A computational approach to measure the linguistic characteristics of psychotherapy timing, responsiveness, and consistency.

Although individual psychotherapy is generally effective for a range of mental health conditions, little is known about the moment-to-moment language use of effective therapists. Increased access to computational power, coupled with a rise in computer-mediated communication (telehealth), makes feasible the large-scale analyses of language use during psychotherapy. Transparent methodological approaches are lacking, however. Here we present novel methods to increase the efficiency of efforts to examine language use in psychotherapy. We evaluate three important aspects of therapist language use - timing, responsiveness, and consistency - across five clinically relevant language domains: pronouns, time orientation, emotional polarity, therapist tactics, and paralinguistic style. We find therapist language is dynamic within sessions, responds to patient language, and relates to patient symptom diagnosis but not symptom severity. Our results demonstrate that analyzing therapist language at scale is feasible and may help answer longstanding questions about specific behaviors of effective therapists.

Amygdala and Insula Connectivity Changes Following Psychotherapy for Posttraumatic Stress Disorder: A Randomized Clinical Trial.

BACKGROUND: Exposure-based psychotherapy is a first-line treatment for posttraumatic stress disorder (PTSD), but its mechanisms are poorly understood. Functional brain connectivity is a promising metric for identifying treatment mechanisms and biosignatures of therapeutic response. To this end, we assessed amygdala and insula treatment-related connectivity changes and their relationship to PTSD symptom improvements. METHODS: Individuals with a primary PTSD diagnosis (N = 66) participated in a randomized clinical trial of prolonged exposure therapy (n = 36) versus treatment waiting list (n = 30). Task-free functional magnetic resonance imaging was completed prior to randomization and 1 month following cessation of treatment/waiting list. Whole-brain blood oxygenation level-dependent responses were acquired. Intrinsic connectivity was assessed by subregion in the amygdala and insula, limbic structures key to the disorder pathophysiology. Dynamic causal modeling assessed evidence for effective connectivity changes in select nodes informed by intrinsic connectivity findings. RESULTS: The amygdala and insula displayed widespread patterns of primarily subregion-uniform intrinsic connectivity change, including increased connectivity between the amygdala and insula; increased connectivity of both regions with the ventral prefrontal cortex and frontopolar and sensory cortices; and decreased connectivity of both regions with the left frontoparietal nodes of the executive control network. Larger decreases in amygdala-frontal connectivity and insula-parietal connectivity were associated with larger PTSD symptom reductions. Dynamic causal modeling evidence suggested that treatment decreased left frontal inhibition of the left amygdala, and larger decreases were associated with larger symptom reductions. CONCLUSIONS: PTSD psychotherapy adaptively attenuates functional interactions between frontoparietal and limbic brain circuitry at rest, which may reflect a potential mechanism or biosignature of recovery.

Assessing the accuracy of automatic speech recognition for psychotherapy.

Accurate transcription of audio recordings in psychotherapy would improve therapy effectiveness, clinician training, and safety monitoring. Although automatic speech recognition software is commercially available, its accuracy in mental health settings has not been well described. It is unclear which metrics and thresholds are appropriate for different clinical use cases, which may range from population descriptions to individual safety monitoring. Here we show that automatic speech recognition is feasible in psychotherapy, but further improvements in accuracy are needed before widespread use. Our HIPAA-compliant automatic speech recognition system demonstrated a transcription word error rate of 25%. For depression-related utterances, sensitivity was 80% and positive predictive value was 83%. For clinician-identified harm-related sentences, the word error rate was 34%. These results suggest that automatic speech recognition may support understanding of language patterns and subgroup variation in existing treatments but may not be ready for individual-level safety surveillance.

Psychotherapy or medication for depression? Using individual symptom meta-analyses to derive a Symptom-Oriented Therapy (SOrT) metric for a personalised psychiatry.

