mania
period of elevated or irritable mood and increased energy and activity lasting for at least 1 week
symptoms of mania
at least 3 of the following
- inflanted self-esteem or grandiosity
- decreased need for sleep
- great talkativeness or pressure speeche
- flight of ideas or racing thoughts
- decreased attention span
- increase in goal directed activity
- poor impulse control
hypomania
- mood elevation with optimism, not grandiosity
- hypersexuality
- have increased energy, feel good, and are more productive
triggers of manic and hypomanic states
changes in activity, appetite, sleep, and sometimes anxiety
initial mood episodes of bipolar tend to be
depressive in younger patients, often mistaking it for depression
mixed episodes
- depressive and manic features occurring concurrently nearly every day
- suicide attempts and substance abuse are increased in likelihood
most common symptom of bipolar disorder
depression
what happens in the course of bipolar disorder if left untreated
inter-episode intervals with gradually become shorter
initial manic/hypomanic episode is trigger by
major acute stressor or sleep deprivation
Bipolar I
at least one episode of mania or mixed depressive/manic symptoms
Bipolar II
at least one major depressive episode and one hypomanic episode
cyclothymic disorder
hypomanic and depressive symptoms that don’t meet criteria for hypomania or MDD that last for at least 2 years
epidemiology of bipolar disorder
- about 1% prevalence of each type
- men/women equally likely
- geographic distribution is similar
- ethinic distribution has asians with lower rate
suicide rate in bipolar patients
10-20 times higher than in general population
main risk factors for bipolar
- urban areas
- institutionalized and homeless
- single has greater risk than married
- Fx of bipolar, schizophrenia, substance abuse
what percentage of bipolar risk is genetic
75-85%
genes implicated in bipolar disorder
BDNF
CLOCK genes
GSK-3beta
most well known neurobiology changes in bipolar
hypofunction of prefrontal cortex and amygdala
shift between mania and depression is caused by
- instability of the electric properties of neurons, likely facilitated by oxidative stress and neuroinflammatory processes
- changes in activity of dopaminergic system
mania neurobiology is associated with
hyperactivity of dopamine neurotransmission
depression neurobiology is associated with
dopaminergic hypoactivity
mood stabilizers for bipolar therapy
- lithium
- valproic acid
- carbamazepine
- lamotrigine
lithium therapeutic index
very narrow
lithium toxicity level
over 1.5 mmol/L
lithium MoA
- may inhibit release of monoamines and ACh from nerve endings AND increase their uptake
- interferes with inositol trisphosphate formation
IP3 is synthesized by
phospholipase C
enzymes inhibited by lithium
IPP
ImpA
GSK-3beta
all 3 help recycle inositol
time it takes to reach therapeutic levels of lithium
about 2 weeks
recommended dose of lithium for acute mania
1800 mg/day in 2-3 daily doses during meals
desired serum level of lithium
1-1.5 mmol?L
lithium side effects
- neurological effects
- ophthalmic
- otic
- psychosis
- CV (arrhythmias)
- endocrine (hypothyroidism)
- GI
- renal
- autoimmune disease risk
- hematologic
- dermatologic
signs of lithium overdose
- persistent diarrhea
- vomiting/ severe nausea
- coarse trembling of hands or legs
- swelling in feet or lower legs
treatment for lithium toxicity
- gastric lavage
- activated charcoal
- IV NS if hypotensive
contraindications of lithium
- renal disease
- CV disease
- Na depletion/dehydration
- pregnancy and lactation
lithium drug interactions
- SSRI
- diuretics
- NSAIDs
- ACE inhibitors
- CCB
- metronidazole