Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.

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They are among the most commonly prescribed drugs .Depression: It is a the most commonly serious disorder of

mood, ranges from mild to very serious condition Types of Depression - Two types

Unipolar Exogenous / Reactive Depression

Endogenous/Major Depression (MDD)

Bipolar

1. Selective Serotonin Reuptake Inhibitor (SSRI)

• Sertraline, Fluoxetine

• Paroxetine, Citalopram, Escitalopram2. Tricyclic Antidepressant (TCA)

• Amitriptyline, Nortriptyline

• Imipramine, Desipramine

• Doxepine, Trimipramine

MAO Inhibitors Phenelzine, moclobemide TranylcypromineAtypical Antidepressants Bupropion, nefazodone, mianserin, Trazodone, venlafaxine Mirtazepine

Amitryptyline Potent sedative Weight gain ++ Anticholinergic ++ Most researched 150mg / day(Therapeutic in 95% of

adults)

Clomipramine Similar side effects to

amitryptyline. Said to be best for

obsessionalsymptoms.

150mg / day

Depression is due to deficiency of nor-epinephrine & serotonin

Normally action of released NE & serotonin is terminated by active reuptake into the nerve terminal from the synapse via specific transporters.

TCAs block the amine transporters (uptake pumps) for nor-epinephrine (NET) & serotonin (SERT) in brain.

Facilitation of NE & serotonin transmission ---- improves symptoms of depression .

Imipramine Stimulant Anticholinergic ++ 150 mg/ day

Dothiepin Sedative Same side effects as

amitryptyline. By far and away the

most toxic antidepressant.

150 mg / day

antimuscarinic effects postural hypotension tachycardia, arrhythmias sedation weight gain jittery feeling sexual dysfunction (ejaculatory)

Citalopram Few interactions

Most expensive

20 mg /day

Fluoxetine Sedation –

Skin s/e

Anxiety +

Cheapest

20-80 mg /day

Fluvoxamine Gut s/e + Insomnia - 200 mg /day

Paroxetine Sedation + Withdrawal problems ?

20 mg /day

Sertraline Diarrhoea 50 mg /day

First choice in elderly. First choice if heart

disease. First choice if suicide

risk. More expensive.

Side effects Like TCA reduce with

time. Gut problems

predominate. Flat dose response

curve – so no need to titrate dose upwards.

?

MOA: Inhibit Serotonin& NE reuptake at all doses by

binding to NET & SERTVenlafaxine: Potent inhibitor of serotonin reuptake & at

medium to high doses. Inhibitor of NE reuptake.Weak Dopamine re-uptake inhibitor at higher

doses.No effect on muscarinic, adrenergic or histaminic

receptors. So they are preferred over TCAs for MDD & pain syndromes.

The old ones block peripheral MAOI ( B ) and central MAOI (A) so a low tyramine diet is needed. ? Obsolete.

Moclobemide. Only MAOI-A. Special place in anxiety disorder. 300-600mg / day.

Trazodone. Unique structure. Low cardiotoxicity, few anticholinergic side

effects. Drowsiness +. Nausea. 150 mg /day.

Mirtazapine : Blocks 5HT2 , & presynaptic α2 receptors.

Enhances release of Serotonin & NEAmoxapine: Potent Nor-Epinephrine uptake inhibitor but

mild inhibition of Serotonin reuptake. Blocks D2 receptors

Bupropion: Inhibitor of NE reuptake, Weak Inhibitor of dopamine reuptake

Maprotiline: Potent Nor-Epinephrine uptake inhibitor.

All are useful in Major depression, in combination with other drugs.

Bupropion is useful in ADHD Bupropion also helps in reducing craving &

attenuating the withdrawal symptoms for Nicotine in tobacco users trying to quit smoking.

Panic attacks, post traumatic stress disorder Obsessive compulsive disorder Nocturnal enuresis Premenstrual syndrome Chronic alcoholism

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ManiaEuphoriaGrandiosityPressured speechImpulsivityExcessive libidoRecklessnessDiminished need for sleep

DepressionDepressionAnxietyIrritabilityHostilityViolence or suicide

Manic, depressed

or mixed

Psychosis

•Delusions

•Hallucinations

•Sensory hyperactivity

Cognition

•Racing thoughts

•Distractability

•Poor insight

•Disorganization

•Inattentiveness

•Confusion16

Mood Disorders:Therapeutic Options

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Lithium* (A, M)

Anticonvulsants

Valproate* (A)

Lamotrigine* (M)

Carbamazepine (A)

