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Self-guided Internet-based cognitive behavior therapy (iCBT) for migraine interventions could improve access to care, but there is poor evidence of their efficacy.
Methods:
A three-arm randomized controlled trial compared: iCBT focused on psychoeducation, self-monitoring and skills training (SPHERE), iCBT focused on identifying and managing personal headache triggers (PRISM) and a waitlist control. The primary treatment outcome was a ≥ 50% reduction in monthly headache days at 4 months post-randomization.
Results:
428 participants were randomized (mean age = 30.1). 240 participants (56.2%) provided outcome data at 4 months. Intention-to-treat (ITT) analysis with missing data imputed demonstrated that the proportion of responders with a ≥ 50% reduction was similar between combined iCBTs and waitlist (48.5/285, 17% vs. 16.6/143, 11.6%, p = 0.20), but analysis of completers showed both iCBT programs to be superior to the waitlist (24/108, 22.2% vs. 13/113, 11.5%, p = 0.047). ITT analysis with missing data imputed showed no difference between the two iCBTs (SPHERE: 24.8/143, 17.3% vs. PRISM: 23.7/142, 16.7%, p = 0.99). Uptake rates of the iCBTs were high (76.9% and 81.69% logged in at least once into SPHERE and PRISM, respectively), but adherence was low (out of those who logged in at least once, 19.01% [21/110] completed at least 50% modules in SPHERE and 7.76% [9/116] set a goal for trying out a given trigger-specific recommendation in PRISM). Acceptability ratings were intermediate.
Conclusions:
Self-guided iCBTs were not found to be superior in our primary ITT analysis. Low adherence could explain the lack of effects as completer analysis showed effects for both interventions. Enhancement of adherence should be a focus of future research.
Major depressive disorder (MDD) is often accompanied by changes in appetite and weight. Prior task-based functional magnetic resonance imaging (fMRI) findings suggest these MDD phenotypes are associated with altered reward and interoceptive processing.
Methods
Using resting-state fMRI data, we compared the fractional amplitude of low-frequency fluctuations (fALFF) and seed-based connectivity (SBC) among hyperphagic (n = 77), hypophagic (n = 66), and euphagic (n = 42) MDD groups and a healthy comparison group (n = 38). We examined fALFF and SBC in a mask restricted to reward [nucleus accumbens (NAcc), putamen, caudate, ventral pallidum, and orbitofrontal cortex (OFC)] and interoceptive (anterior insula and hypothalamus) regions and also performed exploratory whole-brain analyses. SBC analyses included as seeds the NAcc and also regions demonstrating group differences in fALFF (i.e. right lateral OFC and right anterior insula). All analyses used threshold-free cluster enhancement.
Results
Mask-restricted analyses revealed stronger fALFF in the right lateral OFC, and weaker fALFF in the right anterior insula, for hyperphagic MDD v. healthy comparison. We also found weaker SBC between the right lateral OFC and left anterior insula for hyperphagic MDD v. healthy comparison. Whole-brain analyses revealed weaker fALFF in the right anterior insula, and stronger SBC between the right lateral OFC and left precentral gyrus, for hyperphagic MDD v. healthy comparison. Findings were no longer significant after controlling for body mass index, which was higher for hyperphagic MDD.
Conclusions
Our results suggest hyperphagic MDD may be associated with altered activity in and connectivity between interoceptive and reward regions.
Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.
Methods
In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.
Results
Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.
Conclusion
These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
The number of people living with dementia (PWD) is increasing worldwide, corresponding with an increasing number of caregivers for PWD. This study aims to identify and describe the literature surrounding the needs of caregivers of PWD and the solutions identified to meet these needs.
Method:
A literature search was performed in: PsycInfo, Medline, CINAHL, SCIELO and LILACS, January 2007–January 2018. Two independent reviewers evaluated 1,661 abstracts, and full-text screening was subsequently performed for 55 articles. The scoping review consisted of 31 studies, which were evaluated according to sociodemographic characteristics, methodological approach, and caregiver’s experiences, realities, and needs. To help extract and organize reported caregiver needs, we used the C.A.R.E. Tool as a guiding framework.
Results:
Thirty-one studies were identified. The most common needs were related to personal health (58% emotional health; 32% physical health) and receiving help from others (55%). Solutions from the articles reviewed primarily concerned information gaps (55%) and the education/learning needs of caregivers (52%).
