Cost-effectiveness of peer-delivered interventions for cocaine and alcohol abuse among women: a randomized controlled trial

Aims

To determine whether the additional interventions to standard care are cost-effective in addressing cocaine and alcohol abuse at 4 months (4 M) and 12 months (12 M) from baseline.

Method

We conducted a cost-effectiveness analysis of a randomized controlled trial with three arms: (1) NIDA''s Standard intervention (SI); (2) SI plus a Well Woman Exam (WWE); and, (3) SI, WWE, plus four Educational Sessions (4ES).

Results

To obtain an additional cocaine abstainer, WWE compared to SI cost $7,223 at 4 M and $3,611 at 12 M. Per additional alcohol abstainer, WWE compared to SI cost $3,611 and $7,223 at 4 M and 12 M, respectively. At 12 M, 4ES was dominated (more costly and less effective) by WWE for abstinence outcomes.

Conclusions

To our knowledge, this is the first cost-effectiveness analysis simultaneously examining cocaine and alcohol abuse in women. Depending on primary outcomes sought and priorities of policy makers, peer-delivered interventions can be a cost-effective way to address the needs of this growing, underserved population.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01235091","term_id":"NCT01235091"}}NCT01235091     

Pragmatic randomized controlled trial of long‐term psychoanalytic psychotherapy for treatment‐resistant depression: the Tavistock Adult Depression Study (TADS)

This pragmatic randomized controlled trial tested the effectiveness of long‐term psychoanalytic psychotherapy (LTPP) as an adjunct to treatment‐as‐usual according to UK national guidelines (TAU), compared to TAU alone, in patients with long‐standing major depression who had failed at least two different treatments and were considered to have treatment‐resistant depression. Patients (N=129) were recruited from primary care and randomly allocated to the two treatment conditions. They were assessed at 6‐monthly intervals during the 18 months of treatment and at 24, 30 and 42 months during follow‐up. The primary outcome measure was the 17‐item version of the Hamilton Depression Rating Scale (HDRS‐17), with complete remission defined as a HDRS‐17 score ≤8, and partial remission defined as a HDRS‐17 score ≤12. Secondary outcome measures included self‐reported depression as assessed by the Beck Depression Inventory ‐ II, social functioning as evaluated by the Global Assessment of Functioning, subjective wellbeing as rated by the Clinical Outcomes in Routine Evaluation ‐ Outcome Measure, and satisfaction with general activities as assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire. Complete remission was infrequent in both groups at the end of treatment (9.4% in the LTPP group vs. 6.5% in the control group) as well as at 42‐month follow‐up (14.9% vs. 4.4%). Partial remission was not significantly more likely in the LTPP than in the control group at the end of treatment (32.1% vs. 23.9%, p=0.37), but significant differences emerged during follow‐up (24 months: 38.8% vs. 19.2%, p=0.03; 30 months: 34.7% vs. 12.2%, p=0.008; 42 months: 30.0% vs. 4.4%, p=0.001). Both observer‐based and self‐reported depression scores showed steeper declines in the LTPP group, alongside greater improvements on measures of social adjustment. These data suggest that LTPP can be useful in improving the long‐term outcome of treatment‐resistant depression. End‐of‐treatment evaluations or short follow‐ups may miss the emergence of delayed therapeutic benefit.     

Algorithm-based modular psychotherapy vs. cognitive-behavioral therapy for patients with depression,psychiatric comorbidities and early trauma: a proof-of-concept randomized controlled trial

