This document summarizes information about antidepressant and anti-anxiety drugs. It discusses the classification of major affective disorders like episodal depression and mania. It describes the mechanisms and side effects of different classes of antidepressants including tricyclic antidepressants, selective serotonin reuptake inhibitors, atypical antidepressants, and monoamine oxidase inhibitors. It also discusses anti-anxiety drugs like benzodiazepines and their mechanisms and side effects. The precise causes of affective disorders are still unclear but evidence implicates alterations in neurotransmitter systems like norepinephrine and serotonin.

1. Antidepressant, Anti-anxiety Drugs
Dr. Ahmed Morgan
Junior Psychiatry Doctor
The Brain House Medical Center

3. Classification of Major Affective Disorders

4. Episodal (reactive) Depression
Adverse life events.
Physical illness.
Drugs.
Other psychiatric disorders.

5. Reactive (episodal) Depression
 More than 60% of all depressions.
 Core depressive syndrome: feelings of misery, apathy,
inadequacy, pessimism, anxiety, tension, guilt. Ugliness,
Low self –esteem,
 Bodily complaints

6. • Withdrawn.
• Loss of interest in pleasurable activities.
• Indecisiveness, loss of motivation.
• Retardation of thought and action.
• Sleep disturbance

7. • In severe cases, it is accompanied by hallucinations and delusions.
• Recurrent suicidal ideation, a suicide attempt or a specific suicide
plan.
•significant weight change (without dieting )
•Psychomotor agitation or retardation.

8. 1. Has a genetic component.
2. Depression can be drug-induced.
3. Depression can be drug-repressed.
4. Depression can be treated with drugs.
5. Depression can be treated with
Electroconvulsive Therapy (ECT).

9. Mania
Mania alone is rare (10%) and most frequently cycles with
Major/endogenous depression
(Manic-Depressive Disease, Bipolar Disorder).
Core Symptoms:
➢Characterized by an elevated “high” mood.
➢Talkative, go on-and-on about the things they will do.
➢Increased self-esteem.
➢Auditory hallucinations.
➢Decrease need to sleep. Expensiveness, unnecessary buying.
➢Lack judgment, Supermen

10. • The precise cause of affective disorders remains elusive.
• Evidence implicates alterations in the firing patterns of a
subset of biogenic amines in the CNS,
Norepinephrine (NE) and Serotonin (5-HT).
Activity of NE and 5 -HT systems?.

11. Almost all NE pathways in the brain originate from the cell bodies of neuronal cells
in the locus coereleus in the midbrain, which send their axons diffusely to the
cortex, cerebellum and limbic areas
(hippocampus, amygdala, hypothalamus, thalamus).
➢Mood: -- higher functions performed by the cortex.
➢Cognitive function: -- function of cortex.
➢Drive and motivation: -- function of brainstem
➢Memory and emotion: -- function of the hippocampus and amygdala.
➢Endocrine response: -- function of hypothalamus.

12. Serotonin System
As with the NE system, serotonin neurons located in the
pons and midbrain
(in groups known as raphe nuclei)
send their projections diffusely to the cortex, hippocampus,
amygdala, hypothalamus, thalamus, etc. --same areas
implicated in depression.
This system is also involved in:
• Anxiety.
• Sleep.
• Sexual behavior.
• Temperature regulation.
• CSF production.

15. Blocked by antidepressants
Blocked by
antidepressants

16. Serotonin receptors
■ 5–HT1
■ subtypes
■ 5–HT1A, 5–HT1B, 5–HT1D, 5–HT1E, 5–
HT1F
■ primarily responsible for the therapeutic
(antidepressant) effects of increased
intrasynaptic serotonin
■ 5–HT2
■ subtypes
■ 5–HT2A, 5–HT2B, 5–HT2C
■ primarily responsible for the toxic
effects of increased intrasynaptic
serotonin

17. Serotonin receptors
• Over all 14 types divided in to 1, 2, 3, and 4-7 family
• All are G-protein coupled receptors except 3
• 1- decreases cAMP while 4-7 increase
• 3- ligand gated cation channel

18. Alternative Therapies
No way of a priori knowing which therapy will be
best for a patient.
■ Light Therapy
■ Psychological Treatment
■ ECT (patients with suicidal tendency and for quick action)
■ St. John’s Wort (Plant)

