ANTIMANIC

DRUGS
Dr.Ramya
 Mood Affective Disorders
• Change in mood state. May manifest as
• MANIA : Elation or Irritable mood , Reduced sleep ,
Hyperactivity , Uncontrollable thought and speech ,
may be associated with Reckless or Violent
behaviour
• DEPRESSION : Sadness , Loss of interest and
pleasure , worthless , Guilt , Physical & Mental
slowing , Melancholia , Self destruction ideation
• Unipolar / Bipolar
 ANTIMANIC DRUGS
LITHIUM CARBONATE :
• Monovalent cation
• Discovered in 1949 as sedative drug
• Used as Mood stabilizer in manic episode
MOA:
Acts on G-protein coupled receptor &
inhibits the synthesis of second
messenger IP3 & DAG
ACTIONS:
CNS:
• No acute effects
• Neither sedative nor euphoriant
• On prolonged administration : It acts as mood
stabiliser in bipolar disorder
• In Mania : gradually suppress the episode in 1-2
weeks. Continued treatment prevents cyclic mood
changes. Reduced sleep is normalised
OTHER ACTIONS :
• Diabetes insipidus like state
• Insulin like action
• Leukocyte count is increased
• Inhibits release of thyroid hormones
PHARMACOKINETICS:
• Slowly but well absorbed orally
• Neither protein bound nor metabolised
• Excreted in urine , saliva , sweat , kidney handles
Li+ in the same way as Na+sodium depletion
increases Li+ toxicity
• Low therapeutic index  hence TDM is necessary
ADR:
• Nausea , vomiting , & Mild diarrhoea
• Thirst & polyuria
• Fine tremors
• CNS Toxicity : Coarse tremors , giddiness , ataxia ,
motor incoordination , nystagmus , mental
confusion , slurred speech , hyper-reflexia
• Overdose symptoms : In acute intoxication , these
symptoms progress to muscle twitches ,
drowsiness, delirium ,coma , & convulsions
• Vomiting , severe diarrhoea, albuminuria ,
hypotension , & cardiac arrythmias
• On long term use : Renal diabetes insipidus &
weight gain.
• Goitre : interference with release of thyroid
hormonefall in circulating T3 & T4 levelsTSH
secretion from pituitaryenlargement &
stimulation of thyroid. Pt remains Euthyroid
• Lithium induced Goitre & Hypothyroidism does not
warrant discontinuation of therapy
• C/I Pregnancy
• At therapeutic dose : reduction of T wave
amplitude. High dose depresssed SA node & A-V
conduction. C/I sick sinus syndrome
• Dermatitis & Worsen Acne
 INTERACTIONS
• DIURETICS  plasma Lithium level rise.
• Tetracyclines , NSAIDS , ACE Inhibitors  lithium
retention
• pressor response to NA
• Enhance insulin / sulfonylurea induced
hypoglycaemia
• Succinyl choline &Pancuronium  prolonged
paralysis
• Haloperidol  Tremor & Rigidity. Neuroleptic action
is potentiated.
USES:
• Acute Mania
• Prophylaxis In Bipolar Disorder
• Recurrent Unipolar Depression
• Recurrent Neuropsychiatric Illness , Cluster
Headache & Major Depression
• Cancer Chemotherapy induced leukopenia &
Agranulocytosis
• Inappropriate ADH Secretion Syndrome
 ALTERNATIVES TO LITHIUM
SODIUM VALPROATE:

• Reduction in manic episodes

• High dose valproate acts faster than lithium &
it is alternative to antipsychotics & BZD
• Lithium intolerant & non responders
• Lithium + Valproate  Resistant Monotherapy
• Valproate + Atypical Antipsychotic  high
efficacy in Acute mania
•
CARBAMAZEPINE:

• Less effective than Valproate & Lithium.

