Antidepressant Maintenance Research Articles

The Rising Influence of Mindfulness-Based Cognitive Therapy in Depression Treatment

Major depressive disorder is a common and recurring condition that necessitates ongoing advancements in treatment. The integration of mindfulness meditation and cognitive behavioural techniques in mindfulness-based cognitive therapy (MBCT) has shown promise as an effective approach. This review focuses on the current evidence regarding MBCT's efficacy in treating acute depression and preventing relapse. A comprehensive search was conducted across various databases to identify randomized controlled trials, systematic reviews, and meta-analyses from the last decade that evaluate MBCT. The results consistently indicate that MBCT is able to reduce current symptoms of depression and lower the risk of relapse to a similar extent as maintenance antidepressants. Additionally, neuroimaging studies have revealed functional changes in the brain that correlate with clinical improvements following MBCT. There is a growing trend towards expanding the delivery methods for MBCT, including online platforms and applications, while also optimizing traditional in-person settings. However, there are several limitations that need to be addressed. These include issues surrounding patient diversity, teaching quality, cost-effectiveness, and accessibility. To broaden the scope of MBCT and enhance its effectiveness in different care settings, further research on implementation is necessary. To summarize, MBCT has demonstrated consistent efficacy in treating major depression, but there is a need to continuously improve its accessibility and delivery methods as it becomes more widely available

Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression

BackgroundAntidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied.MethodsWe conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression.ResultsOf 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P=0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups.ConclusionsIn a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.)

Neuropsychological markers of antidepressant action: a secondary analysis of the ANTLER randomised controlled trial.

Antidepressants have been proposed to act via their influence on emotional processing. We investigated the effect of discontinuing maintenance antidepressant treatment on positive and negative self-referential recall and the association between self-referential recall and risk of relapse. The ANTLER trial was a large (N = 478) pragmatic double-blind trial investigating the clinical effectiveness of long-term antidepressant treatment for preventing relapse in primary care patients. Participants were randomised to continue their maintenance antidepressants or discontinue via a taper to placebo. We analysed memory for positive and negative personality descriptors, assessed at baseline, 12- and 52-week follow-up. The recall task was completed by 437 participants. There was no evidence of an effect of discontinuation on self-referential recall at 12 [positive recall ratio 1.00, 95% CI (0.90-1.11), p = 0.93; negative recall ratio 1.00 (0.87-1.14), p = 0.87] or 52 weeks [positive recall ratio 1.03 (0.91-1.17), p = 0.62; negative recall ratio 1.00 (0.86-1.15), p = 0.96; ratios larger than one indicate higher recall in the discontinuation group], and no evidence of an association between recall at baseline or 12 weeks and later relapse [baseline, positive hazard ratio (HR) 1.02 (0.93-1.12), p = 0.74; negative HR 1.01 (0.90-1.13), p = 0.87; 12 weeks, positive HR 0.99 (0.89-1.09), p = 0.81; negative HR 0.98 (0.84-1.14), p = 0.78; ratios larger than one indicate a higher frequency of relapse in those with higher recall]. We found no evidence that discontinuing long-term antidepressants altered self-referential recall or that self-referential recall was associated with risk of relapse. These findings suggest that self-referential recall is not a neuropsychological marker of antidepressant action.

Increases in External Sensory Observing Cross-Sectionally Mediate the Repair of Positive Affect Following Mindfulness-Based Cognitive Therapy in Individuals with Residual Depression Symptoms

ObjectivesMindfulness-Based Cognitive Therapy for Depression (MBCT-D) has been shown to be effective at repairing positive affect deficits in depressed individuals, but the mechanism of action underpinning these changes has not been empirically examined. To address this issue, secondary analyses of two randomised controlled trials in individuals with residual depression were conducted.MethodStudy 1 was a cross-sectional mediation analysis of a trial reporting superior effects of MBCT-D to a waitlist control in bolstering momentary positive affect in individuals with residual depression symptoms (n = 130). Study 2 replicated this analysis in the subset of individuals with residual depression symptoms (n = 117) from a second, larger trial comparing MBCT-D to maintenance antidepressants (M-ADM) to prevent depressive relapse that also included a positive affect outcome.ResultsIn Study 1, an increase in external sensory observing uniquely mediated the superiority of MBCT-D over the control in repairing momentary positive affect. Replicating these findings, in Study 2, MBCT-D was superior to M-ADM at repairing positive affect and this was cross-sectionally mediated by changes in external sensory observing.ConclusionsThese findings suggest that one way in which MBCT-D enhances positive affect in individuals with residual depression may be by training the capacity to attend to external sensory experience.

