The impact of treatment resistance on outcome and course of electroconvulsive therapy in major depressive disorder.

INTRODUCTION: Major depressive disorder (MDD) is a common psychiatric disorder. Despite several treatment options, a subgroup of patients will not respond to the commonly used antidepressant treatments and thus express treatment resistance (TRD). TRD can be quantified with the Dutch Measure for Treatment Resistance in Depression (DM-TRD). Electroconvulsive therapy (ECT) is an effective treatment for MDD, also in TRD. Yet, the position of ECT as "treatment-of-last-resort" may decrease the likelihood of beneficial outcome. Our aim was to investigate the association between treatment resistance and outcome and course of ECT. METHODS: We performed a retrospective, multicenter cohort study with 440 patients of which data was retrieved from patient records as collected in the Dutch ECT Cohort database. Linear and logistic regression models were used to explore the association between level of treatment resistance and outcome of ECT. Median split was used to explore the differences between high and low level of TRD and course of treatment. RESULTS: A higher DM-TRD score was associated with significantly smaller reduction of depression symptoms (R2 = 0.160; ß = -2.968; p < 0.001) and lower chance of response (OR = 0.821 [95 CI: 0.760-0.888]; ß = -0.197; p < 0.001). Low level TRD patients underwent fewer ECT sessions (mean 13 ± 6 SD vs. 16 ± 7 SD; p < 0.001) and fewer switches from right unilateral tot bifrontotemporal electrode placement (29% vs. 40%; p = 0.032). CONCLUSION: Reserving ECT as "treatment-of-last-resort" in the treatment algorithm for MDD seems questionable, because in our study lower level of treatment resistance predicted more beneficial ECT-outcome. Moreover, providing ECT in less treatment resistant patients showed fewer needed ECT-sessions and less switches to BL electrode placement, which may decrease the risk for cognitive side-effects.

Polyunsaturated fatty acids changes during electroconvulsive therapy in major depressive disorder.

Polyunsaturated fatty acids (PUFAs) have important electrochemical properties and have been implicated in the pathophysiology of major depressive disorder (MDD) and its treatment. However, the relation of PUFAs with electroconvulsive therapy (ECT) has never been investigated. Therefore, we aimed to explore the associations between PUFA concentrations and response to ECT in patients with MDD. We included 45 patients with unipolar MDD in a multicentre study. To determine PUFA concentrations, we collected blood samples at the first (T0) and twelfth (T12) ECT-session. We assessed depression severity using the Hamilton Rating Scale for Depression (HAM-D) at T0, T12 and at the end of the ECT-course. ECT-response was defined as 'early response' (at T12), 'late response' (after ECT-course) and 'no' response (after the ECT-course). The PUFA chain length index (CLI), unsaturation index (UI) and peroxidation index (PI) and three individual PUFAs (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA] and nervonic acid [NA]) were associated with response to ECT using linear mixed models. Results showed a significant higher CLI in 'late responders' compared to 'non responders'. For NA, 'late responders' showed significantly higher concentrations compared to 'early'- and 'non responders'. In conclusion, this study provides the first indication that PUFAs are associated with the efficacy of ECT. This indicates that PUFAs' influence on neuronal electrochemical properties and neurogenesis may affect ECT outcomes. Thereby, PUFAs form a potentially modifiable factor predicting ECT outcomes, that warrants further investigation in other ECT-cohorts.

Sex-specifics of ECT outcome.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. METHODS: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). RESULTS: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. CONCLUSION: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

