Unpacking the heterogeneity in treatment effects as a path to personalized psychotherapies: Are we there yet?

Solomonov, Nili; Barber, Jacques P.

doi:10.1037/cps0000101

Cited by 5 publications

(3 citation statements)

References 9 publications

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“…Patients in the modular treatment arm were nearly three times as likely to show post-treatment remission (29.4% vs. 11.4%, OR=3.2). This finding provides a preliminary support to the usefulness of a modular mechanism-based approach aimed to personalize psychotherapy 9,45 , in order to address the substantial interindividual heterogeneity in treatment effects among depressed patients [46][47][48][49][50][51][52] .…”

Section: Discussionmentioning

confidence: 71%

Algorithm‐based modular psychotherapy vs. cognitive‐behavioral therapy for patients with depression, psychiatric comorbidities and early trauma: a proof‐of‐concept randomized controlled trial

Schramm,

Elsaesser,

Jenkner

et al. 2024

World Psychiatry

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Effect sizes of psychotherapies currently stagnate at a low‐to‐moderate level. Personalizing psychotherapy by algorithm‐based modular procedures promises improved outcomes, greater flexibility, and a better fit between research and practice. However, evidence for the feasibility and efficacy of modular‐based psychotherapy, using a personalized treatment algorithm, is lacking. This proof‐of‐concept randomized controlled trial was conducted in 70 adult outpatients with a primary DSM‐5 diagnosis of major depressive disorder, a score higher than 18 on the 24‐item Hamilton Rating Scale for Depression (HRSD‐24), at least one comorbid psychiatric diagnosis according to the Structured Clinical Interview for DSM‐5 (SCID‐5), a history of at least “moderate to severe” childhood maltreatment on at least one domain of the Childhood Trauma Questionnaire (CTQ), and exceeding the cut‐off value on at least one of three measures of early trauma‐related transdiagnostic mechanisms: the Rejection Sensitivity Questionnaire (RSQ), the Interpersonal Reactivity Index (IRI), and the Difficulties in Emotion Regulation Scale‐16 (DERS‐16). Patients were randomized to 20 sessions of either standard cognitive‐behavioral therapy alone (CBT) or CBT plus transdiagnostic modules according to a mechanism‐based treatment algorithm (MoBa), over 16 weeks. We aimed to assess the feasibility of MoBa, and to compare MoBa vs. CBT with respect to participants’ and therapists’ overall satisfaction and ratings of therapeutic alliance (using the Working Alliance Inventory ‐ Short Revised, WAI‐SR), efficacy, impact on early trauma‐related transdiagnostic mechanisms, and safety. The primary outcome for efficacy was the HRSD‐24 score at post‐treatment. Secondary outcomes included, among others, the rate of response (defined as a reduction of the HRSD‐24 score by at least 50% from baseline and a score <16 at post‐treatment), the rate of remission (defined as a HRSD‐24 score ≤8 at post‐treatment), and improvements in early trauma‐related mechanisms of social threat response, hyperarousal, and social processes/empathy. We found no difficulties in the selection of the transdiagnostic modules in the individual patients, applying the above‐mentioned cut‐offs, and in the implementation of MoBa. Both participants and therapists reported higher overall satisfaction and had higher WAI‐SR ratings with MoBa than CBT. Both approaches led to major reductions of depressive symptoms at post‐treatment, with a non‐significant superiority of MoBa over CBT. Patients randomized to MoBa were nearly three times as likely to experience remission at the end of therapy (29.4% vs. 11.4%; odds ratio, OR = 3.2, 95% CI: 0.9‐11.6). Among mechanism‐based outcomes, MoBa patients showed a significantly higher post‐treatment effect on social processes/empathy (p<0.05) compared to CBT patients, who presented an exacerbation on this domain at post‐treatment. Substantially less adverse events were reported for MoBa compared to CBT. These results suggest the feasibility and acceptability of an algorithm‐based modular psychotherapy complementing CBT in depressed patients with psychiatric comorbidities and early trauma. While initial evidence of efficacy was observed, potential clinical advantages and interindividual heterogeneity in treatment outcomes will have to be investigated in fully powered confirmation trials.

