Psychopharm Bipolar Disorder

58問 • 10ヶ月前

問題一覧

-Cause: Immune-mediated skin reaction—most commonly from Lamotrigine, especially when titrated too quickly or combined with valproate. -Symptoms: Flu-like prodrome → painful red/purple rash, mucosal involvement, skin sloughing. -Onset: Within first 2–8 weeks of drug initiation. -Labs: Elevated inflammatory markers; skin biopsy confirms.

Stevens-Johnson Syndrome (SJS)

In addition to stopping offending agent and supportive care, which condition may require hemodialysis?

Lithium Toxicity

In addition to stopping offending agent and supportive care, which condition may require dantrolene, bromocriptine, or amantadine (DA agonists)?

Neuroleptic Malignant Syndrome (NMS)

Most commonly caused from lamotrigine, especially when titrated too quickly or combined with valproate.

Stevens-Johnson Syndrome (SJS)

-Cause: Elevated lithium levels due to overdose, dehydration, NSAIDs, diuretics, ACE inhibitors, or renal impairment. -Symptoms: Mild (1.5–2.0 mEq/L): Tremor, nausea, vomiting, diarrhea. Moderate (2.0–2.5 mEq/L): Confusion, ataxia, slurred speech. Severe (>2.5 mEq/L): Seizures, renal failure, coma. -Labs: Elevated serum levels, BUN/Cr, electrolytes.

Lithium Toxicity

-Cause: Dopamine blockade from antipsychotics (especially high-potency like haloperidol or after rapid titration). -Symptoms: FEVER mnemonic: Fever (high, >104°F) Encephalopathy (confusion) Vital instability (labile BP, tachycardia) Elevated CPK (rhabdomyolysis) Rigidity (lead-pipe) -Labs: ↑ CPK, leukocytosis, myoglobinuria, metabolic acidosis.

Neuroleptic Malignant Syndrome (NMS)

Explain why and how atypical antipsychotics might be used in nonpsychotic mania.

Many atypical antipsychotics (SGAs) are FDA-approved for acute manic or mixed episodes—with or without psychosis—because they directly target dopamine and serotonin dysregulation, key central features of mania and mood stabilization.

-Check level 5–7 days after initiation or dose change -Draw level 12 hours after last dose (trough level) Therapeutic range: -Maintenance: 0.6–1.2 mEq/L -Acute mania: up to 1.5 mEq/L Monitor labs: -BUN/Creatinine (renal function) -TSH (risk of hypothyroidism) -Electrolytes (esp. sodium) -EKG in older adults or cardiac risk

Monitoring for Lithium

Toxicity: -Mild (1.5–2.0 mEq/L): Tremor, nausea, vomiting, diarrhea -Moderate (2.0–2.5 mEq/L): Ataxia, slurred speech, confusion -Severe (>2.5 mEq/L): Seizures, coma, renal failure What to Do if Toxic: -Discontinue immediately -Start IV hydration with normal saline Consider hemodialysis if: -Level >2.5 mEq/L with symptoms -Severe renal impairment -Symptoms are progressing

Toxicity and Management of LIthium

Monitoring: -Check level 3–5 days after initiation or dose change -Draw level just before next dose (trough level) -Therapeutic range: 50–125 mcg/mL Monitor labs: -Liver function tests (LFTs) -CBC with platelets -Ammonia (if altered mental status) -Weight and BMI (long-term)

Monitoring of Divalproex

Toxicity: -Common side effects: Tremor, sedation, nausea, weight gain Serious risks: -Hepatotoxicity -Pancreatitis -Thrombocytopenia -Hyperammonemic encephalopathy What to Do if Toxic: -Discontinue med -Check LFTs, amylase/lipase, CBC, ammonia -Provide supportive care Consider hospitalization if: -Severe liver or pancreatic involvement -Altered mental status or systemic decompensation

Toxicity and Management of Divalproex

-Mechanism of Action: Blocks voltage-sensitive sodium channels (VSSCs) on the presynaptic neuron, which reduces excessive neuronal firing and stabilizes mood.\ -Neurotransmitters: Indirectly modulates glutamate (↓ release) and GABA (↑ tone) -Major Side Effects: Dizziness, diplopia, sedation, nausea -Adverse Reactions: -Aplastic anemia, agranulocytosis -Stevens-Johnson Syndrome (SJS)—especially in patients with HLA-B*1502 (Asian descent) -Hyponatremia (SIADH)

