TypesGroups of Antidepressants, their main targets, indications, doses, mechanism of action, side effects, contraindications Selective Serotonin Reuptake Inhibitors (SSRIs) Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Serotonin Modulators and Stimulators (SMSs) Serotonin Antagonists and Reuptake Inhibitors (SARISs) Norepinephrine Reuptake Inhibitors (NRIs) Tricyclic Antidepressants (TCAs) Tetracyclic Antidepressants (TeCAs) Monoamine Oxidase Inhibitors (MAOIs)

1. Types/Groups of Antidepressants
Main Targets
Indications
Doses
Mechanism of Action
Side Effects
Contraindications
Tural Abdullayev

2. Selective Serotonin Reuptake
Inhibitors (SSRIs)

3. Main targets
• The serotonin transporter (SERT or 5-HTT)

4. Indications
• Major depressive disorder
• Anxiety Disorders (eg. Social anciety disorder)
• Panic disorders
• OCD
• Eating disorders
• Chronic stress
• Post trauma (PTSD)

5. Doses
• Escitalopram (least P450 Cytochrome
inhibition)
− Adult: 10–20 mg, once per day

6. Mechanism of Action
• SSRIs inhibit the reuptake of serotonin
• Repeated stimulation of post-synaptic cell
• Chronic use
− Pre-synaptic downregulation of synthesis
− Post-synaptic downregulation of receptors

7. Side effects
• Bone Fractures
• Akathasia
• Suicidal ideation (thoughts of suicide)
• Photosensitivity
• Sexual dysfunction

8. Contraindications
• Combination may precipitate serotonin syndrome
− Linezolid
− Monoamine oxidase inhibitors (MAOIs) including moclobemide, phenelzine, tranylcypromine, selegiline and methylene blue
− Lithium
− Sibutramine
− MDMA (ecstasy)
− Dextromethorphan
− Tramadol
− Pethidine/meperidine
− St. John's wort
− Yohimbe
− Tricyclic antidepressants (TCAs)
− Serotonin-norepinephrine reuptake inhibitors (SNRIs)
− Buspirone
− Triptan
− Mirtazapine
• Reduce efficiency and GI bleeding
− Aspirin
− Ibuprofen
• Use may precipitate Serotonine Syndrome:
− High body temperature
− Agitation
− Increased reflexes
− Tremor
− Sweating
− Dilated pupils
− DIarrhea

9. Serotonin-norepinephrine
Reuptake Inhibitors (SNRIs)

10. Main targets
• The serotonin transporter (SERT or 5-HTT)
(Inhibition)
• Norepinephrine transporter (NET) (Inhibition)

11. Indications
• Major depressive disorder (MDD)
• Posttraumatic stress disorder (PTSD)
• Generalized anxiety disorder (GAD)
• Social anxiety disorder (SAD)
• Panic disorder
• Neuropathic pain
• Fibromyalgia
• Chronic musculoskeletal pain

12. Doses
• Venlafaxine
– Immediate release:
Initial dose: 37.5 mg orally twice a day or 25 mg orally 3 times a day
Maintenance dose: May increase in daily increments of up to 75 mg
orally at intervals of no less than 4 days
Maximum dose: (moderately depressed outpatients): 225 mg orally
per day
Maximum dose (severely depressed inpatients): 375 mg orally per day
– Extended release:
Initial dose: 75 mg orally once a day
Maintenance dose: May increase in daily increments of up to 75 mg
orally at intervals of no less than 4 days
Maximum dose (moderately depressed outpatients): 225 mg orally per
day
Maximum dose (severely depressed inpatients): 375 mg orally per day
Use: Treatment of major depressive disorder (MDD)

13. Mechanism of Action
• SNRIs inhibts reuptake of 5HT & NA
• Increased concentration of substances
• Continuing fiering of postsynaptic neruon

