Mood affective disorders / mood disorders Flashcards
What are mood affective disorders ?
also called mood disorder
0 conditions where there is a disturbance in a person’s mood - the underlying feature.
MAIN TYPES
0 Depression ( uni polar )
0 bipolar disorder (main - depression )
symptoms vary btw individuals - from mild to severe.
What is Bipolar disorder ( manic - depression) ?
Massive shifts in mood , emotions , energy levels. - extreme lows to extreme highs
0 usually happens over days to weeks not suddenly.
0 Lows are the same as major depressive order (uni polar depression )
- symptoms
1. lack of
energy &
focus
2. Hopeless
&
discouraged
3. eating or
sleeping
too much
or too little.
Manic episodes - also experienced ( this is what separates it from major depressive disorder ).
MANIC STATE
0 Energetic
0 Overly happy / optimistic
0 Euphoric
0 High self - esteem.
CONSQUENCES - manic episode
0 pressured speech - constantly & rapidly talking .
0 Racing thoughts - also feel like they don’t need sleep.
0 Full manic episode ( risky - make snap decision e.g gambling - reckless behavior ) - poor decision making (no regard for consequences )
0 delusion of grandeur - false belief in one’s own superiority, greatness, or intelligence.
e. g - personal mission from God - supernatural
- CAN HAVE MIXED EPISODES
( depressive & manic episodes occur at same time )
rapid cycling - 4 or more episodes of mania or depression in a year .
People who have BP often have other disorders e.g anxiety , substance abuse , ADHD , personality disorders.
What are the different types of Bipolar ?
Bipolar 1 - diagnosis
0 Bipiolar 1 - Major low (depressive episode - last lat least 2 weeks ) ———————————————> Major high (manic episode - last at least 1 week or require hosipitalisation)
- untreated manic episodes can last 3-6 months.
Bipolar 2 - diagnosis
0 0 Bipolar 2 - Major low (depressive episode - last lat least 2 weeks ) ———————————————> Hypomania (last at least 4 days )- can last longer
- difference btw 1 and 2 is that 2 has episodes of hypo mania - less severe than manic episodes.
0 Cyclothymia
0 Cyclothymia
Milder lows & highs (or hypomania) - cycles btw these two for at least 2 years.
Causes of Bipolar disorder ?
Unknown
(but genetics + environment - though to have an impact )
person with family history of BP - 10x more likely to have it.
0 Drugs / medicines - can trigger manic episodes e.g SSRI
Treatment of Bipolar disorder ?
No cure
- treatment important - person at risk of hurting themseleves
Lithium salts - mood stabilizers
( better at treating manic episodes vs depressive episodes )- thus need to take other medicines too ( antidepressants )
Antidepressants
- have to be careful some can trigger manic episodes e.g SSRI
0 Antipsychotics
0 Anticonvulsants
0 Benzodiazepines
- these medicines can have severe side effects leading to non - adherence - be aware.
0 Talk therapy
0 Cognitive behavioral therapy . ( especially after manic episode ended )
- help handle stressful situations.
What is Major depressive disorder ( clinical depression / uni polar depression ) ?
Depressive disorder - very serious
0 effects daily life & can lead to person feeling like life is not worth it.
Causes of Major depressive disorder ?
Unknown
but linked with genetics - family history - 3 x more likely - link increases with how closely related they are.
biology - regulation of neurotransmitters
environment & psychology.
Important neurotransmitters in Major depressive disorder ?
Serotonin
Noradrenaline
Dopamine
Medicines that increase the level of these in the synaptic cleft have been shown to be effective antidepressants.
What is the monoamine deficiency theory ?
Underlying pathophysiology of major depresssive disorder is :
0 Depleted levels of serotonin , dopamine , adrenaline in CNS.
these are monomanines ( only have one amine group )
EFFECTS THE NEUROTRANSMITTERS HAVE.
