The acceptability of Internet-based treatment and characteristics of an adult sample with obsessive compulsive disorder: an Internet survey

Background

Obsessive-compulsive disorder (OCD) is a disabling anxiety disorder, but most individuals delay seeking treatment. Internet-based cognitive behavioural therapy (iCBT) is an innovative service delivery method that may help to improve access to care, but the acceptability to consumers of such programs has not yet been established.

Methodology

People with symptoms of OCD were invited to complete an online survey enquiring about demographic characteristics, symptom severity, and acceptability of Internet-based treatment. Demographic and symptom severity data were compared with people with OCD identified in a national epidemiological survey and with a sample of patients with OCD from a specialist outpatient anxiety clinic.

Participants

129 volunteers to an online Internet survey, 135 patients at a specialist anxiety disorders outpatient clinic, and 297 cases identified in a national epidemiological survey.

Main Measures

Demographic characteristics, and severity of symptoms as measured by the Kessler 10-Item scale, the 12-item World Health Organisation Disability Assessment Schedule - Second Edition and the Yale Brown Obsessive Compulsive Scale - Self Report Version.

Principal Findings

The Internet sample was similar demographically but reported more severe symptoms than the comparison groups, although had similar severity of symptoms of OCD compared with other clinical samples reported in the literature. Participants reported Internet-based treatment for OCD would be highly acceptable.

Conclusions

Internet-based treatment may reduce barriers to accessing treatment to people with OCD. Individuals in this study were similar demographically to other samples and had similar severity of symptoms as those identified in other clinical samples, suggesting that Internet-based treatment using techniques employed in face-to-face treatment may be effective in this group. Internet-based treatments for OCD need to be developed and evaluated.     

Effects of Baseline Problematic Alcohol and Drug Use on Internet-Based Cognitive Behavioral Therapy Outcomes for Depression,Panic Disorder and Social Anxiety Disorder

Purpose

Patients’ problematic substance use prevalence and effects were explored in relation to internet-based cognitive behavioral therapy (ICBT) outcomes for depression, panic disorder and social anxiety disorder.

Methods

At baseline and treatment conclusion, 1601 ICBT patients were assessed with self-rated measures for alcohol and drug use (AUDIT/DUDIT), depressive symptoms (MADRS-S), panic disorder symptoms (PDSS-SR) and social anxiety symptoms (LSAS-SR).

Results

Problematic substance use (AUDIT ≥8 for men, ≥6 for women; DUDIT ≥1) occurred among 32.4% of the patients; 24.1% only alcohol, 4.6% only drugs, and 3.7% combined alcohol and drug use. Hazardous alcohol use and probable alcohol dependence negatively affected panic disorder outcomes, and hazardous drug use led to worse social anxiety outcomes. Depression outcomes were not affected by substance use. Treatment adherence was negatively affected by problematic drug use among men and 25–34 year olds; combined substance use negatively affected adherence for women and 35–64 year olds.

Conclusion

Problematic substance use does not preclude ICBT treatment but can worsen outcomes, particularly problematic alcohol use for panic disorder patients and hazardous drug use for social anxiety patients. ICBT clinicians should exercise particular caution when treating men and younger patients with problematic drug use, and women or older patients with combined substance use.     

Impulsive Action but Not Impulsive Choice Determines Problem Gambling Severity

Background

Impulsivity is a hallmark of problem gambling. However, impulsivity is not a unitary construct and this study investigated the relationship between problem gambling severity and two facets of impulsivity: impulsive action (impaired ability to withhold a motor response) and impulsive choice (abnormal aversion for the delay of reward).

Methods

The recruitment includes 65 problem gamblers and 35 normal control participants. On the basis of DSM-IV-TR criteria, two groups of gamblers were distinguished: problem gamblers (n = 38) and pathological gamblers (n = 27) with similar durations of gambling practice. Impulsive action was assessed using a response inhibition task (the stop-signal task). Impulsive choice was estimated with the delay-discounting task. Possible confounds (e.g., IQ, mood, ADHD symptoms) were recorded.

Results

Both problem and pathological gamblers discounted reward at a higher rate than their controls, but only pathological gamblers showed abnormally low performance on the most demanding condition of the stop-signal task. None of the potential confounds covaried with these results.

