EXAM 5 Bipolar disorder Therapy Surbaugh Flashcards
When is a patient diagnosed with Bipolar I disorder?
after ONE manic episode, not explained by any other disorder
average age onset is 18y
When is a patient diagnosed with Bipolar II disorder?
at least ONE hypomanic episode and at least ONE depressive episode
-often mid 20s, and more lifetime episodes
-mixed episodes and rapid cycling (rapid change from manic to depressive episodes)
When is a patient diagnosed with Cyclothymic Disorder?
Fluctuation between depressive and hypomanic
episodes for two years (1 year if adolescent)
-they don’t meet the full criteria for manic, hypomanic, or major depressive disorder
What is rapid cycling?
4 separate mood episodes in the previous 12 months, full remission for at least 2 months in between
What are catatonic features?
if the patient has 3 or more catatonic features during an episode
-staring
-mutism (don’t talk)
-negativism
A patient was diagnosed with bipolar II (at least one HYPOMANIC and one DEPRESSIVE episode). The patient has now experienced a MANIC episode. What is the diagnosis?
It switched from Bipolar II to Bipolar I due to having ONE MANIC episode now
What is considered Mania?
-period of at least 1 week (if hospitalized it is automatically Mania?)
-their mood is elevated, expansive, irritable, they have more energy
minimum of 3 of those symptoms (if the mood is irritable we need 4)
-Grandiosity or inflated sense of self (self-confidence)
-Decreased need for sleep !!!
-Increased quantity of speech or pressured speech
-Flight of ideas or racing thoughts
-Easily distracted – work, social, school
-Increased goal-directed activity
-Engaging in activities that can be detrimental – spending spree, increased sexual activity
-they are not functioning, may need hospitalization
-not caused by drugs
What is Hypomania, difference to Mania
abnormally elevated, expansive, irritable for at least 4 consecutive days
-same symptoms as seen with mania
-not severe, hospitalization is NOT required (not a threat to others or to self, still able to work)
What are conditions that look like bipolar episodes that should be ruled out?
-CNS disorders: like stroke
-Infections
-Electrolyte or metabolite abnormalities
-Endocrine or hormonal dysregulation: low thyroid levels
Meds that induce Manic episodes
-Alcohol
-drug withdrawal
-Antidepressants - can flip patients into mania !!! which ones ???
-Dopamine or NE augmenting agents (more dopamine)
-Hallucinogens, Cannabis
-Stimulants
-Steroids !!!
-Thyroid preparations?
-Xanthanines
-Non-Rx weight loss agents and decongestants
-herbal products
Pathophysiology of Bipolar disorder
not fully understood
-DA, NE, and 5-HT are involved
-GABA deficiency or excess Glutamate (both excitatory effects) can change DA and NE activity
-HPA axis dysregulation: cortisol release - mania, Hypothyroidism is linked to rapid cycling
-sleep can lead to depressive or manic episodes
-second messenger systems
Clinical Presentation - Manic or Hypomania
DIGFAST
Distractibility
Irritable
Grandiose (self-esteem)
Fast ideas
Activity is increased
Sleep is decreases
Talkativeness
First-line options for Mania
-Lithium
-Valproic acid
-Second-Gen antipsychotics
-might use Benzos short-term if they need sleep, anxious features, agitation (Lorazepam)
A patient was diagnosed with depression and started on an SSRI. At her follow-up visit, she presented with manic symptoms. Which drug change is appropriate?
Taper the antidepressant, it can make Bipolar I (ONE manic episode) worse
Antidepressants should not be used as monotherapy for Bipolar disorder
First-line options - Combotherapy
Combo therapy is often used
-Lithium + Benz (+AP) - short-term
-VPA + Benz (+AP) - short-term
-SGA + Benz
Alternative: Carbamazepine then Oxcarbamzepine, has to be titrated to therapeutic level though
Second-line options - Combotherapy
3 drug combo (she has not seen one started with 3 at once, may be added if 2 don’t work)
Lithium + Antiseizure (depakote) + AP
Antiseizure + Antiseizure + AP
Third line options
ECT (electrotherapy) + Clozapine
Clozapine is an effective antipsychotic, but it is a REMS drug and needs lab monitoring and close follow-up
Which drug may be a good choice for acute manic episodes?
Second Gen Antipsychotics - they work faster
Hypomania First-Line treatment
Monotherapy
-Lithium
-VPA
-SGA
-Carbamazepine
Adjunctive options:
-Benzo: Lorazepam, Clonazepam (for sleep)
-Oxcarbazepine
-may optimize dose before going to second line
Hypomania Second-Line treatment
-Lithium + Antiseizure
-Lithium + SGA
-Antiseizure + Antiseizure
-Antiseizure + SGA
Bipolar Depressive episode - First-Line
L drugs
Lithium (1st)
Lamotrigine
SGA:
-Lurasidone (1st)
-Lumateperone
-Quetiapine (1st)
-Olanzapine-Fluoxetine
-use antipsychotics if psychotic features are present
-avoid antidepressant monotherapy - add a mood stabilizer, alone it can flip them into mania !!!
