Clinical Health Updates

Cognitive functioning improved by correcting anemia in young women

Clinical Question:
Does treatment improve cognitive abilities in young women with iron deficiency anemia?

Bottom Line:
Women with iron deficiency anemia, on average, perform worse on cognitive tests than women who have sufficient iron stores. Treatment over 4 months improved measures of cognitive performance (accuracy), as well as the speed of performing the tasks.

Reference:
Murray-Kolb LE, Beard JL. Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr 2007;85:778-787.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Evidence suggests that brain iron deficiency at any time in life may disrupt metabolic processes and subsequently change cognitive and behavioral functioning. Women of reproductive age are among those most vulnerable to iron deficiency and may be at high risk for cognitive alterations due to iron deficiency. The authors examined the relation between iron status and cognitive abilities in young women. A blinded, placebo-controlled, stratified intervention study was conducted in women aged 18-35 y of varied iron status who were randomly assigned to receive iron supplements or a placebo. Cognition was assessed by using 8 cognitive performance tasks (from Detterman’s Cognitive Abilities Test) at baseline (n = 149) and after 16 wk of treatment (n = 113). At baseline, the iron-sufficient women (n = 42) performed better on cognitive tasks (P = 0.011) and completed them faster (P = 0.038) than did the women with iron deficiency anemia (n = 34). Factors representing performance accuracy and the time needed to complete the tasks by the iron-deficient but nonanemic women (n = 73) were intermediate between the 2 extremes of iron status. After treatment, a significant improvement in serum ferritin was associated with a 5-7-fold improvement in cognitive performance, whereas a significant improvement in hemoglobin was related to improved speed in completing the cognitive tasks.

Adjunctive antidepressants not effective for depression in bipolar disorder

Clinical Question:
Is the addition of an antidepressant to a mood stabilizer an effective strategy for short-term treatment of major depressive episodes in patients with bipolar disorder?

Bottom Line:
The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder.

Reference:
Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007;356:1711-1722.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. The authors determined whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P=0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups.

Combination of antipsychotics and mood stabilizers best for acute mania

Clinical Question:
What is the optimal medical management for adults with acute mania?

Bottom Line:
Currently available data suggest that combining SGAs and MSs is the most efficacious treatment of acute mania.

Reference:
Scherk H, Pajonk FG, Leucht S. Second-generation antipsychotic agents in the treatment of acute mania. A systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry 2007;64:442-455.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
Recommendations of treatment guidelines concerning the use of second-generation antipsychotic (SGA) agents for acute mania vary substantially across committees or working groups. Meta-analyses addressing the use of SGAs in the treatment of acute mania are lacking. The author conduct a meta-analysis of the efficacy and safety of SGAs in the treatment of acute mania. Randomized controlled trials comparing SGAs with placebo, first-generation antipsychotic drugs, or mood stabilizers (MSs) in the treatment of acute mania were searched for in the PsiTri and MEDLINE databases (last search: May 2006). The abstracts, titles, and index terms of studies were searched using the following key words: aripiprazole, amisulpride, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zotepine in conjunction with mania, manic, and bipolar. Data on efficacy, global dropout, dropout due to adverse events, dropout due to inefficacy, weight gain, rate of somnolence, and extrapyramidal symptoms were extracted and combined in a meta-analysis. A total of 24 studies with 6187 patients were included. The SGAs were significantly more efficacious than placebo. The analysis demonstrated that adding antipsychotic agents to MS treatment was significantly more effective than treatment with MSs alone. The SGAs displayed efficacy comparable with that of MSs. Some SGAs seemed to induce more extrapyramidal symptoms than placebo. The SGAs were also associated with higher rates of somnolence than placebo.

Atypical antipsychotics minimally effective, poorly tolerated in AD

Clinical Question:
Are the newer atypical antipsychotics effective in patients with Alzheimer’s disease?

Bottom Line:
Atypical antipsychotics are minimally, if at all, effective for patients with Alzheimer’s disease (AD), and they have significant adverse effects. They should not be routinely used for the treatment of psychosis, agitation, or aggression in these patients.

