MOOD STABILISERS

Dr.Navina.S,
Department of Psychiatry, SRMC&RI
INTRODUCTION
 Definition of mood stabiliser: a labile label
 Originally- a drug that treated mania and
prevented the recurrence of mania, thus
“stabilizing” the manic pole of bipolar disorder.
 “there is no such thing as a mood stabiliser”-FDA
 “long live the mood stabilisers”- prescribers
SCOPE OF TOPIC
 Principles
 Mania minded vs depression minded treatments
 Lithium
 Anti convulsants as mood stabilisers
 Atypical antipsychotics as mood stabilisers
 Other agents
 Newer mood stabilisers
PRINCIPLES
 Pharmacotherapy-cornerstone of the management
of bipolar disorder
 Immediate goal- stabilisation of acute episodes
 Equally important-prevention of further mood
episodes
 Choose medication with proven efficacy in both
MANIA MINDED VS DEPRESSION MINDED TREATMENTS

 Drugs can treat any or all of 4 different phases of

the illness
 ie treat from above/ stabilise from above/ treat
from below/ stabilise from below
 Not all drugs have all 4 therapeutic actions
 Include lithium, anticonvulsant mood stabilisers,
atypical antipsychotics and other agents
LITHIUM, THE CLASSIC
 More than 50 years of use
 Ion with uncertain mechanism of action
 MOA at various signal transduction sites
 Alters sodium transport across cell membranes in
nerve and muscle cells
 Alters metabolism of NT including
catecholamines and serotonin
LITHIUM MOA
 inhibits phosphatidyl inositol 2nd messenger
system
 reduces protein kinase C activity
 Increases cytoprotective proteins
 Increases gray matter content by activating
neurogenesis
 Enhances trophic actions that maintain synapses
LITHIUM COMMONLY PRESCRIBED FOR

 Manic episodes for manic depressive illness

 Maintenance treatment for manic-depressive
patients with a history of mania
 Bipolar depression
 MDD (adjunctive)
 vascular head ache
 Neutropenia
bold- FDA approved
HOW TO GO ABOUT WITH LITHIUM
 Takes 1-3 weeks to work
 Goal-complete remission
 If it works-continue indefinitely
 If it doesnt work- partial response/ waxing and
waning/ no response, check plasma drug level,
increase dose, switch to another agent or augment
 Psychotherapy/ ?non-compliance/ comorbid
conditions
LITHIUM DOSING
 Half life 18-30 hours
 Lower absorption on empty stomach

Usual dosage range:

Mania: recommended 1.0-1.5mEq/L
Depression: 0.6-1.0mEq/L
Maintenance: 0.7-1.0 mEq/L
Start 300mg 2-3 times/day and adjust dosage upward as
indicated by plasma levels
Available as tablet,capsule,liquid prep
AUGMENTING LITHIUM
 Partial response/ treatment resistance
 Valproate
 Atypical antipsychotics ( risperidone, olanzapine,
quetiapine, ziprasidone, and aripiprazole)
 Lamotrigine
 Antidepressants-with caution; generally avoid
TCAs, MAOIs
BEFORE STARTING LITHIUM
 RFT,TFT, ECG
 Repeat RFT once a year
 Monitor weight and BMI
 Therapeutic range: 1-1.5 meq/L (acute phase), 0.6-1.2
meq/L(chronic treatment)
 Frequent tests to monitor trough lithium plasma levels- 12
hours after last dose
 Initial monitoring every 1-2 weeks until desired serum
concentration is achieved, then every 2-3 months for the first 6
months
 Stable monitoring every 6-12 months
LITHIUM SIDE EFFECTS (DOSE RELATED)

