Psychiatry SC073: I Am Depressed: Mood Disorders Flashcards
Depression always pathological?
Mood fluctuations in responses to disappointment, frustration, losses in everyday life
- Usually short-lived
- Natural despondency can have important **survival function, resulting in **reorientation + ***maturation
Major depressive disorder:
1. **Severe symptoms
2. **Impair adaptations, often disabling
- when enduring, depression can result in impaired function at work, school, in family
Epidemiology:
- >300 million worldwide
- Increase by >18% from 2005-15
- **F:M ~ 2:1
- Average lifetime and 12 month prevalence estimates of MDD: **14.6% and 5.5% in the ten high income and 11.1% and 5.9% in the eight low to middle income countries
- One of leading causes of total DALYs for 1990, 2006, 2016
- One of major causes of **suicide —> 20x↑ in suicide risk
- Increases **non-suicidal mortality (RR 1.2-4) —> Possible mediators:
1. Behavioural risk factors (e.g. poor adherence to treatment, inactivity, ↑ alcohol consumption)
2. Biological risk factors (e.g. altered thrombogenesis)
3. ↑ Subclinical disease / Prevalent disease (e.g. CVS disease)
Clinical presentations of Depression
***Can vary!!!
First obvious sign in Younger people may be:
1. **Loss of interest in friends
2. **Decline in school performance
3. **Self-injury / **Bulimia / Drug use in a previously stable adolescent
Some older people, symptoms may mimic ***dementia
1. Deterioration of cognitive functioning + self-care
Some case may not have symptoms / masked until found dead by suicide
ICD-10 criteria of Depression
ICD-10:
Cardinal symptoms:
1. Depressed mood
2. Loss of interest (Anhedonia)
3. Loss of energy (Anergia)
Additional symptoms:
4. Reduced concentration
5. Reduced self esteem (present)
6. Guilty feelings (past)
7. Hopelessness and pessimism (future)
8. Self harm / suicidal ideas
9. Sleep disturbance
10. Decreased appetite
11. Loss of libido
12. Psychomotor changes
***DSM-5 criteria of Depression
Major depressive disorders:
1. **>=2 weeks
2. Symptoms cause clinically **significant distress / impairment in social, occupational or other important areas of functioning
3. Episode **not attributable to physiological effects of a substance / another medical condition
4. Not better explained by **schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, other specified and unspecified schizophrenia spectrum and other psychotic disorders
5. Absence of previous **manic / hypomanic episode
6. **Clear-cut changes in affect, cognition, neurovegetative functions
-
**>=5 following symptoms, >=1 is either (1) / (2)
—> (1) **Depressed mood (most of the day, nearly every day) (indicated by subjective report / observation by others / irritable mood in children or adolescents)
—> (2) **Markedly diminished interest / pleasure in all / almost all, activities (most of the day, nearly every day) (either subjective account / observation)
—> (3) **Significant weight loss / weight gain (>5% BW in a month) / appetite increase / decrease (nearly every day) (failure to make expected weight gain in children)
—> (4) **Insomnia / Hypersomnia (nearly every day)
—> (5) **Psychomotor retardation / agitation (nearly every day) (observable by others, not merely subjective feelings of restlessness or being slowed down)
—> (6) **Fatigue / Loss of energy (nearly every day) (沒精打彩)
—> (7) **Feelings of worthlessness / excessive / inappropriate guilt (which may be delusional) (nearly every day) (not merely self-reproach / guilt about being sick) (記: Uselessness, Hopelessness, Helplessness, Guilt)
—> (8) **Diminished ability to think / concentrate / indecisiveness (nearly every day) (either subjective account / observation)
—> (9) **Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan / a suicide attempt or a specific plan for committing suicide
Specifiers for major depressive disorder:
1. Course: Single / Recurrent episode
2. Severity: Mild / Moderate / Severe, with **psychotic features, in partial remission, in full remission, unspecified
3. Other specifiers without codes:
- Anxious distress
- Mixed features
- Melancholic features
- Atypical features
- **Mood-congruent psychotic features (與情緒吻合的症狀)
- ***Mood-incongruent psychotic features
- Catatonia
- Peripartum onset
- Seasonal pattern (recurrent episode only)
With melancholic features (憂鬱型抑鬱)
“Distinct quality” of mood
1 of following present during the most severe period of the current episode:
1. Loss of pleasure in all, or almost all, activities
2. Lack of reactivity to usually pleasurable stimuli (does not feel much better, even temporarily, when something good happens)
> =3 of following:
3. A distinct quality of depressed mood characterised by profound despondency, despair, and/or moroseness or by so-called empty mood
4. Depression that is regularly worse in the **morning (normal human should feel good in morning since refreshed)
5. **Early-morning awakening (i.e. >=2 hours before usual awakening)
6. Marked psychomotor agitation / retardation
7. Significant anorexia / weight loss
8. Excessive / inappropriate guilt
With anxious distress
- High levels of anxiety have been associated with higher suicide risk, longer duration of illness, and greater likelihood of treatment non-response
