This document discusses mood stabilizers, which are medications used to treat mood disorders like bipolar disorder. It describes bipolar disorder and its symptoms. The main types of mood stabilizers are lithium, anticonvulsants like valproate and carbamazepine, and antipsychotics. Lithium was one of the first mood stabilizers and works by interfering with cell signaling pathways. Anticonvulsants also have mood stabilizing effects through mechanisms like enhancing GABA. Antipsychotics are used to treat mania and can have side effects like extrapyramidal symptoms. The goals of treatment are to reduce symptoms, prevent relapse, and improve functioning while reducing risks.

1. Mood
stabilizers

2. Prepared by:
Maryam Abdulwahid
Tanya Muhammad
Hawar Jarjees
Hedi Hamid
Supervised by:
Dr. Suzan

3. Mood stabilizers
• mood stabilizers are medicines used in treating
mood disorders such as bipolar disorder and
depression.

4. Bipolar Disorder:
•Bipolar disorder, also called manic depression, is
characterized by severe mood swings from manic highs to
depressive lows. These cycles can last for months at a time.
symptoms of bipolar disorder can include:
Mania
Depression
Impulsive behaviors
Feelings of hopelessness
Hallucinations
Delusions
Lethargy
Inability to focus
Impaired judgment
Suicide risks

5. Types of bipolar disorder
– Bipolar disorder type I
Bipolar disorder type I is the classic form of the disease in
which patients have periodic episodes of mania and
depression.
– Bipolar disorder type II
Is the form in which patients do not develop severe mania
but go through episodes of hypomania that alternate with
milder depression.
– Rapid cycling bipolar disorder
when patients exhibit more than four manic or depressive
episodes.

7. Types of mood stabilizers
1. Lithium
2. Anticonvulsant medicines
3. Antipsychotic medicines

8. The goals
• 1) reduce residual symptoms
• 2) prevent manic or depressive relapse
• 3) reduce the frequency of cycling into the next manic or
depressive episode.
• 4) improve functioning.
• 5) reduce the risk of suicide.

9. How long do they take to work?
•Lithium may take a week or more to begin working.
•Anticonvulsants such as valproate and the antipsychotics olanzapine
and aripiprazole may work more rapidly to control a manic episode.
•Until the mood stabiliser takes effect, other medicines such as
anipsycotics or sedatives are initially used help control an episode of
mania.
• people with bipolar disorder continue treatment with mood
stabilisers for extended periods of time (usually at least two years) to
help prevent episodes of ill health.
•Other medicines may be added when necessary, typically for shorter
periods, to treat episodes of mania or depression that break through
despite the mood stabiliser.
•Some people with bipolar disorder do better with a combination of
mood stabilisers to help prevent episodes of high and low mood. For
example, lithium or valproate may be used together with an
antipsychotic.

10. Lithium
• Lithium was one of the first mood stabilizers used in the
treatment of bipolar disorder.
• Lithium is a simple ion like sodium found in table salt (sodium
chloride). Lithium comes in two forms—lithium carbonate
(Eskalith-CR, Lithobid Extended-Release) and lithium citrate.
• Lithium carbonate is available in immediate- and controlled-
release capsules and tablets.
• Lithium also comes in a liquid preparation in the form of lithium
citrate. Over several decades of clinical experience, lithium has
been shown to be effective not only in treating mania but also
in preventing relapse of mania and depression in bipolar
disorder.

11. PHARMACOLOGICAL AND MECHANISM OF
ACTION:
• Is clinically effective at plasma concentration of (0.5_1)
mmol/l (narrow therapeutic limit).
• Above 1.5mmol/l produces toxic effects.
• 1 mmol/l of lithium can produce many detectable
biochemical changes but it has no psychotropic effects

12. The therapeutic actions
1.Interference with inositol triphosphate formation:
The phosphatidylinositol(pi)pathway is blocked at a point where
inositol phosphate is hydrolyzed to free inositol.
This step is required for the regeneration of PI in the membrane
after it has been hydrolyzed by agonist action.
Lithium thus causes depletion of membrane PI and accumulation of
intracellular inositol phosphate. The result is inhibition of agonist
stimulated inositol triphosphate formation(stimulates release of
calcium) through various linked Pi linked receptors, therefore block
of many receptor mediated effects.

