Worse off by waiting for treatment? The impact of waiting time on clinical course and treatment outcome for depression in routine care.

BACKGROUND: Long-term untreated major depressive disorder (MDD) is associated with a less favorable clinical course. Waiting time, defined as the interval between diagnostic workup and treatment initiation, may be clinically relevant given the prolongation of the pre-existing duration of untreated MDD. However, it is currently unknown whether and to what extent waiting time affects treatment course in routine outpatient care. METHODS: Retrospectively extracted data from 715 outpatients with MDD who received naturalistic outpatient MDD treatment were examined. Treatment outcome was defined as the difference in depression severity at the start of treatment and six months thereafter. Clinical course during waiting time was defined by the difference in severity at diagnostic workup and at treatment initiation. We analyzed the association between waiting time and treatment outcome and between waiting time and clinical course during this waiting time using multivariable regression analyses. We adjusted for severity and suicidality as potential confounders. RESULTS: An increased duration of the waiting time was associated with a less favorable treatment outcome (B = 0.049, SE = 0.019, p = 0.01). This association persisted after adjustment for potential confounders (B = 0.053, SE = 0.02, p = 0.01). No association was found between length of waiting time and clinical course during waiting time. LIMITATIONS: Strict definitions resulted in smaller sample sizes for the final analyses. The uncontrolled design may be questionable to definitively establish the impact of waiting time on treatment outcome. CONCLUSIONS: A prolonged waiting time is significantly associated with less favorable treatment outcome. Reduction of waiting time deserves priority in depression treatment planning to improve clinical outcomes.

Prevalence and prediction of dropout during depression treatment in routine outpatient care: an observational study.

Efficacious treatments are available for major depressive disorder (MDD), but treatment dropout is common and decreases their effectiveness. However, knowledge about prevalence of treatment dropout and its risk factors in routine care is limited. The objective of this study was to determine the prevalence of and risk factors for dropout in a large outpatient sample. In this retrospective cohort analysis, routinely collected data from 2235 outpatients with MDD who had a diagnostic work-up between 2014 and 2016 were examined. Dropout was defined as treatment termination without achieving remission before the fourth session within six months after its start. Total and item scores on the Dutch Measure for Quantification of Treatment Resistance in Depression (DM-TRD) at baseline, and demographic variables were analyzed for their association with dropout using logistic regression and elastic net analyses. Data of 987 subjects who started routine outpatient depression treatment were included in the analyses of which 143 (14.5%) dropped out. Higher DM-TRD-scores were predictive for lower dropout odds [OR = 0.78, 95% CI = (0.70-0.86), p < 0.001]. The elastic net analysis revealed several clinical variables predictive for dropout. Higher SES, higher depression severity, comorbid personality pathology and a comorbid anxiety disorder were significantly associated with less dropout in the sample. In this observational study, treatment dropout was relatively low. The DM-TRD, an easy-to-use clinical instrument, revealed several variables associated with less dropout. When applied in daily practice and combined with demographical information, this instrument may help to reduce dropout and increase treatment effectiveness.

Functional Limitations among European Older Adults: Cross-Country Differences in Health Improvements and Social Environment Influence.

This study explores differences on health status transitions based on functional health and dead records among older population in Europe. We also study the influence of residence pattern on health changes over time. METHOD: Data used came from EU-SILC registers on individuals aged 50 + from 19 countries. Fixed and Mixed effect Cox Proportional Hazards Models are used to ascertain any country differences on health outcomes and then by co-residence pattern. RESULTS: There are remarkable country heterogeneity among older people to experience changes on their health status, specially, for health improvements and mortality risk. As expected, Baltic and Eastern European countries have a higher propensity for health deterioration and Southern European countries for health improvements on their functional capacities. However, there are exceptions as Bulgaria and Romania, which have a lower risk of deterioration and death transition than average. Overall, living with partner and adult children-rather than living only with a couple shown positive effects for older European to experience health improvements with notably differences in Southern countries as in Italy and Spain. DISCUSSION: country framework differences play a fundamental role to understand changes on health status at older ages, in particular, how health care support toward older people is managed by health systems within European countries and the availability of close relatives among older adult population.

[Geriatric syndromes, multimorbidity and geriatric psychiatry; an integrated perspective]. / Geriatrische syndromen, multimorbiditeit en ouderenpsychiatrie; een geïntegreerd perspectief.

