A randomised controlled trial of psychotherapy and cognitive remediation to target cognition in mood disorders.

OBJECTIVE: To examine the impact of a treatment package combining Interpersonal and Social Rhythm Therapy (IPSRT) and cognitive remediation (CR), vs IPSRT alone, on cognition, functioning, and mood disturbance outcomes in mood disorders. METHODS: A pragmatic randomised controlled trial in adults with bipolar disorder (BD) or major depressive disorder (MDD), recently discharged from mental health services in Christchurch, New Zealand, with subjective cognitive difficulties. Individuals were randomised to a 12-month course of IPSRT with CR (IPSRT-CR), or without CR (IPSRT). In IPSRT-CR, CR was incorporated into therapy sessions from approximately session 5 and continued for 12 sessions. The primary outcome was change in Global Cognition (baseline to 12 months). RESULTS: Sixty-eight individuals (BD n = 26, MDD n = 42; full/partial remission n = 39) were randomised to receive IPSRT-CR or IPSRT (both n = 34). Across treatment arms, individuals received an average of 23 IPSRT sessions. Change in Global Cognition did not differ between arms from baseline to treatment-end (12 months). Psychosocial functioning and longitudinal depression symptoms improved significantly more in the IPSRT compared with IPSRT-CR arm over 12 months, and all measures of functioning and mood symptoms showed moderate effect size differences favouring IPSRT (0.41-0.60). At 18 months, small to moderate, non-significant benefits (0.26-0.47) of IPSRT vs IPSRT-CR were found on functioning and mood outcomes. CONCLUSIONS: Combining two psychological therapies to target symptomatic and cognitive/functional recovery may reduce the effect of IPSRT, which has implications for treatment planning in clinical practice and for CR trials in mood disorders.

Clinical Effectiveness Trial of Adjunctive Interpersonal and Social Rhythm Therapy for Patients With Bipolar Disorder.

OBJECTIVE: This study compared relapse rates at 18 months among patients with bipolar disorder who, after discharge from publicly funded mental health services, received either adjunctive interpersonal and social rhythm therapy (IPSRT) or treatment as usual (general practice medical care). METHODS: Patients diagnosed as having a bipolar I or II disorder who had been discharged from publicly funded mental health services in New Zealand during the previous 3 months were randomly assigned to 18 months of IPSRT or to treatment as usual. The primary outcome measure was the Life Interval Follow-Up Evaluation (LIFE) completed at weeks 26, 52, and 78 of treatment. Secondary measures were scores on the Social Adjustment Scale (SAS) and the Quality of Life-Bipolar Disorder Scale (QoL-BD) and readmission to mental health services. RESULTS: The sample consisted of 88 patients. In this intention-to-treat analysis, no significant differences were observed in rates of mood episodes between the groups (odds ratio=0.93, 95% confidence interval=0.37-2.17, p=0.86). A statistically significant difference was seen between the intervention and treatment-as-usual groups in scores on the SAS (effect size=0.5) but not on the QoL-BD. A significantly lower readmission rate was observed among the intervention group. CONCLUSIONS: This pragmatic clinical effectiveness trial found that a combination of IPSRT and medication management over 18 months did not significantly improve mood relapse but did improve patient functioning.

Can interpersonal psychotherapy be delivered by a community agency?

OBJECTIVES: There are limited options for depressed patients to have access to evidence-based psychotherapies in the community. This pilot study explored the feasibility of delivering interpersonal psychotherapy (IPT) to clients in a community support agency. METHOD: A total of 18 clients with depression completed at least eight sessions of IPT (range 8-13) and 17 completed a range of pre- and post-treatment measures. RESULTS: Clients had a high level of depression and were functioning poorly. All found the delivery of IPT in the community useful and would recommend therapy to others. There was a significant reduction in self-report and clinician-rated depression, and improvement in social functioning. CONCLUSIONS: This study supports the notion that therapy can be delivered by appropriately trained non-mental-health clinicians in the community with good effect and adds to the range of options for delivery of psychiatric care.

Three-year follow-up after psychotherapy for young people with bipolar disorder.