- > =2 ***Anxiety symptoms
- Feeling keyed up / tense
- Feeling unusually restless
- Difficulty concentrating because of worry
- Fear that something awful may happen
- Feeling that the individual might lose control of himself or herself
With mixed features
- A significant risk factor for the development of ***Bipolar I / Bipolar II disorder
- Coexistence of >=3 manic symptoms (insufficient for a manic episode)
- Elevated, expansive mood
- Inflated self esteem / grandiosity
- More talkative than usual or pressure to keep talking
- Flight of ideas or subjective experience that thoughts are racing
- Increase in energy or goal directed activity (either socially, at work or school, or sexually)
- Increased or excessive involvement in activities that have a high potential for painful consequences (e.g. engaging in unrestrained buying sprees, sexual indiscretions, foolish business investments)
- Decreased need for sleep (feeling rested despite sleeping less than usual; to be contrasted with insomnia)
With atypical features
Does not connote an uncommon / unusual clinical presentation as the term implies
- Mood reactivity (i.e. mood brightens in response to actual or potential positive events)
- > =2 of following symptoms:
- Significant weight gain / Increase in appetite
- Hypersomnia
- Leaden paralysis (i.e. heavy, leaden feelings in arms or legs)
- A long standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social / occupational impairment
With psychotic features
- Delusions / Hallucinations are present
- Mood-congruent psychotic features
- Personal inadequacy, **guilt, disease, death, **nihilism (Cotard’s syndrome (delusion of non-existence 幻想自己無左一d部位) / deserved punishment
- Delusion of **persecution
- Delusion of **poverty
- ***Hypochondriacal delusion - Mood-incongruent psychotic features
- Does not involve typical depressive themes
- Or a mixture of mood-incongruent and mood-congruent themes
With catatonia
Catatonic features are present during most of the episode
With peripartum onset (產前/後抑鬱)
Peripartum:
- 50% of “postpartum” major depressive episodes actually begin prior to delivery
- Onset of symptoms occurs **during pregnancy / within **4 weeks following delivery
- With or without psychotic features
- Infanticide is most often associated with command hallucinations to kill the infant / delusions that the infant is possessed
- Postpartum mood (major depressive or manic) episodes with psychotic features occur in from 1 in 500 to 1 in 1,000 deliveries
With seasonal patterns
- Regular ***temporal relationship between onset of major depressive episodes and a particular time of year (e.g. fall / winter)
- ***Full remissions (or a change from major depression to mania or hypomania) also occur at a characteristic time of year (e.g. depression disappears in the spring)
- In the last ***2 years, 2 major depressive episodes have occurred that demonstrate temporal seasonal relationships + no non-seasonal major depressive episodes have occurred during that same period
- Seasonal major depressive episodes substantially outnumber non-seasonal major depressive episodes that may have occurred over the individual’s lifetime
- Often characterised by prominent energy, hypersomnia, overeating, weight gain + craving for carbohydrates
Key changes from DSM-4
-
**Removal of “Bereavement exclusion”
- Depressive symptoms may be understandable / considered appropriate to significant loss (e.g. bereavement, financial ruin, losses from a natural
disaster, a serious medical illness or disability)
- Exercise of clinical judgment based on individual’s history + cultural norms
- Now considered a **precipitating factor - Dysthymia now changed to ***Persistent depressive disorder (include both chronic major depressive disorder + previous dysthymic disorder)
- Introduction of 2 new disorders
- **Disruptive mood dysregulation disorder: persistent irritability + frequent episodes of extreme, out-of-control behaviour in children up to age 18
- **Premenstrual dysphoric disorder: mood symptoms occur during the final week before onset of menses + improve within a few days of menses
Causes of Depression
- Pathophysiology largely unknown
- Several mechanisms have been proposed
- Depressive disorder is caused a combination of biological + social + psychological factors, which disturb the brain’s capacity for stress management
- Biological hypothesis
- Classical “serotonin hypothesis”
- Genetic factors (3x risk among 1st degree relatives)
- Structural brain changes: volume reduction + decreased quantity of glial cells in subgenual cortex, reduced hippocampal size
- Hormonal changes: dysregulation of HPA axis, ↓ estradiol (in women) / testosterone (in men), ↓ triiodothyronine + TSH, ↓ BDNF level - Psychosocial hypothesis
- Early environment: parental separation, physical / sexual abuse, non-caring / overprotective parenting styles
- Lack of supportive networks, poorly functioning relationships, poor social integration
- Stress + trauma: long term difficulties, recent life events (in particular events that lead to feelings of entrapment and humiliation)
- Personality: sociotropy (a strong need for approval), neuroticism (情緒不穩定性)
- Cognitive theory: **Cognitive distortions, e.g.
