General MedicineTier 1Disease (DEADMAN)

Psychiatry - mood disorders

Description

Major depressive disorder - DSM-5

>=5 of 9 symptoms for >=2 weeks, including at least one of depressed mood or anhedonia, causing functional impairment
Mnemonic SIGECAPS: Sleep, Interest, Guilt, Energy, Concentration, Appetite, Psychomotor, Suicide

Specifiers that change treatment

Melancholic - anhedonia, non-reactive mood, diurnal variation worse in the morning, early morning waking, psychomotor change, anorexia/weight loss
Psychotic - mood-congruent delusions (nihilistic, guilt, poverty). Needs antipsychotic + antidepressant, or ECT
Atypical - mood reactivity, hypersomnia, hyperphagia, leaden paralysis, rejection sensitivity
Peripartum, seasonal, mixed features (mixed features flag bipolarity)

Bipolar disorder

Bipolar I - >=1 manic episode (>=7 days, or any duration requiring hospitalisation; psychosis permitted)
Bipolar II - hypomania (>=4 days, no marked impairment, no psychosis) + >=1 major depressive episode
Cyclothymia - >=2 years subthreshold fluctuation
Most of bipolar illness is spent depressed - this is why it is misdiagnosed as unipolar

Other

Persistent depressive disorder (dysthymia) - >=2 years
Premenstrual dysphoric disorder, disruptive mood dysregulation disorder

Epidemiology

Depression: lifetime prevalence ~15%, 12-month ~5-7%. F:M 2:1
Bipolar I ~1%, bipolar II ~1-2%; M=F; onset late teens to mid-20s
Leading cause of non-fatal burden of disease in Australia
~1 in 5 Australians experience a mental disorder in any 12-month period
Suicide: ~3,000 deaths/yr in Australia, M:F ~3:1 for deaths, F>M for attempts
Markedly higher rates in Aboriginal and Torres Strait Islander peoples, LGBTIQ+ populations, and rural/remote communities

Aetiopathogenesis

Biopsychosocial, with heritability ~35% (depression) and ~70-80% (bipolar)
Stress-diathesis: early adversity -> HPA axis dysregulation -> inc cortisol, dec hippocampal volume
Monoamine hypothesis is incomplete - antidepressants raise synaptic monoamines within hours but take weeks to work
- Current model: inc BDNF -> synaptic plasticity and neurogenesis, explaining the lag
- Ketamine/esketamine act via glutamate-NMDA -> rapid synaptogenesis -> response within hours
Inflammation: raised IL-6 and CRP in a subgroup; explains sickness-behaviour overlap
Secondary (organic) mood disorder - always consider
- Drugs: corticosteroids, interferon-alpha, isotretinoin, varenicline, propranolol, levetiracetam, efavirenz, alcohol, stimulant withdrawal
- Endocrine, neurological, nutritional, infective and inflammatory causes - see Associations

Diagnosis

Clinical diagnosis. The task in a physician exam is to separate depression from medical illness and to exclude bipolarity before treating.

Separating depression from medical illness

Points TO depression	Overlaps with medical illness (non-discriminating)
Depressed mood	Fatigue
Anhedonia	Weight loss
Psychomotor retardation or agitation	Sleep disturbance
Recurrent thoughts of death or suicide	Anorexia
Worthlessness or guilt	Poor concentration
Diurnal mood variation

Somatic symptoms in a medically ill patient are worthless diagnostically. Weight the cognitive and affective symptoms

Always ask before starting an antidepressant

Screen for past hypomania or mania - "Have you ever had a period of days where you needed much less sleep, felt unusually energetic or confident, spent or did things out of character?"
- Missing this and prescribing an antidepressant risks a switch to mania. Bipolar diagnosis is delayed by a median of ~6-10 years
Risk assessment: suicidal ideation, plan, intent, means, prior attempt, access to firearms/medication, protective factors
Substance use, psychotic symptoms, capacity, dependants at risk

Tools

PHQ-9 (severity, monitoring), K10, MADRS, Edinburgh Postnatal Depression Scale
Scales monitor; they do not diagnose

Organic workup - directed, not reflexive

FBE, UEC, LFT, TSH, calcium, B12/folate, glucose, iron studies
Consider by context: cortisol, HIV/syphilis serology, ANA, MRI brain (first episode after 50, focal signs, atypical features), sleep study
A first depressive episode after age 60 with cognitive impairment - consider dementia, and consider Parkinson disease, in which depression often precedes motor signs

Management

A. Foundations - every patient

Reassurance, education and support
Allow adequate time for a full assessment; review at a second consultation if one is insufficient
Safety planning; involve family with consent
Sleep, alcohol, exercise, social connection
Australian: GP Mental Health Treatment Plan gives subsidised psychology sessions