OBJECTIVES: (1) To examine the differences between interpersonal and social rhythm therapy (IPSRT) and specialist supportive care (SSC) in the longer term impacts of IPSRT and SSC on cumulative depression and mania symptoms over a further 78-week follow-up period post treatment. (2) To calculate the survival time before recurrence of a new mood episode over the 3-year period. METHODS: One hundred young people with bipolar disorder aged between 15 and 36 years who had been randomized to treatment with either IPSRT or SSC for 78 weeks were followed up for a subsequent 78 weeks. The Longitudinal Interval Follow-up Evaluation was completed at 26-week intervals. A Mann-Whitney U test was used to determine if there were significant differences between therapy types and a Kaplan-Meier survival analysis was used to determine time to recurrence. Cox regression was used to assess the association between time to relapse and therapy type. RESULTS: There were no significant differences between therapies at each of the data points for either depression or mania scores. The mean change in depression and mania in both groups was significantly different for all three follow-up data points. The actuarial cumulative recurrence rates were 53% for IPSRT and 49% for SSC. There was no significant difference between the groups in time to recurrence. CONCLUSIONS: While there were no significant differences between the two therapies, there was an overall reduction in symptoms in both therapies. There may be sustained benefits in providing intensive psychotherapies in conjunction with pharmacotherapy for young people with bipolar disorder.

Predictors of premature termination from psychotherapy for anorexia nervosa: Low treatment credibility, early therapy alliance, and self-transcendence.

OBJECTIVE: Failure to complete treatment for anorexia nervosa (AN) is- common, clinically concerning but difficult to predict. This study examines whether therapy-related factors (patient-rated pretreatment credibility and early therapeutic alliance) predict subsequent premature termination of treatment (PTT) alongside self-transcendence (a previously identified clinical predictor) in women with AN. METHODS: 56 women aged 17-40 years participating in a randomized outpatient psychotherapy trial for AN. Treatment completion was defined as attending 15/20 planned sessions. Measures were the Treatment Credibility, Temperament and Character Inventory, Vanderbilt Therapeutic Alliance Scale and the Vanderbilt Psychotherapy Process Scale. Statistics were univariate tests, correlations, and logistic regression. RESULTS: Treatment credibility and certain early patient and therapist alliance/process subscales predicted PTT. Lower self-transcendence and lower early process accounted for 33% of the variance in predicting PTT. DISCUSSION: Routine assessment of treatment credibility and early process (comprehensively assessed from multiple perspectives) may help clinicians reduce PTT thereby enhancing treatment outcomes.

Assessing the distinctiveness of psychotherapies and examining change over treatment for anorexia nervosa with cognitive-behavior therapy, interpersonal psychotherapy, and specialist supportive clinical management.

OBJECTIVE: Therapist adherence to cognitive-behavior therapy (CBT), interpersonal psychotherapy (IPT), and specialist supportive clinical management (SSCM) for anorexia nervosa (AN), was examined across three phases of therapy in a randomized clinical trial. METHOD: Adherence in early, middle, and late phase therapy sessions from 53 of 56 participants in the trial was assessed using the CSPRS-AN by independent raters after listening to complete therapy sessions. RESULTS: The three forms of psychotherapy were distinguishable by blind raters. Subscale scores were higher for the corresponding therapy than the other therapy modalities. In CBT and SSCM, a phase-by-therapy effect was found, with the CBT subscale highest for CBT, intermediate for SSCM, lowest for IPT, and elevated in the middle phase of CBT and SSCM. The SSCM subscale was highest for SSCM, intermediate for CBT, lowest for IPT, and elevated in the middle phase of SSCM. Adherence to activities around normalizing eating, weight gain, and education about anorexia nervosa was higher in SSCM than in either CBT or IPT. DISCUSSION: Ensuring the distinctiveness of therapies in existing clinical trials with differential treatment outcome is essential. Research on adherence to therapy modalities has the potential to help understanding of the effective components of new and existing treatments for AN. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:958-962).

Childhood predictors of lifetime suicide attempts and non-suicidal self-injury in depressed adults.

