Anti depressants

1. DRUGS USED IN AFFECTIVE
DISORDERS
Samuel Mugambe
Samuel Mugambe
1 11/19/2022

2. What are affective Disorders?
 Affective disorders are a set of psychiatric diseases, also
called mood disorders…
 Affective disorders are the diseases of mind.
 They include: depression, mania and bipolar disorder but
other also include anxiety disorders
 MANIA is a period with abnormally and persistently elevated,
expansive or irritable mood
 Bipolar involves periods of depression and periods of mania
 Range from mild to life threatening
Samuel Mugambe
2 11/19/2022

3. Depression
 Depression, or major depressive disorder, is characterized
by feelings of extreme sadness and hopelessness.
 It is more than simply feeling down for a day or two. If you
have depression, you may experience episodes that last for
several days or even weeks.
 Depression may be classified as Exogenous/Reactive
depression or Endogenous/Major Depression
 A milder form of depression is called dysthymia.
Samuel Mugambe
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4. Epidemiology
 Depression affects approximately 5% of the global
population.
 Suicide from depression is 25-30% of the depressed
population.
 Depression is 2-3 times higher in women.
 Current therapy for depression is effective in about 70%
of patients.
4 Samuel Mugambe
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5. Samuel Mugambe
5
According to World Health Organization (WHO),
depression will be the leading cause of ill mental
health by 2030.
Currently ,1 in 4 suffer from ill mental health and
depression, 800,000 people kill themselves
every year due to ill mental health.
STATUS QUO
11/19/2022

6. Types of Depression
 Depression is of the following types :
a. Unipolar - Mind of subject to mood swing in some
direction
b. Bipolar - Depression associated with
mood swings between manic and depressed state -
some times called manic depression
c. Endogenous or major depression –genetic and
biologic factors
d. Reactive-Depression due to shock or
stressful life events Samuel Mugambe
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7. Causes
Samuel Mugambe
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Freepik
Verywell mind
11/19/2022

8. Samuel Mugambe
8 11/19/2022

9. DEPRESSION
Diagnostic features:
 Persistent low mood (without moments of happiness)
 Anhedonia (reduced capacity to feel pleasure)
 Excessive self-blame and feelings of worthlessness
 Suicidal thoughts or a morbid preoccupation with death
 Somatic symptoms
9 Samuel Mugambe
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10. Symptoms of Depression
 Prolonged sadness
 Irritability or anxiety
 Lethargy and lack of energy
 Lack of interest in normal activities
 Major changes in eating and sleeping
habits
 Difficulty concentrating
 Feelings of guilt
 Aches and pains that have no physical
explanation
 Suicidal thoughts
Samuel Mugambe
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11. Symptoms of Depression…
Samuel Mugambe
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12. DSM-V-TR Criteria for Major Depressive
Diagnosis
12 Samuel Mugambe
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13. The monoamine hypothesis of depression
Major depressive disorders result from functional
deficiencies of norepinephrine (NE) or serotonin (5-
HT) in pathways that function in the expression of
mood.
13 Samuel Mugambe
• In 1950, Reserpine induced Depression and study showed that it
depletes the storage of NE and 5-HT
• Then Biochemical or monoamine theory was proposed in 1965 by
Schildkrant
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14. 14 Samuel Mugambe
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15. 15 11/19/2022 Samuel Mugambe

16. Samuel Mugambe
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17. Treatment
 Psychotherapy
 Electroconvulsive Therapy
 Natural alternatives
 Medication
 The drugs which are used for the relief or
prevention of depression and its symptoms are
known as Anti-depressant Drugs
Samuel Mugambe
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18. Samuel Mugambe
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19. Samuel Mugambe
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ECT
11/19/2022

20. Non-drug therapy
Samuel Mugambe
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21. Treatment
21
 The goals of treatment of the acute depressive episode are to:
– Eliminate or reduce the symptoms of depression,
– Minimize adverse effects,
– Ensure compliance with the therapeutic regimen,
– Facilitate a return to a premorbid level of functioning
– Prevent further episodes of depression.
Samuel Mugambe
11/19/2022

22. PHARMACOLOGIC THERAPY
22
 Factors that influence the choice of ADs include:
 The history of patient’s or familial response
 Concurrent medical conditions
 Presenting symptoms
 Potential for drug-drug interactions
 Comparative side-effect profiles of various drugs
 Patient preference, and
 Drug cost
Samuel Mugambe
11/19/2022