14. Side effects
• Same as SSRIs including:
– Loss of appetite
– Weight-loss
– Insomnia

15. Contraindications
• Uncontrolled pre-existing hypertension
• Chronic liver disease or alcoholism
• Major eating disorders
• Medications on previous slide

16. Serotonin Modulators and
Stimulators (SMSs)

17. Main targets
• Serotonin transporter (SERT or 5-HTT)
• 5-HT1A-receptor (partial agonist)
• 5-HT3-/ 5-HT7-receptors (antagonist)

18. Indications
• Major depressive disorder

19. Doses
• Vortioxetine
– Adult: 5-20 mg per day as tolerated

20. Mechanism of Action
• Modulation of serotonin receptors
• Inhibition reuptake of serotonin (SRI-effect)

21. Side effects
• Nausea
• Diarrhea
• Dry mouth
• Constipation
• Vomiting
• Flatulence
• Dizziness
• Sexual dysfunction
• Serotonine syndrome

22. Contraindications
• Hypersensitivity to Vortioxetine
• MAOIs use within 21 days
(risk of Serotonin Syndrome)

23. Serotonin Antagonists and
Reuptake Inhibitors (SARISs)

24. Main targets
• 5-HT2A/2C serotoninergic receptors
(antagonist)
• 5-HT1A (partial agonist)
• α1 & α2 adrenergic receptors (antagonist)
• H1 histaminergic receptors (antagonist)
• Higher doses:
– The serotonin transporter (SERT or 5-HTT)
(Inhibition)

25. Indications
• Major depressive disorder
• Anxiety disorders
• Insomnia

26. Doses
• Trazodone
– Depression adult: 150-375mg once per day if
extended-release tablet 10h

27. Side effects
• Serotonine Syndrome
• Cardiac arrhythmia
• Priapism (continuous erection)
• Hepatotoxicity
• Elevated prolactin

28. Contraindications
• According side effects
• Also:
– Hypersensitivity
– Age under 18 as combination therapy (may cause
suicidal ideation)

29. Norepinephrine Reuptake
Inhibitors
(NRIs)
Venlafaxine
Desvenlafaxine
Duloxetine

30. Main targets
• Norepinephrine transporter (NET)

31. Indications
• May be effective in treating depression in
patients in whom SSRIs are ineffective
• Sometimes effective in relieving physical
symptoms of neuropathic pain such as
diabetic peripheral neuropathy
• Venlafaxine, desvenlafaxine, and duloxetine
may precipitate a discontinuation syndrome if
treatment is abruptly stopped.

32. Doses
• Venlafaxine
– Immediate release:
Initial dose: 37.5 mg orally twice a day or 25 mg orally 3 times a day
Maintenance dose: May increase in daily increments of up to 75 mg orally at intervals of no
less than 4 days
Maximum dose: (moderately depressed outpatients): 225 mg orally per day
Maximum dose (severely depressed inpatients): 375 mg orally per day
– Extended release:
Initial dose: 75 mg orally once a day
Maintenance dose: May increase in daily increments of up to 75 mg orally at intervals of no
less than 4 days
Maximum dose (moderately depressed outpatients): 225 mg orally per day
Maximum dose (severely depressed inpatients): 375 mg orally per day
Use: Treatment of major depressive disorder (MDD)
• Duloxetine
– Initial dose: 20 mg orally twice a day
– Maintenance dose: 60 mg per day, given either once a day or as 30 mg orally twice a day
– Maximum dose: 120 mg orally per day
Use: Treatment of major depressive disorder (MDD)

33. Mechanism of Action
• Venlafaxine, desvenlafaxine and duloxetine inhibit the reuptake of both
serotonin and norepinephrine
• Both SNRIs and TCAs, with their dual actions of inhibiting both serotonin
and norepinephrine reuptake, are sometimes effective in relieving physical
symptoms of neuropathic pain such as diabetic peripheral neuropathy.
• SNRIs have little activity at adrenergic, muscarinic, or histamine receptors.
• Venlafaxine
– Potent inhibitor of serotonin reuptake
– At medium to higher doses, is an inhibitor of norepinephrine reuptake.
– At high doses is an mild inhibitor of dopamine reuptake.
– Has minimal inhibition of the CYP450 isoenzymes and is a substrate of the
CYP2D6 isoenzyme.
• Duloxetine
– inhibits serotonin and norepinephrine reuptake at all doses.
– Moderate inhibitor of CYP2D6 and CYP3A4 isoenzymes.

