125 Mood stabilizers

Bipolar Disorder

a disorder concerning two poles
Mania
Depression

T or F
Bipolar disorder is erratic

False, do not compare it to weather

Bipolar 1 disorder

≥1 manic episode ± hypomanic episode or major depressive episode

Bipolar 2 disorder

current or past hypomanic episode ± current or past major depressive episode (no manic episode)

SIGECAPS

sleep, interest, guilt, energy, concentration, appetite, psychomotor, suicide

Mood Stabilizers

Drugs that mainly focus at one pole at a time
(some can treat both but only to a certain extent)

T or F
Does Psychotherapy work for both manic and depressive episodes

False, manic episodes can only be treated by medication

4 main medications used in Bipolar Disorder

Lithium Carbamazepine Lamotrigine Valproate

The most effective drug for bipolar
However, not a drug of choice because of narrow therapeutic index

Lithium

Lithium indications

3 R's
Recognizable episodes
periods of Remission (no Sx)
Recurrent
Can also be used as adjunct in depression but mostly for Mania

Contraindications of Lithium

Cardiac and renal disease
Li can act as Na and draw water to it since it is in the same period.

Benefits of Lithium

Unmatched among other mood stabilizers (due to many MOAs)
But you have to stay committed to it

Common Side Effects of Lithium

Polyuria (too much urine leading to urination)
Polydipsia (excessive thirst) (nephrogenic diabetes insipidus)
weight gain (water absorption and thyroid)
goiter
Ataxia
Dysarthria
Delirium
Tremor
Memory problems

Rare Side Effects of Lithium

Lithium toxicity (narrow therapeutic index - see Lithiumeter)(toxicity at Li ≥ 1.5 mM)
MONITOR CREATININE, VERY IMPORTANT
Renal impairment (interstitial nephritis)
Nephrogenic diabetes insipidus
Rare pseudo motor cerebri
Rare seizures
AV block, arrhythmias, ECG changes

Drug interactions of Lithium

Big 3 ANT
ACE inhib, Angiotensin receptor blocker
NSAIDs
Thiazide Diuretic

Lamotrigine mnemonic

pag walang BIDEt, nakaka-DEPRESS, kaya mag-laLAMOn

Indications of Lamotrigine

Focal seizures >>> General seizures
bipolar depression

Onset of Action and administration

several weeks
w/ or w/o food, very slow titration

MOA of Lamotrigine

By decreasing Glutamate release it blocks Ca2+ channels which is toxic to the CNS
Overall decreasing the excitotoxicity

Weak 5-HT3 receptor antagonist and
dihydrofolate reductase inhibitor
Because of Dihydrofolate reductaseinhibition, pregnant women who takeantiepileptics have to take Folate

Main complication/side effect with Lamotrigine

SJS-TEN
Stevens-Johnson Syndrome Toxic epidermal necrolysis
Pediatric: 0.3-0.8%
Adult: 0.08-0.3%

Lamotrigine Side Effects

Common side effects are generally similar with other anti-epileptics
Sedation
Dizziness
Headache
N/V
Benign rash

Rare
SJS-TEN

Drug interactions of Lamotrigine

Lamotrigine is a Uridyl gucuronosyltransferase substrate (UGT)

UGT inducer (>lower Lamotrigine levels)
Carbamazepine
Phenytoin
Phenobarbital
Primidone
Lopinavir/Ritonavir (Ritonavir = CYP Inhibitor but UGT Inducer).
Rifampicin

UGT inhibitor
Valproate

Urine drug test: false positive w/ Phancyclidine

Hormone pills, mutually lower effectiveness

T or F
Lamotrigine safe in pregnancy

True, safest compared to Carbemazapine and Valproate

T or F
Valproate, Valproic acid, Divalproex can be interchanged

False, these are not interchangeable
Do not also change from brand to brand especially in anticonvulsants

With Valproate being a branched chain fatty acid what organs should you monitor

Liver and pancreas

Valproate indications

General seizures and absence seizure (2nd line)
Bipolar mania and Mixed Episodes
(while less effective than Lithium, valporate is the best for mixed episodes)
Chronic Migraine Prophylaxis

MoA of Valproate

Seizure
lessens the flow of ions through Na+ channels
Increase GABA action

Bipolar
Similar pathways as lithium
GSK-3 inhib
Phosphokinase c
MARCKS blockade

Contraindications of Valproate

Pancreatitis
Serious Liver Disease
Pregnant women (can cause serious birth defects) - Fetal valproate syndrome - due to folate depletion

Side effects of Valproate

Common side effects are generally similar with other anti-epileptics
Sedation
Dizziness
Headache - less due to it being a migraine medication
N/V

Weight gain - genetic
Alopecia - micronutrient deficiency

Rare
Hypocartininemia (treatment by parenteral L-carnitine)

Drug interactions of Valproate

Alcohol
Cholestyramine
Clonazepam - may cause absence status
CYP modulation
Enzyme inducers and aspirin
Enzyme inhibitors
Lamotrigine may decrease Valproate concentrations (dose reduction needed)
Topiramate - rare hyperammonemia

Carbamazepine indicationa

focal-to-bilateral seizures
Bipolar mania
trigeminal neuralgia

Carbamazepine MoA

seizure
Na+ channel block

Bipolar mania
Adenosine-1 receoptor antagonist blocking the Ca2+ influx

Contraindications of Carbamazepine

carBaMA(S)epine
Bone Marrow suppression

SJS-TEN for people with HLA-B 1502 allele (1512 here in PH)

