This presentation deals with the various medicines used in the treatment of depression and mania. The drugs used include MAO inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin and noradrenaline reuptake inhibtors and atypical antidepressants with a brief mention of Lithium at the end

1. Depression and Mania
Dr. Karun Kumar JR – II Dept. of Pharmacology

4. Major depressive disorder Bipolar disorder
Depressed mood Recurrent fluctuations in
mood
Loss of interest/pleasure in
life
Extremes of human
experience
Sleep disturbances Mania alternates/occurs
simultaneously with
depression
Feelings of worthlessness Elevated mood, inflated self
esteem
Diminished ability to
think/concentrate
↑ talking, racing thoughts
Recurrent thoughts of
suicide
↑ social/work activity
Irritable/anxious ↓ need for sleep

6. Biogenic amine hypothesis
• Mood disorders  Abn. In 5-HT, NE, DA neurotr.
• Antidep. Drugs  ↑ 5-HT, NE, DA neuotr. In brain

9. Antidepressant drugs
1. MAO inhibitors
1st gen.  Phenelzine, Tranylcypromine (MAO-A+B)
2nd gen.  Moclobemide, Clorgyline (MAO A)
Selegiline  MAO-B
2. Tricyclic antidepressants (TCAs)
A. NA + 5-HT reuptake inhibitors
• Imipramine, Amitriptyline, Clomipramine, Doxepin
B. Predominantly NA reuptake inhibitors
• Desipramine, Nortriptyline, Amoxapine

10. 3. Selective Serotonin Reuptake Inhibitors (SSRIs)
• Fluoxetine, Fluvoxamine, Paroxetine, Sertraline,
Citalopram, Escitalopram, Dapoxetine
4. Serotonin and noradrenaline reuptake inhibitors
(SNRIs)
• Venlafaxine, Duloxetine
5. Atypical antidepressants
• Trazodone, Mianserin, Mirtazapine, Bupropion,
Tianeptine, Amineptine, Atomoxetine

11. SSRIs
• First choice drugs for
1. Depression
2. Obsessive Compulsive Disorder
3. Post-traumatic stress disorder
4. Bulimia nervosa
5. Panic disorder
6. Premenstrual tension syndrome

12. MAO
MAO A MAO B
Location Adrenergic
nerve endings,
intestinal
mucosa &
human placenta
Brain & platelets
Metabolizes 5-HT, NE, DA Phenylethylamin
e, DA
Inhibitors Moclobemide,
Clorgyline
Selegiline

13. Cheese Reaction (DOC  Phentolamine)
Cheese, beer, red wine & banana contain tyramine
↓
In presence of MAOI, it escapes degradation
↓
Reaches systemic circulation
↓
Uptake by adrenergic neuron
↓
Enters storage vesicles & displaces NE
↓
Hypertensive crisis

14. Serotonin syndrome
H  Hyperthermia
A  Autonomic instability (delirium)
R  Rigidity
M  Myoclonus
To avoid s.s. SSRIs should be started at
least 14 days after discontinuation of
MAOIs

15. Side effects of TCAs
T  Tremors
C  Cardiovascular side effects
(Arrhythmias esp. in IHD, postural
hypotension)
A  Anticholinergic s/e (dry mouth,
dysphagia, constipation, urinary
retention, palpitations)
S  Sedation & seizures

16. Side effects of SSRIs
S  Serotonin syndrome
S  Stimulate CNS
R  Reproductive
dysfunctions in male
I  Insomnia

17. Uses of antidepressants
1. D  Depression
2. E  Enuresis (Imipramine)
3. P  Phobia (Fluvoxamine)
4. R  Recurrent panic attacks
5. E  Easting disorders (bulimia)
6. S  Smoking cessation (Bupropion)
7. S  Stress disorder (PTSD)
8. I  Impulse disorder (Kleptomania)
9. O  OCD (Fluvoxamine)
10. N  Neuropathic pain (Amitriptyline, Duloxetine)

