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Complementary therapies for depression Many people use complementary therapies, often at the same time as a conventional medicine. US researchers looked for evidence of efficacy for these therapies in the management of depression, anxiety and sleep disorders in older people ‐ with some positive results ( J Clin Psychiatry 2007;68:1461‐71). Their systematic review found 33 randomised comparative trials with at least 30 participants lasting at least two weeks. Most were small, and few had systematic recruitment criteria or an adequate explanation of methodology; only five included a declaration of interest. The most frequent interventions were mind‐body treatments, eg meditation, music therapy, biologically‐based (melatonin, Ginkgo biloba) and energy‐based treatments (light therapy). Overall, two‐thirds of the studies reported positive results: 77 per cent of those on sleep disturbance and 59 per cent of studies on anxiety and depression. However, the methodological quality of negative studies was higher than that of positive ones due to larger sample sizes and longer duration. Mind‐body therapies were reportedly the most effective (83 per cent positive). Genes associated with suicidal ideation The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study included an analysis of single nucleotide polymorphisms in 68 genes from participants' DNA. US investigators have now reported a correlation between two gene markers and suicidal ideation ( Am J Psychiatry 2007;164:1530‐8). During treatment with citalopram in the initial phase of the study, suicidal ideation occurred 120 of the 1862 patients from whom a DNA sample was obtained. Compared with the other patients (controls), they were more likely to have a higher dose of citalopram, to enter the second phase of the study (for further treatment) and less likely to achieve remission; none actually attempted suicide. Two genes were significantly associated with suicidal ideation; both encoded for ionotropic glutamate receptors and their effects appeared to be additive. Patients carrying both alleles were at 15‐fold increased risk of treatment‐emergent suicidal ideation compared with controls. Parkinson's disease and treatment for depression Depression is relatively common among people with Parkinson's disease (PD) but, say US investigators, there is concern that treatment may be suboptimal ‐ due to concern about worsening PD by antidepressant therapy and patients' reluctance to take additional medication. They compared antidepressant prescribing for older male patients with depression in two matched groups with and without PD (n=7868 for each) ( J Geriatr Psychiatry Neurol 2007;20:161. doi: 10.1177/ 0891988707301866). They found that the risk of comorbid PD and depression increased with age but depression appeared to be more severe in patients who did not have PD. About three‐quarters of patients in each group received at least one prescription for an antidepressant in the 12 months following a consultation for depression, the mean total being only slightly greater for patients with PD (2.50 vs 2.37). The pattern of antidepressant use was also similar: about two‐thirds of scrips in both groups were for SSRIs, though patients with PD were more likely to receive venlafaxine or mirtazapine and less likely to have a tricyclic. The authors conclude that a diagnosis of PD has minimal impact on the treatment of depression. Efforts should be focused on screening and diagnosis, they add. Novel treatment for acute migraine Calcitonin gene‐related peptide (CGRP) is increased during migraine attacks and the triptans may act partly by inhibiting its release. Investigators at Merck Research Laboratories have developed a CGRP receptor antagonist, MK‐0974, which can be taken orally to treat an acute attack ( Neurology 2007;Oct 3. Epub ahead of print). A potential advantage of the novel drug is that it appears to have no vasoconstrictor activity. They randomised 330 patients with moderate to severe migraine to treatment with MK‐0974, rizatriptan 10mg or placebo; a second dose could be taken after two hours if headache persisted. The primary endpoint, pain reduction to mild or none at two hours, occurred in 46 per cent of patients with placebo, 70 per cent with rizatriptan, 68 per cent with MK0974 300 or 600mg, and 48 per cent with MK‐0794 400mg. Similar improvements were seen in other endpoints, including freedom from pain at two hours, improved associated symptoms, and use of a second dose or rescue medication. The overall incidence of adverse effects associated with MK‐0794 was similar to that of rizatriptan; the commonest were nausea, dizziness and headache. Antipsychotics and bipolar disorder Older people with bipolar disorder have greater adherence rates to antipsychotic medication than younger patients but a substantial proportion still have difficulties, according to an analysis of a US case registry ( Int J Geriatr Psychiatry 2007;22:992‐8). The analysis included 26 530 patients aged 60 years or younger (mean 47 years) and 6461 aged over 60 years (mean 69 years); the proportions receiving an antipsychotic were 47 and 37 per cent respectively. Calculating adherence as the medication possession ratio (days of supply received as a proportion of that prescribed), the rates of full adherence (>80 per cent) were 49 per cent in younger patients and 61 per cent in the older group. Partial adherence rates (50 to 80 per cent) were 22 and 19 per cent; non‐adherence rates (<50 per cent) were 29 and 20 per cent. As with younger patients, nonadherence in older patients was associated with substance abuse and homelessness. Mean medication possession ratios (MPRs) were greater for