Conclusions

These results suggest that, whereas abnormal impulsive choice characterizes all problem gamblers, pathological gamblers'' impairments in impulsive action may represent an important developmental pathway of pathological gambling.     

The effects of acute tryptophan depletion on reactive aggression in adults with attention-deficit/hyperactivity disorder (ADHD) and healthy controls

Background

The neurotransmitter serotonin (5-HT) has been linked to the underlying neurobiology of aggressive behavior, particularly with evidence from studies in animals and humans. However, the underlying neurobiology of aggression remains unclear in the context of attention-deficit/hyperactivity disorder (ADHD), a disorder known to be associated with aggression and impulsivity. We investigated the effects of acute tryptophan depletion (ATD), and the resulting diminished central nervous serotonergic neurotransmission, on reactive aggression in healthy controls and adults with ADHD.

Methodology/Principal Findings

Twenty male patients with ADHD and twenty healthy male controls were subjected to ATD with an amino acid (AA) beverage that lacked tryptophan (TRP, the physiological precursor of 5-HT) and a TRP-balanced AA beverage (BAL) in a double-blind, within-subject crossover-study over two study days. We assessed reactive aggression 3.25 hours after ATD/BAL intake using a point-subtraction aggression game (PSAG) in which participants played for points against a fictitious opponent. Point subtraction was taken as a measure for reactive aggression. Lowered rates of reactive aggression were found in the ADHD group under ATD after low provocation (LP), with controls showing the opposite effect. In patients with ADHD, trait-impulsivity was negatively correlated with the ATD effect on reactive aggression after LP. Statistical power was limited due to large standard deviations observed in the data on point subtraction, which may limit the use of this particular paradigm in adults with ADHD.

Conclusions/Significance

Together with previous findings, the data provide preliminary evidence of an inverse association between trait-impulsivity and the ATD effect on reactive aggression after LP (as assessed by the PSAG) in patients with ADHD and that this relationship can be found in both adolescents and adults. Because of limited statistical power larger sample sizes are needed to find main effects of ATD/BAL administration on reactive aggression in adults with ADHD.     

Validation of the Bipolar Disorder Etiology Scale Based on Psychological Behaviorism Theory and Factors Related to the Onset of Bipolar Disorder

Objectives

The aim of this study was to identify psychosocial factors related to the onset of bipolar I disorder (BD). To do so, the Bipolar Disorder Etiology Scale (BDES), based on psychological behaviorism, was developed and validated. Using the BDES, common factors related to both major depressive disorder (MDD) and BD and specific factors related only to BD were investigated.

Method

The BDES, which measures 17 factors based on psychological behaviorism hypotheses, was developed and validated. This scale was administered to 113 non-clinical control subjects, 30 subjects with MDD, and 32 people with BD. ANOVA and post hoc analyses were conducted. Subscales on which MDD and BD groups scored higher than controls were classified as common factors, while those on which the BD group scored higher than MDD and control groups were classified as specific factors.

Results

The BDES has acceptable reliability and validity. Twelve common factors influence both MDD and BD and one specific factor influences only BD. Common factors include the following: learning grandiose self-labeling, learning dangerous behavior, reinforcing impulsive behavior, exposure to irritability, punishment of negative emotional expression, lack of support, sleep problems, antidepressant problems, positive arousal to threat, lack of social skills, and pursuit of short-term pleasure. The specific factor is manic emotional response.

Conclusions

Manic emotional response was identified as a specific factor related to the onset of BD, while parents’ grandiose labeling is a candidate for a specific factor. Many factors are related to the onset of both MDD and BD.     

Hypersensitivity in Borderline Personality Disorder during Mindreading

Background

One of the core symptoms of borderline personality disorder (BPD) is the instability in interpersonal relationships. This might be related to existent differences in mindreading between BPD patients and healthy individuals.

Methods

We examined the behavioural and neurophysiological (fMRI) responses of BPD patients and healthy controls (HC) during performance of the ‘Reading the Mind in the Eyes’ test (RMET).

