8-Drugs used in Depression-new groups 1436.ppt

newer drugs used in depression

1. Drugs used in Depression- Drugs used in Depression-
New groupsNew groups
By By
Profs. Abdulqader AlhaiderProfs. Abdulqader Alhaider
Yieldez Bassiouni Yieldez Bassiouni

2. 1. Selective Serotonin Reuptake 1. Selective Serotonin Reuptake
Inhibitors Inhibitors (SSRIs)(SSRIs)

The SSRIs are currently the most widely The SSRIs are currently the most widely
utilized class of antidepressants in clinical utilized class of antidepressants in clinical
practice.practice.

They act within the brain to increase the level They act within the brain to increase the level
of serotonin (5-HT) in the synaptic gap by of serotonin (5-HT) in the synaptic gap by
inhibiting its re-uptake.inhibiting its re-uptake.


SSRIs are described as 'selective' because SSRIs are described as 'selective' because
they affect only the reuptake pumps they affect only the reuptake pumps
responsible for serotonin.responsible for serotonin.

3. .
Mechanism of Action of SSRIs

4. No effect on NET
 No block to mAch, H, or

1
Adrenoceptor  so no
antimuscarinic nor
sedative effects Except
Paroxetine
Binds to SERT   5-
HT levels in synapse
Fluoxetine
Fluvoxamine
Citalopram
Escitalopram
Sertraline
Paroxetine
They are nearly of comparable efficacy but of preferential
response in each individual

5. Advantages of SSRISAdvantages of SSRIS
- - The Most commonly prescribed antidepressantsThe Most commonly prescribed antidepressants
- - Lacks cardiovascular and anticholinergic side effects Lacks cardiovascular and anticholinergic side effects
compared to TCAcompared to TCA
- - In contrast to MAOI, In contrast to MAOI, they do not cause ‘cheese’ they do not cause ‘cheese’
reactionreaction
- - Safer (low risk of overdose)Safer (low risk of overdose)
- Acute toxicity is less than that of MAOI or TCA- Acute toxicity is less than that of MAOI or TCA

6. PharmacokineticsPharmacokinetics
t1/2 : t1/2 :
Too long (3-11 days): Fluoxetine (Prozac)Too long (3-11 days): Fluoxetine (Prozac)
 Moderate length (~24hr): Sertraline, Paroxetine, Moderate length (~24hr): Sertraline, Paroxetine,
Citalopram. Citalopram.
Metabolism: P450 then conjugation Metabolism: P450 then conjugation

They are enzyme inhibitorsThey are enzyme inhibitors

 Weak inhibitors < Sertraline, Citalopram Weak inhibitors < Sertraline, Citalopram 
interaction interaction

 Strong inhibitors > Fluoxetine, Paroxetine Strong inhibitors > Fluoxetine, Paroxetine 
metabolism of TCA, neuroleptic, some antiarrhythmic, metabolism of TCA, neuroleptic, some antiarrhythmic, ββ--
blockers.blockers.

7. 
Fluoxetine Fluoxetine differs from others members of this class in:differs from others members of this class in:
1- It has a longer t1- It has a longer t
1/21/2 (50hrs). (50hrs).
2- Available 2- Available  as sustained release preparations as sustained release preparations
once weekly.once weekly.
3- Metabolite norfluoxetine = potent as parent drug t3- Metabolite norfluoxetine = potent as parent drug t
1/2 1/2
10 days.10 days.

8. Adverse effects of SSRIs:Adverse effects of SSRIs:

GIT symptoms: Nausea vomiting (due to 5-GIT symptoms: Nausea vomiting (due to 5-
HT3 stim. & diarrhea.HT3 stim. & diarrhea.

Changes in appetite (5-HT3)---weight lossChanges in appetite (5-HT3)---weight loss

Sleep disturbances: Drowsiness with Sleep disturbances: Drowsiness with
Fluvoxamine.Fluvoxamine.

