ANTI DEPRESSANT

NORUL AINI BT ZAKARIYA

Autonomic Pharmacology
 Learning outcomes
At the end of this topic, students should be able to:
 Give causes & symptoms of depression
 State monoamine hypothesis
 Describe drugs used as medication in depression
(trade & generic name, mechanism of action,
side effects)
 Identify drugs that have interaction with tyramine-
containing foods
 DEPRESSION
 Depression is a medical illness that causes a
constant feeling of sadness and lack of interest.
 Depression affects how the person feels,
behaves and thinks.

 According to MediLexicon's Medical Dictionary, depression is:

"a mental state or chronic mental disorder characterized by feelings

of sadness, loneliness, despair, low self-esteem, and self-reproach;
accompanying signs include psychomotor retardation (or less
frequently agitation), withdrawal from social contact, and vegetative
states such as loss of appetite and insomnia."
 Mood Disorders
 The most common mood disorders:
 Major depression (Unipolar depression)
 Manic-depressive illness (Bipolar disorder)
 A mood disorder characterized by alternating episodes of
excitement and depression
 Symptoms of depression

• Feeling of sadness
• Hopelessness & despair
• Inability to concentrate
• The inability to experience pleasure in usual
activities
• Sleeplessness (insomnia)
• Loss appetite
• Suicidal thought
 Causes
 Heredity
 Stress – loss of loved one or a job
 Medications – Long-term use of certain medications
(drugs used to control high blood pressure, sleeping
pills)
 Illness – chronic illness (heart disease, cancer,
diabetes, hypothyroidism)
 Personality - low self-esteem and being overly
dependent
 Postpartum depression
 Hormones – women
 Alcohol, nicotine and drug abuse
 The monoamine hypothesis

 This theory has propose that depression is due to a

deficiency of monoamines, such as noradrenaline
(NE) and serotonin in the brain.

 Conversely, the theory that mania is caused by an

overproduction of these neurotransmitters
 Proposed mechanism of action of
Antidepressant drugs

 Antidepressants drugs increase level of activity of

noradrenaline &/@ serotonin in the brain.

 A delay in onset of antidepressant response (produce

improvement of mood) of at least 1 to 2 weeks occurs
with all antidepressants.
 ANTI-
DEPRESSANT

Drugs used
Amine Atypical
to
Reuptake MAOI Anti-
treat mania
Inhibitors depressants

SSRI TCAs SNRIs

 SELECTIVE SEROTONIN
RE-UPTAKE INHIBITORS (SSRIs)

Generic Name Trade Name

Fluoxetine PROZAC®

Fluvoxamine LUVOX®

Sertraline ZOLOFT®

The SSRIs have largely replaced TCA & MAOI as the drugs of choice
in treating depression
Less severe side effects & have a wide margin of safety in overdose
 MECHANISM OF
ACTION
Specifically inhibit serotonin
re-uptake

Leading to concentrations
of serotonin in the synaptic clefts
 Therapeutic uses

Major Depression

Psychiatric disorder
Obsessive-compulsive disorder
Panic disorder
Generalized anxiety
 Pharmacokinetics
 SSRIs are well absorbed after oral administration
 Food has little effect on absorption
 Plasma T½ : 16-36 hrs
 Metabolism by P450-dependent enzymes &
glucuronide @ sulfate conjugation occur
extensively
 Excretion: primarily through the kidneys, except for
Paroxetine & Setraline; fecal excretion (35-50%)
 Drowsiness Anxiety

Diarrhea

Nausea
Side effects

Sexual
Insomnia dysfunction
 Drug interactions
 Alcohol – toxic sedation
 MAOIs – Serotonin syndrome
 Fever, agitation, hypertension, hyperthermia, muscle rigidity,
myoclonus
 TRICYCLIC ANTIDEPRESSANTS
(TCAs)

Generic Name Trade Name

Amitriptyline TRYPTANOL®

Clomipramine ANAFRANIL®

Imipramine TOFRANIL®

•These drugs are valuable alternative for patients who do

not respond to SSRIs
Mechanism of action
1. Potent inhibitors of
neuronal re-uptake of
noradrenaline & serotonin
into presynaptic nerve
terminals

2. Blocking of receptors:
- Serotonergic, α-adrenergic,
histaminic, muscarinic
 Therapeutic uses
Severe major depression

Neuropathic pain - Amitriptyline

To control bed-wetting in children

(older than six yrs) – Imipramine

Panic disorder

 At present, it is used cautiously because of inducement of

cardiac arrhythmias & other serious cardiovascular problems
 Pharmacokinetics

 Well absorbed upon oral administration

 Lipophilic; widely distributed & readily penetrate
into the CNS
 Metabolized by hepatic microsomal system &
conjugated with glucuronic acid
 Inactive metabolites excreted via the kidney
 Weight gain
Dry mouth Sedation