34. Side effects
• Venlafaxine
– Nausea
– Headache
– Sexual dysfunction
– Dizziness
– Insomnia
– Sedation
– Constipation
– At high doses: increase in blood pressure and heart rate
• Duloxetine
– GI side effects are common including nausea, dry mouth, and constipation. Diarrhea and
vomiting are seen less often.
– Insomnia,
– Dizziness
– Somnolence
– Sweating
– Sexual dysfunction
– Possible risk for an increase in either blood pressure or heart rate.

35. Contraindications
• Duloxetine
– Should not be administered to patients with
hepatic insufficiency.
• Velnafaxine
– Starting Venlafaxine tablets in a patient who is
being treated with MAOIs such as linezolid or
intravenous methylene blue is also
contraindicated because of an increased risk of
serotonin syndrome

36. Tricyclic Antidepressants
(TCAs)
Imipramine
Amitriptylinex
Clomipramine
Doxepin
Trimipramine
Desipramine
Nortriptyline

37. Main targets
• Serotonergic receptors
• α-adrenergic receptors
• Histaminic receptors
• Muscarinic receptors
• Amoxapine also blocks 5-HT2 and D2
receptors.

38. Indications
• The TCAs are effective in treating moderate to severe
depression.
• Some patients with panic disorder also respond to TCAs.
• Imipramine has been used to control bed-wetting in
children (older than age 6 years) by causing contraction of
the internal sphincter of the bladder.
• Amitriptyline,
– have been used to treat migraine headache and chronic pain
syndromes (for example, neuropathic pain) in a number of
conditions for which the cause of the pain is unclear.
• Low doses of TCAs, especially doxepin, can be used to treat
insomnia.

39. Doses
• Amitriptyline
 Usual Adult Dose for Depression
 75 – 100 mg orally per day in divided doses; this may be increased to a
total of 150 mg per day if needed
 Maintenance dose: 40 to 100 mg orally as a single dose at bedtime
 Usual Geriatric Dose for Depression
 10 mg orally 3 times a day with 20 mg at bedtime
 Usual Pediatric Dose for Depression (12 yrs or older)
 10 mg orally 3 times a day with 20 mg at bedtime
• Desipramine
 Usual Adult Dose for Depression – 100 to 200 mg orally per day
(max. 300mg )
 Usual Geriatric Dose for Depression – 25 to 100 mg orally per
day (max. 150mg)

40. Mechanism of Action
1. Inhibition of neurotransmitter reuptake:
• TCAs and Amoxapine are
– potent inhibitors of the neuronal reuptake of norepinephrine and serotonin
into presynaptic nerve terminals.
– At therapeutic concentrations, they do not block dopamine transporters.
– By blocking the major route of neurotransmitter removal, the TCAs cause
increased concentrations of monoamines in the synaptic cleft, ultimately
resulting in antidepressant effects.
– Maprotiline and desipramine are relatively selective inhibitors of
norepinephrine reuptake.
2. Blocking of receptors:
• TCAs also block serotonergic, α-adrenergic, histaminic, and muscarinic
receptors
• Actions at these receptors are likely responsible for many of the adverse
effects of the TCAs.
• Amoxapine also blocks 5-HT2 and D2 receptors.

