Depression refers to both negative affect (low mood) and/or absence of positive affect (loss of interest and pleasure in most activities) and is usually accompanied by an assortment of emotional, cognitive, physical and behavioural symptoms.

It is the most common psychiatric disorder and carries a high burden in terms of treatment costs, effect on families and carers and loss of workplace productivity and is currently ranked fourth in terms of global disease burden by the World Health Organization (WHO). It may become a chronic disorder with ongoing disability, particularly if inadequately treated. More than 80% of patients with depression are managed and treated in primary care, with those seen in secondary care being skewed towards much more severe disease.1


Current National Institute for Health and Clinical Excellence (NICE) guidance2 uses the Diagnostic and Statistical Manual Fourth Edition (DSM-IV) classification. To diagnose major depression, this requires at least one of the core symptoms:

  • Persistent sadness or low mood nearly every day, or
  • Loss of interests or pleasure in most activities.

Plus some of the following symptoms:

  • Fatigue or loss of energy
  • Worthlessness, excessive or inappropriate guilt
  • Recurrent thoughts of death, suicidal thoughts, or actual suicide attempts
  • Diminished ability to think/concentrate or increased indecision
  • Psychomotor agitation or retardation
  • Insomnia/hypersomnia
  • Changes in appetite and/or weight loss

Symptoms should have been present persistently for at least 2 weeks and must have caused clinically significant distress and impairment. They should not be due to a physical/organic factor (e.g. substance abuse) or illness (although illness and depression commonly coexist).
Severity is based on the extent of symptoms and their functional impact:

  • Subthreshold depressive symptoms - <5 symptoms.
  • Mild depression - few, if any, symptoms in excess of the 5 required to make the diagnosis with symptoms resulting only in minor functional impairment.
  • Moderate depression - symptoms or functional impairment are between 'mild' and 'severe'.
  • Severe depression - most symptoms present and the symptoms markedly interfere with normal function. It can occur with or without psychotic symptoms.

Normal sadness exists along a continuum from clinically significant depression: differentiation is based on the severity, persistence and the degree of functional impairment and disability associated with the low mood.

Clinical depression: Lawrence’s story.

Lawrence has depression. He explains how easy it was to ignore the symptoms, despite being a psychiatric nurse, and the problem this caused in his working life. A short video from NHS Choices. (November 2009)


  • The prevalence of major depression in people seen in primary care is between 5% and 10%, and two to three times as many people have depressive symptoms but do not meet the criteria for major depression.3 It is the third most common reason for a consultation in primary care.
  • About two thirds of adults will at some time experience depressed mood of sufficient severity to influence their activities.4 Annually, 6% of adults have an episode of depression, and more than 15% of the population will experience an episode during their lifetime.5 Most depressive states are at the mild-to-moderate end of the spectrum and it is these that are mainly seen in primary care.
  • Chronic physical illness increases the risk of depression: 23% people with two or more chronic physical problems were rated as depressed versus 3.2% of healthy controls.5 NICE recently issued specific guidance regarding depression in adults with a chronic physical health problem.6

Risk factors

  • Female sex - in almost all studies, women have a higher prevalence, incidence and morbidity associated with depressive disorders compared with men. The gender difference is controversial and may be partially attributed to differences in likelihood of reporting symptoms and help seeking/illness behaviour, but there may also be important differences in biological, psychological and sociocultural vulnerabilities.7 There is an increased incidence of depression during pregnancy and in the postnatal period - see separate articles Depression in Pregnancy and Postnatal Depression.
  • Past history of depression.
  • Significant physical illnesses causing disability or pain.
  • Other mental health problems, such as dementia.
  • Depression is much more common in people from the African-Caribbean, Asian, refugee and asylum seeker communities.



This is covered by a separate article on recognition of depression: Screening for Depression in Primary Care.

