The Efficacy of Mindfulness-Based Cognitive Therapy as a Public Mental Health Intervention for Adults with Mild to Moderate Depressive Symptomatology: A Randomized Controlled Trial

Objective

Although there has been growing evidence for the efficacy of mindfulness-based cognitive therapy (MBCT) for different clinical populations, its effectiveness as a public mental health intervention has not been studied. The present study evaluates a community-based MBCT intervention for adults with mild to moderate depressive symptomatology in a large multi-site, pragmatic randomized controlled trial.

Method

The participants with mild to moderate depressive symptomatology were recruited from the general population and randomized to the MBCT intervention (n = 76) or to a waiting list control group (n = 75). Participants completed measures before and after the intervention. Participants in the experimental condition also completed these measures at a 3-month follow-up.

Results

In the experimental condition significant reductions in depression, anxiety, and experiential avoidance, and improvements in mindfulness and emotional- and psychological mental health were found, compared to the waiting list (effect sizes Cohen''s d = 0.31–0.56). These effects were sustained at the 3-month follow-up. The likelihood of a clinically significant change in depressive symptoms was significantly higher for the MBCT group [odds ratio (OR) 3.026, p<0.01 at post-treatment; NNT = 5.10].

Discussion

MBCT as a public mental health intervention for adults with mild to moderate depressive symptoms seems effective and applicable in a natural setting.

Trial Registration

Nederlands Trial Register NTR2096     

Internet-Delivered Cognitive-Behavioral Therapy for Social Anxiety Disorder in Romania: A Randomized Controlled Trial

MethodsParticipants (n = 76) were recruited, screened and randomized to either a nine-week guided iCBT or a wait-list control group in April and May 2012. Self-report measures were collected before (April 2012) and after the intervention (July 2012), as well as six months later (January 2013). Although social anxiety was assessed with multiple measures, the Liebowitz Social Anxiety Scale - Self Report version (LSAS-SR) and Social Phobia Inventory (SPIN) were used as the primary outcome measures.ResultsA significant difference with a large between-group effect size in favor of iCBT was found (Cohen´s d = 1.19 for LSAS-SR and d = 1.27 for SPIN). Recovery rates show that 36.8% (n = 14) in the treatment group score below the SPIN clinical cut-off compared to only 2.6% (n = 1) in the wait-list control group. Post-intervention clinical interviews also revealed that 34.2% (n = 13) of the treatment group was completely recovered (full remission) while additionally 36.8% (n = 14) retained some social anxiety symptoms (partial remission). However, an important study limitation is that post-intervention interviewers were not blinded to the study conditions. The program also effectively reduced depression and dysfunctional thinking (between-group Cohen´s d = 0.84 for depression and d = 0.63 for dysfunctional thinking). Moreover, the iCBT intervention appears to have a long-term impact for participants’ functioning, as the treatment gains were maintained six months later.ConclusionsInternet-delivered interventions display a high potential to quickly and widely disseminate effective evidence-based programs around the world. This study provides support for guided iCBT as a promising treatment approach in Romania.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01557894","term_id":"NCT01557894"}}NCT01557894     

Guided Self-Help Cognitive Behavioural Therapy for Depression in Primary Care: A Randomised Controlled Trial

Background

Access to Cognitive behavioural therapy (CBT) for depression is limited. One solution is CBT self-help books. Trial Objectives: To assess the impact of a guided self-help CBT book (GSH-CBT) on mood, compared to treatment as usual (TAU).Hypotheses:

1. GSH-CBT will have improved mood and knowledge of the causes and treatment of depression compared to the control receiving TAU
2. Guided self-help will be acceptable to patients and staff.

