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

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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