Narong Maneeton

Quetiapine versus haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial

Background Atypical antipsychotic drugs may have low propensity to induce extrapyramidal side effects in delirious patients. This study aimed to compare the efficacy and tolerability between quetiapine and haloperidol in controlling delirious behavior. Methods A 7-day prospective, double-blind, randomized controlled trial was conducted from June 2009 to April 2011 in medically ill patients with delirium. Measures used for daily assessment included the Delirium Rating Scale-revised-98 (DRS-R-98) and total sleep time. The Clinical Global Impression, Improvement (CGI–I) and the Modified (nine-item) Simpson– Angus Scale were applied daily. The primary outcome was the DRS-R-98 severity scores. The data were analyzed on an intention-to-treat basis. Results Fifty-two subjects (35 males and 17 females) were randomized to receive 25–100 mg/day of quetiapine (n = 24) or 0.5–2.0 mg/day of haloperidol (n = 28). Mean (standard deviation) doses of quetiapine and haloperidol were 67.6 (9.7) and 0.8 (0.3) mg/day, respectively. Over the trial period, means (standard deviation) of the DRS-R-98 severity scores were not significantly different between the quetiapine and haloperidol groups (−22.9 [6.9] versus −21.7 [6.7]; P = 0.59). The DRS-R-98 noncognitive and cognitive subscale scores were not significantly different. At end point, the response and remission rates, the total sleep time, and the Modified (nine-item) Simpson–Angus scores were also not significantly different between groups. Hypersomnia was common in the quetiapine-treated patients (33.3%), but not significantly higher than that in the haloperidol-treated group (21.4%). Limitations Patients were excluded if they were not able to take oral medications, and the sample size was small. Conclusion Low-dose quetiapine and haloperidol may be equally effective and safe for controlling delirium symptoms. Clinical trials registration number clinicaltrials.gov NCT00954603.

Bupropion for adults with attention-deficit hyperactivity disorder: Meta-analysis of randomized, placebo-controlled trials

Aim:  The aim of this study was to systematically review the efficacy, acceptability and tolerability of bupropion in comparison to placebo. Only randomized‐controlled trials were included in the meta‐analysis.

Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials.

BackgroundSchizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect.ObjectivesThis meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD). Only the randomized controlled trials (RCTs) comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012.Data sourcesMEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression.Study eligible criteria, participants and interventionsEligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i) depression severity, ii) response rate, iii) overall discontinuation rate, or iv) discontinuation rate due to adverse events. No language restriction was applied.Study appraisal and synthesis methodsAll abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were computed by using a random effect model.ResultsA total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR). The pooled mean change scores of the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D) of the quetiapine-treated group were higher than those of the placebo-treated group with the WMDs (95%CI) of -3.37 (-3.95, -2.79) and -2.46 (-3.47, -1.45), respectively. All studies defined the response and remission as ≥ 50% reduction of the MADRS total score and the MADRS total score of ≤8 at endpoint, respectively. The overall response and remission rates were significantly greater in the quetiapine-treated group with RRs (95%CIs) of 1.44 (1.26, 1.64) and 1.37 (1.12, 1.68), respectively. The pooled discontinuation rate was not significantly different between groups with an RR (95%CI) of 1.16 (0.97, 1.39). The pooled discontinuation rate due to adverse event was greater in the quetiapine group with an RR (95%CI) of 2.90 (1.87, 4.48). With respect to sleep time, the pooled mean change Pittsburgh Sleep Quality Index (PSQI) scores of the quetiapine-treated group was also significantly higher than that of the placebo-treated group [WMD (95%CI) of -1.21 (-1.81, -0.61)].LimitationsVariety of quetiapine XR doses and the small number of RCTs were key limitations of this meta-analysis.ConclusionsBased on the limited evidence obtained from three RCTs, quetiapine XR is effective for adult patients with MDD. The high dropout rate due to adverse events suggests that some MDD patients may not be able to tolerate quetiapine XR. Due to the balance of its efficacy benefit and risk of side effects, as the overall discontinuation rate shown, the acceptability of this agent is not more than placebo. These results should be viewed as the very preliminary one. Further studies in this area are warranted.Implication of key findingsQuetiapine may be an alternative antidepressant. However, both risk and benefit of this agent should be taken into account for an individual patient with MDD.

