Combined drug and psychological therapies may be most effective for depression

The most effective treatment for adults with moderate depression is likely to be a combination of antidepressant drugs and psychological interventions. A new summary provides the strongest evidence to date that the combination of treatments work better than either alone.

The most recent advice from National Institute for Health and Care Excellence (NICE) comes in a clinical knowledge summary (March 2020). It suggests low-intensity psychosocial interventions such as self-help, computerised cognitive behavioural therapy (CBT), or group exercise programmes for mild to moderate depression. Routine use of antidepressants is not suggested for this group. The combination of drug and high intensity psychological therapy is reserved for those with severe depression. 

Routine use of combination treatment will require increased access to psychological therapies, including computerised and group CBT as well as individual treatment.

What’s the issue?

There is clear evidence that drug-based and psychological therapies are effective treatments for depression. How these therapies compare with each other, alone or in combination, is less clear. Previous studies suggested the combination might be more effective than either alone but were not conclusive. 

Combination treatment is likely to be more expensive to deliver than a single treatment. Psychological therapies are more expensive than drug treatments. Commissioners need good evidence if they are to fund psychological therapies and combination treatment. This study was designed to give more precise estimates of how effective each treatment is, to allow treatments to be ranked.

What’s new?

This meta-analysis included 101 trials, with 11,910 participants. The most commonly used psychotherapy was CBT, and the most commonly used group of drugs were the selective serotonin reuptake inhibitors (SSRIs).

The researchers considered that patients had responded to therapy if their symptoms of depression were reduced by half. They found that patients receiving combination psychological and drug therapy were most likely to respond. They were:

  • 27% more likely to respond than those receiving psychotherapy alone 
  • 25% more likely to respond than those receiving drug treatment alone 

There were no significant differences in response rates between psychotherapy alone and drug treatment.

Treatment acceptability was based on the number of patients who dropped out of studies. The study found that:

  • combined treatment was 23% more acceptable than drug treatment alone 
  • psychological therapy alone was 17% more acceptable than drug treatment alone 
  • combined treatment and psychological therapy alone were equally as acceptable

Combination treatment was superior overall for both moderate and severe depression. There were too few studies to calculate the effectiveness of these treatments on mild depression.

Why is this important?

This research suggests that, for people with moderate depression, combination treatment should be offered before antidepressants alone. Where a single treatment is chosen, the results suggest that psychological treatment is more acceptable to patients than drug treatment. 

The added benefit of combined treatment is greatest for those with the highest chance of responding to either therapy alone. When considering treatment options, patient preferences, individual circumstances, and treatment history also need to be taken into account. 

What’s next?

New NICE guidelines on depression in adults are planned. The existing NICE guidelines, published in 2009, recommend a stepped-care model for those with mild to moderate depression. Either psychological therapy or antidepressant drugs were offered only after earlier steps have been exhausted. 

The recent NICE clinical knowledge summary (March 2020) recommends low-intensity psychosocial therapies in newly-diagnosed mild-to-moderate depression. Routine use of antidepressants is not recommended for mild-to-moderate depression unless people have a history of the condition, persistent symptoms, or another ongoing physical health problem. Combination therapy with an antidepressant and a high-intensity psychological intervention is reserved for those with severe depression.

Further research needs to focus on long-term results. Most studies included in this meta-analysis lasted eight to 16 weeks, which is not long enough to consider relapse rates. Further analysis could identify the specific groups likely to benefit from one or another treatment approach. 

You may be interested to read

The full paper: Cuijpers P, and others. A network meta-analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry. 2020;19:92–107.

NICE Clinical Knowledge Summary: Depression (revised in 2020)

NICE guidelines 2009: Depression in adults: recognition and management CLinical guidelines [CG90]


Funding: This study was co-funded by the NIHR Oxford Health Biomedical Research Centre, and supported by the NIHR Oxford Cognitive Health Clinical Research Facility and an NIHR Research Professorship.

Conflicts of Interest: The authors declare no conflicts of interest.

Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.


Study author

We have robust evidence to show that the combination of drugs and psychological treatments is likely to be the best choice for people with mild to moderate depression in real world settings.

We therefore need to increase access to psychological services. Clinicians could learn psychotherapy techniques to use in consultations with patients with depression, so patients are not simply given a drug treatment and referred, especially where there is a long waiting list. This would require changes to the education of doctors and psychiatrists. I’m aware of the costs of psychological therapies but group therapy and online CBT is also acceptable and effective.

This is an average effect. Some patients will benefit more from drugs alone, some with psychological treatments alone and some from the combination. We need to understand individual patients, taking into account the evidence and also their preferences. It is important that patients have their preferences incorporated into the decision-making process.

Andrea Cipriani, Professor of Psychiatry, University of Oxford


There has often been a debate between those who prefer psychotherapies and those who regard antidepressants as the first-line treatment. This excellent network meta-analysis provides good evidence that the choice is not ‘either/or’ but ‘both’. People with depression should be recommended to have both psychotherapy and pharmacotherapy.

However, while antidepressants are readily available without waiting times, the availability of psychotherapies varies around the world. The Increasing Access to Psychological Therapies (IAPT) service in the UK has massively expanded the availability of psychological treatment but there are still problems with waiting times, especially for more intensive psychological treatments as recommended in this review.

The review could only cover the first six months after the start of treatment. People often experience depression over long periods. It will be important to look at longer term outcomes.

Glyn Lewis, Professor of Epidemiological Psychiatry, UCL