Predicting prognosis for adults with depression using individual symptom data: a comparison of modelling approaches.

BACKGROUND: This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data. METHODS: Individual patient data from all six eligible randomised controlled trials were used to develop (k = 3, n = 1722) and test (k = 3, n = 918) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum scores were developed using coefficient weights derived from network centrality statistics (models 1-3) and factor loadings from a confirmatory factor analysis (model 4). Unweighted sum score models were tested using elastic net regularised (ENR) and ordinary least squares (OLS) regression (models 5 and 6). Individual items were then included in ENR and OLS (models 7 and 8). All models were compared to one another and to a null model (mean post-baseline Beck Depression Inventory Second Edition (BDI-II) score in the training data: model 9). Primary outcome: BDI-II scores at 3-4 months. RESULTS: Models 1-7 all outperformed the null model and model 8. Model performance was very similar across models 1-6, meaning that differential weights applied to the baseline sum scores had little impact. CONCLUSIONS: Any of the modelling techniques (models 1-7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression.

Role of age, gender and marital status in prognosis for adults with depression: An individual patient data meta-analysis.

AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8, and 9-12 months post-baseline and remission at 3-4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/. RESULTS: There was no evidence of an association between age and prognosis before or after adjusting for depressive 'disorder characteristics' that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3-4 months post-baseline per-5-year increase in age = 0(95% CI: -0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3-4 months or 9-12 months post-baseline, but men had worse prognoses at 6-8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6-8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive 'disorder characteristics' and employment status (12.23% (-1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive 'disorder characteristics' and all available confounders. CONCLUSION: Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive 'disorder characteristics' in clinic may be important.

The importance of transdiagnostic symptom level assessment to understanding prognosis for depressed adults: analysis of data from six randomised control trials.

BACKGROUND: Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes. METHOD: Individual patient data from six RCTs of depressed patients (total n = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators. RESULTS: Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms. CONCLUSION: The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.

Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) through non-specialist providers and telemedicine: a study protocol for a non-inferiority randomized controlled trial.

BACKGROUND: Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Task sharing of treatment to non-specialist providers with delivery on telemedicine platforms could address such barriers. However, the equivalence of these strategies to specialist and in-person models remains unproven. METHODS: This study protocol outlines the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) randomized trial. SUMMIT is a pragmatic, non-inferiority test of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a brief, behavioral activation (BA) treatment for perinatal depressive and anxiety symptoms. Specialists (psychologists, psychiatrists, and social workers with ≥ 5 years of therapy experience) and non-specialists (nurses and midwives with no formal training in mental health care) were trained in the BA protocol, with the latter supervised by a BA expert during treatment delivery. Consenting pregnant and postpartum women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 10 (N = 1368) will be randomized to one of four arms (telemedicine specialist, telemedicine non-specialist, in-person specialist, in-person non-specialist), stratified by pregnancy status (antenatal/postnatal) and study site. The primary outcome is participant-reported depressive symptoms (EPDS) at 3 months post-randomization. Secondary outcomes are maternal symptoms of anxiety and trauma symptoms, perceived social support, activation levels and quality of life at 3-, 6-, and 12-month post-randomization, and depressive symptoms at 6- and 12-month post-randomization. Primary analyses are per-protocol and intent-to-treat. The study has successfully continued despite the COVID-19 pandemic, with needed adaptations, including temporary suspension of the in-person arms and ongoing randomization to telemedicine arms. DISCUSSION: The SUMMIT trial is expected to generate evidence on the non-inferiority of BA delivered by a non-specialist provider compared to specialist and telemedicine compared to in-person. If confirmed, results could pave the way to a dramatic increase in access to treatment for perinatal depression and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153864 . Registered on November 6, 2019.

[Cognitive therapy and interpersonal psychotherapy for major depressive disorder: how do they work, how long, and for whom?] / Cognitieve therapie en interpersoonlijke psychotherapie voor depressie: hoe werken ze, hoe lang en voor wie?

