4. Mood Disorders Flashcards
Etiology of Depression
- Genetics
- 40-70% chance of developing depressive episode if 1st degree relative suffer from depressive episode - Organic
- Cushing syndrome, Addison disease, Parkinson disease, stroke, epilepsy, coronary artery disease, thyroid
- Medications - Psychosocial Factors
- Adversity in childhood
— Maternal loss, disruption of bonding
— Poor parental care
— Physical / sexual abuse
- Adversity in adulthood
— Women: absence of a confiding relationship
— Men: unemployment, divorce
- Recent life events
— Loss of a child
— Death of a spouse
— Divorce
— Marital separation
— Imprisonment
— Recent death of a close family member
— Unemployment - Presence of cognitive errors
- Magnification: tendency to magnify the magnitude of a failure and dismiss all previous successes
- Overgeneralisation: generalisation of failure in one area of life to other areas of life
- Personalisation: feeling that one is entirely responsible for failure and discounting the role of other individuals in responsibility for failure
- Selective abstraction: choose to focus on negative aspects, forget positive aspects
DSM-5 Diagnostic Criteria for Depressive Disorder
At least __ of the following symptoms for a minimum duration of __ weeks
At least 5 of the following symptoms for a minimum duration of 2 weeks:
MSIGECAPS
1. Low mood for most of the days (core feature)
2. Anhedonia: Diminished interest (no derived pleasure) in almost all activities (core feature)
3. Weight loss, loss of appetite
4. Sleep difficulties
5. Psychomotor changes (agitation or retardation)
6. Low energy
7. Feeling worthless, or excessive guilt
8. Attention and concentration difficulties
9. Recurrent passive or active ideations of self-harm and suicide
+ Symptoms must cause marked impairments in terms of premorbid functioning
More serious depressive subtypes
With psychotic features (mood congruent/incongruent)
With catatonia
Recurrent Depressive Disorder
At least 2 MDD episodes with intervals of at least 2 consecutive months (in which criteria are not met for a major depressive episode)
Cyclothymia
Numerous episodes with hypomanic symptoms and depressive symptoms over a duration of at least 2 years
*episodes do not meet the full diagnostic criteria for hypomania or depression
*must not be free from symptoms for more than 2 months in duration each time
Dysthymia (persistent depressive disorder)
Pervasive depressed mood for most part of the days for a total duration of at least 2 years
For dysthymia, apart from depressed mood, patient should have at least 2 of the following symptoms:
HE’S 2 SAD
Hopelessness
Energy loss or fatigue
Self-esteem is low
2 years minimum of depressed mood most of the day, for more days than not
Sleep is increased or decreased
Appetite is increased or decreased
Decision-making or concentration is impaired
Premenstrual Dysphoric Disorder
Onset of symptoms should be at least in the week prior to the onset of menstruation, and symptoms should improve a few days after the onset of menstruation
Intensity of symptoms should be minimal or resolved post-menstruation
Features of Atypical Depression
Reactive Mood
Appetite increase
Increase sleep
Leaden paralysis (heavy sensations in limbs)
Sensitivity to interpersonal rejection
Differential diagnosis for depressive disorder
Adjustment disorder
Bipolar disorder
Schizoaffective disorder
Schizophrenia with predominant negative symptoms
Dementia
Parkinson’s disease
Post-stroke depression
Organic causes
Substance misuse
Medication-induced
Questionnaires used in depression
- Beck Depression Inventory
- Hamilton Depression Scale
- Montgomery-Asberg Depression Rating Scale
“Psychosocial” management of patients with depression
Cognitive Behavioural Therapy
Interpersonal Therapy
Psychoeducation
Supportive therapy
Counselling
Sleep hygiene advice
“Bio” management of depression
- Selective serotonin reuptake inhibitors (1st line)
- Serotonin noradrenaline reuptake inhibitors (2nd line)
- Noradrenaline Specific Serotonin Antidepressant (NaSSAs)
- Noradrenaline Dopamine Reuptake Inhibitor (NDRI)
- Tricyclic Antidepressants (NEVER 1st line)
- Monoamine Oxidase Inhibitors (MAOi)
Indications of SSRIs
- Depressive disorder
- Anxiety disorder
- Obsessive compulsive disorder
- Bulimia nervosa (fluoxetine)
Absolute contraindication to SSRIs
Mania
MOA of SSRIs
- Selectively block reuptake of serotonin at presynaptic nerve terminals
- Increase serotonin concentration at synapses
Examples of SSRIs
Fluoxetine, fluvoxamine, sertraline, paroxetine, escitalopram
General S/E of SSRIs
- GI (most common): nausea, abdo pain, diarrhoea, constipation
- Autonomic: agitation, tremor, insomnia
- Sexual dysfunction (loss of libido, delayed ejaculation)
- Discontinuation symptoms (flu-like sx upon stopping anti-Ds abruptly)
— depends on half life - [Black box warning] Increased suicidal ideation (in <24yo in first 1-2 weeks of initiation)
- Serotonin syndrome
- Maniac episode if underlying bipolar
- Cardio-toxicity in overdose (very low risk)
- Hyponatremia 2’ SIADH
Discontinuation symptoms
FINISH
- Flu-like symptoms (muscle ache, lethargy, headache)
- Insomnia
- Nausea
- Imbalance
- Sensory disturbances
- Hyperarousal
How does discontinuation symptoms occur?
