Mood Stabilizers Flashcards
What is the difference between Bipolar 1 and Bipolar 2?
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)
What are the diagnostic criteria for a manic episode?
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)
What nonpharmacologic therapies can be applied for bipolar disorder?
- Psychotherapy
2. Electroconvulsive-therapy - good for treatment resistant all states + pregnant women
What classes of drugs fall within “mood stabilizers”?
Lithium, anticonvulsants, and atypical antipsychotics?
When are the anticonvulsants preferred for bipolar treatment, and give an example of one?
Acute mania, especially mixed episodes (irritable / dysphoric mania rather than euphoria)
Example: Valproic acid
What are the atypical antipsychotics good for, and give an example of one?
Treatment of acute mixed episodes, and bipolar depression
Example: Quetiapine - seroquel
What is the postulated mechanism of action of lithium?
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
How does lithium get into the cell?
It mimics the structure of Na+, and is brought across the membrane in its transporters
What bipolar conditions is lithium the firstline treatment for?
Acute mania and maintenance (response in 80+%), less change of suicide
Who is less likely to respond to lithium?
Those in mixed episodes or with BPD with psychotic features
When is lithium useful as an augmentation therapy?
With antidepressants in treatment refractory depression (MDD)
How is lithium absorbed and excreted?
Absorbed well orally, does not bind to protein in plasma, and 95% is excreted by the kidney
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?
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)
What approximates the renal clearance of lithium?
20% of GFR, since it is almost 100% filtered and 80% is reabsorbed
How should lithium toxicity monitoring be done? Why?
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
What are the most common dose-related effects of lithium toxicity and when are these worse?
Worse 1-2 hours after oral dosing, when plasma levels are highest
Include: GI distress, fine hand tremor, and polyuria-polydipsia
What are two endocrine effects of lithium treatment? How?
- Hypothyroidism - due to lithium concentrating in thyroid gland and impairing thyroid synthesis
- Weight gain -> associated with hypothyroidism
Think of the fat snowboarder with a penguin on the board + untied bowtie
Why does lithium cause polyuria and lithium-induced diabetes insipidus (LINDI)?
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)
What is done to treat LINDI?
Give the K+-sparing diuretic amiloride, or HCTZ
At what levels is Lithium toxic, and what are the signs of severe toxicity?
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
What is the treatment of lithium toxicity?
Gastric lavage + IV fluids, with monitoring of electrolyte status.
Hemodialysis may be required at very high levels
What factors predispose to lithium toxicity?
Sodium restriction / loss, dehydration, vomiting / diarrhea, and drug interaction which reduces lithium clearance
What activities are likely to cause sodium loss?
Heavy exercise, saunas, hot weather, and fever
What should patients taking lithium do to avoid lithium toxicity?
Maintain adequate sodium / fluid intake
What three drug interactions are most likely to cause lithium toxicity and why?
- NSAIDs - reduction of GFR increases Na / Li resorption in PCT
- Thiazide diuretics - reduce GFR
- ACE inhibitors - reduce GFR
What are two drugs which decrease lithium levels?
- Caffeine / theophylline - increase diuresis and lithium clearance
- Sodium -> high dietary sodium intake promotes renal clearance of lithium
What BPD drug should be used in children?
Lithium
What considerations should be made in the elderly with regards to lithium toxicity?
Slowed renal elimination and changes in brain chemistry which results in higher lithium levels in brain
-> lower lithium dose is required
What happens to lithium clearance throughout pregnancy?
It is highest in the third trimester -> higher levels are needed to be therapeutic
Should lithium be used in pregnancy and why?
Probably not, especially in first trimister due to two conditions.
- Ebstein’s anomaly - downward displacement of tricuspid valve into right ventricle (think of the snowmen in sketchy)
- Floppy infant syndrome - low apgar scores, hypotonia, lethargy, shallow respiration, hypothyroidism, and goiter
What should new mothers on lithium NOT do?
Breastfeed