BACKGROUND: Although the effectiveness of cognitive therapy (ct) and interpersonal psychotherapy (ipt) for depression has been well established, little is known about how, how long and for whom they work.
AIM: To summarize findings from a large rct to the (differential) effects and mechanisms of change of ct/ipt for depression.
METHOD: 182 adult depressed outpatients were randomized to ct (n = 76), ipt (n = 75), or a two-month wait-list-control condition (n = 31). Primary outcome was depression severity (bdi-ii). Other outcomes were quality of life, social and general psychological functioning and various potential process measures. Interventions were compared at the end of treatment, and up to 17 months follow-up.
RESULTS: Overall, ct and ipt were both superior to the wait-list, but did not differ significantly from one another. However, the pathway through which therapeutic change occurred appeared to be different for ct and ipt, and many patients were predicted to have a clinically meaningful advantage in one of the two interventions. We did not find empirical support for the theoretical models of change.
CONCLUSION: (Long-term) outcomes of ct and ipt appear to not differ significantly. The field would benefit from further refinement of research methods to disentangle mechanisms of change, and from advances in the field of personalized medicine.

Risk factors for relapse and recurrence of depression in adults and how they operate: A four-phase systematic review and meta-synthesis.

PURPOSE: To review and synthesise prognostic indices that predict subsequent risk, prescriptive indices that moderate treatment response, and mechanisms that underlie each with respect to relapse and recurrence of depression in adults. RESULTS AND CONCLUSIONS: Childhood maltreatment, post-treatment residual symptoms, and a history of recurrence emerged as strong prognostic indicators of risk and each could be used prescriptively to indicate who benefits most from continued or prophylactic treatment. Targeting prognostic indices or their "down-stream" consequences will be particularly beneficial because each is either a cause or a consequence of the causal mechanisms underlying risk of recurrence. The cognitive and neural mechanisms that underlie the prognostic indices are likely addressed by the effects of treatments that are moderated by the prescriptive factors. For example, psychosocial interventions that target the consequences of childhood maltreatment, extending pharmacotherapy or adapting psychological therapies to deal with residual symptoms, or using cognitive or mindfulness-based therapies for those with prior histories of recurrence. Future research that focuses on understanding causal pathways that link childhood maltreatment, or cognitive diatheses, to dysfunction in the neocortical and limbic pathways that process affective information and facilitate cognitive control, might result in more enduring effects of treatments for depression.

Prevention of Depression in At-Risk Adolescents: Moderators of Long-term Response.

In a randomized controlled trial, we found that a cognitive behavioral program (CBP) was significantly more effective than usual care (UC) in preventing the onset of depressive episodes, although not everyone benefitted from the CBP intervention. The present paper explored this heterogeneity of response. Participants were 316 adolescents (M age = 14.8, SD = 1.4) at risk for depression due to having had a prior depressive episode or having current subsyndromal depressive symptoms and having a parent with a history of depression. Using a recursive partitioning approach to baseline characteristics, we (Weersing et al. 2016) previously had identified distinct risk clusters within conditions that predicted depressive episodes through the end of the continuation phase (month 9). The present study used the same risk clusters that had been derived in the CBP group through month 9 to reclassify the UC group and then to examine group differences in depression through month 33. We found that in this overall very high-risk sample, the CBP program was superior to UC among youth in the low-risk cluster (n = 33), characterized by higher functioning, lower anxiety, and parents not depressed at baseline, but not in the middle (n = 95) and high-risk (n = 25) clusters. Across conditions, significantly more depression-free days were found for youth in the low-risk cluster (M = 951.9, SD = 138.8) as compared to youth in the high-risk cluster (M = 800.5, SD = 226.7). Identification of moderators, based on purely prognostic indices, allows for more efficient use of resources and suggests possible prevention targets so as to increase the power of the intervention.

Clinical effectiveness of cognitive therapy v. interpersonal psychotherapy for depression: results of a randomized controlled trial.

