• Tricyclic: 1st choice drug, inexpensive, effective, relatively safe, easy administration
• selective serotonin reuptake inhibitiors: just as effective as Tricyclics, better tolerated, expensive, most widely prescribed 
• serotonin and norepinephrine reuptake inhibitors:
• monamine oxidase inhibitor: reserved for pts. who have not responded to TCAs or SSRIs unless pt has atypical depression
• atypical antidepressants

• 5 symptoms must be present 2 weeks or more and must represent a change from previous fx. One of the symptoms must be 1.) depressed mood or 2.) loss of interest or pleasure
• The symptoms do not meet the criteria for a Mixed Episode (a manic depressive)
• The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning
• The symptoms are not due to the direct physiologic effects of a symptoms or a general condition
• Should not be diagnosed in the context of bereavement unless symptoms persist for >2 mos or are characterized by marked fx impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms or psychomotor retardation

• Depressed mood most of the day, nearly every day
• Loss in pleasure or interest in almost all activities
• Weight gain/loss without dieting, or loss/gain in appetite
• Insomnia/hypersomnia
• Psychomotor agitation or retardation
• Fatigue or loss of energy
• Feelings of worthlessness or excessive or inappropriate guilt
• Diminished ability to think or concentrate or indecisiveness
• Recurrent thoughts of death, recurrent suicidal ideation, suicide attempt, suicide plan 

Major Depression is a medical condition. Grief is an appropriate reaction to stressors in life and resolves spontaneously within a few weeks without medical interventions

• Depression is caused by a functional deficiency of monoamine neurotransmitters (norepinephrin, serotonin, or both)
• Evidence by
  • induction of depression with reserpine (a drug that depletes monoamines from the brain or with inhibitors of tyrosine hydroxylase an enzyme needed for monoamine transmitter synthesis
  • relief of depression with drugs that intensify monoamine-mediated NT

1. Pharmacotherapy:

2. Depression-specific psycotherapy:

3. electroconvulsive therapy (ECT): used when a rapid response is needed

4. Vagus nerve stimulation: used only after treatment with at least 4 drugs has failed

• Drug therapy and psychotherapy are equally effective for mild-moderate depression
• For severe depression a combo of drugs and pschotherapy is more effective than either intervention alone

• Safe and effective, rapid benefits, important when speed is critical
•  Used for pts who are
  • severely depressed or suicidal
  • ederly and at risk of starving to death because of depression induced lack of appetite
  • not responding to antidepressant drugs

•  during tx especially early on risk of suicide may actually increase, mainly apply to children, adolescents, and adults under the age of 25
• Prescriptions should be written for the smallest number of doses consistent with good pt. management 
• Dosing of inpatients should be directly observed to ensure that each dose is swallowed and not "cheeked" to prevent intentional overdoses

• Drugs of first choice for many pt with major depression
• The first TCA agent was imipramine in the 50's
• Most common adverse effects are sedation, orthostatic hypotension, and anticholinergic effects
• Most dangerous effect is cardiac toxicity

neuronal,

reuptake,

norepinephrine(NE), and serotonin(5-HT), reuptake, increased

• Long and variable, usually administered in a single daily dose but should be individualized for dosage,

1. Depression: Elevate mood, increase activity and alertness, decrease morbid preoccupation, improve appetite, and normalize sleep patterns.
2. Bipolar Disorder: can help during the depressive episodes

• in addition to blocking uptake of monamine transmitters TCAs cause direct blockade of receptors for histamine, acetylcholine, and NE

• A common response to TCAs
• Caused by a blockade of histamine receptors in the CNS

• rare unless there is a previous cardiac impairment or an overdose
• Decreases vagal influence on the heart ( secondary to muscarinic blockade)
• Act directly on the bundle of His to slow conduction.
• Both effects increases the risk of dysrhythmias 
• To minimize risk all patients undergo electrocardiographic evaluation prior to tx.

Drug Interactions with TCAs:

a.) Monoamine Oxidase Inhibitors
b.) Direct-Acting Sympathomimetic Drugs
c.) Indirect-Acting Sympathomimetic Drugs
d.) Anticholinergic Agents
e.) CNS Depressants

a.) can lead to severe hypertension due to excessive adrenergic stimulation of the heart and blood vessels

b.) potentiates responses to direct-acting sympathomimetics due to TCAs blocking uptake of epinephrine and dopamine into adrenergic nerve terminals, prolonging their presence in synapse

c.) Decreases responses due to TCAs blocking uptake of ephedrine and amphetamine into adrenergic nerves, preventing them from reaching their site of action

d.) intensify effects advise to avoid OTC antihistamines

e.)  Potentiate effeect of CNS depression caused by CNS depressants including alcohol, antihistamines, opiods, and barbiturate

• As effective as TCAs
• Do not cause hypotension, sedation, or anticholinergic effects
• Overdose does not cause cardiotoxicity, rarely death

• Side effects include
  • nausea, agitation/insomnia, and sexual dysfunction
• Adversely interact with MAOIs and other serotonergic drugs
• When used late in pregnancy result in a withdrawal syndrome and persistant pulmonary hypertension in the infant