Bipolar Disorder Flashcards
1
Q
What is mood?
A
It is the pervasive and sustained emotion or feeling tone that influences a person’s behaviour and colour his or her perception of the world
2
Q
What is the impact of bipolar disorder on mood?
A
Mood can be labile, fluctuating, or alternating rapidly between extremes
ex. Laughing out loudly at one monet, tearful the next
3
Q
What is the mood spectrum?
A
It describes a range of moods from psychotic depression to psychotic mania.
Patients with bipolar disease fluctuate between mood depression and mania
4
Q
What are some examples of mood disorders?
A
- Bipolar disorder
- MDD (unipolar depression)
- Cyclothymia (less severe mood swings)
5
Q
What are the two main subtypes of bipolar disorder?
A
BD I and BD II
6
Q
What is the diagnostic criteria for bipolar I disorder (BDI)?
A
A distinct period of at least one week of full manic episode: abnormally & persistently elevated mood and increased energy
7
Q
What is the diagnostic criteria for bipolar II disorder (BDII)?
A
A current or past hypomanic episode and a current or past major depressive episode
8
Q
How common is bipolar disorder in the population?
A
Less than 1% of people have been diagnosed with either BDI or BDII
9
Q
What are the sex differences in symptoms associated with bipolar disorder?
A
Men have more manic episodes, women have more depressive or mixed symptoms
10
Q
Is bipolar disorder an acute condition?
A
No, it is a lifelong illness with variable course
Full recovery is possible with appropriate drug therapy
A cure is not possible at this moment
11
Q
Does bipolar disorder have a simple etiology?
A
No, it is multifactorial
- Developmental
- Psychologic (stresses, especially during development)
- Genetic
- Neurobiologic
12
Q
What are some risk factors associated with bipolar disorder?
A
- First degree relative with bipolar disorder
- Period of high stress (traumatic experiences)
- Major life changes (family deaths)
- Medical conditions (hyperthyroidism, hormonal changes, CNS disorders, CVD)
13
Q
What are some secondary causes of mania?
A
- Alcohol intoxication
- Antidepressants
- DA-augmenting agents (amphetamines, cocaine, reuptake inhibitors)
- Marijuana intoxication
- NE-augmenting agents
- Steroids
- Thyroid preparations
14
Q
What happens when a bipolar disorder patient on an anti-depressant experiences a mania episode?
A
Discontinue anti-depressanr abruptly (drug may be exacerbating mania)
Patient will have to endure withdrawal symptoms
15
Q
What is the onset of bipolar disease?
A
Average age of onset is 20-25
2/3 of bipolar patients have some symptoms (usually depressive) before the age of 18
16
Q
What is the prognosis of bipolar disorder?
A
With treatment, illness usually includes periods of remission with risk of full or sub-syndromal relapses (prevent remission and neurological deterioration)
17
Q
What are some risks of leaving bipolar disorder untreated?
A
Kindling Theory
- Syndromal episodes increase vulnerability to more episodes
Neurodegeneration
- Persistent neurocognitive deficits, increasing impairment delayed functional recovery
18
Q
What are some comorbid conditions with bipolar disorder?
A
- Anxiety disorders (50-60%)
- Substance use disorder (60%)
- ADHD (20%)
- PTSD
- Medical comorbidities (diabetes, dyslipidemia, obesity, CV disease)
19
Q
What is the leading cause of death in patients with bipolar disorder?
A
- 6-7% of identified patients with bipolar disorder die by suicide (20x rate vs. general public)
- 3% of BD patients report suicidal ideation (20-50% attempt suicide at least once)
20
Q
What is the name of the suicide risk assessment tool?
A
Columbia Risk Assessment Tool
review slide 18
21
Q
What is the DSM-5 diagnostic criteria for mania?
A
Persistantly and abnormally
Elevated mood (irritable or expanisve) and energy
With at least 3 of the following changes from usual behaviour:
- Grandiosity (god-complex)
- Decreased need for sleep
- Racing thoughts
- Increased talking/pressured speech
- Distractibility
- Increasing goal-directed or psychomotor agitation
- Excessive engagement in high risk behaviours
22
Q
What is a good symptom mneumonic for mania?