**SOAP
—> **Selective abstraction (斷章取義): focusing on a detail and ignoring more important features of a situation
—> **Overgeneralisation (以偏概全): drawing a general conclusion on the basis of a single incident
—> **Arbitrary inference (妄下判斷): drawing a conclusion when there is no evidence for it and even some evidence against it
—> **Personalisation (過度自責): relating external events to oneself in an unwarranted way
—> **Magnification: blowing things out of proportion (web)
—> **Minimisation: downplaying importance of positive thought, emotion, event (SpC Psychi PP)
- Psychoanalytical theory: loss of an “object”, insecure attachments
Classical “serotonin hypothesis”
- Diminished activity of serotonin pathways
- Antihypertensive drug reserpine (deplete monoamine) produced a depressive state
- Diminished monoaminergic activity was detected in brains of decedents of suicide + bodily fluids of people with depression
- Evidence suggests that cause of depression is far more complicated than reduced level of serotonin
- Monoamines: Serotonin + Norepinephrine + Dopamine are relevant to mood regulation, and play an essential role in regulation of other bodily function
Serotonin:
- Affects body temperature
- Regulates sleep and wakefulness
- Mood and impulse control
- Low level of serotonin metabolites in brains of suicide decedents + spinal fluids of depressed patients
- Serotonin functioning also reduces in depressed patients
Norepinephrine:
- Regulates mood + anxiety levels.
- Mood symptoms emerged among patients who took propranolol
Dopamine:
- Regulates motor + mental activity, attention and motivation
- Dopaminergic neurons in ***mesolimbic reward pathway play an important role in motivation, reinforcement + pleasure response
- Diminished in brains of suicidal decedents with depression
Other neurotransmitter:
Abnormal Glutamate, GABA, Substance P have been detected in patients with depression
Assessment of Depression
- History
- Mental state examination
- Use of standardised instruments
- P/E + Investigation to rule out medical conditions that may cause depressive symptoms
- Basic: CBP, R/LFT, **TFT
- Others:
—> Blood alcohol level
—> Blood and urine toxicology screen
—> HIV test
—> **Cosyntropin (ACTH) stimulation test (for Addison disease)
—> EEG (for epilepsy) / CT / MRI (for organic brain syndrome or hypopituitarism) should be considered if indicated by history / P/E
Objective measures of severity of depression:
1. ***Hamilton Rating Scale for Depression (HAM-D)
2. Montgomery Asberg Depression Rating Scale (MADRS)
3. Patient Health Questionnaire 9 (PHQ 9)
4. Beck Depression Inventory (BDI)
5. Center for Epidemiologic Studies Depression Scale (CES-D)
6. Special patient groups (e.g. Geriatric Depression Scale, Cornell Scale for Depression in Dementia, Edinburgh Postnatal Depression Scale)
- Useful in clinical practice and research but not diagnostic
- Should not be used as a substitute for a clinical diagnosis made from a thorough interview
***DDx of Depression
-
**Psychiatric conditions
- **Adjustment disorder with depressed mood
- **Manic episode with irritable mood / mixed episodes
- **Persistent depressive disorder (formerly Dysthymic disorder)
- ***Anxiety disorder
- Substance / Medication-induced depressive disorder
- Mood disorder due to another medical condition - Medical conditions
- Neurological disorders (e.g. epilepsy, Parkinson’s disease, dementia, multiple sclerosis, Huntington disease, cerebrovascular disease, migraine)
- Endocrine disorders (e.g. hypothyroidism, hyperthyroidism, Cushing’s syndrome, Addison disease, prolactinomas, hyperparathyroidism)
- Drug-related conditions (e.g. antihypertensive esp. reserpine, methyldopa, smoking cessation aids, steroids, sex hormones, medications that affect sex hormones, H2 blockers, sedatives, muscle relaxants, appetite suppressants, chemotherapy agents, alcohol / cocaine / amphetamines / cannabinoids / sedatives / hypnotics / narcotics abuse)
- Infectious disease (e.g. mononucleosis, HIV infection, hep C infection, Lyme disease, syphilis)
- Neoplasia / Paraneoplastic syndromes (e.g. pancreatic cancer)
- Chronic diseases (e.g. coronary artery disease, type II DM)
- Chronic pain + psychosomatic conditions