• As an alternative to Lithium
• High doses  Neurotoxicity & poorly tolerated
• Long – term prophylaxis of Bipolar Disorder 
Suicide is less well established
• Dose & Effective plasma concentration  same as
for treatment of Epilepsy
LAMOTRIGINE:

• Prophylaxis of Depression in Bipolar Disorder

• As Maintanence therapy in of type II Bipolar
disorder
• Not Effective as Treatment & Prevention
• Lamotrigine + Lithium  Improved Efficacy
• Favourable Tolerability
ATYPICAL ANTIPSYCHOTICS:
• OLANZAPINE , RISPERIDONE , ARIPIPRAZOLE ,
QUETIAPINE
• With or without BZD  I st line drug in Acute Mania
• Maintanence therapy with Aripiprazole  prevents
Mania but not depressive episodes
• Lack of metabolic effects , favours its long-term use
• Olanzapine  both Manic & Depressive phases are
suppressed. Not suitable for long term use  Wt gain
, Hyperglycaemia ,
• Atypical Antipsychotics + Valproate / Lithium  High
Efficacy & as well as for Maintenance therapy of
Bipolar Disorder
ANTI ANXIETY
DRUGS
ANXIETY:

Anxiety  an adaptive response which

prepares the person to face the challenges of
life.

Characterised by psycological symptoms

(tension , fear apprehension , lack of
concentration ) as well as by sympathetic &
somatic symptoms (tachycardia , tremors
sweating ,& GIT distress ). Fatigue & sleep
 ANTI – ANXIETY DRUGS:

1. BENZODIAZEPINES : Diazepam ,
Chlordiazepoxide Oxazepam ,
Lorazepam , Alprazolam

2. AZAPIRONES : Buspirone , Gepirone ,

Ispapirone
3. SEDATIVE ANTIHISTAMINIC :
Hydroxyzine
4. BETA – BLOCKER : Propranolol
 BENZODIAZEPINES
• More selective for Limbic system  Improvement in
Anxiety & Stress related symptoms
• Act primarily by facilitating inhibitory GABAergic
transmission
• High dose  induce sleep & Impaired Performance
ADR:
• Sedation , light- headedness ,psychomotor & cognitive
impairment , confusional state ( elderly ) , increased
appetite , weight gain & alterations in sexual function
• Women fail to ovulate on regular use
• Impair mental functions & produce dependance
1. Chlordiazepoxide : T1/2  6-12hrs . Long acting &
preferred in chronic anxiety states. Used to cover
Alcohol Withdrawal.
Dose : 25 -100mg
2 . Diazepam : T1/2 20-30 hrs . Preferred in Acute
Panic states & Anxiety associated with organic
disease dose
Dose : 5- 30mg
3 . Oxazepam : T1/210hrs. Short acting . Preferred
for Elderly & those with liver disease. Used in short
lasting Anxiety disorders
Dose : 30-60 mg
4. Lorazepam : T1/2  10-20hrs . Sedative & capable
of producing marked Amnesia when injected i.V.
Only BZD for I.M use . Preferred for short lasting
anxiety states , Panic , OCD , Tension syndromes &
i.v. Use in Status Epilepticus
Dose : 1-6mg

5.Alprazolam : T1/212hrs . Hypnotic as well as

anxiolytic. Potent Anxiolytic BZD with mood
elevating action in mild depression. Withdrawal
symptoms are more.
Dose : 0.25-1mg
 BUSPIRONE
• 5HT1A Agonist
Advantages :
1. Does not produce significant sedation or cognitive
/ functional impairment
2. Does not interact with BZD receptor or modify
GABAergic transmission
3. Does not produce Tolerance or Physical
dependance
4. Does not suppress BZD or barbiturate withdrawal
syndrome
5. Has no muscle relaxant or anticonvulsant activity
MOA:
Acts as Partial Agonist at the 5HT1A receptor
presynaptically

Stimulates 5 HT1A presynaptic autoreceptor

Reduces activity of dorsal raphe seratonergic

neurones

• S/E : Dizziness , Headache, Nausea , rarely excitement

• Rise in BP on pts on MAO inhibitors
• Pt remain alert , those operating machinery / motor
 HYDROXYZINE
• H1 antihistaminic with sedative , antiemetic ,
antimuscarinic , & spasmolytic properties
• Has selective anxiolytic action but sedation is
marked
• Due to antihistamic & sedative property it is useful
in pruritis & urticaria.
• Dose : 50 – 200mg
 BETA BLOCKER
• Symptoms of Anxiety (Palpitation , rise in BP ,
shaking tremor , gastrointestinal hurrying )  due
to symphathetic overactivity
• β blockers  symptomatic relief
• Do not affect the psychological symptoms such as
worry , tension , & fear
• Valuable in acute stressful situations -->
examination fear , unaccustomed public appearance
, etc ,
• Used for performance / situation anxiety
THANK YOU