Depression is common but is often undetected by the medical profession - only about half of individuals with major depression are identified by their GP. However, a diagnosis of depression in primary care has a sensitivity of about 50% and specificity of 81%, with the risk of misidentification outweighing the risk of missed cases.8 In other words, GPs may be good at ruling out those without depression but may need to consider more cautiously cases where depression might be present.

Somatisation is the most important cause of missed diagnosis but about two thirds of depressed patients present with somatic symptoms, making it critical always to consider emotional health in a differential.1 Many patients seen have a pre-existing physical illness which can also divert attention away from their mental state. In the elderly, depression can present as pseudodementia, with abnormalities of memory and behaviour that are typical of true dementia.

The NICE guidelines encourage a case-finding approach with at-risk groups (individuals with a past history of depression or a chronic health problem with associated functional impairment) using a two question approach:
During the past month, have you:

  • Felt low, depressed or hopeless?
  • Had little interest or pleasure in doing things?

Where there is an affirmative answer to either question, further evaluation should be triggered. Note: negative response does not exclude depression.


Depression real story.

Vanessa Phillips from Hertfordshire had always been strong and always willing to help others. When the 49-year-old had a breakdown, her friends didn’t know she was the one who needed help. A short video from NHS Choices. (September 2007)

Self-report symptom scales are widely used and include:

Whilst these can be helpful in staging depression, do not rely on a symptom count alone to make a diagnosis of depression. The use of standardised tools to assess the severity of depression at outset of treatment and at follow-up (5-12 weeks later) has been rewarded by the Quality and Outcomes Framework (QOF) 2009-2010.11

An individual considered likely to have depression should be fully assessed, including:

  • Full history and examination, including mental state examination, enquiring directly about suicidal ideas, delusions and hallucinations. Consider organic causes of depression such as hypothyroidism or drug side-effect. Establish the duration of the episode.
  • Review of related functional, interpersonal and social difficulties. Involve family members or carers, with the patient's consent, to obtain third-party history if appropriate. Is there evidence of self-neglect, psychosis or severe agitation? Consider cultural factors.
  • Past psychiatric history including past episodes of depression or mood elevation, response to previous treatment and comorbid mental health conditions
  • Patient safety and risk to others - suicidal intent should be assessed regularly.

Depression should be assessed as mild, moderate or severe depending on the extent and impact of symptoms and level of functional impairment and/or disability and this will determine what level of treatment to initiate.2

Differential diagnosis

  • Bipolar affective disorder.
  • Schizophrenia (depression may coexist).
  • Dementia may occasionally present as depression and vice versa.
  • Seasonal affective disorder.
  • Bereavement: depressive symptoms begin within 2-3 weeks of a death (uncomplicated bereavement and major depression share many symptoms but active suicidal thoughts, psychotic symptoms and profound guilt are rare with uncomplicated bereavement).
  • Organic cause, e.g. hypothyroidism.
  • Drug adverse effects are an uncommon cause of depression. Medications that may cause depressed mood include:
    • Centrally acting antihypertensives (e.g. methyldopa).
    • Lipid-soluble betablockers (e.g. propranolol).
    • Benzodiazepines or other central nervous system depressants.
    • Progesterone contraceptives, especially medroxyprogesterone injection.

Associated diseases


Investigations are used to exclude organic causes for depression; they are not mandatory and should be used according to clinical judgement.

  • Blood tests may include blood glucose, U&Es, LFTs, thyroid function tests, calcium levels, FBC and inflammatory markers.
  • Other tests may include magnesium levels, HIV or syphilis serology, or drug screening.
  • Imaging (MRI or CT brain scanning) may be indicated where presentation or examination is atypical or where there are features suspicious of an intracranial lesion (e.g. unexplained headache or personality change). Seek specialist advice.