18. Mood stabilizing drugs
•Normalize the swings of affect in
bipolar disorder
•Reduces both manic and depressive
symptoms and thereby tends to
normalize the mood in patients
with bipolar disorder
•Main use  T/t or prevent the
manic phase of bipolar disorder

20. Side effects of Lithium
LI  Leukocytes Increased
(Leukocytosis)
T  Tremors
H  Hypothyroidism
IU  Increased Urine (Diabetes
insipidus)
M  Moms beware (teratogenic)

21. Review Questions
1. Which one of the following is not a class of
antidepressant medications?
(A) SNRIs
(B) TCAs
(C) MAOIs
(D) acetylcholinesterase inhibitors
(E) SSRIs

22. 2. The older TCAs share all of the following adverse
effects
except which one?
(A) orthostatic hypotension
(B) sedation
(C) seizures
(D) weight gain
(E) sexual dysfunction

23. 3. Foods containing tyramine should be avoided
when taken with which class of medications?
(A) TCAs
(B) MAOIs
(C) SSRIs
(D) atypical antidepressants
(E) antihypertensive medications

24. 4. A 36-year-old woman presents with symptoms of
major depression that are unrelated to a general medical
condition, bereavement, or substance abuse. She is not
currently taking any prescription or over-the-counter
medications. Drug treatment is to be initiated with
paroxetine. In your information to the patient, you would
tell her that
(A) It is preferable that she does not take the drug in
evening
(B) Muscle cramps and twitches can sometimes occur
(C) She should tell you if she anticipates using other
prescription drugs
(D) The antidepressant effects of paroxetine may take 2
weeks or more to become effective
(E) All of the above

25. 5. A 34-year-old male patient who was prescribed
citalopram for depression has decided he wants to
stop taking the drug. When questioned, he said that
it was affecting his sexual performance. You ascertain
that he is also trying to overcome his dependency on
tobacco products. If you decide to reinstitute drug
therapy in this patient, the best choice would be
(A) Bupropion
(B) Fluoxetine
(C) Imipramine
(D) Paroxetine
(E) Venlafaxine

26. 6. A patient under treatment for a major depressive
disorder is brought to the emergency department
after ingesting 30 times the normal daily therapeutic
dose of amitriptyline. In severe tricyclic
antidepressant overdose, it would be of minimal
value to
(A) Administer bicarbonate and potassium chloride
(to correct acidosis and hypokalemia)
(B) Administer lidocaine (to control cardiac
arrhythmias)
(C) Initiate hemodialysis (to hasten drug elimination)
(D) Maintain heart rhythm by electrical pacing
(E) Use intravenous diazepam to control seizures

27. 7. A recently bereaved 73-year-old female patient was treated
with a benzodiazepine for several weeks after the death of
her husband, but she did not like the daytime sedation it
caused even at low dosage. Living independently, she has no
major medical problems but appears rather infirm for her age
and has poor eyesight. Because her depressive symptoms are
not abating, you decide on a trial of an antidepressant
medication. Which of the following drugs would be the most
appropriate choice for this patient?
(A) Amitriptyline
(B) Mirtazapine
(C) Phenelzine
(D) Sertraline
(E) Trazodone

28. 8. SSRIs are much less effective than tricyclic
antidepressants in the management of
(A) Bulimia
(B) Chronic pain of neuropathic origin
(C) Generalized anxiety disorder
(D) Obsessive-compulsive disorder
(E) Premenstrual dysphoric disorder

29. 9. Which of the following drugs is most likely to be of
value in obsessive-compulsive disorders?
(A) Amitriptyline
(B) Clomipramine
(C) Doxepin
(D) Nefazodone
(E) Venlafaxine

30. 10. To be effective in breast cancer, tamoxifen must
be converted to an active form by CYP2D6. Cases of
inadequate treatment of breast cancer have
occurred when tamoxifen was administered to
patients who were being treated with
(A) Bupropion
(B) Clomipramine
(C) Fluoxetine
(D) Imipramine
(E) Phenelzine