23. Antidepressants
Samuel Mugambe
23 11/19/2022

24. CLASSIFICATION OF ANTIDEPRESSANTS
1. Tricyclic antidepressants (TCAs): imipramine, amitriptyline,
clomipramine, doxepin.
2. Selective serotonin reuptake inhibitors (SSRIs): fluoxetine,
paroxetine, sertraline.
3. Serotonin Norepinephrine Reuptake Inhibitors (SNRIs):
Venlafaxine, Duloxetine
4. Monoamine oxidase inhibitors (MAOIs): tranylcypromine,
phenelzine, isocarboxazid.
5. Atypical (heterocyclic second- and third-generation):
 2nd generation: amoxapine, maprotiline, bupropion (NDRI).
 3rd generation:, mirtazapine, nefazodone.
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25. Anti depressants were first developed in 1950’s
 Work by stabilizing and normalizing the level of
neurotransmitters in the brain.
Neurotransmitters like NE and 5-HTplay an important
role in regulating the mood
 Practically all antidepressants affect monoaminergic
transmission in the brain
Anti Depressant Drugs: How do they work
Samuel Mugambe
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26. Mechanism of action
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27. Classification…more examples..
 Selective Serotonin reuptake inhibitors (SSRIs)
- Citalopram
- Escitalopram
- Fluoxetine
- Paroxetine
- Sertraline
Samuel Mugambe
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28. i. NA+5-HT reuptake inhibitors
 Imipramine
 Trimipramine
 Amitriptyline
 Doxepin
ii. Predominantly NA reuptake inhibitors
 Desipramine
 Nortriptyline
 Reboxetine
 Amoxapine Samuel Mugambe
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Classification…more examples..
Tricyclic Antidepressants-TCAs
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29. 5-HT / NE Reuptake Inhibitors (SNRIs)
- Duloxetine
- Venlafaxine
Monoamine Oxidase Inhibitors
- Phenelzine
- Tranylcypromine
Atypical Antidepressants
- Bupropion (NDRI)
- Mirtazapine
- Nefazodone- Trazodone
29
Classification…more examples..
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30. Some sources…
1. MAO inhibitors:
 Irreversible: Isocarboxazid, Iproniazid, Phenelzine and
Tranylcypromine
 Reversible: Moclobemide and Clorgyline
2. Tricyclic antidepressants (TCAs)
 NA and 5 HT reuptake inhibitors – Imipramine, Amitryptiline,
Doxepin, Dothiepin and Clomipramine
 NA reuptake inhibitors – Desimipramine, Nortryptyline,
Amoxapine
3. Selective Serotonin reuptake inhibitors: Fluoxetine, Fluvoxamine,
Sertraline and Citalopram
4. Atypical antidepressants:
Trazodone, Mianserin, Mirtazapine, Venlafaxine, Duloxetine, Bupropion
and Tianeptine Samuel Mugambe
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31. Pharmacology of Individual
Classes
Samuel Mugambe
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32. TRICYCLIC ANTIDEPRESSANTS
(TCAs)
 History
– Imipramine
 Current Drugs
 Mechanism of Action
 Side Effects
Imipramine
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33. TCAS ON THE MARKET
 Amitriptyline
 Desipramine (Norpramin)
 Doxepin (Sinequan)
 Imipramine (Tofranil, Tofranil-PM)
 Nortriptyline (Pamelor)
 Protriptyline (Vivactil)
 Trimipramine (Surmontil)
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34. TCAs SIDE EFFECTS
 Muscarinic M1 receptor antagonism - anticholinergic
effects including dry mouth, blurred vision, constipation,
urinary retention and impotence
 Histamine H1 receptor antagonism - sedation and
weight gain
 Adrenergic α receptor antagonism - postural
hypotension
 Direct membrane effects - reduced seizure threshold,
arrhythmia
 Serotonin 5-HT2 receptor antagonism - weight gain
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35. IMPORTANT DRUG INTERACTIONS OF TCAS
 Alcohol: CNS depressant effects are potentiated.
 Norepinephrine: pressor activity is potentiated.
 Clonidine & methyldopa: antihypertensive action is
reduced.
 MAOIs: excitement, hyperpyrexia, hypertensive episodes
.
 Can lead to mania (Avoid bipolar disorder or manic
depression)
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36. SUMMARY OF PHARMACOLOGICAL PROPERTIES AND ADVERSE
EFFECTS OF TCAS
TRICYCLIC ANTIDEPRESSANTS
Generally highly lipid-soluble and have relatively long plasma half-lives.
Plasma levels used mainly to monitor compliance and toxicity.
CNS adverse effects:
sedation, confusion and memory dysfunction, mania, agitation and psychosis,
tremor, seizures, insomnia & movement disorders.
CVS effects: postural hypotension, tachycardia, conduction defects, arrhythmias.
Autonomic effects: dry mouth, blurred vision, urinary retention, constipation, rarely
may precipitate narrow-angle glaucoma or paralytic ileus.
Rebound/discontinuation effects: dizziness, nausea, headache, fatigue.
Other effects: weight gain, sexual dysfunction, haematologic changes (hemolytic
anaemia, agranulocytosis), allergic reactions, obstructive jaundice. 36
Samuel Mugambe
11/19/2022

