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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and eventual death, usually within 3-5 years. An ALS diagnosis is associated with substantial emotional distress for both the affected person and their family care-partners which impairs the ability to engage in important conversations about long term care planning, negatively impacts ALS symptoms for the patient, and quality of life for both patient and care-partner. Here we 1) discuss published works identified by the authors about psychosocial interventions for the ALS population, 2) identify a lack of early, dyadic interventions to support psychosocial needs of people with ALS and care-partners; 3) describe the Neurodegenerative Diseases (NDD) framework for early dyadic intervention development and 4) propose an adaptation of an evidence-based early dyadic psychosocial intervention, Recovering Together, for the unique needs of people with ALS and their care-partners (Resilient Together-ALS; RT-ALS) using the NDD framework. Future work will use stakeholder feedback to optimize the intervention for subsequent efficacy testing. [ABSTRACT FROM AUTHOR]

Major depressive disorder is a common, recurrent, disabling and costly disorder that is often severe and/or chronic, and for which non-remission on guideline concordant first-line antidepressant treatment is the norm. A sizeable percentage of patients diagnosed with MDD do not achieve full remission after receiving antidepressant treatment. How to understand or approach these 'refractory', 'TRD' or 'difficult to treat' patients need to be revisited. Treatment resistant depression (TRD) has been described elsewhere as failure to respond to adequate treatment by two different antidepressants. This definition is problematic as it suggests that TRD is a subtype of major depressive disorder (MDD), inferring a boundary between TRD and depression that is not treatment resistant. However, there is scant evidence to suggest that a discrete TRD entity exists as a distinct subtype of MDD, which itself is not a discrete or homogeneous entity. Similarly, the boundary between TRD and other forms of depression is predicated at least in part on regulatory and research requirements rather than biological evidence or clinical utility. This paper aims to investigate the notion of treatment failure in order to understand (i) what is TRD in the context of a broader formulation based on the understanding of depression, (ii) what factors make an individual patient difficult to treat, and (iii) what is the appropriate and individualised treatment strategy, predicated on an individual with refractory forms of depression? Expert contributors to this paper were sought internationally by contacting representatives of key professional societies in the treatment of MDD – World Federation of Societies for Biological Psychiatry, Australasian Society for Bipolar and Depressive Disorders, International Society for Affective Disorders, Collegium Internationale Neuro-Psychopharmacologium and the Canadian Network for Mood and Anxiety Treatments. The manuscript was prepared through iterative editing. The concept of TRD as a discrete subtype of MDD, defined by failure to respond to pharmacotherapy, is not supported by evidence. Between 15 and 30% of depressive episodes fail to respond to adequate trials of 2 antidepressants, and 68% of individuals do not achieve remission from depression after a first-line course of antidepressant treatment. Failure to respond to antidepressant treatment, somatic therapies or psychotherapies may often reflect other factors including; biological resistance, diagnostic error, limitations of current therapies, psychosocial variables, a past history of exposure to childhood maltreatment or abuse, job satisfaction, personality disorders, co-morbid mental and physical disorders, substance use or non-adherence to treatment. Only a subset of patients not responding to antidepressant treatment can be explained through pharmacokinetic or pharmacodynamics mechanisms. We propose that non remitting MDD should be personalised, and propose a strategy of 'deconstructing depression'. By this approach, the clinician considers which factors contribute to making this individual both depressed and 'resistant' to previous therapeutic approaches. Clinical formulation is required to understand the nature of the depression. Many predictors of response are not biological, and reflect a confluence of biological, psychological, and sociocultural factors, which may influence the illness in a particular individual. After deconstructing depression at a personalised level, a personalised treatment plan can be constructed. The treatment plan needs to address the factors that have contributed to the individual's hard to treat depression. In addition, an individual with a history of illness may have a lot of accumulated life issues due to consequences of their illness, and these should be addressed in a recovery plan. A 'deconstructing depression' qualitative rubric does not easily provide clear inclusion and exclusion criteria for researchers wanting to investigate TRD. MDD is a polymorphic disorder and many individuals who fail to respond to standard pharmacotherapy and are considered hard to treat. These patients are best served by personalised approaches that deconstruct the factors that have contributed to the patient's depression and implementing a treatment plan that adequately addresses these factors. The existence of TRD as a discrete and distinct subtype of MDD, defined by two treatment failures, is not supported by evidence. [ABSTRACT FROM AUTHOR]

