GIDDINESS

Grandiosity

Increased activity

Decreased judgement

Distractibility

Irritability

Need for sleep decreased

Elevated mood

Speedy thoughts

Speedy speach

DSM-IV-TR

Criteria for a Manic Episode

1. > 1 week of elevated, expansive, or irritable mood
2. Mood Disturbances: > 3 of the following symptoms:

• Grandiosity
• Decreased need for sleep
• Hyperverbal
• FOI
• Distractibility
• Excessive involvement in pleasurable activities
• Increase in goal-directed activity

3. Symptoms must not meet criteria for mixed episode

4. Mood disturbances severe enough to cause marked impairment, need for hospitalization, or psychosis is present

5. Symptoms not due to substance abuse or general medical condition (hyperthyroidism)

• Less severe form of mania
• At least 4 days of persistently elevated mood and associated with > 3 of the following symptoms:

1. inflated self-esteem
2. decreased need for sleep
3. distractibility
4. irritability
5. pressured speech
6. increased activity or excessive involvement in pleasurable activities
7. racing thoughts (FOI)

• Hospitalization NOT required
• NO psychotic features

• Males = Females
• Presence of only 1 manic episode (necessary)
• The manic episode is not better accounted for by schizoaffective disorder

• Females > Males
• Presence or history of 1 or more major depressive episdoes
• Presence or history of at least 1 hypomanic episode
• There has never been a manic episode or a mixed episode
• The mood symptoms are not better accounted for by schizoaffective disorder
• The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning

• > 4 mood episodes (mania, depression, mixed episode, hypomania) in 1 year
• 5-15% of patients with bipolar disorder
• > women (70-90%)
• More difficult to treat

Stage 1 (hypomania)

euphoria, labile mood, grandiosity, overconfidence, racing thoughts, hyperverbal

Stage 2 (mania)

irritability, dysphoria, hostility, anger, delusions, cognitive, disorganization

Stage 3 (psychosis)

terror, panic, bizarre, behavior, hallucinations, disorientation

• Acute manic , mixed, and hypomanic episodes
• Acute major depressive episodes in bipolar disorder
• Maintenance tx of bipolar disorder
• Schizoaffective disorder
• Refractory schizophrenia
• Refractory depression
• Assaultive, aggressive, impulsive behavior

• Lithium
• Valproate
• Carbamazepine
• Lamotrigine
• Atypical Antipsychotics

Most effective for Bipolar Disorder Type I

• Bipolar mania and depression
• Bipolar relapse prevention
• Unipolar depression augmentation
• Suicidality prevention

• Antagonizes Adrenergic and Dopaminergic activity
• Enhances serotonergic activity
• Inhibits neurotransmitter-coupled Adenyly Cyclase activity and cAMP formation
• Inhibits PIP
• Inhibits G-protein coupling to muscarinic cholinergic and beta-adrenergic receptors

0.8-1.5 mEq/L --> acute mania

0.6-1.2 mEq/L --> maintenance

Toxicity may occur if > 1.5 mEq/L

Every 300 mg increase in dose will increase Lithium plasma levels by 0.15-0.35 mEq/L

• Draw plasma levels 12 hrs post-dose
• Obtain plasma level ~ 5 days after initiating therapy or after dose change
• Check plasma levels every 1-2 weeks until patient is stabilized
• Maintenance plasma levels may be measured every 3-6 months

Initial: 300-1200 mg/day in divided doses BID-TID

100 lbs -- 300 mg BID

150 lbs -- 300 mg TID or 450 mg TID

200 lbs -- 600 mg TID

Increase by 300 mg to 600 mg q 5 days depending on Lithium plasma level

Acute dosing range: 1200-2700 mg/day

Usual maintenance dose: 900-1800 mg/day

• Nausea/vomiting
• Diarrhea
• Fine hand tremor
• Muscle weakness
• Fatigue
• Lethargy
• Headache
• Polydipsia and polyuria
• Impaired cognitive functioning
• "Mental clouding or loss of creativity"