A
DIGFAST
D: distractibility
I: irritability
G: grandiosity
F: flight of ideas (racing thoughts)
A: activity increased
S: sleep decreased
T: talkativeness
23
Q
What is the diagnostic criteria for hypomanic episodes?
A
Same symptoms as full blown mania, but only lasts up to 4 days
The episode is not linked to physiological effects of a substance or another medical condition
24
Q
Review slide 26 for diagnostic criteria comparisons between BDI and BDII
A
25
What is the diagnostic criteria for MDD?
- Depressed mood most of the day, nearly every day
- Diminished interest or pleasure in all or most activities
Need to have atleast 3+ of the following symptoms
- Changes in sleep pattern
- Changes in interests and activity
- Feelings of guilt or worry
- Changes in energy
- Changes in concentration
- Changes in appetite
- Psychomotor disturbances
- Suicidal ideation
26
What are some challenges in bipolar disorder diagnosis and treatment?
- Delay to diagnosis (average delay of 8-12 years, usually have history of MDD)
- Misdiagnosis (3/4 of bipolar patients have been misdiagnosed with depression)
- Limited clinical trails (not a lot of quality evidence due to heterogeneous illness, co-morbidities, manic symptoms, etc)
27
How quickly does therapy for mania result in improvement in mood?
Response: 1-2 weeks
Full clinical benefit: 3-4 weeks
28
How quickly does therapy for depression result in mood improvement?
Response: 2-4 weeks
Full clinical benefit: 6-12 weeks
29
What are some non-pharm approaches to managing bipolar disorder?
- Exercise, adequate sleep, health diet, decrease substance use (general self care)
- Bright light (good for depressive symptoms)
- Relapse prevention plan (help support patient adjust doses during relapses)
- Psychoeducation and therapy (can be unaccessible for some patients)
- Medication adherance (identify barriers and help resolve)
30
What are the most commonly used mood stabilizers used in treatment of bipolar disorder?
- Lithium
- Valproic Acid/Divalproex
- Lamotrigine
31
What are the official indications for lithium?
- Bipolar disorder (acute mania treatment and prophylaxis)
- Schizoaffective disorder
- Unipolar depression (anti-depressant augmentation)
32
How does lithium distribute in the body?
Evenly into to the total body water space (can accumulate across the body, poses risk for toxicity)
33
How quickly is lithium cleared from the body?
Half-life is usually within 12-27 hours, longer in elderly due to lower clearance
95% renal clearance, remainder is perspiration
34
What are the therapeutic ranges for lithium?
Acute mania (1.0-1.2mmol/L)
Maintenance therapy (0.6 - 1.0mmol/L)
Elderly (0.6-0.8mmol/L)
35
Is lithium a narrow therapeutic index drug?
Yes, toxic ranges (over 1.5mmol/L) are close to therapeutic ranges(0.6-1.0mmol/L)
Need to monitor closely
36
When are lithium levels drawn?
Unlike other drug levels, serum levels are drawn 12 hours after dosing to capture complete absorption and distribution
Usually done in the morning after an evening dose
37
What is done if lithium drug levels are well above 1.2mmol (toxic levels)?
Hold dose as toxic levels of lithium can be fatal
Repeat plasma level next day (half-life is 24 hours)
Restart therapy when levels are within target range (0.6-1.0mmol/L)
38
Review slides 56 to 62 for lithium dose adjustment
39
What are some factors that can lower expected lithium levels?
- Sodium supplement (can also be dietary)
- Burns (increased total body water, dilutes lithium)
- Caffeine (fluid)
- Hemodialysis (increased clearance)
- Pregnancy
40
What are some factors that can elevate expected lithium levels?
