Randomised controlled trial of Antiglucocorticoid augmentation (metyrapone) of antiDepressants in Depression (ADD Study)

BackgroundDepressed patients who do not respond to second-line antidepressant drugs are characterised as suffering from treatment-refractory depression (TRD). Chronic psychosocial stress hypothalamic–pituitary–adrenal (HPA) axis dysfunction is associated with attenuated responses to antidepressants. Corticosteroid co-administration reduces the increase in forebrain 5-hydroxytryptamine with selective serotonin reuptake inhibitors, whereas antiglucocorticoids have the opposite effect. A Cochrane review suggesting that antiglucocorticoid augmentation of antidepressants may be effective in treating TRD included a pilot study of the cortisol synthesis inhibitor, metyrapone. TheAntiglucocorticoid augmentation of antiDepressants inDepression (ADD Study) was a multicentre randomised placebo-controlled trial of metyrapone augmentation of serotonergic antidepressants in patients with TRD.ObjectiveTo determine the efficacy and safety of augmentation of standard serotonergic antidepressants with metyrapone 500 mg twice a day for 3 weeks in patients with TRD.MethodsA total of 165 patients with moderate to severe TRD aged 18–65 years were randomised to metyrapone 500 mg twice daily or placebo for 3 weeks, in addition to ongoing serotonergic antidepressants. The primary outcome was improvement in Montgomery–Åsberg Depression Rating Scale (MADRS) score 5 weeks after randomisation estimated using analysis of covariance. Secondary outcomes included the degree of persistence of treatment effect for up to 6 months, and also safety and tolerability of metyrapone. ADD included substudies investigating the potential mechanism of action of metyrapone, and utilised a comparator group of healthy participants.ResultsThe estimated mean difference for each of our study outcomes between randomised groups, 5 weeks post randomisation (allowing for variation between centres and whether or not patients originate from primary or secondary care) was MADRS –0.51 [95% confidence interval (CI) –3.48 to 2.46]; Beck Depression Inventory (BDI) –2.65 (95% CI –6.41 to 1.10); Clinical Anxiety Scale 0.46 (95% CI –1.20 to 2.12); State–Trait Anxiety Inventory 1.2 (95% CI –0.6 to 3.0); European Quality of Life-5 Dimensions 0.015 (95% CI –0.069 to 0.099); EuroQol visual analogue scale 5.6 (95% CI –0.7 to 12.0); and Young Mania Rating Scale –0.04 (95% CI –0.52 to 0.45). The differences were not statistically significant and were small in relation to the change from baseline in both groups that was observed immediately after completion of therapy. Endocrinological data required for compliance assessment are not yet available. HPA function, similar in patients and control subjects, was not associated with differing clinical responses. Neuropsychological impairments were found, along with changes in brain structure and function, but no effect of metyrapone was seen on these measures.DiscussionThe inclusion criteria led to the sample being broadly representative of patients with TRD, within the UK NHS, with high anxiety and BDI scores. Metyrapone augmentation of antidepressants is not efficacious for outpatients with TRD who are moderately depressed. There was no obvious benefit associated with the use of metyrapone, either on the primary outcome or over the period of follow-up, and this negative result extended to other secondary outcomes. Metyrapone was well tolerated. There were no serious adverse events attributable to it and adverse events were as common with the placebo. HPA axis function was not associated with differing clinical or neuropsychological outcomes.ConclusionsThe results of the study suggest that although metyrapone augmentation was well tolerated, it is ineffective in the treatment of refractory depression. This finding is contrary to a previous proof of principle study in more acutely unwell patients. Future research should consider whether or not antiglucocorticoid treatments, such as metyrapone, should be targeted at patients with confirmed hypercortisolaemia.Trial registrationCurrent Controlled Trials ISRCTN45338259.Funding detailsThis study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

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Acupuncture with Or without Combined Auricular Acupuncture for Insomnia: A Randomised, Waitlist-Controlled Trial

Acupuncture in Medicine ◽

10.1136/acupmed-2017-011371 ◽

2018 ◽

Vol 36 (1) ◽

pp. 2-13 ◽

Cited By ~ 9

Author(s):

Ka-Fai Chung ◽

Wing-Fai Yeung ◽

Branda Yee-Man Yu ◽

Feona Chung-Yin Leung ◽

Shi-Ping Zhang ◽

...

