The document provides an extensive overview of depression, detailing its types, symptoms, diagnosis, causes, and treatment options, including various pharmaceuticals. It outlines the mechanisms of action and side effects of different classes of antidepressants, such as SSRIs, SNRIs, TCAs, and MAOIs. Additionally, it discusses neurotransmitter-related theories and the importance of patient history in diagnosing depression.

1. ANTIDEPRESSANTS
Sourav Biswas
Group 15
Course 4

2. DEPRESSION
1. Types
2. Symptoms
3. Diagnosis
4. Causes
5. Treatment

3. TYPES OF DEPRESSION
 Major depression
 Chronic depression (Dysthymia)
 Atypical depression
 Bipolar disorder/Manic depression
 Seasonal depression (SAD)

4. SYMPTOMS
• persistently sad, anxious, or empty moods
• loss of pleasure in usual activities (anhedonia)
• feelings of helplessness, guilt, or worthlessness
• crying, hopelessness, or persistent pessimism
• fatigue or decreased energy
• loss of memory, concentration, or decision-making capability
• restlessness, irritability
• sleep disturbances
• change in appetite or weight
• physical symptoms that defy diagnosis and do not respond to
treatment (especially pain and gastrointestinal complaints)
• thoughts of suicide or death, or suicide attempts
• poor self-image or self-esteem (as illustrated, for example, by
verbal self-reproach)

5. DIAGNOSIS
• Extensive patient and family history
• Blood test for hypothyroidism
• Current medication
• DSM-IV
• One of the first two symptoms
• Five other symptoms

6. CAUSES OF DEPRESSION
 Genetics
 Death/Abuse
 Medications

7. TREATMENT FOR DEPRESSION
• Psychotherapy
• Electroconvulsive therapy
• Natural alternatives
• Medication
• SSRIs
• MAOIs
• TCAs
• SNRIs
• NDRIs
• TeCAs

8. NEUROTRANSMITTERS AND THE
CATECHOLAMINE HYPOTHESIS
• Neurotransmitters pass along signal
• Smaller amount of neurotransmitters causes
depression

9. MONOAMINE OXIDASE (MAO) AND
DEPRESSION
• MAO catalyze deamination of intracellular
monoamines
• MAO-A oxidizes epinephrine, norepinephrine,
serotonin
• MAO-B oxidizes phenylethylamine
• Both oxidize dopamine nonpreferentially
• MAO transporters reuptake extracellular
monoamine

10. MONOAMINE OXIDASE INHIBITORS
(MAOIS)
• History
• Isoniazid
• Iproniazid
• Current Drugs
• Mechanism of Action
• Side Effects Isoniazid
Iproniazid

11. MAOIS ON THE MARKET
• MAO Inhibitors (nonselective)
• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Isocarboxazid (Marplan)
• MAO-B Inhibitors (selective for MAO-B)
• Selegiline (Emsam)

12. MAOIS MECHANISM OF ACTION
• MAO contains a
cysteinyl-linked
flavin
• MAOIs covalently
bind to N-5 of the
flavin residue of
the enzyme

14. MAOIS SIDE EFFECTS

15. THE RECEPTOR SENSITIVITY
HYPOTHESIS
Supersensitivity and up-regulation of post-
synaptic receptors leads to depression
Suicidal and depressed patients have increased
5HT-α2 receptors

16. TRICYCLIC ANTIDEPRESSANTS
(TCAS)
• History
• Imipramine
• Current Drugs
• Mechanism of Action
• Side Effects
Imipramine

17. TCAS ON THE MARKET
Amitriptyline
Desipramine (Norpramin)
Doxepin (Sinequan)
Imipramine (Tofranil, Tofranil-PM)
Nortriptyline (Pamelor)
Protriptyline (Vivactil)
Trimipramine (Surmontil)

18. TCAS SIDE EFFECTS
• Muscarinic M1 receptor antagonism - anticholinergic
effects including dry mouth, blurred vision,
constipation, urinary retention and impotence
• Histamine H1 receptor antagonism - sedation and
weight gain
• Adrenergic α receptor antagonism - postural
hypotension
• Direct membrane effects - reduced seizure threshold,
arrhythmia
• Serotonin 5-HT2 receptor antagonism - weight gain
(and reduced anxiety)