 Ataxia, dysarthria, delirium, tremor, memory problems

 Polyuria, polydipsia
 Diarrhoea, nausea
 Weight gain
 Euthyroid/hypothyroid goitre possibly with increased
TSH and reduced thyroxine levels
 Acne,rash, alopecia
 Leukocytosis
 sedation
LITHIUM SIDE EFFECTS
 Lithium toxicity
 Renal impairment
 Nephrogenic diabetes insipidus
 Arrhythmia, cardiovascular changes, sick sinus
syndrome,bradycardia,hypotension
 T wave flattening and inversion
 Rare pseudotumor cerebri
 Rare seizures
DRUG INTERACTIONS
 NSAIDS can increase plasma lithium conc.
 So do diuretics especially thiazides
 Metronidazole –decreased renal clearance
 ACE inhibitors-increase plasma conc.
 Methyldopa, carbamazepine,phenytoin , Ca
channel blockers may increase toxicity
 Lithium with SSRI- may raise risk of dizziness,
confusion, diarrhoea, agitation tremor
STOPPING LITHIUM
 Toxicity- discontinue immediately
 Other reasons- taper gradually over 3 months to
avoid relapse
 Rapid discontinuation increases the risk of
relapse, and possibly suicide
WHEN NOT TO USE LITHIUM
 Severe kidney disease
 Severe cardiovascular disease
 Brugada syndrome
 Severe dehydration
 Sodium depletion
 Proven allergy to lithium
LITHIUM IN SPECIAL POPULATIONS
 Elderly: lower doses, may be more sensitive to adverse
effects, neurotoxicity may occur even at therapeutic
levels
 Children and adolescents: safety and efficacy not
established in children under 12 years, use with caution
 Pregnancy: evidence of increased risk of major birth
defects (2-3 times of general population)
 Lithium may be found in breast milk possibly at full
therapeutic levels- no breastfeeding
LITHIUM - PEARLS
 Possibly underutilized since its older and less promoted
 Maybe best for euphoric mania
 May decrease suicide and suicide attempts not only in
bipolar disorder 1 but also in bipolar II disorder and
unipolar depression
 Maybe useful for a number of patients with episodic,
recurrent symptoms with or without affective illness,
including episodic rage, anger or violence and self
destructive behavior,( personality disorders, organic
disorders, MR)
LITHIUM -PEARLS
 Due to delayed onset of action, lithium
monotherapy may not be first choice in acute
mania
 One of the most useful adjunctive agents to
augment antidepressants for treatment resistant
unipolar depression
 Only 1/3rd of bipolar patients experience adequate
relief with monotherapy
ANTICONVULSANT MOOD STABILISERS

 Based upon theories that mania may kindle

further episodes of mania
 Logical parallel with seizure disorders was drawn
 Thus several anticonvulsants are used, some with
better evidence of efficacy
 Valproate, carbamazepine, lamotrigine,
oxcarbazepine/licarbazepine,riluzole,topiramate,
zonisamide, gabapentin, pregabalin,
levetiracetam
VALPROATE
 acute mania(divalproex) and mixed episodes
 CPS-isolated or in association with other types
of seizures, simple and complex absence
seizures
 Migraine prophylaxis
 Maintenance treatment of bipolar disorder
 Bipolar depression
 Psychosis, schizophrenia (adjunctive)
VALPROATE MOA
 Blocks voltage sensitive sodium channels by an
unknown mechanism
 Increases brain concentrations of GABA by
unknown mechanism
 Duration- for acute maina, effects should occur
within a few days depending upon formulation
 May take several weeks to months to optimize an
effect on mood stabilisation
 Principles of treatment similar to lithium
BEST AUGMENTING COMBOS
 Lithium
 Atypical antipsychotics
 Lamotrigine (with caution, valproate can double
lamotrigine levels)
 Antidepressants (with caution)
VALPROATE PHARMACOKINETICS
 Mean terminal half life 9-16 hours
 Metabolised primarily by the liver, approximately
25% dependent upon CYP450 system
 Inhibits CYP4502C9
 Food slows rate but not extent of absorption
VALPROATE SIDE EFFECTS
 CNS side effects theoretically due to excessive
actions at voltage sensitive sodium channels
 Sedation, dose dependent tremor, dizziness,
ataxia, asthenia, headache
 Abdominal pain, nausea, vomiting, diarrhoea,
reduced appetite, constipation, dyspepsia, weight
gain
 Alopecia(unusual)
VALPROATE-DANGEROUS SIDE EFFECTS

