Depression

drugs used in depression

1. DEPRESSION
&
ANTIDEPRESSANTS

2. WHO Definition
“Depression is a common mental disorder characterized by
sadness, loss of interest or pleasure, feelings of guilt or low self-
worth, disturbed sleep or appetite, feelings of tiredness, and poor
concentration”

3. Dsm 5 criteria for diagnosis of depression=presence of five out of nine symptoms, most of the
day, nearly every day for at least 2 weeks.

4. •Major depressive disorder is also known as major depression or unipolar
depressive disorder
•Common disorder, resulting in significant disability, morbidity, and high
mortality
•In majority of cases it is a recurrent disorder and only few patients experience
a single episode of major depression
•Recovery typically begins within 3 months of onset (2 in 5 patients) and
within 1 year (4 in in 5 patients)
Major Depressive Disorder (MDD)

6. Genetic: Heritability is probably 40% for MDD. First-degree relatives of depressed individuals are 2-4
times likely to develop MDD as compared to the general population.
Changes in Brain: Patients with depression develop changes in the brain structure and possible
abnormalities of the neurotransmitter systems.
Life events: Traumatic events during childhood and stressful life events in adulthood are strongly
associated with the onset of MDD
Drug and alcohol abuse: Alcoholism and substance abuse such as cocaine, amphetamine, narcotics etc.
(about 30% of individuals with substance abuse problems) predisposes to MDD.
Neuroticism:, in case of negative life events, individuals who have a tendency to make negative
attributions about the causes of those events, about themselves, and about future consequences may be
more likely to develop depression
Other medical conditions: Chronic medical conditions including diabetes, cardiovascular disease, morbid
obesity, sleep disorders, anxiety, chronic pain, and attention-deficit hyperactivity disorder (ADHD) increase
the risk for MDD

7. PATHOPHYSIOLOGY
1) Monoamine deficiency theory
Depletion of neurotransmitters in the CNS
- serotonin
- nor adrenaline
- dopamine
2) Neuroendocrine abnormalities
Reduced hippocampal size
Increased cortisol and CRH secretions
Increased adrenal size
3) Neurotrophic hypothesis of depression
Decreased levels of Brain Derived Neurotropic Factor (BDNF)

14. Neurotrophic hypothesis of depression &
Brain Derived Neurotropic Factor (BDNF)
BDNF promotes the growth and development of immature
neurons, including monoaminergic neurons, enhances the
survival and function of adult neurons, and helps maintain
synaptic connections.
Decreased levels of BDNF may contribute to cell atrophy
& even cause cell loss. If monoamine levels are low, then
BDNF levels may correspondingly be low.
Increasing monoamines can increase the availability of
BDNF by initiating signal transduction cascades that
lead to its release.

16. ANTIDEPRESSANTS CLASSIFICATION

1
ST
generation
 Tricyclic Antidepressants-Imipramine,
amitriptyline, clomipramine, doxepin
 MAO inhibitors-
•Reversible-moclobomide, clorgyline.
•Irreversible-phenelzine, tranylcypromine,
isocarboxazid.
 2
nd
generation
 Selective Serrotonin Reuptake
Inhibitors (SSRIs)- fluoxetine,
fluvoxamine, sertraline, paroxetine,
citalopram, escitalopram
 Serotonin Norepinephrine Reuptake
Inhibitors (SNRIs)- venlafaxine,
desvenlafaxine,
Atypical Antidepressants

17. Tricyclic Antidepressants (TCAs)
The tricyclic antidepressants were so named because
their chemical structure contains three rings.
Most of the TCAs block SERT & NET, increasing
the monoamine levels & contributing to the antidepressant
Effect
TCAs are very effective antidepressants but the major
limitations is their unwanted side effects

18. Mechanism
of
action

20. SIDE
EFFECTS

21. ECG-T wave suppression/inversion
interference with intraventricular conduction
NA potentiation+ Ach blocking + direct myocardial depression

22. TCAs ADVERSE EFFECTS
1.Anticholinergic: dry mouth, urinary retention, blurred vision, palpitations
2.Antihistaminic: sedation, confusion
3.Postural hypotension, tachycardia
4.Cardiac arrhythmias
5.Increased appetite and weight gain
6.Mania
7.Lowers seizure threshold
8.Sweating and fine tremors
9.Rashes and jaundice due to hypersensitivity (rare)

23. Advantages of SSRIs over TCAs
To overcome the shortcomings of TCAs newer drugs such as SSRIs were developed
Major advantages of SSRI were
1.Negligible anticholinergic side effects
2.They produce little or no sedation at all
3.Postural hypotension do not occur
4.Low CVS side effects, no arrhythmias
5.No effect on cognition/ psychomotor functions
6.Do not lower seizure threshold
7.Safer in overdose
8.Faster acting than TCAs
9.No complaints of weight gain
10.Better compliance

24. Selective Serrotonin Reuptake Inhibitors (SSRIs)
•SSRIs are now considered to be the first line of drugs in the treatment of depression
•All SSRIs inhibit the serotonin transporter and block the reuptake of serotonin into the
neuron, hence increasing the levels of serotonin at the synapse.

