Drugs for Mood Disorders Flashcards
Pathophys of depression
may involve noradrenergic or serotonergic neurotransmission
Bipolar disorder
periods of depression altering with periods of mania or hypomania (inc activity, dec need for sleep, racing thoughts, elevated mood or irritability, inc self esteem, grandiose ideation, psychotic symptoms, harmful to self or others–> manic)
tx with mood stabilizing agents and antidepressants (depression) or antipsychotics (mania) as needed
Antidepressants
tx depressive symptoms resulting in euthymia (normal mood)- should not elevate mood in non-depressed people -four major classes: MAOI TCAs SSRIs Misc
Mechanism of antidepressants
inc synaptic availability of NE and/or serotonin
-therapeutic effects develop over timea and several weeks of tx may be required before maximal effects are achieved (requires the downregulation and compensatory changes to result in therapeutic effect)
ultimate effect due to:
- secondary changes in receptors- down regulation of a2 and b receptors
- inc in brain derived neurotrophic factor in hippocampus
- cognitive changes, supported by proven efficacy of cognitive therapy
- combination of these effects
MAOIs
Phenelzine
Tranylcypromine
Increase synaptic availability of norepinephrine and serotonin by blocking catabolism
-irreversibly inhibit MAOa (NE and 5-HT) and MAOb (DA)
-in individuals not adequately treated by other antidepressants
Side effects of MAOI
postural hypotension, weight gain, sexual dysfunction
GI side effects
Overdose on MAOI
unusual but can cause seizures, shock, delirium, hyperthermia
potentiate action of other sedatives such as alcohol
MAOIs interactions
numerous drug interactions
esp when used with any drug that increases serotonin or acts at 5-HT receptors–> fatal “serotonin syndrome”
-tremor, muscle rigidity, hyperthermia, htn, tachycardia, myoclonus
food interactions- tyramine containing foods–> htnsive crisis
precautions must be observed for 2 weeks after cessation of drug bc irreversibly inactivation of MAO
older TCAs
amitriptyline
nortriptyline
newer TCAs
clomipramine- improved side effect profiles
TCA mechanism
Inhibit reuptake of norepinephrine and/or serotonin at NE and 5-HT transporters
potent antagonists at various receptors including cholinergic, histamnergic, and alpha-adrenergic
Side effects of TCA
anticholinergic effects, orthostatic hypotension, sexual dysfunction, sleepiness, arrythmias,
discontinuation syndrome
TCAs overdose
life threatening (suicide risk)- coma, arrythmias, seizures, cardiac effects adverse interactions with MAOIs
SSRIs
fluoxetine, sertraline, paroxetine, citalopram, escitalopram
inhibit reuptake of serotonin (selective for serotonin, not specific- can inhibit reuptake of NE at higher doses)
SSRI side effects
GI symptoms, decreased libido, sexual dysfunction
SSRI overdose, interactions
adverse drug interactions with MAOIs- serotonin syndrome
CYP2D6 interactions for fluoxetine (and metabolites) and paroxetine
low risk of fatal overdose
discontinuation syndrome for drugs with short 1/2 lives and anti-muscarinic
adverse effects in pregnancy, enters breast milk, risk of pulmonary htn in newborn
NE and 5-HT uptake inhibitors
Duloxetine, venlafaxine (high inc of discont syndrome), desvenlafaxine, levomilnacipran
newer drugs with improved overall side effect profiles
NE uptake inhibitor
Maprotiline
Vilazodone
5-ht uptake inhibitor plus other things
5-HT1a partial agonist
SE: nausea, vomiting constipation, insomnia
Vortioxetine
serotonin uptake inhibitor plus 5-HT3 antagonist, 5-HT1a agonist
Nausea, vomiting, constipation
Mirtazepine
inc 5-ht and NE release by blocking a2 receptors on nerve terminals
Bupropion
inhibits dopamine reuptake as well as effects on 5-ht and NE
lower incidence of sexual dysfunction
SE: CNS stimulation, anxiety, agitation, insomnia, dizziness, sweating, aggravation of psychosis, seizures
Amoxapine
inhibits reuptake of 5-HT and NE and is a dopamine antagonist- antipsychotic activity
SE: similar to TCAs but also causes EPS and tardive dyskinesia because dopamine antagonism
originally for psychotic depression
Trazodone
Sedating at sub-antidepressant doses
5Ht2A antagonist
Weak inhibitor of NET and SERT
Short acting
Used as hypnotic and pre-anesthetic
PRIAPISM!!!!!
antidepressant metabolism and excretion
hepatic metabolism
eliminated in 7-10 days (except fluoxetine which has active metabolites)
more rapid in children- slower in the aged–> adjust dose
Black box warning for antidepressants
inc risk of suicidal thinking and behavior in children, adolescents, young adults with major dep disorder and other psych disorders
Lithium
affect ion transport, serotonin system, PI cascade, or arachidonic acid signaling
absorbed rapidly but accumulates slowly in brain (6-10 days for therapeutic levels)
95% excreted in urine
Lithium side effects
low therapeutic index
tremor (common, treat with propranolol)
polydipsia and polyuria- nephrogenic diabetes insipidus
acne
Lithium overdose
tremor, nausea, vomiting, diarrhea, sedation
severe: ataxia, confusion, coma,arrhythmias, death
contraindications for lithium
renal or cv disease
pregnancy- teratogenic
carbamazepine
dec glutamate
blood dyscrasias
used for partial seizures
mood stabilizer
valproic acid
enhances GABAergic transmission
used for seizures
mood stabilizer
lamotrigine
inc inactivation of Na channels
absence and partial seizures
mood stabilizer
Mood stabilizers
used for the swings between depression and mania for bipolar disorder
