A large review of research found that talk therapy works about as well as antidepressant medications for treating depression.
The study also looked at other non-drug options, like exercise.
While benefits were similar across treatments, side effects differed.
Key Facts:
- Cognitive behavioral therapy (CBT) achieved comparable results to medications for treating major depression. Remission rates were 41% for CBT versus 44% for antidepressants in one analysis.
- Combining CBT and antidepressants did not lead to better outcomes than antidepressants alone after 12 weeks of treatment.
- Discontinuation due to side effects was lower for talk therapies than medications. For CBT it was 0.8% versus 6.2% for antidepressants.
- Various combinations of medications worked similarly for patients who did not improve with an initial antidepressant. Augmenting with talk therapy or a second medication provided comparable results.
Source: Ann Intern Med. 2023
What is Major Depressive Disorder (MDD)?
Major depressive disorder (MDD) is the medical term for significant, ongoing depression.
It affects over 20% of US adults at some point in their lives. MDD causes substantial disability and suffering for those impacted. Most people receive care for MDD from their primary care provider.
Treatment often begins with antidepressant medications, like selective serotonin reuptake inhibitors (SSRIs).
While medications can help, over 60% of patients experience side effects.
Up to 70% also do not achieve remission after the first medication tried.
When this occurs, next treatment steps include switching medications or adding a second medication or psychological therapy.
Comparing Antidepressant Medications vs. Non-Drug Treatments (2023)
A large review aimed to compare benefits and side effects of medications versus non-drug options for treating MDD.
The focus was on results from gold-standard randomized controlled trials.
For initial treatment the review asked, “How do common antidepressants compare to talk therapy, complementary approaches, exercise, and combination therapy?”
For patients unresponsive to first-step care, the question was, “Which next treatment strategies help?”
Database searches yielded over 11,000 research articles on MDD care.
The 65 most relevant trials with over 13,000 total participants were analyzed.
Results for key outcomes like remission rates, side effects, and study limitations were closely examined.
Talk Therapy (CBT) & Medications = Similar Efficacy
The highest-quality data showed similar efficacy for cognitive behavioral therapy (CBT) versus second-generation antidepressants.
These include SSRIs like sertraline (Zoloft) and SNRIs like duloxetine (Cymbalta).
Findings remained stable even when including weaker studies with a high risk of bias.
Meta-analyses found no differences based on 33 trials with over 5000 participants. Remission rates were 41% for CBT versus 44% for medications.
Response rates were also equivalent. Discontinuation due to side effects favored CBT at 0.8% versus 6.2% for medications.
Data for other talk therapies was limited but suggested comparable results to medications. These include psychodynamic approaches.
Combination Therapy (CBT & Meds)
Two analyses showed no extra improvement from combining CBT with medications versus medications alone.
Remission rates (42% vs 44%) and side effects were similar after 12 weeks of treatment.
Findings were based on 3 trials with over 500 total patients. Further research is still needed in this area.
Herbal Supplements for MDD in Adults
Analyses found the herbal therapy St. John’s wort lead to equivalent improvements compared to antidepressants medications.
However, in most studies the antidepressant doses were less than typical clinical practice.
Additional research is warranted using optimal medication dosing.
Acupuncture: Mixed Data on Efficacy
Results were inconsistent for acupuncture versus medications based on 9 trials and over 1200 patients.
Network meta-analyses suggested similar response rates between groups.
But 3 studies showed higher remission for combined acupuncture + medications than medications alone.
Further data is required to draw conclusions.
Exercise: Limited Evidence in Depression
Only 3 trials examined exercise versus antidepressants, with inconsistent findings reported on efficacy.
Two analyses suggested lower side effects for exercise.
Sample sizes were small, with just over 400 patients included across all exercise studies.
More research is urgently needed given the promise of this low-risk option.
Read: “Running Therapy vs. Antidepressants” & “Exercise as the Best Natural Antidepressant?”
Evaluating Benefits vs. Harms: Challenging Due to Study Limitations
Comparing benefits and harms between treatments was often impossible due to missing data on side effects.
Concerns were noted around short trial lengths, small sample sizes, high drop-out rates, and lack of participant blinding.
Over one-third of the reviewed studies were considered “high risk of bias.” Results should be interpreted very cautiously as a result.
Switching or Augmenting Medications: All Strategies Equally Effective
When patients don’t respond to an initial antidepressant, switching to or adding another medication works about the same based on 5 trials with over 2500 patients.
Specific medications examined were bupropion, buspirone, aripiprazole, escitalopram, mirtazapine, sertraline, venlafaxine, and vortioxetine.
Discontinuation due to side effects ranged widely, from 0-21% across medication regimens.
Adding Talk Therapy: Comparable to Medication Changes
Only 1 trial (with over 400 participants) compared switching medications to adding talk therapy (CBT).
It found no differences in efficacy between these two strategies.
Remission rates were 25% for medications versus 28% for CBT added to the initial medication.
Discontinuation due to side effects was numerically lower for talk therapy than medication changes (9% vs 19%).
Combining Treatments May Offer Small Benefits
Results from 2 trials suggested small improvements in efficacy when combining medications like adding mirtazapine to sertraline or paroxetine.
However, this was compared to switching medications completely.
Findings may indicate overall benefits of continuing initial medications, rather than superiority of combination therapy.
Larger trials are needed comparing augmentation to medication switching head-to-head while maintaining similar dosing levels.
Takeaway: Talk Therapy & Medications Work Well for Depression
In patients with major depression, talk therapy and medications offered similar improvements in a large review of over 60 clinical trials.
Benefits also seemed comparable among exercise, herbs, acupuncture, and combination therapy—though available data was limited.
Meanwhile, side effects and treatment discontinuation consistently favored non-drug options.
Findings underscore the range of evidence-based choices for managing this widespread mental health condition.
Shared decision-making around individual risk factors, prior treatment responses, and personal preferences is warranted.
For patients not responding to initial antidepressant medications, switching to or adding a new medication or talk therapy provided analogous results.
Risks still outweighed benefits for medication regimens.
Future research should continue illuminating comparative outcomes between specific therapies while addressing limitations around biases, trial reporting, and patient diversity.
As the evidence evolves, maintaining an open dialogue around treatment goals and quality of life will serve both clinicians and those suffering with depression.
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