Methods and Findings

Participants: Adults attending seven general practices in Glasgow, UK with a BDI-II score of ≥14. 141 randomised to GSH-CBT and 140 to TAU. Interventions: RCT comparing ‘Overcoming Depression: A Five Areas Approach’ book plus 3–4 short face to face support appointments totalling up to 2 hours of guided support, compared with general practitioner TAU. Primary outcome: The BDI (II) score at 4 months. Numbers analysed: 281 at baseline, 203 at 4 months (primary outcome), 117 at 12 months. Outcome: Mean BDI-II scores were lower in the GSH-CBT group at 4 months by 5.3 points (2.6 to 7.9, p<0.001). At 4 and 12 months there were also significantly higher proportions of participants achieving a 50% reduction in BDI-II in the GSH-CBT arm. The mean support was 2 sessions with 42.7 minutes for session 1, 41.4 minutes for session 2 and 40.2 minutes of support for session 3. Adverse effects/Harms: Significantly less deterioration in mood in GSH-CBT (2.0% compared to 9.8% in the TAU group for BDI—II category change).

Limitations

Weaknesses: Our follow-up rate of 72.2% at 4 months is better than predicted but is poorer at 12 months (41.6%). In the GSH-CBT arm, around 50% of people attended 2 or fewer sessions. 22% failed to take up treatment.

Conclusions

GSH-CBT is substantially more effective than TAU.

Trial Registration

Controlled-Trials.com ISRCTN13475030     

The Potential for Mindfulness-Based Intervention in Workplace Mental Health Promotion: Results of a Randomized Controlled Trial

Objectives

This study aims to intensively evaluate the effectiveness of mindfulness-based intervention (MBI) on mental illness risks (including psychological distress, prolonged fatigue, and perceived stress) and job strain (job control and job demands) for employees with poor mental health.

Methods

A longitudinal research design was adopted. In total, 144 participants were randomized to the intervention group or the control group. The intervention group participated in MBI for eight weeks. Measurements were collected for both groups at five time points: at pre-intervention (T1), at mid-intervention (T2), at the completion of intervention (T3), four weeks after intervention (T4), and eight weeks after intervention (T5). Data were analyzed according to the intention-to-treat principle. A linear mixed model with two levels was employed to analyze the repeated measurement data.

Results

Compared with the control group, the intercepts (means at T3) for the intervention group were significantly lower on psychological distress, prolonged fatigue, and perceived stress when MBI was completed. Even with the demographic variables controlled, the positive effects remained. For growth rates of prolonged fatigue and perceived stress, participants in the intervention group showed a steeper decrease than did the participants in the control group. Regarding job strain, although the intercept (mean at T3) of job demands showed a significant decline when BMI was completed, the significance disappeared when the demographic variables were controlled. Moreover, the other results for job control and job demands did not show promising findings.

Conclusion

As a workplace health promotion program, the MBI seems to have potential in improving mental illness risks for employees with poor mental health. However, there was insufficient evidence to support its effect on mitigating job strain. Further research on maintaining the positive effects on mental health for the long term and on developing innovative MBI to suit job strain are recommended.

Trial Registration

ClinicalTrials.gov NCT02241070     

Canine-assisted Speech Therapy for Children with Communication Impairments: A Randomized Controlled Trial

Developmental dysphasia (DD) is a disorder resulting in a communication impairment. Children diagnosed with this condition are usually referred to a speech therapist. Further to conventional speech therapy it is possible to adopt a complementary animal-assisted approach. For the present study, we assembled a cohort comprising 69 children diagnosed with DD. The children in the experimental group (n = 31; 21 male, 10 female) ranged from 4 to 7 years (M = 5.53 years, SD = 0.81 years). The control group was comprised of children (n = 38; 31 male, 7 female) aged from 4 to 6 years (M = 4.85 years, SD = 0.51 years). While the latter received traditional speech therapy, the experimental group experienced sessions enhanced by animal-assistance therapy (AAT) with a dog present for co-therapy purposes. As primary outcome measures, the Kwint-Stambak (KS) test was adopted (for assessing facial motricity), together with the Bruininks-Oseretsky (BO) test (for evaluating motor proficiency). Both of these revealed statistically significant improvement in some primary outcome measures for the experimental group over the control group. Regarding narrowing and shutting of the eyes, as well as filling up the cheeks with air and smiling (as measured by the KS test), the experimental group did significantly better than the control group. The inclusion of dogs in such therapy increased the chances of success in certain abilities, when assessed by the KS and BO tests (odds ratios for success: 1.6 and 2.0, respectively), compared with the control group. Canine-assisted speech therapy may be a valuable tool for enhancing the effect of speech therapy on children with DD, and we speculate that the reason for this relates to the nature of communication between children and companion animals.     