Antidepressant Drugs and Health-Related Quality of Life

Antidepressant drugs are effective against depression. They also improve subjective and functional outcomes such as disability, work functioning, social functioning, well-being, and health-related quality of life (HRQoL) in depressed patients. However, a recent large retrospective cohort study found that depressed subjects who received vs did not receive antidepressants did not differ in improvement in HRQoL, as measured using the 12-item Short Form (SF-12) Health Survey at the start and at the end of a 2-year period. The authors of the study therefore questioned the benefits of continuation of antidepressant drugs, suggesting a role for nonpharmacological interventions, instead. The study "went viral"; its findings were widely disseminated in the mass media and at medical and health care websites for physicians and for the lay public. The study, however, suffered from serious methodological shortcomings. These shortcomings are systematically explained so that readers understand how to critically read a research paper. This is important because uncritical acceptance of the findings of the study can negatively impact attitudes toward antidepressant medication among patients and health care professionals and may even result in decreased medication adherence in patients receiving antidepressant maintenance therapy.

Cost-Utility Analysis of Discontinuing Antidepressants in England Primary Care Patients Compared with Long-Term Maintenance: The ANTLER Study.

BackgroundDepression is a common mental health condition with considerable negative impact on health and well-being. Although antidepressants are recommended as first-line treatment, there is limited evidence regarding the cost effectiveness of long-term maintenance antidepressants for preventing relapse.ObjectivesOur objective was to calculate the mean incremental costs and quality-adjusted life-years (QALYs) over 12 months of discontinuing long-term antidepressant medication in well patients compared with maintenance, using patient-level trial data.MethodsWe conducted a cost-utility analysis of 478 participants from 150 UK general practices recruited to a randomised, double-blind trial (ANTLER). QALYs were calculated from EQ-5D-5L and 12-Item Short Form survey (SF-12) results, with primary analysis using the EQ-5D-5L value set for England. Resource use was collected from primary care patient electronic medical records and self-completed questionnaires capturing mental-health-related resource use. Costs were calculated by applying standard UK unit costs to resource use. Adjustments were made for baseline variables.ResultsParticipants randomised to discontinuation had significantly worse utility scores at 3 months (− 0.032; 95% confidence interval [CI] − 0.053 to − 0.011) but no significant difference in QALYs (− 0.011; 95% CI − 0.026 to 0.003) or costs (£3.11; 95% CI − 41.28 to 47.50) at 12 months. The probability that discontinuation was cost effective compared with maintenance was 12.9% at a threshold of £20,000 per QALY gained.ConclusionsDiscontinuation of antidepressants was unlikely to be cost effective compared with maintenance for currently well patients on long-term antidepressants. However, this analysis provides no information on the wider impact of antidepressants. Our findings provide information on the potential impact of discontinuing long-term maintenance antidepressants and facilitate improving guidance for shared patient–clinician decision making.Trial RegistrationEudraCT number 2015-004210-26; ISRCTN number ISRCTN15969819.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40258-021-00693-x.

Antidepressant medication to prevent depression relapse in primary care: the ANTLER RCT.