19. Antidepressants
TCAs
TCAs
SSRIs
SSRIs
MAOIs
MAOIs
MAOIs
MAOIs
MAOIs
Venflaxine MAOIs
maprotiline

20. Mechanism of Action
1. Inhibition of MAO enzymes.
(MAOIs).
2. Inhibition of NE and 5-HT reuptake.
(TCAs, SSRIs, Newer TCAs).
3. Prominent alpha blocking and weak 5-HT antagonists.
(Nefazodone, trazodone,)
4. Serotonin and noradrenalin reuptake inhibitor (SNRIs)
(venlafaxine, duloxetine)
5. Noradrenergic and specific serotonergic antidepressants (NaSSA)
(Mirtazapine)
6. Inhibitor of Dopamine and Noradrenalin
(Bupropion)
7. Blockade of pre-synaptic alpha 2 receptors
(Mianserin)
8. Increases rather than inhibiting 5-HT uptake
(Tianeptine, Amineptine)
A
T
Y
P
I
C
A
L

21. MAO ( monoamine oxidase) an enzyme
Two types
• MAO – A
-Peripheral adrenergic nerve endings
-Intestinal mucosa
-Human placenta
-Liver
-Serotonin , Noradrenalin and dopamine
-Inhibited by moclobemide
and clorgyline
■ MAO-B
-brain ( basal ganglia)
-Platelets
-Liver
-Deaminates dopamine
-Inhibeted by selegiline (deprenyl)
Isoniazide, iproniazide, phenelzine, isocarboxazide,tranylcypromine were non selective and
irreversible inhibitors (Hit and run drugs) used previously but not used now due to drug drug and
drug food interactions. Linezolide (new drug against MRSA) Cheese and serotonin syndrome

22. Nonselective MAOIs not favorable
• Cold and Cough medicines contain Ephedrine
(Same result as cheese reaction)
• Levodopa- excitement and hypertension
• Tricyclic antidepressants- excitement, rise in BP, temperature

23. Reversible inhibitor of MAO-A
(RIMAs)
• Moclobemide
• Reversible and selective MAO-A inhibitor
• Short duration of action
• Competitive enzyme inhibition
• Tyramine is able to displace it
• Cheese reaction is less likely
• Devoid of anticholenergic, sedative, cognitive, cardiovascular
effects
• Good for elderly with heart diseases

24. Tricyclic Antidepressants (TCAs)
• Imipramine represents the class (Prototype)
• Inhibit monoamine reuptake
(serotonin and noradrenalin)
• Increase the concentration of Serotonin and NAat synapse
and potentiate the action (therapeutic effects)
• Other receptors acted (Adverse effects)
• Muscarinic- Anticholinergic side effects (dryness etc.) #
• Alpha- alpha blocking actions (postural hypotension etc.) #
• Histamine-Antihistaminic (sedation) #
• Dopamine- antipsychotic (amoxapine, maprotiline)

25. TCAs actions (CNS)
• In Normal person
- Tiredness
- Light-headedness
- Sleepiness
- Difficulty in thinking
- Difficulty in concentration,
- Gait disturbances
- Provoke anxiety
- Unpleasant
■ In Depressed
-Sedation immediately
-Elevation of mood (2-4Weeks)
-Suppresses REM prolongs total
sleep duration

26. TCAs uptake blockade
is not directly responsible for antidepressant action?
• Uptake blockade occurs quickly but antidepressant action occurs after months
• Initially
Pre synaptic alpha 2 and 5-HT1 auto receptors are activated by increased
amount of NA and Serotonin in synaptic cleft resulting in decreased firing
• But on long term
desensitize and down regulation of these receptors and induce adaptive
changes in the number and sensitivity of receptors and amine turnover
leading to enhanced NA and Serotonin transmission required for
antidepressant action.

27. TCAs on other systems
• ANS
•Potent anticholinergic
(dry mouth, blurring of vision,, constipation, urinary hesitancy)
•Weak alpha 1 blocking
(postural hypotension, impairment of ejaculation,)
•H1 antihistaminic
(sedation)
■ CVS
■ Tachycardia
■ Postural hypotension
■ Cardiac arrhythmias (T
wave suppression or inversion)
due to intra ventricular
conduction interference due to
NA and Anti cholinergic actions
Tolerance to Anticholinergic and hypotensive