Blurred
Orthostatic Side effects vision
hypotension

Sexual
Constipation dysfunction
 Drug interactions

 MAOI – Serotonin syndrome (hypertension,

hyperpyrexia, convulsion, coma)
 SSRIs - Serotonin syndrome
 Alcohol – toxic sedation
 Serotonin/Norepinephrine Re-uptake
Inhibitors (SNRIs)

Generic Name Trade Name

Venlafaxine EFEXOR®
Mirtazapine REMERON®
- MOA: Selectively inhibit reuptake of both serotonin & NE
-Effective in treating depression in patients in which SSRIs are
ineffective
-Often effective in relieving physical symptoms of neuropathic pain
(backache & muscle pain)
-Have no activity at adrenergic, muscarinic, or histamine receptor,
thus have fewer side effects than TCAs
-Common side effects: Nausea, dizziness, insomnia, sedation dry
mouth & constipation
 Monoamine Oxidase Inhibitors
(MAOI)

Generic Name Trade Name

Phenelzine NARDIL®

Tranylcypromine PARNATE®

* Use of MAOI is now limited due to the complicated

dietary restrictions required for patients taking MAOI
 Mechanisms of Action

 MAO inhibitor neurotransmitters (NE, D &

serotonin) into the synaptic space

MAO functions is to inactive monoamine neurotransmitters

(NE, dopamine, & serotonin)
 Therapeutic uses

 Depression
 Patient with low psychomotor# activity
 Treatment of phobic states

* Only used if TCAs not effective!!!

#relating to movement or muscular activity associated

with mental processes
 Pharmacokinetics

 Well absorbed on oral administration

 They are metabolized and excreted rapidly in the
urine
 Weight gain
Dry mouth Sedation

Blurred
Orthostatic Side effects vision
hypotension

Sexual
Constipation dysfunction
 Drug interaction
 Indirectly acting sympatomimetics – Risk of hypertensive crisis
 SSRIs – Serotonin syndrome
 Both types of drugs require wash-out periods of 6 weeks
before the other type is administrated.
 TCAs
 Patient take tyramine-containing food with MAOI –
headache, tachycardia, nausea, hypertension, stroke, cardiac
arrythmias
 Food ex: cheeses, chicken liver, beer & red wine, banana,
meat, fish, fermented soy bean
 Atypical Antidepressants

Generic Name Trade Name

Bupropion WELLBUTRIN®

Mirtazapine REMERON®

They are not any more efficacious than the TCAs or SSRIs,
but their side effect profiles are different.
 Treatment of mania/
bipolar disorder
 Lithium salts – the mode of action is unknown

- Lithium competes with cations in the body (Na & K)

 Very toxic – safety factor & therapeutic index are extremely

low.

 Adverse effects – Nausea, diarrhea, tremors, lethargy,

polyuria, confusion, convulsion
 Thyroid function may be decreased & should be monitored
(to detect hypothyroidism)
 For patients not responding to lithium, valproic acid or
carbamazepine may be effective
 Clinical Use of Anti Depressants

 SSRIs usually prescribed first - less side effects and safer if

overdose occurs.
 Patients vary in individual responsiveness to different
antidepressants (reason unknown).
 If patients do not respond to drug in one class, generally
switched to drug of different class rather than different
drug in same class.
 Combination of two antidepressants can be dangerous
& is rarely justified (except under specialist supervision).
The End…

Next lecture:
Antiepileptic Drugs………
 Self-assessment 1
Mr. J is 30 years old & has no active medical problems.
He has been treated with Li+ for manic-depressive illness
for 1 year, & his mood has been stable. He now reports
the gradual onset of fatigue, weight gain, & cold
intolerance. Which single laboratory test is most likely to
lead to the correct diagnosis?
A. Hepatic function panel
B. TSH (thyroid-stimulating hormone)
C. Glucose tolerance test
D. Hematocrit
 Self-assessment 2
The proposed mechanism for MAOIs is:
A. Inhibition of the enzymes that synthesize NE &
serotonin
B. Inhibition of reuptake of NE & serotonin
C. Inhibition of reuptake of NE & dopamin
D. Inhibition of the enzymes involved in the
catabolism of NE & serotonin
 Self-reading

 Briefly discuss Serotonin Syndrome.

 Why tyramine-containing food should be

avoided with MAOI?
Symptoms of depression
• Feeling of sadness
• Hopelessness & despair
• Inability to concentrate
• The inability to experience
pleasure in usual activities
• Sleeplessness (insomnia)
• Loss appetite
• Suicidal thought
Symptoms of mania
• Enthusiasm
• Lack of sleep
• Active all the time
• Rapid thought and
speech pattern
• Extreme self-confidence
• Impaired judgment