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 a variety 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. The World Health Organization (WHO) currently ranks depression as the leading cause of disability globally. 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.
Current National Institute for Health and Care Excellence (NICE) guidance is in the process of being updated and is due to publish in 2020. The current guideline uses the Diagnostic and Statistical Manual Fourth Edition (DSM-IV) classification (which has since been replaced by DSM-5 - see below). To diagnose major depression, this requires at least one of the core symptoms:
- Persistent sadness or low mood nearly every day.
- Loss of interest or pleasure in most activities.
Plus at least three or four of the following symptoms to a minimum total of 5 depressive 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.
- Changes in appetite and/or weight loss.
Symptoms should have been present persistently for at least two weeks and must have caused clinically significant distress and impairment. They should not be due to a physical/organic factor (eg, substance abuse) or illness (although illness and depression commonly co-exist). 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.
DSM-5 was published in 2013. It included the following changes to the classification of depressive disorders:
- Persistent depressive disorder - this term is proposed to encompass both chronic major depressive disorder and dysthymia.
- Other new diagnoses of depressive disorders including disruptive mood dysregulation disorder and premenstrual dysphoric disorder.
- Removal of the major depression bereavement exclusion - the diagnosis of major depression was excluded in people who had recently been bereaved. This has been removed, leaving more leeway for clinical judgement.
- A new category of mixed anxiety/depressive disorder.
- Separation of depressive disorders from bipolar disorders into different categories.
- The WHO estimates 300 million people are affected worldwide.
- Depression is the third most common reason for consulting a GP in the UK.
- Annually, 5% of adults have an episode of depression. About one in four women and one in ten men will develop depression severe enough to require treatment at some time in their lives. 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. NICE issued specific guidance regarding depression in adults with a chronic physical health problem.
- Female gender - in almost all studies, women have a higher prevalence, incidence and morbidity associated with depressive disorders compared with men. The gender difference is likely to be due to a complex interaction between biological, psychological and sociocultural vulnerabilities. There is an increased incidence of depression during pregnancy and in the postnatal period - see the separate Depression in Pregnancy and Postnatal Depression articles. (Men, however, have a higher risk of suicide.)
- Past history of depression.
- Significant physical illnesses, particularly those causing disability or chronic pain.
- Other mental health problems, such as schizophrenia or dementia.
- Psychosocial problems - eg, divorce, unemployment, poverty.
- Risk factors for depression in children and adolescents include family discord, bullying, physical, sexual or emotional abuse, comorbid disorders including drug and alcohol use, a history of parental depression, homelessness, refugee status and living in institutional settings.
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. 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. 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. Many depressed patients present with somatic symptoms, and most of those where the diagnosis is missed, making it critical always to consider emotional health in a differential. 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. NB: negative response does not exclude depression.
Self-report symptom scales are widely used and include:
- The Patient Health Questionnaire (PHQ-9).
- The Hospital Anxiety and Depression (HAD) Scale. (This is not available digitally, and must be purchased in paper format.)
- (the adapted version must be purchased although older versions are available online).
Whilst these can be helpful in staging depression, do not rely on a symptom count alone to make a diagnosis of depression.
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. Note whether there is evidence of self-neglect, psychosis or severe agitation. Consider cultural factors.
- Past psychiatric history, including previous 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. Directly ask about suicidal thoughts. Identify risk factors for suicide, which are discussed in the separate Suicide Risk Assessment and Threats of Suicide article.
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 (see Classification section above) and this will determine what level of treatment to initiate, following guidelines from NICE.
- Bipolar disorder.
- Schizophrenia (depression may co-exist).
- 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 - eg, hypothyroidism.
- Drug adverse effects are an uncommon cause of depression. Medications that may cause depressed mood include:
- Centrally acting antihypertensives (eg, methyldopa).
- Lipid-soluble beta-blockers (eg, propranolol).
- Benzodiazepines or other central nervous system depressants.
- Progesterone contraceptives, especially medroxyprogesterone injection.
- Dysthymia (recently classified by DSM-5 as a subtype of persistent depressive disorder) is a chronic depressive state of more than two years in duration, which does not meet full criteria for major depression and is not the consequence of a partially resolved major depression. People with dysthymia are likely to experience episodes of major depression. Dysthymia increases with age.
- Eating disorders: anorexia nervosa and bulimia nervosa.
- Substance misuse is frequently associated with depression.