 Tachycardia/bradycardia
 Rare hepatotoxicity
 Rare pancreatitis
 Rare drug reacion with eosinophilia (DRESS)
 Rare activation of suicidal ideation and behavior
VALPROATE USUAL DOSAGE RANGE
 Mania – 1200 to 1500mg/day

 Dosage forms- tablet/capsule forms of divalproex

sodium, ER prep, valproic acid capsule,
 Sodium valproate injection (100mg/ml-5ml), syrup
 Divalproex sodium is an enteric coated stable
compound containing both valproic acid and
sodium valproate
VALPROATE DOSING TIPS
 Oral loading with 20-30mg/kg per day may
reduce onset of action to 5 days or less – esp
useful in acute mania
 Given half life of immediate release valproate,
twice daily dosing is ideal,
 ER can be given once daily, however ER prep is
only 80% bioavailable producing 10-20% lower
plasma drug levels
VALPROATE INTERACTIONS
 Valproate inhibits metabolism of lamotrigine, raising
plasma levels
 Aspirin inhibits metabolism of valproate. Plasma
levels may also be increased by chlorpromazine,
fluvoxamine, topiramate, fluoxetine
 Plasma levels lowered by carbamazepine, phenytoin,
phenobarbital, ethosiximide and rifampin
 No likely pharmacokinetic interactions with lithium
or atypical antipsychotics
VALPROATE-OTHER POINTS
 In overdose- Fatalities have been reported; coma,
restlessness, hallucinations, sedation, heart block
 Not to be used in- pancreatitis, serious liver
disease, urea cycle disorders, proven allergy to
valproate
VALPROATE IN SPECIAL POPULATIONS
 Elderly: sedation more common, 1 in 3 may
ultimately develop thrombocytopenia
 Children and adolescents- not recommended for
chidren under age 10
 Pregnancy-use in first trimester may raise risk of
neural tube defects, generally considered safe to
breast feed while taking valproate
VALPROATE- PEARLS
 First line treatment option that may be best for
patients with mixed states, or rapid cycling
 Seems to be more effective in treating manic
episodes than depressive episodes
 Useful adjunct to atypical antipsychotics
 Multivitamins fortified with zinc and selenium
may help reduce alopecia
CARBAMAZEPINE
 First anticonvulsant to be shown effective in manic
phase of BD however did not receive formal FDA
approval till recently
 Prescribed for

-acute mania/mixed mania

-Bipolar depression, bipolar maintenance
-psychosis, schizophrenia(adjunctive)
Also for seizures, pain associated with trigeminal
neuralgia
CARBAMAZEPINE-MOA
 Acts as a use-dependent blocker of voltage
sensitive sodium channels
 Interacts with open conformation of voltage-
sensitive sodium channels
 Interacts at a specific site of the alpha pore-
forming subunit of voltage-sensitive sodium
channels
 Inhibits release of glutamate
CARBAMAZEPINE DURATION OF ACTION

 For acute mania, effects should occur within a few

weeks
 May take several weeks to months to optimize an
effect on mood stabilisation
 Principles of treatment as that earlier discussed
 Tests: before starting- blood count,LFT,RFT,TFT
 blood count every 2-4 weeks for 2 months, then
every 3-6 months throughout treatment, other
parameters every 6-12 months
CARBAMAZEPINE CONTD..
 Consider monitoring sodium levels because of
possibility of hyponatremia
 Before starting: individuals with ancestry across
broad areas of Asia should consider screening for
the presence of the HLA-B*1502 allele, those
who have the allele should not be treated with
carbamazepine
CARBAMAZEPINE PHARMACOKINETICS