MOA Lithium
not fully understood
-decreases 5-HT reuptake
-increases 5-HT receptor sensitivity
-inhibits DA synthesis
-decreases DA receptor sensitivity
-enhances GABA activity
Goal concentration for Lithium
acute mania: 0.8 - 1.2 mEq/L
for maintenance: 0.6-1.0 mEq/L
if able, use once-daily dosing
Lithium dosing for Bipolar disorder
600-900 mg/day
-if they are having a manic episode - closer to 900 if the kidney function is OK
When do patients see the effect of Lithium?
for Mania- 6-10 days (not ideal for an acute manic episode)
for Depression: a week
When should Lithium be checked?
5 days after starting or changing the dose
-may check earlier if signs of toxicity, increase in creatinine levels, elderly patients
-measure the trough
Which kinetic order does Lithium follow?
Linear kinetics
on average 300 mg will raise levels by 0.3 mEq/L
600 mg/daily - we expect levels of 0.6 mEq/L
when increased to 900 mg/d -> 0.9 mEq/L
if they were on 600 mg/d and the level were 0.4 mEq/L and we double the dose to 1200 mg/d we expect the levels to double to 0.8 mEq/L
What reduces Lithium clearance and increases the risk for toxicity?
-dehydration
-Na depletion
-cardiac or renal dysfunction
Counsel: Keep sodium levels consistent (especially when on a diet), drink enough
Side effects of Lithium
Dermatologic:
-Acne
-Psoriasis
-Alopecia (could be caused by low thyroid, so check)
CV:
-QT prolongation (rare)
CNS:
-Benign tremor - consider propranolol
GI: worst at peak concentrations (1-2h post-dose)
-N/V/D ,abdominal pain
Urinary:
Polyuria, AKI (acute toxicity) and CKD
Endocrine:
-Hypothyroidism: alter T3 and T4 release
-Hyperparathyroidism: check Ca2+ and PTH if needed
-weight gain
At what Lithium levels do we expect severe toxicity?
2 - 2.5 mEq/L: moderate to severe
confusion, dysarthria (difficulty speaking), nystagmus (uncontrolled eye movements), hyperreflexia, ataxia
> 3 mEq/L: severe
seizure, coma, myoclonus, hypertonicity, rigidity
What interventions are considered at levels above 4 or 2.5 with neurologic symptoms?
IV fluids or hemodialysis to clear the drug out of the system
Lithium DDI
Increases Lithium level:
-NSAIDs (also Aspirin)
-ACEi and ARBs
-Thiazide diuretic, loops
Decrease Lithium level:
-Theophylline
-Caffeine (if they drink coffee they should keep it consistent)
others that increase Lithium levels: antipsychotics, metronidazole, methyldopa,
phenytoin, and non-DHP CCB
Which labs should be checked before starting Lithium?
-Baseline renal function
-Baseline CBC
-Baseline ECG (due to QTc)
-Pregnancy
-Thyroid level
A patient has presented with tremor. Her lithium level was 0.8 two weeks ago. She had N/V/D from a stomach bug. What is your advice?
-get a lab and check if it is high
-cut be increased due to diarrhea and vomiting (dehydration)
-recommend hydration, if she cant keep it down -> go to the ER (IV fluid)
Role of Valproic acid
-Anti-kindling properties
-LEAST effective in acute depression (go with Lamotrigine for bipolar depression)
-MOA: not fully understood
increases GABA concentration, prevents reuptake and breakdown, normalizes Ca2+ and Na+ levels
VPA Goal concentration
Goal concentration: 50-125 mcg/ml
need to be at the upper end to treat manic symptoms (especially in the acute phase)
When do patients see the effect of VPA?
after 3 days with a loading dose
faster than Lithium (6-10 days)
BBW of VPA
-hepatic failure and pancreatitis
CONTRAINDICATED in:
-hepatic dysfunction
-Pregnancy
Valproic Acid DDI
-Lamotrigine: VPA increases Lamotrigine: titrate VPA slower !!!
-Carbapenem: reduce VPA levlels
-Phenytoin
-Ritonavir: increases clearance of VPA
-Warfarin: increased risk for bleeding
ADE for VPA
-Rash: SJS, TEN, DRESS !!!
-Alopecia
-Weight gain
-Hyperammonemia
-Thrombocytopenia !!!
-GI: N/V/D, constipation
-Neurological: Ataxia, diplopia, dizziness, sedation, tremor
-Pancreatitis!!!
