psyc650 psychopharmacology antidepressants and antimanics that we know and love
TRANSCRIPT
PSYC650 Psychopharmacology
Antidepressants and Antimanics
That We Know and Love
When is an Antidepressant
Relevant?
Up and Down Regulation
The neuron’s attempt to keep from getting bored or overwhelmed
I’d like a volunteer…
Optical Isomers
MAOIs
• Monoamine Oxidase Inhibitors• Manerix (moclobemide)• Nardil (phenelzine)• Parnate (tranylcypromine)
– Indirect Agonist– Decreases the turnover of MAO
• Thus, allowing MAs (e.g., DA, 5-HT, NE) to build up
– Not as many ADRs as other antidepressants• Interactions are worrisome
Cheesy MAOIs• MAOIs also inhibit
tyramine esterase• By inhibiting this, we
allow the tyramine levels to increase
• Excess tyramine can lead to hypertensive crisis
• Lots of food have tyramine– The “cheese effect”
• Thus, MAOIs are less desirable, not so much due to the ADRs, but the interaction potential
MAOIs might be best for…
• Very compliant patients– Don’t give it to someone who wouldn’t be
motivated to monitor diet and other meds
• Those who don’t respond to SSRIs or TCAs– This stuff really isn’t a “first-line” treatment
• Hypersomnolent patients– It kind of wakes you up…not good for
insomniacs
Tricyclic Antidepressants
• So called because of the chemical structure
• Mnemonic: works on three cycles– DA, 5-HT, NE
• Lots of them out there– Elavil (amitriptyline)– Tofranil (imipramine)– Pamelor (nortriptyline)– Norpramin
(desipramine)
Anticholinergic Side Effects
• Major thing with the TCAs– Dry mouth– Blurred vision– Urinary retention– Constipation– Confusion and memory impairment– Tachycardia
• The tachycardia is really the big problem with the TCA’s– Not good for people with heart problems
TCAs are Generally Good For…
• Pain– Fibromyalgia– Migraines
• Doesn’t respond to SSRIs• Need a bit of sedation
– (very sedating stuff)
• Narcolepsy!?– (Aids in cataleptic attacks)
Don’t Use TCA’s in
• Overweight patients– They’ll probably gain more weight
• Suicidal patients– Overdose liability
• Cardiac problems• People sensitive to anticholinergic
side effects– Elderly– Dementia
The SSRIs…well…sort of
• A whole mess of these!• Prozac/Serafem (fluoxetine)• Luvox (fluvoxamine)• Celexa (citalopram)• Lexapro (escitalopram)• Paxil (paroxetine)• Zoloft (sertraline)• Wellbutrin/Zyban (buproprion)• Effexor (venlafaxine)
SNDRI?
• Serotonin, Norepinephrine, and Dopamine reuptake inhibition– Wellbutrin
• Effexor does this at a dose-dependent level– “Prozac with a punch.”– Low dose—just another SSRI– Moderate dose, begins inhibiting NE reuptake– Higher doses, inhibits DA reuptake
• Both are decent alternatives to stimulants for treating ADHD
ADRs
• Nausea• Headache• Insomnia• Weight changes• Sexual dysfunction (Zoloft has a high
liability; Luvox less so)
SSRIs (in general) are pretty good for…
• Depression– Prefrontal cortex
• OCD– Basal ganglia
• Panic Disorder– Via limbic cortex and hippocampus
• Bulimia– Hypothalamus
SSRIs are not a good idea for…
• Patients with sexual dysfunction– Or major relationship issues where
sexual dysfunction will pose a particular issue.