37. SELECTIVE SEROTONIN REUPTAKE INHIBITORS
 Most commonly prescribed class
 Current drugs
 Mechanism of action
 Side effects
Serotonin
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These generally produce fewer serious
adverse effects than TCAs
Cause little sedation, postural
hypotension, anticholinergic activity, and
CVS toxicity.
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38. SSRIs ON THE MARKET
 Citalopram (celexa)
 Dapoxetine (priligy)
 Escitalopram (lexapro)
 Fluoxetine (prozac)
 Fluvoxamine (luvox)
 Paroxetine (paxil)
 Sertraline (Zoloft)
Fluoxetine 1:1
Sertraline
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39. SSRIS SIDE EFFECTS
 Headache.
 Sexual dysfunction (a
leading cause of
noncompliance).
 Gastric irritation.
 Weight loss.
 Stimulation (dysphoria,
marked by agitation, anxiety,
increased motor activity,
insomnia, tremors).
 Apathy.
 Rebound/discontinuation
effects similar to those of
TCAs.
 Suicidal thoughts
 Bruxism (involuntarily
grinding of the teeth) e.g.
Fluoxetine, sertraline
39 Samuel Mugambe
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40. SSRIS SIDE EFFECTS
 Many disappear within 4 weeks (adaption phase)
 Side effects more manageable compared to MAOIs
and TCAs
 Sexual side effects are common
 SSRI cessation syndrome
– Brain zaps (electrical shock sensations in the
brain)
– Sexual dysfunction (ED, Low libido..etc)
40 Samuel Mugambe
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41. IMPORTANT DRUG INTERACTIONS OF SSRIS
 Fluoxetine & paroxetine inhibit liver CYP2D6
and can potentiate actions of other drugs
metabolized by the same enzymes
 MAOIs: “serotonin syndrome”- tremor,
hyperthermia, muscle rigidity & CVS collapse
41 Samuel Mugambe
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42. SEROTONIN-NOREPINEPHRINE REUPTAKE
INHIBITORS (SNRIS)
 Slightly fewer adverse effects than SSRIs
 Current drugs
– Venlafaxine (Effexor)
– Duloxetine (Cymbalta)
 Mechanism of Action
– Works on both neurotransmitters
Venlafaxine 1:1
Duloxetine
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43. ADRS
Venlafaxine:
- Nausea, dizziness, sexual disturbances, anxiety &
insomnia.
– Hypertension
Duloxetine:
- GIT upsets.
- Sexual dysfunction.
- Sleep disturbances (insomnia, sedation).
 Some books put them under Atypical drugs
Samuel Mugambe
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44. MONOAMINE OXIDASE INHIBITORS (MAOIS)
 History
– Isoniazid
– Iproniazid
 Current Drugs
 Mechanism of Action
 Side Effects
Isoniazid
Iproniazid
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45. MAOIS ON THE MARKET
 MAO Inhibitors (nonselective)
– Phenelzine (Nardil)
– Tranylcypromine (Parnate)
– Isocarboxazid (Marplan)
 MAO-B Inhibitors (selective for MAO-B)
– Selegiline (Emsam)
 Irreversible: Isocarboxazid, Iproniazid, Phenelzine and
Tranylcypromine
 Reversible: Moclobemide and Clorgyline
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46. 46 Samuel Mugambe
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47. MAOI SIDE EFFECTS
 Drowsiness/Fatigue
 Constipation
 Seizures
 Nausea, Diarrhea
 Postural hypotension
 Low or high blood
pressure
 Lightheadedness,
 Decreased urine output
 Decreased sexual function
 Sleep disturbances
 Muscle twitching
 Weight gain
 Blurred vision
 Headache, dry mouth
 Increased appetite
 Restlessness
 Shaking
 Weakness
 Increased sweating
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48. MAOIS SIDE EFFECTS
 Side effects have put MAOIs in the second or third line of
defense despite superior efficacy
 MAO-A inhibitors interfere with breakdown of tyramine
– High tyramine levels cause hypertensive crisis (the
“cheese effect”)
– Can be controlled with restricted diet
 In overdose, MAOIs may cause agitation, hyperthermia,
seizures, hypotension or hypertension.
48 Samuel Mugambe
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49. IMPORTANT INTERACTIONS OF MAOIs
Indirectly acting sympathomimetics e.g. tyramine: headache,
nausea, cardiac arrythmias, hypertensive crisis, rarely
subarachnoid bleeding and stroke.
SSRIs: “serotonin syndrome”- hypertensive crisis, hyperpyrexia,
excitement.
TCAs: same effect as SSRIs but not as bad as with SSRIs
Barbiturates, alcohol, opioids: Additive sedation and CNS
depression.
49 Samuel Mugambe
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50. ATYPICAL ANTIDEPRESSANTS
• Amoxapine also blocks D-receptors, TCA
• Trazodone/nefazodone block prejunctional 5-HT1
receptors.
• Mirtazapine has 5-HT2 receptor blocking activity and
also blocks α2-adrenoceptors.
• Maprotiline: Highly sedating and Poses high risk of
cardiotoxicity especially in overdose
Samuel Mugambe
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51. Trazodone & Nefazodone: Highly sedating.
- May also cause postural hypotension in the elderly, and a
rare priapism in men.
- No significant anticholinergic activity.
Bupropion: NDRI..
- More likely than TCAs to cause seizures
- Like SSRIs, causes stimulation, insomnia and weight gain.
- No significant anticholinergic or hypotensive activity. Causes
little sexual dysfunction.
51 Samuel Mugambe
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52. TETRACYCLIC ANTIDEPRESSANTS (TECAS)
 Current Drugs
– Mirtazapine (Remeron)
 Mechanism of Action
 Mirtazapine has 5-HT2 receptor blocking activity
and also blocks α2-adrenoceptors.
52 Samuel Mugambe
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53. NOREPINEPHRINE-DOPAMINE REUPTAKE INHIBITORS
(NDRIS)
 Current drugs
– Bupropion (Wellbutrin)
 Mechanism of Action
– More potent in inhibiting dopamine
– Also a nicotinic antagonist
 Used in depression and cessation of smoking
 Adverse effects
– Lowers seizure threshold
– Suicide
– Less sexual dysfunction
– Doesn’t cause weight gain (weight loss instead)
Bupropion 1:1
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54. THERAPEUTIC USES
1. Major depressive disorders
2. Bipolar affective disorders
3. Anxiety disorders (GAD, panic attacks, phobias, OCD)
4. Enuresis
5. Attention deficit/hyperactivity disorder
6. Chronic pain (including neuropathic pain)
7. Other uses: treatment of nicotine and alcohol dependence,
bulimia etc
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Samuel Mugambe
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55. Non-drug therapy
Samuel Mugambe 55
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56. Thank You
Read the Summaries Below….on
your own..
56 Samuel Mugambe
11/19/2022