Noradrenaline —- anxiety & attention
Serotonin ———> Obsession & complusions
Dopamine ——- > attention , motivation , pleasure.
HOW - not well known
0 Serotonin -
Tryptophan amino acid ( depleted - used make serotonin) ————–> so serotonin depleted ——–> patient may start to get symptoms of depression.
( why depletion occurs is not known ).
Diagnosis of Major depressive disorder ?
Have or the 9 symptoms
- depressive mood.
- sig weight loss/ gain
- diminished interest / pleasure
- inability to sleep / oversleeping
- Psychomotor agitation ( pacing , wringing hands ) or impairment (slowing of through and movement )
- fatigue
- Hopelessness , guilt, worthlness feelings
- Decreased concentration
- thought of death - sucidal thought / attempt.
0 Has to have sig impact on life
0 and not due to medication / condition.
0 cant be explained by other mental health disorder
0 No manic episode at any point.
CONSIDERED CORE SYMPTOMS- IF ONE IS PRESENT ASK ABOUT OTHER DEPRESSION SYMPTOMS
During the last month have you often been bothered by feeling down, depressed, or hopeless?
Do you have little interest or pleasure in doing things?
Subthreshold - 2 or more but less than 5 symptoms
Mild - more than 5 symptoms but mimas impact on functioning
Moderate - moderate - to just below severe symptoms
Severe - nearly all symptoms- severe impact on functioning.
Different types of depression ?
Postpartum depression - occurs after child birth
- most people have depression before
- so more recently called depressive disorder with peripartum
onset .- during
pregnancy - 4 weeks
after birth.
- during
POSSIBLE CAUSES - not known - but linked to :
0 Hormonal changes - estrogen & progesterone
0 Lifestyle changes - can affect fathers too.
Atypical depression
0 Improved mood in response to pleasurable events - mood reactivity + rejection sensitivity ( anxiety at the slightest rejection ) + heavy limbs (laden paralysis )
normal symptoms
Melancholic depression - No improvement of mood when exposed to pleasurable events,
Dysthmia - persistend depressive diosorder - milder symptoms happen over longer period of time. ( e.g 2 + years and 2 or more symptoms )
0 Change in appetite
0 Change in sleep
0 Hopelessness / pessimistic
0 low self - esteem
0 low concentration
0 fatigue / low energy.
Treatment of major depressive disorder ?
Non -pharmological
- exercise - 20 mins x 3 a week - help alleviate symptoms
- health eating
- Talk therapy - preferred for younger and those with milder symptoms.
- Psychotherapy
cognitive
behavior T
PHARMACOLOGICAL
- anti - depressants
SSRI ( selective serotonin retake inhibitors ) - after serotonin release - usually reabsorbed . - monomaine oxidase inhibitors
- tricyclics (TCA)
(less commonly used )
last resort
ECT - electroconvlusive therapy
( small shock passed through brain under general anesthetic - induces seizure )
How is Serotonin - (5 - HT) made ?
Function
Where is it found
Tryptophan ———— > converted to Serotonin
Serotonin - found in brainstem in cluster of neurones - RAPHE nuclei
-these neurones then project throughout brainstem & brain supplying serotonin to CNS.
0 Serotonin transporter (SERT) - removes serotonin from synaptic cleft via reuptake.
ACTIONS
- Boost mood , feeding , reproductive behaviour.
What are Tricyclic antidepressants (TCA ) ?
Treat Major depressive disorder.
0 increase level of serotonin & noradrenaline - to alleviate symptoms.
What are Tricyclic antidepressants (TCA ) ?
Treat Major depressive disorder.
0 increase level of serotonin & noradrenaline - to alleviate symptoms.
2 TYPES
0 Secondary - selective - only inhibit noradrenaline transporters. (increase noradrenaline in cleft)
- disipramine
- nortriptyline.
