Depression (Blue Deck) Flashcards
What are the symptoms of depression (emotional and other domains)?
Emotional:
- Misery, apathy, and pessimism
- low self-esteem (feelings of guilt, inadequacy and ugliness)
- indecisiveness, loss of motivation
Other domains:
- retardation of thought and action
- loss of libido
- sleep disturbances and loss of appetite
What are the 2 major types of depression?
- unipolar depression: mood swings always in same direction
- bipolar depression/affective disorder: alternating depression and mania
What are the two different types of unipolar depression?
- reactive depression
- endogenous depression
What is reactive depression associated with and accompanied by what symptoms?
- non-familial
- associated with life-events
- accompanied by smx of anxiety and agitation
What is endogenous depression associated with and accompanied by what symptoms?
- familial pattern
- not directly related to external stress
FYI what are the manifestations of bipolar depression?
- depression alternates with mania
- periodicity of oscillations in mood vary but usually occur over several weeks
- usually appears in early adulthood
- strongly familial
- some studies suggest genetic similarities to susceptibility to SCHIZOPHRENIA
- Drugs used to treat depressive smx still usually include ANTIDEPRESSANTS
What is the monoamine theory?
- deficits in monoamine neurotransmitters (NA and 5-HT) cause depression
- Basis of most successful pharmacological strategies for treatment of depression
What are the limitations of the monoamine theory?
- formulated for NA first, but later emphasis shifted to 5-HT
- inconsistent and equivocal results
- the hypothesis alone is inadequate to explain all pharmacological actions in depression
5-HT is brokwn down mainly by
MAO-A
NA and dopamine is broken down by
MAO-A and MAO-B; MAO-B more selective on dopamine
What is the MOA of MAOIs?
- increase biological availability of monoamines
- e.g. phenelzine
What is phenelzine?
- non-selective for MAO-A vs MAO-B
- an irreversible MAO inhibitor
What are the adverse effects of MAOIs?
- Postural hypotension: due to sympathetic block produced by accumulation of dopamine in the cervical (neck) ganglia, where it acts as an inhibitory transmitter
- Restlessness and insomnia due to CNS stimulation
- Shouldn’t be combined w or other drugs enhancing serotoninergic function (e.g. pethidine): hyperexcitability, inc muscular tone, myoclonus (jerking, involuntary movements), loss of consciousness
What is the cheese reaction?
- Drug-food interaction
- acute HTN –> throbbing HA, and occasionally intracranial haemorrhage
- major danger from cheeses and concentrated yeast products (marmite)
- amines (tyramine) in foods (cheese) are usually broken down by MAO in the intestines and liver
- MAOIs can lead to accumulation of tyramine and a sympathomimetic effect
- Dangerous food interactions w MAO blockers (e.g. acute HTN)
- Tyramine taken up into adrenergic terminals and competes w NA for vesicular compartment –> inc release of NA into synapses
What are tricyclic antidepressants? (TCAs)
1st gen monoamine reuptake inhibitor antidepressants
(tri) ringed (cyclic) chemical structure
What is Nortripytline?
2nd gen TCA
Milder SE compared to amitriptyline
Improved compliance
What are the adv effects of TCAs? ( 4 effects)
- Sedation (due to h1 histamine receptor antagonism); tolerance to sedation can develop in 1-2wks
- Postural hypotension: due to a-adrenoceptor sympathetic block
- Dry mouth, blurred vision, constipation: due to muscarinic receptor antagonism
- DDI: Plasma protein bound; rely on hepatic metabolism for elimination
What are the examples of TCAs?
Imipramine
Amitriptyline
Nortriptyline
What are selective serotonin reuptake inhibitors (SSRIs)?
- greater 5-HT reuptake selectivity than TCAs
- 50 to -1000- fold selectivity for 5-HT over NA
- Fluoxetine approximately 50-fold selectivity for 5-HT
- Citalopram approximately 1000- fold selectivity for 5-HT
- Fewer adv effects than TCAs
What are the advantages of SSRIs?
- Low affinity for a-adrenoreceptors –> lack of Cardiovascular effects, safer in overdose
- Lack of effect at histamine receptors –> reduced sedation
- low affinity for muscarinic cholinergic receptors –> minimal anticholinergic side effects (e.g. dry mouth and constipation)
What are the adv effects of SSRIs?
- Nausea
- Insomnia
~ Nausea and Insomnia - maybe be discontinuation/rebound smx of withdrawal when plasma levels of drug drop btw doses - Sexual dysfunction
What is the issue with SSRI-induced sexual dysfunction?
men = delayed ejaculation
women = delayed or blocked orgasm (anorgasmia)
reported by up to 50% of pts on SSRIs
But rarely (<10%) leads to discontinuation
Due to inc stimulation of 5HT2 receptors
What is a serotonin syndrome?
- severe reaction can result from DDI with other drugs increasing serotoninergic activity (MAOIs)
effects include: tremor, hyperthermia, cardiovascular collapse
No MAOI with SSRI
After a few weeks of SSRI, whether pt feel hot, or BP high, or shaking
What are noradrenaline reuptake inhibitors? (NARIs)
- greater NA reuptake selectivity than TCAs
- approx 1000-fold selectivity for NA over 5-HT
- Reboxetine approx 1000-fold selectivity for NA
- fewer adv effects than TCAs and SSRIs
Adv effects of reboxetine? (NARIs)
- new drug so adv effects not well described
- dry mouth and constipation due to anticholinergic effects
- insomnia: probably due to incrased NA activiy in CNS
- Tachycardia (inc availability of NA at sympathetic FFF synapses)
What are serotonin and NA reuptake inhibitors? (SNRIs)
similar dual 5-HT and NA reuptake inhibition profiles to non-selective TCAs
- issue of additional receptor antagonism is controversial
- Venlafaxine, Desvenlafaxine (synthetic metabolite of venlafaxine), and Duloxetine are examples in clinical use
Advantages of Venlafaxine? (SNRIs)?
- different structure to TCAs and fewer adv effects than TCAs
- claimed to work slightly faster than other antidepressants
- claimed to work better in treatment-resistant pts
What are the adv effects of SNRIs?
- serotoninergic adv effects similar to SSRIs: nausea, insomnia, sexual dysfn
- serotonin syndrome when combined w other serotoninergic drugs and MAOIs
- withdrawal effects may be more common and stronger than for SSRIs and TCAs