There has been a steady increase in the number of primary care patients receiving long-term maintenance antidepressant treatment, despite limited evidence of a benefit of this treatment beyond 8 months. The ANTidepressants to prevent reLapse in dEpRession (ANTLER) trial investigated the clinical effectiveness and cost-effectiveness of antidepressant medication in preventing relapse in UK primary care. This was a Phase IV, double-blind, pragmatic, multisite, individually randomised parallel-group controlled trial, with follow-up at 6, 12, 26, 39 and 52 weeks. Participants were randomised using minimisation on centre, type of antidepressant and baseline depressive symptom score above or below the median using Clinical Interview Schedule - Revised (two categories). Statisticians were blind to allocation for the outcome analyses. General practices in London, Bristol, Southampton and York. Individuals aged 18-74 years who had experienced at least two episodes of depression and had been taking antidepressants for ≥ 9 months but felt well enough to consider stopping their medication. Those who met an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of depression or with other psychiatric conditions were excluded. At baseline, participants were taking citalopram 20 mg, sertraline 100 mg, fluoxetine 20 mg or mirtazapine 30 mg. They were randomised to either remain on their current medication or discontinue medication after a tapering period. The primary outcome was the time, in weeks, to the beginning of the first depressive episode after randomisation. This was measured by a retrospective Clinical Interview Schedule - Revised that assessed the onset of a depressive episode in the previous 12 weeks, and was conducted at 12, 26, 39 and 52 weeks. The depression-related resource use was collected over 12 months from medical records and patient-completed questionnaires. Quality-adjusted life-years were calculated using the EuroQol-5 Dimensions, five-level version. Between 9 March 2017 and 1 March 2019, we randomised 238 participants to antidepressant continuation (the maintenance group) and 240 participants to antidepressant discontinuation (the discontinuation group). The time to relapse of depression was shorter in the discontinuation group, with a hazard ratio of 2.06 (95% confidence interval 1.56 to 2.70; p < 0.0001). By 52 weeks, relapse was experienced by 39% of those who continued antidepressants and 56% of those who discontinued antidepressants. The secondary analysis revealed that people who discontinued experienced more withdrawal symptoms than those who remained on medication, with the largest difference at 12 weeks. In the discontinuation group, 37% (95% confidence interval 28% to 45%) of participants remained on their randomised medication until the end of the trial. In total, 39% (95% confidence interval 32% to 45%) of participants in the discontinuation group returned to their original antidepressant compared with 20% (95% confidence interval 15% to 25%) of participants in maintenance group. The health economic evaluation demonstrated that participants randomised to discontinuation had worse utility scores at 3 months (-0.037, 95% confidence interval -0.059 to -0.015) and fewer quality-adjusted life-years over 12 months (-0.019, 95% confidence interval -0.035 to -0.003) than those randomised to continuation. The discontinuation pathway, besides giving worse outcomes, also cost more [extra £2.71 per patient over 12 months (95% confidence interval -£36.10 to £37.07)] than the continuation pathway, although the cost difference was not significant. Patients who discontinue long-term maintenance antidepressants in primary care are at increased risk of relapse and withdrawal symptoms. However, a substantial proportion of patients can discontinue antidepressants without relapse. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants and improve shared decision-making. The participants may not have been representative of all people on long-term maintenance treatment and we could study only a restricted range of antidepressants and doses. Identifying patients who will not relapse if they discontinued antidepressants would be clinically important. Current Controlled Trials ISRCTN15969819 and EudraCT 2015-004210-26. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 69. See the NIHR Journals Library website for further project information.

Practical aspects of palliative care & palliative radiotherapy in incurable cervical cancer.

Cervical cancer is the most common cause of cancer-related deaths among economically disadvantaged women. The symptoms of pain, discharge, constipation, foul smell, insomnia and depression can be controlled with inexpensive medicines such as oral morphine, maintenance oral metronidazole, antidepressants and laxatives. These medications should be prescribed according to the palliative care guidelines and titrated to the individual patient’s clinical response, pathophysiology, and metabolic parameters. A hypothetical clinical scenario illustrates some aspects of pain and symptom management, inter-disciplinary palliative care, medical ethics and communication needs in low-resource settings. Palliative radiotherapy is a cost-effective intervention to reduce vaginal discharge, bleeding, pressure effects and nociceptive or neuropathic pain caused by pelvic and para-aortic disease. The role of palliative radiotherapy in patients with malignant fistulae is discussed and the literature on hypo-fractionated pelvic radiotherapy is briefly reviewed.

