Title: Depression
1Depression
- At least 5 of the following symptoms for 2 weeks
(criteria 1 or 2 essential) - 1. Depressed mood.
- 2. Loss of interest or pleasure.
- 3. Significant weight loss or gain.
- 4. Insomnia or hypersomnia.
- 5. Psychomotor agitation or retardation.
- 6. Fatigue or loss of energy.
- 7. Feelings of worthlessness or excessive guilt.
- 8. Impaired thinking or concentration
indecisiveness. - 9. Suicidal thoughts/thoughts of death.
2Depression
- Likely cause inadequate monoamine levels
- Treatment
- Blocking NT reuptake by presynaptic end
3Antidepressants
- Used to relieve symptoms of depression as well as
help patients with anxiety disorders - Major groups
- Tricyclic antidepressants
- Heterocyclic antidepressant
- Selective serotonin reuptake inhibitors
- Monoamine oxidase inhibitors
- Atypical antidepressants
4Antidepressants
- They now have recognised roles in the treatment
of - generalized anxiety disorder,
- panic disorder,
- obsessive compulsive disorder,
- social phobia,
- bulimia nervosa,
- chronic pain and
- Nocturnal enuresis (Imipramine)
5Antidepressants
- On balance, the selective serotonin reuptake
inhibitors (SSRIs) and other newer
antidepressants may be better tolerated and have
a wider safety margin than the tricyclic
antidepressants (TCAs) and irreversible
nonselective monoamine oxidase inhibitors
(MAOIs).
6Antidepressants
- A delay in onset of antidepressant response of at
least 1 to 2 weeks occurs with all
antidepressants.
7Antidepressants
- Tricyclic Antidepressants (TCAs)
- Prototype Imipramine
- Mechanism of Action
- Block neuronal reuptake of norepinephrine and
serotonin which intensifies their effects - Uses Depression, bipolar disorder,
- Considerations Initial responses develop in 1-3
weeks maximal responses over 1 to 2 months.
8Antidepressant Mechanism
TCAs SSRIs Block Here
9TCA Side Effects
- Sedation
- Anticholinergic effects
- Orthostatic hypotension
- Cardiac toxicity
- Ventricular dysrythmias
10Heterocyclic antidepressant
- Second generation antidepressant
- (e.g., Amoxapine, bupropion, maprotiline,
trazodone) and newer, third generation drugs - (duloxetine, mirtazapine, nefazodone,
venlafaxine). - It has less cardiovascular and anticholinergic
adverse effects than the TCAs and has a wider
margin of safety in overdose.
11Antidepressants
- Selective Serotonin Reuptake Inhibitors (SSRIs)
- Most commonly prescribed group of antidepressants
- As effective as TCAs but do not cause
hypotension, sedation, or anticholinergic effects
(dry mouth, blurred vision, photophobia,
constipation, urinary hesitancy, tachycardia). - Use major depression/
- Prototype Fluoxetine (Prozac)
- Mechanism of action
- Produces selective inhibition of serotonin
reuptake - Blockade of transmitter uptake occurs quickly,
therapeutic effects are the result of adaptive
cellular changes that take place in response to
prolonged uptake blockade - Other SSRIs citalopram, fluvoxamine, paroxetine
and sertraline.
12Selective Serotonin Reuptake Inhibitors (SSRIs)
- Block only serotonin (not NE) reuptake
- Elevate serotonin levels
- Fewer side effects than TCS
- No hypotension
- No anticholinergic effects
- No cardiotoxicity
- Most common side effect
- Nausea, diarrhoea, insomnia, sexual dysfunction
13Antidepressants
- Monoamine Oxidase Inhibitors (MAOIs)
- Most dangerous risk of triggering hypertensive
crisis by eating foods rich in tyramine. - MAO is an enzyme found in the liver, the
intestinal wall, and terminals of
monoamine-containing neurons. Their function is
to convert NE, serotonin, and dopamine into
inactive products. - MAO inhibitors block this process.