28. TCAs (Pharmacokinetics)
• Good oral absorption
• Highly bound to Proteins (plasma and tissue)
• Metabolized in liver (oxidation, glucuronide conjugation and CYP2D6,
CYP3A4, CYP1A2
• Many active metabolites may be produced
• Mostly can be given once a day (at bed)
• Have Therapeutic Window phenomenon (50-200ng/ml of
imipramin)

29. TCAs Adverse effects
• Anticholinergic- dry moth, bad taste, constipation, epigastric fullness,
urinary retention (more common in elderly male), blurred vision,
palpitation
• Sedation, mental confusion, weakness
• Increased appetite and weight
• Sweating, fine tremors
• Precipitation of seizures
• Postural hypotension
• Cardiac arrhythmias
• Rashes and jaundice

30. TCAs (Acute Poisoning)
• Usually suicidal attempt
• Presents as
• Excitement
• delirium,
• Anticholinergic symptoms like atropine poisoning
• Muscle spasm
• Convulsions
• Respiratory depression
• Coma
■ Treatment
■ Gastric lavage
■ I.V. line
■ Oxygen
■ Maintenance of BP and
Temperature
■ Diazepam iv
■ Propranolol / lignocain

31. TCAs (Interactions)
• Potentiation of sympathomimetics (direct acting)
• Reduce action of sympathomimetics (indirect acting)
• Reduce antihypertensive action of guanethidine and
clonidine ( by preventing their transport in to neurons)
• Potentiate other CNS sedatives
• SSRIs inhibit metabolism of TCAs
• With MAO inhibitors dangerous hypertensive crisis with excitement and
hallucinations
• Retard the absorption of other drugs
• Phenytoin, phenylbutazone, chlorpromazine, aspirin, displace TCAs and
produce toxicity
• Phenobarbitone induce metabolism and inhibit the effect of the drug

32. Miscellaneous
• Amoxapine
• Tetra cyclic compound
• Blocks D2 reuptake also
• Has mixed antidepressant and neuroleptic effects
• Good for psychotic depression
■ Reboxetine
■ Selective NA
reuptake blocker
■ Weak action on 5-
HT mechanism
■ Anticholinergic
effects are minimal

33. Selective Serotonin Reuptake Inhibitors (SSRIs)
• Limitations of TCAs
• Anticholinergic effects
• Alpha blocking action
• Cardio toxicity
• Sedation, seizures ppt
• Low safety margin
• Weight gain
• Therapeutic window
• Overdose poisoning common
• Lag of 1 month period
• Incomplete response to Tt
■ Answers may be given by SSRIs
■ Selectively inhibit membrane associated
SERT (serotonin transporter)
■ More tolerability and better acceptability
■ Used in depression as well as in OCD,
phobias
■ No sedation, No seizure ppt
■ No alpha blocking action
■ Less chances of arrhythmia
■ No weight gain
■ Now 1st choice for OCD, Panic disorders,
Social Phobia, Eating disorders,
Premenstrual syndrome, Post traumatic
stress

34. Important points
➢TCAs have slightly more efficacy
➢Some patients not responding to TCAs may respond to SSRIs,
➢SSRIs preferred in prophylaxis of recurrent depression
➢In severe depression TCAs appear to be more efficacious

35. Individual compounds
• Fluoxetine
• Prototype of SSRIs
• Longest acting
■ Fluvoxamine
■ Short acting
■ Commonly used in
indoor patients
■ Paroxetine
■ Short acting
■ More GI side effects
■ Sertraline
■ Less chances of drug
interactions due to low
potency to cause
cytochrome enzyme
depression
❑Citalopram
•Similar to sertraline but should be
avoided in patients attempting suicide
❑Escitalopram
•Active enantiomer of citalopram
side effects are less

36. SSRIs
• Side effects
• Gastric upset
• Nausea
• Interfere with ejaculation
• Nervousness
• Restlessness
• Insomnia
• Anorexia
• Headache
• Diarrhea
• Epistaxis
• Ecchymosis
■ Others
■ Inhibit cytochrome enzymes and
elevate the plasma level of other drugs
■ Other serotonergic drug ( MAOIs)
is taken may precipitate Serotonin
Syndrome manifesting as agitation,
restlessness, sweating, twitching,
convulsions

37. Atypical Antidepressants
• Mianserin
• Unique not inhibit NA and 5-HT uptake
• Blocks pre-synaptic alpha 2 receptors increases release and turnover of
NA
• Antagonist at serotonin 2, 1c, and H1 receptors
• Has sedative effect
• Damages liver and bone marrow (Reserve drug)

