Economic Evaluation of an Internet-Based Preventive Cognitive Therapy With Minimal Therapist Support for Recurrent Depression: Randomized Controlled Trial.

BACKGROUND: Major depressive disorder (MDD) is highly recurrent and has a significant disease burden. Although the effectiveness of internet-based interventions has been established for the treatment of acute MDD, little is known about their cost effectiveness, especially in recurrent MDD. OBJECTIVES: Our aim was to evaluate the cost effectiveness and cost utility of an internet-based relapse prevention program (mobile cognitive therapy, M-CT). METHODS: The economic evaluation was performed alongside a single-blind parallel group randomized controlled trial. Participants were recruited via media, general practitioners, and mental health care institutions. In total, 288 remitted individuals with a history of recurrent depression were eligible, of whom 264 were randomly allocated to M-CT with minimal therapist support added to treatment as usual (TAU) or TAU alone. M-CT comprised 8 online lessons, and participants were advised to complete 1 lesson per week. The economic evaluation was performed from a societal perspective with a 24-month time horizon. The health outcomes were number of depression-free days according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria assessed with the Structured Clinical Interview for DSM-IV axis I disorders by blinded interviewers after 3, 12, and 24 months. Quality-adjusted life years (QALYs) were self-assessed with the three level version of the EuroQol Five Dimensional Questionnaire (EQ-5D-3L). Costs were assessed with the Trimbos and Institute for Medical Technology Assessment Questionnaire on Costs Associated with Psychiatric Illness (TiC-P). Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were displayed to assess the probability that M-CT is cost effective compared to TAU. RESULTS: Mean total costs over 24 months were €8298 (US $9415) for M-CT and €7296 (US $8278) for TAU. No statistically significant differences were found between M-CT and TAU regarding depression-free days and QALYs (P=.37 and P=.92, respectively). The incremental costs were €179 (US $203) per depression-free day and €230,816 (US $261,875) per QALY. The cost-effectiveness acceptability curves suggested that for depression-free days, high investments have to be made to reach an acceptable probability that M-CT is cost effective compared to TAU. Regarding QALYs, considerable investments have to be made but the probability that M-CT is cost effective compared to TAU does not rise above 40%. CONCLUSIONS: The results suggest that adding M-CT to TAU is not effective and cost effective compared to TAU alone. Adherence rates were similar to other studies and therefore do not explain this finding. The participants scarcely booked additional therapist support, resulting in 17.3 minutes of mean total therapist support. More studies are needed to examine the cost effectiveness of internet-based interventions with respect to long-term outcomes and the role and optimal dosage of therapist support. Overall, more research is needed on scalable and cost-effective interventions that can reduce the burden of recurrent MDD. TRIAL REGISTRATION: Netherlands Trial Register NTR2503; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2503 (Archived by WebCite at http://www.webcitation.org/73aBn41r3).

Non-fatal disease burden for subtypes of depressive disorder: population-based epidemiological study.

BACKGROUND: Major depression is the leading cause of non-fatal disease burden. Because major depression is not a homogeneous condition, this study estimated the non-fatal disease burden for mild, moderate and severe depression in both single episode and recurrent depression. All estimates were assessed from an individual and a population perspective and presented as unadjusted, raw estimates and as estimates adjusted for comorbidity. METHODS: We used data from the first wave of the second Netherlands-Mental-Health-Survey-and-Incidence-Study (NEMESIS-2, n = 6646; single episode Diagnostic and Statistical Manual (DSM)-IV depression, n = 115; recurrent depression, n = 246). Disease burden from an individual perspective was assessed as 'disability weight * time spent in depression' for each person in the dataset. From a population perspective it was assessed as 'disability weight * time spent in depression *number of people affected'. The presence of mental disorders was assessed with the Composite International Diagnostic Interview (CIDI) 3.0. RESULTS: Single depressive episodes emerged as a key driver of disease burden from an individual perspective. From a population perspective, recurrent depressions emerged as a key driver. These findings remained unaltered after adjusting for comorbidity. CONCLUSIONS: The burden of disease differs between the subtype of depression and depends much on the choice of perspective. The distinction between an individual and a population perspective may help to avoid misunderstandings between policy makers and clinicians.