Increased serotonin due to SSRIs -> upregulation of receptors
When SSRI is withdrawn
-> receptors don’t down-regulate immediately
How long does it take for the anti-Ds to take effect?
2-4 weeks for initial effects
4-6 weeks for good effects
Pros of Fluoxetine
Longest half life
-> lowers risk of discontinuation sx
-> therapeutic effects last longer than 5 days as fluoxetine breaks down into active metabolite which lasts ~1 week
=> requires 5 weeks washout if starting MAOi
Safe in overdose
Duration of washout for fluoxetine if starting MAOi
5 weeks
Cons of Fluoxetine
- Significant P450 interactions -> reduce use in patient with multiple medical co-morbids
- Initial activation -> increase anxiety and insomnia
- Do not give patients with bipolar depression due to long half life -> can lead to mania
Pros of Fluvoxamine
- Possess analgesic properties
- Sedating (give @ night)
- Less initial activation compared to other SSRIs
Cons of Fluvoxamine
- Short half life -> higher risk of discontinuation sx
- Causes weakness
- Significant P450 interactions -> reduce use in patient with multiple medical co-morbids
Pros of Sertraline
- Good in prolonged QTc -> safe for cardiac patient
- Less sedating than paroxetine
- Very weak P450 interactions
- Sleep wake neutral
- Safe for those with recent AMI
- Safest antiD in pregnancy
Cons of Sertraline
- Full absorption requires a full stomach
- Increased number of GI effects especially diarrhoea -> colitis
Pros of Paroxetine
Short half life with no active metabolite -> no build up
Cons of Paroxetine
- Short half life -> discontinuation sx
- Significant CYP206 inhibition
- Sedating
- Weight gain
- Anticholinergic sx
- Avoid in pregnancy (teratogenic)
Pros of Escitalopram
Lesser drug-drug interaction
Sleep wake neutral
Cons of Escitalopram
Not safe to combine with other drugs, causing QTc prolongation
Nausea, headache
Expensive
Examples of Serotonin Noradrenaline Reuptake Inhibitors
Venlafaxine
Duloxetine
MOA of SNRIs
Blocks serotonin and noradrenaline reuptake
Indications for SNRIs
MDD
Anxiety disorders
Good for low energy symptoms
Neuropathic pain (has analgesic properties)
C/I for SNRIs
Hypertension
S/E of SNRIs
Hypertension
Sexual dysfunction
Headache, nausea
Palpitations
Pros of Venlafaxine
Minimal DDI, no P450 activity
Short half life and fast renal clearance
Cons of Venlafaxine
Increase 10-15mmHg diastolic bp
Sexual S/E
QTc prolongation
Examples of Noradrenaline Specific Serotonin Antidepressant (NaSSAs)
Mirtazepine
MOA of NaSSA
5HT2 and 5HT3 antagonist
*effect on 5HT3 receptor is less likely to cause nausea side effect
Indications of NaSSA
MDD
Good for insomnia sx -> very sedating at lower doses
Good for low appetite (increases appetite and weight gain)
S/E of NaSSA
Weight gain (increase serum cholesterol and triglycerides) due to increased appetite
Sedation
Agranulocytosis
Example of Noradrenaline Dopamine Reuptake Inhibitor (NDRI)
Bupropion
Pros of NDRI
Good as augmenting agent
Weight loss effect
Nil sexual dysfunction
Nil sedation
Nil cardiac s/e
Second line ADHD agent
S/E of NDRI
Insomnia
AVOID if risk of seizure (lowers seizure threshold)
Abuse potential
Agitation, anxiety
Examples of Tricyclic Antidepressants
Amitriptyline
Nortriptyline
Desipramine
Imipramine
MOA of TCAs
Inhibit uptake of serotonin (mainly) and noradrenaline
S/E of TCAs
- Lethal in overdose (avoid in suicidal patients)