25. Mechanism of action of SSRIs

32. Uses of SSRIs
SSRIs are 1
st
choice drugs in the treatment of
OCD
Panic disorders
PTSD
Premenstrual syndrome
Social phobia
Eating disorders
Also used in
•Kleptomania
•Anxiety disorders
•Compulsive buying
•Body dysmorphic disorders

33. SSRI SIDE EFFECTS
CNS S/E
GIT S/E
SEXUAL S/E

34. Akathisia,
dystonia

35. GIT Side effects

36. Anorgasmia

37. ATYPICAL ANTIDEPRESSANTS
•Lesser side effects like sedation/anticholinergic side effects
•Safe in overdose
•Effective in patients not responding to TCAs

38. Serotonin partial agonist/reuptake inhibitors (SPARIs)
Vilazodone is a partial agonist at the 5HT1A receptor and also
inhibits serotonin reuptake; thus, it is referred to as a serotonin
partial agonist/reuptake inhibitor (SPARI).
5HT1A immediate partial agonist actions are theoretically additive or
synergistic with simultaneous SERT inhibition, since this leads
to faster and more robust actions at 5HT1A somatodendritic
Autoreceptors than with SERT inhibition alone, including
their downregulation.
Low sexual dysfunction is shown for vilazodone in placebo-controlled
trials

40. Serotonin–norepinephrine reuptake inhibitors
(SNRIs)
d
DULOXETINE
MILNACIPRAN

41. These are similar to TCAs without the blocking action of Alpha, H1, Muscarinic receptors.
Venlafaxine does not produce the usual side effects of TCAs, increases BP rather than depressing it &
are safer in overdose.
Side effects are nausea, sweating, anxiety, dizziness and impotence.
Desvenlafaxine is active substrate of venlafaxine. It has more potent NET blocking action.
Used in perimenopausal women develop hot flushes and other vasomotor symptoms (VMS), including
night sweats, insomnia, and even depression
Duloxetine has established efficacy not only in depression but also in patients with chronic painful physical
symptoms of depression. All sorts of pain are improved by duloxetine like diabetic peripheral
neuropathic pain,fibromyalgia, chronic musculoskeletal pain associated with osteoarthritis and
low back problems.
Milncipran has more potent NET inhibition. It is used for treating fibromyalgia.

42. Norepinephrine–dopamine reuptake inhibitors (NDRIs): bupropion
Bupropion is helpful in patients with “reduced positive affect”
It helps in improvement in the symptoms of loss of happiness,
joy, interest, pleasure, energy, enthusiasm, alertness, and
self-confidence.
It acts as a non competitive antagonist at nAch receptor
Hence useful in smoking cessation.
BUPRION

43. Noradrenergic and specific serotonergic
antidepressant (NaSSA)

44. Blocks presynaptic alpha 2 autoreceptors and heteroreceptors leading to increased release of
NE & Serotonin.
5HT3 antagonists increase norepinephrine and acetylcholine release. It also decreases nausea
And GIT S/E associated with increased levels of serotonin.
5HT2A & 5HT2c antagonists increase release of NE & DA in prefrontal cortex
H1 receptor blocking can reduce insomnia at night and anxiety during day
But also causes sedation, drowsiness & weight gain
Mianserin causes blood dyscrasias and liver dysfunction and can cause seizures in overdose
which has limited its use.

45. Serotonin antagonist and reuptake inhibitor (SARI) : Trazodone

47. Priapism has been reported in few cases taking trazodone leading to impotence.
Sedation occurs due to H1 blocking action.
Postural hypotension due to alpha 1 blocking action
Nefadazone is no longer used due to its hepatotoxicity.

48. MAO Inhibitors
Monoamine oxidase are the enzymes produced by the mitochondria which destroys the
monoamines by oxidative deamination.

49. Mechanism of action

50. Interactions with MAO inhibitors
•Cheese reaction: if certain varieties of cheese, beer, wines, pickled meat, fish & yeast
extracts are ingested along with MAOI. ~> displaces large amount of NA~>
HYPERTENSIVE CRISIS.
Phentolamine is the DOC.
•Cold and cough medications: contains ephedrine, phenylephrine & other
sympathomimetics. Can cause hypertensive crisis.
•Serotonergic drugs: serotonin syndrome-hyperthermia, restlessness, rigidity, tremor,
seizures, coma
•Reserpine, guanethidine, TCA: rise in BP & body temperature, excitement can occur
•Barbiturates, alcohol, opiods, antihistamines: action is intensified and prolonged.

51. CHEESE REACTION

52. CHEESE REACTION

55. SEROTONIN SYNDROME
C/F-hyperthermia, restlessness, rigidity, tremor, seizures, coma
Combined with SSRIs

56. Uses of Antidepressants
Depression
Obsessive compulsive and phobic states- SSRIs are DOC
Anxiety disorders, panic disorders, PTSD- SSRIs
Neuropathic pain- amitriptyline
ADHD- atomoxetine
Nocturnal enuresis- imipramine
Pruritis- topical doxepin
Migraine- amitriptyline
Fibromyalgia, chronic pain syndrome- SNRIs

57. THANK YOU