Antidepressants

What will we Learn…?

1. Classification
2. Mechanism of Action
3. Generic Name & Brand Name
4. Side Effects
5. Management of Side Effects
6. Clinical Indications
7. Alternative Treatment
8. Informational Guide
 What are antidepressants?
Antidepressants are a class of drugs that reduce symptoms of depression by stabilizing
chemical imbalances of neurotransmitters.
 Selective Serotonin Reuptake
Inhibitors (SSRIs)

SSRIs
Serotonin Norepinephrine Reuptake
Inhibitors (SNRIs)

Tricyclic Antidepressants (TCAs)

Monoamine Oxidase Inhibitors (MAOIs)

Atypical Antidepressants
NEUROTANSMITTERS & DEPRESSION
Neurotransmitters are vital, they are chemical messengers that carry and
boost signals between nerve cells and other cells of the body.

The neurotransmitters specific to depression are known to be

1. Serotonin,
2. Dopamine
3. Norepinephrine (also called noradrenalin).
MECHANISM OF ACTION- ANTIDEPRESSANTS
Antidepressants work by balancing /increasing neurotransmitter levels in cells
This can be achieved by

• Decreased breakdown of neurotransmitters (MAOI)

• Decreased reuptake of neurotransmitters (SSRI)

• Increased release of neurotransmitters (Atypical Antidepressants )

Note:- Neurotransmitters involved are SEROTONIN/ NOREPINEPHRINE / DOPAMINE

Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRI specifically inhibit serotonin reuptake by neurons.

SSRI drugs are safe and have less side effects as compared to other
antidepressant drugs

Minimal Drug Interactions

Take 2-12 weeks to produce improvement in mood

Should Be continued for at least 06 months

 Principal mechanism of action
 Block the reuptake of serotonin, increasing its concentrations in the synaptic cleft a
nd its postsynaptic neuronal activity.

 SSRIs ease depression by affecting chemical messengers/ neurotransmitters used to

Communicate between brain cells.
 SSRIs block the reabsorption (reuptake) of the neurotransmitter serotonin in the
brain.
 Common SSRIs
Available in Pakistan

Generic Name Brand Name Price in Pakistan

Citalopram Lexapro 10mg---250Rs

Paroxetine Paraxyl 20mg---180RS

Fluoxetine Prozac 20mg---529RS

Sertraline Zoloft 50mg---1380RS

SSRIs Adverse effects
• Sweating

• Headache

• Weight gain

• Dry mouth

• Anxiety and agitation

• Weakness and fatigue

• Sexual dysfunction
• Sleep disturbances (insomnia and somnolence)
• Suicidal thoughts (young age)
• Serotonin syndrome
• Hyponatremia
 Hyponatremia
•Elderly people who take SSRIs may experience a severe
fall in sodium (salt) levels known as hyponatremia.

•Leads to a build-up of fluid inside the body's cells which

can be potentially dangerous.

•This side effect occurs because SSRIs can block the

effects of a hormone that helps to regulate levels of sodium and fluid in the
body.
•Elderly people are vulnerable because fluid levels become more difficult for th
e body to regulate.
Discontinuation syndrome

All of the SSRIs have the potential to cause a discontinuation syndrome

after abrupt withdrawal

 Dizziness •Fatigue and Irritability

, Headaches •Insomnia
 Difficulty walking •Muscle pain
 Nausea/vomiting
Drug Management

• SSRIs are generally safe for most people. However, in some

circumstances they can cause problems.

• High doses of citalopram may cause dangerous abnormal heart

rhythms, so doses over 40 milligrams (mg) a day should be avoided

• A maximum dose of 20 mg for people over age 60.

• They're not usually recommended if pregnant, breastfeeding or

under 18
•SSRIs also need to be used with caution if you have certain
underlying health problems, including diabetes, epilepsy and
kidney disease.

