The document provides information on antidepressants. It begins by defining depression and describing its various types. It then discusses the different classes of antidepressants, including SSRIs, SNRIs, TCAs, and MAOIs. For each class, it provides details on examples of drugs, their mechanisms of action, pharmacokinetics, therapeutic uses, and adverse effects. The document also discusses non-medication treatments for depression.

1. RAGHAVENDRA INSTITUTE OF
PHARMACEUTICAL EDUCATION AND
RESEARCH
ADVANCED PHARMACOLOGY-I
SEMINAR TOPIC : ANTIDEPRESSANTS
PRESENTED BY: K.SWAPNIKA SAI (19L81S0109)
M.PHARMACY 1ST YEAR ( PHARMACOLOGY)
RIPER (AUTONOMOUS), ANANTHAPURAMU

2. DEFINITION AND TYPES OF DEPRESSION
DEFINITION:
Depression is the most common of the affective disorders [ defined as disorders of
mood]; it may range from a very mild condition, bordering on normality to severe [psychotic]
depression accompanied by hallucinations and delusions.
(or)
Depression is a heterogeneous disorder, with patients presenting with one or more
core symptoms, and depression is often associated with other psychiatric conditions,
including anxiety, eating disorders and drug addiction.
TYPES OF DEPRESSION:
• Major depression
• Chronic depression (Dysthymia)
• Atypical depression
• Bipolar disorder/Manic depression
• Seasonal depression (SAD)
• Post Partum depression (PPD)

3. Depression could be:
1. Unipolar:
• Reactive depression
• Endogenous depression
2. Bipolar mood disorder or manic-depressive illness.
1. UNIPOLAR DEPRESSION:
• Reactive depression is due to stressful and distressing circumstances of life.
• Endogenous depression is major depression and results from a biochemical
abnormality in the brain.
• Deficiency of monoamine [NA,5-HT] activity in the CNS is responsible for endogenous
depression.
2. BIPOLAR DEPRESSION:
• It is characterized by alternative episodes or periods of mania and depression called as
Manic-Depressive Psychosis [MDP] / Manic Depressive Ilness [MDI].
• It is less common and it is associated with a hereditary tendency.
• Mania can be considered opposite of depression with elation, over-enthusiasm, over confidence, often
associated with irritation and aggression.

4. ETIOLOGY
Biological factors
Social factors
Psychological factors

5. BIOLOGICAL FACTORS
• Genetic
• High prevalence in first degree relatives
• High concordance with monozygotic twins
• Short allele of serotonin transported gene
• Medical Illness:
• Parkinson's, Alzheimer's, cancer, diabetes or stroke
• Vascular changes in the brain
• Chronic or severe pain
• Previous history of depression
• Substance abuse

6. SOCIAL FACTORS
• Loneliness, isolation
• Recent bereavement (intense grief)
• Lack of a supportive social network
• Decreased mobility (Due to illness)
PSYCHOLOGICAL FACTORS
• Traumatic experiences
• Damage to body image
• Fear of death
• Frustration with memory loss

7. SYMPTOMS
1. Emotional:
• Low mood, excessive rumination of negative thought, misery,
apathy and pessimism
• Low self-esteem: feelings of guilt, inadequacy and ugliness
• Indecisiveness, loss of motivation
• Anhedonia, loss of reward
2. Biological:
• Retardation of thought and action
• Loss of libido
• sleep
• fatigue

8. PATHOPHYSIOLOGY
• Associated with changes in NE,5-HT,DA systems.
• Associated with changes in neuroendocrine function.
CRF modulates secretion of ACTH.
CRF functions as NT in extra hypothalamic brain.
CRF hypersecreted in depression.
CRF and CRF mRNA expression in hypothalamic brain areas , in locus coeruleus,
in amygdala in animal studies after acute and chronic stress.
Depressed patients exhibited in CSF,CRF concentrations.
23% in no.of CRF binding sites in Frontal cortex of suicide victims,CRF,receptor
mRNA expression in frontal cortex of suicide victims.
• Other neurotransmitters systems
Gamma amino butyric acid(GABA)
Substance P (NT)
Neuropeptide Y(NPY)