Keyword(s):

Adverse Events ◽

Combination Treatment ◽

Primary Outcome ◽

Controlled Trial ◽

Sleep Efficiency ◽

Sleep Diary ◽

Auricular Acupuncture ◽

Wrist Actigraphy ◽

Significant Difference ◽

Secondary Outcomes

Background Few high-quality, large-scale, controlled trials comparing the effectiveness and safety of acupuncture, auricular acupuncture and combined acupuncture treatment for insomnia are available. Objective To carry out a randomised, assessor-blinded, waitlist-controlled trial to test the superiority of combination treatment. Methods After in-person and polysomnography screening, 224 subjects (mean age 53.4 years; 75.4% female) with DSM-5 insomnia disorder, who were free from major psychiatric disorders and with sleep-diary-derived sleep efficiency averaged over 1 week of <85%, were randomised to acupuncture alone, acupuncture plus auricular acupuncture (combination treatment), or a waitlist in a 3:3:1 ratio. Standardised acupuncture and combination treatment were provided three times weekly for 3 weeks. The primary outcome was sleep-diary-derived sleep efficiency. Secondary outcomes included wrist actigraphy and self-reported scales on insomnia, anxiety and depression, fatigue, sleepiness and functioning. Assessments were conducted at baseline, 1 week, 4 weeks and 13 weeks after treatment. Participants on the waitlist were re-randomised to receive acupuncture or combination treatment after the second post-baseline assessment. Results There was no significant difference between acupuncture and combination treatment in the primary outcome and most secondary outcomes at all time points. However, both treatments were better than waitlist in reducing insomnia, anxiety/depressive symptoms and fatigue, and improving function. Within-group improvements were maintained at 13 weeks after treatment. Of 260 adverse events, 243 were mild (93.5%). Discontinuation due to adverse events was 2.1% and 3.1% for acupuncture and combination treatment, respectively. Conclusions Limited by short-term treatment and follow-up, the attempt to augment acupuncture by auricular acupuncture was not supported. Acupuncture and combination treatment were safe and had mild hypnotic effects, which lasted for at least 13 weeks. Trial Registration Number NCT01891097; Results.

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Effectiveness and cost-effectiveness of the PLAN-A intervention, a peer led physical activity program for adolescent girls: results of a cluster randomised controlled trial

International Journal of Behavioral Nutrition and Physical Activity ◽

10.1186/s12966-021-01133-8 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Russell Jago ◽

Byron Tibbitts ◽

Kathryn Willis ◽

Emily Sanderson ◽

Rebecca Kandiyali ◽

...

Keyword(s):