Results

Mental state discrimination was significantly better and faster for affective eye gazes in BPD patients than in HC. At the neurophysiological level, this was manifested in a stronger activation of the amygdala and greater activity of the medial frontal gyrus, the left temporal pole and the middle temporal gyrus during affective eye gazes. In contrast, HC subjects showed a greater activation in the insula and the superior temporal gyri.

Conclusion

These findings indicate that BPD patients are highly vigilant to social stimuli, maybe because they resonate intuitively with mental states of others.     

Facial Mimicry in 6–7 Year Old Children with Disruptive Behavior Disorder and ADHD

Background

Impairments in facial mimicry are considered a proxy for deficits in affective empathy and have been demonstrated in 10 year old children and in adolescents with disruptive behavior disorder (DBD). However, it is not known whether these impairments are already present at an earlier age. Emotional deficits have also been shown in children with attention-deficit/hyperactivity disorder (ADHD).

Aims

To examine facial mimicry in younger, 6–7 year old children with DBD and with ADHD.

Methods

Electromyographic (EMG) activity in response to emotional facial expressions was recorded in 47 children with DBD, 18 children with ADHD and 35 healthy developing children.

Results

All groups displayed significant facial mimicry to the emotional expressions of other children. No group differences between children with DBD, children with ADHD and healthy developing children were found. In addition, no differences in facial mimicry were found between the clinical group (i.e., all children with a diagnosis) and the typically developing group in an analysis with ADHD symptoms as a covariate, and no differences were found between the clinical children and the typically developing children with DBD symptoms as a covariate.

Conclusion

Facial mimicry in children with DBD and ADHD throughout the first primary school years was unimpaired, in line with studies on empathy using other paradigms.     

Improved Planning Abilities in Binge Eating

Objective

The role of planning in binge eating episodes is unknown. We investigated the characteristics of planning associated with food cues in binging patients. We studied planning based on backward reasoning, reasoning that determines a sequence of actions back to front from the final outcome.

Method

A cross-sectional study was conducted with 20 healthy participants, 20 bulimia nervosa (BN), 22 restrictive (ANR) and 23 binging anorexia nervosa (ANB), without any concomitant impulsive disorder. In neutral/relaxing, binge food and stressful conditions, backward reasoning was assessed with the Race game, promotion of delayed large rewards with an intertemporal discounting task, attention with the Simon task, and repeating a dominant behavior with the Go/No-go task.

Results

BN and to a lower extent ANB patients succeeded more at the Race game in food than in neutral condition. This difference discriminated binging from non-binging participants. Backward reasoning in the food condition was associated with lower approach behavior toward food in BN patients, and higher food avoidance in ANB patients. Enhanced backward reasoning in the food condition related to preferences for delayed large rewards in BN patients. In BN and ANB patients the enhanced success rate at the Race game in the food condition was associated with higher attention paid to binge food.

Conclusion

These findings introduce a novel process underlying binges: planning based on backward reasoning is associated with binges. It likely aims to reduce craving for binge foods and extend binge refractory period in BN patients, and avoid binging in ANB patients. Shifts between these goals might explain shifts between eating disorder subtypes.     

Physical Aggression and Language Ability from 17 to 72 Months: Cross-Lagged Effects in a Population Sample

Background

Does poor language ability in early childhood increase the likelihood of physical aggression or is language ability delayed by frequent physical aggression? This study examined the longitudinal associations between physical aggression and language ability from toddlerhood to early childhood in a population sample while controlling for parenting behaviours, non-verbal intellectual functioning, and children’s sex.

Methods

Children enrolled in the Quebec Longitudinal Study of Child Development (QLSCD) (N = 2, 057) were assessed longitudinally from 17 to 72 months via parent reports and standardized assessments.

Results

The cross-lagged models revealed modest reciprocal associations between physical aggression and language performance from 17 to 41 months but not thereafter.

Conclusions

Significant associations between physical aggression and poor language ability are minimal and limited to the period when physical aggression and language performance are both substantially increasing. During that period parenting behaviours may play an important role in supporting language ability while reducing the frequency of physical aggression. Further studies are needed that utilize multiple assessments of physical aggression, assess multiple domains of language abilities, and that examine the potential mediating role of parenting behaviours between 12 and 48 months.     