Prevalence and predictors of depression in patients with systemic lupus erythematosus: a cross-sectional study

Objective The purpose of this study was to estimate the prevalence and examine the predictors of depression in patients with systemic lupus erythematosus (SLE). Methods This cross-sectional study was conducted in the rheumatology clinic of a university hospital. All SLE patients that met the revised American College of Rheumatology (ACR) classification were included in the study. Sociodemographic data and medications were recorded. Disease activity for SLE was assessed with the Mexican-SLE Disease Activity Index (Mex-SLEDAI). All subjects were screened for anxiety and depression by using the Hamilton Anxiety Rating Scale (HAM-A) and the 17-item version of the Hamilton Depression Rating Scale (HAM-D17). Multiple linear regression analyses were used to determine predictors of depressive disorder. Results A total of 62 SLE (61 females and 1 male) patients participated in the study. Based on HAM-D17 and HAM-A, rates of depression and anxiety in SLE patients were 45.2% and 37.1%, respectively. The multiple linear regression analysis revealed that HAM-A score and younger age were significant predictors of depression in SLE patients. Conclusion The findings suggest that depression and anxiety are common in SLE patients. In addition, higher levels of anxiety and a younger age may increase the risk of depression. Because of the small sample size, further studies should be conducted to confirm these results.

Quetiapine for acute bipolar depression: a systematic review and meta-analysis

Background Precise estimated risks and benefits of quetiapine for acute bipolar depression are needed for clinical practice. Objective To systematically review the efficacy and the tolerability of quetiapine, either as monotherapy or combination therapy, for acute bipolar depression. Methods We included all randomized, controlled trials (RCTs) comparing quetiapine with other treatments, including placebo, in patients with acute bipolar depression (bipolar I or II disorder, major depressive episode). Published and unpublished RCTs were identified using the Cochrane Central Register of Controlled Trials, MEDLINE®, Web of Knowledge™, CINAHL®, PsycINFO®, the EU Clinical Trials Register database, and ClinicalTrials.gov. The primary outcome was the change scores of depression rating scales. Results Eleven RCTs (n=3,488) were included. Two of them were conducted in children and adolescents. The change in depression scores was significantly greater in the quetiapine group compared with the placebo group (mean difference, [MD] =−4.66, 95% confidence interval [CI] −5.59 to −3.73). The significant difference was observed from week 1. Compared with placebo, quetiapine had higher incidence rates of extrapyramidal side effects, sedation, somnolence, dizziness, fatigue, constipation, dry mouth, increased appetite, and weight gain but lower risks of treatment-emergent mania and headache. Quetiapine treatment was associated with significant improvement of clinical global impression, quality of life, sleep quality, anxiety, and functioning. Conclusion Quetiapine monotherapy is effective for acute bipolar depression and the prevention of mania/hypomania switching. Its common adverse effects are extrapyramidal side effects, sedation, somnolence, dizziness, fatigue, constipation, dry mouth, increased appetite, and weight gain. The lower risk of headache in quetiapine-treated patients with acute bipolar depression should be further investigated. The evidence for the use of quetiapine combined with mood stabilizers in children and adolescents with acute bipolar depression is too small to support the clinical practice.

A systematic review of randomized controlled trials of bupropion versus methylphenidate in the treatment of attention-deficit/hyperactivity disorder

Background Some trials have suggested that bupropion, as well as methylphenidate, is beneficial in the treatment of attention‐deficit/hyperactivity disorder (ADHD). Objectives The purpose of this systematic review was to summarize the efficacy, acceptability, and tolerability of bupropion in comparison with methylphenidate for ADHD treatment. Included studies were randomized controlled trials (RCTs) that compared bupropion and methylphenidate. Clinical studies conducted between January 1991 and January 2014 were reviewed. Data sources MEDLINE®, EMBASE™, CINAHL, PsycINFO®, and the Cochrane Controlled Trials Register were searched in January 2014. Additionally, clinical trials were identified from the databases of ClinicalTrials.gov and the EU Clinical Trials Register. Study eligible criteria, participants, and interventions All RCTs of bupropion and methylphenidate reporting final outcomes relevant to 1) ADHD severity, 2) response or remission rates, 3) overall discontinuation rate, or 4) discontinuation rate due to adverse events. Language restriction was not applied. Study appraisal and synthesis methods The relevant clinical trials were examined and the data of interest were extracted. Additionally, the risks of bias were also inspected. The efficacy outcomes were the mean changed scores of ADHD rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate and the discontinuation rate due to adverse events were determined. Relative risks and weighted mean differences or standardized mean differences with 95% confidence intervals were estimated using a random effect model. Results A total of 146 subjects in four RCTs comparing bupropion with methylphenidate in the treatment of ADHD were included. The pooled mean changed scores of the Iowa–Conner’s Abbreviated Parent and Teacher Questionnaires and the ADHD Rating Scale‐IV for parents and teachers of children and adolescents with ADHD in the bupropion‐ and methylphenidate‐treated groups were not significantly different. Additionally, the pooled mean changed score in adult ADHD between the two groups, measured by the ADHD Rating Scale‐IV and the Adult ADHD Rating Scale, was also not significantly different. The pooled rates of response, overall discontinuation, and discontinuation due to adverse events between the two groups were not significantly different. Conclusion Based on limited data from this systematic review, bupropion was as effective as methylphenidate for ADHD patients. Additionally, tolerability and acceptability were also comparable. However, these findings should be considered as very preliminary results. To confirm this evidence, further studies in this area should be conducted.