Carbamazepine

Drug Interactions: -Strong CYP450 inducer (auto-induction) -↓ efficacy of OCPs, warfarin, antipsychotics Food Interactions: None significant Labs: -CBC with diff, LFTs, Na+ -Drug level: 4–12 mcg/mL -Genetic screening for HLA-B*1502 Pregnancy Risk: D – Neural tube defects, craniofacial abnormalities

Carbamazepine

-Mechanism of Action: Enhances GABA, inhibits VSSCs, inhibits GSK-3 and intracellular signaling -Neurotransmitters: ↑ GABA; modulates glutamate and DA pathways -Major Side Effects: GI upset, tremor, weight gain, hair loss -Adverse Reactions: Hepatotoxicity Pancreatitis Thrombocytopenia PCOS in women

Divalproex (Valproic Acid)

-Drug Interactions: Inhibits metabolism of lamotrigine (↑ risk of SJS) Protein-bound → displacement interactions -Food-Drug Interactions: Minimal -Lab Tests: LFTs, CBC with platelets, ammonia (if mental status changes) Drug level: 50–125 mcg/mL -Pregnancy Risk: X/D – High risk of neural tube defects (spina bifida), cognitive delay

Divalproex (Valproic Acid)

-Mechanism of Action: Inhibits VSSCs → ↓ glutamate release -Neurotransmitters: Modulates glutamate, aspartate, possible serotonergic effects -Major Side Effects: Headache, dizziness, nausea -Adverse Reactions: Stevens-Johnson Syndrome (SJS)/TEN Rash (mild to severe)—most common within first 8 weeks

Lamotrigine

-Drug Interactions: Valproate: ↑ serum levels (requires slower titration) Carbamazepine/phenytoin: ↓ serum levels -Food-Drug Interactions: None significant -Lab Tests: Not routinely needed unless rash or hepatic symptoms -Pregnancy Risk: C – Considered safer among mood stabilizers

Lamotrigine

-Mechanism of Action: Modulates GSK-3, second messengers, and inositol metabolism → neuroprotective & anti-suicidal -Neurotransmitters: Indirect modulation of dopamine, glutamate, and GABA -Major Side Effects: Tremor, polyuria, GI distress, weight gain -Adverse Reactions: Hypothyroidism Nephrogenic diabetes insipidus Renal insufficiency Cardiac dysrhythmias Toxicity (narrow therapeutic window)

Lithium

-Drug Interactions: ↑ levels: NSAIDs, thiazide diuretics, ACE inhibitors ↓ levels: Caffeine, theophylline -Food-Drug Interactions: Decrease in sodium intake increases serum levels -Lab Tests: BUN/Cr, TSH, electrolytes, lithium level (0.6–1.2 mEq/L) -Pregnancy Risk: D – Risk of Ebstein’s anomaly (1st trimester)

Lithium

-Mechanism of Action: Blocks voltage-sensitive sodium channels via its active metabolite eslicarbazepine -Neurotransmitters: Indirectly modulates glutamate release (↓) -Major Side Effects: Dizziness, sedation, fatigue, nausea -Adverse Reactions: Hyponatremia (higher risk than carbamazepine) Rash (but lower SJS risk than lamotrigine)

Oxcarbazepine

-Drug Interactions: Weak CYP450 inducer (less than carbamazepine) ↓ efficacy of hormonal contraceptives -Food Interactions: None significant -Labs: Serum sodium, CBC, LFTs -Pregnancy Risk: C – Lower risk than valproate or carbamazepine

Oxcartbazepine

This receptor addresses psychotic symptoms in mania

These receptors may reduce non-psychotic mania and depressive symptoms(possibly by decreasing glutamate hyperactivity)

5HT2A and 5HT1A

-“classic mood stabilizer “ -also treats non-bipolar depression as adjunct -Teratogenic (Ebsteins Anomaly) -Renally Excreted -One of few drugs that is anti-suicidal

Lithium

What tests must be checked before starting Lithium?

-Creatinine, Urinalysis -TSH and T4 -Pregnancy test (if applicable) -CBC (optional) -ECG (optional)

As a fun “hack”, what adjunct could you use in addition to Clozapine to counter the Leukocytosis caused my the drug?

Lithium because it increases the WBCs

What’s the therapeutic range for Lithium?

0.6-1.2

What are the s/s of early Lithium toxicity?

