1. Drugs Used in Depression (New group)
DR: Asmaa Fady.
MD., MSC, M.B, B.Ch
اسم ورقم المقرر – Course Name and No.
7/10/2019

2. Learning objectives By the end of the lecture, the student should:
Classify the existing antidepressant drugs new groups.
Explain the Pharmacodynamics potentials, Pharmacokinetics differences Side effects and uses of SSRIs.
Give hint on SNRIs & atypical antidepressants.
اسم ورقم المقرر – Course Name and No.
7/10/2019

3. Wrap up New group antidepressants includes:
1- Second generation: Selective serotonin re-uptake inhibitors (SSRI) e.g. fluoxetine
2- Third generation: : serotonin noradrenaline re- uptake inhibitors (SSNRI)
3-Atypical anti-depressants: bupropion, amoxapine & Mirtazapine.
اسم ورقم المقرر – Course Name and No.
7/10/2019

4. Common SSRIs preparations:
1- Fluoxetine
2- Citalopram
3- Escitalopram
4- Sertraline
5- Fluvoxamine
6- Paroxetine
اسم ورقم المقرر – Course Name and No.
7/10/2019

5. I- Selective Serotonin Reuptake Inhibitors (SSRI): pharmacokinetics
Absorption:
All of the SSRIs are well absorbed after oral administration.
Distribution:
The majority of SSRIs have plasma half-lives that range between 16 and 36 hours.
Metabolism :
By cytochrome P450 (CYP450)
glucuronide conjugation
sulfate conjugation
Excretion:
90% renal
اسم ورقم المقرر – Course Name and No.
7/10/2019

6. I- Selective Serotonin Reuptake Inhibitors (SSRI): pharmacokinetics
Fluoxetine differs from the other members of the class by having a much longer half-life (50 hours), and the half-life of its active metabolite S- norfluoxetine is quite long, averaging 10 days.
Available as a sustained-release preparation allowing once-weekly dosing.
Hepatic microsomal enzyme inhibitor.
اسم ورقم المقرر – Course Name and No.
7/10/2019

7. I- Selective Serotonin Reuptake Inhibitors (SSRI):Pharmacodynamics:
Most commonly prescribed antidepressants. (less side effects)
Fluoxetine (Prozac)
Antidepressant Effect: Elevate mood in depressed patients by selective block of serotonin uptake by nerve endings
The Antidepressant Effect appears after 2-3 WEEKS and lasts for 2-3 WEEKS after stop of SSRI
 Weeks  Weeks 
No anti muscarinic effect.
No alpha 1 blocking effect.
No cardiotoxicity. No hepatotoxicity.
High therapeutic index
اسم ورقم المقرر – Course Name and No.
7/10/2019

8. Therapeutic Uses of Fluoxetine
Psychic depression
panic disorders
Obsessive compulsive disorders (better than the TCA).
Eating disorders e.g. Bulimia nervosa.
اسم ورقم المقرر – Course Name and No.
7/10/2019

9. Advantages of Fluoxetine over TCA
a- Less Adverse Effects :
NO Atropine like effects (Allowed in Glaucoma patients).
NO CVS side effects.
NO weight gain.
b- Low acute toxicity:
NO Cardiotoxicity or Hepatotoxicity
c- Little drug interactions & NO Interaction with food.
High therapeutic index.
اسم ورقم المقرر – Course Name and No.
7/10/2019

10. Adverse Effects of Fluoxetine
a- Anorexia, nausea & diarrhea.
b- Anxiety, insomnia & mania.
c- Increases agression, violence & suicide (used cautiously in teenagers and children).
Sexual dysfunction.
d- Fluoxetine + MAOI Serotonin syndrome
All antidepressants can cause hyponatraemia, due to induction of antidiuretic hormone secretion, but it is reported more frequently with SSRIs than with other antidepressants.
اسم ورقم المقرر – Course Name and No.
7/10/2019

11. Take Care : never ever: Over dose
All SSRIs can cause serotonin syndrome, especially when used in the presence of a MAOI or other highly serotonergic drug.
Serotonin syndrome includes the symptoms of hyperthermia, muscle rigidity, sweating, myoclonus (clonic muscle twitching), and changes in mental status and vital signs (it is a life threating fatal condition).
Overdose with SSRIs does not usually cause cardiac arrhythmias, with the exception of citalopram, which may
cause QT prolongation.
Seizures are a possibility because all antidepressants may lower the seizure threshold
اسم ورقم المقرر – Course Name and No.
7/10/2019

12. Take Care : never ever: Sudden withdrawal
Discontinuation syndrome: All of the SSRIs have the potential to cause a discontinuation syndrome after their abrupt withdrawal. particularly the agents with shorter half-lives and inactive metabolites.
Fluoxetine has the lowest risk of causing an SSRI discontinuation syndrome due to its longer half-life and active metabolite.
Possible signs and symptoms of SSRI discontinuation syndrome include headache, malaise, and flu-like symptoms, agitation and irritability, nervousness, and changes in sleep pattern.
اسم ورقم المقرر – Course Name and No.
7/10/2019

13. Contraindications of Selective Serotonin Reuptake Inhibitors (SSRI):
• hepatic and renal failure
• epilepsy
• manic phase.
اسم ورقم المقرر – Course Name and No.
7/10/2019

14. 2. Serotonin-noradrenaline Reuptake Inhibitors (SNRIs): Venlafaxine
rapid action.
These agents may be effective in treating depression in patients in whom SSRIs are ineffective.
Both SNRIs and the TCAs, with their dual inhibition of both serotonin and norepinephrine reuptake, are effective in relieving backache and muscle aches associated with depression, where SSRIs are ineffective.
They are associated with more cardiac toxicity than the SSRIs.
اسم ورقم المقرر – Course Name and No.
7/10/2019

15. SNRIs (Venlafaxine)
Venlafaxine is a potent inhibitor of serotonin reuptake and, at medium to higher doses, is an inhibitor of norepinephrine reuptake.
The most common side effects of venlafaxine are nausea, headache, sexual dysfunction, dizziness, insomnia, sedation, and constipation.
At high doses, there may be an increase in blood pressure and heart rate (noradrenaline release).
They don’t have anti-muscarininc effect or alpha blocking effect.
7/10/2019

16. III) Atypical antidepressants (NRI.)
The atypical antidepressants are a mixed group of agents that have actions at several different sites.
bupropion
mirtazapine
اسم ورقم المقرر – Course Name and No.
7/10/2019

17. III) Atypical antidepressants.
A. Bupropion is a weak dopamine and norepinephrine reuptake inhibitor
Use:
alleviate the symptoms of depression.
Decrease nicotine craving in smoking withdrawal
Side effects:
dry mouth, sweating, nervousness, tremor, and dose dependent risk for seizures.
Use should be avoided in patients at risk for seizures
اسم ورقم المقرر – Course Name and No.
7/10/2019

18. III) Atypical antidepressants.
B. Mirtazapine;
Mechanism of action:
enhances serotonin and norepinephrine neurotransmission by serving as an antagonist at presynaptic α2 receptors
Blockade of H1 receptors (which likely mediates the sedative effects)
اسم ورقم المقرر – Course Name and No.
7/10/2019

19. III) Atypical antidepressants.
B. Mirtazapine;
It does not cause the anti-muscarinic side effects of the TCAs, or interfere with sexual function like the SSRIs.
Mirtazapine is markedly sedating, which may be an advantage in depressed patients having difficulty sleeping.
Adverse effects:
Weight gain
Sedation
اسم ورقم المقرر – Course Name and No.
7/10/2019

20. اسم ورقم المقرر – Course Name and No.
7/10/2019