 Metabolised in the liver, primarily by CYP4503A4

 Renally excreted
 Initial half life 26-65 hours (ER-35 to 40 hours),
 With repeated doses half life is 12-17 hrs
 Half life of active metabolite is 34 hrs
 Carbamazepine is an inducer of CYP4503A4, thus
inducing its own metabolism, also an inducer of
CYP4502C19
CARBAMAZEPINE SIDE EFFECTS
 CNS effects d/t actions at VSSCs and mild
anticholinergic effects
 Sedation, dizziness, confusion, unsteadiness,
headache
 Nausea,vomiting,diarrhoea
 Blurred vision
 Benign leukopenia,rash
 Long term use may lower libido
CARBAMAZEPINE DANGEROUS SIDE EFFECTS

 Rare aplastic anemia, agranulocytosis

 Rare severe dermatologic reactions
 Rare cardiac problems
 Rare induction of psychosis,mania
 SIADH
 Rare suicidality
 Weight gain(minority)
 Sedation-frequent and can be significant
CARBAMAZEPINE DOSING
 400-1200mg/day
 Under age 6:10—20mg/kg/day
 Tablet,ER and oral suspension
 Take with food to avoid GI side effects
 Overdose can be fatal; nausea,vomiting,
involuntary movements, irregular heartbeat,
urinary retention, trouble breathing, sedation,
coma
CARBAMAZEPINE –BEST AUGMENTING COMBOS FOR PARTIAL
RESPONSE/ TREATMENT RESISTANCE

 Lithium
 Atypical antipsychotics
 Valproate (carbamazepine may reduce valproate
levels)
 Lamotrigine
 Antidepressants (use with caution)
CARBAMAZEPINE DRUG INTERACTIONS

 Enzyme inducing anti-epileptic drugs may lower plasma

levels
 CYP450 3A4 inducers
 CYP4503A4 inhibitors- fluvoxamine, fluoxetine can
increase plasma levels
 Carabamazepine can reduce plasma levels of
clozapine,haloperidol, benzodiazepines, and other
anticonvulsants
 Can decrease plasma levels of hormonal contraceptives
and adversely affect their efficacy
CARBAMAZEPINE NOT TO BE USED IN
 h/o bone marrow suppression
 Positive test for HLA-B*1502 allele
 Proven allergy to any tricyclic compounds or
carbamazepine
CARBAMAZEPINE- SPECIAL POPULATIONS