Nausea and Vomiting

Explain the effect of loop and thiazide diuretics on Lithium levels

Loop - increase and decrease levels thiazide - increase levels

Discuss the interplay of Lithium and Iodine

Both lead to hypothyroidism but do not directly affect each other

Explain the interplay between ACEI and Lithium

ACEI increase lithium levels by increasing sodium and water excretion

Explain the interplay of Lithium with SSRIs

Lithium increases side effects of SSRIs

Explain the interplay of Carbamazepine with Lithium

Carbamazepine increases the neurotoxic side effects of Lithium

Explain the interplay between Lithium and NSAIDs

NSAIDs will decrease clearance of Lithium

Preferred for having less GI and Renal side effects and easier to draw troph level

Controlled Release Lithium

When should you check a lithium level?

-Dose change -Concerns for toxicity

MOA: voltage sensitive sodium channels (VSSC)

Valproate

MOA: alpha subunit of VSSC

Carbamazepine

Reduces the release of glutamate

Lamotrigine

-Teratogenic (neural tube defects) so contraindicated in pregnancy! -Interacts with Lamictal (doubles the level) -Wide therapeutic range

Valproate

Valproate Side Effects

Vomiting, Anorexia, Liver Toxic, Pancreatitis, Retention of Water, Oedema, Alopecia, Teratogenic/Tremor, Enzyme Inhibition

For monotoring, check LFTs and CBC every 6 months, and pregnancy test prior to start (if applicable)

Valproate

-This med is more effective for mania, but less effective for the depressive phase -Inducer of 3A4, so will decrease Lamictal level by 1/2, and also will decrease sodium -Will decrease RBC and WBCs = check CBC -Need genetic testing for Asians (HLA-P 1502); risk of SJS and toxic epidermal necorylysis (TEN)

Carbamazepine

This med is better a treating the depressive phase of bipolar by blocking the alpha subunit of voltage gated sodium channels (VSSCs) thereby reducing the release of glutamate.

Lamotrigine

Everyone taking this has a risk of SJS so you must titrate very slowly every 2 weeks!

Lamotrigine

Carbamazepine + Lamotrigine =

Increases clearance of Lamotrigine

Oral Contraceptives + Lamotrigine =

Increases clearance of Lamotrigine

Valproate + Lamotrigine =

Decreases clearance of Lamotrigine

-Target dose for Bipolar is 200 mg -If missed by more than 5 days have to restart titration -Not good for non-compliant patients

Lamotrigine

Red Flags for Drug Rash

Constitutional Symptoms, Erythroderma, Facial or mucous membrane involvement, Skin tenderness or blistering, Purpura.

-Peaks within days -Settles in 10-14 days -Spotty, nonconfluent, nontender -Has no systemic features, laboratory tests are normal

Benign Rash

-Confluent and widespread, or purpuric or tender -Any prominent involvement of neck or upper trunk -Any involvement of eyes, lips, mouth, etc. -Any associated fever, malaise, pharyngitis, anorexia, or lymphadenopathy -Abnormal laboratory tests for complete blood count, liver function, urea, creatinine

Serious Rash

How long does it take Depakote (Valproate) IR to reach steady state, and how long do you want to check a troph after the last dose?

3 days to steady state, and wait 12 hrs after last dose

How long does it take Depakote (Valproate) ER to reach steady state, and how long do you want to check a troph after the last dose?

Takes 8-9 days to reach steady state, and check a troph level 15 hrs after last dose.

What is the therapeutic range for Valproate?

45-125

-Baseline: TSH, ECG (over 40 yr) -Serum level: at steady state, then every 3-6 months as indicated -Longitudinal monitoring: BUN/Creat, TSH every 3 months initially, then every 6-12 months as indicated. Weight after 6 months, then annually.

Lithium

Baseline: Hematologic and hepatic history Serum level: at steady state as indicated Longitudinal monitoring: weight, CBC, LFTs, and menstrual history every 3 months for the first year then annually; BP, bone densitometry, fasting glucose, lipid profile if there are risk factors.

Valproate

-Baseline: Hematologic and hepatic history -Serum level: 2 levels to establish dose (4 weeks apart to account for autoinduction), as indicated. -Longitudinal monitoring: CBC, LFTs, electrolytes, BUN/Creat monthly for 3 months, then annually.

Carbamazepine or Oxcarbazepine

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