•Some SSRIs can react unpredictably with other medicines,

including some over-the-counter painkillers and herbal remedies
NSAIDS
LITHIUM
TRIPTANS
Side Effect Management Plan
Adopt a strategy for each side effect
•Nausea. Eat small meals more often or suck on hard candies.
Staying hydrated can also help.
•Weight gain. Be physically active and eat a calorie-controlled diet.
•Dry mouth. Stay hydrated and try chewing gum.
•Anxiety. Try relaxation techniques and deep breathing exercises
•Dizziness. Some people experience changes in blood pressure. Take time gettin
g up from a sitting or lying position. Avoid driving,
swimming or using heavy equipment
 Serotonin Norepinephrine Reuptake
Inhibitors (SNRIs)
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of
medications that are effective in treating depression. SNRIs work by increasing the levels
of serotonin and norepinephrine that are active in the brain.

Generic Name Brand Name Price in Pakistan

Desvenlafaxine Lafaxine 10mg---561RS

Duloxetine Dulexin, Dulox 20mg---894RS

Venlafaxine HCL Veflex 75mg---475RS

 Principal Mechanism of Action
 Depression is associated with reduced levels of the monoamines in the brain, such as
serotonin (5-HT) and norepinephrine.

 (SNRIs) are thought to restore the levels of 5-HT and noradrenaline in the synaptic cleft by
binding at their re-uptake transporters preventing the re-uptake and subsequent degradation
of 5-HT and noradrenaline.
Cont.……
 Blockade leads to the accumulation of monoamines, concentration returns to within
the normal range.
 Alleviation of the symptoms of depression.
Side effects of SNRIs
 Nausea (particularly with duloxetine)  Increased heart rate
 Dry mouth  Heart palpitation
 Dizziness  Difficulty urinating
 Insomnia  Tremor
 Increased blood pressure (with venlafa  Headache
xine)  Agitation or anxiety
 Excessive sweating  Changes in appetite
 Sexual Dysfunction  Abnormal vision, such as blurred
vision or double vision
Cont.….
SNRIs Warning and Withdrawal
 Let your doctor know about all medical conditions you have before starting on an SNRI.
 SNRIs can cause a rare problem called serotonin syndrome, which is characterized by
dangerously high levels of serotonins.

 Withdrawal
You may develop withdrawal symptoms if you stop taking an SNRI suddenly or miss several doses
of the drug.

 Anxiety
 Urgent need to urinate
 Dizziness
 Tiredness, chills, muscle aches, or other flu-like symptoms
Clinical Indications
Feature Venlafaxine Desvenlafaxine Duloxetine
Year of Approval 1993 2008 2004
FDA indications • Major depression Major depression • Major depression
• GAD • GAD
• Panic disorder • Diabetic peripher
• Social phobia al neuropathy
• Fibromyalgia
• Musculoskeletal
pain
• Osteoarthritis
Half Life(hours) 5 11 12
SSRIs v/s SNRIs
 SNRIs as the name implies, they block the reuptake of both serotonin and
Norepinephrine, while SSRIs block the reuptake of serotonin.

 SSRIs are sometimes used to treat bipolar depression, there is some controversy as
to how effective they are given their potential to exacerbate the rapid cycling of
moods.

 When compared to SSRIs, SNRIs are less likely to exacerbate rapid mood cycling i
n people with bipolar depression. However, they are commonly used for short-term
therapy as prolonged use may trigger a manic or hypomanic episode.
Tricyclic Antidepressants (TCAs)

• Tricyclic antidepressants are so-named because their

molecular structure is composed of three rings of atoms.
• Block Norepinephrine and serotonin reuptake in to the
neuron.
• It takes about 2-3 weeks before tricyclic antidepressants has any evident action o
n depression.
• Start with a low dose and gradually increase it to
prevent the side effects.
TCAs Actions

Elevate mood, improve mental alertness, increase physical activity,

and reduce morbid preoccupation in 50-70% of individuals with major
depression

 The onset of the mood elevation is slow taking ≥ 2 weeks

 Physical and psychological dependence is rare
 Slow withdrawal to minimize discontinuation syndrome and
cholinergic rebound effects
Principal Mechanism of Action
Inhibition of neurotransmitter reuptake: TCAs are potent inhibitors of
neuronal reuptake of norepinephrine and serotonin into presynaptic nerve terminals

Increase concentrations of monoamines in the synaptic cleft, resulting in

antidepressant effects

Desipramine are relatively selective inhibitors of Norepinephrine reuptake .