13. 2. interference with cAMP production:
hormone induced cAMP production is reduced
For example;
The response of renal tubular cells to ADH
and of thyroid to TSH
• Effect of lithium on these2 second messenger systems
accounts for its therapeutic effects.

14. Pharmacokinetics and toxicity:
• Is given orally as carbonate salt two or three times daily
during meals, often with a higher dosage in the evening.
The sustained release formulation is taken only once in
the evening.
• its excreted by kidney
• Half of an oral dose is excreted with in 12 hours and the
remainder that represents the lithium taken up by cells is
excreted over the next 1_2 weeks.
so the lithium is accumulated slowly with in that 2 weeks
before a steady state is reached.

15. Lithium toxicity
• Lithium therapy requires reaching plasma concentrations
of lithium which are relatively close to the toxic
concentration.
• depletion of sodium reduces the rate of excretion of
lithium by increasing reabsorption of lithium from
proximal tubule .
• Diuretics acting on proximal tubule have the same effect.
• Renal diseases also predispose to lithium toxicity.

16. To prevent toxicity:
• adequate renal function and adequate salt and fluid
intake are essential.
• a decision to initiate lithium therapy should be preceded
by a thorough clinical examination and evaluation of each
patient, including laboratory determinations, ECG, and a
very careful assessment of renal function.
• monitoring of plasma concentration is needed
especially
in case of renal disease, in patients who sweat profusely,
experience diarrhea or vomiting, with infection or fever
causing fluid loss.

17. Side effects of lithium
•Nausea, vomiting, and diarrhea.
•Trembling.
•Increased thirst and increased need to urinate.
•Weight gain in the first few months of use.
•Drowsiness.
•A metallic taste in the mouth.
•Abnormalities in kidney function.
•Abnormalities in thyroid function.

18. Contraindications of lithium
• renal or cardiovascular disease
• sodium depletion
• dehydration
• patients on diuretics
• during pregnancy and lactation

19. Anticonvulsants
• Carbamazepine
(Carbatrol, Tegretol, and Tegretol-XR)
• valproic acid (Depakene)
• divalproex (Depakote)
• lamotrigine (Lamictal )
• gabapentin (Neurontin )
• topiramate (Topamax)
• oxcarbazepine (Trileptal)
• these medications are more recently being used to treat bipolar
disorder.
• about 40% of bipolar pts. are not helped by Li or cannot
tolerate the Li SEs…thus, need an alternative treatment.

20. Valproate
• Is a simple monocarboxylic acid.
• now the 1st choice for treatment of mania (even over Li)
• actually less effective than Li in treating mania, but does also
help decrease depression more effectively than Li
• Effective in 71% of patients.
• Is especially good for treatment of acute mania (alone or with
antipsychotic meds)
• Has low toxicity and lacks sedation.

21. MECHANISM OF ACTION:
• a GABA agonist (enhances synthesis/release of GABA)
• Is aweak inhibitor of GABA transaminase and succinic semi
aldehyde dehydrogenase.
• a glutamate antagonist
• 50% plasma protein bound
• is a liver enzyme inhibitor (of P450 enzymes)

22. Carbamazepine
• Carbamazepine (Carbagen SR, Tegretol, Tegretol retard) was
the first anticonvulsant to be discovered as an effective mood
stabiliser as well as a treatment for epilepsy.
• It tends to cause more side effects than valproate and is less
effective than lithium. It is usually only used in people who have
been unresponsive to lithium, however it may be better for
rapid cycling bipolar illness.
• Many people find that carbamazepine causes unwanted side-
effects, and it can also interact with several other
medicines. Oxcarbazepine (Trileptal) is related to
carbamazepine, but has less potential to affect other medicines
and so may sometimes be used instead.