- Dehydration
- NSAIDs (reduces renal perfusion)
- TZDs (Na+ reabsorption inhibited, body holds on to Na+ and Li+)
- Sodium loss (body holds onto more Li+)
- ACEi/ARBs (reduced GFR)
41
What are some drugs that interact with lithium?
- Diuretics (effect depends on quantity of fluid in the patients body)
- NSAIDs (reduced lithium clearance, and lithium accumulation)
- ACEi/ARBs (reduced renal perfusion, reduced lithium clearance, increased lithium levels)
42
Review slides 65 to 70 for managing lithium drug interactions
43
What are some characteristic lithium adverse effects?
- Increased thirst and polyuria
- Fine tremors to hands/arms
- GI upset (first signs of toxicity)
Serious
- Renal injury (can be irreversible)
- Hypothyroidism
- Bradycardia
44
Review slide 73 for lithium monitoring tips
45
What are some important points to discuss during patient counselling for lithium?
- May take several weeks to see benefit
- Ensure adequate hydration and keep salt/caffeine intake stable
- Self-monitor for signs of toxicity
- Will require regular blood level monitoring
- Avoid NSAIDs
- Consider birth control if the patient has child-bearing potential
46
What are the officially indicated indications for valproic acid?
Seizures (broad-spectrum anti-epileptic activity)
Bipolar disorder (acute mania treatment and maintenance/prophylaxis)
47
What are some potential mechanisms of action for valproic acid in treating bipolar disorder?
1. Inhibition of volage gated Na+ channels (reduces released of glutamate)
2. Increasing action of GABA
3. Modulates signal transduction cascades and gene expression
4 May effect neuronal excitation mediated by the NMDA subtype of glutamate receptors
5. Also effects serotonin, dopamine, aspartate, and T-type Ca2+ channels
48
What is an important drug interaction consideration for valproic acid?
Valproic acid is highly protein bound, and concommitant use with other highly protein bound drugs may result in overdosing at normal doses
49
How is valproic acid cleared?
More than 95% is hepatically cleared (metabolites can cause liver toxicity)
50
What is the therapeutic range for valproic acid in bipolar disorder?
Total 350-700umol/L, free levels are not readily available. Need to inference free levels from total levels and impact of potential drug interactions
51
How are valproic acid levels monitored?
A blood sample is taken at steady state trough, usually 3-4 days following initial therapy and then 1-2 weeks later to check dose level stability
52
How are valproic acid doses adjusted in patients with hepatic dysfunction?
These patients show lower protein binding and clearance of valproic acid, so it is best to avoid this drug in these patients
53
How are valproic acid doses adjusted in elderly patients?
Elderly patients have lower protein binding and hepatic clearance, so use lower initial doses
54
How are valproic acid doses adjusted in patients with renal dysfunction?
No dosage adjustment required
Valproic acid is almost only cleared by the liver, minimal involvement in clearance from the kidneys
55
What are the most common formulations of valproic acid?
- Syrup (Valproate Sodium)
- Capsules (Valproic acid)
- Enteric coated tablets (Divalproex sodium, pro-drug)
56
Which drugs are known to increase valproate levels?
- Macrolides (clarithro, erthro)
- ASA/salicylates (increase unbound VPA)
57
Which drugs are known to decrease valproate levels?
- Carbapenems (erta, imi, mero)
58
Which drug has its levels increased when used concommittantly with valproate?
Lamotrigine (decrease LTG dose by 50% when used with VPA)
59
Review slides 92 to 95 for divalproex prescribing patient case
60
What are some adverse effects associated with valproate?
- GI (lower with divalproex vs valproic acid)
- CNS (tremor, sedation, ataxia, dizziness)
- Skin rash (especially if used in combo with lamotrigine)
- Weight gain (chronic use in 60% of patients, more than lithium)
61
Is valproate a good option for treating bipolar disorder in pregnant women?
No, valproate is teratogenic, so birth control should be considered in women of child bearing age
62
What are some counselling points for valproate?