BACKGROUND: The prevalence of geriatric syndromes, frailty and multimorbidity increases in older age, with a negative impact on health outcomes. Little is known on these problems in older adults with psychiatric disorders. AIM: To evaluate the prevalence of geriatric syndromes and multimorbidity in older adults with psychiatric disorders and their impact on treatment outcomes. METHOD: We conducted a pilot study and a case-control study on older adults with medically insufficiently explained symptoms, a prospective cohort study in older adults, acutely admitted to psychiatric wards and a systematic review to evaluate whether geriatric syndromes were considered in RCTs on depression treatment. RESULTS: Unexplained symptoms were often accompanied by frailty, multimorbidity and psychiatric disorders. Older adults who were acutely admitted to psychiatric wards had a high level of multimorbidity, about half of them were frail, and a third undernourished. Frailty and multimorbidity were independent predictors for not being discharged to their own home. Frailty also strongly predicted the 5-year mortality rate. Geriatric syndromes were hardly considered in study design or as secondary outcome in treatment studies on depression in older adults. CONCLUSION: Overall, geriatric problems are highly prevalent among older adults with psychiatric disorders and have a relevant prognostic impact. The complexity of older psychiatric patients is probably best addressed by interdisciplinary, integrated diagnostic and treatment trajectories.

[Treatment plan for female adolescents in the grip of chronic suicidality]. / Behandelbeleid bij vrouwelijke adolescenten gegijzeld door chronische suïcidaliteit.

BACKGROUND: A psychological autopsy study (Mérelle e.a. 2020) demonstrates a subgroup of female adolescents with chronic suicidal behavior and severe internalizing problems. AIM: To describe characteristics of the suicidal process and the challenges experienced in providing mental health care for this subgroup. METHOD: A case description and review of literature. RESULTS: The persistent suicidal threat and the following despair of the patient and its parents are forcing care providers into an impasse: the primary focus of treatment is to guarantee the patient's safety, whereby the treatment of underlying problems is underexposed. Based on expert knowledge we make recommendations including autonomy-promoting treatment policy, treating suicidality as a transdiagnostic phenomenon, creating a multidisciplinary network of care providers and making chronic suicidality tolerable for care providers. CONCLUSION: We propose preliminary practical recommendations in our quest for optimal mental health care for chronic suicidal adolescents.

Comorbid depression and treatment of anxiety disorders, OCD, and PTSD: Diagnosis versus severity.

BACKGROUND: Although anxiety and depression are highly comorbid disorders, it remains unclear whether and how a concurrent depression affects the outcome of anxiety treatment. METHOD: Using anonymized routine outcome monitoring (ROM) data of 740 patients having received specialized treatment for an anxiety disorder, OCD, or PTSD, this study investigates whether a comorbid diagnosis of depression and/or self-reported depression severity levels relate to the patients' improvement following anxiety treatment. RESULTS: The results show that both the patients with and those without comorbid depression had profited similarly from the anxiety, OCD, or PTSD treatment, regardless of whether depression was merely diagnosed prior to treatment or based on self-reported severity (and assuming a smallest effect size of interest of d = 0.35/r = .2). Importantly, the post-treatment reductions in self-reported depressive symptoms were strongly and positively related to the reductions in self-reported anxiety symptoms and disorder-related disability. LIMITATIONS: Causal inferences cannot be made due to the retrospective cross-sectional design. CONCLUSIONS: The outcomes obtained in a naturalistic patient sample support current treatment guidelines recommending evidence-based treatment for anxiety disorders, OCD, and PTSD in patients with and without a comorbid depression. Future treatment studies are recommended for investigate the (bi)directionality of anxiety and depressive symptoms throughout treatment.

[The best intervention for depression is early detection and prevention in youth]. / De beste behandeling voor depressie is vroegsignalering en preventie bij jeugdigen.

Background A more preventive and proactive approach in youth mental health care can contribute to reduce the severity of psychological problems in young people and help to reduce the risk on treatment resistance. Aim To show opportunities to organize youth mental health care more proactively. Method Discuss new approaches based on existing literature and examples from clinical practice. Results It is essential that young people receive treatment that is appropriate for the severity of their problems. Early detection and prevention can be systematically carried out in collaboration with public health service and schools. In addition, it is imperative that young people receive appropriate (specialized) mental health care based on their prognosis. Conclusion Committing to the right care at the right time is essential to prevent the development of co-morbidities, stagnation in development tasks and therapy resistance. Tijdschrift voor psychiatrie 63(2021)2, 111-114.