TCAs also block α-adrenergic, histaminic, and muscarinic receptors

causing many adverse effects
 TCAs
Generic Name Brand Name Price in Pakistan
Imipramine Tofranil 25mg---232 RS
Clomipramine Anafranil 10mg---135 RS
Desipramine No Brand ---
Amitriptyline Tryptanol/Amitin 25mg---150 RS
Side Effects
Side Effects TCA
Dry mouth Heart conduction defects

Blurred vision Tachycardia

Urinary retention/hesitancy Other side effects

drowsiness Lowered seizure threshold

Constipation sweating

Cardiovascular Weight gain

Postural hypotension
Management plan for side effects
Hypotension:
• Hypotension is treated with sodium bicarbonate and intravenous fluids.
• Vasopressors are recommended for refractory hypotension; best
norepinephrine.
Dysrhythmias:
• Sodium bicarbonate is the first line therapy if tricyclic ingestion is known or strongly s
uspected (life saving).
• Procainamide beta blockers and calcium channel blockers are
contraindicated.
Clinical Indications


• Depression
• Nocturnal Enuresis (Nocturnal enuresis is involuntary urination that happens
at night while sleeping, after the age when a person should be able to contro
l his or her bladder. ) (Imipramine)
• Phobic/ Obsessional states
• Cataplexy(a medical condition in which strong emotion or laughter causes a
person to suffer sudden physical collapse though remaining conscious. )
with narcolepsy
Continue…
• The treatment of a major depressive episode and the prophylactic treatment of
major depressive disorders are the principal indications for using TCAs.

• Imipramine is the TCA most studied for panic disorder with

agoraphobia.

• OCD appears to respond specifically to Clomipramine.

• Clomipramine- premature ejaculation, movement disorders and

compulsive behavior in children with autistic disorders.
Monoamine Oxidase Inhibitors (MAOIs)
 MAOIs were the first type of antidepressant developed.

 A class of enzymes that destroys the monoamines : Dopamine, Norepinephrine and

serotonin. MAOIs increase the concentration of these three neurotransmitters

 This enzyme is found within monoaminergic terminal buttons where it destroys

excessive amount of neurotransmitters.
Monoamine Classification
Classification of Monoamine:
Catecholamine Indolamine

Norepinephrine Serotonin

Dopamine ----

Epinephrine ----
 Types Of Monoamines
There are two types of monoamines:

1. Monoamine A
2. Monoamine B

Monoamine A is found in Liver and Gastrointestinal Tract.

Monoamine B is found in Blood, where it deactivates amines

that are present in foods such as, chocolates, and cheese.
without such deactivation these amines could cause dangerous
Increases in blood pressure.
Principal Mechanism of Action

 Monoamine oxidase (MAO) inactivates norepinephrine, dopamine,

and serotonin

 MAO inhibitors (MAOIs) inactivate MAO, permitting neurotransmitter

molecules to accumulate within the presynaptic neuron and leak into the synaptic
space causing activation of norepinephrine and serotonin receptors .
Mechanism Of Action
MAOIs
The Food and Drug Administration (FDA)
has approved these MAOIs to treat depression:

Generic Name Brand Name Price in Pakistan

Isocarboxazid Marplan 10mg--- 1380RS

Phenelzine Nardil ----

Selegiline Selgin 5mg --- 614RS

(Skin Transdermal
Patch, Emsam)
Tranylcypromine Zamic 250mg --- 350RS
Side effects of MAOIs
 Dry mouth  Low blood pressure
 Nausea, diarrhea, constipation  Reduced sexual desire
 Headache  Difficulty starting a urine flow
 Drowsiness  Muscle cramps
 Insomnia  Weight gain
 Dizziness or lightheadedness  Prickling or tingling sensation in the
 Skin reaction skin.
 Involuntary muscle jerks
 Adverse Effects
All antidepressants can cause Serotonin Syndrome