- May take several weeks to see benefit
- Check with pharmacist or physician before starting any new drugs (concern about starting highly protein binding drugs)
- Use reliable contraception if child-bearing potential
- Avoid excessive alcohol use due to hepatic injury
63
What are the indications for lamotrigine?
Seizures
Bipolar disorder
64
What is the half-life for lamotrigine?
Half-life is 25-33 h for adults and no interacting drugs
65
What is the primary organ that eliminated lamotrigine from the body?
Hepatic and renal metabolism are both important
66
What is an important consideration for lamotrigine dosing?
Slow titration due to risk of severe skin reactions (rash, SJS, and TEN)
Due to skin rash risk, so not start new shampoo, detergents, and perfumes
67
What is the dosing protocol for missing lamotrigine doses?
If the patient has missed doses for more than 5 days (5 half-lives), then they must restart titration to safely resume therapy
68
What are some common adverse effects associated with lamotrigine?
Sedation
Headaches
Nausea
Dizziness
69
What are some rare/serious adverse effects associated with lamotrigine?
Risk of SJS (especially if titrated too quickly), asceptic meningitis, blood dyscrasias, hepatoxicity
70
What are some good variables to monitor for patients on lamotrigine?
Baseline: Hepatic and renal function
Ongoing: Rash
No serum lamotrigine levels necessary
No lab monitoring required other than regular blood work
71
What is the drug interaction between valproate and lamotrigine?
VPA/DVP increase lamotrigine levels two-fold or more
72
What is the drug interaction between carbamazepine, pheny, phenobarb, and topiramate and lamotrigine?
These drugs can decrease lamotrigine levels by 30-50%
73
What is the drug interaction between oral contraceptives (estrogen) and lamotrigine?
Estrogen contraceptives can reduce lamotrigine levels by 50%
74
Review slides 111 to 114 for case example of managing drug interactions and titration of lamotrigine
75
What are some important counselling for lamotrigine?
May take several weeks to see benefit in mood
Adherence is important, may need to repeat titration if doses are missed for more than 5 days
Self-monitoring for rash is very important (stop taking lamotrigine if you see any signs of skin abnormalities, seek ER if rapid development)
Watch out for enzyme inhibitors like VPA and carbamazepine
76
Which drug class is carbamazepine structually similar to?
TCAs, and carbamazepine can cause false positives for TCAs and may confer similar effects due to receptor binding
77
What are the indications for carbamazepine?
Seizures
Bipolar disorder
Neuropathic pain (off-label)
Trigeminal neuralgia
78
What is the general MOA for carbamazepine?
- Blocks voltage-dependent Na+ channels
- Blocks NMDA glutamate receptor
- Decrease synaptic transmission
- Stimulates release of ADH which promotes water resorption (can cause hyponatremia and fluid overload)
79
What is autoinduction in the context of carbamazepine metabolism?
Induces its own metabolism, which can make titration to therapeutic doses a longer and more tedious process
As a result, clearance and half-life are variable
80
What is the therapeutic drug level of carbamazepine?
17-51 umol/L
Taken 1 hour after dose as a trough level
81
How often are carbamazepine levels monitored?
During initiation and auto-induction, monitor every 1-2 weeks until on stable regimen
82
What are some carbamazepine dosing principles?
- Initiate slowly due to avoid side effects
- Best to give in divided doses, usually Q12h or Q8h instead of a single dose
- Dose at meal time
- Not recommended in patients with decompensated liver disease
83
What is the main type of drug interaction with carbamazepine?
Carbamazepine levels are significantly impacted by co-administration with CYP3A4 inhibitors and inducers
84
Which drug classes cause carbamazepine levels to be elevated?
Macrolides (erythro, clarithro)
Azoles (fluco, keto, itra)
CCBs (diltiazem and verapamil)
Grapefruit juice
85
Which drug classes cause carbamazepine levels to be lower than expected?
Anticonvulsants (pheny, phenobarb)
Rifampin
86
What are the two most important drugs whose levels are decreased by concomittant use with carbamazepine?
Warfarin
DOACs (should not be used with carbamazepine)
87
What are some other drugs that are decreased by carbamazepine?