patients treated with two antipsychotics compared with monotherapy in both age groups; for those taking a single drug, MPRs were greater for conventional compared with atypical agents. • A long‐term study suggests that monotherapy with aripiprazole prevents relapse for nearly two years in few patients with bipolar disorder ( J Clin Psychiatry 2007;68:1480‐91). Of 206 patients who were stabilised during an acute episode by aripiprazole 15‐30mg daily for 6‐18 weeks, 161 were randomised to continue aripiprazole or switch to placebo for 26 weeks. Of the 67 who completed this phase without relapsing, 66 continued double‐blind treatment for a further 74 weeks. A further 26 per cent of those taking placebo and 13 per cent taking aripiprazole discontinued due to lack of efficacy; after other withdrawals, only 12 patients completed the entire 100‐week trial. The proportions of patients experiencing relapse by 100 weeks were 33 per cent with aripiprazole and 52 per cent with placebo. The time to relapse was significantly greater with aripiprazole (hazard ratio 0.53), the difference being due to fewer manic episodes. Discontinuation due to adverse effects was more frequent with placebo, though extrapyramidal reactions were more common with aripiprazole (22 vs 15 per cent). • Olanzapine is effective for bipolar mania in adolescents but the penalty of adverse effects is similar to that in adults ( Am J Psychiatry 2007;164:1547‐56). In this three‐week trial, 161 patients aged 13‐17 years with an acute manic or mixed episode were randomised to olanzapine 2.5‐20mg daily (mean 11mg daily) or placebo. Thirty per cent of those assigned to placebo and 11 per cent of those taking olanzapine discontinued due to lack of efficacy. Olanzapine was associated with a significantly greater reduction in the Young Mania Rating Scale score and greater improvement in clinical global assessments. These differences were evident after one week, but not after three to four days. Response rates were 49 per cent for olanzapine and 22 per cent for placebo at three weeks; remission rates were 35 and 11 per cent respectively. Olanzapine was associated with greater weight gain (mean 3.7 vs 0.3kg), raised blood pressure and heart rate, and increases in prolactin, hepatic enzymes, fasting glucose and cholesterol levels than placebo. Augmenting atomoxetine with methylphenidate A pilot study from the US suggests that adding methylphenidate may improve the response to treatment for ADHD when atomoxetine alone is not effective ( Child Adolesc Psychiatry Mental Health 2007;1:10. doi:10.1186/1753‐2000‐1‐10). Twenty‐five children (mean age 10 years) with ADHD, for whom an adequate trial of stimulant therapy had failed, received atomoxetine 1.2mg per kg daily. After four weeks, four were defined as responders and continued on atomoxetine monotherapy; the others were randomised to additional treatment with once‐daily methylphenidate 1.1mg per kg daily or placebo for a further six weeks. Combined therapy was initially more effective than atomoxetine alone but there was no difference after five weeks. Overall, atomoxetine was considered effective, with 43 per cent of children rated as responding to treatment. Adding methylphenidate did not substantially affect adverse event rates. The authors conclude that more studies of combined therapy may be worthwhile. Paliperidone prolonged‐release vs quetiapine Acutely ill, hospitalised patients with schizophrenia showed significant improvement in symptoms after taking paliperidone prolonged‐release tablets as compared with quetiapine and placebo. Significant symptom improvement, as measured by the change in the total Positive and Negative Syndrome Scale (PANSS) score was observed with paliperidone as early as five days into therapy and continued through to the end of the two‐week study period, according to preliminary data presented at the 20th Annual US Psychiatric and Mental Health Congress in Orlando, Florida, in October. In the study, 399 patients with an acute exacerbation of symptoms of schizophrenia were randomised to receive paliperidone prolonged‐release tablets, quetiapine or placebo. These patients were either hospitalised or in need of hospitalisation at the start of the trial and willing to remain hospitalised for a minimum of 10 days. The study involved two phases: a two‐week monotherapy phase (primary endpoint) followed by a four‐week additive therapy phase (secondary endpoint). During the four‐week phase, patients could be prescribed additional psychotropic therapy as clinically indicated to manage psychiatric symptoms. The average doses during the monotherapy phase were 10.4mg daily for paliperidone prolonged‐release tablets and 690.9mg daily for quetiapine. The primary efficacy endpoint was total change in PANSS score from baseline to the end of the monotherapy phase (day 14). The average PANSS score at baseline was 102.8 (±13.1) for the paliperidone prolonged‐release tablets group, 101.6 (± 13.5) for the quetiapine group, and 103.8 (±15.7) for the placebo group. At the end of the monotherapy phase (day 14), the change in the total score from baseline was: ‐23.4 (1.8) for paliperidone, ‐17.1(1.8) for quetiapine and ‐15.0 (2.2) for placebo, with paliperidone showing a significant reduction in symptoms over both quetiapine (p<0.001) and placebo (p<0.001). Discontinuation rates due to adverse events were: paliperidone prolonged‐release tablets (4 per cent), quetiapine (10 per cent) and placebo (6 per cent). In the monotherapy phase, adverse events that occurred with an incidence of >10 per cent were headache (paliperidone prolonged‐release tablets 12 per cent, quetiapine 8 per cent and placebo 14 per cent), somnolence (9 per cent, 12 per cent, 1 per cent