• Take Li with food
• Change to ER product

• Give total dose q HS to decrease urine volume
• Add HCTZ 25-50 mg/day and decrease Li dose or add amiloride

• Check for toxicity and consider decrease Li dose
• Change to ER product
• Add propranolol 20-120 mg/day

• Cardiovascular: prolonged QT interval, T-wave flattening or inversion, AV block, bradycardia
• Dermatologic: worsens acne, alopecia
• Endocrine: hypothyroidism
• Metabolic: weight gain
• Hematologic: benign reversible leukocytosis
• Nephrologic: decreased GFR, diabetes insipidus

• Thyroid (TSH) - q 6 month
• Renal function (SCr and BUN) - q 3 month
• CBC with diff
• Electrolytes (hyponatremia)
• ECG (pt > 40 yo or preexisting heart condition)
• Urinalysis (specific gravity)
• Pregnancy test

Moderate (> 1.5 mEq/L)

• Confusion
• Sedation
• Lethargy
• Muscle weakness
• Ataxia
• Dysarthria
• N/V
• Slurred speech
• Fine to coarse hand tremor

Severe (> 3.0 mEq/L)

• Hyperreflexia
• Delirium
• Seizures
• Coma
• Renal failure
• Death

• Elderly patients
• Drug interactions (NSAIDs, ACEI, ARBs)
• Na+ restricted diets (< 2 g/day)
• Dehydration, heavy exercise, hot weather
• Vomiting and severe diarrhea

• Discontinue Li
• Gastric lavage
• Monitor for fluid imbalance and rehydrate
• Correct electrolyte imbalances
• Intermittent hemodialysis (12 hrs on, 12 hrs off) -- can increase lithium clearance

• NSAIDs -- enhances reabsorption of Li secondary to inhibition of PG synthesis
• Diuretics -- cause Na depletion which causes an increase in proximal tubular reabsorption of Li
• ACEI -- volume depletion = decrease in GFR causing decrease Li excretion and increase Li levels

• Theophylline and Caffeine -- increase the renal clearnace of Li
• Alcohol -- concomitant use of Li + EtOH results in small increase or decrease in Li plasma concentration

• Methyldopa
• Carbamazepine
• CCB (diltiazem, verapamil)
• Phenytoin
• SSRIs (fluvoxamine, fluoxetine)

• Rapid cycling or mixed mania
• Hx of head trauma

• Lower risk of toxicity (OD risk)
• Safer in renal disease
• Less drug interactions (compared to Li)

• Less evidence for relapse prevention
• Hepatotoxicity
• No IM dosage form available

• Enteric Coating Available
• Absorption in the small intestine
• QD-TID dosing
• GI upset +

• No Enteric Coating Available
• Absorption in the stomach
• BID-TID dosing
• GI upset +++
• Liquid capsules

• No Enteric Coating Available
• Absorption in the small intestine
• QD dosing
• GI upset +

Initial Slow Titration

• 250 mg BID or TID, increase by 250-500 mg q 3-7 days as tolerated

Initial Loading Dose

• 20 mg/kg/day
• Add "0" to weight in lbs

Usual Maintenance Dose

• 1000-4000 mg/day

Max Recommended Maintenance Dosage

• 60 mg/kg/day

Dose-Related ADRs

• GI upset (nausea, diarrhea, dyspepsia)
• Sedation, ataxia
• Intentional hand tremor
• Transient elevated LFTs
• Thrombocytopenia (< 100,000 caution; < 50,000 d/c)
• Weight gain
• Amenorrhea - PCOS

Other ADRs

• Alopecia
• Hyperammonemia
• Rash
• Pancreatitis

• Teratogenicity
• Hepatotoxicity
• Pancreatitis

• Obtain plasma level 2-3 days after initiating tx or after dose change
• Draw plasma levels 12 hrs post-dose
• Obtain plasma levels monthly until stable, until q 3 months
• Therapeutic plasma level: 50-125 mcg/mL