Physical Activity ◽

Cost Effectiveness ◽

Randomised Controlled Trial ◽

Primary Outcome ◽

Controlled Trial ◽

Cluster Randomised Controlled Trial ◽

Control Group ◽

Cluster Randomised ◽

Secondary Outcomes ◽

Randomised Controlled

Abstract Background Physical activity is associated with improved health. Girls are less active than boys. Pilot work showed that a peer-led physical activity intervention called PLAN-A was a promising method of increasing physical activity in secondary school age girls. This study examined the effectiveness and cost-effectiveness of the PLAN-A intervention. Methods We conducted a cluster randomised controlled trial with Year 9 (13–14 year old) girls recruited from 20 secondary schools. Schools were randomly assigned to the PLAN-A intervention or a non-intervention control group after baseline data collection. Girls nominated students to be peer leaders. The top 18 % of girls nominated by their peers in intervention schools received three days of training designed to prepare them to support physical activity. Data were collected at two time points, baseline (T0) and 5–6 months post-intervention (T1). Participants wore an accelerometer for seven days to assess the primary outcome of mean weekday minutes of moderate-to-vigorous physical activity (MVPA). Multivariable mixed effects linear regression was used to estimate differences in the primary outcome between the two arms on an Intention-to-Treat (ITT) basis. Resource use and quality of life were measured and a within trial economic evaluation from a public sector perspective was conducted. Results A total of 1558 girls were recruited to the study. At T0, girls in both arms engaged in an average of 51 min of MVPA per weekday. The adjusted mean difference in weekday MVPA at T1 was − 2.84 min per day (95 % CI = -5.94 to 0.25) indicating a slightly larger decline in weekday MVPA in the intervention group. Results were broadly consistent when repeated using a multiple imputation approach and for pre-specified secondary outcomes and sub-groups. The mean cost of the PLAN-A intervention was £2817 per school, equivalent to £31 per girl. Economic analyses indicated that PLAN-A did not lead to demonstrable cost-effectiveness in terms of cost per unit change in QALY. Conclusions This study has shown that the PLAN-A intervention did not result in higher levels of weekday MVPA or associated secondary outcomes among Year 9 girls. The PLAN-A intervention should not be disseminated as a public health strategy. Trial registration ISRCTN14539759–31 May, 2018.

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Diclofenac Sodium Gel in Patients with Primary Hand Osteoarthritis: A Randomized, Double-blind, Placebo-controlled Trial

The Journal of Rheumatology ◽

10.3899/jrheum.081316 ◽

2009 ◽

Vol 36 (9) ◽

pp. 1991-1999 ◽

Cited By ~ 78

Author(s):

ROY D. ALTMAN ◽

RENÉE-LILIANE DREISER ◽

CHESTER L. FISHER ◽

WALTER F. CHASE ◽

DONATUS S. DREHER ◽

...

Keyword(s):

Disease Activity ◽

Pain Intensity ◽

Primary Outcome ◽

Controlled Trial ◽

Diclofenac Sodium ◽

Global Rating ◽

Hand Osteoarthritis ◽

Dominant Hand ◽

Double Blind ◽

Secondary Outcomes

Objective.To measure the efficacy and safety of diclofenac sodium gel in patients with primary hand osteoarthritis (OA).Methods.In a randomized, double-blind, placebo-controlled trial, men and women aged ≥ 40 years diagnosed with primary OA in the dominant hand were randomly assigned to self-apply topical 1% diclofenac sodium gel (Voltaren® Gel) (n = 198) or vehicle (n = 187) to both hands 4 times daily for 8 weeks. Primary outcome measures included OA pain intensity (100-mm visual analog scale), total Australian/Canadian Osteoarthritis Hand Index (AUSCAN) score, and global rating of disease activity at 4 and 6 weeks. Secondary outcomes included onset of efficacy in Weeks 1 and 2, durability of efficacy at 8 weeks, measures of disease activity in the dominant hand, pain intensity in the non-dominant hand, AUSCAN subindices, end of study rating of efficacy, and Osteoarthritis Research Society International response criteria.Results.Diclofenac sodium gel decreased pain intensity scores by 42%–45%, total AUSCAN scores by 35%–40%, and global rating of disease by 36%–40%. Significant differences favoring diclofenac sodium gel over vehicle were observed at Week 4 for pain intensity and AUSCAN, with a trend for global rating of disease activity. At Week 6, diclofenac sodium gel treatment significantly improved each primary outcome measure compared with vehicle. Secondary outcomes generally supported the primary outcomes. The most common treatment-related adverse event (AE) was application-site paresthesia. Most AE were mild. No cardiac events, gastrointestinal bleeding, or ulcers were reported.Conclusion.Topical diclofenac sodium gel was generally well tolerated and effective in primary hand OA. (NCT ID: NCT00171665)