10. TREATMENT
• Non-medical
• Medical

11. NON-MEDICAL INTERVENTIONS
• Exercise
• Balanced diet and Fluids
• Inform about depression
• Avoid stressors
• Avoid alcohol
• Family support/social support
• Focus on positives
• Promote creativity
• Alternate therapy: Pet therapy, horticulture therapy

12. MEDICAL INTERVENTIONS
• Medications
• Psychotherapy
• Electro-convulsive therapy
• Vagal Nerve stimulation
• Combination therapy

13. MEDICATIONS
• Serotonergic
• SSRIs: Citalopram, Escitalopram, Sertraline, Paroxetine, Fluoxetine
• Noradrenergic
• TCAs
• Dopaminergic
• Bupropion
• Dual mechanism
• Venlafaxine, Mirtazapine, Duloxetine, SSRIs + Buproprion

14. Treatment selection
• Serotonergic
• Anxious, agitated, hostile,
• hypochondriac
• Noradrenergic
• Avoid use in elderly.
• Dopaminergic
• Psychomotor retarded, blunted, apathetic.
• Dual mechanism
• Melancholic, atypical, treatment resistant.

15. PSYCHOTHERAPY
• Very helpful in mild to moderate depression
• Response time slower
• Relapse less frequent
• CBT(COGNITIVE BEHAVIORAL THERAPY)
• As effective as antidepressants
• IPT(INTERPERSONAL THERAPY)
more effective than antidepressants
in treating mood suicidal ideations,
and lack of interest, whereas
antidepressants are more
effective for appetite and
sleep disturbances.

16. ELECTRO-CONVULSIVE THERAPY
• Indications:
• Failure of antidepressant trials
• Severe depression with catatonic or psychotic features
• High risk of suicide
• Poor tolerability of oral meds
• Response rates from 70-90%
• Most efficacious antidepressant
• Contraindications: ICP(Intracavernous
pharmacotherapy),
intracranial tumors
• avg number of treatments 8-12,
may need maintenance therapy
• Side effects: Short term memory loss

17. VAGAL NERVE STIMULATION
• Electrical pulses applied to the left vagus nerve in the neck for
transmission to the brain
• Intermittent stimulation
• 30 sec on/5 min off
• Implanted in over 11,500 patients.
• Battery life of 8-12years, weighs 38 gms, 10.3 mm thick.
• Side effects:
• hoarse voice, pain or tingling in the throat or neck, cough, headache
and ear pain, difficulty sleeping, shortness of breath, vomiting.

18. Vagal Nerve Stimulator (VNS)

19. CLASSIFICATION
ANTIDEPRESSANTS
SSRIs SNRIs TCAs MAOIs Atypical
SPECIF2Y
Sertraline- ZOLOFT
Paroxetine- PAXIL
Ecitalopram-
LEXAPRO
Citalopram-CELEXA
Fluoxetine-PROZAC
Fluvoxamine-LUVO
AVOID
Venlafaxine-
EFFEXOR
Duloxetine-
CYMBALTA
Desvenlaflaxin
e-PRISTIQ
Levomilnacipr
an-FETZIMA
TCA DA,NA
Trimipramine
Clomipramin
e
Amitriptyline
Desipramine
Doxepin
Nortryptiline
SELECTIVE
Clorgyline
Moclobemi
de
MUSIC
TELEVISON
MEDIA BUREAU
Mirtazapine
Trazodone
Vinlazodone
Mianserin
Buproprion
NONSELEC
TIVE
STRIP
Selegiline
Tranylcypr
omine
Isocarboxa
mid
Phenelzine

20. SELECTIVE SEROTONIN REUPTAKE
INHIBITORS [SSRIs]
• ADVANTAGES:
• Selectively inhibit membrane associated SERT (serotonin
transporter)
• More tolerability and better acceptability.
• No sedation and no seizures.
• No anticholinergic effects [like constipation, urinary retention]
• No alpha blocking action so no postural hypotension and suits for
elderly.
• No arrhythmias.
• No weight gain.