57. Indications for Antidepressants
1. Endogenous Major Depression:
 Aim: Relieve symptoms of depression and restore Normal social
Behavior
 1st choice – SSRI (atypical ones also may be considered)
 TCAs – in non-responsive cases
(TCAs have to be used in severe depression in adults)
 MAO –A inhibitors in mild and moderate cases
 Maintenance – by TCAs (Imipramine 100 mg)
 Combined with Lithium in Bipolar disorder
 Newer ones are not recommended in children – suicide chance
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58. Indications for
Antidepressants(cont’d)
2. Obsessive Compulsive Disorder (OCD) and Phobic states:
(SSRIs are useful)
– Compulsive eating in Bulimia
– Body dysmorphic disorder
– Compulsive buying
– Kleptomania
3. Anxiety Disorders: BZD
4. Neuropathic pain: Imipramine, Amitriptyline – post herpetic neuralgia
5. Attention Deficit Hyperactivity Disorder: TCAs
6. Enuresis
7. Migraine: Amitryptiline as prophylactic Samuel Mugambe
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60. Pharmacology of Antidepressant Medications
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61. Summary of Side Effects
Classification Side effects Pharmacokinetics
TCAs Blurred Vision , xerostomia ,
constipation, Increased
appetite, Nausea, cardiac
arrhythmia
Well absorbed Orally
Pass BBB
Metabolised in liver
SSRIs Nausea, anxiety, insomnia,
sexual dysfunction, gastric
upset
Well absorbed Orally
Food effects absorption
Metabolised in Liver
SNRIs Nausea, anxiety, insomnia,
sexual dysfunction, gastric
upset
Well absorbed Orally
Metabolised in Liver
Atypical Antidepressant Dry mouth , nervousness,
seizures at high dose
Well absorbed orally
MAOIs Nausea, Headache, Stiff
neck, dry mouth, Drug
interaction
Well absorbed orally
Samuel Mugambe
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62. 62 Samuel Mugambe
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63. 63 Samuel Mugambe
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64. END
 THANK YOU VERY MUCH
Samuel Mugambe
64 11/19/2022