Depression

When we talk about depression, it is important to realise that depression is both a mood and illness.

The characteristics of depression are:

• Persistent low mood
• Loss of interest and enjoyment in daily activities (anhedonia)
• Neurovegetative disturbances - neurovegetative refers to the autonomic nervous system. Disturbances as such refer to appetite, sleep and concentration disturbances.
• Social and occupational disturbances.
• Suicidal ideation

Depressive disorders are common. They vary in duration, severity and symptoms.

What we will discuss here is:

Bipolar disorder can also be included under depressive disorders, however, it will be discussed separately in the CCC on bipolar affective disorder. For now we will focus on unipolar depression solely.

DEPRESSION IN ADULTS

Major depressive disorder is the clinical syndrome that involves mood, cognition and behaviour. It can be considered either reactive (based on circumstances such as stress, without any hereditary component or endogenous (there is a hereditary component but lack of a circumstantial factor).

The aetiology of the disorder is not well understood. Genetic factors have strong links, but no specific genetic factors have been identified. Stressful life events, personality, sex have also all been identified in predisposing someone to depression.

Pathophysiology

Abnormal concentrations of neurotransmitters, dysregulation of the HPA axis, and secondary messenger abnormalities have all been identified.

There are 3 main biological theories for depression:

1. Monoamine theory - the monamines are noradrenaline, adrenaline, dopamine and serotonin. This theory believes that there is impaired monamine signalling to certain regions in the brain.
2. Neuroendocrine theory - overactive cortisol and corticotrophin releasing hormone is the issue, and this then leads to mono amine deficiencies.
3. Trophic/neuroplastic theory - deficiencies in brain-derived neurotrophic factor or the malfunctioning of its receptor lead to neural apoptosis within the hippocampus as opposed to neurogenesis. It is theorised that monoamine activity may be neuro protective.

The common factor in all these theories is that there is some degree of monaminergic impairment\

⚠️ Risk factors

Other risk factors include: substance use, stressful live events and obesity.

Organic diseases that may lead to depression are:

😷 Presentation

Patients with depression have low mood and anhedonia most of the day, nearly every day.

They may suffer functional impairment in social or occupational situations.

🔢 Classification

NICE uses the PHQ-9 score that to classify depression as less severe or more severe:

• Less severe - <16
• More severe - >16

We can classify depression as being mild, moderate, and severe.

🕵️ Screening and investigations

2 simple questions can be used for depression screening:

1. During the last month, have you often been bothered by feeling down, depressed or hopeless?
2. During the last month, have you often been bothered by having little interest or pleasure in doing things?

❓

This is known as the Patient Health Questionnaire-2 (PHQ-2), and is a screening tool. Any positives warrant a PHQ-9 questionnaire.

If the answer to either of the above is yes, a more in-depth assessment should be performed using the Hospital Anxiety and Depression scale (HAD scale), and the Patient Health Questionnaire-9. PHQ-9 has been validated for use in primary care. It also enables objective monitoring in response to therapy.

🧰 Management

[NEEDS UPDATING BASED ON NICE 2022 GUIDELINES]

Treatment of less severe depression:

Treatment of more severe depression:

Mild depression treatment:

1. 🥇 Antidepressant - we will discuss the antidepressants that are used below, but generally SSRIs are first-line along with SNRIs.
2. 🥇 Psychotherapy - CBT has shown to be comparable to antidepressant monotherapy in some studies. Time to response is approximately 3 months. Can also be done online with computer-based CBT.
3. 🥇 Supportive measures - such as bibliotherapy (self-help books), yoga, exercise, music therapy, acupuncture, relaxation training.
4. 🥈 Alternative antidepressant - if no improvement is seen within the first 2 weeks, consider switching. If there has been some improvement, continue for 6-8 weeks. 1/5th of patients do not see improvements until 5 weeks, however.
5. 🥉 St John’s wort - a herb that works by inhibiting SERT. It is safe, but it has significant drug interactions and this must be taken into account before prescribing. However, it must not be given concomitantly with other antidepressants.

Moderate depression treatment:

1. 🥇 Antidepressant
2. 🥇 ± Psychotherapy and supportive measures
3. 🥇 ± Immediate symptom management - we can treat some symptoms such as agitation and anxiety with BDZs or antipsychotics:
1. Benzodiazepines - to treat agitation/anxiety.
1. Lorazepam
2. Clonazepam
2. Antipsychotics - can treat the agitation and also insomnia. More appropriate when there is risk of BDZ dependence. Patients should not drive while on these tranquilising agents.
1. Quetiapine
2. Trazodone
4. 🥈 Alternative antidepressant

Severe depression treatment:

1. 🥇 Psychiatric referral ± hospitalisation ± antidepressant
1. Psychiatric referral - suicide risk management is important.
2. Hospitalisation - if patients have significant suicidal ideation and lack safeguarding measures in their family environment/have intent to hurt others/are unable to look after themselves or adhere treatment/have psychotic symptoms. If they are unwilling, family support is needed and if need be, legal means may be exercised to ensure treatment is given.
3. Antidepressant - the options remain the same.
2. ± 🥇 Immediate symptom management

OR

1. 🥇 Psychiatric referral ± hospitalisation ± electroconvulsive therapy (ECT)
1. Electroconvulsive therapy - ECT may be considered as first-line in patients with psychotic features, have active suicidal thoughts and are intolerant/unresponsive to antidepressants. It is performed under GA 2-3x weekly for 2-4 weeks (6-12 treatments total). The effects are temporary and should be maintained using antidepressants and/or ECT.
2. 🥇 Antidepressant
3. ± 🥇 Immediate symptom management -
4. 🥈 Alternative antidepressant

💊

Antidepressant medications:

SSRIs -typically SSRIs are first line. They increase activity on the post-synaptic 5-HT1a receptor to decrease depression and anxiety.

