Psychotherapeutic Meds pt 3 Flashcards
How long does it take to feel the behavioral effects of antidepressants?
2-10 weeks
How long does it take for antidepressants to have molecular actions?
- basically immediately
- monoamine levels elevated within an hour
What is the paradox with antidepressants?
- While based on their PK/PK they elevate monoamine levels within an hour, it takes weeks for the antidepressant effect to actually take place
shows a disconnect between what we expect biologically vs what is actually perceived by the patient
What do antidepressents increase (besides monoamine levels)?
- Neurogenesis by increasing the amount of synaptic connections
How long does neurogenesis take?
2-3 weeks
What is BDNF and why is it important?
- Brain derived neurotrophic factor
- Critical for neurogenesis: “give life to neurons”
What quality may make antidepressents more efficacious?
more quickly stimulate neurotrophic factor synthesis or neurogenesis
What is the neurotrophic hypothesis of depression?
- As monoamines increase, signaling cascades are stimulated that increase expression of genes for BDNF
- This happening repeatedly everyday will eventually promote new receptors, new neurons, and more dendritic sprouts
- Explains why it takes weeks for mood to be alleviated
Which receptors does ketamine block?
blocks NMDA receptors
What happens if you give a mouse ketamine
dendritic spines increase
Where are NMDA receptors found?
on GABA neuron terminals
What happens when ketamine blocks NMDA receptors?
- By blocking NDMA receptors on GABA neuron terminals, there is less inhibition
- leads to more chances for action potentials and enhanced neural connection strength
When is ketamine used for depression?
Used for treatment resistant depression as a last resort
not overed by insurance
How many people respond to ketamine?
only 1/3 have actual relief and improvement in their symptoms
When does mania appear?
usually appears in 20s to 30s
What is mania?
elevated mood/increased activity
What are the symptoms of mania?
- increased talkativeness
- racing thoughts/ideas
- grandiosity
- decreased sleep
- excessive movement
What is there a desire for in people with bipolar?
to express normal emotions
What is the goal of mood stablizers?
- decrease intensity/duration of manic/depressive episodes
- or prevent them from occuring
What is the first line of treatment for bipolar?
- lithium
- most effective in “typical” bipolar disorder (Bipolar 1)
Why are antidepresants commonly used with lithium?
because lithium treats mania more so than depression
What other drugs are sometimes prescribed with lithium?
- Ca2+ receptor blockers, cholinergic agents, adrenergic blockers
What affects effectiveness of particular drug treatment for mania?
whether patient experiences only manic symptoms or not
How many people have remission due to mood stabilizers?
- 60-80% have partial/complete remission
- more favorable in people with strong genetial link
What did John Cade discover about lithium?
calming effect on animals
When was lithium approved for US? For what?
- approved for use in US in 1970 (Europe much earlier)
- For the treatment of mania and to prevent recurrence
What does lithium do to normal individuals?
possesses negligible effects
What about lithium is highly specific?
relieves mania without over-sedation
What does prophylactic mean?
a preventive meausure: lithium is prophylactic because it decreases/prevents future bipolar episodes
Lithium PK
- important to monitor on a regular basis until assured of stable levels
- slow passage through BBB
Lithium PK- passage through BBB
- concentraton in cerebrospinal fluid is about half plasma
- dependent on sodium intake due to ionic balance (Na+ vs Li+)
What do lithiums’ intracellular effects culminate in?
neuroprotection- promoted in many ways by lithium
this might do nothin in healthy individuals as they are already at the optimal level
What does lithium dampen and inhibit?
- glutamate system/NMDA receptors
- DA system
What are the side effects of mild lithium toxicity?
- diarrhea/vomiting
- drowsiness/confusion
- muscle weakness
What are the adverse effects of lithium?
- tremor
- weight gain
- thirst/fluid retention/frequent urination
side effects generally benign
What do you need to screen for before starting lithium?
need to pre-screen for heart/kidney effects
What can happen as a result of lithium having a small therapeutic window?
- drowsiness/confusion
- blurred vision
- ataxia
- seizures
- cardiovascular issues
- coma/death
What else is lithium effective at treating?
- reccurent hyperactivity in children (not for ADHD under the age of 13)
- premenstrual syndrome
- episodic anger/aggression
What are other treatments for bipolar disorder?
- benzos
- anti-epileptics/convulsants
- anti-depressants
- ECT
limited evidence for atypical antipsychotics
Relapse rate bipolar
60-90% within 4-5 years
What is the likely cause of relapse?
underdosing/noncompliance
What greatly reduces relapse rates of bipolar?
parallel psychotherapy
What is worse than having no treatment for bipolar?
abrupt discontinuation of meds
