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Day # 56: Review Quiz -> Bipolar Part 3

Today will be our third review quiz for the bipolar disorder theme. Take a few minutes and check your learning.

1) Which of the following medications can decrease the serum drug concentration of lithium?

a) Amiloride

b) Thiazides

c) ACE inhibitors


e) Tetracyclines

2) Common side effects of lithium include all of the following except?

a) Nausea, diarrhea

b) Cognitive slowing

c) Coarse tremor

d) Polyuria

e) Acne

3) Which of the following is not an "off-label" use of valproic acid?

a) Agitation/Aggression

b) Schizophrenia

c) Neuropathic pain

d) Migraines




Question 1:

From day #53:

Answer: a

Amiloride decreases serum drug concentration (SDC) of lithium. All other drugs listed in question stem increase SDC.


  • Drugs that increase lithium levels (decrease renal lithium clearance):

  • Thiazides (increase PCT lithium reabsorption)

  • ACE inhibitors (decrease GFR)

  • NSAIDs except aspirin (decrease GFR)

  • Tetracyclines

  • Metronidazole

Other factors that increase lithium levels:

  • Sodium restriction

  • Dehydration (heavy exercise, hot weather, saunas, vomiting, diarrhea, fever)

Drugs that decrease lithium levels:

  • Caffeine

  • Potassium sparing diuretics (eg, amiloride)

  • Theophylline

Question 2:

From day #54:

Answer: c

Common tremor seen in lithium use is a fine hand tremor. Coarse tremor is suggestive of lithium toxicity.


Common side effects include:

  • GI (nausea, vomiting, diarrhea): Diarrhea associated with higher serum drug concentrations (SDC). Taking with food decreases GI side effects. May also consider initial dosing strategy of dosing multiple small IR formulation.

  • Sedation: Commonly sedating particularly during the early phase of treatment and may wear off with time. Consider night time dosing.

  • Tremor: Commonly a fine symmetric hand tremor. Can present at any time during treatment. Caffeine worsens the tremor. Considering decreasing alcohol intake and doses of antipsychotic or SSRI. Can use beta blockers (propranolol) to alleviate as first line but other options include primidone, benzodiazepines, and vitamin B6.

  • Cognitive: Subjective slowness and/or loss of creativity. Interestingly, these complaints may be confounded by decreased mania. This is level-dependent. Consider decreasing dose and addressing confounders.

  • Weight gain: This is a common reason for discontinuation. It is dose-dependent and worse in early treatment. Encourage change in diet, exercise, and decrease high calorie drinks. Additional contributor to weight gain is edema in the legs and face. Also treat other confounders such as hypothyroidism or other medications.

  • Polyuria/Polydipsia: i.e. excessive urination and thirst. Occurs secondary to lithium induced nephrogenic diabetes insipidus. Determine if patient is dehydrated. Consider daily dosing, sugarless gum, or oral moisturizers for thirst. If this does not go away with time, may attempt to decrease the dose or, for the expert, cautiously add a diuretic while reducing lithium dose by 50% and monitoring plasma lithium levels.

  • Sexual dysfunction: Minor dysfunction. Consider phosphodiesterase inhibitor.

  • Skin: Increases risk for development or exacerbation of acne, psoriasis, and alopecia. Consider lowering the dose or treatment with typical dermatological treatments.

  • Leukocytosis: Typically benign elevation of white blood cell count. Of note, in psychotic disorders requiring treatment with clozapine, lithium can be used to counteract the neutropenia.

See full post for all side effects include serious/dangerous side effects.

Question 3:

From day #55:

Answer: d

Valproic acid is FDA approved to treat migraines. All other listed indications in the questions stem are "off-label" uses.


FDA approved indications:

  • Epilepsy: FDA-approved to treat complex partial seizures as well as simple and complex absence seizures. It can also be used as adjunctive treatment in a variety of other seizure types.

  • Bipolar disorder: Can be used as a first line option for mood stabilization in bipolar disorder. Proven efficacy in treating acute mania and preventing mood episodes, but may be less effective in treating and preventing depressive episodes. Some data shows that it is more effective than other options in "mixed episodes". May require antipsychotics and/or benzodiazepines when initiating treatment of acute mania.

  • Migraine prophylaxis: Approved for migraine prophylaxis in adults. IV formulation also available for intractable migraines.

Other off-label indications:

  • Agitation/Aggression: There is little high-quality evidence for this use, however a case series demonstrated a significant reduction in agitation in TBI patients over a two year period. Used for the treatment of agitation/aggression in TBI, dementia, and parkinsonism.

  • Schizophrenia: May be useful as adjunctive treatment with antipsychotics. Limited data.

  • Neuropathic pain: Sometimes used in the treatment of neuropathic pain, fibromyalgia, and trigeminal neuralgia.


If you want to see all of the weekly quizzes you can see them here. Next lesson we will discuss lamotrigine and its' use in bipolar disorder.

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