A Sequential Parallel Comparison Design has two stages, the first comparing drug to placebo and the second comparing drug to placebo among patients who did not respond to placebo in the first stage. The paper, Statistical Inference Problems in Sequential Parallel Comparison Designs, claims that the estimate of the treatment difference in the second stage is biased and that under certain circumstances, a suggested hypothesis test will reject the null hypothesis when it should be accepted. This rejoinder argues that the estimate in the second stage is not biased when the true target of estimation (estimand) is properly understood. Further, the null hypothesis that the authors posit is not the correct null hypothesis for clinical trials, and in the situation, they describe that the treatment should be considered to be effective. [ABSTRACT FROM AUTHOR]

In clinical trials, placebo response can affect the inference about efficacy of the studied treatment. It is important to have a robust way to classify trial subjects with respect to their response to placebo. Simple, criterion-based classification may lead to classification error and bias the inference. The uncertainty about placebo response characteristic has to be factored into the treatment effect estimation. We propose a novel approach that views the placebo response as a latent characteristic and the study sample as an unlabeled mixture of "placebo responders" and "placebo nonresponders." The likelihood-based methodology is used to estimate the treatment effect corrected for placebo response as defined within sequential parallel comparison design. [ABSTRACT FROM AUTHOR]

Objectives: These recommendations were designed to ensure safety for patients with major depressive disorder (MDD) and to aid monitoring and management of adverse effects during treatment with approved antidepressant medications. The recommendations aim to inform prescribers about both the risks associated with these treatments and approaches for mitigating such risks. Methods: Expert contributors were sought internationally by contacting representatives of key stakeholder professional societies in the treatment of MDD (ASBDD, CANMAT, WFSBP and ISAD). The manuscript was drafted through iterative editing to ensure consensus. Results: Adequate risk assessment prior to commencing pharmacotherapy, and safety monitoring during pharmacotherapy are essential to mitigate adverse events, optimise the benefits of treatment, and detect and assess adverse events when they occur. Risk factors for pharmacotherapy vary with individual patient characteristics and medication regimens. Risk factors for each patient need to be carefully assessed prior to initiating pharmacotherapy, and appropriate individualised treatment choices need to be selected. Some antidepressants are associated with specific safety concerns which were addressed. Conclusions: Risks of adverse outcomes with antidepressant treatment can be managed through appropriate assessment and monitoring to improve the risk benefit ratio and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: This pilot study evaluated the effects of Tai Chi training on sleep quality (primary outcomes), and depression and social functioning levels (secondary outcomes) among patients with depression. Participants: Sixteen depressed Chinese patients. Methods: Participants received 1-hr Tai Chi training sessions 2 times per week for 10 weeks. Patients’ subjective sleep quality ratings, objective sleep quality measurements, and depression and social functioning levels were measured before, during, and after the intervention. Results: Sleep quality and depression outcomes improved significantly. Patients reported improved Pittsburgh Sleep Quality Index (PSQI) scores (9.6 ± 3.3 to 6.6 ± 5.2, p = 0.016), and cardiopulmonary coupling (CPC) analysis of electrocardiogram (ECG) showed decreased stable sleep onset latency (75.7 ± 100.6 to 20.9 ± 18.0, p = 0.014), increased stable sleep percentages (31.5 ± 18.7 to 46.3 ± 16.9, p = 0.016), and decreased unstable sleep percentages (45.3 ± 20.1 to 30.6 ± 16.5, p = 0.003). Patients also reported decreased Hamilton Rating Scale for Depression (HAM-D-17; 20.1 ± 3.7 to 7.8 ± 5.9, p < 0.001) and Beck Depression Inventory (BDI) scores (22.3 ± 9.1 to 11.1 ± 10.6, p = 0.006). Significant correlations were found between the changes in subjective sleep assessments ΔPSQI and ΔHAM-D-17 (r = 0.6, p = 0.014), and ΔPSQI and ΔBDI (r = 0.62, p = 0.010). Correlations between changes in objective sleep measurements and changes in depression symptoms were low and not significant. Conclusions: Tai Chi training improved sleep quality and mood symptoms among depressed patients. [ABSTRACT FROM AUTHOR]

