Lecture 11: Bipolar Disorder

Manic Episode Length

Lasting at least 1 week

Hypomanic Episode Length

Lasting at least 4 days

Manic Symptoms

Distractibility (poorly focused, multitasking)

Insomnia (decreased need for sleep)

Grandiosity (inflated self-esteem)

Flight of ideas (racing thoughts)

Activities (increased goal-directed activities)

Speech (pressured)

Thoughtlessness (risk-taking behaviors)

Bipolar I Disorder

Manic Episode

Bipolar II Disorder

Major depressive episode and hypomanic episode

Cyclothymia Disorder

at least 2 years of numerous periods of hypomanic and depressive symptoms

Lithium

Mania and maintenance of Bipolar Disorder

Decreases inositol

Maintenance treatment of choice

Reduces the risk for relapse

Good with impulsive and aggressive behavior

Only mood stabilizer that reduces suicides

Blood levels every 3 months- very low therapeutic index

Thyroid check every 6 months

Excreted by the kidneys

Competes with sodium for reabsorption

Lithium Side Effects

Teratogenic in 1st trimester pregnancy

Tremor

Nausea, vomiting, headache, acne, hair loss, edema

Thyroid disorders

Li + decreases thyroid hormone synthesis and release, uncouples receptor

TSH increases, hypothyroidism should be treated with l-thyroxine, lower dose of Li

Renal dysfunction

Polydipsia/Polyuria: Increased thirst and urine output (ADH inhibition, uncoupling; diabetes insipidus)

Treat with amiloride → blocks entry of Li to collecting duct

Diarrhea, drowsiness, muscular weakness, hyperreflexia and lack of coordination

Ataxia, giddiness, tinnitus, blurred vision and a large output of dilute urine

Cardiac arrhythmia, bradycardia, seizures, coma, death

Lithium Drug Interactions

Thiazide diuretics decrease sodium reabsorption → lithium concentration increases → toxicity

NSAIDS inhibit PG synthesis, decrease Li clearance → lithium concentration increases → toxicity

Valproic Acid

Anticonvulsant with antimanic effects

Efficacy very good, rapid onset

Mania

Useful for Mixed episodes and rapid cycling

Blood levels

Hepatotoxicity

Teratogenicity-Neural tube defects, decreased IQ

Pancreatitis

Rash, Weight gain, Sedation

Leukopenia/Thrombocytopenia

Carbamazepine

Mixed episode and rapid cycling

GI, sedation, ataxia

dermatological (hypersensitivity)

genetic test for HLA-B*1502

Overdose can be serious

Induces P450- drug interactions

Do not use in pregnancy

Metabolized by CYP450

Oxcarbazepine

Mixed episode and rapid cycling

No blood levels to monitor

Few side effects

Useful if weight gain is feared, depression is not prominent

Atypical Antipsychotics

Acute Mixed episode or mania/Maintenance

Bipolar Depression: Quetiapine, Lurasidone, Cariprazine, Lumaterperone

Benzodiazepines

Uses: Anxiety, Insomnia, Agitation, Withdrawal from Alcohol and Barbiturates

Side effects:

CNS depression, impaired motor coordination, confusion, memory loss, and decreased REM sleep

Tolerance and Dependence

Withdrawal can result in death

Metabolized by CYP450

Carbamazepine