Choline elevation in amygdala region at recovery indicates longer survival without depressive episode: a magnetic resonance spectroscopy study

RationaleDepression, with variable longitudinal patterns, recurs in one third of patients. We lack useful predictors of its course/outcome, and proton magnetic resonance spectroscopy (1H-MRS) of brain metabolites is an underused research modality in finding outcome correlates.ObjectivesTo determine if brain metabolite levels/changes in the amygdala region observed early in the recovery phase indicate depression recurrence risk in patients receiving maintenance therapy.MethodsForty-eight patients on stable-dose antidepressant (AD) maintenance therapy were analyzed from recovery onset until (i) recurrence of depression or (ii) start of AD discontinuation. Two 1H-MRS scans (6 months apart) were performed with a focus on amygdala at the beginning of recovery. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and Glx (glutamine/glutamate and GABA) were evaluated with regard to time without recurrence, and risks were assessed by Cox proportional hazard modeling.ResultsTwenty patients had depression recurrence, and 23 patients reached AD discontinuation. General linear model repeated measures analysis displayed three-way interaction of measurement time, metabolite level, and recurrence on maintenance therapy, in a multivariate test, Wilks’ lambda = 0.857, F(2,40) = 3.348, p = 0.045. Cho levels at the beginning of recovery and subsequent changes convey the highest risk for earlier recurrence. Patients experiencing higher amygdala Cho after recovery are at a significantly lower risk for depression recurrence (hazard ratio = 0.32; 95% confidence interval 0.13–0.77).ConclusionCho levels/changes in the amygdala early in the recovery phase correlate with clinical outcome. In the absence of major NAA fluctuations, changes in Cho and Glx may suggest a shift towards reduction in (previously increased) glutamatergic neurotransmission. Investigation of a larger sample with greater sampling frequency is needed to confirm the possible predictive role of metabolite changes in the amygdala region early in the recovery phase.

A randomised controlled trial assessing the use of citalopram, sertraline, fluoxetine and mirtazapine in preventing relapse in primary care patients who are taking long-term maintenance antidepressants (ANTLER: ANTidepressants to prevent reLapse in dEpRession): study protocol for a randomised controlled trial

BackgroundAntidepressants are used both for treating acute episodes and for prophylaxis to prevent future episodes of depression, also called maintenance treatment. This article describes the protocol for a randomised controlled trial (ANTLER: ANTidepressants to prevent reLapse in dEpRession) to investigate the clinical effectiveness and cost-effectiveness in UK primary care of continuing on long-term maintenance antidepressants compared with a placebo in preventing relapse of depression in those who have taken antidepressants for more than 9 months and who are currently well enough to consider stopping maintenance treatment.Methods/designThe ANTLER trial is an individually randomised, double-blind, placebo-controlled trial in which participants are randomised to remain on active medication or to take an identical placebo after a tapering period of 2 months. Eligible participants are those who: are between the ages of 18 and 74 years; have had at least two episodes of depression; and have been taking antidepressants for 9 months or more and are currently taking citalopram 20 mg, sertraline 100 mg, fluoxetine 20 mg or mirtazapine 30 mg but are well enough to consider stopping their medication. The participants will be followed up at 6, 12, 26, 39 and 52 weeks.The primary outcome will be the time in weeks to the beginning of the first episode of depression after randomisation. This will be measured using a retrospective version of the Clinical Interview Schedule—Revised administered at 12, 26, 39 and 52 weeks.Secondary outcomes will include depressive and anxiety symptoms, adverse effects, withdrawal symptoms, emotional processing tasks, quality of life and the resources and costs used. We will also perform a cost-effectiveness analysis based on results of the trial.DiscussionThe ANTLER trial findings will inform primary care prescribing practice by providing a valid and generalisable estimate of the clinical effectiveness and cost-effectiveness of long-term maintenance treatment with antidepressants in UK primary care.Trial registrationControlled Trials ISRCTN Registry, ISRCTN15969819. Registered on 21 September 2015.

Emotional Biases and Recurrence in Major Depressive Disorder. Results of 2.5 Years Follow-Up of Drug-Free Cohort Vulnerable for Recurrence.