- Other psychiatric conditions may co-exist with depression (eg, generalised anxiety disorder, panic disorder, obsessive-compulsive disorder, personality disorders).
- Some medical conditions have known associations with depression:
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, TFTs, calcium levels, FBC and inflammatory markers.
- Other tests may, when relevant, 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 (eg, unexplained headache or personality change). Seek specialist advice.
Doctors and patients can use Decision Aids together to help choose the best course of action to take.
General measures should include:
- Managing comorbidity (particularly alcohol and substance abuse, eating disorders, dementia, psychotic symptoms).
- Managing any safeguarding issues.
- Assessing and mitigating suicide risk.
- Appropriate monitoring/follow-up.
- Advising on sleep hygiene where relevant.
Traditionally, primary care management of depression has been concentrated on the use of antidepressants. There is now evidence supporting the efficacy of non-pharmacological alternatives but these have frequently not been available[11, 12]. The Government has targeted additional money in order to develop new local services since 2008, known as 'Improving Access to Psychological Therapies' (IAPT), the impact of which is beginning to take effect.
Following is a brief summary of the stepped management currently proposed by NICE guidance:
Treatment of persisting subthreshold depressive symptoms or mild-to-moderate depression
- Consider watchful waiting, assessing again normally within two weeks.
- Consider offering one or more low-intensity psychosocial interventions, guided by patient preference, usually via referral to IAPT:
- Guided self-help based on cognitive behavioural therapy (CBT) principles supported by a trained practitioner. This may be by face-to-face contact, telephone sessions, computerised CBT or group-based. There is some evidence that after three months of individual CBT, group CBT can be equally effective.
- Physical activity programmes in facilitated group sessions. There is some evidence for efficacy of exercise in the management of depression.
- Counselling or short-term psychodynamic psychotherapy for those who decline other interventions.
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) or behavioural couples therapy where relevant). (For an individual with a chronic health problem and moderate depression, this should be high-intensity psychological treatment alone in the first instance.)
- 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) is occasionally used by specialists 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.
- 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; also because they are less toxic in overdose.
- The evidence suggests antidepressants are effective in moderate-to-severe depression, but the evidence for efficacy in milder states is less clear. Hence NICE guidelines advise use in mild-to-moderate or subthreshold depression only where other interventions have not been effective.
- Which SSRI?:
- Guidance suggests that we choose a generic SSRI (eg, citalopram, fluoxetine, paroxetine, or sertraline) when treating an individual with antidepressants for the first time, with the assumption that they have equivalent efficacy .
- However, Cochrane reviews and other analyses suggest that escitalopram has the highest probability of remission and may be the most effective and cost-effective pharmacological treatment in a primary care setting, although there is a risk of overestimation of efficacy due to various types of bias[16, 17, 18].
- Where a patient has concurrent physical health problems, sertraline may be preferred, as it has less risk of significant drug interactions.
- 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. Warn about expected side-effects and discontinuation reactions.
- Inform patients about the delay in onset of effect (2-4 weeks), the time course of treatment (at least six months from remission in symptoms to reduce the risk of relapse) and the need to take medication as prescribed. Make available written information appropriate to the patient's needs.
- Remember the increased risk of bleeding with SSRIs, and consider co-prescribing a gastric protection agent, particularly in older people who are on aspirin or other NSAIDs.
- Note a recent meta-analysis of antidepressant use confirms a significant association between antidepressant use and incident diabetes. The exact pathophysiological reason behind this association is not yet known but several possible theories have been suggested: some antidepressants may worsen glucose metabolism through weight gain; some research has suggested that depression can directly increase the risk for diabetes; other researchers have suggested a reverse causation effect, ie diabetes triggers the risk for depression, leading to prescription of antidepressants.
- See patients who are not considered to be at increased risk of suicide, within two weeks of starting treatment and continue to review regularly as appropriate.
- See patients who are considered to be at increased risk of suicide or who are younger than 30 years old, within one week of starting treatment. Regularly review (every 2-4 weeks) in the first three 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.
- Monitor for signs of akathisia, suicidal ideas and increased anxiety and agitation, particularly in the early stages of treatment with an SSRI.
Where there is partial or no response to medication at 3-4 weeks:
- Check adherence to and side-effects from the treatment.
- Consider increasing the dose of the antidepressant.
- Consider switching to an alternative antidepressant - initially ideally another SSRI, or alternatively another class of antidepressant - for example, 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.
- For patients who have benefited from the use of an antidepressant, they should be continued for at least six 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 two 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 four-week period; some people may require longer periods and fluoxetine can usually be stopped without a withdrawal period due to its long half life.
