Slattery- Antidepressants/Drugs for Manic Disorders Flashcards
2 hypotheses for mood disorders
1) Amine Hypothesis
Depression is due to changes in 5HT and NE signals in the brain
Depression occurs with bad receptors or decreased synthesis, storage, or release
2) Neurotrophic hypothesis
Brain-derived neurotrophic factor (BDNF) is important for neural plasticity, resilience, and neurogenesis
BDNF prevents apoptosis and makes new neurons
Depression = loss of BDNF
Antidepressant drug subtypes
Tricyclic antidepressants (TCAs)
Monoamine oxidase inhibitors (MAOIs)
Selective serotonin reuptake inhibitors (SSRIs)
Dual-mechanism drugs
Mood stabilizers subtypes
Lithium carbonate
Anticonvulsants
Atypical antipsychotics
MOA of TCAs
Block the reuptake of NE and/or 5-HT by nerve terminals –> Results in higher concentration of the neurotransmitters at their receptors
Desipramine (Norpramin)
Type: Tricyclic Antidepressant (NE selective)
MOA:
Blocks the reuptake of NE by nerve terminals resulting in higher concentration of the neurotransmitters at their receptors
Uses:
Depression, insomnia
Adverse effects:
Antimuscarinic effects (in parasymps): glaucoma, constipation, confusion
orthostatic hypotension –> Blockade of α adrenoreceptors
weight gain → block histamine
tachycardia and risk of arrhythmia → block Na channels
Disadvantages:
Makes you drowsy, so taken before bed
Low therapeutic index (5-10)→ risk of OD, only can give in 7 day supplies
Metabolized by CYP2D6 → potential for many drug interactions
Imipramine (Tofranil)
Type: Tricyclic Antidepressant (NE/5HT mixed selective)
MOA:
Blocks the reuptake of NE and 5HT by nerve terminals resulting in higher concentration of the neurotransmitters at their receptors
Uses:
Depression, insomnia
Adverse effects:
Antimuscarinic effects (in parasymps): glaucoma, constipation, confusion
orthostatic hypotension –> Blockade of α adrenoreceptors
weight gain → block histamine
tachycardia and risk of arrhythmia → block Na channels
Disadvantages:
Makes you drowsy, so taken before bed
Low therapeutic index (5-10)→ risk of OD, only can give in 7 day supplies
Metabolized by CYP2D6 → potential for many drug interactions
Phenelzine (Nardil)
Type:
Monoamine oxidase inhibitor (MAO)
MAO-A (NE and 5HT) and MAO-B (DA) –> irreversibly blocks
MOA:
Irreversibly blocks the intra-neuronal breakdown of monoamines, resulting in increased levels of these neurotransmitters at their receptors
Uses:
Depression
Disadvantages:
Low therapeutic index
If switching to an SSRI, wait 14 days after stop with MAOI and vice versa
Serotonin syndrome –> Results from overactivation of 5HT-2A (can cause hyperthermia, confusion, irritability, coma or death)
***Must avoid concurrent ingestion of tyramine
Fluoxetine (Prozac), Sertraline (Zoloft), Escitalopram (Lexapro)
Type:
SSRI
MOA:
Selective inhibition of serotonin reuptake by CNS neurons; very complex with several receptor subtypes (clinical effect is in the 5HT 2a receptor).
Specific enough that it has no muscarinic, histaminergic, or α adrenergic receptors
Uses:
Depression, anxiety disorders
Advantages:
are not sedating like TCAs or atypical antidepressants
Disadvantages
Nausea, diarrhea and weight loss (so many will discontinue tx)
Sexual dysfunction
Black box warning
***Do not use alone in bipolar disorder! Need to include a mood stabilizer to prevent rapid mood swings
Venlafaxine (Effexor, Effexor XR)
Type:
Dual Action Antidepressant
MOA:
Is a serotonin AND norepinephrine reuptake inhibitor (SNRI)
Uses:
Depression, OCS, panic, PTSD, phobias
Advantages:
Doesn’t affect:
Adrenergic receptors (sympathetics) –> So no increased heart rate, etc
Histaminergic receptors
Cholinergic receptors (muscarinic/parasymps) –> So will be able to poop!
All equals less side effects
Mirtazapine (Remeron)
Type:
Dual Action Antidepressant
MOA:
Blocks presynaptic α2 receptors:
On adrenergic neurons (Autoreceptors)
-Autoreceptor → block OWN NT if sense too much in the cleft)
On serotonergic neurons (heteroreceptors)
-Heteroreceptors → Sense NE levels from neighboring synapse and inhibits 5HT release from its own neuron
This combination increases NE and 5HT levels
Uses:
Depression
Advantages:
Fewer side effects than TCA drugs
Buproprion (Wellbutrin)
Type:
Dual Action Antidepressant
MOA:
Blocks both NE and DA reuptake
May also involve presynaptic release of NE and DA
Uses:
Depression
Adverse effects:
Stimulation –> agitation, anorexia and insomnia)
***often used in combination with SSRI (no real reason why though)
Ketamine
Type:
injectable anesthetic
MOA:
NMDA antagonist
Uses:
Procedures where you need to be unconscious
Depression
Advantages:
Give 1 dose and within 2 hours get improved depression, however only lasts 1 week
Adverse effects
nightmares and hallucinations
Lithium Carbonate (Eskalith)
Type:
Manic Bipolar Phases
MOA:
Unknown
Best guess: Most likely involves effect on postsynaptic rather than presynaptic neuron
Uses:
Bipolar disorder
Prevention of mood swings
Adverse effects:
Fatigue, weakness, ataxia, slurred speech, and tremor
Causes nephrogenic diabetes insipidus (increased thirst and urination) –> Lithium blocks antidiuretic hormone
Tolerance develops to some sx but never develops for tremor and the constant urination/drinking
SUPER SMALL therapeutic index (toxic dose = 2)
can lead to coma
Valproic acid (Depakene) or sodium valproate (Depacon)
Type:
Anticonvulsant
MOA:
Unknown; good for non-rapid cycling bipolar disorder (superior to Lithium)
Uses:
Anticonvulsant and antidepressant; may work well for acute manic episodes
**can combine with lithium if pts don’t respond to either alone
Carbamazepine (Tegretol)
Type:
Anticonvulsant
MOA:
Unknown; good for non-rapid cycling bipolar disorder (superior to Lithium)
Uses:
Prophylaxis of Bipolar disorder
Lurasidone (Latuda)
Type:
Atypical Antipsychotic
MOA:
Central DA and 5HT receptor antagonists (maybe) but exact mechanism is unknown
Uses:
Bipolar depression
Wake Therapy
What: Keep people awake during the night and don’t let them sleep during the day –> This will alleviate signs of depression
Adverse effects
Relapse as soon as they go to bed
Advantages:
May “jump start” the antidepressant drugs you give them