41. Side effects
• Blockade of muscarinic receptors:
– Blurred vision
– Xerostomia(dry mouth)
– Urinary retention
– Sinus tachycardia
– Constipation
– Aggravation of narrow-angle glaucoma
• Blockage α-adrenergic receptors:
– Orthostatic hypotension (imipramine is the most likely cause)
– Dizziness
– Reflex tachycardia
• Sedation – may be prominent, especially during the first several weeks of treatment
• Weight gain – is a common side effect
• Sexual dysfunction
– Erectile dysfunction in men
– Anorgasmia in women
– incidence is still considered to be lower than the incidence of sexual dysfunction associated
with the SSRIs

42. Contraindications
• TCAs (like all antidepressants) should be used with
caution in patients with bipolar disorder, even during
their depressed state, because antidepressants may
cause a switch to manic behavior
• Depressed patients who are suicidal should be given
only limited quantities of these drugs and be
monitored closely.
• The TCAs may exacerbate certain medical conditions,
such as unstable angina, benign prostatic hyperplasia,
epilepsy, and preexisting arrhythmias. Caution should
be exercised with their use in very young or very old
patients as well.

43. Tetracyclic Antidepressants
(TeCAs)
Amoxapine
Mirtazapine
Maprotiline

44. Main targets
• Adrenergic receptors
• 5-HT receptors
• Dopamine receptors

45. Indications
• Amoxapine
– Indicated for the relief of symptoms of depression in patients
with neurotic or reactive depressive disorders as well as
endogenous and psychotic depressions
– Indicated for depression accompanied by anxiety or agitation
• Maprotiline
– Depressive illness in patients with depressive neurosis
(dysthymic disorder) and manic depressive illness, depressed
type (major depressive disorder)
– It’s also effective for the relief of anxiety associated with
depression.
• Mirtazapine
– Indicated for the treatment of major depressive disorder

46. Doses
• Amoxapine
– Usual Adult Dose for Depression
• Initial dose: 50 mg orally two or three times a day
• Maintenance dose: 100 mg orally two or three times a day
• Maximum dose: 600 mg orally per day
– Usual Geriatric Dose for Depression
• Initial dose: 25 mg orally two or three times a day
• Maintenance dose: 50 mg orally two or three times a day
• Maximum dose: 300 mg orally per day
• Maprotiline
– Usual Adult Dose for Depression
• Initial dose: 75 mg orally once a day or in divided doses
• Maintenance dose: 75 to 150 mg/day
• Maximum dose: 225 mg/day
– Usual Geriatric Dose for Depression
• Initial dose: 25 mg orally once a day or in divided doses
• Maintenance dose: 50 to 75 mg/day
• Mirtazapine
– Usual Adult Dose for Depression
• Initial dose: 15 mg orally once a day at bedtime
• Maintenance dose: 15 to 45 mg orally once a day
• Maximum dose: 45 mg/day

47. Mechanism of Action
• Reduce the uptake of norepinephrine and
serotonin and blocked the response of
dopamine receptors to dopamine.

48. Side effects
• Amoxapine
– Drowsiness
– Dry mouth
– Constipation
– Blurred vision
• Mirtazapine
– Somnolence
– Dry mouth
– Constipation
– Increased appetite
– Weight gain
• Maprotiline
– Dry mouth
– Constipation
– Drowsiness
– Nervousness
– Anxiety
– Insomnia
– Agitation

49. Contraindications
• Amoxapine
– Contraindicated in patients hypersensitive to dibenzoxazepine compounds.
– Should not be given concomitantly with monoamine oxidase inhibitors
(Hyperpyretic crises, severe convulsions, and deaths have occurred in patients
receiving tricyclic antidepressants and monoamine oxidase inhibitors
simultaneously)
• Mirtazapine
– Contraindicated in patients with a known hypersensitivity to mirtazapine or to
any of the excipients.
– in a patient who is being treated with MAOIs such as linezolid or intravenous
methylene blue is also contraindicated because of an increased risk of
serotonin syndrome
• Maprotiline
– Contraindicated in patients hypersensitive to Maprotiline and in patients with
known or suspected seizure disorders.
– Should not be given concomitantly with monoamine oxidase (MAO) inhibitors
– Not recommended for use during the acute phase of myocardial infarction.