To compare outcomes from two different treatment strategies in Latino patients with major depressive disorder (MDD) and psychosis-like symptoms: antidepressant medications alone versus a combination of antipsychotic and antidepressant medications, we retrospectively examined the clinical charts of 37 Latino patients with MDD and psychosis-like symptoms from one of our community affiliated clinics, admitted from January 2010 to June 2011. Outcomes included depressive response and remission based on improvement in Patient Health Questionnaire-9 scores. Psychosis-like symptoms were assessed through a specific database created for the study. To qualify for outcomes analysis, patients had to have had adequate treatment with relevant medications for at least eight weeks at therapeutic doses. In all, 24 subjects met the criteria for analysis, and 11 received an antipsychotic medication. Of the 10 subjects who received an antipsychotic, 3 (30%) achieved depressive response. Of the 14 subjects who did not receive any antipsychotic, 10 (71%) attained depressive response. However, significance for the comparison was lost when Fisher's correction was applied (p= .095). Remission rates from depression were lower in both groups, with the same distribution in favor of subjects treated without antipsychotic, although it was not significant because of the small sample size (10% versus 43%;p= .172). Remission from psychosis-like symptoms occurred in 4 of 9 (44%) and in 12 of 15 (80%) subjects treated with and without antipsychotic (p= .099). Our preliminary data suggest that patients affected by MDD with psychosis-like symptoms are likely to achieve remission from both depressive and psychosis-like symptoms even without antipsychotic augmentation of their antidepressant regimen. [ABSTRACT FROM AUTHOR]

Our objective was to develop: 1) a longitudinal model to describe amyotrophic lateral sclerosis (ALS) disease progression using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R); and 2) a probabilistic model to estimate the presence of clusters of trajectories in ALS progression over 12 months of treatment. Three hundred and thirty-eight patients treated with placebo from the PRO-ACT database were included in the analyses. A non-linear Weibull model best described the ALS disease progression, and a stepwise logistic regression approach was used to select the variables predicting a slow or fast disease progression. Results identified two clusters of trajectories: 1) slow disease progressors (46% of patients with a change from baseline of 13%); 2) fast disease progressors (54% of patients with a change from baseline of 49%). ROC curve analysis estimated the optimal cut-off for classifying patients as slow or fast disease progressors given ALSFRS-R measurements at 2-4 weeks. Results showed that the degree of ALS disease progression quantified by the ALSFRS-R symptomatic change on placebo is highly heterogeneous. In conclusion, this finding indicates the potential interest of disease progression models for implementing a population enrichment strategy to control the level of heterogeneity in the patients included in new trials. [ABSTRACT FROM AUTHOR]

Many depressed Chinese immigrants are unfamiliar with Western psychiatric terminology and have high levels of stigma toward psychiatric illnesses, making it difficult to engage them into psychiatric treatment. We have designed the Engagement Interview Protocol (EIP), a semi-standardized protocol that incorporates cultural components to a standard psychiatric evaluation. The EIP elicits patients’ narratives and uses anthropological questions to explore patients’ illness beliefs, which are integrated with patients’ information on medical and psychiatric history, psychosocial background and mental status examination so that treatment options can be negotiated in a culturally sensitive manner. In our field testing on depressed Chinese immigrants, the EIP model was found to be a practical tool that can be completed within the allotted one-hour time frame and was highly effective in facilitating the enrollment of patients in treatment for depression. The EIP is a concise, time-effective, user-friendly protocol that can be used both in research and real-world clinical settings with diverse patient populations. [ABSTRACT FROM PUBLISHER]

Objectives. To determine the prevalence of major depressive disorder (MDD) and other selected axis-I disorders among women with newly diagnosed, untreated endocrine disorders. Methods. Two hundred and eighteen consecutive women, aged 18-65, with newly diagnosed, untreated endocrine disorders were referred for potential diagnosis of co-morbid axis-I disorders with the use of the Structured Clinical Interview for Axis I-Patient Edition (SCID-P). The SCID-P was re-administered after 12 weeks. Results. At baseline, 64 (29.3%) women met criteria for at least one axis-I disorder. Women who were diagnosed with hyperthyroidism were more likely to meet criteria for generalized anxiety disorder and panic disorder than women without hyperthyroidism. Nine of 154 (5.8 %) women who did not meet criteria for an axis-I disorder at baseline met criteria for at least one axis-I disorder during follow-up. Among them, the presence of diabetes mellitus was statistically correlated with a higher probability of developing major depressive disorder at follow-up. Conclusions. Although preliminary, our findings are consistent with previous studies and suggest an increased prevalence of MDD and other axis-I disorders among women with newly diagnosed endocrine disorders, providing further evidence suggesting that women with endocrine abnormalities may be at increased risk of depression and/or anxiety disorders. [ABSTRACT FROM AUTHOR]