Effect of emotional arousal on inter-temporal decision-making: an fMRI study

Background

Previous research has shown that emotion can significantly impact decision-making in humans. The current study examined whether or not and how situationally induced emotion influences people to make inter-temporal choices.

Methods

Affective pictures were used as experiment stimuli to provoke emotion, immediately followed by subjects’ performance of a delay-discounting task to measure impulsivity during functional magnetic resonance imaging.

Results

Results demonstrate a subsequent process of increased impulsive decision-making following a prior exposure to both high positive and negative arousal stimuli, compared to the experiment subjects’ experiences with neutral stimuli. Findings indicate that increased impulsive decision-making behaviors can occur with high arousal and can be characterized by decreased activities in the cognitive control regions such as prefronto-parietal regions.

Conclusions

These results suggest that ‘stabilization of high emotional arousal’ may facilitate a reduction of impulsive decision-making and implementation of longer term goals.     

Association of Childhood Chronic Physical Aggression with a DNA Methylation Signature in Adult Human T Cells

Background

Chronic physical aggression (CPA) is characterized by frequent use of physical aggression from early childhood to adolescence. Observed in approximately 5% of males, CPA is associated with early childhood adverse environments and long-term negative consequences. Alterations in DNA methylation, a covalent modification of DNA that regulates genome function, have been associated with early childhood adversity.

Aims

To test the hypothesis that a trajectory of chronic physical aggression during childhood is associated with a distinct DNA methylation profile during adulthood.

Methods

We analyzed genome-wide promoter DNA methylation profiles of T cells from two groups of adult males assessed annually for frequency of physical aggression between 6 and 15 years of age: a group with CPA and a control group. Methylation profiles covering the promoter regions of 20 000 genes and 400 microRNAs were generated using MeDIP followed by hybridization to microarrays.

Results

In total, 448 distinct gene promoters were differentially methylated in CPA. Functionally, many of these genes have previously been shown to play a role in aggression and were enriched in biological pathways affected by behavior. Their locations in the genome tended to form clusters spanning millions of bases in the genome.

Conclusions

This study provides evidence of clustered and genome-wide variation in promoter DNA methylation in young adults that associates with a history of chronic physical aggression from 6 to 15 years of age. However, longitudinal studies of methylation during early childhood will be necessary to determine if and how this methylation variation in T cells DNA plays a role in early development of chronic physical aggression.     

Endovascular Treatment of Internal Iliac Artery Stenosis in Patients with Buttock Claudication

Aim

To assess the technical feasibility and clinical outcome of percutaneous transluminal angioplasty (PTA) with and without stent placement for treatment of buttock claudication caused by internal iliac artery (IIA) stenosis.

Methods

Between September 2001 and July 2011, thirty-four patients with buttock claudication underwent endovascular treatment. After angiographic lesion evaluation PTA with or without stent placement was performed. Technical success was recorded. Clinical outcome post-treatment was assessed at three months post-intervention and was classified as: 1) complete relief of symptoms, 2) partial relief, or 3) no relief of symptoms. Complications during follow-up were recorded.

Results

Forty-four lesions in 34 symptomatic patients were treated with PTA. Eight lesions were treated with additional stent placement. Technical success was achieved in 40/44 lesions (91%). Three procedure-related minor complications occurred, i.e. asymptomatic conservatively treated intimal dissections. After a median of 2.9 months, patients experienced no relief of symptoms in 7/34 cases (21%), partial relief in 14/34 cases (41%), and complete relief in 13/34 cases (38%). Six patients required a reintervention during follow-up.

Conclusion

Endovascular treatment of IIA stenosis has a high technical success rate and a low complication rate. Complete or partial relief of symptoms is achieved in the majority (79%) of patients.     

Influence of Mesenchymal Stem Cell Transplantation on Stereotypic Behavior and Dopamine Levels in Rats with Tourette Syndrome

Context

Tourette syndrome (TS) is a heterogeneous neuropsychiatric disorder. Chronic motor and phonic tics are central symptoms in TS patients. For some patients, tics are intractable to any traditional treatment and cause lifelong impairment and life-threatening symptoms. New therapies should be developed to address symptoms and overt manifestations of TS. Transplantation of neurogenic stem cells might be a viable approach in TS treatment.

