• sadness
• hopelessness
• despair
• loss of pleasure in usual activities
• sleep & appetite changes
• decreased energy
• suicidal thoughts

1. directly/indirectly potentiates actions of  norepi/serotonin in brain

2. Biogenic Amine Theory

3. Mania d/t overproduction of these NT

• oversimplistic
• depression d/t deficiency of monoamines @ certain key sites in brain
• does NOT explain time course of drugs
• blocking NT uptake does NOT correlate w/clinically observed results
• down regulation of inhibitory receptors

• opposite of depression
  • enthusiasm
  • rapid thought
  • rapid speech pattern
  • extreme self confidence
  • impaired judgement

1. block reuptake of serotonin leading to increased conc. in the synaptic cleft

2. two wks. - intial mood improvement

3. 12+ wks. - max. benefits felt

4. 40% do NOT respond, so try different drug

5. does NOT produce mood changes in normal individuals

• Depression
• OCD
• Panic disorders
• Generalized Anxiety

• Oral-well absorbed
• Food has little effect
• Plasma 1/2 life = 16-36 hrs.
• P450 met.
• Excretion via kidneys
• Decreased dose in liver impaired patients

• Anxiety
• Drowsiness
• Sleep disorders
• Sexual dysfunction
• Drug interactions
• Nausea

• Paroxetine (Paxil)- sedating
• Fluvoxamine (Luvox) - sedating
• Fluoxetine (Prozac) -good in fatigued pts.

• loss of libido
• delayed ejaculation
  • (these are underreported)
• Buproprion (Wellbutrin) & Mirtazapine (Remeron)
  • both of these have a low incidence of sexual side effects (note that these 2 drugs are actually Atypical antidepressents)

• use with caution
• 1:50 become more suicidal after drug treatment

• do NOT cause cardiac arrhythmias
• Fluoxetine (prozac)
  • seizures possible
  • Can cause Serotonin Syndrome (symptoms of hypothermia, muscle rigidity, myoclonus - in the presence of and MAO inhibitor)
• increased time for drug to wash out

• selectively inhibits reuptake of both Serotinin & Norepi
• NO Activity at: muscarinic, adrenergic, or histamine receptors

• pts. NOT responding to SSRIs
• pts. with neuropathic pain

• Venlafaxine (Effexor)
• Duloxitine (Cymbalta)

ACTIONS:

• potent inhibitor of serotonin reuptake
• incr. dose inhibits norepi reputake
• mild dopamine reuptake inhibition @ incr. doses
• compound/active metabolite 1/2 life=11 hrs.

SIDE EFFECTS:

• nausea
• dizziness
• insomnia
• sedation
• constipation
• high dose = high BP

ACTIONS:

• inhibits serotonin/norepi @ all doses
• liver met.
• kidney excretion
• CONTRAINDICATED in Renal Dz. pts.
• food delays absorption***unlike pharmacokinetics of SSRIs

SIDE EFFECTS:

• n/v
• dry mouth
• constipation, diarrhea
• insomnia, dizziness, somnolence
• sweating
• sexual dysfunction

• Buproprion (Wellbutrin)
• Mirtazipine (Remeron)
• Nefazodoen/Trazodone (Desyrel)

ACTIONS:

• unknown action site
• short 1/2 life
• requries more than 1 per day dose or use extended release
• decr. cravings for nicotine

SIDE EFFECTS:

• dry mouth
• sweating
• tremor
• incr. dose = seizures

ACTIONS:

• central presynaptic alpha 2 adrenergic receptor & 5HT2 receptor
• sedative d/t strong antihistimine activity
• NO antimuscarinic effects of TCA
• NO sexual dysfunction
• incr. appetite + weight gain

SIDE EFFECTS:

• sedation, useful though in insomnia

ACTIONS:

• WEAK serotonin uptake inhibitor
• blocks 5HT1 presynaptic autoreceptors, therefore incr. serotonin release

SIDE EFFECTS:

• sedation potent H1 blocking activity
• priapism (erection that won't go away)

• block norepi/serotonin uptake into neuron
• alternative for pts. that can't use SSRIs

• inhibits NT uptake
• inhibits reuptake of norepi/serotonin @ presynaptic terminals
• blocks receptors
• blocks serotogenic, histaminic, and muscarinic receptors

elevates mood

• improves mental alertness
• incr. physical activity
• decr. morbid preoccupation in 50-75% of pts. w/major depression
• slow onset of mood elevation
• NO effect in normal indvidiuals (RE: mood & stimulation)
• physical dependence & slow W/D

• treat major depression
• panic disorders
• bedwetting -Imipramine (Tofranil)
• neuopathic pain - Amitriptyline (Elavil)

• absorbed well orally
• lipid soluble
• long 1/2 lives
• variable 1st pass met.
• low & inconsistent bioavailability
• dosages MUST be adjusted based on pt. response met. by hepatic microsomal system
• excreted in urine

• Ach receptor blockade
• weight gain - COMMON
• blurred vision
• xerostomia
• urinary retention
• constipation
• aggravation of glaucoma
• epilepsy
• incr. catecholamine activity leads to cardiac stimulation & can be fatal in OD
• TCA block alpa adrenergic receptors which leads to orthostatic hypotension and tach. -Imipramine/Nortriptyline least likely to cause hypotension
• sedation is prominent, d/t H1 histamine receptor blockage

• NARROW therapeutic index
• 5-6X the max. daily dose is lethal

• mitochondrial enzyme found in nerve & other tissues
  • Nerves: acts as a safety valve to inactivate excess NT
• can REVERSIBLY or IRREVERSIBLY inactivate the enzyme that allows NTs to escape degradation, thereby accumulating in the presynaptic neuron
• use limited d/t complcated diet & drug interactions
• NOT considered 1st line meds d/t diet & drug interactions
• extensive side effects

• Phenelzine (Nardil)
• Tranylcypromine (Parnate)

• deactivate MOA
• allow build up of NT
• allow build of of toxic substances such as tyramine

• similar to that of TCSa and SSRIs
• delayed several weeks

• for persons allergic or NOT responding to TCAs
• those w/low psychomotor actvity
• those w/strong anxiety
• ATYPICAL depression:
  • labile moods, rejection sensitivity,eating disorders

• well absorbed, but take 2-4 weeks for antidepressant activity
• enzyme regeneration varies, but takes several weeks
• when switching antidepressants, must wait a min. of 2 weeks

ADVERSE EFFECTS:

• severe & unpredictable effects
• limits its uses
• must avoid tyramine in diet

SIDE EFFECTS:

• drowsiness
• ortho hypotension
• blurred vision
• xerostomia
• dysuria
• constipation

• Treatment: Lithium
  • given orally
  • excreted by kidneys
  • mechanism unknown
  • lithium salts are very toxic
  • Therapeutic index - extremely low

• ataxia
• tremors
• confusion
• convulsions
• dry mouth
• polyuria
• thyroid function decrease
• NOT a sedative, euphoriant, or depressant