Evaluation of three simple methods for predicting therapeutic lithium doses

The bias and accuracy of three simple methods for predicting lithium doses were assessed in this prospective study. In each patient, we computed the predicted doses (PDs) of lithium by applying three formulas. The actual dose (AD), the lowest lithium dose that was enough to produce a serum lithium concentration higher than 0.80 mmol/l, was determined. The PD computed by each formula was then compared with the AD to identify the one with the least bias and the greatest accuracy in predicting therapeutic lithium doses. As mean prediction error (ME) is a convenient measure of bias, the prediction error (PE) of each comparison was computed by subtracting the AD from the PD. Accuracy was assessed as a function of the root-mean-squared prediction error (rMSE). Seventeen psychiatric inpatients participated in this study. The 95% confidence interval of ME of a proposed formula [Zetin, M., Garber, D., De Antonio, M., Schlegel, A., Feureisen, S., Fieve, R., Jewett, C., Reus, V., Huey, L.Y., 1986. Prediction of lithium dose: a mathematic alternative to the test-dose method. Journal of Clinical Psychiatry 47, 175-178] was across zero (-15.48 to 133.72). In addition, the rMSE of that formula was also the lowest one (152.66 mg/day). The method proposed by Zetin et al. (1986) is the least biased and the most accurate way to predict therapeutic lithium doses.

Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: A systematic review and meta-analysis of randomized-controlled trials

Limited options are available for clozapine-resistant schizophrenia and intolerable side effects of clozapine. We conducted a systematic review of randomized-controlled trials (RCTs) to determine the efficacy and safety of aripiprazole augmentation of clozapine for schizophrenia. Electronic databases searched included PubMed, Scopus, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. This review synthesized the data of four short-term (8-24 weeks), placebo-controlled trials (N = 347). The overall relative risk (RR, 95% confidence interval) of discontinuation rates was not significantly different between groups (RR = 1.41, 95% CI = 0.78 to 2.56). The pooled standardized mean differences (SMDs, 95% CIs) (Z-test; number of study; I(2)-index) suggested trends of aripiprazole augmentation benefits on overall psychotic [-0.40 (-0.87 to 0.07) (n = 3; Z = 1.68, p = 0.09; I(2) = 68%)], positive [-1.05 (-2.39 to 0.29) (n = 3; Z = 1.54, p = 0.12; I(2) = 94%)], and negative [-0.36 (-0.77 to 0.05) (n = 3; Z = 1.74, p = 0.08; I(2) = 54%)] symptoms. Despite of no benefit on three cardiometabolic indices (i.e., fasting plasma glucose, triglyceride, and high-density lipoprotein), aripiprazole augmentation was superior for weight change with a mean difference (95% CI) of -1.36 kg (-2.35 to -0.36) (n = 3; Z = 2.67, p = 0.008; I(2) = 39%) and LDL-cholesterol with a mean difference of -11.06 mg/dL (-18.25 to -3.87) (n = 3; Z = 3.02, p = 0.003; I(2) = 31%). Aripiprazole augmentation was not correlated with headache and insomnia but significantly associated with agitation/akathesia (RR = 7.59, 95% CI = 1.43 to 40.18) (n = 3; Z = 2.38, p = 0.02; I(2) = 0%) and anxiety (RR = 2.70, 95% CI = 1.02 to 7.15) (n = 1; Z = 2.00, p = 0.05). The limited short-term data suggested that aripiprazole augmentation of clozapine can minimize the cardiometabolic risk, causes agitation/akathesia, and may be effective in attenuating psychotic symptoms.

Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD.