BACKGROUND: Antidepressant medication (ADM) and psychotherapy are effective treatments for major depressive disorder (MDD). It is unclear, however, if treatments differ in their effectiveness at the symptom level and whether symptom information can be utilised to inform treatment allocation. The present study synthesises comparative effectiveness information from randomised controlled trials (RCTs) of ADM versus psychotherapy for MDD at the symptom level and develops and tests the Symptom-Oriented Therapy (SOrT) metric for precision treatment allocation. METHODS: First, we conducted systematic review and meta-analyses of RCTs comparing ADM and psychotherapy at the individual symptom level. We searched PubMed Medline, PsycINFO, and the Cochrane Central Register of Controlled Trials databases, a database specific for psychotherapy RCTs, and looked for unpublished RCTs. Random-effects meta-analyses were applied on sum-scores and for individual symptoms for the Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) measures. Second, we computed the SOrT metric, which combines meta-analytic effect sizes with patients' symptom profiles. The SOrT metric was evaluated using data from the Munich Antidepressant Response Signature (MARS) study (n = 407) and the Emory Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study (n = 234). RESULTS: The systematic review identified 38 RCTs for qualitative inclusion, 27 and 19 for quantitative inclusion at the sum-score level, and 9 and 4 for quantitative inclusion on individual symptom level for the HAM-D and BDI, respectively. Neither meta-analytic strategy revealed significant differences in the effectiveness of ADM and psychotherapy across the two depression measures. The SOrT metric did not show meaningful associations with other clinical variables in the MARS sample, and there was no indication of utility of the metric for better treatment allocation from PReDICT data. CONCLUSIONS: This registered report showed no differences of ADM and psychotherapy for the treatment of MDD at sum-score and symptom levels. Symptom-based metrics such as the proposed SOrT metric do not inform allocation to these treatments, but predictive value of symptom information requires further testing for other treatment comparisons.

Mortality Among Veterans with Major Mental Illnesses Seen in Primary Care: Results of a National Study of Veteran Deaths.

BACKGROUND: Premature mortality observed among the mentally ill is largely attributable to chronic illnesses. Veterans seen within Veterans Affairs (VA) have a higher prevalence of mental illness than the general population but there is limited investigation into the common causes of death of Veterans with mental illnesses. OBJECTIVE: To characterize the life expectancy of mentally ill Veterans seen in VA primary care, and to determine the most death rates of combinations of mental illnesses. DESIGN: Retrospective cohort study of decedents. SETTING/PARTICIPANTS: Veterans seen in VA primary care clinics between 2000 and 2011 were included. Records from the VA Corporate Data Warehouse (CDW) were merged with death information from the National Death Index. MAIN MEASURES: Mental illnesses were determined using ICD9 codes. Direct standardization methods were used to calculate age-adjusted gender and cause-specific death rates per 1000 deaths for patients with and without depression, anxiety, post-traumatic stress disorder (PTSD), substance use disorder (SUD), serious mental illness (SMI), and combinations of those diagnoses. KEY RESULTS: Of the 1,763,982 death records for Veterans with 1 + primary care visit, 556,489 had at least one mental illness. Heart disease and cancer were the two leading causes of death among Veterans with or without a mental illness, accounting for approximately 1 in 4 deaths. Those with SUD (n = 204,950) had the lowest mean age at time of death (64 ± 12 years). Among men, the death rates were as follows: SUD (55.9/1000); anxiety (49.1/1000); depression (45.1/1000); SMI (40.3/1000); and PTSD (26.2/1000). Among women, death rates were as follows: SUD (55.8/1000); anxiety (36.7/1000); depression (45.1/1000); SMI (32.6/1000); and PTSD (23.1/1000 deaths). Compared to men (10.8/1000) and women (8.7/1000) without a mental illness, these rates were multiple-fold higher in men and in women with a mental illness. A greater number of mental illness diagnoses was associated with higher death rates among men and women (p < 0.0001). CONCLUSIONS: Veterans with mental illnesses, particularly those with SUD, and those with multiple diagnoses, had shorter life expectancy than those without a mental illness. Future studies should examine both patient and systemic sources of disparities in providing chronic illness care to Veterans with a mental illness.

Key Considerations for Incorporating Conversational AI in Psychotherapy.

Conversational artificial intelligence (AI) is changing the way mental health care is delivered. By gathering diagnostic information, facilitating treatment, and reviewing clinician behavior, conversational AI is poised to impact traditional approaches to delivering psychotherapy. While this transition is not disconnected from existing professional services, specific formulations of clinician-AI collaboration and migration paths between forms remain vague. In this viewpoint, we introduce four approaches to AI-human integration in mental health service delivery. To inform future research and policy, these four approaches are addressed through four dimensions of impact: access to care, quality, clinician-patient relationship, and patient self-disclosure and sharing. Although many research questions are yet to be investigated, we view safety, trust, and oversight as crucial first steps. If conversational AI isn't safe it should not be used, and if it isn't trusted, it won't be. In order to assess safety, trust, interfaces, procedures, and system level workflows, oversight and collaboration is needed between AI systems, patients, clinicians, and administrators.

Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder.

A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.

Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD.

OBJECTIVE: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms. METHOD: Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively. RESULTS: Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum. CONCLUSIONS: Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.

PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation.

OBJECTIVE: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment. METHOD: Individuals with PTSD underwent functional MRI (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30). A random subset of the prolonged exposure group (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine whether predictive activation patterns reflect causal influence within circuits. Linear mixed-effects modeling in line with the intent-to-treat principle was used to examine how baseline brain function moderated the effect of treatment on PTSD symptoms. RESULTS: At baseline, individuals with larger treatment-related symptom reductions (compared with the waiting list condition) demonstrated 1) greater dorsal prefrontal activation and 2) less left amygdala activation, both during emotion reactivity; 3) better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex; and 4) greater ventromedial prefrontal/ventral striatal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect. CONCLUSIONS: Capacity to benefit from prolonged exposure in PTSD is gated by the degree to which prefrontal resources are spontaneously engaged when superficially processing threat and adaptively mitigating emotional interference, but not when deliberately reducing negative emotionality.

Side Effects to Antidepressant Treatment in Patients With Depression and Comorbid Panic Disorder.

OBJECTIVE: Side effects to antidepressant medication can affect the efficacy of treatment, but few predictors foretell who experiences side effects and which side effects they experience. This secondary data analysis examined whether depressed patients with comorbid panic disorder were more likely to experience side effects than those without panic disorder. The study also examined whether greater burden of side effects predicted a poorer treatment course for patients with panic disorder than those without panic disorder. To examine the specificity of these effects, analyses also examined 2 other anxiety disorders-social phobia and generalized anxiety disorder (GAD). METHODS: Between 2002 and 2006, a large sample (N = 808) of chronically depressed individuals (assessed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders [SCID-IV]) received antidepressants according to a predetermined algorithm for 12 weeks. Every 2 weeks, depressive symptoms (per the Hamilton Depression Rating Scale) and side effects (specific side effects as well as several indicators of side effect burden) were assessed. RESULTS: Lifetime diagnosis of panic disorder (assessed using the SCID-IV) at baseline was associated with higher likelihood of gastrointestinal (OR = 1.6 [95% CI, 1.0-2.6]), cardiac (OR = 1.8 [95% CI, 1.1-3.1]), neurologic (OR = 2.6 [95% CI, 1.6-4.2]), and genitourinary side effects (OR = 3.0 [95% CI, 1.7-5.3]) during treatment. Increases in side effect frequency, intensity, and impairment over time were more strongly associated with increases in depressive symptoms for patients with panic disorder compared to those without panic disorder. Neither social phobia nor GAD was associated with these effects. CONCLUSIONS: Potentially due to heighte​ned interoceptive awareness of changes in their body, chronically depressed individuals with panic disorder may be at greater risk than those without panic disorder for antidepressant side effects and to experience a worsening of depressive symptoms as a result of these side effects over time. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00057551​.

Convergence in patient-therapist therapeutic alliance ratings and its relation to outcome in chronic depression treatment.

OBJECTIVE: This study tested whether discrepancy between patients' and therapists' ratings of the therapeutic alliance, as well as convergence in their alliance ratings over time, predicted outcome in chronic depression treatment. METHOD: Data derived from a controlled trial of partial or non-responders to open-label pharmacotherapy subsequently randomized to 12 weeks of algorithm-driven pharmacotherapy alone or pharmacotherapy plus psychotherapy. The current study focused on the psychotherapy conditions (N = 357). Dyadic multilevel modeling was used to assess alliance discrepancy and alliance convergence over time as predictors of two depression measures: one pharmacotherapist-rated (Quick Inventory of Depressive Symptoms-Clinician; QIDS-C), the other blind interviewer-rated (Hamilton Rating Scale for Depression; HAMD). RESULTS: Patients' and therapists' alliance ratings became more similar, or convergent, over the course of psychotherapy. Higher alliance convergence was associated with greater reductions in QIDS-C depression across psychotherapy. Alliance convergence was not significantly associated with declines in HAMD depression; however, greater alliance convergence was related to lower HAMD scores at 3-month follow-up. CONCLUSIONS: The results partially support the hypothesis that increasing patient-therapist consensus on alliance quality during psychotherapy may improve treatment and longer term outcomes.

