Antidepressants Flashcards
Pharmacological Treatment of Depression: General
50% of all patients are tx-resistant to AD’s
All classes of AD’s work on the same/ similar neural pathways, but wide range of symptoms (syndrome) suggests large variance in individual neurochemistry
Limited neural area of effect of AD’s may explain the high rates of failure
Disorders treated with Antidepressants
Anxiety disorders
Depressive disorders
Personality Disorders
Schizoaffective Disorder
Eating Disorders
Antidepressant Selection
Most AD efficacy is similar
Selection is based on:
- past response hx
- side effect profile
- coexisting medical conditions
Depression, General
Requires 2 weeks of symptoms (considered a syndrome)
No objective test for depression
Limited understanding of pathophysiology –several brain systems involved
Wide range of symptomatology:
- depressed irritable mood
- anhedonia
- weight changes,*
- sleep changes
- psychomotor agitation
- fatigue
- worthlessness
- guilt*
- diminished concentration
- suicidal ideation / bx
Biological theories of depression
Permissive hypothesis
● Depleted 5-HT increases NE
Catecholamine thoery: decreased NE
Indolamine theory: decreased 5-HT
Tricyclics (TCA)
5-HT and NE reuptake inhibition
Very effective but can have serious side effects
Lethal in overdose
*even 1-week supply can be lethal
Also indicated for neuropathic pain and migraines
E.g.
Imipramine (Tofranil, developed 1951)
Clomiprimine (Anafranil, effective for OCD)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Block presynaptic serotonin reuptake
Similar therapeutic benefits as MAOIs and TCAs, but fewer side effects
SSRI: Paroxetine (Paxil): Pro’s
Short half-life, with no active metabolite
*no long-term build-up
Sedation helps with sleep disturbances
Well absorbed in GI tract, good for patients with absorption problems
Monoamine Oxidase Inhibitors (MAOIs)
Inhibit MAO-A enzyme from being created
*Preventing breakdown of NE, DA, 5-HT
*Very effective for depression
MAOI Side Effects
Weight gain
Dry mouth
Sedation
Sexual dysfunction
Sleep disturbances
Orthostatic hypotension
Serotonin syndrome
MAOI food restrictions
Tyramine leads to hypertensive crisis by increasing the release of norepinephrine (NE)
MAO-A is inhibited and NE levels get too high, leading to dangerous increases in blood pressure (hypertension)
Foods to avoid: Aged meats and cheeses soy sauce draft beer wine avocados
MAOI Indications
Currently used with treatment-resistant patients
[* = non-responsive to at least 3 separate treatments]
e.g. Nardil, Parnate
More effective at treating atypical depression
SSRI: Sertraline (Zoloft) Pro’s
Less sedating
Lower risk of P450 interactions
Short half life with lower build-up of metabolites
SSRI: Fluoxetine (Prozac) Pros:
Long half-life
*decreased risk of overdose and withdrawal
Initially activating, may provide increased energy
SSRI: Citalopram (Celexa) Pro’s:
Fewest drug interactions of all SSRIs
Intermediate half-life lowers risk of discontinuation syndrome
SNRI’s: Serotonin-Norepinephrine Reuptake Inhibitors
e.g. Effexor, Cymbalta
SNRI’s commonly used to treat:
- major depression
- anxiety
- neuropathic pain
Function similarly to TCAs but without antihistamine, antiadrenergic, and anticholinergic side effects
SNRI: Venlafaxine (Effexor) Pro’s
Effexor:
Short half life and fast renal clearance avoids build-up *good for geriatric populations
High therapeutic success rate
*effective for treatment-resistant depression
Quick onset of antidepressant and anxiolytic activity
Minimum interactions
SNRI: Duloxetine (Cymbalta) Pro’s:
Cymbalta:
Effective in elderly patients with recurrent MDD
AD effects may be noticed after one week
**Less BP increase than Effexor
Reduces painful physical symptoms of depression
Low risk of weight gain
Lower rate of sexual side effects vs SSRIs
Low risk hypomania, mania, or hypomanic-like symptoms
Novel/Atypical Antidepressants: Remeron: Indications
Remeron:
MDD, but not a first-line drug
*Good choice for people with depression, anxiety, and insomnia (off label tx of insomnia)