Lurasidone (antipsychotic)
Anti-retrovirals (HIV treatment)
88
What are some common adverse effects associated with carbamazepine?
GI: nausea, vomiting, constipation
CNS: sedation, incoordination, ataxia
CV: Tachycardia, hypotension
89
What are some concerning adverse effects associated with carbamazepine?
SIADH/hyponatremia
Blood dyscrasias
Rash (10% of patients get morbiloform rashes and hypersensitivity reactions)
- especially in patients with Asian & pos. HLA-B*1502 and Caucasian & HLA-A*3101
90
What are the contraindications for carbamazepine use?
History of hepatic disease, CVD, blood dyscrasias (esp when used with clozapine), bone-marrow depression
91
What should be monitored in regular blood work for patients on carbamazepine?
Determine baseline, then monthly for 3 months, then q6-12 months once stable
CBC with diff and platelets
Electrolytes
LFTs
Renal function
92
Review slides 137 and 138 for carbamazepine-induced SIADH case example
93
What are some good counselling points for carbamazepine?
- Take with food to minimize GI upset
- Report rash or flu-like symptoms
- Carbamazepine will decrease efficacy of estrogen or progestin based contraception
- Drug interactions with CYP3A4 inducers and inhibitors
- HLA-B*1502 testing in Asian patients to avoid uneccessary skin reactions
94
What is the primary MOA for antipsychotics?
Dopamine blockade, can be useful for resolving mania
95
What is the main therapeutic difference between atypical and typical antipsychotics?
Atypicals have lower risk of extra-pyramidal symptoms (pseudo-parkinson's)
Typicals are very rarely used for bipolar
96
What are some adverse effects associated with antipsychotics?
EPS (extra-pyramidal syndrome, psuedo-parkinson's)
Hyperprolactinemia, sexual dysfunction
Metabolic disturbance (weight gain, dyslipidemia, DM, CVD)
Sedation
QT prolongation
Seizures
97
What are some common lab values monitored in patients on antipsychotics?
BMI, vitals
A1c, lipids
ECG
Liver function, renal function, lytes, CBC
Prolactin
98
What is the role of antidepressants in bipolar disorder?
Increased risk of switching patients to mania, but bipolar depression can be difficult to treat
Avoid antidepressant monotherapy without antimanic agent and d/c during acute manic episode
Use short courses (3-4 months) of therapy
99
What are the preferred antidepressants for bipolar depression?
Citalopram, Escitalopram Fluoxetine, Sertraline
Trazodone, Mirtazipine, Bupropion, Vortioxetine
100
Review slides 150 to 152 for strategy of treating bipolar disorder with mood stabilizers
101
What are some things that clinicians for assess before treating acute mania (imp. question)?
- Risk of aggressive behaviour or violence to others
- Risk of suicide
- Degree of insight
- Ability to adhere to treatment
- Co-morbidities
- Substance use
- Physical condition & lab tests
- Most appropriate treatment setting (inpatient vs outpatient)
Review slide 159
102
What drugs should be discontinued on the onset of acute mania?
- Antidepressants
- Stimulants (caffeine, amphetamines)
- Alcohol
- Nicotine (gradually d/c)
103
What are some things that need to be ruled out when diagnosing acute mania?
- Prescribed medication
- Illicit-drug use/abuse
- Endocrine disorder
- Neurological disorder
104
Review slides 160 to 163 for antidepressant-induced mania case example
105
What are the first line monotherapies for acute mania?
Lithium, quetiapine (and other atypical antipsychotic), divalproex
50% of patients will respond to monotherapy with improvement in 3-4 weeks (earlier with DVP and APs)
106
What is the first line combo therapy options for acute mania?
Lithium + atypical antipsychotic
OR
Divalproex + atypical antipsychotic
107
What is the advantage of lithium over other options for treatment of acute mania?
Preferred in patients with classical euphoric grandiose mania, few prior episodes of illness, family history of BD, and family history of responding to lithium
108
What is the advantage of divalproex over other options for treatment of acute mania?