Change in patients' interpersonal impacts as a mediator of the alliance-outcome association in treatment for chronic depression.

OBJECTIVE: Theories posit that chronically depressed individuals have hostile and submissive interpersonal styles that undermine their interpersonal effectiveness and contribute to the cause and maintenance of their depression. Recent findings support this theory and demonstrate that chronically depressed patients' interpersonal impacts on their therapist become more adaptive (i.e., less hostile and submissive, and more friendly and assertive) during a targeted chronic depression treatment: cognitive-behavioral analysis system of psychotherapy (CBASP). In this study, the authors examined whether such changes in interpersonal impacts (as rated by clinicians' experiences of interacting with their patients) mediated the association between early patient-rated alliance quality and final session depression. METHOD: Data derived from a large trial for chronic depression that compared the efficacy of CBASP, nefazodone, and their combination. The current subsample (N = 220) included patients in the CBASP and combined conditions who completed at least 1 depression assessment and the alliance measure, and whose therapists completed at least 1 interpersonal impacts assessment. Mediation models were fit using a bootstrapping procedure for assessing indirect effects. RESULTS: As hypothesized, results supported a mediating effect; higher early alliance predicted decreases in patient hostile-submissiveness during therapy, which in turn related to lower final session depression (indirect effect B = -.02, 95% confidence interval: -.07, -.001). This indirect effect accounted for 13% of the total effect of alliance on depression. There was no moderating effect of treatment condition on the indirect effect. CONCLUSIONS: Results further support CBASP change theory and suggest a candidate mechanism of the alliance's effect on outcome. (PsycINFO Database Record

Depression Subtypes in Predicting Antidepressant Response: A Report From the iSPOT-D Trial.

OBJECTIVE: The study aims were 1) to describe the proportions of individuals who met criteria for melancholic, atypical, and anxious depressive subtypes, as well as subtype combinations, in a large sample of depressed outpatients, and 2) to compare subtype profiles on remission and change in depressive symptoms after acute treatment with one of three antidepressant medications. METHOD: Participants 18-65 years of age (N=1,008) who met criteria for major depressive disorder were randomly assigned to 8 weeks of treatment with escitalopram, sertraline, or extended-release venlafaxine. Participants were classified by subtype. Those who met criteria for no subtype or multiple subtypes were classified separately, resulting in eight mutually exclusive groups. A mixed-effects model using the intent-to-treat sample compared the groups' symptom score trajectories, and logistic regression compared likelihood of remission (defined as a score ≤5 on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report). RESULTS: Thirty-nine percent of participants exhibited a pure-form subtype, 36% met criteria for more than one subtype, and 25% did not meet criteria for any subtype. All subtype groups exhibited a similar significant trajectory of symptom reduction across the trial. Likelihood of remission did not differ significantly between subtype groups, and depression subtype was not a moderator of treatment effect. CONCLUSIONS: There was substantial overlap of the three depressive subtypes, and individuals in all subtype groups responded similarly to the three antidepressants. The consistency of these findings with those of the Sequenced Treatment Alternatives to Relieve Depression trial suggests that subtypes may be of minimal value in antidepressant selection.

Impairment and distress patterns distinguishing the melancholic depression subtype: an iSPOT-D report.

BACKGROUND: This study seeks to provide a comprehensive and systematic evaluation of baseline clinical and psychological features and treatment response characteristics that differentiate Major Depressive Disorder (MDD) outpatients with and without melancholic features. Reflecting the emphasis in DSM-5, we also include impairment and distress. METHODS: Participants were assessed pre-treatment on clinical features (severity, risk factors, comorbid conditions, illness course), psychological profile (personality, emotion regulation), functional capacity (social and occupational function, quality of life) and distress/coping (negativity bias, emotional resilience, social skills, satisfaction with life). Participants were randomized to sertraline, escitalopram or venlafaxine extended-release and re-assessed post-treatment at 8 weeks regarding remission, response, and change in impairment and distress. RESULTS: Patients with melancholic features (n=339; 33.7%) were distinguished clinically from non-melancholics by more severe depressive symptoms and greater exposure to abuse in childhood. Psychologically, melancholic patients were defined by introversion, and a greater use of suppression to regulate negative emotion. Melancholics also had poorer capacity for social and occupational function, and physical and psychological quality of life, along with poorer coping, reflected in less emotional resilience and capacity for social skills. Post-treatment, melancholic patients had lower remission and response, but some of this effect was due to the more severe symptoms pre-treatment. The distress/coping outcome measure of capacity for social skills remained significantly lower for melancholic participants. LIMITATIONS: Due to the cross-sectional nature of this study, causal pathways cannot be concluded. CONCLUSIONS: Findings provide new insights into a melancholic profile of reduced ability to function interpersonally or effectively deal with one׳s emotions. This distinctly poorer capacity for social skills remained post-treatment. The pre-treatment profile may account for some of the difficulty in achieving remission or response with treatment.