-Hepatoxic !!! -> BBW
Which labs to monitor for VPA
-CBC
-LFT
-Renal function
-Pregnancy test
-Ammonia levels: if concern for hyperammonemia
-check weight
get VPA levels after 3-5 days or a dose change
Which drug may be used in acute mania?
Carbamazepine
also for mixed epsiodes biopolar I disorder
What is the Goal concentration for Carbamaezpeine?
4-12 mcg/L
-monitoring not needed
Carbamazepine dosing
100-400 mg/d
often divided: 200 mg BID
max dose: 1600 mg/d
titrate slowly
How long does it take to see the effect?
7 days in mania
When to check Carbamazepine levels?
after 4 weeks -> assess for dose adjustments
What is the BBW for Caramazepine?
-SJS, TEN (increased risk with HLA-B*1502)
-aplastic anemia and agranulyctosis
What are the signs of toxicity(side effects with Carbamazepine?
-Hyponatremia (SIADH)
-GI- N/V, constipation, dry mouth
-Neurological: Ataxia, dizziness
At what levels do we see the toxicity of Carbamazepine?
greater than 12 mcg/ml
ataxia and nystagmus (uncontrolled eye movements)
-greater than 40 mcg/ml -> seizure, coma
Carbamazepine DDIs
CYP 3A4, 2D6, 2C9 inducer
-autoinducer
-makes oral contraceptives less effective
-Cimetidine, fluoxetine, ketoconazole, nefadozone inhbitis its metabolism -> increase levels
-don’t give Carbamazepine and Clozapine together (risk for agranulocytosis)
Role of Lamotrigine
-Maintenance of bipolar I (not acute mania!!!)
-acute bipolar depression
-has anti-kindling properties, decreases rapid cycling and mixed episodes
How is Lamotrigine dosed?
-must TITRATE due to risk for RASH
any break of more than 3-5 days requires retritration
first 2 weeks: 25 mg/d
next 2 weeks: 50 mg/d
Week 5: 100 mg/d
Week 6: 200 mg/d
with VPA, start lower (since it increases Lamotrigine) from 12.5 to 100 mg/d
with CYP inducer (decreases levels): start higher
from 50 to 300 mg/d
BBW for Lamotrigine
SJS/TEN
higher risk if not titrated correctly or at a younger age (<13y)
ADE for Lamotrigine
-agranulocytosis, aplastic anemia, neutropenia, pancytopenia,
-N/V/D
-ataxia, dizziness, sedation, aseptic meningitis
Role of SGA
-Acute mania or adjunctive acute mania (SGAs work faster)
-Maintenance therapy
-some can be used in bipolar depression
MOA: dopamine and 5-HT blocking
Which SGAs are approved for bipolar depression?
-Cariprazine
-Lumateperone
-Lurasidone
-Quietiapine
What is the BBW for SGAs?
increased mortality in elderly patients with dementia-related symptoms
ADE of SGA
higher risk for metabolic dysfunction:
-Hyperlipidemia
-diabetes
-weight gain
there are specific ADEs for the specific SGA
First-gens:
EPS side effects
Which labs should be checked for SGA?
Baseline:
-BMI
-waist circumference
-BP
-fasting Glucose (A1c)
-fasting lipid profile
Annually:
-BMI
-waist circumference
-BP
-fasting glucose
What are treatment options for acute mania in pregnant women?
-Antipsychotics (SGA) - quick onset and low risk for teratogenicity
-divide doses of mood stabilizers (once-daily dosing can lead to spikes in pregnancy)
-get levels regularly since the body metabolism of pregnant is different
-ECT
-avoid benzos if possible (withdrawal of the baby)
Which drugs should be avoided during pregnancy?
-Lithium during the first trimester: Esptein’s anomaly and Floppy baby syndrome
-VPA (if not able to avoid, supplement with folate 4 mg)
-> fetal VPA syndrome, cognitive dysfunction, neural tube defects
-Carbamazepine (consider folate 4 mg supplement if not able to avoid)
->spina bifida, developmental delays, and low IQ
-Lamotrigine is favorable !!!
Which antipsychotics are safe for breastfeeding?
-VPA
-Carbamazepine
Contraindicated:
-Lithium (monitor for hyperthermia if used)
-Lamotrigine (risk for SJS)
Which mood stabilizers are cleared through the kidneys?
-Lithium
-Valproic acid
Which drug used for bipolar disorder is hepatoxic?
VPA
Which drugs are approved for children with bipolar disorder?
-Lithium XR and IR for >7 years
-SGA including aripiprazole, risperidone, lurasidone >10 y and many more
-antidepressant with a mood stabilizer (lithium, VPA, carbamazepine)
-Lamotrigine is not FDA approved but it is often used due to minimal weight gain
Drugs for acute mania
-Lithium
-VPA (least effective in depression)
-Carbamazepine
Lamotrigine is effective for…
depression and maintenance therapy
-not effective for acute mania