- Uses depression, bulimia, obsessive-compulsive
disorder, reduce panic attacks - Caution many drug interactions
14Monoamine Oxidase Inhibitors (MAOIs)
- Monoamine oxidase
- Present in liver, intestines MonoAmin releasing
neurons - Inactivates monoamines
- Inactivates dietary tyramine in liver
- Foods rich in tyramine cheese red wine
15MAOI Side Effects
- CNS Stimulation
- Anxiety, agitation
- Orthostatic hypotension
- Hypertensive Crisis
- From increased tyramine consumption
- Excessive arteriole constriction, stimulation of
heart
16MAOI Dietary Tyramine
17Antidepressant Mechanism
TCAs SSRIs Block Here
18Antidepressants
- Atypical Antidepressants
- Bupropion (Wellbutrin)
- Bupropion is an antidepressant which inhibits
neuronal reuptake of dopamine and is a
noncompetitive nicotine antagonist at nicotinic
cholinergic receptors. - Adverse effects include nausea, rashes, facial
swelling, insomnia and dry mouth. - Contraindicated in patients with a seizure
disorder bulimia or anorexia nervosa monoamine
oxidase inhibitor treatment in the previous 14
days
19Antidepressants Agents
- TCAs
- imiprimine (Tofranil)
- amitriptyline (Elavil)
- nortriptyline (Pamelor )
- SSRIs
- fluoxetine (Prozac)
- paroxetine (Paxil)
- sertraline (Zoloft)
- Fluvoxamine
- MAOIs
- phenelzine (Nardil)
- Moclobemide
- Second generation antidepressant
- (eg, Amoxapine, bupropion, maprotiline, trazodine
and newer, third generation drugs (duloxetine,
mirtazapine, nefazodone, venlafaxine).
20Drugs for Bipolar Disorder
- Bipolar Disorder
- Severe biologic illness characterized by
recurrent fluctuations in mood either the mood
is abnormally elevated or depressed. - Drug therapy
- Mood stabilizers
- Antidepressants (used w/mood stabilizer)
- Antipsychotics (used w/mood stabilizer)
21Drugs for Bipolar Disorder
- Mood Stabilizing Drugs
- Provide relief from an acute manic or depressive
episode, preventing symptoms from recurring. - Prototype Lithium
- Low therapeutic index so levels MUST be monitored
(toxicity can occur at blood levels that are only
slightly greater than therapeutic).
22Drugs for Bipolar Disorder
- Prototype Lithium
- Action Specific mechanism unknown alters sodium
transport in nerve and muscle cells
23Drugs for Bipolar Disorder
- Prototype Lithium
- CV Arrhythmias hypotension peripheral
circulatory collapse. - CNS Tremor ataxia dizziness confusion
hallucinations seizures drowsiness muscular
weakness slurred speech.
24Drugs for Bipolar Disorder
- Prototype Lithium
- EENT Blurred vision tinnitus.
- GI Anorexia nausea vomiting diarrhea
sialorrhea dry mouth parotitis. - GU Urinary urgency polyuria albuminuria
sexual dysfunction symptoms of nephrogenic
diabetes decreased creatinine clearance.
25Drugs for Bipolar DisorderLithium Interactions
- Acetazolamide, osmotic diuretics, theophyllines,
urinary alkalinizers Increased renal excretion
of lithium. - ACE inhibitors, thiazide diuretics, loop
diuretics, NSAIDs, fluoxetine Increased lithium
serum levels.
26Drugs for Bipolar Disorder
- Mood Stabilizing Anticonvulsants
- Prototype Valproic acid (Depakene, Depakote)
- It is the only antiseizure agent that has been
approved by the FDA for treatment of BPD. - It is as effective as lithium, works faster, and
has a higher therapeutic index and more desirable
side effect profile. - First line treatment for BPD
27Drugs for Bipolar Disorder
- Valproic acid (Depakene, Depakote)
- Action
- Believed to work by increasing brain levels of
GABA. - It may also inhibit catabolism of GABA,
potentiate postsynaptic GABA responses, and
affect potassium channels or directly stabilize
membranes.
28Drugs for Bipolar Disorder
- Valproic acid (Depakene, Depakote)
- Contraindications Hepatic disease dysfunction.
29Drugs for Bipolar Disorder
- Valproic acid (Depakene, Depakote)
-