The document discusses affective disorders, specifically unipolar and bipolar disorders, emphasizing depression's characteristics, causes, and treatment methods. It outlines various classes of antidepressants, including tricyclics, SSRIs, SNRIs, and MAO inhibitors, detailing their mechanisms of action, side effects, and contraindications. The prevalence and symptomatic differences between reactive and endogenous depression are also highlighted, noting that effective treatment is critical for this mood disorder.

1. Antidepressants
Prof. Amol B. Deore
Department of Pharmacology
MVP’s Institute of Pharmaceutical Sciences, Nashik

2. • AFFECTIVE DISORDERS
• Affective disorders involve a disturbance of mood (cognitive आकलनविषयक /
emotional भािवनक symptoms) associated with changes in behavior, energy,
appetite and sleep (biological symptoms).
• Affective disorders can be thought of as pathological extremes of the normal
continuum of human moods, from extreme excitement (उत्साह)and mania
(उन्माद) to severe depressive states.
• Cognition is defined as 'the mental action or process of acquiring knowledge
and understanding through thought, experience, and the senses.
• (Cognition →Relevance/ Reasonable/ empirical.)

3. There are two types of affective disorder:
• Unipolar affective disorders → Depression
• Bipolar affective disorders (दोन टोकाांचा आजार) →Both depression
and mania

4. euphoria means
अत्यानांदाची अवस्था

5. The Monoamine Theory
• The etiology of major depressive disorders is not clear. Genetic,
environmental and neurochemical influences have all been
examined as possible etiological factors.
• The most widely accepted neurochemical explanation of
endogenous depression involves the monoamines (noradrenaline;
serotonin (5-HT); dopamine).
• The monoamine theory stated that depression resulted from a low
levels of these neurotransmitter, whereas conversely mania was
caused by an excess levels of these neurotransmitter in brain .

6. Noradrenaline, is a neurotransmitter of the brain that plays an essential role in the
regulation of arousal, attention, cognitive function, and stress reactions.
Serotonin plays a key role in such body functions as mood, sleep, digestion, nausea,
wound healing, bone health, blood clotting and sexual desire.
Dopamine is a type of neurotransmitter and hormone. It plays a role in many important
body functions, including movement, memory and pleasurable reward and motivation.
High or low levels of dopamine are associated with several mental health and neurological
diseases

7. Unipolar affective disorders
•A common unipolar affective disorder is depression,
which is characterized by misery, malaise, despair,
guilt, apathy (उदासीनता), indecisiveness (अननर्णय),
low energy and fatigue, changes in sleeping pattern,
loss of appetite and suicidal thoughts.
•Attempts have been made to classify types of
depression as either ‘reactive’ or ‘endogenous’ in
origin.

8. • Reactive depression is where there is a clear psychological cause, e.g.
bereavement. It involves less-severe symptoms and less likelihood of
biological disturbance.
• It affects 3–10% of the population, with the incidence increasing with
age, and it is more common in females.
• Endogenous depression is where there is no clear cause and more
severe symptoms, e.g. suicidal thoughts, and a greater likelihood of
biological disturbance, e.g. insomnia, anorexia.
• It affects1%of the population, usually starting in early adulthood, and
affecting both sexes equally.

10. Depression
• Depression is a mood disorder that causes a persistent
feeling of sadness and loss of interest.
• Also called major depressive disorder or clinical
depression, it affects how you feel, think and behave
and can lead to a variety of emotional and physical
problems.
• You may have trouble doing normal day-to-day
activities, and sometimes you may feel as if life isn't
worth living.

11. Treatment of unipolar depressive disorders
(depression)
• Antidepressants are a type of medicine used to treat clinical
depression.
• The major classes of drug that are used to treat depression, and
their mechanisms of action, are summarized in next slides.

12. Classification of antidepressants

14. Tricyclic antidepressants (TCAs and related drugs)
• Examples of TCAs and related drugs include amitriptyline,
imipramine, and lofepramine.
• Mechanism of action—
• TCAs act by blocking serotonin (5-HT) and noradrenaline
uptake into the presynaptic terminal from the synaptic cleft
(Figure).
• Thereby increase the levels of serotonin and noradrenaline in
brain.
• They also have a certain affinity for H1 and muscarinic
receptors, and for alpha 1- and alpha-2 adrenergic receptors.

15. Adverse effects—
• Although TCAs are an effective therapy for depression, their
adverse effects can reduce patient compliance and acceptability.
• Side-effects include:
• Muscarinic blocking effects such as a dry mouth, blurred vision,
constipation a-Adrenergic blocking effects causing postural
hypotension
• Noradrenaline uptake block in the heart, increasing the risk of
arrhythmias
• Histamine-blocking effects leading to sedation
• Weight gain.

