Depression

Major depressive disorder (MDD), also known as depression, is a type of mood disorder which causes low mood and various other emotional and physical symptoms.

Pathophysiology

The pathogenesis of depression is likely multifactorial with both biological and environmental factors at play. There are a number of different proposed theories; we only summarise a few here but there are many more.

1. Monoamine hypothesis: This is the proposal that patients with depression have a deficiency of serotonin, dopamine, and noradrenaline. This theory came about via experiments whereby giving drugs which resulted in depletion of the presynaptic stores of these neurotransmitters resulted in symptoms similar to that seen in depression.
2. Genetic factors: Twin studies have revealed there is likely a genetic component to depression.
3. Neurotrophin hypothesis: Depression may also involve disruptions in neuroplasticity, the brain's ability to adapt and change. Factors like brain-derived neurotrophic factor (BDNF), which supports the growth, differentiation, plasticity, repair and maintenance of nerve cells, have been found to be reduced in postmortem peripheral blood in people with depression. Compounds that focus on the BDNF system have demonstrated the ability to generate effects similar to those seen with antidepressants.
4. Hypothalamic-pituitary-adrenal axis: The HPA axis has been found to be overactive in times of stress in patients with depression. Remember, the HPA axis is important in the stress response and ultimately causes increased release of glucocorticoids such as cortisol from the adrenal glands.
5. Environmental triggers: stress and traumatic life events can trigger depression.

Risk Factors

• Female sex
• History of other mental health conditions
• Family history
• Chronic health conditions
• History of domestic violence
• Social factors e.g., stress, unemployment, homelessness

Clinical Features

• Low mood
• Anhedonia: Loss of interest/pleasure in usual activities
• Fatigue and reduced energy
• Reduced concentration/attention
• Reduced self-esteem
• Feelings of worthlessness and/or guilt
• Pessimism and hopeless
• Loss of libido
• Sleep disturbance: Insomnia or hypersomnia
• Appetite changes
• Weight changes: Loss or gain
• Psychosis
• Psychomotor disturbances: Slowing down of movements (psychomotor retardation) or being more agitated than usual (psychomotor agitation)
• Self-harm
• Suicidal ideation/attempts

DSM-V Criteria

≥5 symptoms in a two-week period that are different from previous function

• Low mood
• Anhedonia
• Decreased concentration
• Worthlessness or excessive guilt
• Fatigue
• Weight changes
• Sleep disturbances
• Psychomotor agitation/retardation
• Thoughts of death or suicide

Symptoms must not be due to the effects of a substance, medical condition, or another psychiatric condition such as schizoaffective disorder. There must not be a history of hypomania/mania.   

Investigations

As depression is largely a clinical diagnosis, investigations are not routinely performed. However, if there is suspicion that the depression is secondary to something else e.g. Cushing’s, it may be prudent to carry out investigations.

Depression Questionnaires

These can be used to aid a diagnosis as well as class the severity of depression.

• PHQ-9
• Hospital Anxiety and Depression Scale
• Beck Depression Inventory

Bloods

• FBC, U&Es, LFTs
• Thyroid function test
• Glucose
• Calcium study
• Dexamethasone suppression test: Cushing’s

Differential Diagnosis

• Grief reaction: Normal reaction to bereavement although certain aspects such as psychosis, suicidal thoughts, hopelessness and excessive guilt tend not to occur with grief reactions.
• Dysthymia: When patients are feeling low but do not meet the diagnostic criteria for major depressive disorder.
• Anxiety disorders: Can coexist with depression.
• Substance misuse: Use of cocaine, opiates, alcohol.
• Endocrine disorders: Hypothyroidism, Cushing’s disease.

Management

The NICE guideline for depression now classifies into two categories – less severe depression, and more severe, defined as a score of <16 and >16 on the PHQ-9 respectively.

• The first line management option for less-severe depression is any of the following treatment options listed below. Antidepressants should not be offered as first-line treatment in patients with less severe depression unless that is the patient’s preference.
• In more severe depression, any of the below treatments can be used first-line although NICE recommend individual CBT with an antidepressant as first-line.

Psychological and Psychosocial Interventions

• Guided self-help
• CBT: Cognitive behavioural therapy which can be delivered in a group setting or individual setting. Looks at the interplay between thoughts, feelings, and behaviour.
• Group exercise
• Group meditation and mindfulness therapies
• Behavioural activation: Again, individual or group based. Helps people understand the relationship between activity and mood. Utilises behaviours to activate positive feelings.
• Interpersonal psychotherapy: Understanding a patient’s interpersonal problems and how relationships affect mental health.
• Counselling
• Short-term psychodynamic psychotherapy: Helping people understand subconscious feelings that subsequently result in dysfunctional thinking.

Antidepressants

SSRIs: Fluoxetine, Sertraline, Citalopram, Paroxetine. Increase risk of GI bleeding so shouldn’t be co-prescribed with NSAIDs/aspirin.

SNRIs (Serotonin and norepinephrine reuptake inhibitors): Venlafaxine. Increase risk of GI bleeding so shouldn’t be co-prescribed with NSAIDs/aspirin.

NaSSA (Noradrenergic and specific serotonergic antidepressant): Mirtazapine

TCA (Tryclic Antidepressants): Nortriptyline, Amitriptyline, Imipramine

MAOIs (Monoamine Oxidase Inhibitors): Phenelzine - these are mainly used in atypical cases.

It’s important to counsel patients on the following points:

• Not to stop taking antidepressants abruptly, miss doses, or not take the full dose as they can experience withdrawal symptoms such as altered sensations, sweating, vertigo, and sleeping difficulties.
• There may be an initial period of increase in suicidal ideation, agitation, anxiety, self-harm, and suicide in the initial stages of treatment with antidepressants particularly in people under the age of 25. It is important to review patients a week after starting antidepressants.
• It can take up to 4 weeks for medication to start working.
• TCAs and venlafaxine are the most toxic in an overdose scenario so they shouldn’t be used in people who are high risk.
• Anti-depressants lower seizure threshold which is important to bear in mind in patients on anti-epileptic drugs.

Electroconvulsive Therapy

• ECT is used in the treatment of severe depression. It involves passing a small electrical current through the brain (either unilaterally or bilaterally) whilst the patient is under general anaesthesia in order to induce a seizure.
• You need informed consent for ECT.
• Side effects include
  • Nausea
  • Headache
  • Memory loss
  • Confusion
  • Fatigue

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181668/

https://onlinelibrary.wiley.com/doi/full/10.1002/mco2.156

https://www.mdcalc.com/calc/10195/dsm-5-criteria-major-depressive-disorder

https://cks.nice.org.uk/topics/depression/

https://www.nice.org.uk/guidance/ng222/chapter/Recommendations#choice-of-treatments

https://www.mind.org.uk/information-support/drugs-and-treatments/electroconvulsive-therapy-ect/