Multimodal multi-center analysis of electroconvulsive therapy effects in depression: Brainwide gray matter increase without functional changes.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for severe depression and induces gray matter (GM) increases in the brain. Small-scale studies suggest that ECT also leads to changes in brain functioning, but findings are inconsistent. In this study, we investigated the influence of ECT on changes in both brain structure and function and their relation to clinical improvement using multicenter neuroimaging data from the Global ECT-MRI Research Collaboration (GEMRIC). METHODS: We analyzed T1-weighted structural magnetic resonance imaging (MRI) and functional resting-state MRI data of 88 individuals (49 male) with depressive episodes before and within one week after ECT. We performed voxel-based morphometry on the structural data and calculated fractional amplitudes of low-frequency fluctuations, regional homogeneity, degree centrality, functional connectomics, and hippocampus connectivity for the functional data in both unimodal and multimodal analyses. Longitudinal effects in the ECT group were compared to repeated measures of healthy controls (n = 27). RESULTS: Wide-spread increases in GM volume were found in patients following ECT. In contrast, no changes in any of the functional measures were observed, and there were no significant differences in structural or functional changes between ECT responders and non-responders. Multimodal analysis revealed that volume increases in the striatum, supplementary motor area and fusiform gyrus were associated with local changes in brain function. CONCLUSION: These results confirm wide-spread increases in GM volume, but suggest that this is not accompanied by functional changes or associated with clinical response. Instead, focal changes in brain function appear related to individual differences in brain volume increases.

Case Report: "Niemann-Pick Disease Type C in a Catatonic Patient Treated With Electroconvulsive Therapy".

We describe a case of an adolescent male with Niemann-Pick Type C (NP-C), a neurodegenerative lysosomal lipid storage disorder, who presented with recurrent catatonia which required repeated treatment with electroconvulsive therapy (ECT). During the ECT-course, seizure threshold increased substantially, leading to questions about the influence of NP-C on neuronal excitability. In this exemplary ECT-patient, NP-C was diagnosed not until after the first ECT-course when initial psychopharmacology for catatonia had failed and antipsychotics and benzodiazepines showed significant side-effects. Clinicians should be aware of NP-C in patients referred for ECT, especially in the case of treatment resistance, neurological symptoms and intolerance of psychopharmacological drugs. As was shown in our NP-C patient, ECT can be repeatedly effective for catatonic features. In the literature, effectiveness of ECT in patients with NP-C has sparsely been reported. This case demonstrates that detection of NP-C is beneficial for patients because more optimal treatment with ECT can be provided earlier without further exposure to side-effects.

[Reaction on 'Persistant underuse of ECT for persistant depressive disorder?'] / Reactie op 'Persisterend ondergebruik van ECT bij persisterende depressieve stoornis?'.

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[Integral care necessary for patients with complex somatic, psychic and social problems]. / Integrale zorg vereist voor patiënten met complexe somatische, psychische en sociale problematiek.

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[Electroconvulsion therapy for persistent depression in the Netherlands; very low application rate]. / Elektroconvulsietherapie bij persisterende depressie in Nederland; zeer lage toepassingsgraad.

BACKGROUND: Of all depressive disorders, 20% has a persistent course. For persistent depressive patients, electroconvulsive therapy (ect) is recommended for this patient population, since it is the most potent treatment for depression. The Dutch depression guideline advises the use of ect for persistent depressive disorder at approximately 12 months after inadequate efficacy of psychotherapy and/or pharmacological treatment.
AIM: To quantify the use of electroconvulsive therapy in persistent depressive patients in the Netherlands.
METHOD: Quantitative research using the Dutch registration system (diagnosis-treatment-combination; dbc) information system (dis) of the Dutch Healthcare Authority (nza).
RESULTS: Of the patients within the dbc system (in 2014) with the main diagnosis of unipolar depression, 23,597 (26%) were registered for more than two years and could be classified as having a persistent depressive episode. Of these latter patients, only 278 (1.2%) received ect.
CONCLUSION: In the Netherlands, only 1.2% of patients with a persistent depression received ect, whereas this treatment could have been considered for 26% of this group. The low application rate might be caused by professionals' inadequate knowledge about ect and the premature use of the handicap model.

[Electroconvulsive therapy in the Netherlands: the practice in 2015 compared to that in 2008]. / Elektroconvulsietherapie in Nederland: de praktijk in 2015 vergeleken met die in 2008.