0 tertiary - non - selective- inhibit serotonin/ noradrenaline transporters. (increase noradrenaline & serotonin in cleft)
1. amitriptyline
2. imipramine 3. clomipramine
SLOW ACTING - takes time for serotonin & noradrenaline to accumulate in cleft. 2-4 WEEKS BEFORE IMPROVEMENTS SEEN.
SEVERE SIDE EFFECTS - not first line - used when no response to SSRI etc
What are Tricyclic antidepressants (TCA ) ?
Treat Major depressive disorder.
0 increase level of serotonin & noradrenaline - to alleviate symptoms.
2 TYPES
0 Secondary - selective - only inhibit noradrenaline transporters. (increase noradrenaline in cleft)
- disipramine
- nortriptyline.
0 tertiary - non - selective- inhibit serotonin/ noradrenaline transporters. (increase noradrenaline & serotonin in cleft)
1. amitriptyline
2. imipramine 3. clomipramine
SLOW ACTING - takes time for serotonin & noradrenaline to accumulate in cleft. 2-4 WEEKS BEFORE IMPROVEMENTS SEEN.
SEVERE SIDE EFFECTS - not first line - used when no response to SSRI etc
SEDATION - block histamine 1 (H1 ) receptors
Orthostatic Hypertension - Block Alpha 1 receptors.
Muscarinic receptors - Atropine - like side effects
(Constipation; drowsiness; dry mouth; palpitations; skin reactions; tachycardia; urinary disorders; vision disorders; hallucinations Confusion
Indications of TCA ?
Major depressive disorder
0 Phobic disorders
0 Chronic neuropathic pain
(peripheral neuropathies )
Migraine prophylaxis.
clomipramine - OCD.
imipramine - nocturnal enuresis - involuntary urination while sleeping.
What are SNRI ?
Serotonin - neuroadenaline reuptake inhibitors - inhibit reuptake of both.
MOSTLY TREAT
- treat major depressive disorder / clinical depression / unipolar
Increase levels of serotonin & noradrenaline - to alleviate symptoms.
CAN TREAT
anxiety
neuropathic pain e.g peripheral neuropathy
EXAMPLES
0 VENLAFAXINE
0 o can treat :
o Social
anxiety
o Panic
disorders
o PTSD
o OCD
o Postmenopausal hot flashes - sudden intense feelings of heat - usually over chest , face & neck
0 DESVENLAFAXINE ( active metabolite of venlafaxine )
0 MILNACIPRAN
0 LEVOMILNACIPRAN
0 DULXETINE
o can treat :
Urinary
incontinence
o fibromylagia
Side effects of SNRI ?
0 Insomnia
0 Nausea
0 Sexual dysfunction
DUE TO INCREASED NA
0 High BP
0 Sweating
0 Headaches
MOST DANGEROUS
0 Suicidal ideation - thinking about committing suicide.
0 Serotonin Syndrome - serotonin accumulation —————————————–> overstimulation of nervous system - Life threatening.
(usually triggered by SNRI or SSRI + another antidepressant that raises serotonin levels / st johns wort/ monoamine oxidase inhibitors)
SYMPTOMS - flushing - agitation - hyperthermia Muscle rigidity - seizures - coma
Abrupt withdrawal from SNRI - can experience withdrawal symptoms
- Insomnia
- headaches
- irritable
Venlafaxine - inhibits CYP450 enzymes
reduce rate of elimination of other drugs
e.g benzodiazepine - accumulate
Duloxetine
- hepatotoxic
How do you treat Serotonin Syndrome ?
Cyproheptadine
- Serotonin antagonist - block 5-HT2 inhibitors.
What is Lithium ?
Treatment of Bipolar disorder
- Mood stabilizer - smoothes out highs and low. - decreases frequency & magnitude of low and highs.
( can be used of acute manic episode - but usually antipsychotics are used
or unipolar depression - resistant to antidepressants)
HOW ?
Control release of neurotransmitters e.g serotonin
0 inositol needed for neurotransmitter release.
