Mood Stabilizers

Question 1

What is the difference between Bipolar 1 and Bipolar 2?

Answer 1

Bipolar 1: At least one manic or mixed mood episode, often followed by a depressive episode

Bipolar 2: At least one hypomanic episode, following a depressive episode (less dramatic form of manic episode)

Question 2

What are the diagnostic criteria for a manic episode?

Answer 2

1 week period of abnormal / persistent elevated mood with 3 of the following criteria (4 if the mood is irritable):

• High self esteem
• Less need for sleep
• increased talking
• racing thoughts / ideas
• distractability
• increased activity (social, work, sexually)
• excessive high risk, pleasurable activities (shopping sprees, risky investments)

Question 3

What nonpharmacologic therapies can be applied for bipolar disorder?

Answer 3

1. Psychotherapy

2. Electroconvulsive-therapy - good for treatment resistant all states + pregnant women

Question 4

What classes of drugs fall within “mood stabilizers”?

Answer 4

Lithium, anticonvulsants, and atypical antipsychotics?

Question 5

When are the anticonvulsants preferred for bipolar treatment, and give an example of one?

Answer 5

Acute mania, especially mixed episodes (irritable / dysphoric mania rather than euphoria)

Example: Valproic acid

Question 6

What are the atypical antipsychotics good for, and give an example of one?

Answer 6

Treatment of acute mixed episodes, and bipolar depression

Example: Quetiapine - seroquel

Question 7

What is the postulated mechanism of action of lithium?

Answer 7

Stabilization of catecholamine receptors, altered Ca+2 mediated intracellular functions, and increased GABA activity

Second messenger system inhibition:

• > Inhibits IMP in the Gq signalling system
• > inhibits adenylate cyclase in Gs signalling system
• > Reduces glycogen synthase kinase activity signalling cascade

Question 8

How does lithium get into the cell?

Answer 8

It mimics the structure of Na+, and is brought across the membrane in its transporters

Question 9

What bipolar conditions is lithium the firstline treatment for?

Answer 9

Acute mania and maintenance (response in 80+%), less change of suicide

Question 10

Who is less likely to respond to lithium?

Answer 10

Those in mixed episodes or with BPD with psychotic features

Question 11

When is lithium useful as an augmentation therapy?

Answer 11

With antidepressants in treatment refractory depression (MDD)

Question 12

How is lithium absorbed and excreted?

Answer 12

Absorbed well orally, does not bind to protein in plasma, and 95% is excreted by the kidney

Question 13

How long does it take for lithium action to be seen? What should be done to treat acute episodes of mania in light of this?

Answer 13

Halflife is 24 hours -> onset of action is around 10-14 days

Thus, in acute episodes, start lithium and acutely treat with an antipsychotic or benzodiazepine (i.e. valium)

Question 14

What approximates the renal clearance of lithium?

Answer 14

20% of GFR, since it is almost 100% filtered and 80% is reabsorbed

Question 15

How should lithium toxicity monitoring be done? Why?

Answer 15

Measure electrolytes prior to first dosage to see how things are changed with lithium (many systemic interactions)

Measure at steady state 5 days after starting therapy, weekly for two weeks, then every 3-6 months once stable

Done due to narrow therapeutic window

Question 16

What are the most common dose-related effects of lithium toxicity and when are these worse?

Answer 16

Worse 1-2 hours after oral dosing, when plasma levels are highest

Include: GI distress, fine hand tremor, and polyuria-polydipsia

Question 17

What are two endocrine effects of lithium treatment? How?

Answer 17

1. Hypothyroidism - due to lithium concentrating in thyroid gland and impairing thyroid synthesis
2. Weight gain -> associated with hypothyroidism

Think of the fat snowboarder with a penguin on the board + untied bowtie

Question 18

Why does lithium cause polyuria and lithium-induced diabetes insipidus (LINDI)?

Answer 18

Polyuria - due to inhibitory effect on vasopressin -> increase in urine volume and thirst

LINDI - due to loss of responsiveness to antidiuretic hormone in the kidney (lithium is brought in principle cells and reduces the expression of aquaporin-2)

Question 19

What is done to treat LINDI?

Answer 19

Give the K+-sparing diuretic amiloride, or HCTZ

Question 20

At what levels is Lithium toxic, and what are the signs of severe toxicity?

Answer 20

Toxic > 2 mEq/L

Signs:
extreme GI distress
Loss of coordination (ataxia / falling snowboarder, coarse hand tremor, slurred speech)
Cognition changes -> poor concentration, disorientation, apathy, coma

Question 21

What is the treatment of lithium toxicity?

Answer 21

Gastric lavage + IV fluids, with monitoring of electrolyte status.

Hemodialysis may be required at very high levels

Question 22

What factors predispose to lithium toxicity?

Answer 22

Sodium restriction / loss, dehydration, vomiting / diarrhea, and drug interaction which reduces lithium clearance

Question 23

What activities are likely to cause sodium loss?

Answer 23

Heavy exercise, saunas, hot weather, and fever

Question 24

What should patients taking lithium do to avoid lithium toxicity?

Answer 24

Maintain adequate sodium / fluid intake

Question 25

What three drug interactions are most likely to cause lithium toxicity and why?

Answer 25

1. NSAIDs - reduction of GFR increases Na / Li resorption in PCT
2. Thiazide diuretics - reduce GFR
3. ACE inhibitors - reduce GFR

Question 26

What are two drugs which decrease lithium levels?

Answer 26

1. Caffeine / theophylline - increase diuresis and lithium clearance
2. Sodium -> high dietary sodium intake promotes renal clearance of lithium

Question 27

What BPD drug should be used in children?

Answer 27

Lithium

Question 28

What considerations should be made in the elderly with regards to lithium toxicity?

Answer 28

Slowed renal elimination and changes in brain chemistry which results in higher lithium levels in brain
-> lower lithium dose is required

Question 29

What happens to lithium clearance throughout pregnancy?

Answer 29

It is highest in the third trimester -> higher levels are needed to be therapeutic

Question 30

Should lithium be used in pregnancy and why?

Answer 30

Probably not, especially in first trimister due to two conditions.

1. Ebstein’s anomaly - downward displacement of tricuspid valve into right ventricle (think of the snowmen in sketchy)
2. Floppy infant syndrome - low apgar scores, hypotonia, lethargy, shallow respiration, hypothyroidism, and goiter

Question 31

What should new mothers on lithium NOT do?

Answer 31

Breastfeed