OBJECTIVE: Adverse childhood experiences are well-recognized risk factors for a variety of mental health issues, including depression, suicide attempts and non-suicidal self-injury. However, less is known about whether childhood adversity, in the form of low parental care, overprotection and abuse, is associated with suicide attempt and non-suicidal self-injury within a sample of depressed adults. METHOD: The sample of outpatients (n = 372) was drawn from two randomized depression trials. Childhood adversity variables, depression severity, age of first depressive episode (major depression episode onset), lifetime suicide attempt and non-suicidal self-injury were recorded at baseline. The association between variables and outcome measures was examined using partial correlations, univariate and multivariate logistic regressions. RESULTS: Low maternal care was significantly associated with suicide attempt; low paternal care was associated with non-suicidal self-injury; overprotection was not associated with either outcome. Other risk factors for suicide attempt were major depression episode onset and baseline depression severity. Major depression episode onset was also a risk factor for non-suicidal self-injury. Abuse, regardless of how it was measured, was not significantly associated with either behaviour after adjusting for its correlations with low maternal or paternal care. CONCLUSION: In this sample of depressed adults, the quality of ongoing, intra-familial relationships, as measured by levels of parental care, had a greater impact on suicide attempt and non-suicidal self-injury than abuse. As the findings were not a priori hypotheses, they require replication. Although the cross-sectional study design limits causal determination, the findings suggest different childhood risk factors for suicide attempt and non-suicidal self-injury and underscore the impact of low parental care on these two behaviours. These findings signal to clinicians the importance of asking specifically about suicide attempts, and non-suicidal self-injury, as well as levels of parental care in childhood. When endorsed, low parental care may be considered an important factor in contextualizing a patient's depression and potential risk for suicide and non-suicidal self-injury.

Prospective rates of suicide attempts and nonsuicidal self-injury by young people with bipolar disorder participating in a psychotherapy study.

OBJECTIVE: Bipolar disorder is a chronic relapsing disorder associated with high rates of suicide, suicide attempts and nonsuicidal self-injury. The study aimed to prospectively identify the rates of suicide attempts and nonsuicidal self-injury in young people participating in an adjunctive randomised controlled psychotherapy for bipolar disorder and to identify differences in individuals who engaged in nonsuicidal self-injury, made suicide attempts or did both. METHOD: In all, 100 participants aged 15-36 years with bipolar disorder received 78 weeks of psychotherapy and were followed up for a further 78 weeks. Data were collected using the Longitudinal Interval Follow-up Evaluation. RESULTS: Suicide attempts reduced from 11% at baseline to 1% at the end of follow-up (week 156). Similarly, self-harm reduced from 15% at baseline to 7% at the end of follow-up. Individuals who engaged in both nonsuicidal self-injury and made suicide attempts differed from those with who only made suicide attempts, engaged in nonsuicidal self-injury or did neither. They were characterised by a younger age of illness onset and higher comorbidity. CONCLUSION: Adjunctive intensive psychotherapy may be effective in reducing suicide attempts and nonsuicidal self-injury and warrants further attention. Particular attention needs to be paid to individuals with early age of onset of bipolar disorder.

Randomized, controlled trial of Interpersonal and Social Rhythm Therapy for young people with bipolar disorder.

OBJECTIVE: This randomized, controlled clinical trial compared the effect of interpersonal and social rhythm therapy (IPSRT) to that of specialist supportive care (SSC) on depressive outcomes (primary), social functioning, and mania outcomes over 26-78 weeks in young people with bipolar disorder receiving psychopharmacological treatment. METHODS: Subjects were aged 15-36 years, recruited from a range of sources, and the patient groups included bipolar I disorder, bipolar II disorder, and bipolar disorder not otherwise specified. Exclusion criteria were minimal. Outcome measures were the Longitudinal Interval Follow-up Evaluation and the Social Adjustment Scale. Paired-sample t-tests were used to determine the significance of change from baseline to outcome period. Analyses of covariance were used to determine the impact of therapy, impact of lifetime and current comorbidity, interaction between comorbidity and therapy, and impact of age at study entry on depression. RESULTS: A group of 100 participants were randomized to IPSRT (n = 49) or SSC (n = 51). The majority had bipolar I disorder (78%) and were female (76%), with high levels of comorbidity. After treatment, both groups had improved depressive symptoms, social functioning, and manic symptoms. Contrary to our hypothesis, there was no significant difference between therapies. There was no impact of lifetime or current Axis I comorbidity or age at study entry. There was a relative impact of SSC for patients with current substance use disorder. CONCLUSIONS: IPSRT and SSC used as an adjunct to pharmacotherapy appear to be effective in reducing depressive and manic symptoms and improving social functioning in adolescents and young adults with bipolar disorder and high rates of comorbidity. Identifying effective treatments that particularly address depressive symptoms is important in reducing the burden of bipolar disorder.