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A randomized controlled trial on a self-guided Internet-based intervention for gambling problems

Scientific Reports ◽

10.1038/s41598-021-92242-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lara Bücker ◽

Josefine Gehlenborg ◽

Steffen Moritz ◽

Stefan Westermann

Keyword(s):

Randomized Controlled Trial ◽

Depressive Symptoms ◽

Primary Outcome ◽

Controlled Trial ◽

Group Differences ◽

Control Group ◽

Gambling Problems ◽

Randomized Controlled ◽

Secondary Outcomes ◽

Internet Based Intervention

AbstractThe majority of individuals with problematic and pathological gambling remain untreated, and treatment barriers are high. Internet-based interventions can help to address existing barriers, and first studies suggest their potential for this target group. Within a randomized controlled trial (N = 150) with two assessment times (baseline and post-intervention), we aimed to investigate the feasibility, acceptance, and effectiveness of a self-guided Internet-based intervention targeted at gambling problems. We expected a significant reduction in gambling symptoms (primary outcome) and depressive symptoms as well gambling-specific dysfunctional thoughts (secondary outcomes) in the intervention group (IG) compared to a wait-list control group with access to treatment-as-usual (control group, CG) after the intervention period of 8 weeks. Results of the complete cases, per protocol, intention-to-treat (ITT), and frequent user analyses showed significant improvements in both groups for primary and secondary outcomes but no significant between-group differences (ITT primary outcome, F(1,147) = .11, p = .739, ηp2 < .001). Moderation analyses indicated that individuals in the IG with higher gambling and depressive symptoms, older age, and comorbid anxiety symptoms showed significant improvement relative to the CG. The intervention was positively evaluated (e.g., 96.5% rated the program as useful). Possible reasons for the nonsignificant between-group differences are discussed. Future studies should include follow-up assessments and larger samples to address limitations of the present study. Trial Registration ClinicalTrials.gov (NCT03372226), http://clinicaltrials.gov/ct2/show/NCT03372226, date of registration (13/12/2017).

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An Internet-Based Cognitive Behavioral Therapy Program Adapted to Patients With Cardiovascular Disease and Depression: Randomized Controlled Trial

JMIR Mental Health ◽

10.2196/14648 ◽

2019 ◽

Vol 6 (10) ◽

pp. e14648 ◽

Cited By ~ 9

Author(s):

Peter Johansson ◽

Mats Westas ◽

Gerhard Andersson ◽

Urban Alehagen ◽

Anders Broström ◽

...

Keyword(s):