16. Contraindications—
• TCAs and related drugs should not be used in:
• Recent myocardial infarction or arrhythmias (especially
heart block) since TCAs increase the risk of conduction
abnormalities
• Manic phase
• Severe liver disease
• Epilepsy, where TCAs lower the seizure threshold
• Patients taking other anticholinergic drugs, alcohol and
adrenaline as TCAs potentiate the effects of these.

17. Selective serotonin reuptake
inhibitors (SSRIs)
•SSRIs are the most recently introduced class of
antidepressant agent. Fluoxetine is an SSRI.
Other examples include citalopram,
fluvoxamine, paroxetine and sertraline.

18. Mechanism of action—
•SSRIs act with a high specificity for potent
inhibition of serotonin reuptake into nerve
terminals from the synaptic cleft, while
having only minimal effects on
noradrenaline uptake

19. Mechanism of action—
•SSRIs act with a high specificity for potent inhibition
of serotonin reuptake into nerve terminals from the
synaptic cleft, while having only minimal effects on
noradrenaline uptake (see Fig. 5.8).
•They block serotonin transporters.

20. Therapeutic notes
•SSRIs have a similar efficacy to that of TCAs.
•It is their clinical advantages and lack of side-
effects that have led to their popularity. SSRIs
are now the most widely prescribed
antidepressants.

21. Serotonin-noradrenaline reuptake inhibitors
• Venlafaxine is the most commonly used serotonin-
noradrenaline reuptake inhibitor(SNRI)-type antidepressant.
• Mechanism of action—SNRIs cause potentiation of
neurotransmitter activity in the CNS, by blocking the
norepinephrine and serotonin reuptake transporter.
• Contraindications— The drug interactions of SNRIs are
much like those of SSRIs; however, extra care must be taken
with hypertensive patients as venlafaxine raises blood
pressure.

22. MAO inhibitors
•Examples of irreversible MAO inhibitors
include phenelzine, tranylcypromine and
isocarboxazid, and an example of reversible
inhibitors of MAOA (RIMAs) is moclobemide.

23. Mechanism of action—
• MAO inhibitors block the action of MAOA and MAOB, which
are neuron enzymes that metabolize the monoamines
(noradrenaline, 5-HT and dopamine) (see Figure).
• MAO has two main isoforms, MAOA and MAOB. Inhibition of
the MAOA form correlates best with antidepressant efficacy.
• Both nonselective irreversible blockers of MAOA and MAOB,
and drugs that reversibly inhibit MAOA are available.

24. • These are the drugs which inhibit the action of MAO enzyme which is
involved in the metabolism of monoamine neurotransmitters (NA,
Adrenaline, Dopamine and Serotonin) and thus increase the availability of
these neurotransmitters in the brain, thereby elevate the mood.
• Deficiency of these monoamine neurotransmitters in mesolimbic system
of brain produces mental depression.
• MAO was found to exist in two forms: MAO-A and MAO-B.
• MAO-A preferentially metabolises NA, Dopamine and Serotonin.
• MAO-B preferentially metabolises Dopamine and Phenylethylamine.

25. • Non-selective MAO inhibitors produce irreversible inhibition of both
MAO-A and MOA-B.
• Thereby increase the concentrations of NA, adrenaline, serotonin and
dopamine in the brain. MAO inhibition produces feeling of well-being
and increase in motor activity.

26. • Tyramine is an amino acid which is utilized for synthesis of
catecholamines. Catecholamines help regulate blood pressure.
• Tyramine present naturally in the body and also found in cheese,
chocolates, citrus fruits, chicken liver, yeast, dairy milk products, red
wines etc.
• Monoamine oxidase enzyme promote metabolism of tyramine in the
body whereas Monoamine oxidase inhibitors (MAOIs) block
monoamine oxidase enzyme.
• Blocking this enzyme helps relieve depression by raising the levels of
catecholamines (NA, adrenaline, dopamine) and serotonin in the brain.

27. • If MAO inhibitors and high-tyramine rich food taken simultaneously
then tyramine can quickly reach dangerous levels. This can cause a
serious hypertensive crisis (Alpha and Beta adrenergic action) and
require emergency treatment.
• Hypertensive crisis include severe hypertension, cardiac arrhythmia,
cerebral hemorrhage etc.
• Therefore avoid taking MAO inhibitor therapy with consumption of
dairy products as well as red meat.

28. Adverse drug reactions MAO inhibitors
• MAO inhibitors are not specific, and they reduce the
metabolism of barbiturates, opioids and alcohol. Side-
effects include CNS stimulation causing excitement and
tremor, sympathetic blockade causing postural hypotension,
and muscarinic blockade causing a dry mouth and blurred
vision.
• Phenelzine can be hepatotoxic.