Reference:
Schneider LS, Tariot PN, Dagerman KS, et al, with the CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006;355:1525-1538.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Although atypical antipsychotics are widely used in the treatment of psychosis, agitation, and aggression in patients with AD, clinical trials to date have been of limited duration and have not adequately addressed the tolerability of the drugs. In addition, there are new concerns regarding the safety of these drugs, with recent studies* finding an increased risk of death (relative risk = 1.6 – 1.7). In this study, the authors identified 421 outpatients with probable AD, a Mini-Mental State score between 5 and 26, and delusions, hallucinations, aggression, or agitation. They were randomized in a 2:2:2:3 ratio to olanzapine (Zyprexa, 2.5 mg or 5.0 mg), quetiapine (Seroquel, 25 mg or 50 mg), risperidone (Risperdal, 0.5 mg or 1.0 mg), or placebo. Whether to use the smaller or larger dose of each drug was determined by the study physicians, who were blinded to treatment assignment. They chose an unidentified small or large pill from an envelope, then adjusted the dose on the basis of patient response. Patients were followed up for up to 3 years; the primary outcomes were the time to discontinuation of the study drug and the degree of improvement on the Clinical Global Impression of Change (CGIC) scale at week 12. Groups were balanced at the start of the study and analysis was by intention to treat. The patients’ mean Mini-Mental State score was 15, their average age was 78 years, 56% were women, and 18% were African-American.

The average final doses of each drug were olanzapine 5.5 mg, quetiapine 56 mg, and risperidone 1.0 mg. The mean time to discontinuation was between 5.3 weeks and 8.1 weeks for the 4 groups, with no significant difference between groups. The atypical antipsychotics were more likely to be discontinued because of adverse effects (16% – 24% vs 5% for placebo), while placebo was more likely to be discontinued because of lack of efficacy (70% vs 39% – 53% vs 70% for active drugs). There was no significant difference between groups regarding the response as measured by the CGIC scale at 12 weeks (21% for placebo vs 26% – 32% for active drugs). Adverse effects occurring more frequently in patients receiving an active drug included parkinsonism or extrapyramidal signs (olanzapine and risperidone), sedation and weight increase (all 3 active drugs), and confusion (olanzapine and risperidone).

Light tx for SAD effective short-term

Clinical Question:
In patients with seasonal affective disorder or other types of depression, is light therapy effective as sole therapy or as an adjunct therapy?

Bottom Line:
Many reports of the efficacy of light therapy are not based on rigorous study designs. This analysis of randomized, controlled trials suggests that bright light treatment and dawn simulation for seasonal affective disorder and bright light for nonseasonal depression are efficacious, with effect sizes equivalent to those in most antidepressant pharmacotherapy trials. Adopting standard approaches to light therapy’s specific issues (e.g., defining parameters of active versus placebo conditions) and incorporating rigorous designs (e.g., adequate group sizes, randomized assignment) are necessary to evaluate light therapy for mood disorders.

Reference:
Golden RN, Gaynes BN, Ekstrom RD, et al. The efficacy of light therapy in the treatment of mood disorders: A review and meta-analysis of the evidence. Am J Psychiatry 2005;162:656-62.

Study Design:
Systematic review

Synopsis:
The purpose of this study was to assess the evidence base for the efficacy of light therapy in treating mood disorders. The authors systematically searched PubMed (January 1975 to July 2003) to identify randomized, controlled trials of light therapy for mood disorders that fulfilled predefined criteria. These articles were abstracted, and data were synthesized by disease and intervention category. Only 13% of the studies met the inclusion criteria. Meta-analyses revealed that a significant reduction in depression symptom severity was associated with bright light treatment (eight studies, having an effect size of 0.84 and 95% confidence interval [CI] of 0.60 to 1.08) and dawn simulation in seasonal affective disorder (five studies; effect size=0.73, 95% CI=0.37 to 1.08) and with bright light treatment in nonseasonal depression (three studies; effect size=0.53, 95% CI=0.18 to 0.89). Bright light as an adjunct to antidepressant pharmacotherapy for nonseasonal depression was not effective (five studies; effect size=-0.01, 95% CI=-0.36 to 0.34).