Cognitive reactivity, self-depressed associations, and the recurrence of depression.

BACKGROUND: Mixed evidence exists regarding the role of cognitive reactivity (CR; cognitive responsivity to a negative mood) as a risk factor for recurrences of depression. One explanation for the mixed evidence may lie in the number of previous depressive episodes. Heightened CR may be especially relevant as a risk factor for the development of multiple depressive episodes and less so for a single depressive episode. In addition, it is theoretically plausible but not yet tested that the relationship between CR and number of episodes is moderated by the strength of automatic depression-related self-associations. AIM: To investigate (i) the strength of CR in remitted depressed individuals with a history of a single vs. multiple episodes, and (ii) the potentially moderating role of automatic negative self-associations in the relationship between the number of episodes and CR. METHOD: Cross-sectional analysis of data obtained in a cohort study (Study 1) and during baseline assessments in two clinical trials (Study 2). Study 1 used data from the Netherlands Study of Depression and Anxiety (NESDA) and compared never-depressed participants (n=901) with remitted participants with either a single (n=336) or at least 2 previous episodes (n=273). Study 2 included only remitted participants with at least two previous episodes (n=273). The Leiden Index of Depression Sensitivity Revised (LEIDS-R) was used to index CR and an Implicit Association Test (IAT) to measure implicit self-associations. RESULTS: In Study 1, remitted depressed participants with multiple episodes had significantly higher CR than those with a single or no previous episode. The remitted individuals with multiple episodes of Study 2 had even higher CR scores than those of Study 1. Within the group of individuals with multiple episodes, CR was not heightened as a function of the number of episodes, even if individual differences in automatic negative self-associations were taken into account. LIMITATIONS: The study employed a cross-sectional design, which precludes a firm conclusion with regard to the direction of this relationship. CONCLUSIONS: The findings are consistent with the view that high CR puts people at risk for recurrent depression and is less relevant for the development of an incidental depressive episode. This suggests that CR is an important target for interventions that aim to prevent the recurrence of depression.

Understanding emotion and emotional scarring in recurrent depression.

BACKGROUND: A single-item assessment of sad mood after remission from MDD is predictive of relapse, yet the mechanisms that play a role in depressive relapse remain poorly understood. METHODS: In 283 patients, remitted from recurrent depression (DSM-IV-TR criteria; HAM-D17 score ≤ 10), we examined emotional scarring, that is, whether the number of previous depressive episodes was associated with higher levels of sad mood as assessed with a 1-item Visual Analogue Mood Scale (VAMS). We then fitted a cross-sectional multivariate regression model to predict sad mood levels, including the Dysfunctional Attitude Scale Version-A, cognitive reactivity (Leiden Index of Depression Sensitivity), Ruminative Response Scale, and Everyday Problem Checklist. RESULTS: Patients with greater numbers of prior episodes experienced higher levels of sad mood after remission. In multivariate regression, intensity of daily stress and dysfunctional beliefs were associated with the VAMS (Adj. R(2)=.091) although not over and above depressive symptomatology (Adj. R(2)=.114). Cognitive reactivity was not associated with sadness. CONCLUSIONS: Our finding that patients with more previous MDEs reported higher levels of sad mood while remitted could be indicative of emotional scarring. Dysfunctional beliefs and intensity of daily stress were associated with sad mood but not over and above residual symptoms. Thus, illness related characteristics especially are associated with sad mood after remission. More negative affect after remission could result in lower stress tolerance or more stress intensity could result in negative affect. Future studies should examine premorbid sadness in a longitudinal cohort, and should study the exact pathway from stress, affect, and cognition to relapse.

Effectiveness of psychological interventions in preventing recurrence of depressive disorder: meta-analysis and meta-regression.