A Randomized Controlled Trial of Multicomponent Exercise in Older Adults with Mild Cognitive Impairment

Background

To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions.

Methodology/Principal Findings

Subjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05).

Conclusions/Significance

The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI.

Trial Registration

UMIN-CTR UMIN000003662 ctr.cgi&quest;function&hairsp;&equals;&hairsp;brows&amp;action&hairsp;&equals;&hairsp;brows&amp;type&hairsp;&equals;&hairsp;summary&amp;recptno&hairsp;&equals;&hairsp;R000004436&amp;language&hairsp;&equals;&hairsp;J.     

Internet and Computer-Based Cognitive Behavioral Therapy for Anxiety and Depression in Youth: A Meta-Analysis of Randomized Controlled Outcome Trials

Background

Anxiety and depression in children and adolescents are undertreated. Computer- and Internet-based cognitive behavioral treatments (cCBT) may be an attractive treatment alternative to regular face-to-face treatment.This meta-analysis aims to evaluate whether cCBT is effective for treating symptoms of anxiety and depression in youth.

Methods and Findings

We conducted systematic searches in bibliographical databases (Pubmed, Cochrane controlled trial register, PsychInfo) up to December 4, 2013. Only randomized controlled trials in which a computer-, Internet- or mobile-based cognitive behavioral intervention targeting either depression, anxiety or both in children or adolescents up to the age of 25 were compared to a control condition were selected. We employed a random-effects pooling model in overall effect analyses and a mixed effect model for sub-group analyses. Searches resulted in identifying 13 randomized trials, including 796 children and adolescents that met inclusion criteria. Seven studies were directed at treating anxiety, four studies at depression, and two were of a transdiagnostic nature, targeting both anxiety and depression. The overall mean effect size (Hedges’ g) of cCBT on symptoms of anxiety or depression at post-test was g=0.72 (95% CI:0.55-0.90, numbers needed to be treated (NNT)=2.56). Heterogeneity was low (I²=20.14%, 95% CI: 0-58%). The superiority of cCBT over controls was evident for interventions targeting anxiety (g=0.68; 95% CI: 0.45-0.92; p < .001; NNT=2.70) and for interventions targeting depression (g=0.76; 95% CI: 0.41-0.12; p < .001; NNT=2.44) as well as for transdiagnostic interventions (g=0.94; 95% CI: 0.23-2.66; p < .001; NNT=2.60).

Conclusions

Results provide evidence for the efficacy of cCBT in the treatment of anxiety and depressive symptoms in youth. Hence, such interventions may be a promising treatment alternative when evidence based face-to-face treatment is not feasible. Future studies should examine long-term effects of treatments and should focus on obtaining patient-level data from existing studies, to perform an individual patient data meta-analysis.     

Cost-Effectiveness of a Community Pharmacist Intervention in Patients with Depression: A Randomized Controlled Trial (PRODEFAR Study)

Background

Non-adherence to antidepressants generates higher costs for the treatment of depression. Little is known about the cost-effectiveness of pharmacist''s interventions aimed at improving adherence to antidepressants. The study aimed to evaluate the cost-effectiveness of a community pharmacist intervention in comparison with usual care in depressed patients initiating treatment with antidepressants in primary care.

Methods

Patients were recruited by general practitioners and randomized to community pharmacist intervention (87) that received an educational intervention and usual care (92). Adherence to antidepressants, clinical symptoms, Quality-Adjusted Life-Years (QALYs), use of healthcare services and productivity losses were measured at baseline, 3 and 6 months.

Results

There were no significant differences between groups in costs or effects. From a societal perspective, the incremental cost-effectiveness ratio (ICER) for the community pharmacist intervention compared with usual care was €1,866 for extra adherent patient and €9,872 per extra QALY. In terms of remission of depressive symptoms, the usual care dominated the community pharmacist intervention. If willingness to pay (WTP) is €30,000 per extra adherent patient, remission of symptoms or QALYs, the probability of the community pharmacist intervention being cost-effective was 0.71, 0.46 and 0.75, respectively (societal perspective). From a healthcare perspective, the probability of the community pharmacist intervention being cost-effective in terms of adherence, QALYs and remission was of 0.71, 0.76 and 0.46, respectively, if WTP is €30,000.