Cardiovascular Disease ◽

Randomized Controlled Trial ◽

Cognitive Behavioral Therapy ◽

Primary Outcome ◽

Behavioral Therapy ◽

Controlled Trial ◽

Cognitive Behavioral ◽

Randomized Controlled ◽

Secondary Outcomes ◽

Eq Vas

Background Depression is a common cause of reduced well-being and prognosis in patients with cardiovascular disease (CVD). However, there is a lack of effective intervention strategies targeting depression. Objective The study aimed to evaluate the effects of a nurse-delivered and adapted internet-based cognitive behavioral therapy (iCBT) program aimed at reducing depression in patients with CVD. Methods A randomized controlled trial was conducted. A total of 144 patients with CVD with at least mild depression (Patient Health Questionnaire–9 [PHQ-9] score ≥5) were randomized 1:1 to a 9-week program of iCBT (n=72) or an active control participating in a Web-based discussion forum (online discussion forum [ODF], n=72). The iCBT program, which included 7 modules, was adapted to fit patients with CVD. Nurses with an experience of CVD care provided feedback and a short introduction to cognitive behavioral therapy. The primary outcome, depression, was measured using PHQ-9. Secondary outcomes were depression measured using the Montgomery-Åsberg Depression Rating Scale–self-rating version (MADRS-S), health-related quality of life (HRQoL) measured using Short Form 12 (SF-12) survey and EuroQol Visual Analogue Scale (EQ-VAS), and the level of adherence. An intention-to-treat analysis with multiple imputations was used. Between-group differences in the primary and secondary outcomes were determined by the analysis of covariance, and a sensitivity analysis was performed using mixed models. Results Compared with ODF, iCBT had a significant and moderate treatment effect on the primary outcome depression (ie, PHQ-9; mean group difference=−2.34 [95% CI −3.58 to −1.10], P<.001, Cohen d=0.62). In the secondary outcomes, compared with ODF, iCBT had a significant and large effect on depression (ie, MADRS-S; P<.001, Cohen d=0.86) and a significant and moderate effect on the mental component scale of the SF-12 (P<.001, Cohen d=0.66) and the EQ-VAS (P<.001, Cohen d=0.62). Overall, 60% (n=43) of the iCBT group completed all 7 modules, whereas 82% (n=59) completed at least half of the modules. No patients were discontinued from the study owing to a high risk of suicide or deterioration in depression. Conclusions Nurse-delivered iCBT can reduce depression and improve HRQoL in patients with CVD, enabling treatment for depression in their own homes and at their preferred time. Trial Registration ClinicalTrials.gov NCT02778074; https://clinicaltrials.gov/ct2/show/NCT02778074

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The effect of referral for brief intervention for alcohol misuse on repetition of deliberate self-harm: an exploratory randomized controlled trial

Psychological Medicine ◽

10.1017/s0033291709991899 ◽

2010 ◽

Vol 40 (11) ◽

pp. 1821-1828 ◽

Cited By ~ 19

Author(s):

M. J. Crawford ◽

E. Csipke ◽

A. Brown ◽

S. Reid ◽

K. Nilsen ◽

...

Keyword(s):

Alcohol Consumption ◽

Health Information ◽

Brief Intervention ◽

Primary Outcome ◽

Alcohol Misuse ◽

Controlled Trial ◽

Information Leaflet ◽

Deliberate Self Harm ◽

Self Harm ◽

Secondary Outcomes

BackgroundReferral for brief intervention among people who misuse alcohol is reported to be effective but its impact among those who present to services following deliberate self-harm (DSH) has not been examined.MethodConsecutive patients who presented to an Emergency Department (ED) following an episode of DSH were screened for alcohol misuse. Those found to be misusing alcohol were randomly assigned to brief intervention plus a health information leaflet or to a health information leaflet alone. The primary outcome was whether the patient reattended an ED following a further episode of DSH during the subsequent 6 months. Secondary outcomes were alcohol consumption, mental health and satisfaction with care measured 3 and 6 months after randomization.ResultsOne hundred and three people took part in the study. Follow-up data on our primary outcome were obtained for all subjects and on 63% for secondary outcomes. Half those referred for brief intervention received it. Repetition of DSH was strongly associated with baseline alcohol consumption, but not influenced by treatment allocation. There was a non-significant trend towards the number of units of alcohol consumed per drinking day being lower among those randomized to brief intervention.ConclusionsReferral for brief intervention for alcohol misuse following an episode of DSH may not influence the likelihood of repetition of self-harm. Longer-term interventions may be needed to help people who deliberately harm themselves and have evidence of concurrent alcohol misuse.

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A Controlled Trial of Extended-Release Guanfacine and Psychostimulants on Executive Function and ADHD

Journal of Attention Disorders ◽

10.1177/1087054717751197 ◽

2018 ◽

Vol 24 (2) ◽

pp. 318-325 ◽

Cited By ~ 1

Author(s):

Judy P. M. van Stralen

Keyword(s):