BACKGROUND: Major depression is probably best seen as a chronically recurrent disorder, with patients experiencing another depressive episode after remission. Therefore, attention to reduce the risk of relapse or recurrence after remission is warranted. The aim of this review is to meta-analytically examine the effectiveness of psychological interventions to reduce relapse or recurrence rates of depressive disorder. METHODS: We systematically reviewed the pertinent trial literature until May 2014. The random-effects model was used to compute the pooled relative risk of relapse or recurrence (RR). A distinction was made between two comparator conditions: (1) treatment-as-usual and (2) the use of antidepressants. Other sources of heterogeneity in the data were explored using meta-regression. RESULTS: Twenty-five randomised trials met inclusion criteria. Preventive psychological interventions were significantly better than treatment-as-usual in reducing the risk of relapse or recurrence (RR=0.64, 95% CI=0.53-0.76, z=4.89, p<0.001, NNT=5) and also more successful than antidepressants (RR=0.83, 95% CI=0.70-0.97, z=2.40, p=0.017, NNT=13). Meta-regression showed homogeneity in effect size across a range of study, population and intervention characteristics, but the preventive effect of psychological intervention was usually better when the prevention was preceded by treatment in the acute phase (b=-1.94, SEb=0.68, z=-2.84, p=0.005). LIMITATIONS: Differences between the primary studies in methodological design, composition of the patient groups and type of intervention may have caused heterogeneity in the data, but could not be evaluated in a meta-regression owing to poor reporting. CONCLUSIONS: We conclude that there is supporting evidence that preventive psychological interventions reduce the risk of relapse or recurrence in major depression.

Personality and cognitive vulnerability in remitted recurrently depressed patients.

INTRODUCTION: Personality disorders (PDs) have been associated with a poor prognosis of Major Depressive Disorder (MDD). The aim of the current study was to examine cognitive vulnerability (i.e., dysfunctional beliefs, extremity of beliefs, cognitive reactivity, and rumination) that might contribute to this poor prognosis of patients with PD comorbidity. METHODS: 309 outpatients with remitted recurrent MDD (SCID-I; HAM-D17 ≤ 10) were included within two comparable RCTs and were assessed at baseline with the Personality Diagnostic Questionnaire-4(+) (PDQ-4(+)), the Dysfunctional Attitude Scale Version-A (DAS-A), the Leiden Index of Depression Sensitivity (LEIDS), the Ruminative Response Scale (RRS), and the Inventory of Depressive Symptomatology-Self Report (IDS-SR). RESULTS: We found an indication that the PD prevalence was 49.5% in this remitted recurrently depressed sample. Having a PD (and higher levels of personality pathology) was associated with dysfunctional beliefs, cognitive reactivity, and rumination. Extreme 'black and white thinking' on the DAS was not associated with personality pathology. Brooding was only associated with a Cluster C classification (t(308) = 4.03, p < .001) and with avoidant PD specifically (t(308) = 4.82, p < .001), while surprisingly not with obsessive-compulsive PD. LIMITATIONS: PDs were assessed by questionnaire and the analyses were cross-sectional in nature. CONCLUSION: Being the first study to examine cognitive reactivity and rumination in patients with PD and remitted MDD, we demonstrated that even after controlling for depressive symptomatology, dysfunctional beliefs, cognitive reactivity, and rumination were associated with personality pathology. Rumination might be a pathway to relapse for patients with avoidant PD. Replication of our findings concerning cognitive vulnerability and specific PDs is necessary.

How do you feel? Detection of recurrent Major Depressive Disorder using a single-item screening tool.

Mood is a key element of Major Depressive Disorder (MDD), and is perceived as a highly dynamic construct. The aim of the current study was to examine whether a single-item mood scale can be used for mood monitoring. One hundred thirty remitted out-patients were assessed using the Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I), Visual Analogue Mood Scale (VAMS), 17-item Hamilton Depression Rating Scale (HAM-D17), and Inventory of Depressive Symptomatology-Self Report (IDS-SR). Of all patients, 13.8% relapsed during follow-up assessments. Area under the curves (AUCs) for the VAMS, HAM-D17 and IDS-SR were 0.94, 0.91, and, 0.86, respectively. The VAMS had the highest positive predictive value (PPV) without any false negatives at score 55 (PPV=0.53; NPV=1.0) and was the best predictor of current relapse status (variance explained for VAMS: 60%; for HAM-D17: 49%; for IDS-SR: 34%). Only the HAM-D17 added significant variance to the model (7%). Assessing sad mood with a single-item mood scale seems to be a straightforward and patient-friendly avenue for life-long mood monitoring. Using a diagnostic interview (e.g., the SCID) in case of a positive screen is warranted. Repeated assessment of the VAMS using Ecological Momentary Assessment (EMA) might reduce false positives.