Conclusion

A brief community pharmacist intervention addressed to depressed patients initiating antidepressant treatment showed a probability of being cost-effective of 0.71 and 0.75 in terms of improvement of adherence and QALYs, respectively, when compared to usual care. Regular implementation of the community pharmacist intervention is not recommended.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00794196","term_id":"NCT00794196"}}NCT00794196     

The Effects of Extracorporeal Shock Wave Therapy in Patients with Coccydynia: A Randomized Controlled Trial

Coccydynia is pain in the coccygeal region, and usually treated conservatively. Extracorporeal shock wave therapy (ESWT) was incorporated as non-invasive treatment of many musculoskeletal conditions. However, the effects of ESWT on coccydynia are less discussed. The purpose of this study is to evaluate the effects of ESWT on the outcomes of coccydynia. Patients were allocated to ESWT (n = 20) or physical modality (SIT) group (n = 21) randomly, and received total treatment duration of 4 weeks. The visual analog scale (VAS), Oswestry disability index (ODI), and self-reported satisfaction score were used to assess treatment effects. The VAS and ODI scores were significantly decreased after treatment in both groups, and the decrease in the VAS score was significantly greater in the ESWT group. The mean proportional changes in the ODI scores were greater in the ESWT group than in the SIT group, but the between-group difference was not statistically significant. The patients in the ESWT group had significantly higher subjective satisfaction scores than SIT group. We concluded that ESWT is more effective and satisfactory in reducing discomfort and disability caused by coccydynia than the use of physical modalities. Thus, ESWT is recommended as an alternative treatment option for patients with coccydynia.

Trial Registration

ClinicalTrials.gov NCT02313324     

Reduction of Seizure Occurrence from Exposure to Auditory Stimulation in Individuals with Neurological Handicaps: A Randomized Controlled Trial

Background

The purpose of this work was to determine in a clinical trial the efficacy of reducing or preventing seizures in patients with neurological handicaps through sustained cortical activation evoked by passive exposure to a specific auditory stimulus (particular music). The specific type of stimulation had been determined in previous studies to evoke anti-epileptiform/anti-seizure brain activity.

Methods

The study was conducted at the Thad E. Saleeby Center in Harstville, South Carolina, which is a permanent residence for individuals with heterogeneous neurological impairments, many with epilepsy. We investigated the ability to reduce or prevent seizures in subjects through cortical stimulation from sustained passive nightly exposure to a specific auditory stimulus (music) in a three-year randomized controlled study. In year 1, baseline seizure rates were established. In year 2, subjects were randomly assigned to treatment and control groups. Treatment group subjects were exposed during sleeping hours to specific music at regular intervals. Control subjects received no music exposure and were maintained on regular anti-seizure medication. In year 3, music treatment was terminated and seizure rates followed. We found a significant treatment effect (p = 0.024) during the treatment phase persisting through the follow-up phase (p = 0.002). Subjects exposed to treatment exhibited a significant 24% decrease in seizures during the treatment phase, and a 33% decrease persisting through the follow-up phase. Twenty-four percent of treatment subjects exhibited a complete absence of seizures during treatment.

Conclusion/Significance

Exposure to specific auditory stimuli (i.e. music) can significantly reduce seizures in subjects with a range of epilepsy and seizure types, in some cases achieving a complete cessation of seizures. These results are consistent with previous work showing reductions in epileptiform activity from particular music exposure and offers potential for achieving a non-invasive, non-pharmacologic treatment of epilepsy.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01459692","term_id":"NCT01459692"}}NCT01459692     

Effects of Short-Term Cognitive Remediation on Cognitive Dysfunction in Partially or Fully Remitted Individuals with Bipolar Disorder: Results of a Randomised Controlled Trial

Introduction

Cognitive dysfunction is common in bipolar disorder (BD) but is not sufficiently addressed by current treatments. Cognitive remediation (CR) may improve cognitive function in schizophrenia but no randomised controlled trial has investigated this intervention in BD. The present study aimed to investigate the effects of CR on persistent cognitive dysfunction in BD.

