Dr .

Heba Mostafa Elsanhory

Lecturer of Pharmacology& Toxicology
Sinai University

sinaiuniversity.net
 Pharmacology II(PHO3205)
Lec .7
Antidepressant drugs
Monday 10:30-12:30

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DENTISTRY/ second year/ SU/ lect 6 www.su.edu.eg
 • Learning objectives P.4

• Definition of depression P.5

• Common symptoms of depression P.6

• Causes of depression P.7

• Mechanism of action of antidepressant drugs P.9

• Classes of antidepressants P.11

INDEX

• SSRIAs P.12

• SNRIs P.15

• TCAs P.17
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• MAOIs P.20 info@su.edu.eg
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• Atypical antidepressants P.22
Learning objectives
• Definition of depression
• Knowing symptoms and causes of depression
• Understanding the mechanism of action of antidepressant drugs
• Studying different classes of antidepressant drugs
 Depression:

• Depression (major depressive disorder) is a common and serious

medical illness that negatively affects how you feel, the way you
think and how you act. Fortunately, it is also treatable.
Depression causes feelings of sadness and/or a loss of interest in
activities once enjoyed. It can lead to a variety of emotional and
physical problems and can decrease a person’s ability to
function at work and at home.

@Sinaiunieg info@su.edu.eg www.su.edu.eg

 Common symptoms of depression are:
1. deep feelings of sadness
2. dark moods
3. feelings of worthlessness or hopelessness
4. appetite changes- weight loss or gain unrelated to dieting
5. sleep changes- Trouble sleeping or sleeping too much
6. Increase in purposeless physical activity (e.g., hand-wringing or pacing) or
slowed movements and speech
7. lack of energy or increased fatigue
8. inability to concentrate
9. difficulty getting through normal activities
10. lack of interest in things that paient used to enjoy
11. withdrawing from friends
12. Thoughts of death or suicide
N.B.: These Symptoms must last at least two weeks for a
diagnosis of depression.
Causes of depression
Causes of depression
1) Stressful events: bereavement or a relationship breakdown.
2) Personality: low self-esteem or being overly self-critical.
3) Family history: If someone in your family has had depression in the past
4) Feelings of loneliness
5) Alcohol intake and drugs abuse.
6) longstanding or life-threatening illness, such as coronary heart disease or
cancer.
7) Certain illness: head trauma, Hypothyrodism,
8) Giving birth: Some women are particularly vulnerable to depression after
pregnancy. The hormonal and physical changes, as well as the added
responsibility of a new life, can lead to postnatal depression.
 Mechanism of action of antidepressant drugs
• The most widely accepted explanations for mind changes evolved in
depression cites abnormal brain chemistry.
• Previous Researches suggested that, for some people, having too little of
neurotransmitters in the brain could contribute to depression.
• Restoring the balance of these brain neurotransmitters help to alleviate
symptoms of depression.
• The main neurotransmitters implicated in depression are Norepinephrine&
Serotonin
• Theory, which proposes that depression is due to a deficiency of
norepinephrine and serotonin, at certain key sites in the brain. Conversely,
the theory proposes that mania is caused by an overproduction of these
neurotransmitters
Classes of Antidepressant drugs
 I-Selective serotonin reuptake inhibitors (SSRIs)
• MOA:
SSRIs are a group of antidepressant drugs that specifically inhibit serotonin reuptake
leading to increased concentrations of the neurotransmitter in the synaptic cleft.
• Duration of action:
At least 2 weeks to produce significant improvement in mood, and maximum benefit
may require up to 12 weeks or more.
Therapeutic uses
1. The primary indication for SSRIs is depression 2. Obsessive–compulsive disorder
3. Panic disorder 4. Generalized anxiety disorder
5. Posttraumatic stress disorder 6. social anxiety disorder
7. Premenstrual dysphoric disorder (severe irritability, depression, or anxiety in the
week or two before period
 I-Selective serotonin reuptake inhipitors (SSRIs)
• The SSRIs include:
Fluoxetine, Citalopram, Escitalopram, Fluvoxamine, Paroxetine and Sertraline.
• Possible side effects of SSRIs may include:
1. Nausea, vomiting or diarrhea.
2. Headache.
3. Drowsiness.
4. Dry mouth.
5. Insomnia.
6. Nervousness, agitation or restlessness.
7. Dizziness.
8. Sexual problems
9. Hyponatremia
 I-Selective serotonin reuptake inhibitors (SSRIs)
• Advantage of SSRI over TCA and SNRI
That SSRIs have little blocking activity at muscarinic, α-adrenergic, and histaminic H1
receptors. Therefore, common side effects associated with TCAs, such as orthostatic
hypotension, sedation, dry mouth, and blurred vision, are not commonly seen.
• Use in children and teenagers:
Antidepressants should be used cautiously in children and teenagers, because about 1
out of 50 children report suicidal ideation.
• Overdose of SSRIs:
1. Citalopram may induce arrhythmia
2. Possibility Seizures because all antidepressants may lower the seizure threshold
3. Serotonin Syndrome, (include the symptoms of hyperthermia, muscle rigidity,
sweating, clonic muscle twitching and changes in mental status and vital signs.
