Psychopharmacology - depression Flashcards
What is depression? (who it affects / impact)
Most common mood disorder, increasing
1 in 5 people, female > male
*false number? - women more likely to present to GP, substance abuse generally higher in male population - self-medication?
2nd highest cause of death among 20-35 year olds
Overall mortality ~15%
Predicted to be leading cause of DALY (disability-associated adjusted life years)
- High rates of alcohol & substance misuse, impact on relationships / productivity
How is depression classified?
Mild / moderate / severe (major depressive disorder)
Mild - responds best to psychological therapy
Moderate - responds best to psychological + pharmacology
Severe - drastic e.g. ECT
Depression: how much genetic influence?
Cause & aetiology is unknown
40% genetic predisposition but very confounded by being raised by someone with a mood disorder
Multiple social & environmental factors involved - early life adversity is the clearest risk factor
Core symptoms of depression
7 or more of…
- Depressed mood: most of day, nearly every day
- Anhedonia (diminished interest/pleasure in all/almost all activities most of the day
- Significant change in appetite & weight
- Insomnia or hypersomnia nearly every day
- Psychomotor agitation / retardation nearly every day
- Fatigue / loss of energy nearly every day
- Worthlessness / excessive or inappropriate guilt (may be delusional)
- Poor concentration, or indecisiveness, nearly every day
- Recurrent thoughts of death / suicidal ideation with / without specific plan
What are the main theories about why people get depressed?
1) Monoamine functional deficit
* i.e. not just not enough monoamines - something functionally wrong in the system
(MA drugs increasing mood, riserpine - depletes brain monoamines → depression)
2) Stress-induced neuro-adaptive pathology
HPA hyperactivity, ↑ cortisol - in almost all cases of depression can see stress trigger (even if a small trigger)
(lots of animal data pointing to chronic uncontrollable stress)
3) Immune-mediated
(sickness behaviour like transient depression, interferon-alpha treatment for hep C causes depression in >50% people. stress links to immune system & causes similar symptoms to sickness symptoms)
*Changes in cytokines -subpopulation of depressed patients have altered cytokines in blood
4) Early-life adversity
epidemiological data - major factors on disease analysed - shows early life adversity as strongest factor,
*maternal separation model in rats
5) Cognitive neuropsychological hypothesis
* negative schema - perpetuates disease
6) Genetic predisposition ~40% heritability (may be less)
* Gene x environment - epigenetic changes
* e.g. early life adversity changes way genetic information is read - more sensitive to immune mediated triggers?
How do most antidepressants work?
- Stop breakdown of monoamines
- Block re-uptake from the synapse
- Interact with monoamine receptors to modulate neurotransmission
*Increase monoamine concentration in brain → mood elevation
But:
- side effects
- delayed onset of action (4-6 weeks)
- lack of efficacy
What are the theories to explain the time lag in antidepressant efficacy?
Pharmacokinetic: time to reach peak (plasma level rise)
Pharmacodynamic: receptor adaptation
Neurotrophic: hippocampal neurogenesis, synaptogenesis (stress interacts with this process + animal evidence that ADs increase neurogenesis)
Cognitive: interaction between drugs & psychological processes
Evidence against the pharmacokinetic theory of the time lag in AD efficacy?
Night terrors and pain respond to AD drugs after 1-2 doses
Therefore biochemical levels of drug should be there quickly
Dosing etc. not been effective for ADs
Evidence against the receptor adaptation theory of the time lag in AD efficacy?
Sleep deprivation & ECT induce rapid onset effects, ketamine (IV) also rapid onset antidepressant effect (40 mins later - 7 days later return to baseline symptom level)
However, receptor adaptation theory implies you cannot get better until brain has adapted
- this also goes against neurotrophic theory