Method

Patients with BD in partial remission with cognitive complaints were randomised to 12 weeks group-based CR (n=23) or standard treatment (ST) (n=23). Outcomes were improved verbal memory (primary), sustained attention, executive and psychosocial function (secondary) and additional measures of cognitive and psychosocial function (tertiary). Participants were assessed at baseline and weeks 12 and 26.

Results

Of the 46 randomised participants five dropped out and one was excluded after baseline. CR (n=18) had no effect on primary or secondary measures of cognitive or psychosocial function compared with ST (n=22). However, CR improved subjective sharpness at week 12, and quality of life and verbal fluency at week 26 follow-up (tertiary outcomes). Although the trial turned out to have suboptimal statistical power for the primary outcome analysis, calculation of the 95% confidence interval showed that it was highly unlikely that an increase in sample size would have rendered any beneficial effects of CR vs. ST on the verbal memory.

Conclusions

Short-term group-based CR did not seem to improve overall cognitive or psychosocial function in individuals with BD in full or partial remission. The present findings suggest that that longer-term, more intensive and individualised CR may be necessary to improve cognition in BD.

Trial Registration

ClinicalTrials.gov NCT01457235     

Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial

Background

Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined.

Methods and Findings

A5164 was a randomized strategy trial of “early ART” - given within 14 days of starting acute OI treatment versus “deferred ART” - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) ≥50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS.282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively.The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events.

Conclusions

Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00055120","term_id":"NCT00055120"}}NCT00055120     

The Real World Mental Health Needs of Heart Failure Patients Are Not Reflected by the Depression Randomized Controlled Trial Evidence

Introduction

International depression screening guidelines in heart failure (HF) are partly based on depression treatment efficacy from randomized controlled trials (RCTs). Our aim was to test the external validity of depression RCT criteria in a sample of real-world HF patients.

Methods

HF patients admitted to 3 hospitals in South Australia were referred to a HF psychologist if not already receiving current psychiatric management by psychologist or psychiatrist elsewhere. Screening and referral protocol consisted of the following; (a). Patient Health Questionnaire ≥10; (b). Generalized Anxiety Disorder Questionnaire ≥7); (c). positive response to 1 item panic attack screener; (d). evidence of suicidality. Patients were evaluated against the most common RCT exclusion criteria personality disorder, high suicide risk, cognitive impairment, psychosis, alcohol or substance abuse or dependency, bi-polar depression.

Results

Total 81 HF patients were referred from 404 HF admissions, and 73 were assessed (age 60.6±13.4, 47.9% female). Nearly half (47%) met at least 1 RCT exclusion criterion, most commonly personality disorder (28.5%), alcohol/substance abuse (17.8%) and high suicide risk (11.0%). RCT ineligibility criteria was more frequent among patients with major depression (76.5% vs. 46.2%, p<.01) and dysthymia (26.5% vs. 7.7%, p = .03) but not significantly associated with anxiety disorders. RCT ineligible patients reported greater severity of depression (M = 16.6±5.0 vs. M = 12.9±7.2, p = .02) and were higher consumers of HF psychotherapy services (M = 11.5±4.7 vs. M = 8.5±4.8, p = .01).

Conclusion

In this real-world sample comparable in size to recent RCT intervention arms, patients with depression disorders presented with complex psychiatric needs including comorbid personality disorders, alcohol/substance use and suicide risk. These findings suggest external validity of depression screening and RCTs could serve as a basis for level A guideline recommendations in cardiovascular diseases.     

Directly Administered Antiretroviral Therapy for HIV-Infected Individuals in Opioid Treatment Programs: Results from a Randomized Clinical Trial

Background

Data regarding the efficacy of directly administered antiretroviral therapy (DAART) are mixed. Opioid treatment programs (OTPs) provide a convenient framework for DAART. In a randomized controlled trial, we compared DAART and self-administered therapy (SAT) among HIV-infected subjects attending five OTPs in Baltimore, MD.

