1. PSYC650 Psychopharmacology Antidepressants and Antimanics That We Know and Love

2. When is an Antidepressant Relevant?

3. Up and Down Regulation The neuron’s attempt to keep from getting bored or overwhelmed I’d like a volunteer…

4. Optical Isomers

5. 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

6. 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

7. 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

8. 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)

9. 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

10. 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)

11. 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

12. 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)

13. 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

14. ADRs Nausea Headache Insomnia Weight changes Sexual dysfunction (Zoloft has a high liability; Luvox less so)

15. SSRIs (in general) are pretty good for… Depression –Prefrontal cortex OCD –Basal ganglia Panic Disorder –Via limbic cortex and hippocampus Bulimia –Hypothalamus

16. 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)

17. 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

18. 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

19. 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

20. 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

21. 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)

22. 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

23. 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

24. Lithium Most worrisome ADRs occur within the first 2 weeks, then disappear –Nasuea –Vomiting –Diarrhea –Tummyache Longer lasting ones: –Tremors –Fatigue –Muscle weakness

25. 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

26. 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

27. 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)

28. 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!)

29. Your patient on Paxil has shown some improvement over the last 5 months and seems stable. It may be time to… 1.Take her off the Paxil ‘cold turkey’ 2.Maintain the dose indefinitely 3.Increase the dose 4.Decrease the dose by half and monitor for a short time

30. Which of the following is true regarding lithium? 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