• Consistent insomnia or agitation• Where weight gain might be a
problem• Patients with nocturnal myoclonus
(periodic limb movement)
Buproprion (Wellbutrin, Zyban)
• Great for– Patients with hypersomnia– Those who don’t respond or cant’ tolerate
other SSRIs– Those concerned about sexual side effects– Those with cognitive slowing/pseudodementia
• Bad idea for:– Seizure disorder– Head injury (also lower seizure threshold)– Agitated, insomniac patients
Venlafaxine (Effexor)
• At low doses, no different than any other SSRI• At moderate to high doses, good for:
– Severely depressed– Hospitalized– Not responding to other antidepressants– Hypersomnolent– Those for whom weight gain is a problem
• Bad idea for:– Agitated– Insomniac– Those for whom weight loss is a problem– Those with hypertension
General Recommendations
• Garden variety depression– Zoloft, Prozac, Paxil
• OCD– Luvox, Zoloft, Prozac
• GAD– Paxil—(Don’t use Prozac…has been known to
make it worse)• Panic Disorder
– Zoloft, Paxil (Again, no Prozac)• Eating Disorder
– Prozac
More Disorder-Specific
Recommendations• Tourette’s
– Prozac (though some reports also support Luvox)
• Trichotillomania– Prozac, Paxil
• PMDD– Prozac (Serafem)
• Sleep Disorder– Paxil (don’t use Prozac)
• Seasonal Affect Disorder– Paxil
• PTSD– Zoloft
A few more tips…
• Paxil (and Zyprexa, BTW) tends to interfere with insulin– If diabetic, don’t give Paxil…try Zoloft
instead
• Luvox increases 5-HT and GABA– Great for OCD– But not OCPD (tends to make it worse)
No Quitting Cold Turkey
• Paxil “discontinuation syndrome”
• General episode lasts about 3 months
• Cut dose in half for 2 weeks and monitor
• If symptoms do not return, cut again for 2 weeks
• If symptoms still do not return, discontinue– If symptoms do return,
go back to the previous dose
Antimanics: Lithium
• In use for roughly 150 years– Probably longer– “healing waters”
• Strong cation– Competes with Na+
• Lots of ADR liability– TI = roughly 2– ADR not often
severe enough to warrant discontinuation
Lithium
• Most worrisome ADRs occur within the first 2 weeks, then disappear– Nasuea– Vomiting– Diarrhea– Tummyache
• Longer lasting ones:– Tremors– Fatigue– Muscle weakness
Lithium: ADRs
• Most ADRs are reversible with the removal of the drug
• Some cases of permanent hand trembling
• Strange dose-relationship– Severity, yes– Occurrence, no
Lithium Toxicity• If more that 2mmol in DBL, coma and death• Takes several hours to set in• Some warning signs (24 – 72 hours ahead of
time)– Involuntary eye rolling– Confusion– Disorientation– Hyperreflexia– Incoordination– Seizures– Tremor– Vomiting– Nystagmus (wobbly eyes)
• Regular blood level checks are important
Carbamazepine (Tegretol)
• Really an anticonvulsant• Good for trigeminal pain• Not sure why it works
– Probably GABA• ADRs
– Allergic skin reaction– Double vision– Dizziness– Drowsiness– Headache– Nausea– Vomiting
• Auto-Inducing– Alternative: Trileptal
(oxcarbamazepine)
Depakote (divalproex,
valproate, valproic acid)• Another anticonvulsant that’s good for
mania• ADRs:
– Diarrhea– Dizziness– Headache– Nausea & Vomiting– Somnolence– Tremor
• Liver failire– Quite rare, but children may be at a higher risk– Given to kids like candy, though (Depakote
Sprinkles on ice cream!)
Your patient on Paxil has shown some improvement over the last 5 months and
seems stable. It may be time to…
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1. Take her off the Paxil ‘cold turkey’
2. Maintain the dose indefinitely
3. Increase the dose4. Decrease the
dose by half and monitor for a short time
Which of the following is true
regarding lithium?
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83%1. It is only a last resort
in treating bipolar disorder
2. It competes with salts in the kidney tubules for excretion
3. It is metabolized by a highly specialized enzyme, which becomes depleted in the kidney
4. As a negatively charged ion, it does not cross the BBB