- Sleep-related disorders, in particular OSA
Management of Depression
- Pharmacological
- Non-selective monoamine reuptake inhibitors
- Selective serotonin reuptake inhibitors (SSRI)
- Serotonin and norepinephrine reuptake inhibitors (SNRI)
- Norepinephrine + Dopamine reuptake inhibitors
- Monoamine oxidase inhibitors + Reversible inhibitors of MAO-A
- Melatonergic antidepressants
- Others (Trazodone, Mirtazapine) - Psychosocial
- Interpersonal therapy
- CBT
- Problem solving therapy
- Supportive therapy - Physical activity
- Aerobic / Nonaerobic execise
- Home-based - Physical treatment
- Electroconvulsive therapy (ECT)
- Deep brain stimulation
- Transcranial magnetic stimulation (TMS)
- Transcranial direct current stimulation (TDCS) - Diet
- Pharmacological treatment
- Non-selective monoamine reuptake inhibitors
- TCA (Amitriptyline, Imipramine, Nortriptyline, Clomipramine, Dothiepin, Trimipramine, Desipramine)
- Tetracyclic antidepressants (Mianserin) - Selective serotonin reuptake inhibitors (SSRI)
- Fluoxetine, Paroxetine, Sertraline, Citalopram, Escitalopram, Vortioxetine - Serotonin and norepinephrine reuptake inhibitors (SNRI)
- Duloxetine, Venlafaxine, Desvenlafaxine - Norepinephrine + Dopamine reuptake inhibitors
- Bupropion - Monoamine oxidase inhibitors + Reversible inhibitors of MAO-A
- Tranylcypromine, Phenelzine, Isocarboxazid, Selegiline, Moclobemide - Melatonergic antidepressants
- Agomelatine (SpC Psychi: Need to monitor ***LFT) - Others (Trazodone, Mirtazapine)
Systematic review:
- Agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine are more effective than other antidepressants
- Agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine are more tolerable than other antidepressants
- Older antidepressants (e.g. tricyclics, MAOIs) associated with significant adverse events + drug-drug interactions
- Marked inter-individual variation in antidepressant tolerability
- Choice of medication determined by clinical circumstances, patient’s physical comorbidity + concomitant medications
- Psychosocial treatment
- Systematic psychological treatment with well-defined objectives
- CBT, Interpersonal therapy highly effective in remedying mild and moderate depression
- As many as 85 % of patients receiving both antidepressants + psychotherapy achieve remission
- Interpersonal therapy
- Problems are understood in interpersonal context
- e.g. facilitate grieving process, encourage ***role transition, explore interpersonal disputes, improve interpersonal skills - CBT
- Monitor, evaluate + modify negative dysfunctional thoughts + distorted perceptions and beliefs
- Use cognitive techniques (e.g. list pros & cons, examine evidence)
- Increase activity scheduling - Problem solving therapy
- Improve ability to deal with specific everyday problems + life crisis
- Identify problems, brainstorm ways to solve problems + evaluate effectiveness —> best possible solution - Supportive therapy
- Facilitate expression of affect, highlight positive and successful experiences, offer empathy, impart therapeutic optimism
- Empathic listening, reflection, emotional processing, encouragement
- Physical activity
- Aerobic exercise (e.g. running, walking)
- Nonaerobic exercise (e.g. strength training, progressive resistance training)
- Inverse association between duration of intervention + magnitude of the association of exercise with depression
Mechanisms:
- Normalise BDNF level
- Change neurotransmitter functioning, especially serotonin and endorphin
- Improve psychological health + social sense of wellbeing
- Physical treatment
-
**Electroconvulsive therapy (ECT)
- Where **prompt action is needed e.g. strongly suicidal
- SE: headache, **confusion, **memory impairment, **seizure induction
- Need for **anaesthesia, costs
- Inconvenience to the patient, stigma - Deep brain stimulation
- Require ***craniotomy - Transcranial magnetic stimulation (TMS)
- **Non-invasive
- Hand-held, plastic-coated coil placed close to the scalp
- Creates a potent (near 1.5T) but brief (µs) **magnetic field that stimulates electrical activity in the nerve tissue below the coil
- Carried out while the person ***awake and alert
- Limited SE