Effect sizes of psychotherapies currently stagnate at a low-to-moderate level. Personalizing psychotherapy by algorithm-based modular procedures promises improved outcomes, greater flexibility, and a better fit between research and practice. However, evidence for the feasibility and efficacy of modular-based psychotherapy, using a personalized treatment algorithm, is lacking. This proof-of-concept randomized controlled trial was conducted in 70 adult outpatients with a primary DSM-5 diagnosis of major depressive disorder, a score higher than 18 on the 24-item Hamilton Rating Scale for Depression (HRSD-24), at least one comorbid psychiatric diagnosis according to the Structured Clinical Interview for DSM-5 (SCID-5), a history of at least “moderate to severe” childhood maltreatment on at least one domain of the Childhood Trauma Questionnaire (CTQ), and exceeding the cut-off value on at least one of three measures of early trauma-related transdiagnostic mechanisms: the Rejection Sensitivity Questionnaire (RSQ), the Interpersonal Reactivity Index (IRI), and the Difficulties in Emotion Regulation Scale-16 (DERS-16). Patients were randomized to 20 sessions of either standard cognitive-behavioral therapy alone (CBT) or CBT plus transdiagnostic modules according to a mechanism-based treatment algorithm (MoBa), over 16 weeks. We aimed to assess the feasibility of MoBa, and to compare MoBa vs. CBT with respect to participants’ and therapists’ overall satisfaction and ratings of therapeutic alliance (using the Working Alliance Inventory - Short Revised, WAI-SR), efficacy, impact on early trauma-related transdiagnostic mechanisms, and safety. The primary outcome for efficacy was the HRSD-24 score at post-treatment. Secondary outcomes included, among others, the rate of response (defined as a reduction of the HRSD-24 score by at least 50% from baseline and a score <16 at post-treatment), the rate of remission (defined as a HRSD-24 score ≤8 at post-treatment), and improvements in early trauma-related mechanisms of social threat response, hyperarousal, and social processes/empathy. We found no difficulties in the selection of the transdiagnostic modules in the individual patients, applying the above-mentioned cut-offs, and in the implementation of MoBa. Both participants and therapists reported higher overall satisfaction and had higher WAI-SR ratings with MoBa than CBT. Both approaches led to major reductions of depressive symptoms at post-treatment, with a non-significant superiority of MoBa over CBT. Patients randomized to MoBa were nearly three times as likely to experience remission at the end of therapy (29.4% vs. 11.4%; odds ratio, OR = 3.2, 95% CI: 0.9-11.6). Among mechanism-based outcomes, MoBa patients showed a significantly higher post-treatment effect on social processes/empathy (p<0.05) compared to CBT patients, who presented an exacerbation on this domain at post-treatment. Substantially less adverse events were reported for MoBa compared to CBT. These results suggest the feasibility and acceptability of an algorithm-based modular psychotherapy complementing CBT in depressed patients with psychiatric comorbidities and early trauma. While initial evidence of efficacy was observed, potential clinical advantages and interindividual heterogeneity in treatment outcomes will have to be investigated in fully powered confirmation trials.     

Effectiveness and costs associated with a lay counselor–delivered,brief problem-solving mental health intervention for adolescents in urban,low-income schools in India: 12-month outcomes of a randomized controlled trial

BackgroundPsychosocial interventions for adolescent mental health problems are effective, but evidence on their longer-term outcomes is scarce, especially in low-resource settings. We report on the 12-month sustained effectiveness and costs of scaling up a lay counselor–delivered, transdiagnostic problem-solving intervention for common adolescent mental health problems in low-income schools in New Delhi, India.Methods and findingsParticipants in the original trial were 250 school-going adolescents (mean [M] age = 15.61 years, standard deviation [SD] = 1.68), including 174 (69.6%) who identified as male. Participants were recruited from 6 government schools over a period of 4 months (August 20 to December 14, 2018) and were selected on the basis of elevated mental health symptoms and distress/functional impairment. A 2-arm, randomized controlled trial design was used to examine the effectiveness of a lay counselor–delivered, problem-solving intervention (4 to 5 sessions over 3 weeks) with supporting printed booklets (intervention arm) in comparison with problem solving delivered via printed booklets alone (control arm), at the original endpoints of 6 and 12 weeks. The protocol was modified, as per the recommendation of the Trial Steering Committee, to include a post hoc extension of the follow-up period to 12 months. Primary outcomes were adolescent-reported psychosocial problems (Youth Top Problems [YTP]) and mental health symptoms (Strengths and Difficulties Questionnaire [SDQ] Total Difficulties scale). Other self-reported outcomes included SDQ subscales, perceived stress, well-being, and remission. The sustained effects of the intervention were estimated at the 12-month endpoint and over 12 months (the latter assumed a constant effect across 3 follow-up points) using a linear mixed model for repeated measures and involving complete case analysis. Sensitivity analyses examined the effect of missing data using multiple imputations. Costs were estimated for delivering the intervention during the trial and from modeling a scale-up scenario, using a retrospective ingredients approach. Out of the 250 original trial participants, 176 (70.4%) adolescents participated in the 12-month follow-up assessment. One adverse event was identified during follow-up and deemed unrelated to the intervention. Evidence was found for intervention effects on both SDQ Total Difficulties and YTP at 12 months (YTP: adjusted mean difference [AMD] = −0.75, 95% confidence interval [CI] = −1.47, −0.03, p = 0.04; SDQ Total Difficulties: AMD = −1.73, 95% CI = −3.47, 0.02, p = 0.05), with stronger effects over 12 months (YTP: AMD = −0.98, 95% CI = −1.51, −0.45, p < 0.001; SDQ Total Difficulties: AMD = −1.23, 95% CI = −2.37, −0.09; p = 0.03). There was also evidence for intervention effects on internalizing symptoms, impairment, perceived stress, and well-being over 12 months. The intervention effect was stable for most outcomes on sensitivity analyses adjusting for missing data; however, for SDQ Total Difficulties and impairment, the effect was slightly attenuated. The per-student cost of delivering the intervention during the trial was $3 United States dollars (USD; or $158 USD per case) and for scaling up the intervention in the modeled scenario was $4 USD (or $23 USD per case). The scaling up cost accounted for 0.4% of the per-student school budget in New Delhi. The main limitations of the study’s methodology were the lack of sample size calculations powered for 12-month follow-up and the absence of cost-effectiveness analyses using the primary outcomes.ConclusionsIn this study, we observed that a lay counselor–delivered, brief transdiagnostic problem-solving intervention had sustained effects on psychosocial problems and mental health symptoms over the 12-month follow-up period. Scaling up this resource-efficient intervention is an affordable policy goal for improving adolescents’ access to mental health care in low-resource settings. The findings need to be interpreted with caution, as this study was a post hoc extension, and thus, the sample size calculations did not take into account the relatively high attrition rate observed during the long-term follow-up.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03630471","term_id":"NCT03630471"}}NCT03630471.