BACKGROUND: The most recent information about the use of ECT in the Netherlands dates from 2008. An update version of the guideline for the use of ECT in the Netherlands was issued in 2010. AIM: To obtain insight into the practice of ECT in the Netherlands five years after implementation of the guideline. METHOD: Our study is based on a questionnaire about the use of ECT by psychiatrists in all Dutch institutions (n=33). Questions concerned the use and availability of ECT as well as the implementation of the updated guideline; they also served as a check on the expertise and training of ECT-psychiatrists. RESULTS: All institutions responded. The total number of ECT-sessions performed in 2015 was 15,633, a 16% increase compared to 2008. In 2015 more institutions were using 7x24 ECT and more had an ECT-nurse available. Nearly all psychiatrists were acquainted at the time with the revised guideline of 2010 and nearly 50% of them had adjusted the way they practised ECT. However, just under 40% of psychiatrists did not have the correct knowledge about some technical details regarding ECT. CONCLUSION: The revised guideline on ECT and its implementation have most likely improved the practice of ECT in the Netherlands.

[Medical Psychiatric Units in the Netherlands: an investigation into distribution and quality]. / Medisch-psychiatrische units in Nederland.

OBJECTIVE: One of the spearheads of psychiatric healthcare in the Netherlands is hospital care for patients with a psychiatric comorbidity. In 2014, the Netherlands Psychiatric Association published ten field standards for Medical Psychiatric Units (MPUs). We catalogued healthcare in the Netherlands on the basis of these field standards. DESIGN: Telephone screening, followed by a questionnaire investigation. METHOD: In the period May-August 2015, psychiatrists in 90 hospitals in the Netherlands were approached by telephone with 4 screening questions. If the department complied with the screening criteria for an MPU, a structured interview comprising 51 questions followed. The interview script was tested against the field standards using the Delphi method. RESULTS: The screening identified 40 potential MPUs; 37 (92.5%) wards participated in the complete interview. CONCLUSION: MPUs are unevenly distributed across the country; care content is adequate, but education, tighter multidisciplinary cooperation and availability of somatic nursing expertise on every shift could improve care on MPUs. The departments should also pay more attention to care chain arrangements. The field standards are too stringent; these could be improved by defining 'essential care' and application of differentiated assessment of subcriteria.

[Hypernatremia caused by treatment with GHB obtained via a doctor's prescription]. / Hypernatriëmie door GHB op doktersrecept.

In the last few years, gamma hydroxybutyric acid (GHB) has been used increasingly as a party drug; this has led to a marked increase in the number of requests for professional help with the treatment of GHB addiction. Pharmaceutical GHB (sodium oxybate, the sodium-salt of GHB), registered for cataplexia in narcolepsy patients, is used off-label to treat the withdrawal symptoms associated with GHB addiction. Pharmaceutical GHB has a high sodium load. In this report we present the cases of two patients who developed symptomatic hypernatremia following treatment with pharmaceutical GHB and who thereafter needed intensive care for the severe withdrawal symptoms that they experienced.

A functional MRI marker may predict the outcome of electroconvulsive therapy in severe and treatment-resistant depression.

Electroconvulsive therapy (ECT) is effective even in treatment-resistant patients with major depression. Currently, there are no markers available that can assist in identifying those patients most likely to benefit from ECT. In the present study, we investigated whether resting-state network connectivity can predict treatment outcome for individual patients. We included forty-five patients with severe and treatment-resistant unipolar depression and collected functional magnetic resonance imaging scans before the course of ECT. We extracted resting-state networks and used multivariate pattern analysis to discover networks that predicted recovery from depression. Cross-validation revealed two resting-state networks with significant classification accuracy after correction for multiple comparisons. A network centered in the dorsomedial prefrontal cortex (including the dorsolateral prefrontal cortex, orbitofrontal cortex and posterior cingulate cortex) showed a sensitivity of 84% and specificity of 85%. Another network centered in the anterior cingulate cortex (including the dorsolateral prefrontal cortex, sensorimotor cortex, parahippocampal gyrus and midbrain) showed a sensitivity of 80% and a specificity of 75%. These preliminary results demonstrate that resting-state networks may predict treatment outcome for individual patients and suggest that resting-state networks have the potential to serve as prognostic neuroimaging biomarkers to guide personalized treatment decisions.

[Hallucinations and vivid dreams by use of metoprolol]. / Hallucinaties en levendige dromen bij metoprololgebruik.

