Transcript Drugs used to treat Bipolar Disorder

Drugs Used to Treat
Bipolar Disorder
Background Information
Episodes of Mania and Depression
 Intervention when mood swings are
severe, disrupt life of the patient and/or
family
 4 % population prevalence
 At least 1 manic,hypomanic,or mixed
episode
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Types/Common Terms
Bipolar I- Most severe, obscures normal
functioning, hospitalization common
 Bipolar II- Hypomanic,Full manic episodes
rare. Depression often still severe
 Cyclothymia- Milder form of BP II, “Bipolar
Spectrum Disorder”
 “Rapid Cycling”- 4 or more episodes in a
12 month period,may not be permanent
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Effects:
Estimated 1 out of 4-5 commit suicide
from inadequate or no treatment
 Onset of illness around 25 yrs old and
untreated, often results in loss of approx.
9 yrs of life, 14 yrs of activity, 12 of
normal health
 Prime candidates for lifetime treatment
express at least 2 episodes of mania
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Mania vs.
Depression:Treatment
options
Manic Episode- anti-psychotics (ex.
Zyprexa), or benzodiazepines (sedating)
 Depressive Episode- temporary coadministration with antidepressants
 As a whole- mood stabilizers, classicallyLithium. Anti-epileptics are also currently
being used ( Tegretol, Depakote,
Neurontin, Lamictal)
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Lithium
Widely recommended treatment for
Bipolar Disorder
 60-80% success in reducing acute manic
and hypomanic states
 However… issues in non-compliance to
take medication, side effects, and relapse
rate with its use are being examined in
terms of being the best option

History
1920’s- used as a sedative, hypnotic,
and anti-convulsant
 1940’s- investigated as a salt
substitute for heart disease patients
-How did this work out?
- Poorly- many people died from
toxicity
- The Doctors decided that maybe
it wasn’t such a good idea

History Cont.
1949- experiments with animals led to
lethargy, and use for acute mania.
 The logic was simply to make them too
tired to run out and repaint the entire
house, have wild sex and go shopping
 This is where non-compliance fits in
(seen in up to 50% of patients)…
the patient feels they are being robbed of
their fun by taking meds, so they give
them up.
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More On Non-compliance
Other reasons patients refuse meds:
-weight gain
- less energy, productivity
- feel disease has resolved, no longer
need medication
Relapse rate is high regardless of withdrawal
being gradual or acute, suicide risk back up
episodes are often worse than original
symptoms, so treatment is often life-long
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So where does this leave
us?
Since its discovery, Lithium has been found to
be superior to placebo
 In recent years though, efficacy is being
questioned:
-Long term results not as good as
expected
-28% discontinue use, 38% experience
relapse on the drug
*Even so, it is widely prescribed, demonstrates
considerable efficacy, and reduction in
mortality risks
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Pharmacokinetics:
Peak blood levels reached in 3 hrs, fully
absorbed in 8 hrs
 Absorbed rapidly and completely orally
 Efficacy correlates with blood levels
 Crosses blood-brain barrier slowly and
incompletely
 Usually taken as a single daily dose

Kinetics Cont.
Approx. 2 wks to reach a steady state
within the body
 ½ of oral dose excreted in 18-24 hrs,rest
within 1-2 wks
 Recommended .75-1.0 mEq/L, optimum
would be .5-.7 mEq/L, with 2 mEq/L
displaying toxicity
 Metabolized b/f excretion
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Important:

Because of its resemblance to table salt,
when Na+ intake is lowered or loss of
excessive amounts of fluid occurs, blood
levels may rise and create intoxication
Pharmacodynamics
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No psychotropic effect on non-Bipolars
Affects nerve membranes, multiple receptor
systems and intracellular 2nd messenger
impulse transduction systems.
Interacts with serotonin
Potential to regulate CNS gene expression,
stabilizing neurons w/ associated multiple
gene expression change.
How does a simple ion do all
of this?

Even as a simple ion, it has complex
effects on multiple transmitter systems
and mood stabilizing attributes
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This is due to a latter effect reducing a
neuron’s response to synaptic input, and
therefore stabilizing the membrane
Side Effects and Toxicity
Relate to plasma concentration levels, so
constant monitoring is key
 Higher concentrations ( 1.0 mEq/L and up
produce bothersome effects, higher than 2
mEq/L can be serious or fatal
 Symptoms can be neurological,
gastrointestinal, enlarged thyroid, rash,
weight gain, memory difficulty, kidney
disfunction, cardiovascular
 Not advised to take during pregnancy, affects
fetal heart development
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Combination Therapy
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Combination therapy with Lithium and
anti-epileptics may demonstrate better
protection against relapse, greater
therapeutic efficacy, and studies support
this as a rule vs. an exception
Illegal Drug Use
More than 55% of Bipolar patients have a
history of drug abuse
 Some abuse might occur before the first
episode, or after diagnosis
 Used by some as a way to self-medicate
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If Lithium Doesn’t Work
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40% of Bipolars are resistant to lithium or
side effects hinder its effectiveness
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Therefore, we must consider alternative
agents for treatment
Valproic Acid (Depakote)
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An anti-epileptic, it is the most widely used
anti-manic drug
Augments the post-synaptic action of GABA at
its receptors (increasing synthesis and
release)
Best for rapid-cycling and acute-mania
Therapeutic blood levels: 50-100 Mg/L
Side effects include GI upset, sedation,
lethargy,tremor, metabolic liver changes and
possible loss of hair
Can also be used for anxiety, mood, and
personality disorders
Carbamazepine (Tegretol)
Superior to lithium for rapid-cycling,
regarded as a second-line treatment for
mania
 Correlation between therapeutic and
plasma levels (estimated between 5-10
Mg/L)
 Side effects may include GI upset,
sedation, ataxia and cognitive effects
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Gabapentin
Primarily an anti-convulsant, yet also “off
label,” or without FDA approval for treatment
of Bipolar and many other anxiety, behavioral
and substance abuse problems, possibly pain
disorders
 GABA analogue
 not bound to plasma proteins, not
metabolized, few drug interactions
 Half-Life is 5-7 hours
 Side Effects include
sleepiness,dizziness,ataxia and double vision
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Lamotrigine
Reported effective with Bipolar,
Borderline Personality, Schizoaffective,
Post-Traumatic Stress Disorders
 98% of administered drug reaches plasma
 Half-Life is 26 hrs.
 Inhibits neuronal excitability and
modifies synaptic plasticity
 Side Effects may include dizziness,
tremor, headache, nausea, and rash
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Topiramate and Tiagabine
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Two newer anti-convulsants that have
potential for use in the treatment of
Bipolar disorder
Atypical Anti-psychotics
3 types that may be used for BPClozapine, Risperidone, and Olanzapine
 Risperidone seems more anti-depressant
than anti-psychotic
 Clozapine is effective, yet not readily
used due to potential serious side effects
 Olanzapine is approved for short-term
use in acute mania
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Acetylcholinesterase
Inhibitors
Potentiating the action of acetylcholine
may exert relief from mania
 This potentiation is the result of
inhibiting the enzyme acetylcholine
esterase
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Omega-3 Fatty Acids
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Obtained from plant or marine sources
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Known to dampen neuronal signaling
transduction systems in a variety of cell
systems
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Being investigated as a treatment for
Bipolar Disorder
Psychotherapeutic and
Psychosocial Treatments
Combination drug and psychotherapeutic
intervention is the most effective
treatment
 Goals of Psychotherapeutic treatment are
to reduce distress and improve function
between episodes
 May include cognitive behavioral,
psychodynamically oriented, family,
couples, interpersonal, and self-help
group therapies
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