The document discusses mania, a state characterized by high energy and mood elevation, often associated with bipolar disorder. It outlines the stages of mania, possible causes, pathophysiology, symptoms, and treatment options including pharmacological, psychosocial treatments, and electroconvulsive therapy. The document also mentions drugs in development for bipolar disorder and animal models used for research.

1. MANIA
Presented by:
A . Ruchitha Sai
M Pharm,1st year
Department of Pharmacology

2. Contents
 Introduction
 Definition of mania
 Pathophysiology of mania
 Drugs to treat mania
 Management of mania
 Drugs in pipeline
 Animal models

3. MANIA
 Mania is derived from the Greek word meaning “Madness and Frenzy”.
 The term mania describe a state of mind characterised by high energy,
excitement, and euphoria over a sustained period of time. It’s an extreme
change in mood and cognition that can interfere with school, work, or
home life.
 Mania is also the main feature of bipolar disorder

4. Definition
 Mania is an alteration in mood that is expressed by
feelings of elation, inflated, self esteem, extreme
happiness, hyperactivity, accelerated thinking and
speaking.
 In simple terms, mania makes abnormally energised
both physically and mentally

5. Stages of mania
 Stage 1 :- Hypomania
it is a mild form of mania that may not be recognised as a significant symptom
by those around the person experiencing it. While hypomania affects sleep and activity and may
lead to increased impulsivity. it usually doesn’t require hospitalization or cause psychosis.
 Stage 2 :- Acute Mania
During acute mania, an individual may experience increased impulsivity that
causes them to act in a way that is inappropriate or promiscuous. People with acute mania will
also likely have increased energy, little to no sleep and talk very quickly, often jump from topic to
topic. they may experience some symptoms of psychosis.

6. Cont…
 Stage 3 :- Delirious mania
it is the most severe of the three stages of mania. Its symptoms are similar to acute
mania. Its symptoms are similar to acute mania, with addition of delirium. Delirium is temporary
confusion and a decreased ability or inability to connect with reality. This stage can also involve a
combination of mania and psychosis. Because delirious mania can be profoundly disorientation,
many people experiencing it need to be hospitalized to prevent injury to themselves or other

7. Causes of mania
 There isn’t one single or clear cut reason that someone may become manic. It seems to be a
combination of long-term and short- term factors,which differs from person to person
 Possible causes of mania include
• High levels of stress
• Change or lack of sleep
• Seasonal changes, eg; some people likely to experience mania in spring
• significant changes in life
• child birth (postpartum psychosis)
• Family history – if a family member who experiences bipolar moods you are more likely to
experience mania
• Drugs eg; steroids, levodopa, other dopaminergic agents and hallucinogens

8. Pathogenesis


9. Pathophysiology:
 According to biogenic amine hypothesis, mood disorder results from abnormalities
in serotonin, norepinephrine or dopamine neurotransmission
 Serotoninergic fibres projecting from the raphei nuclei in the midbrain to limbic
structures are important in regulating mood
 The serotoninergic system is activated during behavioural arousal and increase
cortical awareness of emotional reactions to environmental events
 Impaired serotonin neurotransmission can decrease emotional activation leads to
mania

10. Cont…
 Nor adrenergic fibers that project from the locus ceruleus to the cerebral
cortex can also play role in depression.

11. Signs and symptoms
 Elevated expansive or irritable mood
 Stages of elevated mood
• Euphoria(stage1):increased sense of psychological well being and happiness
• Elation(stage2): moderate elevation of mood with increased psychomotor activity
• Exalation(stage3):intense elevation of mood with delusion of grandeur
• Ecstasy (stage4):severe elevation of mood intense sense of blissfulness

12. Cont…
Behavioural symptoms
• Aggressiveness
• Hyperactivity
• Increased motor activity
• Irresponsibility
• Irritability
• Argumentativeness
• Increased social activity
• Sexual hyperactivity

13. Cont…
Physiological symptoms
• Dehydration
• Little need of sleep
• Weight loss
• Inadequate nutrition

14. Treatment modalities
 There are basically 3 types of treatment modalities:
• Pharmacological treatment
• Psycho- social treatments
• ECT
Pharmacological treatment
 Mood stabilizer’s:
Lithium-drug of choice
Carbamazepine
Sodium valproate

15. Lithium carbonate
 Lithium a small monovalent cation, was found to be effective in
bipolar manic depressive illness.
 It mainly prevent the mood swings.
 A close control of serum concentration is required for safe and
effective use of lithium due to its therapeutic index.
 The desired therapeutic serum levels of lithium achieved in 8
days.
 Dose : Adults-300mg oral dose thrice a day
elders- 600mg

16. Mechanism of action
Mechanism of action
 The exact mechanism of action of lithium is unknown but the possible mechanism
of action may be due to the following effects,
1. Effects of electrolytes and ion transport: Lithium acts partially by replacing the
sodium ions in the body. this leads to changes in ionic fluxes across the brain cells.
2. Effects of neurotransmitter: lithium decreases the release and action of
neurotransmitter, such as dopamine and noradrenaline in the brain.
3. Effects of secondary messengers and intracellular enzymes.

