Gemma D. Kok

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.

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

BackgroundMajor 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/designThe 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.DiscussionInternet-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 registrationNetherlands Trial Register (NTR): NTR2503

The three-month effect of mobile internet-based Cognitive Therapy on the course of depressive symptoms in remitted recurrently depressed patients: Results of a Randomized Controlled Trial

Background: Internet-based cognitive therapy with monitoring via text messages (mobile CT), in addition to treatment as usual (TAU), might offer a cost-effective way to treat recurrent depression. Method: Remitted patients with at least 2 previous episodes of depression were randomized to mobile CT in addition to TAU (n = 126) or TAU only (n = 113). A linear mixed model was used to examine the effect of the treatment condition on a 3-month course of depressive symptoms after remission. Both an intention-to-treat analysis (n = 239) and a completer analysis (n = 193) were used. Depressive symptoms were assessed using the Inventory of Depressive Symptomatology (IDS-SR30) at baseline and 1.5 and 3 months after randomization. Results: Residual depressive symptoms showed a small but statistically significant decrease in the intention-to-treat group over 3 months in the mobile CT group relative to the TAU group (difference: -1.60 points on the IDS-SR30 per month, 95% CI = -2.64 to -0.56, p = 0.003). The effect of the treatment condition on the depressive symptomatology at the 3-month follow-up was small to moderate (Cohens d = 0.44). All analyses among completers (≥5 modules) showed more pronounced treatment effects. Adjustment for unequally distributed variables did not markedly affect the results. Conclusions: Residual depressive symptoms after remission showed a more favorable course over 3 months in the mobile CT group compared to the TAU group. These results are a first indication that mobile CT in addition to TAU is effective in treating recurrently depressed patients in remission. However, demonstration of its long-term effectiveness and replication remains 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.

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.

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.

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 4th 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.

The scars of childhood adversity: Minor stress sensitivity and depressive symptoms in remitted recurrently depressed adult patients

Background Childhood adversity may lead to depressive relapse through its long-lasting influence on stress sensitivity. In line with the stress sensitization hypothesis, minor (daily) stress is associated with depressive relapse. Therefore, we examine the impact of childhood adversity on daily stress and its predictive value on prospectively assessed depressive symptoms in recurrently depressed patients. Method Daily stress was assessed in recurrently depressed adult patients, enrolled into two randomized trials while remitted. The reported intensity and frequency of dependent and independent daily stress was assessed at baseline. Independent stress is externally generated, for example an accident happening to a friend, while dependent stress is internally generated, for example getting into a fight with a neighbor. Hierarchical regression analyses were performed with childhood adversity, independent and dependent daily stress as predictor variables of prospectively measured depressive symptoms after three months of follow-up (n = 138). Results We found that childhood adversity was not significantly associated with a higher frequency and intensity of daily stress. The intensity of both independent and dependent daily stress was predictive of depressive symptom levels at follow-up (unadjusted models respectively: B = 0.47, t = 2.05, p = 0.041, 95% CI = 0.02–0.92; B = 0.29, t = 2.20, p = 0.028, 95% CI = 0.03–0.55). No associations were found between childhood adversity and depressive symptoms at follow-up. Conclusion No evidence was found supporting stress sensitization due to the experience of childhood adversity in this recurrently depressed but remitted patient group. Nevertheless, our research indicates that daily stress might be a target for preventive treatment. Trial Registration Trial A: Nederlands Trial Register NTR1907 Trial B: Nederlands Trial Register NTR2503

Economic evaluation of an internet-based preventive cognitive therapy with minimal therapist support for recurrent depression: results of a randomized controlled trial (Preprint)

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

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

9415) for M-CT and €7296 (US