Detecting critical decision points in psychotherapy and psychotherapy + medication for chronic depression.

OBJECTIVE: We sought to quantify clinical decision points for identifying depression treatment nonremitters prior to end-of-treatment. METHOD: Data came from the psychotherapy arms of a randomized clinical trial for chronic depression. Participants (n = 352; 65.6% female; 92.3% White; mean age = 44.3 years) received 12 weeks of cognitive behavioral analysis system of psychotherapy (CBASP) or CBASP plus an antidepressant medication. In half of the sample, receiver operating curve analyses were used to identify efficient percentage of symptom reduction cut points on the Inventory of Depressive Symptoms-Self-Report (IDS-SR) for predicting end-of-treatment nonremission based on the Hamilton Rating Scale for Depression (HRSD). Sensitivity, specificity, predictive values, and Cohen's kappa for identified cut points were calculated using the remaining half of the sample. RESULTS: Percentage of IDS-SR symptom reduction at Weeks 6 and 8 predicted end-of-treatment HRSD remission status in both the combined treatment (Week 6 cut point = 50.0%, Cohen's κ = .42; Week 8 cut point = 54.3%, Cohen's κ = .45) and psychotherapy only (Week 6 cut point = 60.7%, Cohen's κ = .41; Week 8 cut point = 48.7%, Cohen's κ = .49). Status at Week 8 was more reliable for identifying nonremitters in psychotherapy-only treatment. CONCLUSIONS: Those with chronic depression who will not remit in structured, time-limited psychotherapy for depression, either with therapy alone or in combination with antidepressant medication, are identifiable prior to end of treatment. Findings provide an operationalized strategy for designing adaptive psychotherapy interventions.

The relationship between the therapeutic alliance and treatment outcome in two distinct psychotherapies for chronic depression.

OBJECTIVE: This study tested whether the quality of the patient-rated working alliance, measured early in treatment, predicted subsequent symptom reduction in chronically depressed patients. Secondarily, the study assessed whether the relationship between early alliance and response to treatment differed between patients receiving cognitive behavioral analysis system of psychotherapy (CBASP) vs. brief supportive psychotherapy (BSP). METHOD: 395 adults (57% female; Mage = 46; 91% Caucasian) who met criteria for chronic depression and did not fully remit during a 12-week algorithm-based, open-label pharmacotherapy trial were randomized to receive either 16-20 sessions of CBASP or BSP in addition to continued, algorithm-based antidepressant medication. Of these, 224 patients completed the Working Alliance Inventory-Short Form at Weeks 2 or 4 of treatment. Blind raters assessed depressive symptoms at 2-week intervals across treatment using the Hamilton Rating Scale for Depression. Linear mixed models tested the association between early alliance and subsequent symptom ratings while accounting for early symptom change. RESULTS: A more positive early working alliance was associated with lower subsequent symptom ratings in both the CBASP and BSP, F(1, 1236) = 62.48, p < .001. In addition, the interaction between alliance and psychotherapy type was significant, such that alliance quality was more strongly associated with symptom ratings among those in the CBASP treatment group, F(1, 1234) = 8.31, p = .004. CONCLUSIONS: The results support the role of the therapeutic alliance as a predictor of outcome across dissimilar treatments for chronic depression. Contrary to expectations, the therapeutic alliance was more strongly related to outcome in CBASP, the more directive of the 2 therapies.

Dysfunctional attitudes as a moderator of pharmacotherapy and psychotherapy for chronic depression.