Hypersensitivity to tricyclics

liver porphyrin (porphyria)

Side effects of Carbamazepine

Common side effects are generally similar with other anti-epileptics
Sedation
Dizziness
Headache
N/V

Rare
SJS-TEN
Bone marrow suppresion
SIADH Hyponatremia
Agranulocytosis

Drug interactions of Carbamazepine

A lot
CYP inducer - 1A2, 2B6, 2C9, 2C19, 3A4,5,7
Anticonvulsants
Antipsychotics
decreased paracetamol bioavailability
increase clearance of Valproate
May increase the serum concentration of CBZ's active 10, 11-epoxidemetabolite

Side effect management

Tolerance builds over time
Gastrointestinal Symptoms (N/V, diarrhea,etc.) - Take with food/take at bedtime
Weight Gane (Lithium, DVP) -Non-pharmacological Management
Sedation - Take at bedtime
Tremors (Li) - Consult a doctor on caffeine intake (stimulants in general for BD)
Alopecia (Li) - Check Cu/Zn levels

Antipsychotics for bipolar

Haloperidol - mania, prone to depressive switch
Olanzapine & Quetiapine - mania and depression - too many S/E
Paliperidone, Risperidone, Aripiprazole - used for mania

RISEperidone - Manic phase only
Paliperidone - Same as Risperidone
OLAnZZZapine - OLA (HI! Manic Phase) andZZZ (Bipolar Depression)
ARIpiprazole -> Ari -> Own -> Mine ->Explosion -> Mania Only

can antidepressants be used for Bipolar depression?

Controversial since Antidepressants cancause a rare risk of Manic Switch

Always has to be paired with mood stabilizer

ADHD biological factors

untuned D1 and a2A receptors
D1 - spam filter
a2A - signal, regulates attention

Tx for ADHD

Amphetamines - 1st line but not available in the PH
Methylphenidate
Atomoxetine

Methylphenidate MoA

NET adn DAT blocker
by blocking this it allows DA and NE to bind more to D1 and a2A

Indications of methylphenidate

ADHD, narcolepsy (daytime sedation only)

onset of methylphenidate

Fast onset
20-60 min (IR)
30-120 min (XL)

ADR of methylphenidate

If you dont have ADHD you only experience BP increase
Loss of appetite > Anorexia (counsel to eat before taking methyphenidate)
Insomnia, irritability, manic switch - can cause sedation in some as their conciuosness is now calmer
dependency and addiction

drug interactions of Methylphenidate

Antacids/Antihistamines/Protein Pump Inhibitors: Increased Absorption
False positive for amphetamines in Urine Drug Screen

Atomoxetine MoA

NET blocker only
- part of the brain that has not DAT thus DA is also transported by NET

Indications and Onset of Atomoxetine

ADHD
4-6 weeks but 1 dose lasts the whole day unlike methylphenidate

Which lasts longer Methylphenidate or atomoxetine

Atomoxetine

Side effects of Atomoxetine

GI dry mouth, constipation
CNS fatigue, dizziness, irritability
Unrinary retention (older men)
less effect on appetite compared to methylphenidate

Alzheimer's diseases drugs mnemonic

DONE RIVAtalizing MEMory GALAna tayo! Pero bago gumala iTApon sa basuraang MABaho

GALA, TA, MAB not available in the PH
DONEpezil
RIVAstigmine
MEMantine

Acetylcholinesterase inhibitors

Donepezil
rivastigmine

MoA of Donepezil and Rivastigmine

In alzhiemer's cholinergic neurons degenerates leading to lower ACh

blocking AChase will allow ACh to not be metabolised

Indications of Donepezil and Rivastigmine

Alzheimer's
Dementia with Lewey bodies

Onset of Donepezil and Rivastigmine

6 weeks for Sx improvement
Months for stabilization of degeneration

Donepezil once daily at bedtime

Rivastigmine & Galantamine - 2x daily with food, lower Cmax higher AUC

Ravastigmine restarting dose cautions

After stopped for > 3 days you need to restart titration of medication
or else it will cause vomiting with esophageal rupture.

Side effects and interactions of Donepezil and Ravastigmine

Insomnia
Peptic Ulcer and GI bleeds
Bradycardia (could be fatal)

Avoid other antiACh's

Memantine indications

Adjunct to Alzheimer's
only for moderate to severe

MoA of Mementine

uncompetetive NMDA receptor antagonist
thus blocking the entry of Ca2+

Side effects and interactions of Memantine

Dizziness Insomnia constipation

Drugs that raise urine pH can reduceelimination of Memantine

T or F
Donepezil, Rivastigmine, and Memantine all cure Alzheimer's

False, there is no cure, only Tx for Sx

Ginko Biloba contains what chemicals that are useful for alzhiemer's Tx

Flavonoids, Bioflavonoids
Proanthocyanidins
Trilactonic Diterpenes

But there are only low quality studies with inconsistent findings.

T or F
Psychotherapy for bipolar disorder works for both

False, It is only used in depression, and only as adjunct not Tx

Types of Psychotherapy

Psychoeducation
Cognitive Behavioral Therapy
Family focused therapy
Interpersonal and Social Rhythm Therapy
Peer Support