Novel/Atypical Antidepressants: Bupropion (Wellbutrin/Zyban): General
Wellbutrin (NDRI):
Popular as augmenting agent for first-line SSRI
Also used as a second or third-line ADHD tx
Selective Serotonin Reuptake Enhancers (SSREs)
e.g. Coaxil
Opposite mechanism of SSRI
SSRE reduces 5-HT levels
5-HT and DA inversely related
MDD tx: decrease 5-HT to increase DA
Norepinephrine Reuptake Inhibitors (NRI or NERI)
Lower abuse potential than stimulants
Strattera: ADHD
Edronax: MDD
SSRI’s: Common Side effects
GI complaints
Anxiety, Restlessness, Insomnia
Sedation, Fatigue, Dizziness
Sexual dysfunction (30% chance)
Less Common:
Low risk of cardiotoxicity in overdose
SSRI’s: Discontinuation Syndrome
Agitation
Nausea
Disequilibrium
Dysphoria
Serotonin syndrome
Group of mild to severe symptoms that may occur following use of certain serotonergic medications or drugs:
High body temperature
Agitation
Increased reflexes
Tremor
Sweating
Dilated pupils
Diarrhea
TCA’s: Side Effects
Lethal in overdose
Anticholinergic effects
Q-T interval prolongation
*Slows down blood flow through the heart
Common Anticholinergic Side Effects
Blurred vision
Constipation
Decreased sweating
Dizziness
Dry mouth
Difficulty urinating and/or kidney failure
Future of Antidepressants
Since 1950s, all antidepressants/anti-anxiety medications attempt to alter DA, 5-HT, NE
Anxiety and Depression are both linked with increased activation in the HPA axis
*excessive release of the corticotrophin-releasing hormone or factor (CRF)
Current push to discover medications that act as CRF-antagonists
Antidepressants: Delayed Onset
Often a 3-6 week delay before sx improvement after tx dose is achieved
*Likely due to 2nd messenger process
SSRI: Paroxetine (Paxil): Cons
Contraindicated in Pregnancy
Weight gain
Increased risk of drug interaction
More prone to discontinuation symptoms
Atypical Depression
Increased sensitivity to loss
Dysthymia
Limbs feeling heavy
Melancholic depression (weight / sleep disturbances)
*Treated with MAOI’s (e.g. Nardil, Parnate)
SSRI: Sertraline (Zoloft): Cons:
Zoloft Cons:
Requires full stomach
Strong GI disruptions
SSRI: Fluoxetine (Prozac) Cons:
Prozac Cons:
Long half-life may cause buildup
Significant drug-drug interactions
May increase anxiety and insomnia
More likely to induce mania
SSRI: Citalopram (Celexa) Cons:
Celexa Cons:
GI issues
May cause initial anxiety
May be overly sedating
Affects cardiovascular health
SNRI: Venlafaxine (Effexor) Cons:
Effexor Cons:
- Hypertension
- High rate of tx-emergent mania and hypomania
Nausea and Increased GI effects
Short half-life: Withdrawal sx possible after missing a single dose
More toxic than SSRIs in overdose
SNRI: Duloxetine (Cymbalta) Cons:
Cymbalta Cons:
Nausea, sedation, Insomnia
May cause severe withdrawal symptoms
Patients with preexisting liver disease or excessive alcohol use are at a greater risk of liver injury
Unstable absorption rate a fraction of a dose is taken
Novel/Atypical Antidepressants:
Mirtazapine (Remeron) Pros:
Remeron Pro’s:
Good for severe depression and insomnia
*Indicated for depressed geriatric population who show failure to thrive and marked weight loss
Selective effects on serotonin receptors
*good augmentation strategy for SSRI’s
Novel/Atypical Antidepressants:
Mirtazapine (Remeron) Cons:
Remeron Cons:
Significant weight gain and sedation
Increases cholesterol
Beneficial effects decrease as dosage increases
May cause agranulocytosis
Novel/Atypical Antidepressants:
Bupropion (Wellbutrin/Zyban) Pro’s:
Wellbutrin (NDRI) Pro’s:
Less weight gain
Less sexual dysfunction
Less sedation or cardiac risks
Little risk of inducing mania
Novel/Atypical Antidepressants: Bupropion (Wellbutrin/Zyban) Cons:
Wellbutrin Cons:
Cost: $75-$100 per day
Increased risk of seizure
*can’t be used with TBI, bulimia, or anorexia
Interactions with TCAs
Can increase anxiety, agitation, and insomnia
Abuse potential, can induce psychosis in high dosages
Non-response to AD, considerations
If no improvement after at least 2months at adequate dose:
- switch to another antidepressant
- or augment with another agent