[Consultation from centers of excellence in Dutch mental healthcare; the value for patient and specialist]. / Hoogspecialistische consultatie in de sggz; de waarde voor patiënt en specialist.

The consultation function of centers of excellence is still used to a limited extent. In this article we explain possibilities and contributions of highly specialized consultation to support standard mental healthcare by means of vignettes. Case descriptions from the consultation practice of four centers of excellence are presented. More intensive use of consultation options by mental health care providers can help improve the quality, efficiency and effectiveness of care.

A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression.

BACKGROUND: Treatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. RESEARCH QUESTION: Does high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? METHOD: We performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. RESULTS: An interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p < 0.01). There were no differences however between the treatment arms (F(1.30) = 1.5;p = 0.23). We did find a negative correlation between the change in HDRS score and DM-TRD in the active rTMS group, but this correlation was not significantly different from the sham group. CONCLUSION: "Standard" 4-week rTMS treatment is not effective in chronic, severe treatment-resistant depressed patients. While a replication of our data in this patient group may be ethically difficult, further research with less treatment resistant patients might help in positioning rTMS within the current stepped care approach to depression.

[The effectiveness of monoamine oxidase inhibitors in treatment-resistant depressive disorders in clinical practice; a retrospective open-label study]. / De effectiviteit van monoamineoxidase-remmers bij therapieresistente depressie in de klinische praktijk; een retrospectieve openlabelstudie.

BACKGROUND: Monoamine oxidase (mao)-inhibitors are often prescribed in patients suffering from treatment-resistant depression, but the evidence of its effectiveness in this type of depression is limited: a restricted amount of similar studies describes response-rates of 12-75%.
AIM: To get more insight in the effectiveness of mao-inhibitors in treatment-resistant depression in clinical practice.
METHOD: We investigated medical files of patients with a uni- or bipolar, treatment-resistant depression and looked at the difference in score on the Inventory of Depressive Symptomatology - Self Report (ids-sr) before and after 3 months of treatment with a mao-inhibitor. After that, we investigated how often patients achieved remission, response, partial response, no response or drop-out due to of side-effects.
RESULTS: The included 17 patients achieved a mean decrease of 8.6 (sd:15.1) points, which corresponded with a decrease of 16.8% (p = 0.032). One patient (6%) achieved remission, 2 patients (12%) achieved response, 5 patients (29%) had partial response and 7 patients (41%) did not respond at all. Three patients (18%) quitted because of side-effects.
CONCLUSION: The results of this and similar studies are modest and ask for critical thinking and critical prescribing of mao-inhibitors, because of the possibly limited effectiveness in treatment-resistant depressions.

[Decrease of depression and outcome in treatment of anxiety disorders - an observational study of ROM data]. / Afname van depressie en de uitkomst bij de behandeling van angststoornis ­ een observationele studie van ROM-data.

BACKGROUND: Most mental health hospitals in the Netherlands use disorder specific standards of care. In case of comorbidity, we lack evidence in choosing the treatment of preference when both depressive- and anxiety disorder(s) are present in the same patient.
AIM: To investigate the prevalence of depression and anxiety (including obsessive compulsive disorder and post-traumatic stress disorder) in an outpatient mental health hospital population treated for their anxiety disorder, and to investigate the difference in outcome of (anxiety) treatment between patients with and without a comorbid depressive disorder.
METHOD: A retrospective study using outcome data from 2012 to 2017. In this period, we identified 127 patients for whom outcome data and diagnostic criteria were available. Comorbidity in this group was determined by a clinical interview. During treatment symptoms were monitored using self-reporting scales, among others the Inventory of Depressive Symptomatology (IDS) and the Beck Anxiety Inventory (BAI).
RESULTS: In 46,5% of the patients a comorbid depressive disorder was diagnosed. No significant difference in treatment outcome was observed between the group of patients with and the group of patients without a comorbid depressive disorder. However, the amount of reduction of depressive symptoms measured by the ids was a good predictor of the reduction of anxiety: a faster reduction of depressive symptoms predicts a better outcome of the treatment of anxiety.
CONCLUSION: Comorbid depressive disorders were observed in almost half of the patients treated in specialized (outpatient) clinics for anxiety disorders. A slower reduction of depressive symptoms predicts worse outcome of the treatment of anxiety.