Methods

HIV-infected individuals attending OTPs were eligible if they were not taking antiretroviral therapy (ART) or were virologically failing ART at last clinical assessment. In subjects assigned to DAART, we observed one ART dose per weekday at the OTP for up to 12 months. SAT subjects administered ART at home. The primary efficacy comparison was the between-arm difference in the average proportions with HIV RNA <50 copies/mL during the intervention phase (3-, 6-, and 12-month study visits), using a logistic regression model accounting for intra-person correlation due to repeated observations. Adherence was measured with electronic monitors in both arms.

Results

We randomized 55 and 52 subjects from five Baltimore OTPs to DAART and SAT, respectively. The average proportions with HIV RNA <50 copies/mL during the intervention phase were 0.51 in DAART and 0.40 in SAT (difference 0.11, 95% CI: −0.020 to 0.24). There were no significant differences between arms in electronically-measured adherence, average CD4 cell increase from baseline, average change in log₁₀ HIV RNA from baseline, opportunistic conditions, hospitalizations, mortality, or the development of new drug resistance mutations.

Conclusions

In this randomized trial, we found little evidence that DAART provided clinical benefits compared to SAT among HIV-infected subjects attending OTPs.

Trial Registration

ClinicalTrails.gov {"type":"clinical-trial","attrs":{"text":"NCT00279110","term_id":"NCT00279110"}}NCT00279110 {"type":"clinical-trial","attrs":{"text":"NCT00279110","term_id":"NCT00279110"}}NCT00279110&quest;term&hairsp;&equals;&hairsp;{"type":"clinical-trial","attrs":{"text":"NCT00279110","term_id":"NCT00279110"}}NCT00279110&amp;rank&hairsp;&equals;&hairsp;1     

Biological Effects of Add-On Eicosapentaenoic Acid Supplementation in Diabetes Mellitus and Co-Morbid Depression: A Randomized Controlled Trial

Background

Eicosapentaenoic acid (EPA) may reduce increased risks for (cardiovascular) morbidity and mortality in patients with diabetes mellitus (DM) and comorbid major depressive depression (MDD). Yet, effects of EPA-supplementation on biological risk factors for adverse outcomes have not been studied in DM-patients with MDD.

Methods

We performed a randomized, double-blind trial (n = 25) comparing add-on ethyl-EPA-supplementation to placebo on (I) oxidative stress, (II) inflammatory, (III) hypothalamic-pituitary-adrenal (HPA)-axis, (IV) one-carbon-cycle, (V) fatty acid metabolism and (VI) lipoprotein parameters during 12-weeks'' follow-up.

Results

Besides increases in supplemented α-tocopherol [estimate (95% CI); 3.62 (1.14–6.11) µmol/l; p = 0.006] and plasma and erythrocyte EPA, the intervention did not influence other oxidative stress, inflammatory or one-carbon-cycle parameters compared to placebo. HPA-axis reactivity significantly decreased in the EPA-group (N = 12) [AUC_i: −121.93 (−240.20–−3.47) min×nmol/l; p = 0.045], not in the placebo-group (N = 12). Furthermore, EPA-supplementation increased erythrocyte and plasma docosapentaenoic acid, and decreased plasma arachidonic acid (AA) concentrations [−1.61 (−3.10–−0.11) %; p = 0.036]. Finally, EPA had a multivariate influence on lipoprotein concentrations (p = 0.030), reflected by relative increases in high density lipoprotein [HDL; 0.30 (0.02–0.58) mmol/l; p = 0.039] and total cholesterol concentrations [1.01 (0.29–1.72) mmol/l; p = 0.008].

Conclusion

Overall, add-on EPA-supplementation had limited effects on biological risk factors for adverse outcome in this sample of DM-patients with comorbid MDD. Besides increases in concentrations of supplemented α-tocopherol and EPA, AA decreased, and inconclusive effects on HPA-axis (re)activity and lipoprotein concentrations were observed. Therefore, further studies on the alleged beneficial effects of EPA-supplementation on biological risk factors for adverse outcome in DM-patients with comorbid MDD seem warranted, preferably using clinical outcomes such as (cardiovascular) DM-complications.

Trial Registration

Controlled-Trials.com ISRCTN30877831 ISRCTN30877831