 Lower dose in renal impairment

 Caution in hepatic impairment and cardiac
impairment
 Approved use for epilepsy in children and
adolescents
 First trimester of pregnancy-neural tube defects
risk
 Breastfeeding-recommended to discontinue drug or
bottle feed
CARBAMAZEPINE-PEARLS
 ER formulation has better evidence of efficacy
and improved tolerability
 Risk of serious side effects is greatest in first few
months of treatment
 May be effective in patients who fail to respond
to lithium or other mood stabilisers
LAMOTRIGINE
 Used in
 Maintenance treatment of bipolar I disorder
 Bipolar depression
 Bipolar mania (adjunctive and second line)
 Psychosis,schizophrenia (adjunctive)
 Major depressive disorder (adjunctive)
 Various types of seizures, in neuropathic pain/
chronic pain
LAMOTRIGINE-MOA
 Acts as a use-dependent blocker of voltage-
sensitive sodium channels
 Interacts with the open channel conformation of
voltage-sensitive sodium channels
 Interacts at a specific site of the alpha pore-
forming subunit of voltage-sensitive sodium
channels
 Inhibits release of glutamate and aspartate
LAMOTRIGINE- DURATION TO ACT
 May take several weeks to improve bipolar
depression
 May take several weeks to months to optimize an
effect on mood stabilisation
 Best augmenting combos- lithium,atypical
antipsychotics,valproate and antidepressants
 No tests required
LAMOTRIGINE-SIDE EFFECTS
 Benign rash (approximately 10%)
 Dose dependent: blurred or double vision, dizziness,
ataxia
 Sedation, head ache, tremor, insomnia, poor coordination,
fatigue
 Nausea(dose dependent),vomiting , dyspepsia
 Serious side effects- rare serious rash, rare multiorgan
failure, rare aseptic meningitis, rare blood dyscrasias, rare
suicidality
 Not much sedation or weight gain
LAMOTRIGINE PHARMACOKINETICS
 Elimination half life after single dose- approx 33
hrs
 Patients receiving concomitant valproate- 59 hrs
 Concomitant enzyme inducing antiepileptic
drugs- approximately 14 hrs
 Metabolised in liver, renally excreted
 Rapidly and completely absorbed, biavailability
not affected by food
LAMOTRIGINE DOSING
 Monotherapy for BD- 100-200mg/day
 Adjunctive treatment for BD: 100mg/day in
combination with valproate
 Tablet,ER preparations
 For bipolar disorder- for first 2 weeks administer
25mg/day ; at week 3 increase to 50mg/day, at
week 6 increase to 200mg/day (max dose)
LAMOTRIGINE-SPECIAL POPULATIONS
 Not approved for patients under 16 years of age for
psychiatric disorders
 Risk of rash increased in pediatric patients
 For bipolar patients, lamotrigine should generally
be discontinued before aniticipated pregnancies
 Generally recommended to dicontinue drug if
breastfeeding or bottle feed
 Do not start lamotrigine within 2 weeks of a viral
infection,rash or vaccination
LAMOTRIGINE-PEARLS
 First-line treatment option that may be best for
patients with bipolar depression
 (treats from below better than it treats from above)
 Low levels of use may be based upon exaggerated
fears of skin rashes or lack of knowledge about
how to manage skin rashes
 May actually be one of the best tolerated mood
stabilisers with little weight gain or sedation
OXCARBAZEPINE
 Bipolar disorder
 Similar MOA as other anticonvulsants
 For acute mania effects should occur within a few
weeks
 May take several weeks to months to optimize an
effect on mood stabilisation
 1200-2400mg/day
 Tablet and liquid forms
OXCARBAZEPINE CONTD
 Initial 600mg/day in 2 doses; increase every 3 days
by 300mg/day
 Dose needs to be about 1/3rd higher than that of
carbamazepine for similar results
 Monitor for hyponatremia in first 3 months
 Metabolised in liver, renally excreted
 Inhibits CYP450 2C19,
 half life of parent drug is 2 hrs, main metabolite is
licarbazepine with half life 9 hrs
OXCARBAZEPINE CONTD
 Older pts may have reduced creatinine clearance
requiring reduced dosing
 Ages 4-16:initial 8-10mg/kg/day or less than
600mg/day increase over 2 weeks to 900-
1800mg/day depending on weight
 Pregnancy- use in first trimester-risk of neural
tube defects
 Breast feeding not recommended
ATYPICAL ANTIPSYCHOTICS AS MOOD STABILISERS

 Actions similar to lithium and various

anticonvulsants
 Core non psychotic symptoms of mania and
maintenance treatment to prevent recurrence of
mania
 Some atypicals are effective for bipolar
depression
PUTATIVE PHARMACOLOGICAL MECHANISM OF
ATYPICAL ANTIPSYCHOTICS IN BIPOLAR DISORDER

 5HT2A and 5HT1A partial agonist properties

may account for reduction of nonpsychotic manic
and depressive symptoms
 Via reduction of glutamate hyperactivity from
overly active pyramidal neurons by 5HT2A
antagonist actions
 D2 antagonism/partial agonism
PUTATIVE PHARMACOLOGICAL MECHANISM OF
ATYPICAL ANTIPSYCHOTICS IN DEPRESSION