•Agitation or restlessness.
•Confusion.
•Rapid heart rate and high blood pressure.
•Loss of muscle coordination or twitching muscles.
•Muscle rigidity.
•Heavy sweating.
•Diarrhea.
 Clinical Indications
Clinical Uses:

MAOIs have been found to be effective in the treatment of

1. Panic disorder
2. Agoraphobia,
3. Social phobia,
4. Anxiety disorder,
5. Post-traumatic stress disorder.
Note:
MAOIs can also be used in the treatment of Parkinson's disease by
targeting MAO-B
 MAOIs Contraindications

 MAOIs and SSRIs should not be co-administered due to the risk of the
life-threatening “serotonin syndrome” that include symptoms of hyperthermia,
muscle rigidity, sweating, myoclonus (clonic muscle twitching), and changes in
mental status.

 Both types of drugs (SSRIs & MAOIs) require washout periods of atleast 2 weeks
before the other type is administered

 Fluoxetine should be discontinued atleast 6 weeks before a MAOI is initiated

 Combination of MAOIs and bupropion can produce seizures

 Atypical Antidepressants
Atypical antidepressants are considered “atypical” because these agents do not
fit into any of the other classes of antidepressants. Each medicine in this category
has a unique mechanism of action in the body.

Like other types of antidepressants, atypical antidepressants affect neurotransmitters

including dopamine, serotonin and norepinephrine.

Changing the balance of these chemicals seems to help brain cells send and
receive messages, which in turn boosts mood.
 Atypical Antidepressants
 Bupropion (which under the name Zion is
used to aid in smoking cessation)
 Mirtazapine (Remeron)
 Nefazodone
 Trazodone, which is also used to treat Insomnia
(Depril)
Bupropion
Mechanism of Action:
 Weak dopamine and Norepinephrine reuptake inhibitor .
Clinical Indication:
 Smoking cessation.
 Can help with cocaine withdrawal.

Mirtazapine
Mechanism of Action
 Enhances serotonin and norepinephrine neurotransmission by blocking
presynaptic α2 receptors and 5-HT2 receptors
Nefazodone and Trazodone
 Weak inhibitors of serotonin reuptake

 Block postsynaptic 5-HT2A receptors

 With chronic use may desensitize 5-HT1A presynaptic auto receptors increasing seroton
in release
Clinical Uses
Primilary for insomnia
Adverse side effects
Very sedating
orthostatic hypotension
Safety Issues:
Bupropion should not be used by people who have a seizure disorder or an eating disorder
such as bulimia or anorexia
Mirtazapine has been associated with an increase in cholesterol
Nefazodone has been linked to liver failure in some people, don’t take it if you already hav
e liver problem.
Trazodone has been linked to heart rhythm problem, so if you have heart disease, ask your
doctor whether this medication is safe for you.
 Alternative Treatment
Phases of treatment:
1. Supportive Counseling
2. Antidepressants (SSRIs)
3. Referral for psychological Counseling (CBT..REBT..Interpersonal Therapy)
4. Combine treatment with Antidepressants and Psychological Treatment
5. Proper Diet Plan
 Interactions with food and drinks
 The SSRI, fluvoxamine, is also known to enhance the effects of caffeine, so people
who drink large amounts of caffeine may experience unpleasant symptoms such
as palpitations, feeling sick, restlessness and insomnia.

Avoid drinking large amounts of caffeinated drinks, such as tea, coffee, energy drinks
and cola, while taking fluvoxamine.

Always read the information leaflet that comes with your SSRI
medication to check if there are any medicines you need to avoid
• National depression day will be on Thursday
,10,October,2019.

• 311 Days from Today

Important Precautions
Contact a healthcare provider immediately if changes in depression symptoms or
behavior occur, or if signs of a possible suicide emerge.

Observe the patient closely within the first few months of treatment and when there
is a dose change.

However, it is important to remember that depression and other psychiatric

problems are linked to suicide, as well.

Patients who are using antidepressant therapy should be closely monitored by

family and healthcare providers for suicidal signs and symptoms.