Clinical characteristics associated with premature termination from outpatient psychotherapy for anorexia nervosa.

AIM: The literature on clinical characteristics associated with premature termination of treatment (PTT) is beset with conflicting and non-replicated findings. This study explores clinical characteristics potentially associated with PTT in a randomised controlled outpatient psychotherapy trial for anorexia nervosa (AN). METHODS: Participants were 56 women aged 17-40 years with spectrum AN. The completer group (n = 35) included those completing at least 15/20 planned sessions with the remainder of the sample comprising the PTT group (n = 21). Variables examined included demographic factors, psychosocial functioning, psychiatric history, lifetime comorbidity, temperament and eating disorder characteristics. Logistic regression was used to examine significant variables. A Kaplan-Meier survival curve was used to illustrate time taken to PTT. RESULTS: The mean number of sessions in the PTT group was 8.1. Lower self-transcendence scores on the Temperament and Character Inventory were associated with PTT. CONCLUSIONS: Recognising and addressing personality factors have the potential to enhance retention in treatment.

Relationship between baseline cognition and 18-month treatment response in bipolar disorder.

BACKGROUND: To date, few studies have examined baseline cognitive function as a predictor of clinical outcome following treatment in bipolar disorder (BD). The aim of this analysis was therefore to examine the relationship between baseline cognitive function and treatment outcome in a sample of young adults with BD receiving Interpersonal Social Rhythm Therapy (IPSRT) or Specialist Supportive Care (SSC) with adjunctive pharmacotherapy. METHODS: Eighty-six BD patients underwent baseline cognitive testing and completed 18 months of IPSRT or SCC. Univariate analyses examined the relationship between baseline cognitive function (global and individual cognitive domains) and change in mood symptom burden, and psychosocial functioning, from baseline to treatment-end. RESULTS: Baseline global cognition was not predictive of change in mood symptom burden over 18 months of treatment. However, poorer baseline psychomotor speed performance was associated with less improvement in mood symptom burden at treatment-end. Neither baseline global cognition nor individual cognitive domain scores were associated with change in psychosocial functioning. LIMITATIONS: Due to the exploratory nature of the study, correction was not made for multiple comparisons. Data was obtained from a relatively small sample and has been the subject of prior analysis, thereby increasing the likelihood of chance findings. CONCLUSION: Although global cognition was not associated with outcome, when examining individual domains, poorer baseline psychomotor speed predicted less change in mood symptom burden following 18-months of psychotherapy and pharmacotherapy. This suggests that pre-treatment measures of psychomotor speed may help to identify those who require additional, and more targeted, intervention. Further large-scale research is required.

The long-term efficacy of three psychotherapies for anorexia nervosa: a randomized, controlled trial.

OBJECTIVE: To evaluate the long-term efficacy of three psychotherapies for anorexia nervosa. METHOD: Participants were women with broadly defined anorexia nervosa who had participated in a RCT comparing specialized psychotherapies (cognitive behavior therapy, CBT, and interpersonal psychotherapy, IPT) with a control condition (specialist supportive clinical management, SSCM), and attended long-term follow-up assessment (mean 6.7 years ± 1.2). RESULTS: Forty three of the original sample of 56 women participated in long-term follow-up assessment (77%). No significant differences were found on any pre-selected primary, secondary or tertiary outcome measures among the three psychotherapies at long-term follow-up assessment. Significantly different patterns of recovery were identified for the psychotherapies across time on the primary global outcome measure. Although SSCM was associated with a more rapid response than IPT, by follow-up all three treatments were indistinguishable. DISCUSSION: Potential implications for the timing of interventions to improve treatment response in anorexia nervosa are critically examined.

Childhood-, teenage-, and adult-onset depression: diagnostic and individual characteristics in a clinical sample.

