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Cochrane Central Register of Controlled Trials databases, a database specific for psychotherapy RCTs, and looked for unpublished RCTs.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.

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.

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.

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.

Early adversity in chronic depression: clinical correlates and response to pharmacotherapy.

BACKGROUND: There is growing evidence suggesting that early adversity may be a marker for a distinct pathway to major depressive disorder (MDD). We examined associations between childhood adversity and a broad variety of clinical characteristics and response to pharmacotherapy in a large sample of patients with chronic forms of MDD. METHODS: Subjects included 808 patients with chronic forms of MDD (chronic MDD, double depression, or recurrent MDD with incomplete recovery between episodes and a total continuous duration of >2 years) who were enrolled in a 12-week open-label trial of algorithm-guided pharmacotherapy. Baseline assessments included a semi-structured diagnostic interview, and clinician- and self-rated measures of depressive symptoms, social functioning, depressotypic cognitions, and personality traits, and childhood adversity. Patients were re-evaluated every 2 weeks. RESULTS: A longer duration of illness; earlier onset; greater number of episodes, symptom severity, self-rated functional impairment, suicidality, and comorbid anxiety disorder; and higher levels of dysfunctional attitudes and self-criticism were each associated with multiple forms of childhood adversity. A history of maternal overcontrol, paternal abuse, paternal indifference, sexual abuse, and an index of clinically significant abuse each predicted a lower probability of remission. Among patients completing the 12-week trial, 32% with a history of clinically significant abuse, compared to 44% without such a history, achieved remission. CONCLUSIONS: These findings indicate that a history of childhood adversity is associated with an especially chronic form of MDD that is less responsive to antidepressant pharmacotherapy.

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.

Faster remission of chronic depression with combined psychotherapy and medication than with each therapy alone.

The main aim of the present novel reanalysis of archival data was to compare the time to remission during 12 weeks of treatment of chronic depression following antidepressant medication (n = 218), psychotherapy (n = 216), and their combination (n = 222). Cox regression survival analyses revealed that the combination of medication and psychotherapy produced full remission from chronic depression more rapidly than either of the single modality treatments, which did not differ from each other. Receiver operating characteristic curve analysis was used to explore predictors (treatment group, demographic, clinical, and psychosocial) of remission. For those receiving the combination treatment, the most likely to succeed were those with low baseline depression (24-item Hamilton Rating Scale for Depression [HRSD; M. Hamilton, 1967] score < 26) and those with high depression scores but low anxiety (HRSD = 26 and Hamilton Anxiety Rating Scale [M. Hamilton, 1959] < 14). Both profiles were associated with at least 40% chance of attaining full remission. The model did not identify predictors for those receiving medication or psychotherapy alone, and it did not distinguish between the 2 monotherapies. The authors conclude that combined antidepressant medications and psychotherapy result in faster full remission of chronic forms of major depressive disorder.

Integrative cognitive therapy for depression: A randomized pilot comparison.

This pilot study examined the efficacy of an integrative form of cognitive therapy (ICT) for depression that incorporates specific strategies for addressing alliance ruptures. Although a previous study on depression found that ICT was superior to a wait-list condition (L. G. Castonguay et al., 2004), the current study provides the 1st direct comparison between ICT and traditional cognitive therapy (CT). Twenty-two depressed adults were randomly assigned to ICT or CT (11 patients per condition), which were delivered by clinicians in training. Outcome was assessed with a specific depression measure and a global symptomatology measure. The groups were also compared on patient-perceived alliance quality and therapist empathy. Effect size estimates revealed that ICT patients evidenced greater posttreatment improvement on both outcome measures (with small to medium effects) and more clinically significant change than did CT patients. ICT patients also had higher alliance and empathy scores across treatment (with medium to large effects). The findings, albeit very preliminary, support the potential viability of ICT and the potential causal influence of the rupture-repair interventions on treatment process and outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Interpersonal styles of chronically depressed outpatients: Profiles and therapeutic change.

Theoretical accounts posit that chronically depressed individuals are perceived as hostile and/or submissive, which compromises their ability to satisfy their interpersonal needs. The current study assessed the interpersonal tenets of McCullough's (2000) chronic depression theory and examined change in interpersonal functioning following McCullough's treatment for chronic depression (viz., Cognitive-Behavioral Analysis System of Psychotherapy; CBASP). Data derive from a randomized 12-week clinical trial that compared the efficacy of CBASP, nefazodone, and their combination for chronic depression. To assess patients' interpersonal impacts, CBASP therapists completed the Impact Message Inventory (IMI) following an early and a late session. IMI data were compared to normative and clinical comparison samples to assess depression-related interpersonal profiles and clinically significant change in interpersonal functioning. As predicted, chronically depressed patients were initially perceived as more submissive and hostile than the comparison groups. Patients' interpersonal impacts on their therapists changed in adaptive, theoretically predicted ways by the end of CBASP treatment, either with or without medication. Individual-level clinical significance data were less robust. The findings generally substantiate McCullough's interpersonal theory and provide preliminary evidence of change in interpersonal impacts following treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Dropouts versus completers among chronically depressed outpatients.