Role of Aerobic exercise to seniors with mood disorder

Clinical Question:
Do aerobic exercise improve quality of life in old age patients with mood disorder?

Bottom Line:
The data suggest that an aerobic exercise program at VT-1 intensity suffices to promote favorable modifications in depressive and anxiety scores to improve the quality of life in seniors.

Reference:
Depression, anxiety and quality of life scores in seniors after an endurance exercise program.Antunes HK, Stella SG, Santos RF, Bueno OF, Mello MT.Rev Bras Psiquiatr. 2005 Dec;27(4):266-271.

Synopsis:
Mood disorders are a frequent problem in old age, and their symptoms constitute an important public health issue. These alterations affect the quality of life mainly by restricting social life. The participation in a regular exercise program is an effective way of reducing or preventing the functional decline associated with aging. The aim of the present study was to examine the effects of fitness-endurance activity (at the intensity of Ventilatory Threshold 1 (VT-1)) in depression, anxiety and quality of life scores in seniors. The study involved 46 sedentary seniors aged 60-75 (66.97 +/- 4.80) who were randomly allocated to two groups: 1) Control group, which was neither asked to vary their everyday activities nor to join a regular physical fitness program; and 2) Experimental group, whose members took part in an aerobic fitness program consisting of ergometer cycle sessions 3 times a week on alternate days for six months working at a heart rate corresponding to ventilatory threshold (VT-1) intensity. Subjects were submitted to a basal evaluation using the geriatric depression screening scale – GDS, STAI trait/state (anxiety scale) and SF-36 (quality of life scale). Comparing the groups after the study period, we found a significant decrease in depressive and anxiety scores and an improvement in the quality of life in the experimental group, but no significant changes in the control group.

Small increased risk of death with atypical antipsychotics for dementia

Clinical Question:
Do atypical antipsychotic drugs increase the risk of death for patients with dementia?

Bottom Line:
Atypical antipsychotic drugs may be associated with a small increased risk for death compared with placebo. This risk should be considered within the context of medical need for the drugs, efficacy evidence, medical comorbidity, and the efficacy and safety of alternatives. Individual patient analyses modeling survival and causes of death are needed.

Reference:
Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia. Meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934-43.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease and other dementia; however, concerns have arisen about the increased risk for cerebrovascular adverse events, rapid cognitive decline, and mortality with their use. To assess the evidence for increased mortality from atypical antipsychotic drug treatment for people with dementia. MEDLINE (1966 to April 2005), the Cochrane Controlled Trials Register (2005, Issue 1), meetings presentations (1997-2004), and information from the sponsors were searched using the terms for atypical antipsychotic drugs (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone), dementia, Alzheimer disease, and clinical trial. Published and unpublished randomized placebo-controlled, parallel-group clinical trials of atypical antipsychotic drugs marketed in the United States to treat patients with Alzheimer disease or dementia were selected by consensus of the authors. Trials, baseline characteristics, outcomes, all-cause dropouts, and deaths were extracted by one reviewer; treatment exposure was obtained or estimated. Data were checked by a second reviewer. Fifteen trials (9 unpublished), generally 10 to 12 weeks in duration, including 16 contrasts of atypical antipsychotic drugs with placebo met criteria (aripiprazole [n = 3], olanzapine [n = 5], quetiapine [n = 3], risperidone [n = 5]). A total of 3353 patients were randomized to study drug and 1757 were randomized to placebo. Outcomes were assessed using standard methods (with random- or fixed-effects models) to calculate odds ratios (ORs) and risk differences based on patients randomized and relative risks based on total exposure to treatment. There were no differences in dropouts. Death occurred more often among patients randomized to drugs (118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was 1.54; 95% confidence interval [CI], 1.06-2.23; P = .02; and risk difference was 0.01; 95% CI, 0.004-0.02; P = .01). Sensitivity analyses did not show evidence for differential risks for individual drugs, severity, sample selection, or diagnosis.