BACKGROUND: The age at which a depressive episode is first experienced may be associated with particular individual and clinical characteristics. This study compares individual, clinical, and family characteristics across individuals who experienced their first major depressive episode when a child, teenager, or adult. METHODS: Participants were 372 depressed outpatients who participated in 2 completed randomized trials for depression. The first compared fluoxetine and nortriptyline, whereas the second compared cognitive behavior therapy and interpersonal psychotherapy. Assessment across the studies included structured clinical interviews for Diagnostic and Statistical Manual of Mental Disorders (DSM) Axis I/II diagnoses and a range of self-report measures of symptoms, functioning, and childhood experiences. RESULTS: Participants with childhood- and teenage-onset depression had a greater number of comorbid Axis I diagnoses, were more likely to meet criteria for Avoidant and Paranoid personality disorder (PD), and were more likely to have attempted suicide than those with adult-onset depression. Those with teenage-onset depression were more likely to meet criteria for a PD than those with adult-onset depression. Participants with childhood- and teenage-onset depression reported lower perceptions of paternal care before the age of 16 years, compared to participants with adult-onset depression. LIMITATIONS: Retrospective recall was used to classify individuals into childhood-, teenage-, and adult-onset groups and is subject to recall biases. The sample also consisted of treatment-seeking individuals. CONCLUSION: There were relatively few differences between teenage and childhood depression. Depressive episodes that begin in childhood or teenage years are associated with more comorbid diagnoses, a higher likelihood of Avoidant and Paranoid PD, a greater likelihood of attempted suicide, and poorer perceptions of paternal care. Compared to adult-onset depression, childhood-onset depression is associated with greater comorbidity.

The five year outcome of major depression: Effects of baseline variables and type of treatment.

BACKGROUND: Depression is commonly a relapsing or chronic disorder. Long-term outcome is therefore important. We report on the outcome of major depression five years after receiving treatment with medication or psychotherapy. METHODS: 472 patients were treated in three consecutive randomised controlled trials in one clinical research centre. 298 were followed up at five years. Of these, 106 patients were treated with medications, while the remaining 192 were given psychotherapy. The a priori outcome measure was mood symptoms in the two years prior to the assessment. RESULTS: The majority (56%) of patients had no depressive symptoms in the prior two years. One third (32%) had fluctuating depression, while 12% were chronic depressed. Predictors of outcome were few; baseline severity, suicidality, personality pathology, and type of treatment. Those receiving medication did somewhat worse, even when adjusted for this group's higher depression severity, suicidality and personality pathology at baseline. CONCLUSIONS: Long-term depressive symptoms are common after evidence-based treatment, although over half the patients appear to recover. Psychotherapy may be superior to medication in reducing the level of symptoms in the longer term. Personality remains one of the few baseline predictors of long-term outcome.

Childhood neglect and abuse as predictors of antidepressant response in adult depression.

BACKGROUND: Childhood neglect and abuse are recognized as risk factors for depression, but are not often studied as predictors of treatment response in depression. METHODS: Clinically depressed outpatients (n=195) were asked about childhood experiences before beginning a randomized antidepressant trial with either fluoxetine or nortriptyline. Three treatment outcomes were measured: Adequate trial, six-week response and two months sustained recovery. RESULTS: Patients reporting low paternal care (paternal neglect), as measured by the Parental Bonding Instrument (PBI), were less likely to complete an adequate six-week trial of medication. Patients who reported high maternal protection (maternal overprotection) on the PBI had poorer treatment response in the short-term at six weeks, and longer term, for two months of sustained recovery. However, abuse, whether sexual, physical, or psychological in nature, did not predict treatment response. CONCLUSIONS: The experience of having a neglectful father or an overprotective mother was more predictive of response to treatment for depression than abuse, suggesting that the quality of ongoing intra-familial relationships has a greater impact on treatment outcomes for depression than experiences of discrete abuse in childhood.

The Yale-Brown-Cornell eating disorder scale in women with anorexia nervosa: what is it measuring?

OBJECTIVE: The Yale-Brown-Cornell Eating Disorder Scale (YBC-EDS) assesses eating disorder preoccupations, rituals, and symptom severity. This study examines the YBC-EDS in relation to eating disorder psychopathology, obsessionality, and impulsivity variables in women with anorexia nervosa (AN) and sensitivity of the YBC-EDS to change after psychotherapy. METHOD: Participants were 56 women with "spectrum" AN (14.5 < BMI < 19). Variables examined in relation to the YBC-EDS were as follows: eating pathology, obsessionality (obsessive compulsive disorder and personality diagnoses, perfectionism), and impulsivity (borderline personality, impulsive traits, and behaviors). YBC-EDS scores were examined pre- and post-treatment. RESULTS: Eating Disorder Examination scores most strongly predicted the YBC-EDS. As expected, perfectionism was significantly associated, but so was impulsivity. YBC-EDS scores were significantly different in those with good versus poor global outcome after therapy. Unexpectedly, maximum lifetime BMI was correlated with the YBC-EDS. DISCUSSION: The YBC-EDS most strongly measured eating disorder severity and reflected change after psychotherapy for AN.