Executive Function ◽

Adverse Events ◽

Extended Release ◽

Rating Scale ◽

Controlled Trial ◽

Severity Of Illness ◽

P Value ◽

Serious Adverse Events ◽

Double Blind ◽

Stimulant Therapy

Objective: To evaluate the effectiveness of guanfacine extended-release (GXR) versus placebo as adjunct therapy to usual care stimulant therapy in improving executive function in children aged 6 to 12 years diagnosed with ADHD. Method: In this single center, double-blind placebo-controlled crossover trial, subjects continued to take their psychostimulant and were randomly assigned at baseline to receive active treatment or placebo first. Efficacy measures included Behavioural Rating Inventory of Executive Function (BRIEF-P), ADHD Rating Scale IV (ADHD-RS IV), and Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) scales. Safety measures included adverse events and vital signs. Results: Significant benefits of GXR plus psychostimulant were observed on BRIEF-P ( p value = .0392), ADHD-RS-IV ( p < .0001), CGI-S ( p = .0007), and CGI-I ( p = .003). There were no serious adverse events and no new safety signals. Conclusion: Use of GXR as adjunctive therapy to stimulant therapy significantly improves executive function in children with ADHD.

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A randomised controlled trial of intrapleural balloon intercostal chest drains to prevent drain displacement

European Respiratory Journal ◽

10.1183/13993003.01753-2021 ◽

2021 ◽

pp. 2101753

Author(s):

Rachel M Mercer ◽

Eleanor Mishra ◽

Radhika Banka ◽

John P Corcoran ◽

Cyrus Daneshvar ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Adverse Events ◽

Standard Care ◽

Primary Outcome ◽

Controlled Trial ◽

Clinical Problem ◽

Outcome Data ◽

Chest Drain ◽

Drain Removal ◽

Randomised Controlled

BackgroundChest drain displacement is a common clinical problem, occurring in 9–42% of cases and results in treatment failure or additional pleural procedures conferring unnecessary risk. A novel chest drain with an integrated intrapleural balloon may reduce the risk of displacement.MethodsProspective randomised controlled trial comparing the balloon drain to standard care (12 F chest drain with no balloon) with the primary outcome of objectively-defined unintentional or accidental chest drain displacement.Results267 patients were randomised (primary outcome data available in 257, 96.2%). Displacement occurred less frequently using the balloon drain (displacement 5/128, 3.9%; standard care displacement 13/129, 10.1%) but this was not statistically significant (Odds Ratio (OR) for drain displacement 0.36, 95% CI 0.13 to 1.0, χ2 1df=2.87, p=0.09). Adjusted analysis to account for minimisation factors and use of drain sutures demonstrated balloon drains were independently associated with reduced drain fall out rate (adjusted OR 0.27, 95% CI 0.08 to 0.87, p=0.028). Adverse events were higher in the balloon arm than the standard care arm (balloon drain 59/131, 45.0%; standard care 18/132, 13.6%; χ2 1df=31.3, p<0.0001).ConclusionBalloon drains reduce displacement compared with standard drains independent of the use of sutures but are associated with increased adverse events specifically during drain removal. The potential benefits of the novel drain should be weighed against the risks, but may be considered in practices where sutures are not routinely used.

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SMS education for the promotion of diabetes self-management in low & middle income countries: a pilot randomized controlled trial in Egypt

BMC Public Health ◽

10.1186/s12889-017-4973-5 ◽

2017 ◽

Vol 17 (1) ◽

Cited By ~ 18

Author(s):

Haitham Abaza ◽

Michael Marschollek

Keyword(s):

