Antidepressants reduce depression symptoms in primary care.

primary care

Photo credits: Gennadiy Ratushenko  


Why are antidepressants in primary care important?


Depression is very common. The majority of patients with clinical depression are treated in primary care (with a family physician) but most of the research has included patients who have been referred to a specialist (secondary care). Therefore, it is important to understand whether antidepresseants are effective for patients treated in primary care settings.


Do antidepressants work for depression in primary care?

  • Both tricyclic antidepressants (TCAs and selective serotonin reuptake inhibitors (SSRIs) are effective for depression treated in primary care.
  • The effectiveness of antidepressants increases over time so a response may take up to 4 weeks.


Equity: do antidepressants work in the disadvantaged?

  • None of the included studies were conducted in low- or middle-income countries and participant details were not provided in the review. However, there is no reason to believe that TCAs and SSRIs would be less effective in disadvantaged populations, as long as there is access to primary care physicians and the antidepressants are available.

Intervention Delivery

  • The medications were provided in tablet or capsule form in various doses, including
  • 25 mg 4 tablets increasing to 5 or 6 tablets over 4 weeks
  • 75 mg/ day plus amylobarbiton 150 mg per day
  • 75 mg for first week increasing to 100 mg in second week and up to 125-175 mg if needed
  • 150 mg/ day
  • 150 mg/ day plus amylobarbiton 150 mg per day
  • 75 mg increasings to 150 mg after 2 weeks
  • 25 mg to start then on days 2-4 increasing to 2 capsules, increasing to 3 capsules on days 5-7, then days 8-15 increasing to 2 capsules 3 times daily
  • 50 mg 3 times daily increasing to 75 mg 3 times daily at 2-4 days, then 100 mg 3 times daily
  • 50 mg increasing to >200 mg after 1 week
  • 10 mg 3 times nightly increasing to up to 6 times nightly
  • 30 mg/ day increasing to 60 mg at 1 week, 90 mg/ day at 4 weeks, maximum of 120 mg/ day at 6 weeks
  • 20 mg which could be doubles at 4 and 6 weeks
  • 10 mg/ day, could double at 4-6 weeks
  • 50 mg plus dothiepin 75 mg for 2 weeks then could double the dose
  • 50 mg/ day increasing to 100 mg by 3rd week and up to 150 mg at 4 weeks, maximum of 200 mg at 6 weeks

Population and Setting

  • All patients were recruited from primary care settings
  • Participants had a range of depressive disorders although 4 studies included only patients with major depressive disorder
  • Among those studies that reported on the sex of participants, the majority of patients were women (ranging from 70-100% female participants)
  • Patients with comorbidities were excluded (e.g. those with an eating disorder, alcoholism) as well as pregnant and breastfeeding women.


Summary of Findings [SOF] Table: Antidepressants vs. placebo for depression in primary care

Patient or population: Adults aged 18-65 diagnosed with unipolar depression or whom their GP though was depressed
Settings: Primary care, high-income countries
Intervention: anti-depressants 
Comparison: placebo



Anticipated absolute effects per year

Relative effect
(95% CI)

No of Participants

Quality of the evidence




Antidepressants vs. placebo - standardized mean difference (SMD)




Depression symptoms after treatment


0.49 fewer depression symptoms (from 0.32 to 0.67 fewer)



1233 (13)




Risk with placebo

Risk difference with antidepressants

Clinical response (depression remission) after treatment


49 per 100

12 more (from 5 to 19 more)

RR 1.24 (1.11 to 1.38)

1058 (8)


Adverse effects


16 per 100

16 more (from 9 to 25 more)

RR 2.01 (1.59 to 2.55)

1015 (9)


RR=risk ratio

CI=confidence interval

About quality of evidence (GRADE)
High quality (High
): Further research is very unlikely to change our confidence in the estimate of effect. 
Moderate quality (Moderate
): Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality (Low
): Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality (Very low
): We are very uncertain about the estimate.

1. There may be some publication bias. The funnel plot suggests that small studies with small effect sizes may be missing. Many of the studies were small and of variable quality. The majority of systematic reviews concerning antidepressant efficacy fail to report a detailed examination of methodological quality and therefore fail to include such criteria when examining treatment effects. 

2. Moderate heterogeneity (I2= 50%)


Relevance of the review for disadvantaged communities

Antidepressants reduce depression symptoms in primary care. 
There is no reason to suspect that antidepressants would be less effective for disadvantaged populations.



Equity - Which of the PROGRESS groups examined

All included studies were conducted in high-income countries.

The results appear to be generalizable to adults diagnosed with depression. If patients have access to primary care providers and antidepressants (TCAs and SSRIs) then the effectiveness is likely the same. Future trials should examine whether antidepressants are effective in low-resource settings.

The effectiveness of antidepressants among population subgroups was not explored.

There is a lack of evidence on the effectiveness of antidepressants among various population subgroups in primary care. All of the studies reporting on population characteristics reported that more women than men were included (ranging from 0-30% male patients). However, no sex disaggregated results are available. Additionally, no evidence is available on the effectiveness of these anti-depressants among those with co-morbidities.

Equity Applicability

The included studies reported on patients with a range of depression conditions.

The results apply to major depressive disorder as well as heterogeneous depression which are common diagnoses in primary care. The results are likely applicable to depression in other primary care settings.

The review summarized findings based on studies in which the level of organization may be higher than that outside of the research setting.

Factors to consider when assessing whether the intervention effects are transferable to your local setting are:

  • the availability of information on who may benefit from the intervention
  • the financial and ogranizational resources to provide the intervention (GPs, pharmacists, medicication).


The review does not report on the cost-effectiveness of antidepressants.

Policymakers need to consider the costs of antidepressants (TCAs and SSRIs) which may vary depending on location. The cost for the patient will vary depending on the local health system and insurance providers.


 Comments on this summary? Please contact Jennifer Petkovic.

This summary was prepared by Elian Bogers.