• LFTs, Bilirubin
• CBC with diff
• Routine weight
• Ammonia levels (if symptomatic)
• Vagina consult
• Prego test

• Aspirin and Anticoagulants -- increase risk for bleeding
• Lamotrigine, lorazepam -- increase blood levels of lamotrigine, lorazepam
• Alcohol and CNS depressants -- increase toxicity of CNS depressants

• weeks 1-2 initiate therapy with 25 mg QD
• weeks 3-4 give 50 mg QD
• week 5 give 100 mg QD
• weeks 6-7 and thereafter, give 200 mg QD

• weeks 1-2 initiate therapy 25 mg every other day
• weeks 3-4 give 25 mg QD
• weeks 5 give 50 mg QD
• weeks 6-7 and thereafter, give 100 mg QD

• weeks 1-2 initiate therapy with 50 mg QD
• weeks 3-4 give 50 mg BID
• week 5 give 100 mg BID
• week 6 give 150 mg BID
• week 7 and thereafter, > 200 mg BID

• Dizziness
• Somnolence
• Ataxia
• N/V
• Blurred vision
• HA

• Skin for rash
• LFTs annually
• No plasma blood monitoring necessary

Oral dosage regular-release tab

• Initially dose 200 mg BID
• Increase q 3-4 days to achieve therapeutic serum conc.
• Usual range 600-1600 mg QD in divided dose

• CNS: sedation, slurred speech, dizziness, ataxia, diplopia
• Hyponatremia
• Transient LFT increases: cholestatic jaundice
• Severe rash: rare

• Agranulocytosis
• Aplastic anemia

• Obtain plasma level 7 days after initiating therapy or after dose change (need 1 week to reflect new steady state)
• Draw plasma levels 12 hr post dose
• Obtain level weekly during titration; every 3 months or as clinically necessary thereafter

• 4-12 mcg/mL (tx of seizure disorder)
• 8-12 mcg/mL (establish adequate trial)

• Liver (ALT/AST)
• CBC
• Urinalysis and BUN
• Metabolic Panel
• ECG
• Pregnancy test

• Initiate at 300 mg BID
• Increase (as tolerated) by 300 mg QD every third day or 600 mg QD at weekly intervals
• Usual maintenance dose: 1200-2400 mg QD given in divided doses

• Better tolerated than CBZ
• CNS -- sedation, dizziness, ataxia, HA
• Hyponatremia
• Rash
• Nausea

• Metabolic panel -- significant hyponatremia (Na<125mmol/L) may develop usually during 1st 3 months of tx
• Monitor at baseline, monthly for 1st 3 months and when s/sx of hyponatremia occur --> nausea, malaise, HA, lethargy, confusion

• 25-50 mg/day
• Titrate in increments of 25-50 mg/week  (max = 1600 mg/day)

• Weight loss (nausea,dyspepsia)
• Kidney stones
• Narrow angle glaucoma
• Oligohydrosis
• Metabolic acidosis
• Cognitive dysfunction

• Usually used to help stabilize pts who are acutely manic or agitated
• Generally not accepted as monotherapy for maintenance, although olanzapine and aripiprazole are indicated for maintenance treatment
• Pts with mood disorders may be more sensitive to EPS, which is a possibility with the atypical antipsychotics

• 1st line -- Li, VPA, or SGA
• 2nd line -- carbamazepine, oxcarbazepine

• 1st line -- Li or lamotrigine or quetiapine
• Other -- fluoxetine + olanzapine combo
• Psychosis or high suicide rate -- add SGA or ECT
• May add on antidepressants in more severely ill pts

• 1st line -- Combo therapy -- VPA may be more effective than Li
• Rapid cycling -- d/c all antidepressants

• Adequate sleep hygeine
• Stress reduction
• Psychoeducaiton
• Balanced diet (L-tryptophan) + omega-3 fatty acids
• ECT (tx refractory)