Mod 9 Mood Stabilizers

Bipolar Disorder

• Manic-depressive illness

• Unusual shifts in mood, energy, activity levels

• Inability to carry out daily activities

• Can lead to suicide

Manic Episode

Abnormally, persistently observed (≥1 week, most of the day, nearly everyday):

• Increased / expansive / irritable mood

• ↑ Goal-directed activity or energy

Characterized by more than 3 of the ff. (4 if only irritable mood is present):

• ↑ self-esteem, grandiosity

• ↓ need for sleep

• More talkative than usual or pressured to keep talking (rapid / loud / difficult to interrupt)

• Flight of ideas / racing thoughts (disorganized speech, abrupt topic shifts)

• Distractibility 

• ↑ goal-directed activity (social / school /  work / sex) or psychomotor agitation 

• Excessive involvement in activities w/ high potential for painful consequences 

  • i.e. gambling, shopping, bad investments, dangerous activities etc.

Hypomanic Episode

Abnormally, persistently observed (≥4 consecutive days, most of the day):

• Same as Manic Episode

Characterized by more than 3 of the ff. (4 if only irritable mood is present):

• Same as Manic Episode

Additionally:

• Associated w/ uncharacteristic change in functioning

• Observable by others

• May not be severe enough to impair social / occupational functioning

Major Depressive Episode

Observed everyday or almost everyday:

• Depressed mood (sadness, emptiness, hopelessness)

• Anhedonia

• Significant weight loss/gain

insomnia/oversleeping

• Psychomotor agitation/retardation

• Fatigue, loss of energy

• Feelings of worthlessness, excessive/inappropriate guilt

• Diminished activity to think/concentrate → indecisiveness

• Recurrent thoughts of death, suicidal ideation w/o a specific plan, OR suicide attempt or specific plan for committing suicide

• SIGECAPS

BPD Diagnosis

Symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning

Rule Out:

• Unipolar major depressive disorder (69% misdiagnosed, Tx delay 10 years)

• Comorbidities and other drugs or substances

• Anxiety disorders

• Substance use disorders

• ADHD

BPD I

≥ 1 manic episode ± hypomanic episode or major depressive episode

BPD II

• Current or past major depressive episode ± current or past hypomanic episode

• No manic episode, hypomanic instead

BPD Pathophysiology Genetics

• 7-fold risk w/ 1st degree relative

• 50% of diagnosed have family history

• Concordance rate

  • Monozygotic: 40-80%

  • Dizygotic: 14-20%

BPD Pathophysiology Neuroplasticity

• Intracellular signaling cascades

• Gene regulation

• Synapse modifications

• Axonal/dendritic architecture changes

• BDNF/GDNF expression

  • Same goal as anti-depressants. Improve communications between neurons.

  • GDNF - Glial cell line-derived neurotrophic factor

BPD Pathophysiology Epigenetics

• Histone protein modification

  • Hyper-CH3 causing downregulation in expression of genes in GABAergic interneurons

• Covalent DNA modification

• Regulation by noncoding RNA

BPD Pathophysiology HPA, Inflammation, etc.

• Cortisol

  • Stress hormone (stress tolerance

• Interleukins

• Glutamate

• Intrinsic apoptosis of neurons

  • Programmed cell death in response to stressors

Lithium

• Drug of choice due to superior clinical efficacy

• Narrow therapeutic index (toxic > 1.5mM)

• Reduces risk of both attempted suicide and death by suicide by up to 80%

• Adjunct for depression

Lithium Common ADRs

Relatively little weight gain

Lithium Rare / Potentially Fatal ADRs

• Lithium toxicity

• Renal impairment (interstitial nephritis)

• Vasopressin resistance (Nephrogenic diabetes insipidus)

• Rare seizures

• AV block, arrhythmias, ECG changes

• Seizure, disorientation, and potentially coma

Lithium Contraindication/s

• Severe kidney disease

• Severe cardiovascular disease

• Severe debilitation

• Severe dehydration, sodium depletion

Lithium Indication/s

Bipolar disorder, acute & maintenance

Lamotrigine Indication/s

-Focal seizures

-Bipolar depression (Pag walang BIDEt, nakaka-“”depress””, kaya magla-LAMOn)

Lamotrigine Rare ADRs

Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN)

• Presents with abnormal rashes on the skin

• Epidermal necrolysis meaning death of skin

  • Pediatric: 0.3-0.8%

  • Adult: 0.08-0.3%

Divalproex & Valproate Indication/s

• Seizures

  • Tonic-clonic

  • Myoclonic

• Bipolar mania

  • Mixed episodes

• Chronic migraine prophylaxis

Divalproex & Valproate Common ADRs

• Weight gain

• Alopecia

• Polycystic ovaries

• Hyperandrogenism

• Hyperinsulinemia

• Lipid dysregulation

• Decreased bone mineral density

Valproate Rare / Potentially Fatal ADRs

• Hepatotoxicity

  • Hypocarnitinemia

    • Impaired mitochondrial fatty acid oxidation and impaired valproate metabolism

    • Valproate combines with carnitine, causing its depletion

  • Lipid peroxidation and glutathione depletion

• Hyperammonemic encephalopathy

  • Hypocarnitinemia

    • Impairment of urea cycle

  • Rare pancreatitis

  • Activation of suicidal ideation

Divalproex & Valproate Contraindication/s

• Urea cycle disorder

• Pancreatitis

• Serious liver disease

• Mitochondrial disorders 

• Pregnancy, women of childbearing potential (unless no alternatives)

  • Valproic acid can cause neural tube defects in developing fetus

  • Possible presentations of neural tube defects: cleft palate, spina bifida

• Thrombocytopenia

Carbamazepine Indication/s

• Focal and focal-to-bilateral seizures  

• 1st line for benign occipital epilepsies  

• Bipolar mania

• Trigeminal neuralgia

Carbamazepine Rare / Potentially Fatal ADRs

• Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN)

  • Avoid w/ paracetamol

• Blood dyscrasias

• Bone marrow suspension

• Hyponatremia

• Rare induction of psychosis, mania 

• Rare cardiac problems 

• Rare activation of suicidal ideation

Blood Dyscrasias

An imbalanced number of blood cells

Carbamazepine Contraindication/s

• Positive test for HLA-B*1502 allele

• AV block  

• History of bone marrow suppression  

• Hepatic porphyria  

• Hypersensitivity to CBZ, tricyclics

Lamotrigine Storage Requirements

Controlled room temperature

Divalproex & Valproate Storage Requirements

Controlled room temperature or < 30 degrees celcius

Carbamazepine Storage Requirements

• Tablet:

  • Protect from light and moisture

• MR tablet:

  • Moisture protection

• Syrup:

  • Protect from light