Depression and Mania

Dr. Karun Kumar JR – II Dept. of Pharmacology

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/occurssimultaneously 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

Biogenic amine hypothesis

• Mood disorders Abn. In 5-HT, NE, DA neurotr.

• Antidep. Drugs ↑ 5-HT, NE, DA neuotr. In brain

Antidepressant drugs

1. MAO inhibitors

1st gen. Phenelzine, Tranylcypromine (MAO-A+B)

2nd gen. Moclobemide, Clorgyline (MAO A)

SelegilineMAO-B

2. Tricyclic antidepressants (TCAs)

A. NA + 5-HT reuptake inhibitors

• Imipramine, Amitriptyline, Clomipramine, Doxepin

B. Predominantly NA reuptake inhibitors

• Desipramine, Nortriptyline, Amoxapine

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

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

MAO

MAO A MAO B

Location Adrenergicnerve endings, intestinal mucosa & human placenta

Brain & platelets

Metabolizes 5-HT, NE, DA Phenylethylamine, DA

Inhibitors Moclobemide, Clorgyline

Selegiline

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

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

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

Side effects of SSRIs

S Serotonin syndrome

S Stimulate CNS

R Reproductive dysfunctions in male

I Insomnia

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)

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

Side effects of Lithium

LI Leukocytes Increased (Leukocytosis)

T Tremors

H Hypothyroidism

IU Increased Urine (Diabetes insipidus)

M Moms beware (teratogenic)

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

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

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

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

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

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

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

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

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

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