Toshiaki A. Furukawa

Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis

BACKGROUND Conventional meta-analyses have shown inconsistent results for efficacy of second-generation antidepressants. We therefore did a multiple-treatments meta-analysis, which accounts for both direct and indirect comparisons, to assess the effects of 12 new-generation antidepressants on major depression. METHODS We systematically reviewed 117 randomised controlled trials (25 928 participants) from 1991 up to Nov 30, 2007, which compared any of the following antidepressants at therapeutic dose range for the acute treatment of unipolar major depression in adults: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine. The main outcomes were the proportion of patients who responded to or dropped out of the allocated treatment. Analysis was done on an intention-to-treat basis. FINDINGS Mirtazapine, escitalopram, venlafaxine, and sertraline were significantly more efficacious than duloxetine (odds ratios [OR] 1.39, 1.33, 1.30 and 1.27, respectively), fluoxetine (1.37, 1.32, 1.28, and 1.25, respectively), fluvoxamine (1.41, 1.35, 1.30, and 1.27, respectively), paroxetine (1.35, 1.30, 1.27, and 1.22, respectively), and reboxetine (2.03, 1.95, 1.89, and 1.85, respectively). Reboxetine was significantly less efficacious than all the other antidepressants tested. Escitalopram and sertraline showed the best profile of acceptability, leading to significantly fewer discontinuations than did duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine. INTERPRETATION Clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favour of escitalopram and sertraline. Sertraline might be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favourable balance between benefits, acceptability, and acquisition cost.

Twelve-month prevalence, severity, and treatment of common mental disorders in communities in Japan: preliminary finding from the World Mental Health Japan Survey 2002-2003.

Abstract  To estimate the prevalence, severity, and treatment of Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM‐IV) mental disorders in community populations in Japan, face‐to‐face household surveys were conducted in four community populations in Japan. A total of 1663 community adults responded (overall response rate, 56%). The DSM‐IV disorders, severity, and treatment were assessed with the World Mental Health version of the World Health Organization (WHO) Composite International Diagnostic Interview (WMH‐CIDI), a fully structured lay‐administered psychiatric diagnostic interview. The prevalence of any WMH‐CIDI/DSM‐IV disorder in the prior year was 8.8%, of which 17% of cases were severe and 47% were moderate. Among specific disorders, major depression (2.9%), specific phobia (2.7%), and alcohol abuse/dependence (2.0%) were the most prevalent. Although disorder severity was correlated with probability of treatment, only 19% of the serious or moderate cases received medical treatment in the 12 months before the interview. Older and not currently married individuals had a greater risk of having more severe DSM‐IV disorders if they had experienced any within the previous 12 months. Those who had completed high school or some college were more likely to seek medical treatment than those who had completed college. The study confirmed that the prevalence of DSM‐IV mental disorders was equal to that observed in Asian countries but lower than that in Western countries. The percentage of those receiving medical treatment was low even for those who suffered severe or moderate disorders. Possible strategies are discussed.

Cross-cultural validation of the Beck Depression Inventory-II in Japan.

The Beck Depression Inventory has undergone substantial revision recently as the BDI-II to correspond to DSM-IV criteria. We developed the Japanese version of the BDI-II and examined its psychometric properties. The linguistic equivalence was verified by a back-translation method. The final translation was administered to the visitors at a public health care center, and the responses of 766 adults (age = 24-82 years, women = 40%) were analyzed. Half of the participants completed the Center for Epidemiologic Studies Depression Scale (CES-D) as well. A high level of internal consistency reliability (Cronbachs alpha = 0.87) and item homogeneity was confirmed. Exploratory factor analysis showed a two-factor structure (cognitive and somatic-affective), which was almost identical to the original model demonstrated by Beck et al. (1996, Manual for the Beck Depression Inventor Psychological Corporation, San Antonio, TX, USA). The following confirmatory factor analysis also supported the two-factor structure. Adequate correlation (r = 0.69, P < 0.001) between the total score of the BDI-II and that of the CES-D was observed. A higher score for women compared to men, without significant age differences, was consistent with the results of previous reports. We conclude that the Japanese version of the BDI-II is psychometrically robust and can be used to assess depressive symptoms in Japanese people.