Conclusion:
This review identified the needs of caregivers of PWD. Caregivers’ personal health emerged as a key area of need, while provision of information was identified as a key area of support. Future studies should explore the changes that occur in needs over the caregiving trajectory and consider comparing caregivers’ needs across different countries.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Methods
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Results
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
Conclusions
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
The important developments in our understanding and harnessing the biology of migraine have not diminished the need to consider the psychology of migraine. Psychological treatments especially relaxation training and biofeedback have been well validated as effective in treating frequent migraine. When the frequency and severity of migraine warrants more than analgesics, these treatments are the first line treatment for adults who cannot or do not wish to take abortive or prophylactic medications and for adolescents. The use of psychological interventions to enhance compliance to treatment or treatment effects is an underutilized resource. Psychological measurement is also critical in development and understanding of quality of life scales and the examination of decision-making by patients in taking medication. Modern clinical psychology has much to offer in the study of migraine and the amelioration of suffering from this common problem.
There are few clinical or biologic predictors of response to treatments for depression. This article reviews growing evidence that electrophysiologic and neurocognitive measures of brain function may be of value as predictors of therapeutic response to antidepressants. Initial studies using dichotic listening, quantitative electroencephalography, or event-related brain potential measures have found differences between treatment responsive and nonresponsive subgroups of depressed patients. The neurophysiologic basis for these differences and the potential clinical utility of electrophysiologic and dichotic predictors of treatment out come remain to be determined in future studies.
Objective/Introduction: We sought to characterize the impact of the 90-item Symptom Checklist (SCL-90) subscales for paranoid ideation (PI) and psychoticism (P) in patients with major depressive disorder (MDD), on acute anti-depressant response and on relapse prevention.
Methods: Subjects with Structured Clinical Interview for DSM Disorders-diagnosed non-psychotic MDD were recruited into a clinical trial of open-label fluoxetine 10–60 mg/day for 12 weeks, followed by double-blind randomization of responders (n=262) to fluoxetine continuation or placebo for 12 months. PI and P were assessed with the patient-rated SCL-90. The association of these symptoms with response to treatment was assessed by logistic regression.
Results: We found significant decreases in PI and P during acute treatment phase for fluoxetine responders and nonresponders, although only 10.3% and 7.5% of patients experienced a ≥50% reduction in PI and P scores, respectively. Neither PI nor P scores significantly predicted time to relapse. P scores predicted a lower response rate to treatment with fluoxetine.
Discussion: The results of the present study suggest that there is a significant relationship between the presence of psychoticism in patients with nonpsychotic MDD, and the likelihood of overall depressive symptom improvement following a trial of monotherapy with fluoxetine.
Conclusion: An increased burden of psychoticism in depressed subjects may confer poorer response to fluoxetine, but not increased risk of relapse among fluoxetine responders.
Dialectical behavior therapy (DBT) is a form of cognitive behavior therapy (CBT) for mood disorders. There are three categories of core strategies employed in DBT: change strategies, acceptance and validation strategies, and dialectical strategies. Change strategies in DBT, for the most part, are based on learning principles. One rationale for using DBT to treat mood disorders is the significant co-morbidity between borderline personality disorder (BPD) and mood disorders. Adapting DBT is different from adopting DBT. In the latter, DBT, e.g. the modes of treatment delivery, may be changed to meet the needs of the setting or target population. Programs which adopt comprehensive DBT benefit from the existing evidence base. DBT is an efficacious treatment proven to reduce suicidal behavior and nonsuicidal self-injury. DBT has been adapted for both bipolar adolescents and geriatric patients with treatment-resistant depression or depression co-morbid with BPD.
This chapter deals with brain imaging techniques. MRI and computer tomography (CT) scans have been used to identify changes in brain morphology in major depressive disorder (MDD). Functional MRI (fMRI), positron emission tomography (PET), and single photon emission computer tomography (SPECT) have all been utilized to identify regions of the brain that are differentially activated in MDD when compared to healthy control subjects. Altered correlation of activity between the frontal lobe and the amygdale has been reported during fMRI studies of patients with MDD. Both bipolar disorder and MDD are likely heterogeneous conditions with different molecular, cellular, genetic, or environmental causes that produce the same clinical phenotype of the disorder. Technical advances in neuroimaging techniques may allow for new questions to be asked into the biological underpinnings of mood disorders and may be used to predict responses to treatments.