BACKGROUND: Although both cognitive therapy (CT) and interpersonal psychotherapy (IPT) have been shown to be effective treatments for major depressive disorder (MDD), it is not clear yet whether one therapy outperforms the other with regard to severity and course of the disorder. This study examined the clinical effectiveness of CT v. IPT in a large sample of depressed patients seeking treatment in a Dutch outpatient mental health clinic. We tested whether one of the treatments was superior to the other at post-treatment and at 5 months follow-up. Furthermore, we tested whether active treatment was superior to no treatment. We also assessed whether initial depression severity moderated the effect of time and condition and tested for therapist differences. METHOD: Depressed adults (n = 182) were randomized to either CT (n = 76), IPT (n = 75) or a 2-month waiting list control (WLC) condition (n = 31). Main outcome was depression severity, measured with the Beck Depression Inventory - II (BDI-II), assessed at baseline, 2, 3, and 7 months (treatment phase) and monthly up to 5 months follow-up (8-12 months). RESULTS: No differential effects between CT and IPT were found. Both treatments exceeded response in the WLC condition, and led to considerable improvement in depression severity that was sustained up to 1 year. Baseline depression severity did not moderate the effect of time and condition. CONCLUSIONS: Within our power and time ranges, CT and IPT appeared not to differ in the treatment of depression in the acute phase and beyond.

[The efficacy of psychological treatments for depression: a review of recent research findings]. / De effectiviteit van psychologische behandelingen voor depressie: een overzicht van nieuwe onderzoeksbevindingen.

BACKGROUND: Psychological treatments for depression have been shown to be effective, but there is room for improvement. AIM: To summarise new research findings concerning the efficacy of psychological treatments for depression, as reported in a recent dissertation. METHOD: Four systematic reviews and meta-analyses and one randomised clinical trial are described. RESULTS: As has been shown in the case of patients treated with antidepressants, the efficacy of psychological treatments for depression when compared to strict control conditions, might be greater in patients with more severe depressive symptoms than in patients with milder symptoms. The efficacy of psychological treatments for depression when compared to control conditions is overestimated as a result of systematic publication of positive findings, as has been reported with regard to antidepressant medication too. There is increasing academic support for the efficacy of brief psychodynamic therapy for depression and there are no differences in the efficacy of short-term psychodynamic supportive psychotherapy and cognitive behavioural therapy for depression. Certain patient characteristics were found to be related to the differential efficacy of these two types of psychological treatments, but further validation is needed. A large number of patients with depression who seek help from second-line psychiatric clinics in the Netherlands fail to achieve remission following psychological treatment, irrespective of whether that treatment is combined with antidepressants. CONCLUSION: Improved efficacy of psychological treatments for depression is urgently needed and can be facilitated by means of high quality research.

The methods and outcomes of cultural adaptations of psychological treatments for depressive disorders: a systematic review.

BACKGROUND: Cultural adaptations of evidence-based psychological treatments (PTs) are important to enhance their universal applicability. The aim of this study was to review systematically the literature on adaptations of PTs for depressive disorders for ethnic minorities in Western countries and for any population in non-Western countries to describe the process, extent and nature of the adaptations and the effectiveness of the adapted treatments. METHOD: Controlled trials were identified using database searches, key informants, previous reviews and reference lists. Data on the process and details of the adaptations were analyzed using qualitative methods and meta-analysis was used to assess treatment effectiveness. RESULTS: Twenty studies were included in this review, of which 16 were included in the meta-analysis. The process of adaptation was reported in two-thirds of the studies. Most adaptations were found in the dimensions of language, context and therapist delivering the treatment. The meta-analysis revealed a statistically significant benefit in favor of the adapted treatment [standardized mean difference (SMD) -0.72, 95% confidence interval (CI) -0.94 to -0.49]. CONCLUSIONS: Cultural adaptations of PTs follow a systematic procedure and lead primarily to adaptations in the implementation of the treatments rather than their content. Such PTs are effective in the treatment of depressive disorders in populations other than those for whom they were originally developed.

Is prior course of illness relevant to acute or longer-term outcomes in depressed out-patients? A STAR*D report.