Objective

We used mesenchymal stem cell (MSC) transplantation to treat TS. We discuss the mechanism of action, as well as the efficiency of this approach, in treating TS.

Settings and Design

An autoimmune TS animal model was adopted in the present study. Forty-eight Wistar rats were randomly allocated to the control group and the 2 experimental groups, namely, TS rats+vehicle and TS rats+MSC. MSCs were co-cultured with 5-bromodeoxyuridine (BrdU) for 24 h for labeling prior to grafting.

Methods

Stereotypic behaviors were recorded at 1, 7, 14, and 28 days after transplantation. Dopamine (DA) content in the striatum of rats in the 3 groups was measured using a high-performance liquid chromatography column equipped with an electrochemical detector (HPLC-ECD) on day 28 after transplantation.

Statistical analysis

Statistical analysis was performed by repeated measurements analysis of variance to evaluate stereotypic behavior counts at different time points.

Results

TS rats exhibited higher stereotypic behavioral counts compared with the control group. One week after transplantation, TS rats with MSC grafts exhibited significantly decreased stereotypic behavior. Rats with MSC grafts also showed reduced levels of DA in the striatum when compared with TS rats, which were exposed only to the vehicle.

Conclusions

Intrastriatal transplantation of MSCs can provide relief from the stereotypic behavior of TS. Our results indicate that this approach may have potential for developing therapies against TS. The mechanism(s) of the observed effect may be related to the suppression of DA system by decreasing the content of DA in TS rats.     

Predictors of the Onset of Manic Symptoms and a (Hypo)Manic Episode in Patients with Major Depressive Disorder

Objective

One third of patients with a major depressive episode also experience manic symptoms or, even, a (hypo)manic episode. Retrospective studies on the temporal sequencing of symptomatology suggest that the majority of these patients report depressive symptoms before the onset of manic symptoms. However, prospective studies are scarce and this study will, therefore, prospectively examine the onset of either manic symptoms or a (hypo)manic episode in patients with a major depressive disorder. In addition, we will consider the impact of a large set of potential risk factors on both outcomes.

Methodology

Four-year follow-up data were used to determine the onset of manic symptoms as well as a CIDI-based (hypo)manic episode in a large sample (n = 889, age: 18–65 years) of outpatients with a major depressive disorder and without manic symptoms at baseline. Baseline vulnerability (i.e., sociodemographics, family history of depression, childhood trauma, life-events) and clinical (i.e., isolated manic symptoms, depression characteristics, and psychiatric comorbidity) factors were considered as potential risk factors.

Results

In our sample of depressed patients, 15.9% developed manic symptoms and an additional 4.7% developed a (hypo)manic episode during four years. Baseline isolated manic symptoms and comorbid alcohol dependence predicted both the onset of manic symptoms and a (hypo)manic episode. Low education only predicted the onset of manic symptoms, whereas male gender, childhood trauma and severity of depressive symptoms showed strong associations with, especially, the onset of (hypo)manic episodes.

Conclusions

A substantial proportion (20.6%) of patients with a major depressive disorder later developed manic symptoms or a (hypo)manic episode. Interestingly, some identified risk factors differed for the two outcomes, which may indicate that pathways leading to the onset of manic symptoms or a (hypo)manic episode might be different. Our findings indirectly support a clinical staging model.     

Hostility, physical aggression and trait anger as predictors for suicidal behavior in Chinese adolescents: a school-based study

Purpose

This study explored the extent to which trait aggression is associated with suicidal behavior in a nationwide school-based sample of adolescents.

Methods

A nationwide sample of 14,537 high school students in urban areas of China was recruited. Information concerning suicide ideation, plans, attempts, trait aggression and other risk factors was collected by a self-reported questionnaire. Multivariate regression analyses were employed to predict suicidal behavior.

Results

Approximately 18.5% of students reported suicide ideation, 8.7% reported suicide plans, and 4.1% reported attempts during the past one year. Hostility and trait anger had a significant positive association with suicidal ideation. Hostility and physical aggression were positively related to suicide plans. Hostility had a positive correlation with suicide attempts, while trait anger was inversely associated with suicide attempts.