21. FLUOXETINE
• Prototype of SSRIs
• Long acting due to active metabolites,
duration 7-10 days
• Plasma t½ - 2 days
• Used for children (7 years) and older
people .
• It is demethylated in liver to form
active metabolite Nor-fluoxetine.
• Causes more agitation and
dermatological reactions than other
SSRIs.
• Less suitable for rapid effect in patients
due to slower onset of action.
SERTALINE
• Plasma t½ -26hrs
• Produces long acting active metabolite.
• Milder enzyme inhibition – DI lower due
to less potency to cause cytochrome
enzyme depression.
• Weak inhibitor of dopamine uptake.
• Bioavailability is low – 45%

22. FLUVOXAMINE
•Plasma t½ -18hrs
•Short acting, no
active metabolite
•Less agitation
•Commonly used in
hospitalized
patients and in
some anxiety
disorders.
PAROXETINE
•Plasma t½ -20hrs
•Short acting, no
active metabolite
•More GI side
effects and
weight gain.

23. CITALOPRAM
•Plasma t½ - 33hrs
•No active
metabolite is
known
•Similar to
Sertraline but
should be avoided
in patients with
suicidal
tendencies.
ESCITALOPRAM
•Active S(+)
enantiomer of
citalopram
•Effective at half
the dose.
•Less side effects
and Drug
Interactions(DI)

24. PHARMACOKINETICS OF SSRIs
• Half-lives are from 15-75 hrs.
• These are well absorbed so given oral route administration.
• Most are bound to plasma proteins and have large volume of
distribution.
• Metabolized in liver through microsomal enzymes.
• Excretion takes place through renal system (90 %)

25. MECHANISM OF ACTION
SSRIs
Inhibits Serotonin Transporter activity (SERT)
Increases serotonin levels in the synapse
Stimulates post-synaptic serotonin receptors
Enhances transcription of related proteins
Increased production of BDNF (Brain Derived Neutropic Factor)
[Which is a NT modulator that enhances cognition] and other proteins
Anti depressant effect

26. MECHANISM OF ACTION OF SSRIs

27. THERAPEUTIC USES OF SSRIs
• Depression
• Obsessive compulsive disorder (OCD)
• Panic disorders
• Premenstrual syndrome
• Social anxiety disorder
• Bulimia nervosa ( eating disorder – excessive eating )

28. ADVERSE EFFECTS OF SSRIs
• Nausea, vomiting, diarrhea and Headache
• Sweating
• Anxiety and agitation
• Sexual dysfunction
• Changes in weights
• Sleep disturbances ( Insomnia and Somnolence )
Paroxetine and Fluvoxamine are more sedating drugs.
Fluoxetine and Sertraline are more activating SSRIs.
• Serotonin syndrome (hyperthermia, muscle rigidity, changes in
mental status and vital signs)
• Overdose can cause seizures, but Citalopram causes QT
Elongation.

29. SEROTONIN/ NOREPINEPHRINE REUPTAKE
INHIBITORS(SNRIs)
• Inhibit the reuptake of both serotonin and norepinephrine.
• May be effective in treating depression in patients where
SSRIs are in effective.
• MECHANISM OF
ACTION:

30. SNRIs
• These are effective against chronic painful symptoms, such as
backache and muscle aches, against which SSRIs are relatively
ineffective ( this pain is modulated by 5-HT and NE pathways
in CNS)
• Both SNRIs and TCAs inhibits both 5-HT and NE reuptake ,
sometimes effective in relieving physical symptoms of
neuropathic pain such as Diabetic peripheral neuropathy.

31. VENLAFLAXINE
• Fast acting
• Short t½ -5 hrs, given
twice daily
• Safe in over dosage
• Withdrawal symptoms and
troublesome if doses are
missed.
DULOXETINE
• Potent non-selective
5-HT/NA uptake
• Plasma t½ -14hrs
• Well absorbed
• Metabolized by
microsomal enzymes
• Also used to treat urinary
incontinence and for
anxiety disorders.
• SIDE EFFECTS:
• Sedation,dizziness,nausea
and sexual dysfunction

32. TRICYCLIC ANTIDEPRESSANTS(TCAs)
• In the late 1950s,Imipramine was noted to be effective for
the symptomatic treatment of depression.
• A number of chemical congeners of imipramine have been
synthesized and tested for antidepressant properties, they
are collectively known as TCAs.
• They have characteristic three ring nucleus.
IMIPRAMINE

33. PHARMACOKINETICS
• Good oral absorption.
• Mostly given once a day at bed time to avoid daytime
sedation.
• High plasma protein binding ,high lipid solubility.
• TCAs are converted to active metabolites shows long action.
• Metabolism takes place in the liver and many active
metabolites are produced.
• Excretion takes place through renal.

