Lecture 13 Bipolar Disorder and Mood Stabilizers

Question 1

What is bipolar disorder?

Answer 1

Manic episode

Question 2

What is the prevalence of bipolar disorder?

Answer 2

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

Question 3

What are the symptoms of mania?

Answer 3

elevated mood, irritable mood

inflated self esteem, increased goal oriented activity, decreased need of sleep, risk taking, distractible, more talkative, racing ideas

Question 4

Hypomania

Answer 4

A minor form of mania

Question 5

Dysthmia

Answer 5

A minor form of depression although longer acting

Question 6

Bipolar I

Answer 6

One or more manic episodes

depressive or hypomanic episode not required for diagnosis, but frequently occurs

Question 7

Bipolar II

Answer 7

Predominantly depressive but combined with hypomania and not mania

Question 8

Cyclothymic

Answer 8

Cycling between hypomania and dysthmia

Question 9

What comorbidities are common with the manic phase?

Answer 9

Anxiety disorder, drugs & alcohol, psychosis, aggression, ADHD and borderline personality disorder

Question 10

What are some possible causes bipolar disorder?

Answer 10

Genetic factors, neurochemical factors, environmental factors

Question 11

What are the concordance rates in monozygotic twins?

Answer 11

for Bipolar I, concordance rates ~40% in monozygotic twins, ~10% in dizygotic twins

Question 12

What genes may be affected in bipolar disorder?

Answer 12

Clock genes: regulate circadian rhythms and sleep

Question 13

What are the environmental factors for bipolar disorder?

Answer 13

traumatic/stressful childhood events in genetically susceptible individuals, substance abuse

Question 14

What are the neurochemical factors for bipolar disorders?

Answer 14

dysregulated monoamines, glutamate/GABA balance, disrupted cell signaling

Question 15

Why aren’t antidepressants used in the depressive phase?

Answer 15

Often times bipolar patients “over respond” to antidepressants and can lead to a manic response

Question 16

What are some side effects of lithium carbonate?

Answer 16

dry mouth, frequent urination, nausea, acne, tremor, sedation, fuzzy cognition

Question 17

What is a common mood stabilizer?

Answer 17

Lithium Carbonate

Question 18

What is Lithium carbonate effective at treating?

Answer 18

• Effective at treating and preventing recurrent mania
• May be effective at stabilizing depression phase
• Established to prevent suicide in bipolar patients

Question 19

What are the mechanisms of action of lithium?

Answer 19

• 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

Question 20

What is an issue with lithium?

Answer 20

• Lithium has a very narrow therapeutic index
• Lithium has some CNS toxicity
• Renal and thyroid toxicity
• Requires regular blood monitoring

Question 21

What are some effects of CNS toxicity of lithium?

Answer 21

Moderate-restlessness, irritability and sedation

Severe-delirium, seizures, coma and death

Question 22

Name 3 anticonvulsants that are used in bipolar disorder

Answer 22

Valproic acid, carbamazepine, and lamotrigine

Question 23

What is the mechanism of anticonvulsants?

Answer 23

• 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)

Question 24

What is an issue with anticonvulsants?

Answer 24

Numerous side effects, also a known teratogen

Question 25

What is valproic acid effective at treating?

Answer 25

• Effective at treating acute mania, but not preventing future manic episodes
• Some efficacy in reducing depression

Question 26

What are carbamazepine and lamotrigine effective at treating?

Answer 26

May be more effective at treating mixed episodes and rapid cycling

Question 27

What is another type of mood stabilizer other than lithium and anticonvulsants?

Answer 27

Atypical antipsychotics

Primarily quetiapine (Seroquel) and lurasidone (Latuda)

Question 28

What are side effects of atypical antipsychotics? and what is the mechanism of action

Answer 28

• 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