Traditionally primary care management of depression has been concentrated on the use of antidepressants. There is now evidence supporting the efficacy of nondrug alternatives,12,13 but these have frequently not been available. The Government has targeted additional money in order to develop new local services, known as 'Improving Access to Psychological Therapies' (IAPT), the impact of which is still to be realised.14

A brief summary of the stepped management proposed by NICE guidance:2

Treatment of mild-to-moderate depression

  • Consider watchful waiting, assessing again normally within 2 weeks.
  • Consider offering one or more low-intensity psychosocial interventions, guided by patient preference:
    • Encourage exercise. Benefits of structured group-based exercise programmes (3 x 45-minute sessions per week for 10-12 weeks) have been shown.15
    • Guided self-help based on cognitive behavioural therapy (CBT) principles - book prescription schemes, or internet resources.
    • Computerised CBT.16
    • Relaxation therapy - more effective than no, or minimal, treatment.17
    • Brief psychological interventions (6-8 sessions) including problem-solving therapy, brief CBT and counselling.

Antidepressants are not recommended for the initial treatment of mild depression, because the risk-benefit ratio is poor. However, their use may be considered:

  • If mild depression persists after other interventions, or is associated with psychosocial and medical problems.
  • In mild depression complicating the care of physical health problems.
  • When a patient with a history of moderate or severe depression presents with mild depression.
  • With subthreshold depressive symptoms present for at least two years or persisting after other interventions.

Treatment of moderate-to-severe depression

  • Offer antidepressant medication combined with high-intensity psychological treatment (CBT or interpersonal therapy (IPT)). (For an individual with a chronic health problem and moderate depression, this should be high-intensity psychological treatment alone in the first instance.6)
  • Make an urgent psychiatric referral if the patient has active suicidal ideas or plans, is putting themself or others at immediate risk of harm, is psychotic, severely agitated or is self-neglecting. The use of the Mental Health Act may be necessary in some instances.
  • Electroconvulsive therapy (ECT) may be used to gain fast and short-term improvement of severe symptoms after all other treatment options have failed, or when the situation is thought to be life-threatening.18

Drug treatment

  • What sort of antidepressant? Selective serotonin reuptake inhibitors (SSRIs) are used as first-line antidepressants in routine care because they are as effective as tricyclic antidepressants and less likely to be discontinued because of side-effects, and are less toxic in overdose.2
  • Recent meta-analyses have concluded that SSRIs have benefit in severely depressed patients19 but evidence for their efficacy in mild-to-moderate depression above placebo effects is much less clear.20
  • Which SSRI?:
    • Guidance5 suggests that we choose a generic SSRI (e.g. citalopram, fluoxetine, paroxetine, or sertraline) when treating an individual with antidepressants for the first time, with the assumption that they have equivalent efficacy.21
    • However, a recent meta-analysis suggested that there are clinically important differences in efficacy and acceptability between new-generation antidepressants in favour of sertraline and escitalopram, although there are cost implications.22
    • Where a patient has concurrent physical health problems, citalopram or sertraline may be preferred as they have less risk of significant drug interactions.5
    • Where a patient has previously been treated for depression, be guided by past patterns of response/non-response to antidepressants.
    • Treatments such as dosulepin, phenelzine, combined antidepressants, and lithium augmentation of antidepressants should be initiated only by specialist mental healthcare professionals.
    • St John's wort should not be recommended because of uncertainty about appropriate doses, variation in the nature of preparations, and potential serious interactions with other drugs.
  • Prior to initiating any medication, discuss the patient's fears of addiction or other concerns about medication; over a quarter of patients newly prescribed an antidepressant by their GP never obtain their prescription or take more than a single dose.23 Warn about expected side-effects and discontinuation reactions.
  • Inform patients about the delay in onset of effect, the time course of treatment and the need to take medication as prescribed. Make available written information appropriate to the patient's needs.


  • See patients who are not considered to be at increased risk of suicide 2 weeks after starting treatment and continue to review regularly as appropriate.
  • Monitor for signs of akathisia, suicidal ideas, and increased anxiety and agitation, particularly in the early stages of treatment with an SSRI.
  • See patients who are considered to be at increased risk of suicide or who are younger than 30 years old 1 week after starting treatment. Regularly review (every 2-4 weeks) in the first 3 months or until the risk is no longer significant. Where there is a high risk of suicide, prescribe a limited quantity of antidepressants and consider additional support such as more frequent contacts with primary care staff, or telephone contacts.