34. MECHANISM OF ACTION

35. MECHANISM OF ACTION
• INITIALLY
Presynaptic alpha2 and 5-HT1 auto receptors are activated
by increasing amount of NA and serotonin in synaptic cleft resulting
in decreasing firing.
• BUT ON LONGTERM
Desensitize and down regulation of these receptors and induce
adaptive changes and sensitivity of receptors and amine turnover
leading to enhanced NA and 5-HT transmission required for
antidepressant action.

36. PHARMACOLOGICAL ACTIONS
1)ANS:
• Potent anticholinergic (drymouth,blurring of
vision,constipation,urinary hesitancy)
• Weak alpha 1 blocking (Postural hypotension, impairement
of ejaculation)
• H1 antihistaminic – sedation
2)CVS:
• Tachycardia
• Postural hypotension
• Cardiac arrhythmias (T- wave suppression or inversion) due
to intraventricular conduction interference due to NE and
anticholinergic actions.

37. 3) CNS:
• Dizziness
• Confusion, difficulty in thinking.
ADVERSE EFFECTS:
• Muscarinic M1 receptors antagonism – Anticholinergic effects
including drymouth,blurred vision,constipation,urinary retention
and impotence.
• Histamine H1 receptor – sedation and weight gain.
• Adrenergic α-receptor antagonism-postural hypotension.
• Direct membrane effects –reduced seizure threshold,
arrhythmias.
• 5-HT2 receptor antagonism- weight gain and reduced anxiety.
• High potency leads to Mania.

38. DRUG INTERACTIONS
• Potentiation of Sympathomimetics can cause hypertension
(direct acting)
• Reduce action of Sympathomimetics (indirect acting)
• Reduce antihypertensive action of Guanethidine and
Clonidine (by preventing their transport into neurons)
• Potentiate other CNS sedatives.
• With MAOs inhibitors dangerous hypertensive crisis with
excitement and hallucinations.
• Retard the absorption of other drugs.
• Phenytoin, phenyl butazone and chlorpromazine, aspirin,
displaces the TCAs and produce toxicity.
• Phenobarbitone induce metabolism and inhibit the effect
drug.

39. THERAPEUTIC USES
• Effective in treating moderate to severe depression.
• Some patients with panic disorders also respond to TCAs.
• Imipramine has been used to control bed wetting in children
by causing contraction of the internal sphincter of the
bladder.
• Used cautiously at present because of inducement of cardiac
arrhythmias and other CVS problems.
• TCAs particularly amitriptyline used to treat migraine and
chronic pain syndromes(Neuropathic pain)
• Low doses of TCAs especially Doxepin can be used to treat
Insomnia.

40. MOA INHIBITORS
• Monoamine oxidase (MOA) is an enzyme which metabolizes
NE,5-HT and DA.
• Drugs which inhibit this enzyme, enhances the neuronal levels
of monoamines like NE,5-HT and DA.
• MAO exists as two enzymes:
1) MAO-A inhibitor( selective for 5-HT)
2) MAO-B inhibitor:
 Selegiline (EMSAM,DEPRENYL)- Parkinson's disease
brain( basal ganglia),platelets, liver
Deaminates dopamine

41. Irreversible and non-selective
MAOI
• Peripheral adrenergic nerve endings
• Intestinal mucosa
• Human placenta
• Liver
• Inhibits 5-HT,NA and DA
• Inhibited by Moclobemide and
Clorgyline
• Drugs: phenelzine (NARDIL)
tranylcypromine(PARNATE)
isocarboxamid (MARPLAN)
Reversible and selective MAOI
• Moclobemide (AURORIX)
MAO –A INHIBITORS

42. NON-SELECTIVE AND IRREVERSIBLE
MAO INHIBITORS
• Irreversibly inhibit the enzyme MAO and enhance neuronal
levels of NA,5-HT and DA.
• SIDE EFFECTS:
• Orthostatic hypotension
• Restlessness
• Weight gain
• Insomnia(due to CNS stimulation)
• Anticholinergic effects
• Abrupt stoppage can result in withdrawal syndrome with
confusion, excitement and even psychosis.