23. pharmacokinetics:
• Is well absorbed.
• 75% protein bound.
• Plasma half life is about 30 hours when given as a single
dose and shortens to 15 hours when given repeatedly.
• is a liver enzyme inducer (CYP-3A4 especially)

24. Side effects
Drowsiness
Dizziness
Ataxia
Water retention
Gastrointesinal distress
Cardiovascular side effects
Bone marrow suppression leading to neutropenia(rarely)
decrease the amount of platelets.

25. Contraindication
• Pregnant women should not take anticonvulsants
without consulting with their doctor because they may
increase the risk of birth defects.
• Many anticonvulsants can cause problems with the liver
over the long term. Also, anticonvulsants can interact
with other drugs, even aspirin and cause serious
problems.

26. Antipsychotics
A. Typical Antipsychotics:
Are blockers of dopamine D2 postsynaptic receptors, includes:
• Phenothiazines :, fluphenazine, trifluoperazine,
thioridazine,Chlorpromazine
• Thioxanthines : chlorprothixene, thiothixene
• Butyrophenones : haloperidol, droperidol, Others :loxapine,
molindone, pimozide

27. B.Atypical Antipsychotic Drugs:
Lower relative blockade of D2 receptors, no or low Extra
pyramidal effects.
Includes:
• Clozapine
• Risperidone
• Olanzapine
• Quetiapine : Similar to clozapine
• Sertindole
• Aripiprazole

28. MECHANISM OF ACTION:
•Antipsychotic effects correlate with effect on mesolimbic/mesocortical
dopamine pathway.
• There are two classes of dopamine receptors:
D1 includes D1 and D5 receptors and D2 include D2, D3, and D4 receptors.
• D2 receptors are the main targets for the antipsychotic activity.
If the 80% of the D2 receptors get occupied, then it causes the
antipsychotic activity.
• Most of them also block other monoamine receptors especially5-HT2
receptor. Clozapine also blocks D4 receptor.
• Many of antipsychotics also block cholinergic,adrenergic, and histaminergic
receptors (resulting in side effects).
• antipsychotic drugs takes some week to show their action even though they
bind as soon as they are administered.

29. PHARMACOKINETICS:
• The levels of the antipsychotics in the plasma and their effect is
not related.
• incompletely absorbed.
• Significannt 1st pass metabolism.
• Most are highly lipid soluble.
• Most are highly protein bounded(92_98 %)
• High volume of distribution.
• the toxicity caused by these drugs is very less.
• Plasma half life : 15 to 30 hours
• Route of administration : oral route or IM injection

30. Side effects:
A.EXTRAPYRAMIDAL MOTOR DISTURBANCE: by blockage of
niigrostriatal pathway.
B. On endocrine system:
Neurons present in the tuberohypophyseal pathway liberate
dopamine which is stops the prolaction secretion. So
antiphychotics disturbs this process and more amount of prolactin
is produced .

31. Side effects:continued
• Sedation , weight gain and hypotension are also
common.
• dry mouth, blurred vision
• Obstructive jaundice with phenothiazine some
times
• With clozapine leucopenia is common requiring
routine monitoring.
• Antipsychotic malignant syndrome is rare but
potentially dangerous.

32. Contraindications
•hypersensitivity
•blood dyscrasias
•Parkinson’s disease
•severe hypotension

33. Reference
• Rang & Dale’s Pharmacology, 6th Edition, Chapter 38
(John A. Harvey, Ph.D.)
• http://www.webmd.com/bipolar-disorder/mood-stabilizing-me
• http://www.pharmainfo.net/sivaganesh/blog/antipsycho
tics
• http://
support4hope.com/medications/mood_stabilizers/index.htm
• http://en.wikipedia.org/wiki/Lithium_pharmacology

35. Questions &comments