- Cardiotoxic -> QT prolongation even at therapeutic serum level
- Lower seizure threshold
- Hyponatremia
- Anticholinergic (dry eyes, dry mouth, constipation, urinary retention, blurred vision)
- Anti-histaminic (sedation and weight gain)
- Anti-adrenergic (orthostatic hypotension, sedation, sexual dysfunction)
Examples of Monoamine Oxidase Inhibitors (MAOi)
Moclobemide
MOA of MAOi
Binds irreversibly (but moclobemide binds irreversibly) to monoamine oxidase -> increases noradrenaline, serotonin, dopamine
S/E of MAOi
Serotonin syndrome (if combined with other antiDs)
Tyramine HTN crisis
- > avoid wines, cheese, fermented beancurd, cheese, cured meats, sympathomimetics
(Tyramine will increase release of noradrenaline hence if patient is on MAOi and eats tyramine, it will increase noradrenaline)
What is the washout period before starting MAOi for other drugs?
2 weeks washout period except fluoxetine - 5 weeks
Treatment mx for 1st episode of depression
Continue tx for 6-9 months after resolution of sx
If stopped immediately upon recovery, 50% can have relapse
Treatment mx for repeated episodes of depression
Continue tx for longer eg 2 years after resolution of sx
What is tx resistant depression?
MDD that fails to respond to 2 different antiDs (given as monotherapy at optimum doses)
Mx for tx resistant depression
- Change antiD
- Combine antiD (beware serotonin syndrome esp MAOi)
- Augmentation (combine antiD with mood stabilisers/anti-psychotics or neurostimulation)
- ECT (actively suicidal, refusing food, catatonic, refractory to meds)
6 major conditions for ECT
- Major depressive disorder
- Bipolar disorder (mania/depression)
- Schizophrenia
- Schizoaffective disorder
- Catatonia
- Neuroleptic malignant syndrome
*ECT also helps improve motor deficits in parkinson’s
Types of patient that would benefit from ECT
- Suicidal
- Not eating
- Pregnant
- Severe, not responding to previous treatments, or previously responded well with ECT
*Must be used along with maintenance phase antiD tx
Contraindications of ECT
NO absolute C/I
Relative C/I:
1. Raised ICP
2. Recent cerebrovascular event
3. Brain aneurysm or vascular malformations that are susceptible to rupture in the event of increased blood pressure or raised ICP
4. Unstable cardiovascular illness such as recent myocardial infarctions, unstable angina, or poorly compensated heart failure
5. Poor anaesthetic risks
6. Retinal detachment
7. Phaeochromocytoma
S/E of ECT
Early (Usually transient or temporary):
- Short-term memory loss, usually resolves completely within a few hours
- Headache
- Muscle aches
- Nausea/vomiting
- Giddiness
- Confusion
- Treatment-emergent mania: ECT may cause depressed patients to become manic
Late:
- Memory impairment
+ GA risks
*Cognitive risks are dependent on strength of current, electrode placement and number of applications
Electrode Placement - Bitemporal
Strongest, fastest response rate, highest chance of cognitive side effects
Conditions: Catatonia / NMS / Urgent response needed
Electrode Placement - Bifrontal
Strong, fast response rate, lower chance of cognitive side effects, better for psychosis
Conditions: Schizophrenia / Psychosis
Electrode Placement - Right unilateral
Milder, avoid directly stimulating L brain-memory and cognition, may require 1 or 2 more sessions
Conditions: Depression / Mania
Which, out of the 6 conditions, has the highest remission rate from using ECT?