 II- Serotonin/Norepinephrine reuptake inhibitors
(SNRIs)
• MOA:
Inhibit the reuptake of both serotonin and norepinephrine
• Duration of action:
At least 2 weeks to produce significant improvement in mood, and maximum benefit
may require up to 12 weeks or more.
Therapeutic uses:
1. Effective in treating depression in patients in whom SSRIs are ineffective
2. Their dual inhibition of both serotonin and norepinephrine reuptake make them
effective in relieving physical pain associated with depression diabetic peripheral
neuropathy, postherpetic neuralgia, fibromyalgia, and low back pain.
 II- Serotonin/Norepinephrine reuptake inhibitors
(SNRIs)
• The SNRIs include:
• Venlafaxine, desvenlafaxine, levomilnacipran and duloxetine
• Possible side effects of SNRIs may include:
1. Duloxetine may increase blood pressure or heart rate.
2. Venlafaxine are nausea, headache, sexual dysfunction, dizziness, insomnia,
sedation, and constipation.
• Advantage of SNRI over TCA:
The SNRIs, unlike the TCAs, have little activity at α-adrenergic, muscarinic, or histamine
receptors and, thus, have fewer of these receptor-mediated adverse effects than the
TCAs.
 III- Tricyclic Antidepressants (TCA)
• MOA:
1. The TCAs block norepinephrine and serotonin reuptake into the presynaptic neuron
2. They block serotonergic, α-adrenergic, histaminic, and muscarinic receptors.
• The TCAs include:
1. Tertiary amines like imipramine, amitriptyline, clomipramine, doxepin
2. Secondary amines desipramine and nortriptyline
• Pharmacological actions:
1. The TCAs elevate mood improve mental alertness
2. Increase physical activity
3. Reduce morbid preoccupation in 50% to 70% of individuals with major depression
 III- Tricyclic Antidepressants (TCA)
• Therapeutic uses
1. The TCAs are effective in treating moderate to severe depression.
2. Some patients with panic disorder also respond to TCAs.
3. Imipramine and desmopressin are used to control bed-wetting in children older
than 6 years
4. amitriptyline, have been used to help prevent migraine headache and treat
chronic pain syndromes (for example, neuropathic pain) in a number of
conditions for which the cause of pain is unclear.
5. Low doses of TCAs, especially doxepin, can be used to treat insomnia.
 III- Tricyclic Antidepressants (TCA)
• Adverse effects
1. Blockade of muscarinic receptors leads to blurred vision, xerostomia (dry mouth),
urinary retention, sinus tachycardia, constipation, and aggravation of angle-closure
glaucoma.
2. These agents affect cardiac conduction similarly to quinidine and may precipitate life-
threatening arrhythmias in an overdose situation. The TCAs also
3. Blocking α-adrenergic receptors, causing orthostatic hypotension, dizziness, and reflex
tachycardia.
4. Sedation may be prominent, especially during the first weeks of treatment, due to the
blocking of histamine H1 receptors.
5. Weight gain is a common
 IV- Monoamine oxidase inhibitors (MAOI)
• M. O. A.:
• MAOIs may irreversibly or reversibly inactivate MAO enzyme, permitting
neurotransmitters to escape degradation and, therefore, to accumulate within the
presynaptic neuron and leak into the synaptic space. This results in increased stores
of norepinephrine, serotonin, and dopamine within the neuron and subsequent
diffusion of excess neurotransmitter into the synaptic space
• The four MAOIs currently available for treatment of depression include:
1. Phenelzine
2. Tranylcypromine
3. Isocarboxazid
4. Selegiline
 IV- Monoamine oxidase inhibitors (MAOI)
• Therapeutic uses
1. The MAOIs are indicated for depressed patients who are unresponsive or allergic to TCAs
and SSRIs or who experience strong anxiety.
2. Atypical depression, may respond preferentially to MAOIs.
• Because of their risk for drug–drug and drug–food interactions, the MAOIs are considered last-
line agents in many treatment settings.
• Adverse effects:
1. drowsiness
2. orthostatic hypotension
3. blurred vision, dry mouth, and constipation.
• Contraindications:
1. The use of MAOIs with other antidepressants as SSRIs is contraindicated due to the
risk of serotonin syndrome
2. Tyramine containing food is contraindicated with MAOIs to avoid the incidence of
hypertensive crisis
V- Atypical antidepressant
• Bupropion
• M.O.A. : Bupropion is a weak dopamine and norepinephrine reuptake
inhibitor
• Ther. Use: is used to alleviate the symptoms of depression.
• Side effects:
1. Dry mouth, sweating, nervousness, tremor, and a dose-dependent
2. Increased risk for seizures. So, use of bupropion should be avoided in
patients at risk for seizures.
 V- Atypical antidepressant
• Mirtazapine
• M.O.A.:
1. It enhances serotonin and norepinephrine neurotransmission by serving as an
antagonist at presynaptic α2 receptors.
2. antagonism at 5-HT2 receptors.
3. It is sedating because of its potent antihistaminic activity, may be an advantage
in depressed patients having difficulty sleeping.
• Advantage over TCAs& SSRIs:
1. It doesn’t cause the anti-muscarinic side effects of the TCAs
2. Doesn’t interfere with sexual function like the SSRIs.
• Side effect: Increased appetite and weight gain
 THANK YOU
For any questions feel free
to contact me by mail
heba.elsanhory@su.e
du.eg

Dr . Heba Mostafa Elsanhory

Lecturer of Pharmacology& Toxicology
(FOP-SU)