- Suitable for use in medically unwell people who cannot tolerate antidepressants or ECT
- Monotherapy / Adjunct - Transcranial direct current stimulation (TDCS)
- ***Non-invasive
- Anode: ↑ cortical activity and excitability
- Cathode: ↓ cortical activity and excitability
- Modulates spontaneous neuronal network activity
- Modifies responsivity of the targeted brain regions to afferent input or efferent demand
- Limited SE
- Diet
- Healthy diet may help as part of the overall depression treatment though **NO specific diet has been proven to relieve depression
1. **Food rich in antioxidants (e.g. blueberries, oranges, carrots, nuts)
2. **Complex carbohydrates (e.g. whole grains) can have a calming effect
3. **Protein-rich foods (e.g. turkey, tuna, and chicken) boost alertness
4. **Mediterranean diet as a source for B vitamins
5. **Omega-3 fatty acids - Essential polyunsaturated lipids that influence cellular metabolism and function
- Earlier studies linked low seafood intake (a major source of omega-3 FAs) and mood disorders, and positive results with fish oil intervention —> subsequent results more diversified
- EPA rather than DHA as the effective component
- Monotherapy / Adjunct therapy
Suicide risk assessment (Ryan Ho)
Stage of suicide:
Depressed mood
—> Hopelessness
—> Pointlessness of life (I can’t see any future)
—> Passive rejection of life (I’d be better off dead)
—> Active rejection of life (I wish I were dead)
—> Passive thoughts of self-harm (I could take an overdose)
—> Active thoughts of self-harm (I will take an overdose)
—> Act
Past:
1. Demographic factors
2. Psychiatric + Medical history
3. Recent stressors
Present:
1. Current mental state
2. Suicidal attempts / intent / thoughts
- Depressed mood
- Negative thoughts (Guilt, Worthlessness, Hopelessness)
- Suicidal acts
—> Purpose (expectation of dying, perceived lethality of means)
—> Plans
—> Preparations (will, suicide note, putting affairs in order)
—> Concealment (avoid discovery, delayed being rescued)
—> Communication (not telling others, no help sought after act)
—> Attempts
Future:
1. Amenable risk factors
2. Protective factors
***Assessment of suicidal attempts (Ryan Ho)
- Background
- Establish suicidal attempt / ideation
- Reason for suicide (life stressors, mood disorder, delusion, hallucination, substance abuse) - Before
- **Suicidal ideation (duration, frequency, intensity)
- **Belief of intent (true intention vs attention seeking, perceived lethality)
- ***Suicidal plan + preparation + communication
—> Purpose (expectation of dying, perceived lethality of means)
—> Plans
—> Preparations (will, suicide note 遺書, putting affairs in order 身後事)
—> Communication (not telling others)
—> Concealment (avoid discovery, delayed being rescued) - During
- **When, Where, Who, How
- Lethality of means
- **Concealment (avoid discovery, delayed being rescued)
- ***How patient was saved - After
- **Communication (sought help / informing others after act)
- **Remorse / Reaction
- Future attempts / plans - Risk factors
- **Previous attempts
- Friend / Relative completing suicide
- Psychiatric disease
- Medical disease
- **Substance abuse
- Impulsivity - ***Protective factors (有咩留戀)
- Good social + family support
- Good coping skills (e.g. positive problem-solving)
- Engagement in responsibilities (e.g. children, pregnancy, pets)
(Electroconvulsive therapy (ECT) (Ryan Ho))
MOA:
- Induction of seizure to treatment psychiatric disorders
- Underlying MOA unknown
Indications (ECT: Emergency, Catatonia, Treatment-resistant):
1. **Severe depression
- Rapid definitive response required
- Life-threatening situations e.g. persistent suicidal intent
- Refractory to treatment
- Previous good response to ECT
2. Mania
3. **Catatonia
4. Puerperal psychosis with prominent mood symptoms (rapid treatment to allow reuniting with baby)
5. ***Schizophrenia (Treatment-resistant)
Course:
- 6-12 treatment
- 2-3 per week
Process:
- 5 mins **GA
- 2 electrodes deliver electric pulse —> induce **>=15s of generalised tonic-clonic seizure
- Unilateral vs Bilateral: Bilateral more effective but more cognitive impairment
SE:
- **Confusion
- **Amnesia (Anterograde / Retrograde)
CI (Relative):
- Heart disease
- ↑ ICP
- ICH risk
- Poor anaesthetic risk