Equally effective in treating classical and dysphoric mania
Multiple prior mania episodes
Predominant irritable or dysphoric mood
Comorbid substance abuse
History of head trauma
109
Review slides 167 to 169 for treatment of mania
110
What are the second-line monotherapies for acute mania?
Olanzapine, carbamazepine, ziprasidone, haloperidol
111
What is the second-line combo therapy for acute mania?
Olanzapine + lithium or divalproex
112
What is the role of electroconvulsive therapy in treating acute mania?
Limited number of controlled clinical trials, but suggets up to 80% of patients see marked clinical improvement
113
Is lamotrigine recommended in acute mania treatment?
No, it does not help with mania specifically
114
What factors should clinicians assess when treating bipolar I depression?
- Severity of depression
- Risk of suicide/self-harm behaviour
- Ability to adhere to treatment
- Psychosocial support network
- Ability to function
- Previous treaments
- Outpatient vs. inpatient
115
Which drugs should be discontinued when treating bipolar I depression?
Stimulants (nicotine, caffeine), drug, and alcohol use
116
What conditions need to be ruled out before diagnosing a patient with bipolar I depression?
- Symptoms due to alcohol/drug abuse, medication adverse events, other treatments
- General medical condition
117
What is the first line monotherapy for bipolar I depression?
Quetiapine/lurasidone + lithium/DVP
or
lithium alone
or
lamotrigine monotherapy/adjunct
or
lurasidone monotherapy
118
What is the second line treatment for bipolar I depression?
Divalproex
119
What is the second line add-on therapy for bipolar I depression?
Adjuntive SSRI or bupropion (added to lithium/divalproex or atypical antipsychotic)
Olanzapine-fluoxetine
120
Review slide 183 to 185 for treatment optimization for bipolar disorder with suicidal ideation
121
What is the purpose of bipolar I maintenance therapy?
Effective maintenance treatment early in illness, even after first episode:
- Reverse cognitive impairment
- Preserve brain plasticity
- May lead to improved prognosis and minimization of illness progression
122
What are risk factors for reccurent episodes of bipolar I?
- Younger age at onset
- Psychotic features
- Rapid cycling
- More previous episodes
- Comorbid anxiety
- Comorbid substance use
123
What is the role of psychosocial therapy in bipolar I maintenance therapy?
Pharmacotherapy may be the foundation to BD maintenance therapy, but alone is often ineffective to prevent recurrence
Adjunctive psychosocial treatment decreases recurrence rates by 15%
124
What are some factors that should be assessed before starting bipolar I maintenance therapy?
- Are medications effective in acute phase (only use antidepressants for 4-8 weeks until depressive symptoms subside)
- History (clinical course, response to previous therapy, family history)
- Psychiatric comorbidities
- Predominant illness polarity
- Polarity of most recent illness
125
What drugs should be discontinued before starting bipolar I maintenance therapy?
Stimulant, nicotine, caffeine, drug, and alcohol use
126
What drug has the most real-world evidence in bipolar disorder maintenance therapy?
Lithium
127
How long should adjunt atypical antipsychotics be used with lithium maintenance therapy?
Up to 6 months, benefits are not significant past that point
128
For patients experiencing manic and depressive bipolar symptoms, what is the best course of action from a pharmacological standpoint?
d/c antidepressants (can worsen mania)
Monotherapy: atypical antipsychotic (fast acting)
Combination therapy (lithium or divalproex + atypical antipsychotic)
129
For pregnant patients with bipolar disease, what are some treatment tips?
Avoid DVP/VPA and carbamazepine because they are teratogens
Lithium has lower risk
Lamotrigine seems to be the safest option while maintaining adequate bipolar maintenance treatment
130
What is the best agent for bipolar patients experiencing suicidal ideation?
Lithium has the most evidence to reduce the risk of suicide in patients with bipolar disorder
ECT can be used as adjuct in cases of high risk of suicide