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Section: Discussionmentioning

confidence: 71%

Algorithm‐based modular psychotherapy vs. cognitive‐behavioral therapy for patients with depression, psychiatric comorbidities and early trauma: a proof‐of‐concept randomized controlled trial

Schramm,

Elsaesser,

Jenkner

et al. 2024

World Psychiatry

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“…Instead, mostly average group-level treatment effects of repeated cross-sectional measures with low temporal resolution are investigated based on the doubtful assumption that patients with shared diagnoses represent homogeneous populations. However, there is substantial heterogeneity between patients with depression regarding their individual symptom profiles [5] and the variability of treatment effects [6, 7], resulting in an overestimated group-to-individual generalizability [8, 9]. To provide effective personalized treatments, investigations of these individual differences and characteristics of patients are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Clusters of Long-Term Trajectories in Patients with Early-Onset Chronic Depression: 2 Years of Naturalistic Follow-Up after Extensive Psychological Treatment

Elsaesser,

Feige,

Kriston

et al. 2023

Psychother Psychosom

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Introduction: In clinical trials, mostly group-level treatment effects of repeated cross-sectional measures are analyzed. However, substantial heterogeneity regarding individual symptom profiles and the variability of treatment effects are often neglected, especially over the long-term course. To provide effective personalized treatments, investigations of these characteristics are urgently needed. Methods: Depression severity ratings over 104 weeks of follow-up after year-long treatment with the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or Supportive Psychotherapy (SP) were analyzed. Longitudinal cluster analysis and multinomial logistic regression analysis were conducted to investigate intraindividual trajectories from one of the largest psychotherapy trials in early-onset chronic depression. Results: Two-year post-study-treatment trajectories of N = 188 patients with early-onset chronic depression were grouped into four prototypical clusters. Overall, 16.0% of patients remitted (cluster 1) and most of them did not receive any treatment during the 2-year follow-up. However, 84.0% of patients continued to experience subthreshold (37.2% cluster 2) or major depressive symptoms (46.8% clusters 3–4) and spent on average more than half of the follow-up in pharmacological and psychological treatment. Hierarchical regression analysis indicated that previous study treatment with CBASP or SP did not significantly predict cluster allocation, while baseline variables accounted for a large proportion of explained variance (R2 N = 0.64). Conclusion: While some patients experienced stable remission over 2 years of follow-up, the majority of patients experienced subthreshold or major depressive symptoms regardless of former study treatment with CBASP or SP. This calls for a long-term perspective implementing staging and innovative treatment approaches such as the sequential model or modular psychotherapy.

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“…Instead, mostly average group-level treatment effects of repeated cross-sectional measures with low temporal resolution are investigated, based on the doubtful assumption that patients with shared diagnoses represent homogeneous populations. However, there is substantial heterogeneity between patients with depression regarding their individual symptom profiles (5) and the variability of treatment effects (6,7), resulting in an overestimated group-to-individual generalizability (8,9). To provide effective personalized treatments, investigations of these individual differences and characteristics of patients are needed.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal clusters of long-term trajectories in patients with early-onset chronic depression: Two years of naturalistic follow-up after extensive psychological treatment

Elsaeßer¹,

Feige²,

Kriston³

et al. 2023

Preprint

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Introduction: In randomized trials, mostly group-level treatment effects of repeated cross-sectional measures are analyzed. However, substantial heterogeneity regarding individual symptom profiles and variability of treatment effects are often neglected, particularly over the long-term course.Objective: Ratings of depression severity over 104 weeks of follow-up after yearlong acute and continuation treatment with the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or Supportive Psychotherapy (SP) were investigated to cluster intraindividual trajectories and identify risk and protective factors. Methods: Longitudinal cluster analysis and multinomial logistic regression analysis were conducted to group intraindividual long-term trajectories from one of the largest psychotherapy trials in early-onset chronic depression.Results: Two-year post-treatment trajectories of N=176 patients with early-onset chronic depression were clustered into four groups. Only 16.5% of patients remitted (Cluster 1), while the majority continued to experience subthreshold (35.8% Cluster 2) or major depressive symptoms (47.7% Cluster 3-4). Patients previously treated with the CBASP had a 45% lower risk of experiencing major depressive symptoms (Cluster 3) than patients in the SP group (RR=0.55, 95% CI=0.31 to 0.97, p=.03). Further treatment in the health care system during follow-up, especially psychological outpatient treatment, reduced depression severity. Comorbid disorders or childhood emotional/physical abuse had detrimental effects.Conclusion: Despite significant effects in favor of acute treatment with CBASP compared to SP, the majority of patients experienced subthreshold or major depressive symptoms over two years of follow-up. This calls for a long-term perspective with innovative treatment approaches such as the sequential model or modular psychotherapy.

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Unpacking the heterogeneity in treatment effects as a path to personalized psychotherapies: Are we there yet?

Cited by 5 publications

References 9 publications

Algorithm‐based modular psychotherapy vs. cognitive‐behavioral therapy for patients with depression, psychiatric comorbidities and early trauma: a proof‐of‐concept randomized controlled trial

Algorithm‐based modular psychotherapy vs. cognitive‐behavioral therapy for patients with depression, psychiatric comorbidities and early trauma: a proof‐of‐concept randomized controlled trial

Longitudinal Clusters of Long-Term Trajectories in Patients with Early-Onset Chronic Depression: 2 Years of Naturalistic Follow-Up after Extensive Psychological Treatment

Longitudinal clusters of long-term trajectories in patients with early-onset chronic depression: Two years of naturalistic follow-up after extensive psychological treatment

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