An interesting factor explaining recurrence risk in Major Depressive Disorder (MDD) may be neuropsychological functioning, i.e., processing of emotional stimuli/information. Negatively biased processing of emotional stimuli/information has been found in both acute and (inconclusively) remitted states of MDD, and may be causally related to recurrence of depression. We aimed to investigate self-referent, memory and interpretation biases in recurrently depressed patients in remission and relate these biases to recurrence. We included 69 remitted recurrent MDD-patients (rrMDD-patients), 35–65 years, with ≥2 episodes, voluntarily free of antidepressant maintenance therapy for at least 4 weeks. We tested self-referent biases with an emotional categorization task, bias in emotional memory by free recall of the emotion categorization task 15 min after completing it, and interpretation bias with a facial expression recognition task. We compared these participants with 43 never-depressed controls matched for age, sex and intelligence. We followed the rrMDD-patients for 2.5 years and assessed recurrent depressive episodes by structured interview. The rrMDD-patients showed biases toward emotionally negative stimuli, faster responses to negative self-relevant characteristics in the emotional categorization, better recognition of sad faces, worse recognition of neutral faces with more misclassifications as angry or disgusting faces and less misclassifications as neutral faces (0.001 < p < 0.05). Of these, the number of misclassifications as angry and the overall performance in the emotional memory task were significantly associated with the time to recurrence (p ≤ 0.04), independent of residual symptoms and number of previous episodes. In a support vector machine data-driven model, prediction of recurrence-status could best be achieved (relative to observed recurrence-rate) with demographic and childhood adversity parameters (accuracy 78.1%; 1-sided p = 0.002); neuropsychological tests could not improve this prediction. Our data suggests a persisting (mood-incongruent) emotional bias when patients with recurrent depression are in remission. Moreover, these persisting biases might be mechanistically important for recurrence and prevention thereof.

Managing Antidepressant Discontinuation: A Systematic Review.

We aimed to determine the effectiveness of interventions to manage antidepressant discontinuation, and the outcomes for patients. We conducted a systematic review with narrative synthesis and meta-analysis of studies published to March 2017. Studies were eligible for inclusion if they were randomized controlled trials, quasi-experimental studies, or observational studies assessing interventions to facilitate discontinuation of antidepressants for depression in adults. Our primary outcomes were antidepressant discontinuation and discontinuation symptoms. Secondary outcomes were relapse/recurrence; quality of life; antidepressant reduction; and sexual, social, and occupational function. Of 15 included studies, 12 studies (8 randomized controlled trials, 2 single-arm trials, 2 retrospective cohort studies) were included in the synthesis. None were rated as having high risk for selection or detection bias. Two studies prompting primary care clinician discontinuation with antidepressant tapering guidance found 6% and 7% of patients discontinued, vs 8% for usual care. Six studies of psychological or psychiatric treatment plus tapering reported cessation rates of 40% to 95%. Two studies reported a higher risk of discontinuation symptoms with abrupt termination. At 2 years, risk of relapse/recurrence was lower with cognitive behavioral therapy plus taper vs clinical management plus taper (15% to 25% vs 35% to 80%: risk ratio = 0.34; 95% CI, 0.18-0.67; 2 studies). Relapse/recurrence rates were similar for mindfulness-based cognitive therapy with tapering and maintenance antidepressants (44% to 48% vs 47% to 60%; 2 studies). Cognitive behavioral therapy or mindfulness-based cognitive therapy can help patients discontinue antidepressants without increasing the risk of relapse/recurrence, but are resource intensive. More scalable interventions incorporating psychological support are needed.

Cost-effectiveness, cost-utility and the budget impact of antidepressants versus preventive cognitive therapy with or without tapering of antidepressants.

As depression has a recurrent course, relapse and recurrence prevention is essential.AimsIn our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/-AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact. Data were analysed (n=289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model. Mean total costs over 24 months were €6814, €10264 and €13282 for AD+PCT, antidepressants only and PCT/-AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/-AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/-AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/-AD. Adding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/-AD will become cost-effective.Declaration of interestC.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.