Background Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD). Objectives This systematic review was undertaken to summarize LDX efficacy, acceptability, and tolerability in adult ADHD. All randomized controlled trials (RCTs) of lisdexamfetamine compared with placebo were included for synthesis. Clinical trials published between January 1991 and January 2014 were evaluated. Methods The database of MEDLINE®, EMBASE™, CINAHL®, PsycINFO® and Cochrane Controlled Trials Register were searched in January 2014. Studies were also searched in ClinicalTrials.gov and the EU Clinical Trials Register database. Study eligibility criteria, participants, and interventions were considered. All RCTs of LDX vs placebo reporting final results of: 1) severity of ADHD symptoms and executive function deficit, 2) response or remission rates, 3) overall discontinuation rate, or 4) discontinuation rate due to adverse events were included. The language of the papers was not restricted. All abstracts of studies gathered from the database were examined. After excluding irrelevant trials, the full text version of relevant studies were assessed and extracted for outcomes of interest. Examination of risks of bias, based on the Cochrane bias assessment, was carried out. The efficacy outcomes consisted of the mean end point or change scores for ADHD rating scales, the response rate, and the remission rate. The overall discontinuation rate and the discontinuation rate due to adverse events were measured for acceptability and tolerability, respectively. A random effect model was applied for the synthesis of relative risks (RRs), and weighted mean differences or standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results A total of 806 final study or safety participants were included. The dosage of lisdexamfetamine was 30 to 70 mg/day. The pooled mean scores of mean change and mean end point scores between LDX- and placebo-treated groups also had a significant difference (SMD [95% CI] of −0.97 [−1.15, −0.78], I2=18%). The pooled response rates for adult ADHD between the two groups had a significant difference (RR [95% CI] of 1.99 [1.50, 2.63], I2=0%). Based on the Behavior Rating Inventory of Executive Function – Adult version (BRIEF-A), the pooled end point mean scores for the Global Executive Composite (GEC) for the LDX-treated groups was greater than that of placebo-treated groups (MD [95% CI] of −9.20 [−14.11, −4.29], I2=34%). The pooled overall discontinuation rates between the two groups had no significant difference (RR [95% CI] of 0.82 [0.59, 1.14], I2=0%). Similarly, the pooled discontinuation rates due to adverse events between the two groups was not significantly different (RR [95% CI] of 1.77 [0.71, 4.40], I2=0%). Conclusion The number of included studies was limited (five RCTs), but based on this meta-analysis, LDX is efficacious and well tolerated in the treatment of adult ADHD. Additionally, it also improved the executive function deficits in this population. However, its acceptability is no higher than placebo. These findings should be carefully interpreted and considered as preliminary outcomes. To confirm these results, further studies are warranted. LDX is a viable alternative psychostimulant for adult ADHD.

Efficacy, tolerability, and acceptability of bupropion for major depressive disorder: a meta-analysis of randomized–controlled trials comparison with venlafaxine

Background Bupropion and venlafaxine are effective antidepressants with unique pharmacological profiles. Objectives The purpose of this meta-analysis was to determine the efficacy, acceptability, and tolerability of bupropion and venlafaxine therapies for adults with major depressive disorder (MDD). The authors searched clinical trials with low risk of bias, performed from January 1985 to February 2013. Data sources The searches of MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Controlled Trials Register were conducted in February 2013. Included populations consisted of adult patients with MDD or major depression. Study eligible criteria, participants, and interventions Included studies were randomized controlled trials (RCTs) comparing bupropion and venlafaxine in adult patients with MDD and offering endpoint results relevant to: (1) severity of depression; (2) response rate; (3) remission rate; (4) overall discontinuation rate; or (5) discontinuation rate due to adverse events. Limitation of language was not utilized. Study appraisal and synthesis methods The abstracts located from the electronic databases were reviewed. The completed reports from pertinent studies were examined, and essential data were extracted. Based on the Cochrane’s bias assessment, risks of bias were assessed. Any study with two risks or more was excluded. Efficacious outcomes included the mean changed scores of rating scales for depression, overall response rates, and overall remission rates. Acceptability was determined by the overall discontinuation rates. The discontinuation rates due to adverse events were the measurement of tolerability. Relative risks (RR) and weighted mean differences or standardized mean differences with 95% confidence intervals (CI) were computed using a random effect model. Results A total of 1,117 participants in three RCTs were included. Depression rating scales used in one and two studies were the 17-item Hamilton Depression Rating Scale and the Montgomery–Asberg Depression Rating Scale, respectively. The pooled mean changed scores of the bupropion-treated group were comparable to those of the venlafaxine-treated group with standardized mean differences (95% CI) of 0.05 (−0.16 to 0.26). The overall response and remission rates were similar with the RRs (95% CI) of 0.92 (0.79–1.08) and 0.97 (0.75–1.24), respectively. The pooled overall discontinuation rate and discontinuation rate due to adverse events were not different between groups with the RRs (95% CI) of 1.00 (0.80–1.26) and 0.69 (0.44–1.10), respectively. Limitations The small number of RCTs included in the meta-analysis. Conclusion According to the limited data obtained from three RCTs, bupropion XL is as effective and tolerable as venlafaxine XR for adult patients with MDD. Further studies in this area should be conducted to confirm these findings.