BACKGROUND: Premature termination is common among patients treated for depression with either pharmacotherapy or psychotherapy. Yet little is known about factors associated with premature treatment termination among depressed patients. METHODS: This study examines predictors of, time to, and reasons for dropout from the 12-week acute phase treatment of nonpsychotic adult outpatients, age 18-75, with chronic major depression who were randomly assigned to nefazadone alone (MED), cognitive behavioral analysis system of psychotherapy alone (CBASP) or both treatments (COMB). RESULTS: Of 681 randomized study participants, 156 were defined as dropouts. Dropout rates were equivalent across the three treatments. Among dropouts, those in COMB remained in treatment (Mean=40 days) significantly longer than those in either MED (Mean=27 days) or CBASP (Mean=28 days). Dropouts attributed to medication side-effects were significantly lower in COMB than in MED, suggesting that the relationship with the psychotherapist may increase patient willingness to tolerate side-effects associated with antidepressant medications. Ethnic or racial minority status, younger age, lower income, and co-morbid anxiety disorders significantly predicted dropout in the full sample. Within treatments, differences between completers and dropouts in minority status and the prevalence of anxiety disorders were most pronounced in MED. Among those receiving CBASP, dropouts had significantly lower therapeutic alliance scores than completers. LIMITATIONS: The sample included only individuals with chronic depression. CONCLUSIONS: Predictors of dropout included baseline patient characteristics, but not early response to treatment. Ethnic and racial minorities and those with comorbid anxiety are at higher risk of premature termination, particularly in pharmacotherapy, and may require modified treatment strategies.

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​.

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.

Comorbid depression, chronic pain, and disability in primary care.

OBJECTIVES: The objectives of this study were to provide estimates of the prevalence and strength of association between major depression and chronic pain in a primary care population and to examine the clinical burden associated with the two conditions, singly and together. METHODS: A random sample of Kaiser Permanente patients who visited a primary care clinic was mailed a questionnaire assessing major depressive disorder (MDD), chronic pain, pain-related disability, somatic symptom severity, panic disorder, other anxiety, probable alcohol abuse, and health-related quality of life (HRQL). Instruments included the Patient Health Questionnaire, SF-8, and Graded Chronic Pain Questionnaire. A total of 5808 patients responded (54% of those eligible to participate). RESULTS: Among those with MDD, a significantly higher proportion reported chronic (i.e., nondisabling or disabling) pain than those without MDD (66% versus 43%, respectively). Disabling chronic pain was present in 41% of those with MDD versus 10% of those without MDD. Respondents with comorbid depression and disabling chronic pain had significantly poorer HRQL, greater somatic symptom severity, and higher prevalence of panic disorder than other respondents. The prevalence of probable alcohol abuse/dependence was significantly higher among persons with MDD compared with individuals without MDD regardless of pain or disability level. Compared with participants without MDD, the prevalence of other anxiety among those with MDD was more than sixfold greater regardless of pain or disability level. CONCLUSIONS: Chronic pain is common among those with MDD. Comorbid MDD and disabling chronic pain are associated with greater clinical burden than MDD alone.

Chronic depression: medication (nefazodone) or psychotherapy (CBASP) is effective when the other is not.

CONTEXT: Although various strategies are available to manage nonresponders to an initial treatment for depression, no controlled trials address the utility of switching from an antidepressant medication to psychotherapy or vice versa. OBJECTIVE: To compare the responses of chronically depressed nonresponders to 12 weeks of treatment with either nefazodone or cognitive behavioral analysis system of psychotherapy (CBASP) who were crossed over to the alternate treatment (nefazodone, n = 79; CBASP, n = 61). DESIGN: Crossover trial. SETTING: Twelve academic outpatient psychiatric centers. PATIENTS: There were 140 outpatients with chronic major depressive disorder; 92 (65.7%) were female, 126 (90.0%) were white, and the mean age was 43.1 years. Thirty participants dropped out of the study prematurely, 22 in the nefazodone group and 8 in the CBASP group. INTERVENTIONS: Treatment lasted 12 weeks. The dosage of nefazodone was 100 to 600 mg/d; CBASP was provided twice weekly during weeks 1 through 4 and weekly thereafter. MAIN OUTCOME MEASURES: The 24-item Hamilton Rating Scale for Depression, administered by raters blinded to treatment, the Clinician Global Impressions-Severity scale, and the 30-item Inventory for Depressive Symptomatology-Self-Report. RESULTS: Analysis of the intent-to-treat sample revealed that both the switch from nefazodone to CBASP and the switch from from CBASP to nefazodone resulted in clinically and statistically significant improvements in symptoms. Neither the rates of response nor the rates of remission were significantly different when the groups of completers were compared. However, the switch to CBASP following nefazodone therapy was associated with significantly less attrition due to adverse events, which may explain the higher intent-to-treat response rate among those crossed over to CBASP (57% vs 42%). CONCLUSIONS: Among chronically depressed individuals, CBASP appears to be efficacious for nonresponders to nefazodone, and nefazodone appears to be effective for CBASP nonresponders. A switch from an antidepressant medication to psychotherapy or vice versa appears to be useful for nonresponders to the initial treatment.

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