A 71-year-old man had had visual hallucinations and vivid dreams for two years after starting to take metoprolol. When metoprolol was replaced by atenolol the patient's symptoms disappeared within five days. Side-effects of beta-blockers on the central nervous system are relatively uncommon. The mechanisms underlying these side-effects are not fully understood. Lipophilic beta-blockers can cross the blood-brain barrier, whereas hydrophilic beta-blockers cannot. Doctors need to be alerted to the varying side-effects of specific beta-blockers.

[Consultation-liaison psychiatry and general hospital psychiatry in the Netherlands: on the way to psychosomatic medicine]. / Consultatieve en ziekenhuispsychiatrie in Nederland: op weg naar psychosomatische geneeskunde.

Consultation-liaison psychiatry and general hospital psychiatry have played a major role in promoting the concept of integrated care. New models for care have been developed and policy assurances about the quality of care have been expressed in the form of guidelines and indicators relating to procedure and performance. General hospital psychiatry is playing an increasingly important role in the training of psychiatrists. Due to the ageing population there is greater awareness of the importance of comorbidity and more support for the concept of integrated care. These changes will promote the further development of general hospital psychiatry.

[Palliative care in a psychiatric-somatic care unit]. / Palliatieve zorg op een psychiatrisch-medische unit.

Patients with severe psychiatric and somatic disorders may require admission to a combined psychiatric-somatic care unit. These units provide specialised psychiatric and somatic care as well as palliative care. This is illustrated by two case reports. A 51-year-old man with a malignant brain tumour was admitted to our psychiatric-somatic care unit after threatening his wife and children. He was aggressive and confused. Seizures were suspected and palliative care was needed. Within a few weeks his condition deteriorated. He died 1 day after terminal sedation had been initiated. A 78-year-old woman was admitted to receive daily electroconvulsive treatment (ECT) for depression with catatonia. The ECT had to be interrupted repeatedly due to comorbid infections and complications. She died 3 days after palliative care was initiated.

[Guidelines in Dutch mental health institutions for dealing with persons attempting suicide]. / Richtlijnen voor de opvang van suïcidepogers in Nederlandse ggz-instellingen.

BACKGROUND: Attempted suicide is a frequent occurrence, even in mental health institutions (mhis). The World Health Organization strongly supports the development and implementation of guidelines for dealing with cases of attempted suicide in mhis. aim To check on the existence, content and quality of guidelines for dealing with persons attempting suicide within mhis in the Netherlands and to compare these guidelines with those available in university and general hospitals. METHOD: A questionnaire was sent to all mhis. Criteria for assessing the content of existing guidelines were derived from the literature. The quality of the guidelines was then assessed on the basis of the Appraisal of Guidelines for Research and Evaluation (agree), a tool developed to evaluate guideline quality. results Thirty-eight out of 48 (72.2%) psychiatric institutions responded, giving us access to 12 sets of guidelines. The content and quality of these guidelines were compared with the content and quality of the guidelines available in university and general hospitals; there were several differences, but on the whole the mhi-guidelines were better. CONCLUSION: Guidelines were only available in a limited number of mhis. Most of the guidelines were adequate with regard to content, but some of the mhi-guidelines lacked some important elements. The quality of the mhi-guidelines was rather low but nevertheless better that that of the hospital guidelines.

[Neuroleptic malignant syndrome: a life-threatening complication that can be treated effectively]. / Maligne neurolepticasyndroom: een levensbedreigende complicatie, die goed te behandelen is.

Two patients with the neuroleptic malignant syndrome (NMS), a man aged 31 years and a woman aged 83 years, were referred for electroconvulsive therapy after 70 and 7 days, respectively. Both patients benefited from the treatment, but the patient who had had the syndrome longer had persistent contractures. NMS is potentially lethal. Diagnosis and treatment should be done as soon as possible to prevent mortality and complications. Admission to a general hospital and early consultation of NMS-experienced colleagues is strongly advised. Electroconvulsive therapy is indicated ifa trial course of lorazepam yields insufficient improvement.