Catatonia
Advantages of repetitive Transcranial Magnetic Stimulation (rTMS)
- Enables focal stimulation of smaller areas of the brain than is possible
- Non-invasive
- No need for anaesthesia
- No cognitive side effects
S/E of rTMS
- Headaches
- Light-headedness
- Scalp, facial, eye, jaw twitches/discomfort
- Dizziness
- Nausea
- Tinnitus
- Hypomanic switch (<1%)
- Most serious known risk: unintended seizure
Contraindications
-History of epileptic seizures
- Foreign metal body in eye or cranium (excluding braces or dental fillings)
Risk factors for seizures in rTMS
- Personal or family history of epilepsy
- Post-stroke or head injury with neurologic sequelae
- Use of seizure-lowering threshold medications
- Recent dose reduction of medication with anticonvulsant properties (eg. Benzodiazepines)
- Neurologic disorders or medical conditions that may be associated with lowered seizure threshold
eg. Sleep deprivation, raised ICP, substance withdrawal
rTMS vs ECT
Both are neurostimulation methods that are effective for treatment of MDD
- Patient profile recommended for ECT differ from those recommended for rTMS
- rTMS response rates are poor in patients whom ECT has failed
- TMS uses a magnetic coil to stimulate specific regions of the brain that are thought to play a role in depressions symptoms vs ECT uses electrical currents to induce a seizure in a sedated patient’s brain
Current indications for rTMS
Depression
Post stroke rehabilitation for motor function
Factors increasing seizure threshold
Male
Old age
Baldness
Paget disease
Dehydration
Previous ECT and BZD tx
Factors lowering seizure threshold
Caffeine
Low CO2 saturation of blood
Hyperventilation
Sleep deprivation
Raised ICP
Substance withdrawal
What is Cognitive Behavioural Therapy?
Cognitive: identify and challenge negative automatic thoughts
- dysfunctional thought diary
- consists of: defining high risk situation
Behaviour: activity scheduling (for depressed) / relaxation techniques (mixed anxiety and depression)
What is interpersonal therapy?
- depression precipitated by interpersonal problems
- improve interpersonal relationships
Duration of depressive disorder (mild/severe/chronic)
Mild/moderate depressive disorder: 4-30 weeks
Severe depressive disorder: 6 months
Chronic disorder: 2 years
Favourable prognostic factors of depression remittance
Acute onset, reactive depression, earlier age of onset
Favourable prognostic factors of depression remittance
Acute onset, reactive depression, earlier age of onset
Poor prognostic factors for depression remittance
Insidious onset, old age of onset, neurotic depression, low self esteem, residual symptoms
What is bipolar disorder?
Bipolar disorder is a mood disorder with 2 different phases (manic phase and depressive phase)
Aetiology of bipolar disorder
Genetics: children of parents suffering from bipolar disorder have a -fold increase risk
Monoamine theory:
- increased levels of dopamine, noradrenaline and serotonin
- excitatory neurotransmitter glutamate
Onset of 1st manic episode
mid-20s
Precipitants of 1st manic episode
- Often precipitated by life events eg. bereavement, personal separation, work-related problems, loss of role
- In patients predisposed to bipolar disorder, antidepressant monotherapy can precipitate 1st manic episode
Important precipitating factors of manic episodes
High expressed emotion
Sleep deprivation
Flying overnight from west to east
Antidepressant monotherapy is a recognised precipitant of first manic episode in patients predisposed to bipolar disorder
-
Organic causes of mania
- Cerebrovascular event
- Head injury
- Endocrine causes
- Illicit substances (cannabis, amphetamine, cocaine)
- Medications
- Other CNS disorders
Lesions in the ____ are associated with mania
right cerebral hemisphere
DSM-5 Criteria for Manic Episode
Individual having persistent elevated or irritable mood for most of the days within a time period of at least 1 week
+ at least 3 of the following sx (4 if mood is only irritable):
RADSSSS
1. Increased self- confidence
2. Reduced need for sleep
3. Increased talkativeness, with increased pressure to talk (hard to interrupt)
4. Racing thoughts
5. Easily distractible
6. Increase in number of activities engaged
7. Engage in activities with potential risks for serious consequences
+ Marked functional impairment
RADSSSSSS
- Racing thoughts
- increase in number of - - Activities engaged
- easily Distractible
- Self-confidence increase
- Speech - increased talkativeness
- Sleep - reduced
- Serious consequences
- Sexual indiscretions
- Superpower (Grandiose delusions)
What is Bipolar 1 Disorder?
