A psychotherapy designed to boost positive emotions outperformed a standard approach focused on reducing negative feelings in patients with depression and anxiety.

Results of the randomized clinical trial showed the positive affect treatment (PAT), which targets reward processing, led to small but statistically significant improvements in overall clinical outcomes compared with negative affect treatment (NAT), which is driven primarily by reductions in depression and anxiety symptoms.

Although the effect size was modest, experts say the findings are notable because they support a shift toward targeting reward processes — an area not well addressed by current treatments and closely linked to poor outcomes in depression.

“We were really thrilled with the results,” study investigator Alicia E. Meuret, PhD, professor, Clinical Psychology Division, Department of Psychology, Southern Methodist University, Dallas, told Medscape Medical News.

“PAT is the first and only intervention that has consistently shown that targeting positive affect or anhedonia yields clinically superior improvements.”

The findings were published online on April 24 in JAMA Network Open.

A Novel Approach

Anhedonia — the reduced ability to experience pleasure — is a core feature of major depressive disorder and is associated with suicidal behaviors and poorer treatment response. It is driven by disruptions in reward processing, which involves three key phases, namely, anticipation, attainment, and learning, regulated by the mesocorticolimbic circuit.

Conventional treatments have largely focused on reducing negative emotions but have shown limited effectiveness in addressing anhedonia, contributing to an increased risk for relapse.

PAT is a novel psychosocial intervention that targets deficits in reward processing believed to underpin anhedonia and diminished positive affect.

Results of two previous randomized clinical trials showed that PAT produced greater improvements in clinical status — a composite of low positive affect, depression, anxiety, and interviewer-rated anhedonia — and greater engagement of reward-related target processes than NAT.

The investigators sought to replicate prior findings and test whether changes in reward and threat processing mediate clinical improvement, consistent with an experimental therapeutics approach.

They also examined whether PAT could modify these mechanisms and translate into improvements in low positive affect, anhedonia, depression, and anxiety.

The study included 98 adults with low positive affect — defined as a score of 24 or lower on the 10-item Positive Affect subscale of the Positive and Negative Affect Schedule (PANAS-P) as well as moderate-to-severe depression or anxiety, based on the 21-item Depression, Anxiety, and Stress Scales (DASS-21), and clinically significant functional impairment. Participants’ mean age was 32.8 years, 66.3% were female, and 61.2% were White.

Researchers excluded individuals who were taking medications that might influence reward response, such as dopaminergic drugs.

Participants were randomly assigned to receive individual 1-hour sessions of PAT or NAT every week for 15 weeks. All sessions were delivered via telehealth.

Positive, Pleasurable Activities

The PAT program focuses on enhancing reward processing by encouraging patients to plan and engage in pleasurable activities, envision positive future experiences, and use cognitive strategies to shift attention toward positive aspects of their lives. It also incorporates structured practices to cultivate positive emotions.

In contrast, NAT targets the reduction of distress, anxiety, and threat sensitivity. Sessions include gradual exposure to feared or avoided situations, cognitive restructuring of negative thought patterns, and techniques to reduce physiologic arousal.

“We really tried, as best we could, to create two mechanistically distinct treatments: one aimed at increasing positive experiences and one aimed at decreasing negative affect,” said Meuret.

The main outcome was a multivariate index of clinical status comprising positive affect, anhedonia, depression, and anxiety symptoms. Positive affect was measured using the PANAS-P, whereas anxious and depressive symptoms were assessed using the total score of the DASS-21. Anhedonia was rated during assessor-blinded interviews.

The researchers also used multimodal measures to assess reward anticipation-motivation, response to reward attainment, reward learning, and threat processes.

Results showed that clinical status improved more with PAT than with NAT (b = -0.06; 95% CI, -0.11 to -0.01; P = .02; d = 0.27). PAT was also associated with higher clinical status scores at the 1-month follow-up than NAT (b = -0.21; 95% CI, -0.41 to -0.02; P = .04; d = 0.21).

PAT was also associated with significantly greater improvements than NAT on the DASS-21, although changes in interviewer-rated anhedonia and self-reported positive affect (PANAS-P) did not differ between the two treatments.

Improvements in reward anticipation-motivation and reward attainment were comparable between the two therapies. Of seven self-reported reward and threat measures, six mediated improvements in clinical status, whereas none of the behavioral or physiologic measures did.

“Our mechanistic analysis supports the crucial role of targeting reward systems in obtaining therapeutic change in patients with severe anhedonia and depression and anxiety,” said Meuret.

The findings underline the importance of mental health care providers “going beyond just reducing distress” to “help patients rebuild positive emotions,” she added. “Recovery is not only about removing negative feelings but also about helping people reconnect with purpose, meaning, and rewarding experiences — and PAT does both.”

Meuret and colleagues are now analyzing the study data to determine characteristics that might predict which patients are most likely to benefit from PAT.

“Just like in other areas of medicine, the idea is that using patient profiles will tell us who is going to respond best to a certain treatment,” she said.

Experts See Promise, Urge Caution

Echoing this shift toward more tailored approaches, an accompanying editorial highlighted the broader significance of the findings.

In an accompanying editorial, Charles T. Taylor, PhD, Department of Psychiatry, University of California, San Diego, said the study “represents an emerging paradigm shift in the conceptualization and treatment of anxiety and depressive disorders.”

Taylor described the study as a rigorous replication that reinforces the value of targeting reward processes in treating anxiety and depression.

“As the field moves beyond approaches focused primarily on the reduction of negative affect to those that also prioritize the restoration of positive affect and related outcomes (eg, social connectedness or well-being), interventions that explicitly address deficits in reward processing represent a promising direction.”

Adding to this perspective, another expert pointed to the broader clinical implications of the findings. Gregory Scott Brown, MD, of the Tilman J. Fertitta Family College of Medicine at the University of Houston in Houston, said the findings point to “an exciting area of clinical research,” particularly given the limited treatment options for patients with depression and anhedonia.

Brown said PAT represents a different approach that could shift how clinicians understand and treat anxiety and depressive disorders. However, he cautioned that this enthusiasm should be tempered to ensure enthusiasm doesn’t outpace the science.

He pointed out that the study has several limitations, including unmeasured third variables, dynamic shifts over time, possible experience sampling, and memory bias.

“I’m looking forward to future PAT studies with larger sample sizes that may address some of these limitations,” he said.

The study received support from the National Institute of Mental Health. Disclosure information for study authors and commentator is available in the original study publication. Brown reported no relevant conflict of interest.