 Interact with multiple receptor subtypes for both

dopamine and serotonin and have effects on other
NT system as well
 5HT1A partial agonism, 5HT1B/D, 5HT2C,
5HT3 and 5HT7 antagonism
 Serotonin and norepinephrine reuptake inibition
 Alpha 2 antagonism
?APPROVED
 All atypical antipsychotics are approved for
schizophrenia and most for mania
 for bipolar depression- quetiapine and multiple
positive clinical trials for lurasidone
 Increasingly,treatment of bipolar disorder is not
only with two or more agents, but with one of
those agents being an atypical antipsychotic
RISPERIDONE
 Acute mania/mixed mania,ages 10 and older,
monotherapy/adjunct
 Bipolar maintenance
 Bipolar depression
 MOA- D2 and 5HT2A antagonism, 5HT7
antagonism may contribute to antidepressant
actions
 Psychotic and manic symptoms can improve within
1 week, wait 4-6 weeks
RISPERIDONE CONTD...
 Many bipolar patients may experience a
reduction of symptoms by half or more
 May also prevent recurrencces of mania
 Metabolised by CYP450 2D6
 Parent drug oral formulation half life- 20-24 hrs
 Dosage- 2-8mg/day orally; 12.5-50mg depot im
every 2 weeks
 Tablets,liquid,LA im inj
RISPERIDONE CONTD..
 Consider augmenting rather than raising the dose in
partial responders
 Approved for use upto 16mg/day orally,but EPS
more above 6mg/day
 Lower doses in children and elderly- well accepted
 Risperidone may be preferable to anticonvulsant
mood stabilisers if treatment required during
pregnancy
 Breastfeeding not recommended
OLANZAPINE
 Acute mania/mixed mania
(monotherapy/adjunct)
 Bipolar maintenance
 Bipolar depression in combination with
fluoxetine
 Treatment resistant depression in combination
with fluoxetine
OLANZAPINE-CONTD
 D2-5HT2A antagonism, 5HT2C antagonism
 Duration to work similar to risperidone
 Dosage 10-20mg/day (oral or IM)
 6-12mg olanzapine/25-50mg fluoxetine
 150-300mg/2 weeks or 300-405mg/4 weeks
olanzapine pamoate
 Maximum approved dose is 20mg/day
 Tablet,OD,im and depot
OLANZAPINE-CONTD
 Parent drug 21-54 hr half life
 Substrate for CYP4501A2 and 2D6
 Can be used in children(ages 13 or older) for
manic /mixed episodes;
 Lower doses in elderly
 Early findings of infants exposed to olanzapine
in utero currently do not show adverse
consequences
OLANZAPINE-CONTD
 Olanzapine may be preferable to anti convulsant
mood stabilisers if treatment is required during
pregnancy
 Breastfeeding not recommended
 Well accepted for use in bipolar disorder including
difficult cases
 Documented efficacy in treatment resistant MDD
and bipolar depression especially in combination
with fluoxetine
QUETIAPINE
 Acute mania in adults and ages 10-17,
(monotherapy/adjunct)
 Bipolar maintenance
 Bipolar depression
 Depression (adjunct)
 Mixed mania
 D2-5HT2A antagonism, 5HT1A partial agonism,
5HT2C and 5HT7 antagonism and norepinephrine
reuptake blockade
QUETIAPINE-CONTD
 400-800mg/day in 1 or 2 doses for bipolar mania
 300g once daily for bipolar depression
 Tablet,ER preparations
 Parent drug has 6-7 hr half life
 Substrate for CYP450 3A4
 Lower dose in elderly
 Approved for manic/mixed episodes in children
aged 10 and older
QUETIAPINE-CONTD
 Pregnancy-controlled studies not conducted; use
with caution; avoid breastfeeding
 More sedation-benefit in acutely manic/psychotic
pts but not for stabilised pts in long term
maintenance
 Essentially no motor side effects or prolactin
elevation
ZIPRASIDONE
 Bipolar maintenance
 Bipolar depression
 D2-5HT2A antagonism, 5HT2C and 5HT1A
receptor interactions, 5HT1D,5HT7 and NET
actions