Where there is partial or no response to medication at 2-4 weeks:

  • Check adherence to and side-effects from the treatment.
  • Consider increasing the dose of the antidepressant.
  • Consider switching to an alternative antidepressant - either another SSRI, mirtazapine, moclobemide, reboxetine, venlafaxine or a tricyclic. Always check guidance regarding switching and the need for 'wash out times' and careful dosage adjustment. Avoid tricyclic antidepressants or venlafaxine when there is a risk of overdose.

Treatment duration:

  • For patients who have benefited from the use of an antidepressant, they should be continued for at least 6 months after remission to reduce the risk of relapse.
  • Patients who have had two or more depressive episodes in the recent past, and who have experienced significant functional impairment during the episodes, should be advised to continue antidepressants for 2 years. A much longer duration of treatment may be required for some patients.
  • Patients who are considered to be at substantial risk of relapse or who have residual symptoms, should be considered for referral for either individual CBT or Mindfulness-based cognitive therapy.

When stopping antidepressants:

  • Reduce doses gradually over a 4-week period; some people may require longer periods, and fluoxetine can usually be stopped over a shorter period.
  • For mild discontinuation/withdrawal symptoms, reassure the patient and monitor symptoms. For severe symptoms, consider reintroducing the original antidepressant at the effective dose (or another antidepressant with a longer half-life from the same class) and reduce gradually while monitoring symptoms.


In addition to the urgent referral necessary when an individual is actively suicidal, referral to secondary care may be necessary where there is:5

  • Uncertain diagnosis, including possible bipolar disorder
  • Failed response to two or more interventions
  • Recurrence of depression <1 year from previous episode
  • More persistent suicidal thoughts
  • Comorbid substance, physical, or sexual abuse.
  • Severe psychosocial problems.
  • Rapid deterioration
  • Cognitive impairment


  • Depression is a major cause of impaired quality of life and reduced productivity. Social difficulties are common (e.g. social stigma, loss of employment, marital break-up). Associated problems, such as anxiety symptoms and substance misuse, may cause further disability.
  • Depression is also associated with increased mortality:
    • More than half of all individuals who commit suicide have evidence of major depressive illness. Depressed men are at higher risk of suicide than women, particularly in combination with alcohol misuse and impulsive or aggressive personality traits24. Clinical predictors of suicide in people with depression include:
      • A history of attempted suicide
      • High levels of hopelessness
      • High ratings of suicidal tendencies
    • Depression increases the risk of developing and dying from coronary heart disease.25


The outlook varies with the severity of the condition:

  • The average length of an episode of depression is 6-8 months and, with mild depression, spontaneous recovery is likely.5
  • For major depression: approximately 80% of people who have received psychiatric care for an episode will have at least one more episode in their lifetime, with a median of four episodes.
  • The outcome for those seen in primary care also seems to be poor, with only about a third remaining well over 11 years and about 20% having a chronic course.26 In light of this, some argue for a model of chronic disease management for depression, akin to that for diabetes or asthma.27
  • Risk factors for increased risk of depression recurrence include:1
    • ≥3 episodes of major depression
    • High prior frequency of recurrence
    • An episode in the previous 12 months
    • Residual symptoms during continuation treatment
    • Severe episodes, e.g. 'suicidality', psychotic features
    • Long previous episodes
    • Relapse after drug discontinuation