38. Atypical Antidepressants
• Tianeptine / and Amineptine
• Increases rather inhibiting 5-HT uptake
• Neither sedative nor stimulant
• Effective in anxiodepressive states
■ Venlafaxine / Duloxetine
■ SNRI selective in action
■ Faster onset of action
■ Increases BP
■ Duloxetine increases uretheral tone
used in urinary incontinence ( over
active bladder)
■ Mirtazapine (NaSSA)
■ Noradrenergic and specific
serotonergic antidepressant
■ Blocks alpha 2 auto receptor (on
NA neuron) and hetero- (on 5-
HT neuron) receptors increasing
both NA and serotonin release.
■ Bupropion
■ Inhibits DA and NA uptake
has excitant effect
■ Used to reduce smoking

39. Antidepressant uses
• Depression (ECT may be needed in severely depressed and
patients having suicidal tendency)
• Bipolar affective disorders TCAs and lithium or SSRIs with lithium or
valporate/ lamotrigine
• SSRIs with atypical antipsychotic in psychotic depression
• Obsessive compulsive disorders (SSRI and Clomipramine)
• Eating disorders

40. • Anxiety disorders
• Neuropathic pain
• Attention deficit hyperactivity disorder in children
• Enuresis- (Imipramine 25mg at night)
• Overactive bladder (stress incontinence)
• Migraine prophylaxis
• Pruritus (Topical doxepin)

41. Anti-anxiety Drugs
• Anxiety - emotional state
- Unpleasant
- Associated with uneasiness
- Discomfort
- Fear
- Undefined threat
- Fear about future

42. Anti-anxiety Drugs
• Drugs producing restful state of mind without interfering with
normal mental or physical functions.
• Have no effect on thought control
• Don’t produce extra pyramidal side effects
• Can Produce physical dependence
• May Have abuse potential
• Don’t selectively block conditioned avoidance response in
animals
• Have anticonvulsant activity

43. Anti-anxiety Drugs
• Benzodiazepine
• Diazepam
• Chlordiazepoxide
• Oxazepam
• Lorazepam
• Alprazolam
■ Azapirones
■ Buspirone
■ Gepirone
■ Ispapirone
■ Others
■ Beta blocker- Propranolol
■ Antihistaminics- Hydroxyzine
■ SSRIs and other
antidepressant drugs
PHO/BIG/DOCLA

44. Benzodiazepines
• Relieve anxiety at low dose ( higher dose induce sleep and
impair performance )
• Selective taming effect
• More selective to limbic system
• Have low side effects in Antianxiety dose
• Lorazapam and clonazepam IM for psychotic and manic
patients
• Act by facilitating GABAergic transmission

45. Benzodiazepines
• Adverse effects
• Sedation
• Light headedness
• Psychomotor impairment
• Cognitive impairment
• Vertigo
• Confusional state
• Increased weight
• Impaired sexual functions
• Potential to produce dependence
• All are almost similar selection is empirical

46. Benzodiazepines (Individual drugs)
• Chlordiazepoxide
• First BZD
• Long lasting effect
• Chronic anxiety
■ Diazepam
■ Has two phase of metabolism
■ Broken in to active metabolites
■ Long duration of action
■ Oxazepam
■ Polar compound
■ Penetration In brain is slow
■ No active metabolite
■ Used in short lasting anxiety state
■ Lorazepam
■ Less lipid soluble
■ Slow entry in brain
■ No active metabolite
■ IM

47. Buspirone
• Does not produce sedation, cognitive impairment,
• Does not interact with BZD receptor or modify GABAergic transmission
• No tolerance
• No physical dependence
• No muscle relaxant
• No anticonvulsant property

48. Buspirone
• Relieves mild to moderate generalized anxiety
• Effects develop slowly (not used for acute)
• Partial agonist on 5HT1A (pre-synaptic) and antagonist on 5HT
postsynaptic receptors
• Presynaptic auto-receptors stimulated leading to reduced activity of
dorsal raphe serotonergic neurones
• Also has weak D2 blocking effect

49. • Hydroxyzine
• H1 antihistaminic
• Sedative, anti -emetic and spasmolytic
• Anti - Pruritus
■ Propranolol
■ Reduces sympathetic
symptoms like rise in BP,
Tremors, sweating etc.
■ Performance or situational
anxiety
(like examination fear, social
phobia, public lecture)

50. Thanks