14th February 2025

Depressive disorders

Overview of depressive disorders

Depressive disorders are common, underdiagnosed, and an important cause of disability and time off work. They are a leading contributing factor for suicide and increase the morbidity and mortality associated with pre-existing organic illnesses such as myocardial infarction.

Epidemiology and aetiology of depressive disorders

Around 10-20% of the population will experience a depressive episode during their lifetime. Incidence is increasing in the younger population, and although prevalence is higher in females, it is believed that males are underdiagnosed.

Risk factors include family history of depressive or anxiety disorders, adverse childhood or adult experiences (in particular loss events), anxious personality, divorce, low socioeconomic status, and unemployment. Those with chronic, severe or painful organic illness are also more likely to develop a depressive disorder. Concurrent psychiatric illness is common, such as anxiety disorders, substance or alcohol misuse, or personality disorders.

Presentation and diagnosis of depressive disorders

Core and additional symptoms

The triad of core depressive symptoms is low mood, anergia and anhedonia (lack of enjoyment).

Additional symptoms include poor concentration, feelings of worthlessness or hopelessness, suicidal ideation, increased or decreased sleep, and decreased appetite. Depression can present with cognitive impairment (pseudodementia), which can cause diagnostic uncertainty in the older population.

Core and additional symptoms of depression can be quantified with the Hospital Anxiety and Depression Score (HADS).

Symptoms must be present for most of the day, on most days, for a period of at least 2 weeks to diagnose a depressive episode. If this occurs more than once, with resolution in between, it is a recurrent depressive disorder.

Psychotic symptoms

Depressive disorders can present with psychotic symptoms, usually only when severe. These tend to be congruent with mood. Delusions may be nihilistic, such as Cotard’s, where the individual believes that they are dead, non-existent, lacking in organs or blood, or rotting. There may be hallucinations, such as auditory hallucinations of criticising voices, olfactory hallucinations of unpleasant smells, or visual hallucinations of the devil.

Subtypes of depressive disorders

Depressive episodes are categorised according to severity (as determined by the number of core and additional symptoms), presence of somatic symptoms, and presence of psychotic symptoms. There may be accompanying symptoms of anxiety, leading to a diagnosis of depression with anxiety.

Depressive disorders also include the milder, subclinical syndromes of cyclothymia and dysthymia. Cyclothymia is a milder version of bipolar affective disorder in which high and low episodes occur but do not meet diagnostic criteria for mania or bipolar depression. Dysthymia is a milder version of recurrent depressive disorder in which low episodes occur without meeting diagnostic criteria for a depressive episode.

Differential diagnoses

Other psychiatric disorders can present similarly to depression such as adjustment disorder, post-traumatic stress disorder, anxiety disorders, eating disorders and personality disorders. The key in differentiating between them is the time course and predominance of certain features.

Organic illnesses are also important differential diagnoses. Common mimics include anaemia, dementia, Parkinson’s, stroke, Addison’s disease, hypothyroidism, menopause, hypercalcaemia, and sleep apnoea. As such, a thorough history and examination are essential, with consideration of investigations including FBC, U&Es, LFTs, TFTs, B12, folate, glucose, bone profile and morning cortisol.

Medications can also cause depressive symptoms, such as beta blockers, steroids, sedatives, interferon, oestrogen and antipsychotics. Recreational drugs such as alcohol, cannabis, cocaine and amphetamines can also be responsible.

Management of depressive disorders

Management of an acute depressive episode

First line for an acute mild-to-moderate depressive episode is a low-intensity psychological intervention, e.g. CBT.

If the response is inadequate, the symptoms have been mild but long lasting, or the episode is moderate to severe, NICE recommends high-intensity psychological interventions and antidepressant treatment.

Usually, an SSRI (e.g. sertraline) is first line. If ineffective, another SSRI (e.g. fluoxetine) may be trialled, then another class, such as an SNRI (e.g. venlafaxine). Switching antidepressants should be done cautiously and under specialist guidance due to the risk of serotonin syndrome.

In the initial period of antidepressant treatment suicide risk may increase due to improved energy and motivation.

For treatment-resistant depressive episodes, NICE recommends combination therapy with either two antidepressants (commonly mirtazapine and venlafaxine) or an antidepressant with lithium or an antipsychotic. The choice of agent is usually determined by the symptoms and what the patient has responded to in the past; for example, with psychotic symptoms, one might preferentially use an antipsychotic for augmentation.

For depressive disorders which are highly treatment-resistant and/or posing a threat to life (e.g. through poor oral intake), ECT is an important and effective management option.

Maintenance therapy for depressive disorders

NICE recommends at least 6 months of antidepressant treatment on recovery to reduce the risk of relapse or 2 years if there is a higher risk. Cessation of therapy should be gradual due to the risk of discontinuation syndromes. Lifelong treatment may be considered, especially if the episode was severe and/or this is the patient’s preference.

ECT is only recommended by NICE as treatment of acute depressive episodes, not as maintenance therapy.

Antidepressants

An oversimplified and commonly understood mechanism of action of all antidepressants is by increasing monoamine availability (serotonin, noradrenaline and dopamine).

Table 1 Common examples of antidepressants by class with key clinical features

References

• Semple D, Smyth R. Oxford handbook of psychiatry. Oxford; New York: Oxford University Press; 2019
• World Health Organization. ICD-11 for Mortality and Morbidity Statistics [Internet]. WHO; 2019 [cited 2022 Mar 12]. Available from: https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/1707067746
• National Institute of Health and Care Excellence Depression in adults [Internet]. NICE; 2009 [cited 2022 Mar 12]. Available from: https://www.nice.org.uk/guidance/cg90
• MacKinnon D. Depression in adults [Internet]. BMJ Best Practice; 2021 [cited 2022 Mar 12]. Available from: https://bestpractice.bmj.com/topics/en-gb/55