BACKGROUND: Major depressive disorder (MDD) is commonly chronic and/or recurrent. We aimed to determine whether a chronic and/or recurrent course of MDD is associated with acute and longer-term MDD treatment outcomes. METHOD: This cohort study recruited out-patients aged 18-75 years with non-psychotic MDD from 18 primary and 23 psychiatric care clinics across the USA. Participants were grouped as: chronic (index episode >2 years) and recurrent (n = 398); chronic non-recurrent (n=257); non-chronic recurrent (n=1614); and non-chronic non-recurrent (n = 387). Acute treatment was up to 14 weeks of citalopram (≤ 60 mg/day) with up to 12 months of follow-up treatment. The primary outcomes for this report were remission [16-item Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR(16)) ≤ 5] or response (≥ 50% reduction from baseline in QIDS-SR(16)) and time to first relapse [first QIDS-SR16 by Interactive Voice Response (IVR) ≥ 11]. RESULTS: Most participants (85%) had a chronic and/or recurrent course; 15% had both. Chronic index episode was associated with greater sociodemographic disadvantage. Recurrent course was associated with earlier age of onset and greater family histories of depression and substance abuse. Remission rates were lowest and slowest for those with chronic index episodes. For participants in remission entering follow-up, relapse was most likely for the chronic and recurrent group, and least likely for the non-chronic, non-recurrent group. For participants not in remission when entering follow-up, prior course was unrelated to relapse. CONCLUSIONS: Recurrent MDD is the norm for out-patients, of whom 15% also have a chronic index episode. Chronic and recurrent course of MDD may be useful in predicting acute and long-term MDD treatment outcomes.

The effects of psychotherapy for adult depression are overestimated: a meta-analysis of study quality and effect size.

BACKGROUND: No meta-analytical study has examined whether the quality of the studies examining psychotherapy for adult depression is associated with the effect sizes found. This study assesses this association. METHOD: We used a database of 115 randomized controlled trials in which 178 psychotherapies for adult depression were compared to a control condition. Eight quality criteria were assessed by two independent coders: participants met diagnostic criteria for a depressive disorder, a treatment manual was used, the therapists were trained, treatment integrity was checked, intention-to-treat analyses were used, N >or= 50, randomization was conducted by an independent party, and assessors of outcome were blinded. RESULTS: Only 11 studies (16 comparisons) met the eight quality criteria. The standardized mean effect size found for the high-quality studies (d=0.22) was significantly smaller than in the other studies (d=0.74, p<0.001), even after restricting the sample to the subset of other studies that used the kind of care-as-usual or non-specific controls that tended to be used in the high-quality studies. Heterogeneity was zero in the group of high-quality studies. The numbers needed to be treated in the high-quality studies was 8, while it was 2 in the lower-quality studies. CONCLUSIONS: We found strong evidence that the effects of psychotherapy for adult depression have been overestimated in meta-analytical studies. Although the effects of psychotherapy are significant, they are much smaller than was assumed until now, even after controlling for the type of control condition used.

The contribution of active medication to combined treatments of psychotherapy and pharmacotherapy for adult depression: a meta-analysis.

OBJECTIVE: Although there is sufficient evidence that combined treatments of psychotherapy and pharmacotherapy are more effective for depression in adults than each of the treatments alone, it remains unclear what the exact contribution of active medication is to the overall effects of combined treatments. This paper examines the contribution of active medication to combined psychotherapy and pharmacotherapy treatments. METHOD: Meta-analysis of randomised controlled trials comparing the combination of psychotherapy and pharmacotherapy with the combination of psychotherapy and placebo. RESULTS: Sixteen identified studies involving 852 patients met our inclusion criteria. The standardised mean difference indicating the differences between the combination of psychotherapy and pharmacotherapy and the combination of psychotherapy and placebo was 0.25 (95% CI: 0.03-0.46), which corresponds to a numbers-needed-to-be-treated of 7.14. No significant differences between subgroups of studies were found. CONCLUSION: Active medication has a small but significant contribution to the overall efficacy of combined treatments.

Can pharmacotherapists be too supportive? A process study of active medication and placebo in the treatment of depression.

BACKGROUND: This study examined therapist-patient interactions during clinical management with antidepressant medication and pill-placebo. METHOD: The sample consisted of 80 patients on active medication and 40 patients in a pill-placebo condition from a randomized controlled trial for moderate to severe depression. Pharmacotherapist-patient interactions were characterized using observer ratings of the therapeutic alliance, pharmacotherapist-offered facilitative conditions, pharmacotherapist adherence to clinical management treatment guidelines and pharmacotherapist competence. Patients, therapists and raters were blind to treatment condition and outcome. RESULTS: Provision of greater non-specific support (facilitative conditions) in early sessions predicted less subsequent improvement in depressive symptoms for patients receiving pill-placebo but not those receiving active medications, for which none of the process ratings predicted subsequent change. Early symptom change predicted later alliance and adherence in both conditions and therapist competence in the active condition. CONCLUSIONS: Higher levels of support in early sessions predict poorer subsequent response among placebo patients. It remains unclear whether patients who are likely to be refractory elicit greater non-specific support or whether the provision of such support has a deleterious effect in unmedicated patients. Differences in treatment process variables between conditions late in treatment are likely to be largely a consequence of symptom relief produced by active medications.