Document references

  1. Timonen M, Liukkonen T; Management of depression in adults. BMJ. 2008 Feb 23;336(7641):435-9.
  2. Depression in adults, NICE Clinical Guideline (October 2009); Depression: the treatment and management of depression in adults
  3. Katon W, Schulberg H; Epidemiology of depression in primary care. Gen Hosp Psychiatry. 1992 Jul;14(4):237-47. [abstract]
  4. Stewart DE, Gucciardi E, Grace SL; Depression. BMC Womens Health. 2004 Aug 25;4 Suppl 1:S19. [abstract]
  5. Depression, Clinical Knowledge Summaries (February 2010)
  6. Depression with a chronic physical health problem, NICE Clinical Guideline (October 2009); The treatment and management of depression in adults with chronic physical health problems
  7. Piccinelli M, Wilkinson G; Gender differences in depression. Critical review. Br J Psychiatry. 2000 Dec;177:486-92. [abstract]
  8. Mitchell AJ, Vaze A, Rao S; Clinical diagnosis of depression in primary care: a meta-analysis. Lancet. 2009 Aug 22;374(9690):609-19. Epub 2009 Jul 27. [abstract]
  9. Hospital Anxiety and Depression (HAD) Scale, NHS Specialist Libraries; MS Word document
  10. Hospital Anxiety and Depression (HAD) Scale, GL Assessments; for purchase of questionnaire from copyright owners
  11. Department of Health; Quality and Outcomes Framework (QOF)
  12. SIGN Non-pharmaceutical management of depression in adults, Jan 2010
  13. Cuijpers P, van Straten A, van Schaik A, et al; Psychological treatment of depression in primary care: a meta-analysis. Br J Gen Pract. 2009 Feb;59(559):e51-60. [abstract]
  14. Department of Health; Improving Access to Psychological Therapies implementation plan (February 2008).
  15. Mead GE, Morley W, Campbell P, et al; Exercise for depression. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD004366. [abstract]
  16. Depression and anxiety - computerised cognitive behavioural therapy (CCBT), NICE Technology Appraisal (2006)
  17. Jorm AF, Morgan AJ, Hetrick SE; Relaxation for depression. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD007142. [abstract]
  18. Electroconvulsive therapy (ECT), NICE (2003); The clinical effectiveness and cost effectiveness of electroconvulsive Therapy (ECT) for depressive illness, schizophrenia, catatonia and mania.
  19. Fournier JC, DeRubeis RJ, Hollon SD, et al; Antidepressant drug effects and depression severity: a patient-level JAMA. 2010 Jan 6;303(1):47-53. [abstract]
  20. Kirsch I, Deacon BJ, Huedo-Medina TB, et al; Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008 Feb;5(2):e45. [abstract]
  21. Gartlehner G, Gaynes BN, Hansen RA, et al; Comparative benefits and harms of second-generation antidepressants: background Ann Intern Med. 2008 Nov 18;149(10):734-50. [abstract]
  22. Cipriani A, Furukawa TA, Salanti G, et al; Comparative efficacy and acceptability of 12 new-generation antidepressants: a Lancet. 2009 Feb 28;373(9665):746-58. [abstract]
  23. van Geffen EC, Gardarsdottir H, van Hulten R, et al; Initiation of antidepressant therapy: do patients follow the GP's prescription? Br J Gen Pract. 2009 Feb;59(559):81-7. [abstract]
  24. Hawton K, van Heeringen K; Suicide. Lancet. 2009 Apr 18;373(9672):1372-81. [abstract]
  25. Barth J, Schumacher M, Herrmann-Lingen C; Depression as a risk factor for mortality in patients with coronary heart Psychosom Med. 2004 Nov-Dec;66(6):802-13. [abstract]
  26. Evidence-based guidelines for treating bipolar disorder: revised second edition, British Association for Psychopharmacology (March 2009)
  27. Tylee A, Walters P; We need a chronic disease management model for depression in primary care. Br J Gen Pract. 2007 May;57(538):348-50.


EMIS is grateful to Dr Chloe Borton for writing this article and to Dr Colin Tidy for earlier versions. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2010.
Document ID: 2037
Document Version: 25
Document Reference: bgp611
Last Updated: 9 Jun 2010