Antidepressants Flashcards
what is bipolar disorder
episodes of mania/hypomania altering with episodes of depression
monoamine etheory of bipolar disorder
- decreased monoamine transmission leads to depression
- increased monoamine transmission leads to increased mood (overactivation linked to mania/psychosis)
treatment strategies for bipolar disorder
- management of longterm course of illness
- can use single drug treatment or multiple medications
single drug treatment for BPD
mood stabilizer (lithium)
antipsychotic (e.g. haloperidol, olanzapine)
multiple medication treatment for BPD
antipsychotic + antidepressant
lithium + antipsychotic
lithium + antidepressant
whay can’t we use an antidepresant alone to treat BPD
can lead to hypomania
characteristics of lithium - mood stabilizer
- small monovalant cation with narrow theraputic index
- more effective against manic phase of BPD
- mechanism for mood stabilization unknowns
- theory that lithium increases serotonin and GABA and decreases DA and glutamate
- best characterized mechanism = action on second messenger system
Lithium in blocking precursors for IP3
- causes decreased IP3 and DAG synthesis when receptors linked to these second messengers are activated
- M, a1 and 5-HT2A receptors decreased activity
therapy for depression
- drugs used act on one or more monoamine systems
- either amine reuptake blocking drugs or monoamine oxidase inhibitors
amine reuptake blockiing drugs
- can either be selective (e.g. SSRI) or non selecttive (e.g. TCAs, SNRI)
TCAs to treat depression
- an amine reuptake blocking drug
- prevent reuptake of NE and Serotonin
- not used as first line due to side effects and drug-drug interactions
- conmmon TCA = imipramine
adverse effects of TCAs
- block cardiac sodium channels (like quinidine)
- antagonisrt at M receptors (cause dry mouth and constipation)
- antagonist at H1 and a1 receptors (cause sleepiness/sedation)
selective serotonin reuptake inhibitors to treat depression
- inhibit reuptake of Ser by presynaptic cell
- has drug interaction with CYP2D6 (inhibits it)
- common side effects = insomnia and sexual dysfunction
- overdose notdangerous unless combined with other antidepressants
- common SSRI = fluoxetine (prozac)
uses for SSRIs other than treating depression
panic disorder
anxiety
OCD
bulimia
what is serotonin syndrome
- combination of 2 or more serotonin agonists leads to adverse effects of receptor activation (e.g. TCA + MAO inhibitor)
- mental status changes, autonomic instability, neuromuscular abnormalities
newer classes of antidepressants
- SNRIs
- NRIs
- 5-HT receptor agonists or antagonists
- atypical agents
Bupropion - atypical agent to treat depression
- inhibit re-uptake of DA and NE
- fewer side-effects than TCAs (no sleepiness/sedation)
- has anti-muscarinic and anti-nicotinic effects
- inhibits CYP2D6 - alters metabolism of TCAs, B-blockers and haloperidol
MAO inhibitors to treat depression
- non-selective for MAO-A or MAO-B, so all monoamine pathways affected
- only use if tricyclic antidepressants are not effective
- common MAO inhibitor = Phenelzine
toxicity of MAO inhibitors
- hypertensive crisis if tyramine, cocaine or amphetamine are also present
- should not be taked with SSRIs, SNRIs or tricyclic antidepressants because can lead to serotonin syndrome
clinical effectiveness of antidepressants
- SSRI perscribed first (least side effetcs)
- tharapy startes at low dose , can take 3-8 weeks to see effects
- patients vary in individual responsiveness
why do MAO levels change after a single dose
adaptive changes resulting from sustained elevation of MAOs - i.e. what they are doing
antidepressant action not seen for weeks
long term treatment with antidepressants
- alter levels or sensitivity of CNS receptors and neuronal growth factors
- depressed state - BDNF regulated by monoamines
- treated state - increased monoammine input therefore increased BDNF