• Citalopram - 20mg OD (maximum 40mg/day).
• Escitalopram - 10mg OD (maximum 20mg/day).
• Fluoxetine - 20mg OD (maximum 80mg/day, if the dose is >20mg then it should be given in 2 doses).
• Paroxetine - 20mg OD (maximum 50mg/day).
• Sertraline - 50mg OD (maximum 200mg/day).

Adverse effects: nausea, headache, constipation, GI effects, agitation, ↑suicide risk on initiation serotonin syndrome (rare).

SNRIs - similar MOA to SSRIs (increasing serotonin) but also increase noradrenaline activity by inhibiting the NA reuptake transporter.

• Desvenlafaxine - 50mg OD (maximum 400mg/day).
• Duloxetine

Adverse effects: abnormal dreams, anorexia, anxiety, dizziness, dry mouth, GI upset, hypertension, menstrual disturbances.

NA-selective reuptake inhibitor

• Bupropion - 100mg BD. Rarely used for depression, mainly used for smoking cessation.

Monamine receptor antagonists

• Mirtazapine - 15mg OD.

Monoamine oxidase inhibitors (MAOIs):

• Isocarboxazid - 10mg TD.
• Phenelzine - 15mg TD.
• Selegiline transdermal - 6mg/24 hour patch.

Let’s discuss tricyclic antidepressants (TCAs):

Not used as commonly nowadays due to their side-effect profile and toxicity that occurs with overdose.

Nowadays, they are commonly used for neuropathic pain and for migraine prophylaxis.

Some common TCAs are:

• Amitryptaline - most dangerous in overdose. Also is more sedative. Low dose is used for neuropathic pain and migraine prophylaxis.
• Clomipramine
• Dosulepin
• Trazodone
• Nortriptyline
• Lofepramine

Common side-effects include:

1. Drowsiness
2. Dry mouth
3. Blurred vision
4. Constipation
5. Urinary retention
6. QT prolongation

💬 Starting antidepressant therapy Discussion prior to starting antidepressants should cover:

• Patient’s concerns
• Importance taking medication as prescribed even into remission
• Potential side effects
• ↑ risk of suicide initially
• Risk of discontinuing. Patients should aim to continue antidepressants for at least 6 months after feeling better. This is the general rule-of-thumb.

🚨 Serotonin discontinuation syndrome - these are symptoms that develop after stopping serotonergic medication too quickly. Reduction should be tapered over a few weeks

Review (if not suicidal):

• Initially 2 weeks then 2-4 weeks
• Review symptoms
• Risk assessment
• Review side effects
• Concordance

Treatment-refractory depression:

1. 🥇 Reassess and switch to alternative antidepressant/combination therapy
2. ± 🥇 Augmentation therapy
1. Lithium
2. Aripiprazole
3. Olanzapine
3. ± 🥇 Psychotherapy

1. 🥈 Monamine oxidase inhibitor - options are outlined below
2. 🥈± Psychotherapy

1. 🥉Electroconvulsive therapy

Pregnancy and depression

1. 🥇 Active monitoring and/or antidepressant and/or ECT
1. With mild depression where fetal risk is low, non-pharmacological techniques are preferred.
2. Moderate/severe episodes may indicate antidepressant usage. However, there is some evidence suggesting increased risk of preterm birth with antidepressant usage in pregnancy.
3. In very severe depression, where the foetus is at risk due to poor maternal self-care or suicide, ECT is the treatment of choice. ECT poses no known risk to the foetus.
2. ± 🥇 Psychotherapy

💡 An important fact to remember is that sertraline or paroxetine are the SSRIs of choice in breastfeeding women.

DEPRESSION IN CHILDREN

Childhood depression is likely to be caused by endogenous factors and their interactions with the environment. Life stress is a big risk factor.

😷 Presentation

The criteria does not differ from adult depression. However, what we may see is significant impairments in school, social settings, or with family.

🧰 Management

Mild depression in children:

1. 🥇 Active monitoring + supportive care - up to 6 weeks of monitoring with supportive care is appropriate. Mild depression often resolves with non-specific treatment. Lifestyle changes in diet and exercise may facilitate treatment.
2. ± 🥇 Management of associated symptoms - such as insomnia, anxiety, ADHD.

1. 🥈 Psychotherapy + supportive care - CBT/digital CBT or interpersonal psychotherapy.
2. ± 🥈 Management of associated symptoms - such as insomnia, anxiety, ADHD.

Moderate/severe depression in children:

1. 🥇 SSRI + supportive care
1. Fluoxetine is first-line in children.
2. Escitalopram
3. Sertraline
4. Citalopram

OR

1. 🥇 Psychotherapy + supportive care

OR

1. 🥇 Psychotherapy + SSRI + supportive care

2. 🥈 Switch to different SSRI + psychotherapy + supportive care

3. 🥉 Non-selective SSRI + psychotherapy + supportive care

SEASONAL AFFECTIVE DISORDER

Seasonal affective disorder (SAD) refers to a depression occurring around winter months. It should be treated the same as mild depression per NICE guidelines. Sleeping tablets should not be given as this can make symptoms worse.

Light therapy has limited evidence at this point so it is not routinely recommended.