B. Matched to severity

Severity	Approach
Mild	Psychotherapy first-line. Antidepressants have little advantage over placebo in mild depression
Moderate	Psychotherapy or antidepressant; combination better than either
Severe	Antidepressant + psychotherapy. Consider ECT if psychotic, catatonic, refusing intake, or high suicide risk

C. Psychotherapy

Cognitive behavioural therapy - strongest evidence base for mild-to-moderate depression
- Identify unhelpful automatic thoughts using a thought diary, test them, generate alternative responses
- Behavioural activation - scheduling rewarding activity, often the most effective single component
Interpersonal therapy, behavioural activation, mindfulness-based cognitive therapy (relapse prevention)
EMDR and trauma-focused CBT for PTSD

D. Pharmacotherapy

SSRI first-line - sertraline, escitalopram (best tolerability/efficacy balance)
- Review at 1-2 weeks for agitation and suicidality, especially under 25
- Response takes 2-4 weeks; assess adequacy at 4-6 weeks at a therapeutic dose
Second-line: switch within or between classes (SNRI - venlafaxine, duloxetine; mirtazapine if insomnia/weight loss; agomelatine; vortioxetine)
Augmentation for partial response: lithium, aripiprazole/quetiapine, thyroxine
Continue for at least 6-12 months after remission; indefinitely after >=3 episodes
Taper slowly - discontinuation syndrome (dizziness, paraesthesia, "brain zaps"), worst with paroxetine and venlafaxine
Key harms: hyponatraemia (SIADH, especially elderly - check Na at 2-4 weeks), bleeding risk with NSAID/anticoagulant, sexual dysfunction, QT prolongation (citalopram), serotonin syndrome

E. Depression complicating medical illness

Treat the underlying disorder and review contributing drugs first
Drug-induced (e.g. interferon-alpha - mild-to-moderate depression, suicidal ideation, delirium)
- Review ongoing need for and response to the causative drug
- General supportive measures
- SSRI (citalopram, sertraline) or low-dose nortriptyline
  - Nortriptyline is one of the few antidepressants with a measurable therapeutic level - but carries significant overdose risk
- Interferon is now rarely used - DAAs have replaced it for hepatitis C. The principle transfers to checkpoint inhibitors, corticosteroids and isotretinoin

F. Bipolar disorder

Mania: antipsychotic (olanzapine, risperidone, quetiapine, aripiprazole) +/- lithium or valproate; cease antidepressants
Bipolar depression: quetiapine, lurasidone, olanzapine-fluoxetine, lamotrigine
- *Never an antidepressant as monotherapy*
Maintenance: lithium - the only agent with clear anti-suicide effect
- Level 0.6-0.8 mmol/L; monitor level, UEC, TSH, calcium 3-6 monthly
- Toxicity precipitated by NSAIDs, ACE inhibitors/ARBs, thiazides, dehydration
- Valproate is contraindicated in women of childbearing potential - neural tube defects and neurodevelopmental harm

G. Treatment-resistant depression

Definition: failure of >=2 adequate trials
ECT - fastest and most effective; memory effects usually transient
Esketamine (intranasal), rTMS - both available in Australia; PBS/MBS criteria apply

Associations

Neurological

Stroke (post-stroke depression ~30%), Parkinson disease (often precedes motor signs), Huntington disease, multiple sclerosis, epilepsy, dementia, traumatic brain injury

Endocrine/metabolic

Thyroid disorders (hypo- and hyper-), Cushing syndrome, Addison disease, hypocalcaemia, hyperparathyroidism, diabetes

Nutritional

B12 and folate deficiency, thiamine, vitamin D

Infective

EBV, hepatitis B and C, HIV, syphilis, post-viral syndromes

Inflammatory/malignant

SLE, cancer (especially pancreatic), paraneoplastic

Other

Obstructive sleep apnoea, chronic pain, CKD, heart failure, alcohol and substance use disorders

Natural history & complications

Median untreated episode ~6-12 months; ~50% recur after one episode, ~70% after two, ~90% after three
~20-30% become chronic or treatment-resistant
Depression is an independent risk factor for cardiac mortality post-MI, and worsens adherence and outcome in every chronic disease
Bipolar: highly recurrent, ~10 episodes over a lifetime; life expectancy reduced by 10-20 years, mostly cardiovascular
Lifetime suicide risk: ~4-6% in mood disorders overall, higher in bipolar
- Highest risk periods: first weeks of treatment, and the first weeks after discharge

Monitor

PHQ-9 or MADRS at each review
Sodium at 2-4 weeks after starting an SSRI in the elderly
Metabolic screening on antipsychotics - weight, BP, glucose, lipids at baseline, 3 months, then annually
Lithium level, renal and thyroid function 3-6 monthly
Emergence of hypomania at every review of anyone on an antidepressant

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