 Bipolar disorder: 80-160mg/day in divided doses
orally
 10-20mg intramuscularly
 Available in capsule and inj.forms
ZIPRASIDONE CONTD.
 Mean half life 6.6 hrs
 Metabolised by CYP450 3A4
 Absorption is doubled approx. when taken with food
 dosing many patients at 20-40mg twice a day is too
low and in fact activating, perhaps d/t potent 5HT2C
antagonist properties
 Such activation reduced by increasing dose upto 60-
80mg twice a day perhaps d/t increasing D2
antagonism
ZIPRASIDONE CONTD
 Contraindicated in pts with known h/o QTc
prolongation,recent acute MI or uncompensated
HF
 Not officially recommended for patients under
age 18
 In pregnancy, profile similar to earlier discussed
atypicals
ASENAPINE
 Acute mania/mixed mania,monotherapy (ages
10-17 and in adults)
 Acute mania,mixed mania , adjunct to lithium
or valproate(adults)
 Bipolar maintenance
 Bipolar depression
 Treatment resistant depression
ASENAPINE CONTD
 5HT2A and D2 antagonism
 5HT2C,5HT7 and alpha 2 antagonist properties
may contribute to antidepressant actions
 10-20mg/day in 2 divided doses for bipolar
mania
 Sublingual tablet , pt may not eat or drink for
10mins foll admin
 Reduce dosage in children, pediatric patients may
be more sensitive to dystonia after initial dosing
ASENAPINE CONTD
 Rapid onset of action, can be used on prn basis
 Half life 13-39 hrs
 Inhibits CYP450 2D6, substrate for CYP450 1A2
 Asenapine’s chemical structure is related to
mirtazapine and shares its pharmacologic binding
propertie
ARIPIPRAZOLE
 Acute mania/mixed mania (ages 10 and older;
monotherapy and adjunct)
 Bipolar maintenance (monotherapy and
adjunct)
 Depression (adjunct)
 Bipolar depression
 D2 partial agonism,action at D3 receptors,
5HT2A ,2C and 7 receptor blockade and 5HT1A
partial agonism
ARIPIPRAZOLE CONTD
 15-30mg/day for mania
 2-10mg/day for augmenting SSRIs and SNRIs in
depression
 300-400mg/4 weeks
 441mg,662mg,882mg monthly or every 6 weeks
 Tablet,OD,oral solution,injection,depot
 Metabolism-CYP450 2D6 and CYP4503A4
ARIPIPRAZOLE CONTD
 Half life- 75hrs; major metabolite-94 hrs
 Takes longer to reach steady state when initiating
dosing and longer to wash out when stopping
 Less sedation than most other antipsychotics
 Reports of problems with impulse control in patients
taking aripiprazole
 Can be used in children ages 10 and older for
manic/mixed episodes
 Pregnancy&breastfeeding-similar to previous atypicals
LURASIDONE
 Bipolar depression
 Acute mania/mixed mania
 Bipolar maintenance
 Treatment-resistant depression
 D2 and 5HT2A antagonism,5HT7 antagonism,
5HT1A partial agonism and alpha 2A and 2C
antagonism
LURASIDONE CONTD
 20-60mg/day for bipolar depression, some upto
120mg/day
 Tablet form
 Metabolised by CYP450 3A4
 Half life 18-31 hours
 Safety and efficacy in children not established
 Pregancy-similar to other atypicals
LURASIDONE CONTD
 Only atypical antipsychotic documented not to
cause QTc prolongation
 One of the best studied agents for depression with
mixed features,showing efficacy in a large
randomized controlled trial
 Not yet approved for mania
THE FOLLOWINGARE ALSO BEING STUDIED FOR USE

 Anticonvulsants- levetiracetam, vigabatrin,

topiramate, tiagabine,riluzole, zonisamide,
acamprosate
 Antipsychotic- cariprazine
 NMDA receptor blocker- memantine
 Non-steroidal anti-oestrogen-tamoxifen
 MT1 and MT2 receptor agonist- Rozerem
 Ketamine
 NSAIDS
THE FOLLOWINGARE ALSO BEING STUDIED FOR USE

 DAT blockers-Modafinil and armodafinil

 Hormones and natural products- omega 3 fatty
acids, inositol, L-methyl folate, thyroid hormone