Lecture 13 Bipolar Disorder and Mood Stabilizers Flashcards
What is bipolar disorder?
Manic episode
What is the prevalence of bipolar disorder?
2.5% of population
equal among males and females
first episode tends to be mania in men and in women it tends to be depressed
What are the symptoms of mania?
elevated mood, irritable mood
inflated self esteem, increased goal oriented activity, decreased need of sleep, risk taking, distractible, more talkative, racing ideas
Hypomania
A minor form of mania
Dysthmia
A minor form of depression although longer acting
Bipolar I
One or more manic episodes
depressive or hypomanic episode not required for diagnosis, but frequently occurs
Bipolar II
Predominantly depressive but combined with hypomania and not mania
Cyclothymic
Cycling between hypomania and dysthmia
What comorbidities are common with the manic phase?
Anxiety disorder, drugs & alcohol, psychosis, aggression, ADHD and borderline personality disorder
What are some possible causes bipolar disorder?
Genetic factors, neurochemical factors, environmental factors
What are the concordance rates in monozygotic twins?
for Bipolar I, concordance rates ~40% in monozygotic twins, ~10% in dizygotic twins
What genes may be affected in bipolar disorder?
Clock genes: regulate circadian rhythms and sleep
What are the environmental factors for bipolar disorder?
traumatic/stressful childhood events in genetically susceptible individuals, substance abuse
What are the neurochemical factors for bipolar disorders?
dysregulated monoamines, glutamate/GABA balance, disrupted cell signaling
Why aren’t antidepressants used in the depressive phase?
Often times bipolar patients “over respond” to antidepressants and can lead to a manic response
What are some side effects of lithium carbonate?
dry mouth, frequent urination, nausea, acne, tremor, sedation, fuzzy cognition
What is a common mood stabilizer?
Lithium Carbonate
What is Lithium carbonate effective at treating?
- Effective at treating and preventing recurrent mania
- May be effective at stabilizing depression phase
- Established to prevent suicide in bipolar patients
What are the mechanisms of action of lithium?
- How lithium carbonate produces mood stabilizing effects has eluded scientists for decades
- Recent evidence suggests in blocks the formation of inositol (a second messenger required for activation of protein kinase C) and glycogen synthase kinase 3 beta (GSK-3β)
- The results are altered gene expression, but the details are still unclear
What is an issue with lithium?
- Lithium has a very narrow therapeutic index
- Lithium has some CNS toxicity
- Renal and thyroid toxicity
- Requires regular blood monitoring
What are some effects of CNS toxicity of lithium?
Moderate-restlessness, irritability and sedation
Severe-delirium, seizures, coma and death
Name 3 anticonvulsants that are used in bipolar disorder
Valproic acid, carbamazepine, and lamotrigine
What is the mechanism of anticonvulsants?
- Inhibits voltage-sensitive sodium and/or calcium channels to suppress glutamate release
- Inhibits GSK-3β and PKC activity
- Inhibits GABA reuptake and breakdown via GABA transaminase (GABA-T)
What is an issue with anticonvulsants?
Numerous side effects, also a known teratogen
What is valproic acid effective at treating?
- Effective at treating acute mania, but not preventing future manic episodes
- Some efficacy in reducing depression
What are carbamazepine and lamotrigine effective at treating?
May be more effective at treating mixed episodes and rapid cycling
What is another type of mood stabilizer other than lithium and anticonvulsants?
Atypical antipsychotics
Primarily quetiapine (Seroquel) and lurasidone (Latuda)
What are side effects of atypical antipsychotics? and what is the mechanism of action
- Side effects vary but include weight gain, sedation, dry mouth and metabolic disorders
- Mechanisms of action include D2 and 5-HT2A antagonism, and 5-HT1A partial agonism