Glycemic Control ◽

Primary Outcome ◽

Controlled Trial ◽

Self Management ◽

Chi Square ◽

Middle Income ◽

Middle Income Countries ◽

Randomized Controlled ◽

Secondary Outcomes ◽

Management Behaviors

Abstract Background Due to the ubiquity of mobile phones in low and middle income countries, we aimed to examine the feasibility of SMS education among diabetic patients in Egypt, and assess the impact of educational text messages, compared to traditional paper-based methods, on glycemic control and self-management behaviors. Methods We conducted a 12-week randomized controlled trial at Misr University for Science & Technology hospital in Cairo-Egypt. Known as MUST diabetes awareness program, patients were included if they had diabetes, owned a mobile phone, and could read SMS messages or lived with someone that could read for them. Intervention patients received daily messages and weekly reminders addressing various diabetes care categories. We expected greater improvement in their glycemic control compared to controls who only received paper-based educational material. The primary outcome was the change in HbA1c, measured by the difference between endpoint and baseline values and by the number of patients who experienced at least 1% reduction from baseline to endpoint. Key secondary outcomes included blood glucose levels, body weight, treatment and medication adherence, self-efficacy, and diabetes knowledge. Data were analyzed using ANCOVA, chi-square, and t-tests. Results Thirty four intervention and 39 control patients completed the study. Over 12 weeks, 3880 messages were sent. Each intervention patient received 84 educational and 12 reminder messages plus one welcome message. Our primary outcome did not differ significantly (Δ 0.290; 95% CI -0.402 to 0.983; p = 0.406) between groups after 3 months, demonstrating a mean drop of −0.69% and −1.05% in the control and intervention group respectively. However, 16 intervention patients achieved the targeted 1% drop versus only 6 controls, suggesting clear association between study group and 1% HbA1c reductions (chi-square = 8.655; df = 1; p = 0.003). Secondary outcomes seemed in favor of intervention patients at endpoint, with considerable improvements in treatment and medication adherence, self-efficacy, and knowledge scores. Participants also indicated full satisfaction with the program. Conclusions SMS education is a feasible and acceptable method for improving glycemic control and self-management behaviors among Egyptian diabetics. However, whether it is more effective than traditional paper-based methods needs further investigation. Trial registration ClinicalTrials.govNCT02868320. Registered 9 August 2016. Retrospectively registered.

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The Effect of Combined Patching and Citalopram on Visual Acuity in Adults with Amblyopia: A Randomized, Crossover, Placebo-Controlled Trial

Neural Plasticity ◽

10.1155/2019/5857243 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Alice K. Lagas ◽

Joanna M. Black ◽

Bruce R. Russell ◽

Robert R. Kydd ◽

Benjamin Thompson

Keyword(s):

Visual Acuity ◽

Selective Serotonin Reuptake Inhibitors ◽

Controlled Trial ◽

Drug Dose ◽

Small Sample ◽

Cortical Function ◽

Double Blind ◽

Recruitment Challenges ◽

Part Time ◽

Secondary Outcomes

Nonhuman animal models have demonstrated that selective serotonin reuptake inhibitors (SSRIs) can enhance plasticity within the mature visual cortex and enable recovery from amblyopia. The aim of this study was to test the hypothesis that the SSRI citalopram combined with part-time patching of the fellow fixing eye would improve amblyopic eye visual acuity in adult humans. Following a crossover, randomized, double-blind, placebo-controlled design, participants completed two 2-week blocks of fellow fixing eye patching. One block combined patching with citalopram (20 mg/day) and the other with a placebo tablet. The blocks were separated by a 2-week washout period. The primary outcome was change in amblyopic eye visual acuity. Secondary outcomes included stereoacuity and electrophysiological measures of retinal and cortical function. Seven participants were randomized, fewer than our prespecified sample size of 20. There were no statistically significant differences in amblyopic eye visual acuity change between the active (mean±SD change=0.08±0.16 logMAR) and the placebo (mean change=−0.01±0.03 logMAR) blocks. No treatment effects were observed for any secondary outcomes. However, 3 of 7 participants experienced a 0.1 logMAR or greater improvement in amblyopic eye visual acuity in the active but not the placebo blocks. These results from a small sample suggest that larger-scale trials of SSRI treatment for adult amblyopia may be warranted. Considerations for future trials include drug dose, treatment duration, and recruitment challenges. This study was preregistered as a clinical trial (ACTRN12611000669998).

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