Development and validation of a clinical prediction tool to estimate the individual risk of depressive relapse or recurrence in individuals with recurrent depression

ObjectivesMany studies examined predictors of depressive relapse/recurrence but no simple tool based on well-established risk factors is available that estimates the risk within an individual. We developed and validated such a prediction tool in remitted recurrently depressed individuals. MethodsThe tool was developed using data (n = 235) from a pragmatic randomised controlled trial in remitted recurrently depressed participants and externally validated using data (n = 209) from a similar randomised controlled trial of remitted recurrently depressed participants using maintenance antidepressants. Cox regression was used with time to relapse/recurrence within 2 years as outcome and well-established risk factors as predictors. Performance measures and absolute risk scores were calculated, a practically applicable risk score was created, and the tool was externally validated. ResultsThe 2-year cumulative proportion relapse/recurrence was 46.2% in the validation dataset. The tool included number of previous depressive episodes, residual depressive symptoms, severity of the last depressive episode, and treatment. The C-statistic and calibration slope were 0.56 and 0.81 respectively. The tool stratified participants into relapse/recurrence risk classes of 37%, 55%, and 72%. The C-statistic and calibration slope in the external validation were 0.59 and 0.56 respectively, and Kaplan Meier curves showed that the tool could differentiate between risk classes. ConclusionsThis is the first study that developed a simple prediction tool based on well-established risk factors of depressive relapse/recurrence, estimating the individual risk. Since the overall performance of the model was poor, more studies are needed to enhance the performance before recommending implementation into clinical practice.

Adherence and healthcare utilization among older adults with COPD and depression

Background and objectiveAdherence to chronic obstructive pulmonary disease (COPD) maintenance medications and antidepressants may reduce healthcare utilization among multimorbid individuals with COPD and depression. We quantified the independent effects of adherence to antidepressants and COPD maintenance medications on healthcare utilization among individuals co-diagnosed with COPD and depression. ProceduresWe conducted a retrospective cohort study using a 2006–2012 5% random sample of Medicare beneficiaries co-diagnosed with COPD and depression who had two or more prescription fills of both COPD maintenance medications and antidepressants. We measured adherence to medications using the proportion of days covered per 30-day period. The primary outcomes were all-cause emergency department (ED) visits and hospitalizations. Beneficiaries were followed over a minimum 12-month follow-up period. ResultsOf the 16,075 beneficiaries meeting inclusion criteria, 21% achieved adherence ≥80% to COPD maintenance medications and 55% achieved adherence ≥80% to antidepressants. Compared to no use and controlling for antidepressant adherence and potential confounders, higher (≥80%) levels of adherence to COPD maintenance medications were associated with decreased risk of ED visits (hazard ratio (HR) 0.79; 95% CI 0.74, 0.83) and hospitalizations (HR 0.82; 95% CI 0.78, 0.87). Similarly, higher levels (≥80%) of adherence to antidepressants resulted in decreased risk of ED visits (HR 0.74; 95% CI 0.70, 0.78) and hospitalizations (HR 0.77; 95% CI 0.73, 0.81) compared to no use. ConclusionsClinicians can assist in the improved management of their multimorbid patients' health by treating depression among patients with COPD and monitoring and encouraging adherence to the regimens they prescribe.

Maintenance pharmacotherapy for recurrent major depressive disorder in primary care: A 5-year follow-up study

BackgroundMost practice guidelines recommend maintenance antidepressant treatment for recurrent major depressive disorder. However, the degree to which such guidance is actually followed in primary health care has remained obscure. We investigated the provision of maintenance antidepressant treatment within a representative primary care five-year cohort study. MethodsIn the Vantaa Primary Care Depression Study, a stratified random sample of 1119 adult patients was screened for depression using the Prime-MD. Depressive and comorbid psychiatric disorders were diagnosed using SCID-I/P and SCID-II interviews. Of the 137 patients with depressive disorders, 82% completed the prospective five-year follow-up. A graphic life chart enabling evaluation of the longitudinal course of episodes plus duration of pharmacotherapies was used. In accordance with national guidelines, an indication for maintenance treatment was defined to exist after three or more lifetime major depressive episodes (MDEs); maintenance treatment was to commence four months after onset of full remission. ResultsOf the cohort patients, 34% (46/137) had three or more lifetime MDEs, thus indicating the requirement for maintenance pharmacotherapy. Of these, half (54%, 25/46) received maintenance treatment, for only 29% (489/1670) of the months indicated. ConclusionsIn this cohort of depressed primary care patients, half of patients with indications for maintenance treatment actually received it, and only for a fraction of the time indicated. Antidepressant maintenance treatment for the prevention of recurrences is unlikely to be subject to large-scale actualization as recommended, which may significantly undermine the potential public health benefits of treatment.