Mind the gap: Improving the dissemination of CBT.

Empirically supported psychological treatments have been developed for a range of psychiatric disorders but there is evidence that patients are not receiving them in routine clinical care. Furthermore, even when patients do receive these treatments there is evidence that they are often not well delivered. The aim of this paper is to identify the barriers to the dissemination of evidence-based psychological treatments and then propose ways of overcoming them, hence potentially bridging the gap between research findings and clinical practice.

Empirically supported psychological interventions for social phobia in adults: a qualitative review of randomized controlled trials.

BACKGROUND: Social phobia is a chronic disorder that results in substantial impairment. We conducted a qualitative review of randomized controlled trials (RCTs) of psychological interventions for social phobia. METHOD: Articles were identified through searches of electronic databases and manual searches of reference lists. They were classified by psychological interventions evaluated. Data regarding treatment, participants and results were then extracted and tabulated. We identified which psychological interventions are empirically supported, using the scheme proposed by Chambless & Hollon (Journal of Consulting and Clinical Psychology 1998, 66, 7-18). RESULTS: Thirty studies evaluating the efficacy of social skills training (SST), exposure therapy and/or cognitive treatments were identified. Cognitive behavior therapy (CBT), involving cognitive restructuring and exposure to feared and avoided social situations or behavioral experiments, was found to be an efficacious and specific treatment for social phobia. Exposure therapy was found to be an efficacious treatment since most of the evidence of its efficacy was from comparisons with no treatment. There were mixed findings regarding the relative efficacy of CBT and in vivo exposure. Some studies reported that the interventions were equivalent, while others found that patients treated with CBT had a better outcome. There was little evidence to support the use of SST. CONCLUSIONS: CBT is the psychological intervention of choice for social phobia. The findings of this review are compared to those of other major reviews and limitations are discussed.

Defining empirically supported therapies.

A scheme is proposed for determining when a psychological treatment for a specific problem or disorder may be considered to be established in efficacy or to be possibly efficacious. The importance of independent replication before a treatment is established in efficacy is emphasized, and a number of factors are elaborated that should be weighed in evaluating whether studies supporting a treatment's efficacy are sound. It is suggested that, in evaluating the benefits of a given treatment, the greatest weight should be given to efficacy trials but that these trials should be followed by research on effectiveness in clinical settings and with various populations and by cost-effectiveness research.

The efficacy and effectiveness of psychotherapy relative to medications.

A recent survey by Consumer Reports (1994) found that people who received psychotherapy were generally pleased with their experience and that their satisfaction was unrelated to the type of treatment or the addition of medications. M.E.P. Seligman (1995) argued that these findings demonstrate the value of psychotherapy and suggested that such survey methodologies may be superior to randomized clinical trials in this regard because they study what occurs in actual clinical practice. Although such approaches provide important information, they are no substitute for controlled clinical trials when it comes to drawing causal inferences. However, the study does highlight the importance of defining outcome in the broadest possible fashion and of addressing the external validity of the findings obtained. Attention to such considerations has implications for the relative value of drugs and psychotherapy.

Cognitive-behavior therapy versus pharmacotherapy: Now that the jury's returned its verdict, it's time to present the rest of the evidence.

Recent reanalyses suggest that pharmacotherapy was superior to cognitive-behavior therapy in the acute treatment of more severely depressed outpatients in the National Institute of Mental Health Treatment of Depression Collaborative Research Program (TDCRP). At the same time, this finding was neither robust across sites within the TDCRP nor consistent with findings from other studies. D.F. Klein has argued that those other studies were inherently flawed because they did not include pill-placebo controls, an argument that he extended to drug-psychotherapy comparisons in the treatment of panic as well. It is agreed that the inclusion of such controls would have facilitated the interpretation of the findings, but it is not agreed that their omission rendered those studies uninterpretable. Cognitive-behavior therapy remains a viable alternative to pharmacotherapy in the treatment of depression and a particularly promising intervention in the treatment of panic disorder.