Individual must have at least 1 manic episode
What is Bipolar 2 Disorder?
Individual must have a past or current hypomania episode + past or current major depressive episode
+ sx affects functioning but must not be severe enough to cause marked impairment
What is a hypomania?
Individual having persistent elevated or irritable mood for most of the days within a time period of at least 4 days
+ at least 3 of the following sx (4 if mood is only irritable):
RADSSSS
1. Increased self- confidence
2. Reduced need for sleep
3. Increased talkativeness, with increased pressure to talk (hard to interrupt)
4. Racing thoughts
5. Easily distractible
6. Increase in number of activities engaged
7. Engage in activities with potential risks for serious consequences
+ level of function will NOT be markedly impaired
Difference between mania and hypomania
Duration: 1 week (M) vs 4 days (HM)
Functional impairment: Marked impairment (M) vs not markedly impaired (HM)
What is Rapid Cycling Disorder?
Consists of at least 4 episodes of mood disturbance in one year
- Mania
- Hypomania
- Major depressive episode
*more common in women
Questionnaire used in Bipolar Disorder
Young mania rating scale
Mania: Acute Management
- Antipsychotics: Haloperidol, olanzapine, quetiapine
- Mood stabiliser: sodium valproate or carbamazepine monotherapy
- For agitation: Haloperidol, olanzapine or lorazepam
Bipolar Depression: Acute management
For MILD depressive sx: review patients in 1 to 2 weeks without giving an antiD
For MODERATE to SEVERE sx: add antiD to mood stabiliser
- Mood stabiliser: Lithium
- Antipsychotics: Quetiapine or olanzapine monotherapy or olanzapine-fluoxetine combi
- Anti-depressants (use with CAUTION): combine fluoxetine with mood stabilisers
- Psychotherapy: CBT
Maintenance treatment for bipolar disorder
Lithium, valproate or olanzapine may be used to prevent relapse
Examples of mood stabilisers
- Lithium
- Sodium valproate
- Carbamazepine
- Lamotrigine
Indications of Lithium
- 1st line tx in bipolar disorder
- Benefit of reduced suicide rate
- Effective prophylaxis of both mania and depressive episodes
Baseline investigations before starting lithium
FBC, RP, TFT
+ UPT in woman
Monitoring for lithium
- Steady state achieved after 5 days
- Check lithium levels 12h after last dose
- Once stable -> check lithium levels every 3 months and TFT & RP every 6 months
- Goal
Depression: 0.4-0.6
Bipolar: 0.6-1.2
S/E of lithium
- Metallic taste
- Nausea
- Polydipsia
- Polyuria
- Edema
- Weight gain
- Fine tremor
Long term complications of lithium
Hypothyroidism
Renal failure
Lithium toxicity - causes of a raised lithium level
Drugs
- Thiazides
- ACE-i
- NSAIDs
- Antibiotics
Dehydration
Chronic Kidney Disease (reduced excretion)
Signs of mild lithium toxicity (1.5-2mmol/L)
Drowsiness
GE-like symptoms (Diarrhoea)
Fine tremor
Nystagmus
Signs of moderate lithium toxicity (2-3mmol/L)
Arrythmia
Coarse tremor
Ataxia
Signs of severe lithium toxicity (>3mmol/L)
Confusion, convulsion, coma
Severe oliguria
Management of lithium toxicity
Cessation of lithium and haemodialysis
Use of lithium in pregnant woman can cause
Ebstein abnormality in foetal hearts -> pathology of tricuspid valve
Sodium valproate as prophylaxis
As effective as lithium in mania prophylaxis but less so for depression prophylaxis
Indications to use sodium valproate
- Rapid cycling bipolar patients (F>M)
- Comorbid substance abuse (eg. alcohol)
- Mixed (mania and depressive sx for at least 1 week)
- Comorbid anxiety disorder
- Irritable mania
C/I of sodium valproate
Patients with liver failure
S/E of sodium valproate
GI effects
Weight gain
Hair loss
Tremors
5Ts
- Tremor
- Thicc: weight gain
- Thrombocytopenia
- Transaminitis: Hepatotoxicity
- Teratogenic: neural tube defects
Serious S/E of sodium valproate
Hepatotoxic
Pancreatitis
Thrombocytopenia
Polycystic ovary syndrome
Use of sodium valproate in pregnant woman can cause
Increase risk of neural tube defect
-> folic acid supplementation to be given
Baseline investigations before starting sodium valproate
FBC, LFT, pregnancy test
Benefit of using carbamazepine over lithium/valproate
Does not cause weight gain
S/E of carbamazepine
Severe adverse cutaneous reaction (SCAR) - test for HLA-B*1502)
Agranulocytosis
Leucopenia
Reduce efficacy of oral contrapceptives if taken together
Dizziness, headache, drowsy
What must be tested for before starting carbamazepine?