Innositol ——————————> IP3 - converted through series of steps.
- IP3 needs to recycled back to inositol -
done by series of dephosphorisation steps by enzymes ;
0 inositol polyphosphate phosphatase
0 inositol
monophosphate
Mg 2+ needed as c factor by these enzymes
Lithium displaces Mg inhibiting enzymes - so IP3 not recycled t inositol ——————————> decreased neurotransmitter release.
STEPS
IP3 - diffuses into endoplasmic reticulum - binds to calcium ion channels -
CA2+ channels release stored CA into cytoplasm.
Vesicles moves towards Pre SM , fuse and release neurotransmitter into synaptic cleft.
IP3 recycled to Inositol.
What is Lithium ?
Treatment of Bipolar disorder
- Mood stabilizer - smoothes out highs and low. - decreases frequency & magnitude of low and highs.
( can be used of acute manic episode - but usually antipsychotics are used
or unipolar depression - resistant to antidepressants)
Route of administration
0 Oral
- absorbed rapidly in GI tract - not metabolised by liver - only kidneys excrete it.
- narrow therapeutic range - close mointoring of serum lithium levels
- especially for those with :
o impaired renal function
o taking medicines that reduce GFR- NSAIDS
- THIAZIDES ]
- LOOP
DIUERTICS - ACE
INHIBITORS
(as easy to overdose - in these situ - ineffective elimation)
toxic levels ------------------------------->
0 Acute renal failure
0 Severe neurological symptoms
- Ataxia
- confusion
- dysarthria - speech difficulties
- coma
- death
What is Lithium ?
Treatment of Bipolar disorder
- Mood stabilizer - smoothes out highs and low. - decreases frequency & magnitude of low and highs.
( can be used for acute manic episode - but usually antipsychotics are used
or unipolar depression - resistant to antidepressants)
Route of administration
0 Oral
- absorbed rapidly in GI tract - not metabolised by liver - only kidneys excrete it.
- narrow therapeutic range - close mointoring of serum lithium levels
- especially for those with :
o impaired renal function
o taking medicines that reduce GFR- NSAIDS
- THIAZIDES ]
- LOOP
DIUERTICS - ACE
INHIBITORS
(as easy to overdose - in these situ - ineffective elimation)
toxic levels ------------------------------->
0 Acute renal failure
0 Severe neurological symptoms
- Ataxia - degnerative disease of NS
- confusion
- dysarthria - speech difficulties
- coma
- death
Symptoms of Lithium ?
GI - nausea
- vomiting
- diarrohea
Mild tremour
0 CAUSES NEPHROGENIC DIABETES INSIPIDUS
Inhibits ADH /vaspressin - so little wate reabsorbed in kidney tubule
- urine diluted ———————-> Polyuria (loss of large volume of urine )————————————————-> increased plasma osmolality ( less water in blood ) ————————————————-> polydipsia ( thirst triggered )
0 Blocks TSH binding to receptor———————————————–> Hypothyroidism ( & its symptoms ) - goitre - reactive hypertrophy & hyperplasia - gland grows larger cells increase in number & size to compensate for lost thyroid hormones.
0 Leukocytosis - increased WBC count.
Lithum & pregnancy ?
DONT USE
- Increased risk of congenital heart defects
e. g Epstein anomaly - leaflets of tricuspid valve - located lower than normal into RV
What are monoamine oxidase inhibitors (MAOIs) ?
HOW DOES IT WORK?
Treat major depressive D - not first line due to severe side effects
especially effective in treatment of atypical depression (improve mood in response to positive events)
0 Increase levels of serotonin , NA , dopamine
inhibit monoamine oxidases which break down neurotransmitter e.g serotonin after they have been reuptaken from synaptic cleft by their transporter
- PREVENTS BREAKDOWN OF NEUROTRNASMITTERS
if not broken down neurotransmitter packages into vesicles awaiting release.