Kanika Malik, Daniel Michelson, and colleagues study the sustained effectiveness of a lay counsellor-delivered problem solving intervention to mental health of adolescents enrolled in low-income schools in New Delhi, India.     

A community mobilisation intervention to prevent violence against women and reduce HIV/AIDS risk in Kampala, Uganda (the SASA! Study): study protocol for a cluster randomised controlled trial

ABSTRACT: BACKGROUND: Gender based violence, including violence by an intimate partner, is a major global human rights and public health problem, with important connections with HIV risk. Indeed, the elimination of sexual and gender based violence is a core pillar of HIV prevention for UNAIDS. Integrated strategies to address the gender norms, relations and inequities that underlie both violence against women and HIV/AIDS are needed. However there is limited evidence about the potential impact of different intervention models. This protocol describes the SASA! Study: an evaluation of a community mobilisation intervention to prevent violence against women and reduce HIV/AIDS risk in Kampala, Uganda. METHODS: The SASA! Study is a pair-matched cluster randomised controlled trial being conducted in eight communities in Kampala. It is designed to assess the community-level impact of the SASA! intervention on the following six primary outcomes: attitudes towards the acceptability of violence against women and the acceptability of a woman refusing sex (among male and female community members); past year experience of physical intimate partner violence and sexual intimate partner violence (among females); community responses to women experiencing violence (among women reporting past year physical/sexual partner violence); and past year concurrency of sexual partners (among males). 1583 women and men (aged 18-49 years) were surveyed in intervention and control communities prior to intervention implementation in 2007/8. A follow-up cross-sectional survey of community members will take place in 2012. The primary analysis will be an adjusted cluster-level intention to treat analysis, comparing outcomes in intervention and control communities at follow-up. Complementary monitoring and evaluation and qualitative research will be used to explore and describe the process of intervention implementation and the pathways through which change is achieved. DISCUSSION: This is one of few cluster randomised trials globally to assess the impact of a gender-focused community mobilisation intervention. The multi-disciplinary research approach will enable us to address questions of intervention impact and mechanisms of action, as well as its feasibility, acceptability and transferability to other contexts. The results will be of importance to researchers, policy makers and those working on the front line to prevent violence against women and HIV.     

Nitrous oxide (N<Subscript>2</Subscript>O) and subsequent open-label SSRI treatment of adolescents with depression (NOTAD): study protocol for a randomised controlled trial

Background

The first line of pharmacological treatment for severe depressive disorders in young people is selective serotonin reuptake inhibitors (SSRIs). However, beneficial clinical effects are rarely observed before several weeks into treatment. Nitrous oxide (N₂O) has a long-standing safety record for pain relief and has been used in adults and young people. In adults with severe treatment-resistant depression, a single dose of N₂O had significant antidepressant effects, with maximum antidepressant effects observed 24 h after administration. However, the antidepressant effects of N₂O have never been investigated in adolescents with a confirmed diagnosis of depression in a prospective trial. The aims of this study are to (1) investigate whether a single inhaled N₂O administration leads to antidepressant effects in adolescents with depression at 24 h, (2) determine whether combined N₂O and SSRI administration (commenced after N₂O intervention) provides a clinically significant improvement in mood over and above the benefits from SSRI administration alone, and, (3) investigate whether the effect seen following N₂O administration can be used as a predictor of SSRI treatment response.

Methods/design

In this study, we will use a single-blind, randomised, placebo-controlled design. Patients aged between 12 and 17 years with major depressive disorder will be recruited. This study will consist of two phases: phase A and phase B. During phase A, participants will be randomised to receive either inhaled N₂O or placebo (air) for 1 h. In phase B, participants will receive open-label pharmacological treatment with the SSRI fluoxetine and will be followed over a 12-week period. Participants will undertake mood assessments at 2 and 24 h after N₂O or placebo administration (phase A) and weekly during the 12-week follow up in phase B.

Discussion

We expect an antidepressant effect from a single dose of inhaled N₂O compared with placebo at 24 h after administration. Additionally, we expect that subjects treated with N₂O will also show greater improvements than the placebo group after 6 and 12 weeks into fluoxetine treatment because of potential additive antidepressant effects. Such findings would be of clinical importance because currently children and adolescents often do not experience any symptom alleviation for several weeks following the initiation of SSRIs.

Trial registration

Australian and New Zealand Clinical Trials Registry, ACTRN12616001568404. Registered on 14 November 2016.