Double trouble: does co-morbid chronic somatic illness increase risk for recurrence in depression? A systematic review.

OBJECTIVE: To perform a systematic review, and if possible a meta-analysis, to establish whether depressed patients with co-morbid chronic somatic illnesses are a high risk "double trouble" group for depressive recurrence. METHOD: The databases PubMed, EMbase and PsycINFO were systematically searched until the 4(th) of December 2012 by using MeSH and free text terms. Additionally, reference lists of retrieved publications and treatment guidelines were reviewed, and experts were consulted. Inclusion criteria were: depression had to be measured at least twice during the study with qualified instruments and the chronic somatic illness had to be assessed by self-report or by a medical professional. Information on depressive recurrence was extracted and additionally risk ratios of recurrence were calculated. RESULTS: The search generated four articles that fulfilled our inclusion criteria. These studies showed no differences in recurrence over one- two- three- and 6.5 years of follow-up for a total of 2010 depressed patients of which 694 patients with a co-morbid chronic somatic illness versus 1316 patients without (Study 1: RR = 0.49, 95% CI, 0.17-1.41 at one year follow-up and RR = 1.37, 95% CI, 0.78-2.41 at two year follow-up; Study 2: RR = 0.94, 95% CI, 0.65-1.36 at two year follow-up; Study 3: RR = 1.15, 95% CI, 0.40-3.27 at one year follow-up; RR = 1.07, 95% CI, 0.48-2.42 at two year follow-up and RR = 0.99, 95% CI,0.55-1.77 at 6.5 years follow-up; Study 4: RR = 1.16, 95% CI, 0.86-1.57 at three year follow-up). CONCLUSION: We found no association between a heightened risk for depressive recurrence and co-morbid chronic somatic illnesses. There is a need for more longitudinal studies to justify the current specific treatment advice such as long-term pharmacological maintenance treatment for this presumed "double trouble" group.

Disrupting the rhythm of depression using Mobile Cognitive Therapy for recurrent depression: randomized controlled trial design and protocol.

BACKGROUND: Major depressive disorder (MDD) is projected to rank second on a list of 15 major diseases in terms of burden in 2030. The major contribution of MDD to disability and health care costs is largely due to its highly recurrent nature. Accordingly, efforts to reduce the disabling effects of this chronic condition should shift to preventing recurrence, especially in patients at high risk of recurrence. Given its high prevalence and the fact that interventions are necessary during the remitted phase, new approaches are needed to prevent relapse in depression. METHODS/DESIGN: The best established effective and available psychological intervention is cognitive therapy. However, it is costly and not available for most patients. Therefore, we will compare the effectiveness and cost-effectiveness of self-management supported by online CT accompanied by SMS based tele-monitoring of depressive symptomatology, i.e. Mobile Cognitive Therapy (M-CT) versus treatment as us usual (TAU). Remitted patients (n = 268) with at least two previous depressive episodes will be recruited and randomized over (1) M-CT in addition to TAU versus (2) TAU alone, with follow-ups at 3, 12, and 24 months. Randomization will be stratified for number of previous episodes and type of treatment as usual. Primary outcome is time until relapse/recurrence over 24 months using DSM-IV-TR criteria as assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). For the economic evaluation the balance between costs and health outcomes will be compared across strategies using a societal perspective. DISCUSSION: Internet-based interventions might be helpful in empowering patients to become their own disease managers in this lifelong recurrent disorder. This is, as far as we are aware of, the first study that examines the (cost) effectiveness of an E-mental health program using SMS monitoring of symptoms with therapist support to prevent relapse in remitted recurrently depressed patients. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2503.