Anxiety & Tremors.Anxiety & Tremors.

Sexual dysfunction: Loss of libido , Sexual dysfunction: Loss of libido , delayed delayed
ejaculation (stim of 5-HT2A).ejaculation (stim of 5-HT2A).
Discontinuation syndrome:Discontinuation syndrome:

Symptoms are headache ,malaise & flu like Symptoms are headache ,malaise & flu like
symptoms, agitation , irritability & symptoms, agitation , irritability &
nervousnessnervousness

9. Drug Cardiotoxicty Nausea Anticholinergic SedationDrug Cardiotoxicty Nausea Anticholinergic Sedation
effectseffects
Citalopram Citalopram ? ++ _ _ ? ++ _ _
FluoxetineFluoxetine - ++ _ _ - ++ _ _
FluvoxamineFluvoxamine _ +++ _ + _ +++ _ +
Paroxetine Paroxetine _ ++ + + _ ++ + +
SertralineSertraline _ ++ _ _ _ ++ _ _
Side effects of SSRIs

10. Therapeutic Uses of SSRIsTherapeutic Uses of SSRIs
Same as for TCA, in addition effective in the Same as for TCA, in addition effective in the
following conditionsfollowing conditions

Depression.Depression.

Anxiety Disorder.Anxiety Disorder.

Eating disorders- bulimia nervosa Eating disorders- bulimia nervosa
(fluoxetine), (fluoxetine), Anorexia nervosa Anorexia nervosa ..

Post traumatic stress disorder. Post traumatic stress disorder.

Premenstrual dysphoric disorder.Premenstrual dysphoric disorder.

Attention Deficit Hyperkinetic Disorder.Attention Deficit Hyperkinetic Disorder.

Treatment of Treatment of premature ejaculation (via premature ejaculation (via
stim of 5-HT2A)stim of 5-HT2A)..

11. Drug interactions of SSRIs
•SSRIs are potent inhibitors of liver microsomal
enzymes. Therefore they should not be used in
combination with TCAs because they can inhibit their
metabolism increasing their toxicity.
•SSRIs should not be used in combination with MAOIs
because of the risk of life-threatening "serotonin
syndrome" (tremors, hyperthermia, cardiovascular
collapse and death). Both drugs require a "washout"
period of 6 weeks before the administration of the
other.

12. 2. Noradrenergic and specific Serotonergic
Antidepressant (NaSSA)
Mirtazapine
-α2 receptor antagonist
-Increase NE and 5HT levels
-Blocks 5HT2A, 5HT3 and thus
reduces side effects of anxiety, and sexual
dysfunction
Blocking 5HT2C, and H1 receptors cause
side effects: sedation, and weight gain.

13. Mirtazapine
Preferred in cancer patients because:Preferred in cancer patients because:
1. Improves appetite1. Improves appetite
2- 2- nausea nausea & vomiting ( 5-HT& vomiting ( 5-HT
33 blocking) blocking)
3- 3-  body weight body weight
4- Sedation (potent antihistaminic)4- Sedation (potent antihistaminic)
5- Less sexual dysfunction (5-HT5- Less sexual dysfunction (5-HT
2 2 blocking)blocking)
6- Has no anti-muscarinic effect .6- Has no anti-muscarinic effect .

14. 3. Serotonin-2A Antagonist and Reuptake
Inhibitors (SARI)
Trazodone, Nefazodone
Blocks 5HT uptake selectively but in a less potent manner
than tricyclics. This reduces depression.
However, they are powerful 5HT2A antagonists, blockade
of 5HT2A receptors stimulates 5HT1A receptors, which
may help reduce depression.
5HT2A antagonism also reduces the risk of anxiety,
sedation or sexual dysfunction which is normally
associated with SSRIs.
 Nefazodone: Structurally related to trazodone but has
less sedative effect and does not block α- adrenoceptors ,
however; it likes most SSRI inhibit P450 3A4 isoenzyme.

