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Bipolar Disorder (General Information (Subtypes (Bipolar I Mania +…

- - - - Antipsychotics
        MOA: DA and 5-HT ANTAgonists
        
        Atypical
        May be sole treatment initially
        or used to control psychosis agitation
      - Anticonvulsants
        MOA: Voltage-gated Na+ channel blockers,
        reducing the ability to recover from inactivation
        (this prevents neurons from firing at high frequencies)
        TREATMENT: combined with atypical and antipsychotics
        
        Acute Mania
        
        Valproic Acid
        • Non-specific binding to VG Na+ channels
        • Facilitate GABA-ergic neurotransmission
        • Has a more rapid antimanic effect at 3-5 days (vs lithium)
        
        Adverse Effects
        
        CNS
        Weight Gain
        
        Carbamazepine
        • Effect for acute mania
        • Requires ER due to neurological s/e like dizziness and ataxia
        
        Specific affinity for open-channel
        configuration of the
        alpha-subunit of Na+ channels
        
        Carbamazepine Warning
        Steven-Johnson Syndrome
        requires hospitalization
        HLA-allele B*1502 genotype is a marker for
        carbamazepine-induced SJS and
        toxic epidermal necrolysis (TEN)
        Prevalence: >15% in certain Asian populations
        
        Bipolar Maintenance
        
        Lamotrigine
        Inhibits glutamatergic neurotransmission
      - Lithium Carbonate
        Best treatment for preventing future manic and depressive phases as well as reduction of suicidality
        
        MOA:
        unknown
        
        Treatment
        • Rarely used alone
        • Effective for acute mania
        but takes 5-7 days for clinical effect
        
        Adverse Effects
        
        CNS
        • Mental fatigue and cognitive dulling
        • Uncoordination, ataxia, slurred speech
        • Hand tremor (dose dependent)
        • Tolerance over time (may require beta-antagonist intervention)
        • Weight gain (possibly due to hypothalamic/appetite stimulation)
        
        Renal
        • Kidney's ability to concentrate urine decrease during Li+ therapy
        • ~60% of patients experience polyuria, polydipsia due to decreased renal re-absorption of water
        • Common 24-hour urinary output: 3 L/day
        
        Thyroid
        • Enlargement in some patients even with normal function
        • 7-10% have overt HYPOthyroidism
        • 23% have subclinical effects
        • 3-9x greater risk in females than males
        
        Cardiovascular
        • Effects on cardiac conduction and pacemaker automaticity
        • Overdose → sinus bradycardia, atrioventricular blocks, and cardiovascular compromise
        
        Skin
        • Allergic reactions and inflammation
        • Dermatitis, acne, psioriasis, and alopecia
        
        Pregnancy
        Lithium, Valproate, and Carbamazepine → Category D
        
        Early Pregnancy
        
        Lithium has CV defects (Ebstein's Anomaly)
        
        Valproic Acid leads to irreversible neural tube defects
        
        Carbamazepine leads to irreversible neural tube defects
        
        Antipsychotics or ECT potentially safer for acute mania in the first trimester.
        
        Later Pregnancy
        
        Polyuria is exacerbated by Lithium
        
        Lithium passes the placental barrier, leading to fetal/neonatal toxicity within the maternal therapeutic range, causing:
        
        Neonatal goiter
        
        CNS depression
        
        Hypotonia
        
        Cardiac murmur
        
        Standard Practice is to withhold lithium 24-48 hours before delivery.
        
        Toxicity Effects
        There is NO antidote and the patient has to ride out the effects.
        
        Mild
        • N/V/D
        • Sedation
        • Fine Tremors
        
        Acute
        • Vomiting
        • Profuse Diarrhea
        • Coarse Tremor
        • Ataxia
        • Coma
        • Convulsions
        
        Serious
        • Mental Confusion
        • Hyperreflexia
        • Gross Tremor
        • Dysarthria
        • Seizures
        • Coma
        • Death