Times to Discontinue Antidepressants Over 6 Months in Patients with Major Depressive Disorder.

ObjectiveThe aim of the present study was to investigate differences in discontinuation time among antidepressants and total antidepressant discontinuation rate of patients with depression over a 6 month period in a naturalistic treatment setting.MethodsWe reviewed the medical records of 900 patients with major depressive disorder who were initially prescribed only one kind of antidepressant. The prescribed antidepressants and the reasons for discontinuation were surveyed at baseline and every 4 weeks during the 24 week study. We investigated the discontinuation rate and the mean time to discontinuation among six antidepressants groups.ResultsMean and median overall discontinuation times were 13.8 and 12 weeks, respectively. Sertraline and escitalopram had longer discontinuation times than that of fluoxetine, and patients who used sertraline discontinued use significantly later than those taking mirtazapine. No differences in discontinuation rate were observed after 24 weeks among these antidepressants. About 73% of patients discontinued antidepressant treatment after 24 weeks.ConclusionSertraline and escitalopram tended to have longer mean times to discontinuation, although no difference in discontinuation rate was detected between antidepressants after 24 weeks. About three-quarters of patients discontinued antidepressant maintenance therapy after 24 weeks.

Influence of Genetic Polymorphisms and Concomitant Anxiolytic Doses on Antidepressant Maintenance Doses in Japanese Patients with Depression.

To prevent recurrent depression, patients should ideally continue treatment for >6 months with the antidepressant dose that effectively suppressed acute depressive symptoms. However, there are inter-individual differences in the antidepressant doses required to achieve response and maintenance. Therefore, this study was conducted to examine the role of clinical features, including genetic polymorphisms, on the antidepressant dose required for maintenance therapy in 82 Japanese patients with depression. We calculated the antidepressant dose using the imipramine equivalent scale and the dose of concomitant anxiolytics and hypnotics using the diazepam equivalent scale. The 82 participants were classified into two groups based on the median imipramine equivalent dose, and we examined the influence of patient characteristics and the presence of genetic polymorphisms of brain-derived neurotropic factor (BDNF; rs6265) and cyclic adenosine monophosphate responsive element-binding protein 1 (CREB1; rs2253306, rs4675690, rs769963) on the antidepressant maintenance dose. Using a multivariate logistic regression analysis, we found that the concomitant diazepam equivalent dose and presence of the CREB1 rs4675690 polymorphism were significantly associated with the antidepressant maintenance dose. We concluded that these factors influenced the antidepressant dose in maintenance therapy among Japanese patients with depression. However, further research is required in large cohorts.

Prescriptions séquentielles : arguments en faveur d’une modification des schémas thérapeutiques dans les dépressions résistantes

Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses and recurrences, in antidepressant maintenance. These data support the interest of therapeutic strategies based on evolutionary criteria. Sequential models inspired by statistical methods may incorporate the effects of a future treatment by measuring the current one.

Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial

Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months. In this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654. Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance antidepressants. The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67-1·18; p=0·43), nor did the number of serious adverse events. Five adverse events were reported, including two deaths, in each of the MBCT-TS and maintenance antidepressants groups. No adverse events were attributable to the interventions or the trial. We found no evidence that MBCT-TS is superior to maintenance antidepressant treatment for the prevention of depressive relapse in individuals at risk for depressive relapse or recurrence. Both treatments were associated with enduring positive outcomes in terms of relapse or recurrence, residual depressive symptoms, and quality of life. National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.