The purpose of this meta-analysis is to examine the relationship between selective serotonin reuptake inhibitor (SSRI) starting dose and treatment outcome in major depressive disorder (MDD). Medline/Pubmed, EMBASE, the Cochrane database, as well as a number of online clinical trial registries were searched for double-blind, placebo-controlled, fixed-dose trials comparing different starting doses of SSRIs for MDD. Data from nine trials ( n=2340) were combined using a random-effects model. Patients randomized to receive the usual starting dose (10 mg escitalopram; 20 mg fluoxetine, paroxetine, citalopram; 50 mg sertraline and fluvoxamine) were less likely to respond than patients who received higher starting doses (RR=0.9; P=0.04; response rate 50.8 vs. 54.8%). The rate of discontinuation due to adverse events was lower among the usual starting dose group (9.8%) compared to the higher starting dose group (16.5%).Initiating treatment with SSRIs at doses higher than those typically used in clinical trials/settings is associated with higher response rates but also higher rates of discontinuation due to intolerance. Developing treatment strategies allowing clinicians to deliver higher initial SSRI doses while enhancing the tolerability of treatment may represent an alternative approach to improving the efficacy of treatment of MDD. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of psychotic-like symptoms in non-psychotic major depressive disorder and to monitor the response of these symptoms to monotherapy with fluoxetine. Methods: We reviewed the charts of 384 subjects (54.7% women; mean age 39.9±10), all outpatients diagnosed with non-psychotic major depressive disorder by the Structured Clinical Interview for DSM-IV (SCID), aged 18-65 years, with an initial 17-item Hamilton Depression (HAM-D-17) score of 16 or greater. Subjects were treated openly with fluoxetine 20 mg/day for 8 weeks. Subjects were administered the SCID-II (Structured Clinical Diagnostic Interview for Personality Disorder) prior to entering acute treatment and at the completion of the acute phase of treatment. We monitored the course of psychotic-like symptoms following this course of therapy. Results: 187 subjects endorsed at least one psychotic-like symptom, including not trusting close acquaintances (item 51), picking up hidden meanings (item 52), believing that others were talking about them (item 57), magical thinking (item 60) or unusual perceptual experiences (item 62). None of these patients met criteria for delusional depression as defined by the SCID. Overall response rates were 36.4% for patients who endorsed psychotic-like symptoms, and 53.3% for those who did not endorse psychotic-like symptoms (chi-squared = 11.1, P=0.001). The decrease in psychotic-like symptoms during the course of fluoxetine monotherapy was significant (P<0.05) in both responders and non-responders to treatment. Conclusion: A significant percentage of patients with non-psychotic major depression endorse subtle psychotic-like symptoms, many of which abate during monotherapy with fluoxetine regardless of response of the depressive symptoms. [ABSTRACT FROM AUTHOR]

Family functioning and parenting were hypothesized to mediate the relation between remission of maternal depression and children's psychosocial adjustment. Participants were 114 mother-child dyads participating in the Sequenced Treatment Alternatives to Relieve Depression Child 3-month follow-up. All mothers had been diagnosed with major depressive disorder and were treated initially with citalopram; 33% of mothers experienced remission of depressive symptoms. Youth ranged in age from 7 to 17. Remission of maternal depression was associated with changes in children's reports of their mothers' warmth/acceptance, which in turn partially mediated the relation between maternal depression remission and youth internalizing symptoms, accounting for 22.9% of the variance. [ABSTRACT FROM AUTHOR]

Anxiety sensitivity is the fear of anxiety-related sensations, and is measured by the 16-item Anxiety Sensitivity Index (ASI; Reiss, Peterson, Gursky, & McNally, 1986). Despite the popularity and utility of the ASI in research, a number of studies have provided evidence for the inadequacy of several items, and item-to-scale correlations for the ASI have not been published. In this study, a converging set of analyses to evaluate the item adequacy and factor structure of the ASI was used. The results of these multiple analyses converged nicely suggesting that Items 1, 5, 7, 8, and 13 should be considered for removal from the instrument. The impact of removing these problematic items from the scale was explored through the reanalysis of data from 3 previously published studies that compared the original ASI with the new 11-item version (the ASI minus the 5 problematic items). The results of these analyses suggest that the 2 scales function comparably in many respects but that the new version may be a more precise measure of anxiety sensitivity. The 11-item ASI appears to tap 2 primary aspects of anxiety sensitivity: fears of somatic sensations of anxiety and fears of loss of mental control. Suggestions for further development of the ASI are offered. [ABSTRACT FROM AUTHOR]