43. CHEESE REACTION
Patients on MAOIs takes tyramine containing food like
cheese,beer,wine,yeast,buttermilk etc.
Tyramine is normally metabolized by MAO in gut wall but due
to irreversible inhibition of MAO by drugs results in
Tyramine escapes metabolism and displaces noradrenaline
from nerve endings
leads to Hypertension
TREATMENT: Phentolamine,prazosin

44. SEROTONIN SYNDROME
• SSRIs with MAOI concurrently administered then there will be
significant increase in serotonin levels in the synapses.
• It includes hyperthermia,restlessness,sweating,muscle
rigidity,aggressive behavior,tremors,seizures and coma.
• Because of the side effects and drug interactions MAOI are not
preferred antidepressants.
REVERSIBLE INHIBITORS OF MAO-A INHIBITORS
MOCLOBEMIDE:
• Competitive enzyme inhibition
• Short duration of action
• Effective in action and devoid of anticholinergic,sedative,cognitive and
CVS effects.
• Good for elderly with heart diseases.

45. MECHANISM OF ACTION OF MAOIs

46. THERAPEUTIC USES OF MAOIs
• Indicated for depressed patients who are unresponsive or
allergic to TCAs or who experience strong anxiety.
• Treatment of phobic states.
• Treatment of atypical depression (labile mood, rejection
sensitivity , and appetite disorders.
• Considered to be last line drugs in treatment because of their
risk of drug-drug and drug-food interactions.

47. ATYPICAL ANTIDEPRESANTS
• Act at several different sites.
MIRTAZAPINE
• Nor-adrenergic and specific
serotonergic antidepressant.
• Blocks α-2 auto receptor
increasing NE and 5-HT1
receptor action.
• SIDE EFFECTS:
• Sedation
• Increased appetite
• Weight gain
TRAZODONE
• Weak 5-HT uptake block,α-
block,5-HT2 antagonist.
• No anticholinergic
• No arrhythmias
• No seizures
• SIDE EFFECTS:
• Postural hypotension
• Priapism(prolonged and
painful erection)

48. MIANSERIN
• Unique not inhibit NA and 5-HT
uptake
• Blocks pre-synaptic α2 receptors
increases release and turnover of
NA
• Antagonist and 5-HT and H1
receptors
• Has sedative effect
BUPROPRION
• Weak inhibitor of NE and DA
uptake (NDRI)
• Non-sedative but excitant effect
• Used in treatment of depression
and cessation of
smoking(decreases craving and
attenuating the withdrawal
symptoms)
• Can help with cocaine withdrawal.
• SIDE EFFECTS:
• Dry mouth
• Nervousness
• Tremors
• Increased risk for seizures at high
doses.

49. RECENT ADVANCEMENTS
1. ESKETAMINE:
Approved on march 5,2019
by FDA.
Generally used as general
anesthetic but had reduced
symptoms of severe depression.
It binds to NMDA-glutamatergic
ion receptor antagonist that exhibit a direct action on the
excitatory glutamatergic neurotransmission system such as
ketamine.

50. 2) BREXANOLONE:
-first drug for postpartum depression in
females.
- it modulates the allosteric GABA -A
receptors.
- it is given through I.V Infusion into vein
and shows action 60hrs

51. NEW CLASSIFICATION OF
ANTIDEPRESSANTS
• Serotonin 5-HT1A auto receptor partial agonist with serotonin
reuptake inhibition (SPARI) such as Vinlazodone.

52. Norepinephrine
reuptake inhibitor
with serotonin
receptors
antagonism (NRISA)
such as maprotiline.
Serotonin-norepinephrine
reuptake inhibitor and serotonin
receptors antagonism
antidepressant with potent
antipsychotic D2 receptor
blockade/antagonism (SNRISA
with potent antipsychotic D2
receptor blockade/ antagonism)
such as amoxapine (asendin)

53. • Atypical antipsychotics that exhibit weak D2 receptor antagonism with potently
strong 5-HT2A receptor blockade such as Olanzapine, Quetiapine, Risperidone,
lurasidone, and Aripiprazole.

54. ARIPIPRAZOLE
QUETIAPINE
LURASIDONE

55. REFERENCES
• http://www.amhsjournal.org/article.asp?issn=2321-
4848;year=2018;volume=6;issue=1;spage=81;epage=94;aulast=
Fasipe