HLA-B*1502
Use of Lamotrigine is more effective for __ than __
Use of Lamotrigine is more effective for bipolar depression than mania (acute and prophylactic)
S/E of lamotrigine
Severe adverse cutaneous reaction (SCAR)
- a/w SJS & TEN but less so compared to carbamazepine
*stop if rash develops
Questionnaire to assess suicide risk
SAD PERSONS
Sex: male
Age: <19 or >45
Depression/hopelessness
Previous suicide attempt
Excessive alcohol/drug use
Rational thinking loss -> Psychosis
Separated/widowed/divorced
Organised & serious attempt
No social support
Stated future intent
C/I of lithium
Renal failure patients
Abnormal grief can be…
- inhibited
- delayed
- chronic
Which gene is associated with increased risk of depression?
Presenilin-1 gene on chromosome 14
What herb is most commonly used to treat mild to moderate depression?
St. john’s wort
MOA of lamotrigine
Acts at voltage sensitive sodium channels
Inhibits release of excitatory amino acid neurotransmitters
5 stages of bereavement (normal grief)
1: Denial
2: Anger
3: Bargaining
4: Depression
5: Acceptance
- guilty about certain action to be taken at the time of death
- feeling like I should have died instead of the deceased person
- sensations about seeing & hearing the deceased person
Inhibited grief
absence of expected grief symptoms at any stage
Delayed grief
avoidance of painful symptoms within 2 weeks of loss
chronic grief
continued significant grief-related symptoms > 6 months after loss of
Indicators of progression of bereavement into depression
- symptoms still present 2 months after loss
- guilt, suicide thoughts, hallucinations unrelated to the dead person
- marked worthlessness
- marked psychomotor retardation
- prolonged and marked functional impairment
If patient presents with low mood first, and then have psychosis for a short duration of time… what ddx to consider?
Psychosis depression
Treatment for pseudodementia (depression first then dementia) and rather acute onset)
Vortioxetine
Common psychiatric co-morbidities of MDD
- Anxiety disorder
- Other depressive disorders eg dysthymia
- Personality disorder
- Substance use disorder
Which mood stabiliser has anti-suicide property?
Lithium
MDD vs Dysthymia
MDD is episodic vs Dysthymia is pervasive
Risk factors for pathological grief
Multiple losses
Psychiatric illness
Traumatic/unnatural death
Lack of closure
Enmeshed relationship with deceased
No avenue to grief
Poor social support
Mania vs hypomania
- Presents with psychotic features
- Hospitalised due to symptoms
- Functional impairment
- Duration (7 days vs 4 days)
Medications that may cause mania
BAAD MACS
Bronchodilators
Antidepressants
Anticholinergics
Dopamine agonist
MDMA
Amphetamines
Cocaine
Steroids
For lithium level > ____, emergent haemodialysis is required
4mmol
Drugs that decreases lithium serum levels
Potassium sparing diuretics (spironolactone)
Theophylline