[Antidepressants are frequently prescribed but still critized; a perspective on causes and solutions]. / Antidepressiva: al decennia voor­geschreven én toch nog steeds bekritiseerd; een perspectief op oorzaken en oplossingen.

BACKGROUND: From around 1980, antidepressants (ad) have increasingly been prescribed, for longer periods of time, especially selective serotonin reuptake inhibitors (ssris). Paradoxically, their effectiveness is still doubted, especially outside the psychiatric profession.
AIM: To explain increase and offer a perspective on causes and solutions, and to indicate how to reach consensus.
METHOD: Position paper with critical analysis and synthesis of relevant literature.
RESULTS: The rise in AD prescriptions results from: 1. increased safety and ease of prescribing, 2. increased presentation and recognition of depression in primary care, 3. extension of indication criteria, 4. effective marketing strategies, and 5. effectiveness in acute phase (aad) and of relapse/recurrence prevention in continuation/maintenance phases (coad).Critics point to: 1. low added value of aad relative to placebo, 2. many drop-outs and non-responders, 3. relapse/recurrence prevention with coad works only for responders to aad, 4. relapse/recurrence after AD discontinuation often involves withdrawal symptoms, and 5. publication bias, selective reporting, selective patient selection, and suboptimal blinding, resulting in overestimated effectiveness and underestimated disadvantages.Factors that keep fueling the controversy are: 1. critics stress the net effectiveness of AD whereas proponents point at gross effectiveness which includes spontaneous recovery and placebo effect; 2. persistence of distrust in industry-funded rcts; 3. ideological positions, reinforced by conflicts of interest and selective citations; 4. lack of rcts with relevant long-term outcome measurements.
CONCLUSION: Although consensus is difficult to achieve given the ideological component, there are options. Three factors are critically important: confer to establish which data convince the opposition, response prediction (what works for whom), and rcts with long-term functional outcomes.

[Routine outcome monitoring (ROM) early in treatment and disorder specific. Observational study into generic and specific questionnaires to measure the early change in depression treatment]. / ROM vroeg in de behandeling en specifiek; observationeel onderzoek naar generieke en specifieke vragenlijsten bij meten van vroege verandering bij depressiebehandeling.

BACKGROUND: Mental health care institutions use routine outcome monitoring (ROM) to determine whether a patient responds well to treatment. However, it has been still unanswered whether disorder specific or generic measurement instruments can best be used for this purpose. In addition, little is known about when a first indication can be given for the outcome of the treatment.
AIM: To provide insight into the sensitivity to change of two questionnaires: a generic and a specific one, which were both used for clients with a depressive disorder. An additional objective is to provide insight into when a first indication can be given for the outcome of the treatment.
METHOD: An observational cohort study with data from 518 patients with a depressive disorder. The Outcome Questionnaire (OQ-45.2) and the Inventory of Depressive Symptomatology (IDS-SR) were used to measure the course of treatment.
RESULTS: The depression specific IDS-SR appeared to be more sensitive to change than the generic OQ-45.2, especially at the beginning of treatment. With a measurement frequency of once every four weeks, the best time to get a first indication on the outcome of the treatment was between week 4 and week 8.
CONCLUSION: For clients and practitioners whose treatment focus is reducing depressive symptoms, a disorder specific questionnaire is preferable to monitor this. The measurement between 4 and 8 weeks is important for, if necessary, adjusting the treatment, and to improve the treatment outcome.

[Lithium augmentation to monoamine oxidase-inhibitors in treatment-resistant depressive disorders: case report and overview of literature]. / Lithiumadditie bij monoamine-oxidaseremmers bij therapieresistente depressie: casusbeschrijvingen en literatuuroverzicht.

Three patients suffering from a treatment-resistant depression were being treated with a monoamine oxidase (mao-)inhibitor and received lithium augmentation to achieve better recovery. One patient showed significant improvement of depressive symptoms within 24 hours, one patient showed very little respons and one patient did not respond at all. Literature research led to other casereports, where adding lithium to mao-inhibitors had also been effective. The growing amount of arguments of a positive effect of lithium augmentation to mao-inhibitors asks for more research to collect more evidence and a better understanding of this new, potentially effective treatment.

[Consensus statement on the application of rTMS in depression in the Netherlands and Belgium]. / Consensusverklaring voor de toepassing van rTMS bij depressie in Nederland en België.

