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Question 1

Bipolar Age of onset and illness burden

Answer 1

• Age of onset is 25. Those with ealier age of onset tend to have longer delay to treatment, increase depression symptom severity, and increase comoribid anxiety and substance use.
• Illness burden - symptomatic or syndromal (especially depression for 1/2 life); unable to maintain work for 30% of the time; impairments are greater in those with depressed symptims, in those with more episodes, and those with reduced cognition

Question 2

Cyclothymia Vs. BDII VS. BD1

Answer 2

• Cyclothymia - subthreshold hypomanic and depressive symptoms
• BD II - Hypomanic episodes (distinct and observable, but not of significant enough severity or duration to cause significant functional impairment, hospitilzation, or psychosis) + depressed episodes
• BD 1 - Manic episodes (increase self esteem, decrease need for sleep, pressure speech, reacing thoughts, distractibility, psychomotor agitation, risky behaviour, +/- psychotic features)

Question 3

Psychosocial interventions bipolar disorder

Answer 3

• Adjunctive psychosocial interventions may be helpful for acute depressive episodes and in maintenance treatment
• Provision of psychoeducation is recommended for all patients and family members

Question 4

Acute management of bipolar mania

Answer 4

• First line monotherapy - 50% will respond to monotherapy with significant improvement in manic symptoms within 3-4 weeks.
  
  • Lithium, quetipaine, divealproex, asenapine, aripiprazole, paliperidone, risperidone, and cariparzine
• First line combination - have greater efficiacy than monotherapy. May be preferred because 20% more people will respond. Recommended to go with combination therapy when you require a faster response, patient is at risk, or more severe manic episode
  
  • Combination of atypicals - quetiapine, aripiprazole, risperidone, or asenapine + Lithium or divalprox

Question 5

Mangement of agitation in mania

Answer 5

• Common feature in mania, especially among those with mixed features.
• Agitation can manifest as pacing, fidgeting, threatening, or aggressive behaviours
• If agitation is due to mania, antimanic agents with rapid onset should be considered first, if this fails, you can try IM aripiprazole (9.75mg), IM lorazepam (2.5mg), - however, even PO preparations can be appropriate.

Question 6

Acute management of bipolar depression

Answer 6

• Frist line treatment
  
  • Quetiapine (300mg) - effective for acute depression, prevention of mood epsiodes, depression, and mania
  • Lurasidone +Li/DVP - effective for acute depression
  • Lithium (levels of 0.8-1.2) - 2nd level for acute depression, 1st level for prevention of mood episodes, depression, and mania
  • Lamotrigine (200mg) - 2nd level for acute depression, 1st for prevention of mood, depression, and mania (not effective for acute mania).

Question 7

Antidepressants in bipolar

Answer 7

• Adjunctive treatment of bipolar depression with an antidepressant is current a second-line option. Must be used with lithium/Divalproex or an atypical.
• It should be avoided in those with antidepressant induced mania, mixed features, rapid cycling.
• Antidepressant monotherapy should NOT be used
• SNRI and MAOIs have the greatest propensity to cause a manic switch

Question 8

Maintenance Therapy in Bipolar

Answer 8

• Maintenance therapy is necessary in BP as it is a neuroprogressive disease where recurrences are associated with decrease drey and white matter volume, increase cognitive impairment, increase relapse, and decrease treatment reponse. Maintenance therapy early in disease course can reverse cognitive impairment and preserve brain plasticity.
• Generally, meds that were found to be helpful in the first phase should be continued during maintenace phase
• First line: Lithium, quetiapine, divalproex, lamtrigine (should not be used in those with frequent manic episodes), quetiapine + Li/DVP, aripiprazole + Li/DVP (aripiprazole does not work in acute depression).

Question 9

Treatment Bipolar II

Answer 9

• Hypomania - evidence suggests use of mood stabilizers (Li or DVP) and/or atypical
• Acute depression - Quetiapine is only recommened first line treatment. Second line = LI, sertraline, venlafaxine, lamotrigine
• Maintenane - First line = Quetiapine, Li, and lamotrigine. Second line = venalfaxine, fluoxetine

Question 10

Lithium

Answer 10

• An ion used in the treatment of BD although the MOA is unclear.
• It is proven to be effective in maintenance and manic episodes, and to a lesser extent, depression.
• Been shown to reduce suicidality in patients with BD.
• Side effects - GI, weight gain, hair loss, acne, tremor, sedation, decreased cognition, and incoordination. In the long term can cause thyroid and kidney damage.
• Has very narrow therapeutic window and requries frequent monitoring
• Dose - start at 300mg PO BID, increasing ny 300mg/day depending on levels. Usualy dose is 900-1500mg/day.

Question 11

Lithium Interactions

Answer 11

• Increase lithium levels
  
  • Thiazide diuretics
  • NSAIDs (except aspirin)
  • ACE inhibitors
  • Antibiotics tetracyclines and metronidazole
• Decrease lithium levels
  
  • Potassium-sparing diuretics
  • Theophylline
• May increase or decrease lithium level
  
  • Loop diuretics
  • Calcium channel blockers

Question 12

Valproic acid

Answer 12

• Used in treatment of BD. MOA is uncertain. Thought that it might inhibit voltage-sensitive Na channels, boost the action of GABA, and regulate downstream signal transduction cascades.
• Effective for acute mania and commonly used to prevent mania recurrence. It is not as effective in stabilization of depression.
• Series adverse effects - hepatotoxicity, teratogenity, pancreatits
• Common side effects - thrombocytopenia, bradycardia, GI, weight gain, amenorrhea, PCOS
• Dose - start at 250BID. Increase by 250mg weekly (dose 750-1250, depending on weight).

Question 13

Carbamazepine

Answer 13

• Anticonvulsant used in treatment of BD
• MOA is unknown but thought to act on voltage sensitive sodium channels.
• Contraindicated in those with sensitivity to TCAs, those with hepatic dsiease, history of bone marrow depression, in those takes MAOIs, in patients with AV heart block.
• Carbamazepine induced CYP 450 enzyme system resulting in decrease levels of neuroleptics, benzodiazepines, TCAs, and anticonvulsants.
• Series adverse effects - angranulocytosis and aplastic anemia, stevens-johnson syndrome, and toxic epidermal necrolysis.
• Side effects - CNS disturbances (drowsiness, HA, dizziness), GI

Question 14

Lamotrigine

Answer 14

• Approved to prevent recurrance of both mania and depression. Used frequently in bipolar depression. It is generally well tolerated.
• Rare life threatening Stevens-Johnsons Syndrome. Minimize the risk with a slow titration schedule
• Interactions:
  
  • Valproate - inhibits lamotrigine glucuronidation and thus will increase lamotrigine plasma levels. You need to start titration very slowly.
  • Carbamazepine - induces lamotrigine glucuronidate and thus will reduce lamotrigine plasma levels.
• Dose: Start at 25mg OD. Increase by 25mg every 1-2weeks. (50-200mg/day).

Question 15

Atypicals in bipolar disorders

Answer 15

• Effectove in those presenting with psychotic features, as well as in the prevention of recurrence of mania.
• Some of the atypicals are even effective in bipolar depression
• MOA if bipolar is unknown - may have something to do with anti-glutamate action
• Most atypicals are approved for mania; only quetiapine and lurasidone are effective in bipolar depression