OBJECTIVE: Individuals with chronic depression exhibit heterogeneous responses to treatment. Important individual differences may therefore exist within this particularly difficult to treat population that act as moderators of treatment response. METHOD: The present study examined whether pretreatment levels of dysfunctional attitudes (DA) moderated treatment response in a large sample of chronically depressed individuals. Data were taken from the Research Evaluating the Value of Augmenting Medication with Psychotherapy (REVAMP) treatment study--a multi-site treatment and augmentation study of 808 chronically depressed individuals. REVAMP comprised two phases: 1) a 12-week open-label antidepressant trial and 2), a subsequent phase, in which phase 1 non-remitters (N = 491) were randomized to either receive an ongoing medication algorithm alone, medication plus cognitive behavioral analysis system of psychotherapy, or medication plus brief supportive psychotherapy. RESULT: In phase 1, compared to the pharmacotherapy response of patients with lower DA scores, the response for patients with higher DA scores was steeper, but leveled off toward the end of the phase. In phase 2, DA predicted a differential response in the medication only arm, but not in the two psychotherapy + medication conditions. Specifically, in the phase 2 medication only condition, patients with higher DA improved while those with lower DA scores did not. CONCLUSION: These results indicate that the relation between DA and treatment response in chronic depression is complex, but suggest that greater DA may be associated with a steeper reduction and/or better response to pharmacotherapy.

Patient treatment preference as a predictor of response and attrition in treatment for chronic depression.

BACKGROUND: Findings regarding the relationship between patient treatment preference and treatment outcome are mixed. This is a secondary data analysis investigating the relationship between treatment preference, and symptom outcome and attrition in a large two-phase depression treatment trial. METHODS: Patients met DSM-IV criteria for chronic forms of depression. Phase I was a 12-week, nonrandomized, open-label trial in which all participants (n = 785) received antidepressant medication(s) (ADM). Phase I nonremitters were randomized to Phase II, in which they received 12 weeks of either cognitive-behavioral system of psychotherapy (CBASP) + ADM (n = 193), brief supportive psychotherapy (BSP) + ADM (n = 187), or ADM only (n = 93). Participants indicated their treatment preference (medication only, combined treatment or no preference) at study entry. Symptoms were measured at 2-week intervals with the 24-item Hamilton Rating Scale for Depression (HAM-D). RESULTS: A large majority of patients reported a preference for combined treatment. Patients who preferred medication only were more likely to endorse a chemical imbalance explanation for depression, whereas those desiring combined treatment were more likely to attribute their depression to stressful experiences. In Phase I, patients who expressed no treatment preference showed greater rates of HAM-D symptom reduction than those with any preference, and patients with a preference for medication showed higher attrition than those preferring combined treatment. In Phase II, baseline treatment preference was not associated with symptom reduction or attrition. CONCLUSIONS: Treatment preferences may moderate treatment response and attrition in unexpected ways. Research identifying factors associated with differing preferences may enable improved treatment retention and response.

The relation between changes in patients' interpersonal impact messages and outcome in treatment for chronic depression.

OBJECTIVE: Interpersonal theories posit that chronically depressed individuals have hostile and submissive styles in their social interactions, which may undermine their interpersonal effectiveness and maintain their depression. Recent findings support this theory and also show that patients' interpersonal impact messages, as perceived by their psychotherapists, change in theoretically predicted ways following cognitive-behavioral analysis system of psychotherapy (CBASP) alone or with medication. This study extended these previous findings by examining whether such changes were associated with their depression change and response status. METHOD: Data derived from a large clinical trial for chronic depression compared the efficacy of CBASP, nefazodone, and their combination. To assess patients' impact messages, CBASP clinicians completed the Impact Message Inventory (IMI; Kiesler & Schmidt, 1993) following an early and late session. Our subsample (N = 259) consisted of patients in the CBASP and combined conditions who had depression severity data for at least 1 post-randomization visit and whose clinicians completed at least 1 IMI rating. We used hierarchical linear modeling (HLM) to calculate IMI change scores and to model depression change. We used HLM and logistic regression to test our predictor questions. RESULTS: As hypothesized, decreases in patients' hostile-submissive impact messages were significantly associated with depression reduction (γ = 0.27, 95% CI [0.11, 0.43], p < .01) and favorable treatment response (B = -0.05, 95% CI [-0.09, -0.01], p = .03), regardless of treatment condition. CONCLUSIONS: The findings support CBASP theory, suggesting that interpersonal change is related to depression reduction among chronically depressed patients.