Depression, inflammation, and pain in patients with rheumatoid arthritis

OBJECTIVE An association between depression and inflammation has been suggested. In patients with rheumatoid arthritis (RA), pain is a major symptom associated with depression and inflammation. We examined the independent associations between depression, the inflammation marker C-reactive protein (CRP) level, and pain in patients with RA. METHODS In total, 218 RA outpatients completed self-administered questionnaires, using the Beck Depression Inventory II to measure depressive symptoms and a visual analog scale to quantify their perceived pain. Functional disability and CRP level were also measured. RESULTS Depression scores were mildly and positively correlated with the CRP level (r = 0.46, P < 0.001). Both the depression score (standardized beta = 0.35, P < 0.001) and the CRP level (standardized beta = 0.35, P < 0.001) were significantly associated with pain, even after adjustment for clinical covariates in regression analysis. In logistic analysis, the combined effects on the risk of severe pain (pain score in the upper tertile) increased with depression scores and CRP levels linearly. CONCLUSION Depression severity and inflammation were associated with each other and appeared to have independent effects on perceived pain. Therefore, a clinical approach that takes into account both the body and the mind could have benefits and could enable optimal pain control.

Systematic Review and Meta-analysis of Cannabis Treatment for Chronic Pain

SETTING Cannabis preparations have been used as a remedy for thousands of years in traditional medicine. Clinical use of cannabinoid substances is restricted, due to legal and ethical reasons, as well as limited evidence showing benefits. OBJECTIVE To assess the efficacy and harms of cannabis preparations in the treatment of chronic pain. DESIGN Systematic review and meta-analysis of double-blind randomized controlled trials that compared any cannabis preparation to placebo among subjects with chronic pain. An electronic search was made in Medline/Pubmed, Embase, and The Cochrane Controlled Trials Register (TRIALS CENTRAL) of all literature published until February 2008, as well as specific web pages devoted to cannabis. Studies were cross-checked, selected, and assessed. RESULTS Eighteen trials were included. The efficacy analysis (visual analog scales) displayed a difference in standardized means in favor of the cannabis arm of -0.61 (-0.84 to -0.37), with statistical homogeneity (I(2) = 0.0%; P = 0.50). For the analysis of harms, the following Odds Ratios (OR) and number needed to harm (NNH) were obtained: for events linked to alterations to perception, OR: 4.51 (3.05-6.66), NNH: 7 (6-9); for events affecting motor function, 3.93 (2.83-5.47), NNH: 5 (4-6); for events that altered cognitive function, 4.46 (2.37-8.37), NNH: 8 (6-12). CONCLUSIONS Currently available evidence suggests that cannabis treatment is moderately efficacious for treatment of chronic pain, but beneficial effects may be partially (or completely) offset by potentially serious harms. More evidence from larger, well-designed trials is needed to clarify the true balance of benefits to harms.

Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials

Background: Concern has been raised about the efficacy of antidepressant therapy for major depression in adults. We undertook a systematic review of published and unpublished clinical trial data to determine the effectiveness and acceptability of paroxetine. Methods: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, the Cochrane Central Register of Controlled Trials, the GlaxoSmithKline Clinical Trial Register, MEDLINE and EMBASE up to December 2006. Published and unpublished randomized trials comparing paroxetine with placebo in adults with major depression were eligible for inclusion. We selected the proportion of patients who left a study early for any reason as the primary outcome measure because it represents a hard measure of treatment effectiveness and acceptability. Results: We included in our review 29 published and 11 unpublished clinical trials, with a total of 3704 patients who received paroxetine and 2687 who received with placebo. There was no difference between paroxetine and placebo in terms of the proportion of patients who left the study early for any reason (random effect relative risk [RR] 0.99, 99% confidence interval [CI] 0.88–1.11). Paroxetine was more effective than placebo, with fewer patients who did not experience improvement in symptoms of at least 50% (random effect RR 0.83, 99% CI 0.77–0.90). Significantly more patients in the paroxetine group than in the placebo group left their respective studies because of side effects (random effect RR 1.77, 95% CI 1.44–2.18) or experienced suicidal tendencies (odds ratio 2.55, 95% CI 1.17–5.54). Interpretation: Among adults with moderate to severe major depression in the clinical trials we reviewed, paroxetine was not superior to placebo in terms of overall treatment effectiveness and acceptability. These results were not biased by selective inclusion of published studies.

Antidepressant medications and other treatments of depressive disorders: a CINP Task Force report based on a review of evidence

According to the World Health Organization, depression is one of the most debilitating disorders affecting humankind. The social and economic costs of chronic ill health resulting from untreated or inadequately treated depression are considerable and frequently underestimated. The CINP established the Task Force on Antidepressant Medications in 2004 to examine all aspects of therapy with antidepressant drugs. This was considered necessary as, despite the availability of effective antidepressants for the past 50 years, a substantial minority of depressed patients either remains untreated or under treated. As the only international organization devoted to the promotion of research, education and the applications of neuropsychopharmacology to the clinic, the main task of the CINP is to extend the knowledge of the drugs that are available with the aim of improving the management of mental disorders. The purpose of this Task Force document was not to produce an academic monograph nor a set of guidelines, but to provide mental health and other professionals with comprehensive and objective information about the different aspects of the use of antidepressants important in clinical practice. The Task Force consisted of 15 experts in psychiatry, psychopharmacology, public health, economics and family care. The majority of its members are senior members of the CINP. The Task Force was also advised to rely in the course of its work on advisors in different countries selected because of their outstanding expertise in the matters covered by the review. The report presented here was approved by the Executive Committee and the Council of the CINP at its meeting in Chicago in July 2006. As a service to those engaged in mental health care and to ensure maximum impact, the Task Force review is being published as a supplement to the CINPs journal, the International Journal of Neuropsychopharmacology. In addition, the information will later …

Determinants of the Quality of Life in Alzheimer’s Disease Patients as Assessed by the Japanese Version of the Quality of Life – Alzheimer’s Disease Scale

Background: Although QOL is an important indicator to assess multiple facets of life, the QOL of Alzheimer’s disease (AD) subjects with impaired cognitive ability due to dementia has not yet been fully investigated. In this study, we developed the Japanese version of the Quality of Life – Alzheimer’s disease (QOL-AD) scale by means of back-translation, and ascertained its reliability and validity for evaluating the quality of life in AD subjects. We also hypothesized that the presence of neuropsychiatric symptoms may determine the characteristics and determinants of both the patients’ and the caregivers’ responses to the patients’ QOL questionnaire. Methods: We administered the QOL-AD questionnaire to subjects with mild or moderate AD (n = 140). The test-retest reliability was evaluated by the same interviewer after a month’s interval. Data from the following tests were also collected to ascertain the validity of the questionnaire: Short Memory Questionnaire (SMQ), Neuropsychiatry Inventory (NPI), Hyogo Activities of Daily Living Scale (HADL) and Mini-Mental State Examination (MMSE). Results: The Japanese version of the QOL-AD questionnaire demonstrated good internal reliability for both the patients’ (Cronbach’s α = 0.84) and the caregivers’ responses (Cronbach’s α = 0.82) and good test-retest reliability for both the patients’ (intraclass correlation coefficient = 0.84) and caregivers’ reports (intraclass correlation coefficient = 0.91). The concordance between the patients’ self-report and the caregivers’ observation was moderate (Pearson correlation coefficient = 0.60). The score for the ‘mood factor’ (apathy, depression/dysphoria) in NPI predicted the overall QOL score as determined from both the patients’ and the caregivers’ responses for subjects with mild (MMSE≧21, n = 88) and moderate (MMSE<21, n = 52) AD. The score for the ‘psychosis factor’ (delusions, hallucinations, anxiety, agitation, disinhibition, irritability, aberrant motor activity) in NPI predicted the total QOL score as determined by the patients and the caregivers among subjects with moderate AD only. Conclusions: As hypothesized, the presence of neuropsychiatric symptoms may be an important predictor of both the patients’ and caregivers’ responses to the patients’ QOL questionnaire. QOL-AD appears to be a promising measure of the QOL of subjects with mild to moderate AD in Japan.

Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials

No systematic review or meta-analysis using a hard outcome has been conducted on the role of benzodiazepines for generalized anxiety disorder (GAD). The objective of this study was to assess the effectiveness and efficacy of benzodiazepines in the treatment of GAD based on trial drop-out rates. We used a systematic review of randomized controlled trials that compared any of the three best established benzodiazepines (diazepam, Lorazepam and aLprazolam) against placebo. Our primary outcome for effectiveness was withdrawal for any reason. Our secondary outcome tapping efficacy was withdrawal due to lack of efficacy, and that tapping side effects was withdrawals due to adverse events. We included 23 trials. Pooled analysis indicated less risk of treatment discontinuation due to lack of efficacy for benzodiazepines, compared to placebo, relative risk (RR) 0.29 (95% CI 0.18—0.45; p < 0.00001). Nevertheless, pooled analysis showed no conclusive results for risk of all-cause patient discontinuation, RR 0.78 (95% CI 0.62—1.00; p = 0.05). Meta-regression model showed that 74% of the variation in logRR across the studies was explained by year of publication (p <0.001). This systematic review did not find convincing evidence of the short-term effectiveness of the benzodiazepines in the treatment of GAD. On the other hand, for the outcome of efficacy, this review found robust evidence in favour of benzodiazepines. Due to the heterogeneity induced by year of publication, three hypotheses are plausibLe when it comes to being able to account for the differences between efficacy and effectiveness observed in the outcomes (publication bias, quality of the trial literature and a non-differential response to the placebo effect).

Psychosocial factors, disease status, and quality of life in patients with rheumatoid arthritis ☆

OBJECTIVE To explore the interrelationships between the psychosocial and illness factors that determine the disease status of patients with rheumatoid arthritis (RA) and to identify how each factor is associated with quality of life (QOL). METHODS The study group comprised 120 RA outpatients who completed a series of health examinations and questionnaires. Disease severity, functional disability, counts of swollen and/or tender joints, duration of RA, frequency of arthritis surgery, and C-reactive protein level were assessed by rheumatologists. Self-report inventories completed by the patients were used to assess perceived degree of pain, fatigue (visual analogue scales), depression (Beck Depression Inventory-II), anxiety (Hospital Anxiety and Depression Scale), and social support (Social Support Questionnaire). Mental and physical components of health-related QOL were evaluated using the Short-Form 36 Health Survey. RESULTS After z-transformation of the data, a principal axis factor analysis was conducted. A four-factor structure was identified in which the components reflected psychosocial factors, disease activity, current symptoms, and physical functional status, respectively. There was no significant association between psychosocial factors and disease activity, while the other components were moderately correlated with each other. Multiple regression analysis revealed that physical QOL was determined by current symptoms and physical functions. Mental QOL was determined by psychosocial factors, current symptoms, and physical functions. CONCLUSION Disease activity was independent from psychosocial factors and failed to reflect the perceived physical and mental QOL of RA patients. Clinicians should therefore evaluate psychosocial factors, as well as subjective disease status, to improve the QOL of patients with RA.