Psychopharmacology of Bipolar Disorder (J16)

Psychopharmacology 
of Bipolar Disorder

Bipolar Disorder
Characterized by recurrent episodes of mania & depression.
Occurs in est. 1% to 4% of people.
Bipolar I = severe;
Bipolar II = less severe.
Many famous persons with Bipolar.
>55% of bipolar pts have hx of substance abuse (ETOH 82% of that).

Lithium (Li)
Historically, the most recommended drug for tx. of bipolar disorder.
Effectively treats 60% - 80% of acute hypomanic and manic episodes.
Less effective than predicted by clinical trials; patients noncompliant.
Natural course of bipolar is worse with Li non-compliance than with untreated disease.

Lithium (Li)
Efficacy is in question.
Research suggests that Li is a good adjunct to antidepressant medication in people with treatment resistant depression.
Li & antiepileptic drug (combination tx) is common.

Lithium (Li)
Pharmacokinetics
Oral administration > rapid and complete absorption.
Not metabolized. Excreted unchanged mostly via kidneys.
Long half-life. Steady state is reached in about 2 weeks.
Narrow theraputic range. Too low = no effect. Too high = toxic. Blood levels need close monitored (not always the case).
Closely resembles table salt. Lower salt intake or increased loss (aerobic activity) > toxicity.

Lithium (Li)
Pharmacodynamics
No psychotropic effect in normal people @ clinical dose.
Specific action on mania without other brain effects.
No one really knows the mechanism of acction.

Lithium (Li)
Narrow therapeutic range; blood levels need close monitoring.
Not taken when pregnant.
No antidote.
Course of disease probably worse if Li stopped, compared with never taken .

Lithium (Li)
Toxicity (Side Effects):
GI tract (nausea, vomiting, diarrhea, abdominal pain), 
kidneys (>urine output, thirst), thyroid (enlarged), 
cardiovascular system, 
skin (rash), 
nervous system(slight tremor, lethargy, confusion, slurred speech, ataxia, muscle weakness, nystagmus).
Long term: weight gain (30%>obese), poor memory,

Lithium (Li)
Lifelong commitment.
Noncompliance 
(because of toxic effects).
50% stop Li a.m.a.
> morbidity 
>manic episodes >suicide

Anticonvulsants
Tegretol (carbamazipine)

Much better than Li for rapid cycling bipolar.
Toxic effects: GI upset, sedation, ataxia, visual disturbances, rashes, mild reduced cognition.
Contraindicated during pregnancy.
Adverse blood reactions can occur; blood needs to be monitored.
Drug interactions are common & tolerance develops.

Anticonvulsants
Depakote (valproic acid)
The most widely used antimanic drug.
Very effective in tx of acute mania, mixed states, schizo-affective disorder, & rapid-cycling bipolar disorder.
Used in combination with Li for some; used in pregnant women. Also used for Borderline PD, and behavioral disorders, and anxiety.
Toxic effects: GI upset, sedation, hand tremor, hair loss, liver changes, cognitive decline.

Anticonvulsants
Neurontin (gabapentin)
“off label”: bipolar, anxiety, behavioral dyscontrol, substance dependency, borderline PD, peripheral neuropathy.
pharmacokinetics: not bound to plasma proteins, not metabolized, excreted unchanged thru kidneys, few drug interactions.
Used to augment Li (and other drugs).
Toxic (side) effects: sleepiness, dizziness, ataxia, nystagmus, double vision.

Psychotherapy
A combination of drug therapy & psychotherapy is the most effective treatment for bipolar illness.