Oxcarbazepine*

Topiramate

Gabapentin

Psychotherapy

Cognitive behavioral therapy Marital/family counseling

Interpersonal therapy Group therapy

Pharmacological/Somatic

Antidepressants; OLZ/FLU* (D)

Quetiapine* (D)

Electroconvulsive therapy

Possibly:» Bright light therapy

» Transcranial magnetic stimulation

» Vagal nerve stimulation

» Sleep deprivation

First generation

antipsychotics

Second

generation

antipsychotics

Clozapine

Olanzapine* (A, M)

Risperidone* (A)

Quetiapine* (A)

Ziprasidone* (A)

Aripiprazole* (A)

* FDA approved© Janicak 17

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Drug Desired

Cp

Distribution Metabolism Elimination

Lithium 0.6-1.0

mEq/L

No PB

kidneys,

thyroid

None Renally,

18-20

hours

CBZ 6-12

mcg/ml

Complete Hepatic,

Auto

inducer

10,11

epoxide

15-28

hours

VPA 50-120

mcg/ml

Rapid in

CNS

Hepatic,

Inhibitor or

Inducer

8-17 hours

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Narrow therapeutic index Slow onset of action Numerous adverse effects

DISADVANTAGES

BIPOLAR DISORDER

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Impaired Renal Function Pregnancy Sodium balance Medications

Diuretics → Na depletion → Li reabsorption

Caffeine ↓ lithium levels

ACE Inhibitors → ↓ GFR → increase Li concentration

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Organ System Clinical Presentation Comments

Cardiovascular ECG changes T wave suppression, delayed or irregular rhythm, increase in PVCs

Sick sinus node syndrome (SSNS)

Myocarditis

Dermatologic Acne

Psoriasis

Rashes

Worsens

Treatment-refractory worsening

Maculopapular and follicular

Endocrine Hypothyroid state About 5% goiter; about 4% clinically significant hypothyroidism

Hyperparathyroid state Clinically nonsignificant

Fetus (teratogenic) Tricuspid valve malformation

Atrial septal defect

Ebstein’s anomaly

Gastrointestinal Anorexia

Nausea (10-30%)

Vomiting

Diarrhea (5-20%)

Usually early in treatment and usually transient; may be early sign

of toxicity

Slow release preparations may help

Hematological Granulocytosis May be useful in disorders such as Felty’s syndrome, iatrogenic

neutropenia. May counter CBZ-induced leukopenia

Renal Polyuria-polydipsia

(Nephrogenic diabetes

insipidus)

May be an indication of morphologic changes

Requires adequate hydration

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Neurological Cognitive; tremors

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Usually inhibits hepatic metabolism Occasionally induces hepatic metabolism

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Adverse effects

Weight gain

Tremors

Hyperammonemia

PCOS (?)

DISADVANTAGES

BIPOLAR DISORDER

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Pancreatitis

Hepatotoxicity

Teratogenicity

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Oxidation to CBZ-10,11-epoxide Potent enzyme inducer

antidepressants, anticonvulsants, antipsychotics

Autoinduction

serum level should stabilize within 4 weeks

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Slow titration to avoid rash Adverse effects

Serious rashes

▪ SJS

▪ TEN

BIPOLAR DISORDER

DISADVANTAGES

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Have predominantly stimulant effect onthe central nervous system

Convulsants and respiratory stimulants Psychomotor stimulants Hallucinogens

Little effect on mental function

Act mainly on the brain stem and spinal cord

Higher dosage causes convulsions

Sometimes called analeptics

Obtained from the fishberry also blocks the action of GABA on chloride channels

Similar to the above drugs Bigger margin of safety between

respiratory stimulation and convulsions Causes nausea, coughing and restlessness,

which limit its usefulness Occasionally used as an intravenous

infusion in patients with acute respiratory

Cause excitement and euphoria Decrease feelings of fatigue Increase motor activity

Methylxnthines Nicotine Methylphenidate Cocaine Amphetamine Vareneciline

Theophylline (tea)Theobromine (cocoa)Caffeine

Caffeine, the most widely consumed stimulant in theworld,is found in highest concentration in coffee

Also present in tea, cola drinks, chocolatecandy, and cocoa.

Translocation of extracellular calcium

Increase in CAMP and CGMP caused by inhibition of phosphodiesterase

Blockade of adenosine receptors

Cocaine has a local anesthetic Applied topically as a local anesthetic during eye,

ear, nose, and throat surgery Local anesthetic action due to a block of voltage-

activated sodium channels Only local anesthetic that causes vasoconstriction.

This effect is responsible for necrosis Perforation of the nasal septum is seen with chronic

inhalation of cocaine powder