Antidepressants and talk therapy show similar results, but medication leads in severe depression cases

New research published in the journal Clinical Psychology: Science and Practice suggests that while antidepressants and short-term psychodynamic therapy both help alleviate depression, medication might offer a slight advantage for individuals starting with more severe symptoms. The findings provide evidence that both options lead to similar improvements in self-reported mood and anxiety, but antidepressants tend to yield slightly better scores when a professional clinician evaluates the patient. These insights help clarify how different people might respond to common depression treatments and guide more personalized care.

Depression is the leading cause of disability worldwide. Because of its heavy toll on individuals and society, identifying effective and efficient treatments is a top priority for mental health professionals. The two main treatment options are antidepressant medications and various forms of talk therapy.

Medical guidelines often recommend combining medication and therapy for moderate to severe depression. Many patients prefer to use only one method. Some people worry about the side effects of medications or the prospect of taking them for a long period. Others find that attending weekly therapy sessions requires too much time and money.

Because single-treatment approaches are so common, scientists need to understand how different options compare. Short-term psychodynamic psychotherapy is one widely used talk therapy. It typically involves twelve to twenty-four weekly sessions with a trained professional.

During these sessions, a therapist helps the patient explore underlying emotional conflicts and unconscious defense mechanisms. These issues often stem from past negative experiences and relationships. While this therapy is popular and widely taught, its effectiveness compared directly to antidepressant medication is not fully understood.

Free daily newsletter

“There has been a longstanding debate about the efficacy and empirical standing of psychodynamic treatments,” said Frederik J. Wienicke, a Ph.D. candidate in the Department of Clinical Psychology at the Behavioral Science Institute of Radboud University in Nijmegen, the Netherlands.

To explore this issue, Wienicke and his colleagues initiated a broad project to evaluate existing evidence on this specific type of therapy. Previous research comparing depression treatments often relied on standard meta-analyses. A meta-analysis is a statistical technique that combines the summary results of many different studies to find a general trend.

This approach can be problematic because it relies on published averages. Published averages can sometimes overstate the benefits of a treatment or obscure important details about individual patients. Standard meta-analyses also struggle to identify which specific types of patients benefit most from a given treatment.

To solve these problems, the authors of the current study used a method called an individual participant data meta-analysis. Instead of looking at study-wide averages, they gathered the raw, original data for every single person who participated in the earlier trials.

“This means that, rather than relying only on summary statistics reported in published papers, we combine and reanalyze participant-level data from multiple trials,” Wienicke explained. He noted that this approach “can provide more precise estimates and allows us to examine which patients may benefit more from one treatment than another.”

The researchers systematically searched medical databases for clinical trials comparing antidepressants and short-term psychodynamic psychotherapy. They looked for studies involving adults diagnosed with depression who were randomly assigned to receive either medication or therapy.

“At the time of our literature searches, we identified only six trials comparing short-term psychodynamic psychotherapy with antidepressant medication, so the evidence base was smaller than one might expect for such a clinically important question,” Wienicke said.

The systematic search, completed in May 2024, identified a total of 472 participants across those six trials. The scientists then contacted the original researchers to request their raw data. They successfully obtained the individual participant data for four of the trials. This provided a final sample of 310 participants to analyze, representing roughly 66 percent of the total available pool.

The participants in the final analysis had an average age of about 38 years, and approximately 65 percent were women. The medications used in the trials included common antidepressants like fluoxetine, sertraline, and venlafaxine. The therapy groups received between eight and twenty sessions of manual-based short-term psychodynamic psychotherapy.

To measure depression, the trials used standardized rating scales. The primary measure was a clinician-rated scale, where a trained professional interviews the patient to score their symptoms based on a structured rubric. They also looked at self-reported questionnaires, where patients rate their own feelings of depression, anxiety, and general physical health without the input of a clinician.

The researchers found that at the end of the treatment programs, antidepressants were slightly more effective than the psychodynamic therapy at reducing depression symptoms. This specific advantage was seen only on the clinician-rated symptom scales. The effect size, which measures the magnitude of a difference between two groups, was relatively small.