0 Monoamine oxidase A - breaks down :
0 Serotonin
0 NA
0 dopamine
0 Monoamine oxidase B : breaks down-
0 dopamine
What are the different types of MAOIs ?
Non selective / irreversible - inhibit MAO A & B - bind irreversibly to enzyme
0 increases level of :
0 Serotonin
0 NA
0 Dopamine
Selective - inhibit MAO B
0 increases Dopamine
( more commonly used to treat Parkinson’s disease vs depression.
What are the different types of MAOIs ?
Non selective / irreversible - inhibit MAO A & B - bind irreversibly to enzyme
0 increases level of :
0 Serotonin
0 NA
0 Dopamine
ex - isocarboxazid
phenelzine
Tranylcypromine
Selective - inhibit MAO B
0 increases Dopamine
( more commonly used to treat Parkinson’s disease vs depression.
ex - selegiline
rasagiline
Side effects of MAOIs ?
MOST DANGEROUS
0 Serotonin syndrome -
commonly happens when taking SSRI with MAOIs / medicine that raises serotonin
recommended that if starting a new antidepressant - MAOIs should be stopped for at least 2 weeks before starting new one.
0 Hypertensive crisis - characterised by
- Increased BP
- Tachycardia
- Arrhythmias
- -Hyperthermia
- agitation.
- commonly occurs in :
those taking MAOIs + tyramine rich foods : - CHEESE
- wine & bear
MAOIs inhibit MAO in cells in gut wall -which break down excess tyramine
Tyramine - (catecholamine releasing agent ) - regulates BP - vasoconstriction of BV - causes BP to rise.
more tyramine absorbed ————————————————-> more NA released ——————————————–> hypertensive crisis
Treatment of Hypertensive crisis ?
Phentolamine - adrenergic antagonist
What are SSRI ?
Selective Serotonin reuptake inhibitors
inhibit serotonin reuptake transporter .
slow acting - serotonin needs to accumulate - at first there is a negative feedback mechanism - increased serotonin release activates receptor which slows release - over time this break /receptor is downregulated /stop working ———–> SSRI takes affect )
First line treatment - major depressive disorder - has milder side effects
- * can also treat : OCD PTSD Chronic anxiety eating disorders
ex-
0 Citalopram
0 Escitalopram
0 sertraline
0 Fluoxetine
0 Fluvoxamine
0 paraxetine - pregnancy category D - been shown to cause congenital heart defects.
- most of them are pregnancy category C - potential risk to pregnancy
Side effects of SSRI ?
0 Anxiety 0 Insomnia 0 GI distress 0 sexual dysfunction 0 SIADH - syndrome of inappropriate antidiuretic hormone
MOST DANGEROUS
0 suicidal ideation
0 Serotonin syndrome
WITHDRAWAL - sudden stopping of SSRI
- irritable
- insomnia
- headache
Citalopram - prolongation of QT interval ventricular arrhythmias
0 Fluoxetine
0 Fluvoxamine
0 paroxetine -
inhibit CYP450 - can cause toxic levels to occur - ineffective elimination.
Contraindications of SSRI
0 In a manic phase of bipolar disorder.
0= poorly controlled epilepsy.
0
known QT interval prolongation, or congenital long QT syndrome (citalopram and escitalopram).
0 Taking other medicines that are known to prolong the QT interval (citalopram and escitalopram).
0 severe hepatic impairment (sertraline).
CAUTION
in people who are at risk of previous contraindications.
0 sig bradycardia
0 Diabtetes mellitus
0 cardiac disease
Contraindications of TCA
0 Acute porphyrias.
0 Arrhythmias.
0 Heart block.
0 Severe hepatic & renal impairment (lofepramine - renal).
0 During the manic phase of bipolar disorder.
0 In the immediate recovery period after myocardial infarction.
0 Taking monoamine oxidase inhibitor (MAOI).
