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De-pathologising depressed mood

Should we consider de-pathologising depressed mood? Is it a universal genetic mechanism for coping with specific problems?
Depressed person
© University of York/HYMS

So we’ve just learned that Brian, the 81 years old man with chronic knee pain is feeling low in mood. However, should we jump to a diagnosis of depression, or should we initially be taking a step back here?

We know that mental health problems are common, particularly in people like Brian with long-term health conditions1.

  • 20% of people in England have mental health problems (10.2m people)
  • 30% of people living with a long term physical condition have a mental health problem (4.6 million people).

If we were to follow NICE guidelines, we would use the case finding questions to identify potential depression, then perform a more detailed assessment using a validated tool such as the PHQ-9 scale.

So, lets say you’ve completed a PHQ-9 score and Brian is classed as having mild/ moderate depression. You explore his preferences for care. He recounts taking citalopram for years, but stopping it recently as it wasn’t helping. He wonders if he’s become “resistant” to this, asking if he could try an alternative.

So, will antidepressants help? What does the evidence tell us?

A recent systematic review and meta-analysis of randomised controlled trials examined the efficacy of 21 different antidepressants against placebos2. Overall, the trials involved 116,477 participants. The outcome measure was >50% drop in symptom score by 20 weeks. All antidepressants were found to be more effective than placebo. However, the absolute response rate was 40% in the placebo group, compared to 50% in the treatment group, suggesting a number needed to treat of 8-10.
In other words, we have to treat 8-10 patients with antidepressants for one to benefit from the tablets. But almost half the people taking antidepressants will feel better, but not as a direct effect of taking the tablet.
This would imply that for many patients, placebo is as effective as antidepressants, which should encourage us to consider exploring alternative approaches to managing these problems.
If we consider other available evidence, the PANDA study was a randomized placebo-controlled trial, involving 179 GP surgeries across four cities3. Patients were randomly assigned to treatment with sertraline or placebo. Primary outcome analyses were of 550 patients. Sertraline when used in primary care was found to be unlikely to improve depression within six weeks. However, improvements in anxiety and quality of life were observed.
In a further study, 480 adults were recruited to a randomised placebo-controlled trial to determine the effectiveness of adding mirtazapine to an SSRI in people with treatment resistant depression4. No significant improvement in symptoms was observed, though there were more adverse effects.
So from the above, we know antidepressants may offer a small benefit compared to placebo, but often no benefit is observed and patients may experience side-effects.
In the case of Brian, he has had several recent changes in his daily life which have impacted on his mood, so rather than changing his medication, would a better approach be to take a whole-person centred approach to reviewing his mental health?

Brian and his dog

Should we consider taking a different approach to helping Brian with his depressed mood?

  • Psychologist Emmy Gut argues that getting depressed is a ‘universal genetic mechanism for coping with specific problems’5.
  • Depressed mood forcing us to opt out of everyday routine and work can serve a productive function.
  • Rather than taking an antidepressant so we can keep going with more of the same, perhaps we need a different approach.

So how can we help Brian with his mood concern?

We can take a generalist approach, making a whole-person assessment. The flipped consultation approach (week 2) could help us to frame his problem differently, keeping his care on the illness side of the gate (generalist gatekeeper role, week 2).

Furthermore, we can use the exhaustion cycle to help us to engage Brian in using behavioural activation techniques. We can also try to draw on Brian’s creative self, to help him to address his mood concerns.

We will discuss these approaches in more detail within the following steps…


  1. The Kings Fund. Mental Health: The connection between mental and physical health. Available from: [Accessed 17/02/2022]
  2. Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. The Lancet. 2018; 391 (10128): 1357-1366. DOI:
  3. Lewis G, Duffy L, Ades A, Amos R, Araya R, Brabyn S et al. The clinical effectiveness of sertraline in primary care and the role of depression severity and duration (PANDA): a pragmatic, double-blind, placebo-controlled randomised trial. The Lancet Psychiatry. 2019; 6 (11): 903-914. DOI:
  4. Kessler DS, MacNeill SJ, Tallon D, Lewis G, Peters TJ, Hollingworth W et al. Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR). BMJ. 2018; 383: k4218. DOI:
  5. Gut E. Productive and unproductive depression. New York: Basic Books; 1989.
© University of York/HYMS
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