19. TCAS SIDE EFFECTS
 Nonselectivity results in
greater side effects
 TCAs can also lead to
cardiotoxicity
 Increased LDH leakage
 Slow cardiac conduction
 High potency can lead to
mania
 Contraindicated with
persons with bipolar
disorder or manic depression

20. TETRACYCLIC ANTIDEPRESSANTS
(TECAS)
 Current Drugs
 Mirtazapine (Remeron)
 Mechanism of Action
 Same as TCAs
 Side Effects

21. SELECTIVE SEROTONIN REUPTAKE
INHIBITORS
Most commonly prescribed class
Current drugs
Mechanism of action
Side effects
Serotonin

22. SSRIS ON THE MARKET
• citalopram (Celexa)
• dapoxetine (Priligy)
• escitalopram (Lexapro)
• fluoxetine (Prozac)
• fluvoxamine (Luvox)
• paroxetine (Paxil)
• sertraline (Zoloft)
• zimelidine (Zelmid) (discontinued)
• indalpine (Upstene) (discontinued)
Fluoxetine 1:1
Sertraline

23. SSRIS MECHANISM OF ACTION
 Exact mechanism remains uncertain
 Ser-438 residue in the human serotonin
transporter (hSERT) appears to be a determining
factor in SSRI potency
 Antidepressants interact directly with hSERT
 http://www.mayoclinic.com/health/antidepressant
s/MM00660

24. SSRIS SIDE EFFECTS

25. SEROTONIN-NOREPINEPHRINE
REUPTAKE INHIBITORS (SNRIS)
• Slightly greater efficacy than SSRIs
• Slightly fewer adverse effects than SSRIs
• Current drugs
• Venlafaxine (Effexor)
• Duloxetine (Cymbalta)
• Mechanism of Action
• Very similar to SSRIs
• Works on both neurotransmitters
• Side effects
• Similar to SSRIs
• Suicide
Venlafaxine 1:1
Duloxetine

26. NOREPINEPHRINE-DOPAMINE
REUPTAKE INHIBITORS (NDRIS)
 Current drugs
 Bupropion (Wellbutrin)
 Mechanims of Action
 Similar to SSRIs and SNRIs
 More potent in inhibiting dopamine
 Also anα3-β4 nicotinic antagonist
 Adverse effects
 Lowers seizure threshold
 Suicide
 Does not cause weight gain or sexual dysfunction
(even used to treat the two)
Bupropion 1:1

27. REFERENCES
 http://ajp.psychiatryonline.org/cgi/reprint/157/11/1901
 http://www.webmd.com/depression/
 http://pn.psychiatryonline.org/content/41/24/21.full
 http://www.mayoclinic.com/health/maois/MH00072
 http://www.springerlink.com/content/b9b8668ff59f89d7/fulltext.pdf
 http://www.emsam.com/pi_emsam.pdf
 http://www.nevdgp.org.au/info/topics/depression_theory.htm
 http://www.uspharmacist.com/content/t/psychotropic_disorders/c/11467/
 http://www.jbc.org/content/284/15/10276.full.pdf+html
 http://www.aafp.org/afp/981200ap/cadieux.html
 http://www.mayoclinic.com/health/antidepressants/MH00071
 http://books.google.com/books?id=R0W1ErpsQpkC&pg=PA565&lpg=PA565&dq=tcas+mechanism+
of+action&source=bl&ots=oASle2Z-pr&sig=36CB_3JY4uD3LIYvqXWmAb3nliY&hl=en&ei=HzfFS9
OrB4Tu9gTD6_ixDg&sa=X&oi=book_result&ct=result&resnum=8&ved=0CCoQ6AEwBw#v=onepa
ge&q=tcas%20mechanism%20of%20action&f=false
 http://www.informaworld.com/smpp/content~content=a916036122&db=all