BACKGROUND: Since 2017, repetitive transcranial magnetic stimulation (rTMS) has become eligible for reimbursement for the treatment of therapy-resistant depression in the Dutch healthcare system.
AIM: To initiate a guideline in the Netherlands and Belgium for the safe and effective application of rTMS for the treatment of depression.
METHOD: Based on literature review, existing guidelines and consensus among Dutch rTMS experts, recommendations were developed regarding the implementation of rTMS as a treatment of depression. All available evidence was weighed and discussed among all co-authors and recommendations were reached by consensus among the group.
RESULTS: rTMS targeting the dorsolateral prefrontal cortex (DLPFC) should be seen as a first choice in the treatment of depression using high-frequency rTMS (left) or, as an alternative, low-frequency rTMS (right). Stimulation protocols should use more than 1000 pulses per session for an average of 20-30 sessions, offered in 2-5 sessions per week. Contraindications for rTMS include epilepsy, intracranial presence of (magnetisable) metals, pacemaker and cochlear implant.
CONCLUSION: rTMS, performed by competent professionals is an effective and safe treatment for depression.

[Prevalence and recognition of bipolarity in patients with a treatment-resistant depressive disorder: a systematic review]. / Prevalentie en herkenning van bipolariteit bij patiënten met een therapieresistente depressieve stoornis; een systematische review.

BACKGROUND: Studies have indicated an association between treatment refractoriness in unipolar depression and unrecognised bipolar spectrum disorder (bsd). If confirmed, this may have implications for diagnosis and treatment.
AIM: To provide an overview on the prevalence and recognition of bsd in treatment resistant depression (trd).
METHOD: A search was made in PubMed concerning the prevalence of bsd in trd and clinical features that may be suggestive of bipolar depression.
RESULTS: Three articles were found that examined the prevalence of bsd in trd; they reported that 26-47% of patients with trd had an underlying bsd. Five cross-sectional studies described the predictors of clinical features in patients with a major depression. The following features occurred significantly more often: positive family history of bsd, young age of onset, higher number of recurrences, and atypical features.
CONCLUSION: There seems to be an association between trd and having an underlying bsd. A few clinical features may help to detect bsd in trd.

[The care standard 'Depressive disorders']. / De zorgstandaard Depressieve stoornissen.

BACKGROUND: The care standard 'Depressive disorders' describes the complete patient journey for patients with depressive symptoms and disorders from the age of 8 years onwards.
AIM: To describe the most important recommendations in this care standard.
METHOD: The care standard is an adaptation of the existing guidelines for depression, supplemented with practical knowledge from professionals and patients' values and preferences.
RESULTS: Core elements in the care for depression are an appropriate use of care and a focus on relapse prevention. A combination of psychotherapy and medication is indicated for persistent depression and more sessions of psychotherapy might be required. There is some evidence for the use of repetitive transcranial magnetic stimulation in treatment-resistant depression.
CONCLUSION: The care standard is an important instrument to improve the quality of care for depression at both the organisational and the regional level.

Predicting clinical course in major depressive disorder: The association between DM-TRD score and symptom severity over time in 1115 outpatients.

BACKGROUND: The Dutch Measure for Quantification of Treatment Resistance in Depression (DM-TRD) is a promising prediction tool for major depressive disorder (MDD) based on variables associated with treatment outcome. The objective of our study was to examine the association between the DM-TRD and clinical course in a large cohort of MDD outpatients receiving treatment as usual. Furthermore, we examined whether the addition of an item measuring the presence of childhood adversity improved this association. METHODS: We included 1115 subjects with MDD (according to the DSM-IV) who were naturalistically treated at seven outpatient departments of a secondary mental healthcare center in the Netherlands. Data on subjects who had a diagnostic work-up between June 2014 and June 2016 were analyzed. Multilevel analyses were performed to examine the association between the DM-TRD score at baseline and clinical course, defined by symptom severity according to scores on the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) over time. We also investigated whether an extra item measuring childhood adversity improved the model. RESULTS: The model including the DM-TRD and its interaction with time was superior to previous models. The addition of childhood adversity and its interaction with time did not improve the model. CONCLUSIONS: In depressed outpatients receiving treatment as usual, the solid longer-term association between higher DM-TRD scores and worse clinical course supports its usefulness in clinical practice. Childhood adversity did not improve the model value indicating that-counterintuitively-this parameter offers no additional predictive power to the variables included.