17. Mechanism of action
• When neurotransmitter bind to Gq protein coupled
receptor , phospholipase-C (PLC) gets stimulated.
Activated PLC in turn hydrolyses PIP2 to IP3 and DAG.
IP3 is sequentially inactivated to IP1, IP2 and inositol.
This inositol acts as precursor for PIP and
PIP2(membrane phosphoinositides) which are the
sources of IP3 and DAG.
• In mania, these neuronal circuits becomes hyperactive
which results in more IP3 and DAG production. Lithium
selectively inhibits the hydrolysis of IP2 to IP1 and IP1 to
inositol. As result, the levels of inositol decrease and
this inturn decrease IP3 and DAG levels.

18. • Pharmacokinetics:
Lithium is slowly but readily absorbed from the gastrointestinal tract. Intially lithium
gets distributed in intracellular fluid, then in intracellular fluid and finally is slowly
enters into CNS.
The apparent volume of distribution of lithium is 0.5 L/kg (intial) and 0.8 L/kg at steady
state.
Lithium is not metabolised in the body and is almost completely excreted in urine
(96%), a very small amount of lithium excreted in saliva and sweat (4%).
The plasma half life of lithium is 20 hours.
The desired therapeutic plasma concentration of lithium is 0.6-1.4mEq/L, and toxicity
occur when it exceeds 1.5 mEq/L.
.

19. Toxicity
mild toxic effects include nausea, vomiting, diarrhoea, tremors, ataxia, blurred vision,
oedema, polyuria and allergy.
Chronic effects are seizures, ECG changes, hypothyroidism, coma and leucocytosis.
Therapeutic uses:
Acute mania : in acute mania episodes, lithium is administered in combination with atypical
antipsychotics(eg ; Olanzapine)
Alcohol dependence: As lithium reduces alcohol consumptions , it is used to treat alcohol withdrawal.
Leukopenia and agranulocytes: As lithium increases leukocytes count it is used in the treatment of
leukopenia and agranulocytosis, which are induced by cancer chemotherapy

20. Alternative to lithium:
Carbamazepine
It is used in the prophylaxis and treatment of acute mania. Combination of lithium with carbamazepine is
effective in treating patients with rapid cycling of mood or behavioural states.
 Mechanism of action
Reduces the influx of sodium ions into neurons, increases the serotonergic and dopaminergic post synaptic
activity and blocks the adenosine receptors
 Adverse effects
Dizziness, vertigo, sedation, ataxia, hypersensitivity reactions
 Therapeutic use
Prophylaxis and treatment of acute maniac episodes
 Dose
200mg orally twice a day

21. Psycho-Social treatment
 Family therapy
 Cognitive therapy
 Individual psychotherapy
 Group therapy
Electro- convulsive therapy
 ECT can also be used for acute manic excitement, if not adequately responding to
antipsychotics and lithium

22. Management of mania

23. Drugs in pipeline
 The drugs in late stage pipeline will enter the bipolar disorder market prior
to 2030 they are
 Fanapt (iloperiodone)- Vanda pharmaceuticals
 Dexmedetomidine- Bioxcel therapeutics
 RP5063 – Reviva pharmaceuticals

24. Animal models of mania
 These are 4 major features of mania that could be modelled:
Hyperactivity, Elation, Irritability, Insomnia
Sleep deprivation model
• The rat is kept on a small platform surrounded by water for 72h
• At the end of the period, it returns to its home cage and doesn’t ready to fall asleep
• Symptoms presented during this time: insomnia , hyperactivity, aggressiveness,
hypersexuality.
• Benefits: effective, economic, no invasive manipulation
Drug screening test
In this test latency to sleep and motor activity are measured.

26. Reference
 A textbook of pharmacology I – Dr.Shaik Harun Rasheed
 Brenner and stevens pharmacology- George M. Brenner, Craig W. Stevens
 Internet source