shown that high use of triptans is not associated with an increased risk of cardiovascular events; instead, events tend to occur in patients with risk factors ( Eur J Clin Pharmacol 2007;63:801‐7). In a cohort of 8625 who used triptans for the first time in 2002/03, 51 per cent of patients received only one prescription. Of the others, the maximum rates at which a triptan was supplied per 30day period were: eight defined daily doses (DDDs) or fewer in 15 per cent of patients; 9‐14 DDDs in 22 per cent; 15‐29 DDDs in 10 per cent; and 30 or more DDDs in 2 per cent . In virtually all patients, these prescribing peaks occurred after about 10 months. Compared with matched controls with no cardiovascular outcomes, the 155 patients with a cardiac event were more likely to be older, male and to have a history of cardiovascular disease or risk factors. Cardiac events did not correlate with intensity of trip‐tan use and 80 per cent of both cases and controls did not use a triptan in the 30 days preceding the event. Ergot use was lower among cases than controls. NSAIDs and cognitive function Protection from NSAIDs against cognitive decline may depend on early use and genetic make‐up, US epidemiologists suggest ( Neurology 2007;69:275‐82). Although randomised trials do not support a link between NSAIDs and preserved cognitive function, observational data suggest that timing and the APOE genotype may be important factors. This eight‐year analysis of the US Cache County Study found that in those who started NSAID use (at least four doses per week for more than a month at baseline) prior to age 65 years who had no APOEϵ4 alleles performed similarly to non‐users. However, those with APOEϵ4 alleles scored 0.4 points per year higher on MMSE than non‐users. Those who started NSAID use after age 65 years with APOEϵ4 alleles had higher baseline scores but showed no significant change in MMSE score over time. The authors conclude that NSAIDs may help prevent cognitive decline if started in midlife, especially in those with APOEϵ4 alleles. Copyright © 2007 Wiley Interface Ltd