Medication 101:
Everything you wanted to know but
were afraid to ask
Depression: A Mood Disorder
What is a mood disorder?
• A biological illness
• A disturbance of mood accompanied by
other symptoms such as alterations in:
• sleep, appetite, energy, thought, behavior
Depression: Important Facts
• 17% of population will have depression
in their lifetime
• ~ 3.4% of patients diagnosed with depression
will commit suicide
• Total annual cost –
$50 billion, 55% of
which is due to lost productivity
Kessler RC et al. Arch Gen Psychiatry. 1994;51:8-19.
Depression Guideline Panel. AHCPR publication 93-0550. 1993.
Greenberg PE et al. J Clin Psychiatry. 1993;54:405-418.
Economics of Depression Total Annual Cost ~$50 Billion
Lost productivity—
55%
Suicide—17%
Outpatient care—
6%
Greenberg PE et al. J Clin Psychiatry. 1993;54:405-418.
Pharmaceuticals—
3%
Inpatient care—
19%
Diagnostic Criteria for Major Depression
• Depressed mood OR decreased interest or
pleasure in activities AND some of these:
•
•
•
•
•
•
•
Significant weight gain or loss
Decreased or increased amount of sleep
Agitation or sluggishness
Fatigue or loss of energy
Feelings of worthlessness or guilt
Decreased concentration
Recurrent thoughts of death/suicide
Course of Depressive Episode
•
A recurrent illness
• Episodes last average of 6-12 mos. if
untreated
• Commonly, people return to normal between
episodes
Antidepressants: Major Classes
CLASS
EXAMPLES
Serotonin reuptake inhibitors
(SSRIs)
Serotonin-Norepinephrine
Reuptake Inhibitors (SNRIs)
Dopamine-Norepinephrine
Reuptake Inhibitors
Atypical antidepressants
Prozac, Zoloft,
Paxil, Lexapro
Effexor, Cymbalta
Wellbutrin
Remeron
Tricyclic Antidepressants
Elavil, Pamelor
(TCAs)
Monoamine Oxidase Inhibitors Nardil, Parnate
(MAOIs)
Developments in Treatment of Depression
1900
1st century
’30s
“Black bile”
ECT
’40s
’50s
’60s
’70s
TCAs MAOIs
’80s
’90s
SSRIs
Heterocyclics
Lithium
Kaplan HI, Sadock BJ. In: Pocket Handbook of Psychiatric Drug Treatment. 1996.
Pharmacologic
Refinements
Antidepressants
How do they work?
• All increase levels of neurotransmitters
• chemical messengers between cells in the brain
• May help depression by changing brain
circuits that regulate moods
Antidepressants
What do they do?
• Produce significant decrease in symptoms over
4-6 weeks in 60-70% of people
• Help to prevent future episodes
• All have potential side effects
Problems with current treatments for
depression
• 2-4 week time lag before improvement begins
• Too many people don’t respond to them
• No ADs that work completely differently
• Lack of long-term studies
• Side effects still cause problems
FDA approvals for depression in past 10
years
Year
Drug Name
2013
vortioxetine, levomilnacipran
2011
vilazodone
2008
desvenlafaxine
2006
selegeline transdermal
2004
duloxetine
Antidepressants
How effective are they?
• Evidence differs depending on:
• Response vs. remission
• Clinical trials vs. naturalistic
Effectiveness of antidepressants
• Only 1/3 of patients get fully better with 1st
treatment
• 1/2 of patients who have good response have
significant residual symptoms
Selective Serotonin Reuptake Inhibitors
(SSRIs)
Prozac, Zoloft, Paxil, Lexapro, Celexa
• Work by increasing serotonin levels in the brain
• Safer and better tolerated than older
antidepressants
• Main side effects – nausea, tremor, sexual
dysfunction
Serotonin and Norepinephrine Acting
Antidepressants:
Effexor, Duloxetine, Pristiq
• Increase serotonin and norepinephrine in the
brain
• Side effects: similar to SSRIs but more likely to
cause anxiety or increased BP or HR
Other Antidepressants:
Wellbutrin
• Increases norepinephrine and dopamine in the
brain
• side effects: agitation, nausea, insomnia,
seizures (4 out of 1000)
Newly approved medications
Levomilnacipran (Fetzima)
• Related to milnacipran which is approved for
depression outside U.S.
• Works by increasing serotonin and
norepinephrine (SNRI)
Vilazodone (Viibryd)
• Works by increasing serotonin and modulating
serotonin receptors
• Potential Advantages –
• earlier onset of action?
Vortioxetine (Brintellix)
• Mechanism - "serotonin modulator"
• Increases serotonin AND modulates receptors
•
5-HT1a receptor
•
5-HT1b receptor
•
5-HT3a receptor
•
5-HT7 receptor
Ketamine
• Blocks portion of the glutamate receptor
• Studies show patients have a rapid response
after single i.v. dose1 which lasts up to 1 week
• Uncertain if response is sustained and safety of
longer use is concern
1Zarate
et al., 2006