Conclusions

This study suggests that hostility, physical aggression and trait anger may be able to be used to predict suicidal behavior among adolescents. Suicide prevention programs should target at attenuating the severity of hostility, anger and physical aggression. But teachers and parents should also give close attention to students with low trait anger.     

A 6 week randomized double-blind placebo-controlled trial of ziprasidone for the acute depressive mixed state

Objective

To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD).

Methods

73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d) or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE), while also meeting 2 or 3 (but not more nor less) DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery- Åsberg Depression Rating Scale (MADRS) scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo.

Results

The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038). Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036). Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms.

Conclusions

There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00490542","term_id":"NCT00490542"}}NCT00490542     

Onset Pattern and Long-Term Prognosis in Schizophrenia: 10-Year Longitudinal Follow-Up Study

Background

Although the duration of untreated psychosis (DUP) plays an important role in the short-term prognosis of patients with schizophrenia, their long-term prognosis generally is not determined by DUP alone. It is important to explore how other clinical factors in the early stage are related to DUP and consequent disease courses.

Methods

A total of 664 patients with untreated psychosis were surveyed for this study. At the first examination, we divided them into the severe positive symptoms cases (SC) or the less severe cases (NonSC) and compared the prognosis among the two groups after a 10-year follow-up. In all, 113 patients in the SC group and 43 patients in the NonSC group were follow-up completers.

Results

Whereas DUP was not different between the two groups, patients with nonacute onset in both groups had significantly longer DUP than those in patients with acute onset. For all clinical measures, there was no difference in prognosis between the two groups or among the four groups classified by mode of onset (MoO) and initial severity of positive symptoms. However, the degree of improvement of global assessment of functioning (GAF) was significantly smaller in the NonSC-nonacute group than in the SC-acute and SC-nonacute groups.

Conclusions

These results suggest that neither DUP nor MoO alone necessarily affects the initial severity of positive symptoms. Moreover, it is possible that patients with low impetus of positive symptoms onset within long DUP experience profound pathologic processes. Therefore, the current study results indicated that long DUP and nonacute onset were related to poor long-term prognosis, regardless of initial positive symptoms.     

Long-stay psychiatric patients: a prospective study revealing persistent antipsychotic-induced movement disorder

Objective

The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness.

Method

Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia.

Results

The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder.

Conclusions

Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation.     

Characterization of Treatment Resistant Depression Episodes in a Cohort of Patients from a US Commercial Claims Database

Context

Treatment Resistant Depression (TRD) is a significant and burdensome health concern.

Objective

To characterize, compare and understand the difference between TRD and non-TRD patients and episodes in respect of their episode duration, treatment patterns and healthcare resource utilization.

Design and Setting

Patients between 18 and 64 years with a new diagnosis of major depressive disorder (MDD) and without a previous or comorbid diagnosis of schizophrenia or bipolar disease were included from PharMetrics Integrated Database, a claims database of commercial insurers in the US. Episodes of these patients in which there were at least two distinct failed regimens involving antidepressants and antipsychotics were classified as TRD.

Patients

82,742 MDD patients were included in the analysis; of these patients, 125,172 episodes were identified (47,654 of these were drug-treated episodes).

Main Outcome Measures

Comparison between TRD and non-TRD episodes in terms of their duration, number and duration of lines of treatment, comorbidities, and medical resource utilization.

Results

Of the treated episodes, 6.6% (N = 3,134) met the criteria for TRD. The median time to an episode becoming TRD was approximately one year. The mean duration of a TRD episode was 1,004 days (vs. 452 days for a non-TRD episode). More than 75% of TRD episodes had at least four lines of therapy; half of the treatment regimens included a combination of drugs. Average hospitalization costs were higher for TRD than non-TRD episodes: $6,464 vs. $1,734, as were all other health care utilization costs.

Conclusions

While this study was limited to relatively young and commercially covered patients, used a rigorous definition of TRD and did not analyze for cause or consequence, the results highlight high unmet medical need and burden of TRD on patients and health care resources.