There has been considerable controversy over the correct diagnosis for patients with mood disorder associated with the lifetime occurrence of hypomanic symptoms which are sub-threshold for the diagnosis of bipolar disorder. Extrapolating from the accelerating accumulation of knowledge of the biology of psychiatric disorders over the last several decades, it is easy to anticipate that this trend will continue and that such knowledge will define the molecular pathways whereby genes and environment affect the risk for mood disorders. There are early efforts to apply proteomic methods to mood disorders. Electrophysiology, primarily in the form of electroencephalographic recording, has shown significant promise in application to mood disorder therapeutics. An important intellectual trend is that the rapidly advancing technologies of quantitative neuroscience and molecular genetics appear to be making enormous progress toward demonstrating a neurobiological substrate of mood disorder.
This chapter discusses potential mechanisms of antidepressant action and outlines areas of active research in electroconvulsive therapy. Electroconvulsive treatment (ECT) remains the most effective treatment for major depression. During the seizure itself, and for a period of hours afterward, there is higher sympathetic tone with markedly elevated heart rate and blood pressure during ictus and for several minutes postictally. Pre-existing seizure disorder is generally not a contraindication for ECT; however, in patients with seizures, it should be ascertained that the seizure is not caused by a mass lesion or vascular malformation which could constitute higher risk with ECT. ECT requires the consent of the patient or, in the event that the patient lacks capacity, a ruling from a legal authority regarding procedures for substituted consent if available. The most common adverse effects of ECT are headache and myalgia.
Diagnosis of major depressive disorder is entirely clinical at present, and based on criteria such as DSM-IV. The classes of medications include antidepressants, selective serotonin reuptake inhibitors (SSRIs), older dual-action reuptake inhibitors, newer dual-action antidepressants, norepinephrine reuptake inhibitors (NRIs) and monoamine oxidase inhibitors. Successful treatment of major depression may require a multi-modal approach including pharmacotherapy, education, and psychotherapy. Patient response to treatment needs systematic monitoring, not only to improve compliance, but to make sound decisions about the need to raise the dose to achieve an optimal antidepressant effect and to monitor side effects. A history of episodes lasting more than 6 months require longer continuation treatment of up to 12 months, and generally continuation treatment will be longer for psychotic depression. Antidepressant and adjunctive pharmacological agents allow successful acute treatment and prevention of future episodes of major depression in most patients.
This chapter discusses models of unipolar mood disorder that incorporate both current neuroscience and clinical research. Severe major depressive disorder (MDD) is associated with higher basal cortisol secretion and higher peak levels, as well as dexamethasone resistance, indicating failure of feedback inhibition at both the higher stimulated cortisol levels and the lower resting cortisol levels. Post-traumatic stress disorder (PTSD) is associated with lower basal cortisol and increased glucocorticoid receptor (GCR) expression, indicating that the response to stress can be different in different disorders. The fundamental concept of the gene-environment interaction model is that whether a result of genes or early environmental trauma, or both, early life stress results in functional and structural changes in the brain that confer a life-long hyperactive stress response mediated by the hypothalamic pituitary adrenal (HPA) axis. Direct genetic effects or purely environmental effects may result in depressions.
This chapter focuses on a member of a much larger family of interventions known as cognitive behavior therapy (CBT). Cognitive therapy (CT) was first developed as a time-limited treatment of depression. Dysfunctional cognitions about medication can be modified with CT, and behavioral interventions, such as reminder systems and behavioral plans to overcome obstacles to adherence, can be used. The efficacy of CT has been subjected to hundreds of controlled investigations across a wide range of disorders. CT is the most exhaustively studied psychosocial intervention for depressive disorders. The primary analyses of six subsequent studies, all making greater efforts to ensure that pharmacotherapy was adequately administered, found CT and pharmacotherapy to be comparably effective across 12-16 weeks. It is noteworthy that the two most recent studies used selective serotonin reuptake inhibitors and, hence, have greater generalizability to contemporary practice.
Diagnosis of major depressive disorder is entirely clinical at present, and based on criteria such as DSM-IV. The classes of medications include antidepressants, selective serotonin reuptake inhibitors (SSRIs), older dual-action reuptake inhibitors, newer dual-action antidepressants, norepinephrine reuptake inhibitors (NRIs) and monoamine oxidase inhibitors. Successful treatment of major depression may require a multi-modal approach including pharmacotherapy, education, and psychotherapy. Patient response to treatment needs systematic monitoring, not only to improve compliance, but to make sound decisions about the need to raise the dose to achieve an optimal antidepressant effect and to monitor side effects. A history of episodes lasting more than 6 months require longer continuation treatment of up to 12 months, and generally continuation treatment will be longer for psychotic depression. Antidepressant and adjunctive pharmacological agents allow successful acute treatment and prevention of future episodes of major depression in most patients.