"I actually don't know who I am": the impact of bipolar disorder on the development of self.

The majority of patients with bipolar disorder have onset prior to twenty years with early onset associated with increased impairment. Despite this, little attention has been given to the psychosocial developmental impact of this disorder. This qualitative study explored the impact of having bipolar disorder on the development of a sense of self and identity. Key findings from this qualitative study identified that for these participants, bipolar disorder had a significant impact in the area of self and identity development. Bipolar disorder created experiences of confusion, contradiction, and self doubt which made it difficult for these participants to establish continuity in their sense of self. Their lives were characterized by disruption and discontinuity and by external definitions of self based on their illness. Developing a more integrated self and identity was deemed possible through self-acceptance and incorporating different aspects of themselves. These findings would suggest that it is critical to view bipolar disorder within a psychosocial developmental framework and consider the impact on the development of self and identity. A focus on the specific areas of impact and targeting interventions that facilitate acceptance and integration thus promoting self and identity development would be recommended.

An association study of DRD2 and COMT polymorphisms with novelty seeking and harm avoidance scores, in two independent samples of depressed patients.

BACKGROUND: It was recently reported that an interaction of the dopamine D2 receptor (DRD2) and catechol-O-methyltransferase (COMT) influences the behavioural approach system--as measured using Carver and White's Behavioural Inhibition and Behavioural Approach System (BIS/BAS) scales--in a sample of healthy German subjects. The Temperament and Character Inventory (TCI), in particular the novelty seeking (NS) and harm avoidance (HA) scales, correlates moderately with the BIS/BAS measure. This study aimed to examine support for an association of DRD2 and COMT with behavioural activation, using the TCI within two independent samples of depressed outpatients (for both samples n = 146). METHODS: Two clinical samples of depressed patients were ascertained to assess the efficacy of two different pharmacotherapy and psychotherapy treatments. Analysis of variance (ANOVA) was used to analyse NS and HA scale and subscale scores with respect to gene loci within each clinical sample. Analysis of covariance were undertaken to examine the association of age and gender with NS and HA scores. An association of age group or gender with gene loci were explored using chi-squared tests, in each sample. RESULTS: No significant effect of DRD2 or COMT, either independently or as an interaction, on NS or HA scores was observed, within either sample. Whilst age was significantly negatively associated with NS scores, including age in the two- and three-way interactions did not affect the significance of the association of personality with gene loci. CONCLUSION: This study suggests that the COMT-DRD2 Equilibrium Model of Positive Emotionality recently proposed by Reuter and his colleagues is not applicable amongst currently depressed individuals, whose behavioural approach and inhibition tendencies have been assessed using the TCI.

Six months of treatment for depression: outcome and predictors of the course of illness.

OBJECTIVE: The goals of this study were to determine the course of illness in a cohort of depressed patients undergoing treatment for 6 months and whether there are clinically useful predictors of their course of illness. METHOD: A cohort of 175 depressed outpatients undergoing drug treatment were followed prospectively for 6 months. Patients were initially randomly assigned to fluoxetine or nortriptyline. Those who responded were encouraged to continue taking their drugs for the 6 months. Those who did not were switched to other drugs or drug combinations. RESULTS: Of the 175 patients, 101 (58%) had a good outcome (achieved recovery and remained well), 54 (31%) had a fluctuating outcome (achieved recovery or remission but suffered a relapse or recurrence), and 20 (11%) had a poor outcome (remained depressed for the 6 months). Factors predicting good outcome included early response and a low level of schizoid personality disorder symptoms, and variables predicting poor outcome included a high score for harm avoidance and the absence of an early response. CONCLUSIONS: Depression is a recurring and chronic disorder. Personality factors such as a high harm avoidance score and schizoid traits were associated with a worse outcome, but demographic features, depression characteristics, depression subtypes, and comorbidity were not. Early response was strongly associated with the course of illness, but none of these features added significantly to the clinicians' ability to predict outcome.