50. Monoamine Oxidase Inhibitors
(MAOIs)
Phenelzine
Tranylcypromine
Isocarboxazid
Selegiline

51. Main targets
• Monoamine oxidase (MAO) – mitochondrial
enzyme

52. Indications
• Phenelzine
– Effective in depressed patients clinically
characterized as "atypical," "nonendogenous," or
"neurotic."
• Tranylcypromine
– Major Depressive Episode Without Melancholia
• Isocarboxazid
– Treatment of depression

53. Doses
• Phenelzine
– Usual Adult Dose for Depression:
• Initial dose: 15 mg, orally, 3 times a day
• Early phase treatment: Increase to at least 60 mg per day fairly rapidly, as
tolerated
-90 mg per day may be needed for sufficient MAO inhibition
-Clinical response may not be seen until at least 4 weeks at 60 mg per day
dosing
• Maintenance dose: After maximal benefit is achieved, reduce dose slowly over
several weeks.
• Tranylcypromine
– Usual Adult Dose for Depression:
• Usual effective dose: 30 mg per day, orally, in divided doses (max. 60mg)
• Isocarboxazid
– Usual Adult Dose for Depression:
• Initial dose: 10 mg, orally, 2 times a day (max. 60 mg, divided into 2 to 4 doses
per day)

54. Mechanism of Action
• Most MAOIs, such as phenelzine, form stable complexes with the
enzyme, causing irreversible inactivation.
– This results in increased stores of norepinephrine, serotonin,
and dopamine within the neuron and subsequent diffusion of
excess neurotransmitter into the synaptic space
• These drugs inhibit not only MAO in the brain, but also MAO in the
liver and gut that catalyze oxidative deamination of drugs and
potentially toxic substances, such as tyramine, which is found in
certain foods. The MAOIs, therefore, show a high incidence of drug-
drug and drug-food interactions.
• Although MAO is fully inhibited after several days of treatment, the
antidepressant action of the MAOIs, like that of the SSRIs and TCAs, is
delayed several weeks.

55. Side effects
• Phenelzine
– Most important adverse event reported is hypertensive crisis, which has been associated with
intracranial bleeding and has been fatal.
• Tranylcypromine
– The most important adverse event is hypertensive crisis, which may be fatal. The most
common adverse event is insomnia, which can frequently be overcome by giving the last dose
of the day no later than 3 pm or reducing dosage
• Isocarboxazid
– Disturbances in cardiac rhythm
– Hypertensive crisis
– Dizziness
– Headache
– Blurred vision
– Nausea
– Dry mouth
– Hallucinations have been reported with high doses

56. Contraindications
• Phenelzine
– Should not be used in patients who are hypersensitive to the drug or its ingredients, with
pheochromocytoma, congestive heart failure, severe renal impairment or renal disease, a
history of liver disease, or abnormal liver function tests.
– Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS
depressants such as alcohol and certain narcotics.
– Phenelzine sulfate should not be administered together with or in rapid succession to other
MAO inhibitors because HYPERTENSIVE CRISES and convulsive seizures, fever, marked
sweating, excitation, delirium, tremor, coma, and circulatory collapse may occur.
• Tranylcypromine
– In patients with cerebrovascular defects or cardiovascular disorders
– In the presence of pheochromocytoma
– In combination with MAO inhibitors or with dibenzazepine-related entities
• Isocarboxazid
– Hypersensitivity to isocarboxazid or any component of the formulation; cardiovascular disease
(including hypertension); cerebrovascular defect (suspected or confirmed); history of
headache; history of hepatic disease or abnormal liver function tests; pheochromocytoma;
severe renal impairment