When looking at the questionnaires filled out by the patients themselves, the researchers found no significant differences between the two treatments. Patients in both groups reported similar improvements in their depression, anxiety, and overall physical health. There were also no significant differences between the groups during follow-up assessments conducted months after the treatments ended.

“The main takeaway is that short-term psychodynamic psychotherapy is an efficacious treatment for depression, with outcomes that were largely comparable to antidepressant medication,” Wienicke told PsyPost.

A major goal of the study was to find out if certain traits made one treatment better than the other. The scientists tested several potential moderators, such as gender, age, and education. They found that the severity of a person’s depression before starting treatment played a significant role in their outcome.

For participants with lower levels of initial depression severity, both treatments worked equally well. For participants who started with more severe depression, antidepressants tended to produce larger decreases in symptoms than the psychodynamic therapy.

“The findings themselves were broadly in line with current treatment guidelines,” Wienicke added. “We found indications that antidepressant medication may be preferable to short-term psychodynamic psychotherapy for patients with higher baseline depression severity.”

The researchers suggest that severe depression might make it harder for patients to engage in the deep self-reflection required for psychodynamic therapy. A severely depressed person might lack the energy or emotional tolerance to confront painful past experiences in a short time frame. Medication, by contrast, operates on a biological level and does not require the patient to actively process difficult emotions to begin experiencing relief.

While the study provides detailed insights into depression care, the researchers warn against drawing sweeping conclusions. “The observed difference between antidepressant medication and short-term psychodynamic psychotherapy was statistically significant but small,” Wienicke cautioned. “In practical terms, this should not be interpreted as showing that antidepressants are clearly or generally superior to STPP for all patients.”

Wienicke emphasized that “the small significant difference on observer-rated depressive symptoms should not be overinterpreted.” There are several limitations to keep in mind when evaluating the research. The overall number of participants in the analysis was relatively modest for an individual participant data meta-analysis. A larger sample size might be needed to detect subtle differences in how these treatments work over longer periods, particularly at the follow-up stage.

The diversity of the participants was also limited. The sample primarily consisted of middle-aged women from moderate-income to high-income countries. It is possible that men, individuals from different cultural backgrounds, or people in low-income nations might respond differently to these specific treatments.

The study also relied on older clinical trials, with the most recent data coming from a study conducted more than a decade ago. Psychiatric treatment practices and the specific antidepressant medications prescribed can evolve over time. Some of the original trials also had methodological flaws, such as the evaluating clinicians knowing which treatment the patients were receiving, which could intentionally or unintentionally influence their symptom ratings.

The practical impact of the findings should also be kept in perspective. When the researchers looked at the raw score differences on the clinician-rated depression scales, the advantage for antidepressants was fewer than two points. Many experts argue that a difference of three to eight points is required for a patient to notice a meaningful change in their daily life.

The authors caution against interpreting the findings as a rigid rule for treating severe depression. The connection between initial depression severity and medication success is an observational finding based on past data. It requires validation from new, large-scale clinical trials designed specifically to test this severity relationship.

Future research should continue to explore how different patient characteristics influence treatment success. Identifying these patterns helps advance the field of personalized medicine in mental health care. “The clinically relevant question is not which treatment is best on average, but which treatment is best for which patient,” Wienicke noted.

“We are currently working on a similar project comparing short-term psychodynamic psychotherapy with cognitive behavioral therapy, one of the most commonly used psychotherapies for depression,” Wienicke said of his future plans. “Our team is also working on projects that aim to better predict who is most likely to drop out from treatment, who may relapse after treatment ends, and how clinical prediction models can be used to improve depression treatment selection.”

The study, “Antidepressant Medication or Short-Term Psychodynamic Psychotherapy for Depression? A Systematic Review and Meta-Analysis of Individual Participant Data,” was authored by Frederik J. Wienicke, Jack J. M. Dekker, Jaap Peen, Henricus L. Van, Jacques P. Barber, Kevin S. McCarthy, Nili Solomonov, Hasse Karlsson, Jarmo Hietala, Jaime López-Rodríguez, Valerio Villamil-Salcedo, William J. Burk, Jan Spijker, Jos W. R. Twisk, Zachary D. Cohen, Pim Cuijpers, and Ellen Driessen.