For those who requested to see my notes on the subject- Enjoy.
Bipolar ( depressive and manic episodes)
Depressive (unipolar) disorders- low state + sadness, lack energy, self worth, guilt etc
Two types:(2)
Major Depressive disorder-severe pattern depression= disabling but NOT caused by drugs or general medical condition.Dysthymic disorder ( dysthymia)-less disabling BUT longer lasting ( chronic)
Number one difficulty-diagnosis
Wide variety of symptoms, difficult to distinguish when normal FLUCTUATIONS in mood become depression and No single objective test to establish diagnosis.
Since: based on interview using diagnostic criteria (2):
-DSM-IV ( Diagnostic Statistical Manual by American Psychiatric Association)
-Example- depressed mood nearly every day either by subjective report or observation made by others. Plus, diminished interest almost in all activities.
-ICD-10 International Classification of Disease ( WHO)
-Example-typical symptoms- depressed mood, anhedonia, reduced energy
-common symptoms- reduced concentration, self-esteem ( confidence), ideas of guilt/unworthiness, negative/pessimistic views on the future, ideas of self hamr/suicide, disturbed sleep, diminished appetite
Example of a screening question ( clinical interview)- during the past moneth have you often been bothered by feeling down, depressed or hopeless.( /little interest/plesure in doing things)
Patients normally affected
Gender- twice as many women ( up to 25% W, 12% M)
Age-1st episode late adolescence or early adulthood, but onset is decreading in recent years- life more stressful/diagnosing more with depression?
Important Factors ( Suicide/Comorbidity)
Suicide thoughts common in patients-20% attempt, 10% severe depressives commit
Commonly comorbid with i.e drug abuse
Comorbidity
Terminal/Chronic illness ( pain), Thyroid dysfunction, Neurological disease, Stroke, Drug abuse, Parkinsons, anxiety ( i.e common comorbidity- manifest more severe symptoms, less responsive to treatment, higher risk of suicide... which one cause which?)
Causes
Genetic predisposition-first degree relative (20%), monozygotic ( up to 50%), general population(3.2)
Environ- Loss/stressors/social isolation
Neurobiological factors
- deficit NT NoA and serotonin ( i.e with reserpine) but elevating this alleviates depression ( i.e MAOI)
- Lack of neurogenesis ( new nerve cells not produced) ( i.e rodent sub-ventricular zone/dentate gyrus or from stress hormone studies)
Treatment options consist of the four main types (4)
Psychological treatment
-CBT:aiding recognition & change negaitive cognitive processes thus improve mood/counterproductive behaviours
-Interpersonal therapy:assumes depression multi-factorial but interpersonal difficulties play central role in depressive symptoms.
MAOI ( First generation AD)
- catalysis breakdown on DA, 5-HT, NoA ( located in nerve terminal/liver/intestine+ vesicular MA protected from MAO)
- irreversible inhibiton i.e phenelzine, tranylcypromine & isocarboxazid
-ADRs: high incidence= CNS stimulation (i.e insomnia), postural hypotension, hypertensive crisis ( after ingestion of certain foods* cheese effect*= reversal of effects take 2 weeks until NEW ENZYME formation ( hence don't start new AD until 2 weeks after MOAI
-Cheese effect*=MAO in gut inhibited, dietry amines cheesei.e high conc tyramine get into circulation acts as indirect sympathomimetic displacing NoA from vesicles.
-MOA subtypes
-A: metabolises 5-HT & DA
-Both:metabolise tyramine & DA
-Where? ( A= intestine), B ( striatum= caudate, putamen,accumbens)
- Selective: older, non= phenelzine, tranylcyp&isocarb. BUT selective: A ( clorgyline), B ( selegiline)
-Reduced tyramine, "cheese effect": with reversible inhibitors ( RIMA i.e moclobemide)
TCA ( 2nd generation AD)
-inhibit monoamine reuptake
-those with secondary amine group show greater selectivity for inhibiting NA VS 5-HT i.e. desipramine, nortriptyline, protriptyline
- tertiary amine group show greater selectivity for 5-HT VS NA i.e imipramine, amitryptaline, doxepin
N.B. DA not inhibited as much as NA & 5-HT
-ADRs: anticholinergic i.e dry mouth, blurred vision, consitipation, tachycardia, cardiac arrhythmia ( lead to orthostatic falls), tremour, weight gain ( neuroendocrine effects), lower seizure threshold ( contraindicate in epileptics?), TOXIC in overdose ( self poisoning common, hyperpyrexia, cardiac problems, seizures, coma)
SSRIs ( 3rd generation AD)
-MORE selective 5-HT reuptake blockade than TCA.
-For example: Paroxetine, Fluoxetine ( Prozac), Fluvoxamine, Setraline, Citalopram
-ADRs (2)- 5-HT2 mediated ( Headache, Agitation/nervousness, sexual dysfunction), 5-HT3 mediated ( nausea, vomiting, reduced appetite)
-NB: Safer in overdose than TCA + devoid of MUSCARINIC effects
SSRI ( NICE recommends)in synapse, more selevtive in the molecules to which they bind, don't bind to receptors on other classes of neurons ( hence less ADR)
More recent ADS SNRIs
-Seratonine &NorAdrenaline reuptake inhibitors i.e duloxetine
- combined SERT inhibition & 5-HT2 receptor antagonist i.e nefazadone
-5HT2/3 & NA a2 antagonist- i.e Mirtazapine
Overview- AD advancement
- reduced ADRs+ less toxicitiy in overdose
- speed of action & proportion of patients who respond hasn't changed
- need to be given 4-6 months after symptoms disappear & may require lifetime treatment
Example: ( overdose 10^6 .... 14,12 , 2 ( MOAI, TCA, SSRI)
Current treatment Limitations:4-6 wks for clinical effect, don't work for everyone, ADRs, some not better than placebo, some increase suicide rates
ADRs- Dry, Urinary Ret., Blurred, Constip, Sed, Sleep disrupt, Wt Gain, Headache, NAusea, GI dist./diarr., Abdominal pain, loss of libido ( inability orgasm/erection), agitation/anxiety
children/adolescents- increased suicide rates on paroxetine
Pathophysiology- 5HT pathya- raphe nuclei ( from brain stem to frontal cortex)
DA pathway ( nigrostriatal): Substantia Nigra to Stiatum.
DA pathway ( mesolimbic): ( Brain stem to hypothalamus to frontal cortex)
ventricles?
Presynaptic autoreceptors- negative feedback get diagram- terminals/cell bodies.SSRIs reduce 5-HT neuronal firing via 5HT1A receptors
5-HT autoreceptor control of cell firing/ release toeards Post synaptic 5HT1A Receptors ( control raphe cell firing) B/D control 5HT release at terminals
Overall- SSRI augmentation with 5HT (Pindolol) antagonists work in some not all i.e sustained response diff btwn groups taking SSRI & placebo
Better than placebo- major significance in those with severe depression
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