- For mild discontinuation/withdrawal symptoms, reassure the patient and monitor symptoms. For severe symptoms, consider re-introducing 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:
- 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 (eg, social stigma, loss of employment, marital break-up). Associated problems, such as anxiety symptoms and substance misuse, may cause further disability.
- Depression is associated with increased mortality: depression increases the risk of death by suicide, and also increases the mortality rate in comorbid conditions such as coronary heart disease.
- Depression exacerbates pain and disability associated with physical conditions.
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.
- Risk of recurrence is at least 50% after a first episode, and higher after further episodes. About 10% develop persisting symptoms.
- Prognosis is worse where there are psychotic features, prominent anxiety, underlying personality disorder or symptoms which are particularly severe.
- There is inadequate evidence to determine the clinical effectiveness or cost-effectiveness of low-intensity interventions for the prevention of relapse or recurrence of depression.
- Risk factors for increased risk of depression recurrence include:
- ≥3 episodes of major depression.
- High prior frequency of recurrence.
- An episode in the previous 12 months.
- Residual symptoms during continuation treatment.
- Severe episodes - eg, 'suicidality', psychotic features.
- Long previous episodes.
- Relapse after drug discontinuation.
- One study found that people reporting poor or fair self-rated health had a worse prognosis with respect to long-term depression than those reporting good or excellent health.
Further reading and references
; Exploring thoughts of suicide. BMJ. 2017 Mar 30356:j1128. doi: 10.1136/bmj.j1128.
; NICE Interventional Procedure Guidance, December 2015
; Modafinil Improves Episodic Memory and Working Memory Cognition in Patients With Remitted Depression: A Double-Blind, Randomized, Placebo-Controlled Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Mar2(2):115-122. doi: 10.1016/j.bpsc.2016.11.009.
; Fact Sheet from the World Health Organization (WHO), March 2018
; Management of depression in adults. BMJ. 2008 Feb 23336(7641):435-9.
; NICE Clinical Guideline (April 2016)
; Major Depressive Disorder in DSM-5: Implications for Clinical Practice and Research of Changes from DSM-IV. Depress Anxiety. 2013 Nov 22. doi: 10.1002/da.22217.
; NICE CKS, October 2015 (UK access only)
; NICE Clinical Guideline (October 2009)
; NICE Clinical Guideline (March 2015)
; Clinical diagnosis of depression in primary care: a meta-analysis. Lancet. 2009 Aug 22374(9690):609-19. Epub 2009 Jul 27.
; GL Assessments
; Depression Decision AId
; Effectiveness of psychological treatments for depressive disorders in primary care: systematic review and meta-analysis. Ann Fam Med. 2015 Jan-Feb13(1):56-68. doi: 10.1370/afm.1719.
; Scottish Intercollegiate Guidelines Network - SIGN (January 2010)
; NHS England, 2017
; Group psychological therapies for depression in the community: systematic review and meta-analysis. Br J Psychiatry. 2012 Mar200(3):184-90. doi: 10.1192/bjp.bp.111.092049.
; Exercise for depression. Cochrane Database Syst Rev. 2013 Sep 129:CD004366. doi: 10.1002/14651858.CD004366.pub6.
; Citalopram versus other anti-depressive agents for depression. Cochrane Database Syst Rev. 2012 Jul 11(7):CD006534. doi: 10.1002/14651858.CD006534.pub2.
; Escitalopram versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2009 Apr 15(2):CD006532. doi: 10.1002/14651858.CD006532.pub2.
; Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model. PLoS One. 20127(8):e42003. doi: 10.1371/journal.pone.0042003. Epub 2012 Aug 2.
; Initiation of antidepressant therapy: do patients follow the GP's prescription? Br J Gen Pract. 2009 Feb59(559):81-7.
; The risk of new-onset diabetes in antidepressant users - A systematic review and meta-analysis. PLoS One. 2017 Jul 3112(7):e0182088. doi: 10.1371/journal.pone.0182088. eCollection 2017.
; The clinical effectiveness and cost-effectiveness of low-intensity psychological interventions for the secondary prevention of relapse after depression: a systematic review. Health Technol Assess. 2012 May16(28):1-130. doi: 10.3310/hta16280.
; Self-rated health and long-term prognosis of depression. Ann Fam Med. 2014 Jan-Feb12(1):57-65. doi: 10.1370/afm.1562.
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