respectively), tremor (14 per cent, 5 per cent, 8 per cent), and insomnia (10 per cent, 9 per cent, 11 per cent). Antipsychotics, mortality and dementia Antipsychotics are not recommended for elderly patients or those with dementia. An analysis of prescriptions for 10 615 patients over 65 with dementia found that 12‐month mortality was increased up to two‐fold by antipsychotics ( Am J Psychiatry 2007;164:1568‐76). In patients using other psychotropic medication, 12‐month mortality was 14.6 per cent. There was little difference between conventional (25.2 per cent mortality) and atypical antipsychotics (22.6 per cent), though use of both agents increased the risk further (29.1 per cent). There was no evidence that comorbidity contributed to the risk but more deaths due to dementia‐related causes occurred with antipsychotic use. Atypical antipsychotics and metabolic syndrome Metabolic syndrome is relatively common and is a risk factor for cardiovascular events and diabetes. The prevalence of the syndrome is higher among people with schizophrenia, and their risk may be increased further by treatment with an atypical antipsychotic. Workers from Bristol‐Myers Squibb now suggest that the company's antipsychotic aripiprazole is associated with a lower risk than olanzapine ( J Clin Psychiatry 2007;68:1510‐6). Pooling data from four randomised trials, they found that the incidence of metabolic syndrome among 91 placebo recipients was 14.3 per cent compared with 5.3 per cent of those 151 patients assigned to aripiprazole. When those with metabolic syndrome at baseline were included, the prevalence was 26 and 20 per cent respectively. In comparative trials, the incidence associated with olanzapine (n=212) was 27 per cent compared with 16 per cent for aripiprazole (n=198), with a prevalence of 42 and 28 per cent respectively. Less postcode prescribing of clozapine In 2000, there was a 34‐fold variation in prescribing of clozapine between mental health trusts in England. Has this changed following the advent of generic clozapine in 2004 and NICE guidance on the management of schizophrenia in 2002? Psychiatrists from Kent and London evaluated prescribing data for 2005/06 from 45 of 75 trusts contacted ( Psychiatric Bull 2007;31: 384‐7). They found the variation between trusts was now down to a factor of five. However, they estimated that only 30 per cent of the 63 000 patients identified by NICE as eligible for treatment were actually being treated with clozapine. Glutamatergic agents for schizophrenia There is some evidence that agents enhancing glutamatergic function may improve the negative symptoms of schizophrenia. A joint US‐Israeli study has now evaluated glycine 15‐60g daily and D‐cycloserine 25‐50mg daily in a placebo‐controlled trial in 157 patients with moderate to severe negative symptoms ( Am J Psychiatry 2007; 164:1593‐602). Conventional treatment, with the exception of clozapine, was continued. After 16 weeks there were no differences in symptom scores, responder rates or effects on cognition between the groups. Glycine was associated with nausea or dry mouth in about one‐third of patients. Cognitive effects of antipsychotics Two studies have recently evaluated the possible effects of atypical antipsychotics on cognitive function. One compared risperidone, olanzapine and haloperidol in 100 patients ( Am J Psychiatry 2007;164:1585‐92), carrying out multiple assessments of cognitive function over eight weeks. There were no differences between the drugs, and no changes in emotion and social perception. All drugs were associated with improved general cognitive ability. The second trial ( Arch Gen Psychiatry 2007;64:1115‐22) compared cognitive performance in 104 patients with first‐episode schizophrenia treated with olanzapine or risperidone with that in 84 healthy controls. Cognitive assessments carried out at baseline, six and 16 weeks found no overall difference between patients and controls, or between the two drugs. Of 16 measures used, improvement occurred in nine; two (visual designs and trail making) improved more in patients than in controls. Overall, the authors conclude, changes in cognitive function during antipsychotic treatment were attributable to practice effects of repeated measurement. Six‐month data for agomelatine Six‐month efficacy data for agomelatine were presented at the European College of Neurospsychopharmacology (ECNP) annual congress in Vienna in October. The international study showed agomelatine's efficacy in preventing relapse in outpatients with major depressive disorder (MDD) over six months, irrespective of the severity of depression. The data were from a multi‐centre, randomised, double‐blind study involving 492 patients with recurrent MDD according to DSMIV classification. The primary outcome of the study was time to relapse (relapse defined as HAMD17 score ≥16 or any withdrawal for lack of efficacy according to the investigator's opinion during the randomised period). Overall, agomelatine was associated with a significantly lower relapse rate compared with placebo (p=0.0001). Nearly half of all patients who received placebo relapsed (46.6 per cent) compared with 21.7 per cent of patients who received agomelatine over a six‐month treatment period, representing a 54 per cent reduction of the risk of relapse for patients treated with agomelatine. These results were further confirmed in the more severely depressed subpopulation of the study. In patients with a baseline HAM‐D17 score of ≥25, agomelatine was associated with significantly fewer cumulative relapses (22.7 per cent) than placebo (50.4 per cent ) over six months. A registration file for agomelatine is being considered by the EMEA. Copyright © 2007 Wiley Interface Ltd