15. 4. Serotonin and Noradrenaline Reuptake 4. Serotonin and Noradrenaline Reuptake
Inhibitors (SNRIsInhibitors (SNRIs))
Venlafaxine (Effexor)(Effexor)
• It is used primarily for the treatment of depression, generalized It is used primarily for the treatment of depression, generalized
anxiety disorder, and social anxiety disorder in adults. anxiety disorder, and social anxiety disorder in adults.
VenlafaxineVenlafaxine is the first and most commonly used SNRI. is the first and most commonly used SNRI.
• Selective 5HT and NE uptake blockers combines the action of
SSRI and NRI.
• But without α1, M1 cholinergic or H receptor
blocking properties.


Desvenlafaxine Desvenlafaxine is a metabolite of Venlavaxineis a metabolite of Venlavaxine
Venlafaxine

16. Bupropion
5. Norepinephrine and Dopamine Reuptake
Inhibitor (NDRI)
Is unique in possessing significant
potency as NE and DA reuptake
inhibitor, with no direct action on 5HT.
Therapeutic uses:
1- Treatment of major depression and
bipolar depression.
2- Can be used for smoking cessation.
As it reduces the severity of nicotine
craving & withdrawal symptoms
Advantages: No sexual dysfunction given in young
No weight gain [ No 5HT effect ]
No orthostatic hypotension.
Side effects: Seizures; it  threshold of neuronal firing

17. 6. NE Selective Reuptake Inhibitors (NRIs)
Block only NET
No affinity for 5HT, DA, ADR, H,
mAch receptors
So, has positive effects on the
concentration and motivation in
particular.

Safe to combine with SSRIs
Minimal side effects only related
to activation of ADR system as
tremor, tachycardia, and urinary
hesitancy
Reboxetine

18. Side effects of atypical antidepressantsSide effects of atypical antidepressants
DrugDrug Toxicity Toxicity SedationSedation HypotensionHypotension Anticholinergic Anticholinergic
effectseffects
MirtazepineMirtazepine
NefazodoneNefazodone
TrazodoneTrazodone
VenlafaxineVenlafaxine
--
--
++
++
++++
++
++++++
++++
--
++
++++++
--
++
--
--
++

19. Clinical uses of Antidepressant Drugs.
A.A.Endogenous Depression ( SSRIs (first Choice) New Endogenous Depression ( SSRIs (first Choice) New
generation and Tricyclics can be usedgeneration and Tricyclics can be used
B.B.Panic Disorders ( Imipramine or SSRIs)Panic Disorders ( Imipramine or SSRIs)
C.C.Obsessive Compulsive Disorders (SSRIs and Obsessive Compulsive Disorders (SSRIs and
Clomipramine)Clomipramine)
& Chronic pain (& Chronic pain (AmitriptylineAmitriptyline))
D.D.Anorexia nervosa and Bulemia (SSRIs)Anorexia nervosa and Bulemia (SSRIs)
E.E.Schizo-Afective Disorders (Amoxapine or SSRI + Schizo-Afective Disorders (Amoxapine or SSRI +
HaloperidolHaloperidol))
F. Premature ejaculation (SSRI)F. Premature ejaculation (SSRI)

20. Clinical Uses of Antidepressants
(Continue…)
G. G. Anxiety disorders (Anxiety disorders (AmitriptylineAmitriptyline))
H. Migraine and Anxiety & IBS (H. Migraine and Anxiety & IBS (AmitriptylineAmitriptyline) )
I. I. Nocturnal Enuresis in children e.g. ImipramineNocturnal Enuresis in children e.g. Imipramine
K. Neuropathic Pain (Dual NE and 5-HT reuptake K. Neuropathic Pain (Dual NE and 5-HT reuptake
Blocker) Blocker)

21. Thank YouThank You
Any \questionsAny \questions
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