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3153 IC9,10,11,12,14 Psychiatric > Bipolar > Flashcards

Bipolar Flashcards

1
Q

Peak onset of Bipolar disorder

A

15-19y

(VS schizophrenia 23y)

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2
Q

Bipolar is a __________ mood disorder

A

Lifelong, cyclical mood disorder with variable course

  • Recurrent fluctuations in mood, energy, behavior
  • Note that it is usually dominated by depressive episodes (80%)
  • Cycle frequency accelerates as illness progresses
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3
Q

Bipolar 1st episode presentation in males and females

A

Males - commonly manic episodes
Females - commonly depressive episodes

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4
Q

What is “rapid cycling”?

A

Rapid cycling

  • 4 or more mood episodes of mania, hypomanic, or depressive episodes, within 12 months
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5
Q

Risk factors of bipolar disorder

A
  • Genetics
  • Treatment-induced mania (antidepressant, ECT)
  • Induced by general medical conditions
  • History of trauma - perinatal trauma, head trauma, physical abuse
  • Physical stressors
  • Seasonal changes
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6
Q

Antidepressant-induced mania

  • Mechanism
  • Onset
A

Mechanism is unknown: incr in NE and Dopamine transmission

Fast onset: initial few days to 2 weeks (as fast as 3 days)

Use of antidepressant increases the risk of developing mania/bipolar disorder (diagnosis: bipolar depression rather than MDD)

*Antidepressants can induce mania in 1-2 weeks or within 3 days, induce suicidality in 1-2 months

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7
Q

ECT-induced mania

  • Mechanism
A

1 in 4 will switch from depressed to hypomania/manic mood due to the fast release of neurotransmitters from electrical stimulation in the brain

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8
Q

What are some medical conditions that induce mania?

A

CNS disorders

  • brain tumor, stroke, head injuries, multiple sclerosis

CNS infections

  • encephalitis, sepsis, HIV

Electrolyte or metabolic abnormalities

  • calcium or sodium fluctuations, hyper or hypoglycemia

Endocrine or hormonal dysregulation

  • cushing disease (incr ACTH, incr cortisol), hyperthyroidism

Vitamins and nutritional deficiencies

  • amino acids, fatty acids, vit B
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9
Q

What are some medications/drugs that induce mania?

A
  • Alcohol intoxication
  • Drug withdrawal states (alcohol, a2 agonist, antidepressants, barbiturates, BZDs, opiates)
  • Antidepressants
  • DA-augmenting agents (CNS stimulants - amphetamines, sympathomimetics; DA agonists)
  • NE-augmenting agents (a2 antagonist, B agonists, NE reuptake inhibitors)
  • Steroids (esp systemic - cause anxiety, psychosis, depression)
  • Thyroid preparations (T3 or T4)
  • Xanthines (caffeine, theophylline)
  • OTC weight loss and decongestants (ephedra - Ma huang, pseudoephedrine)
  • St John Wort

Avoid agents that increases NE and Dopamine activity

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10
Q

Clinical presentation of bipolar disorder

*Key feature is history of mania/hypomania not caused by any other medical conditions/substances

A
  1. Abnormal and persistently elevated/expansive/irritable mood
  2. DIGFAST
  • Distractability
  • Irresponsibility
  • Grandiosity
  • Flight of ideas
  • Activity increased (incr goal directed activity, or psychomotor agitation)
  • Sleep need is decreased (*not the same as insomnia)
  • Talkativeness (more talkative than usual, pressured speech)

Manic episode: at least 3 symptoms + elevated/expansive mood OR at least 4 symptoms + irritable mood

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11
Q

Duration of mood episode:

  • Major depressive
  • Manic
  • Hypomanic
A
  • Major depressive: >2 weeks + functional impairment
  • Manic: >=1 weeks + functional impairment
  • Hypomanic: >=4 days, no functional impairment, no psychosis
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12
Q

Bipolar I vs Bipolar II

A

Bipolar I - mania +/- depressive episodes

Bipolar II - hypomania + depressive episodes

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13
Q

General assessments

A
  • History of present illness
  • Psychiatric history – history of manic/hypomanic episodes - bipolar depression cannot use antidepressants, risk of manic switch
  • Substance use – cigarettes, alcohol, substances
  • Complete medical history and medication history (Drug allergy? Other medications? Compliance? Surgical history - thyroid glands etc.)
  • Family, social, forensic, developmental, and occupational history (1st-degree FH of illness, treatment, and response; review psychosocial circumstances every visit)
  • Physical and neurological exam (Injury? Esp head trauma?)
  • Mental state exam (Suicidal, homicidal ideations and risks; Reassess MSE every interview to evaluate efficacy and tolerability)
  • Labs and other investigations - Vital signs (BP, O2), weight, BMI, FBC, urea, electrolyte, creatinine, LFTs, TFTs, ECG, FBG, lipid panel, urine toxicology, pregnancy test

FBC: rule out anemia, infection
Kidney and Liver function: LFT not required for Lithium
TFTs: rule out hyperthyroidism - manic mood
ECG: cardiac abnormalities (lithium, antipsychotics - ziprasidone, haloperidol) may cause arrhythmias)
Urine toxicology: barbiturates, amphetamines, BZDs, cocaine, cannabinoids
Pregnancy test: valproate and lithium are teratogenic
PGx test: Carbamazepine

Exclude general medical conditions or substance-induced/withdrawal symptoms (e.g., psychosis, depression, mania, anxiety, insomnia)

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14
Q

Goals of treatment in bipolar disorders

A
  1. Reduce frequency, severity, and duration of mood episodes (since bipolar is lifelong)
  2. Prevent suicide
  3. Maximize adherence with therapy
  4. Minimize adverse effects
  5. Acute treatment phase: eliminate mood episode with remission of symptoms
  6. Maintenance/Continuation treatment phase: goals 1,2 + regain psychosocial functioning, avoidance of stressors or substances that may precipitate an acute mood episode
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15
Q

Non-pharmacological treatment in bipolar

A

Psychoeducation

  • recognize early signs and symptoms of mania and depression
  • chart mood changes (e.g., in diary)
  • compliance
  • psychosocial, physicals stressors, substances/drugs that may precipitate episode
  • strategies for coping with stressful life events
  • development of a crisis intervention plan

Psychotherapy

  • e.g., CBT

Stress reduction techniques

  • relaxation techniques

Sleep hygiene

  • regular bedtime and awake schedule; avoid alcohol or caffeine intake prior to bedtime

Nutrition

  • regular intake of protein-rish foods or drinks and essential fatty acids; supplemental vitamins and minerals

Exercise

  • Regular aerobic and weight training at least 3x per week
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16
Q

Pharmacological treatment of bipolar disorder

A
  1. Short course of PRN benzodiazepines (adjunctive during acute phase)
  2. Start mood stabilizer for acute phase treatment
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17
Q

[Pharmacological treatment of bipolar disorder]

Short course of PRN benzodiazepines (adjunctive during acute phase)

  • Use?
A
  • Help patient relax and sleep
  • Onset within hours
  • Short-term symptom relief until mood stabilizers are effective
  • Taper off when condition improved and mood stabilizer optimized
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18
Q

[Pharmacological treatment of bipolar disorder]

Start mood stabilizer for acute phase treatment

  • List the mood stabilizer options
  • Explain choice of mood stabilizer
A

Goal of acute phase treatment: eliminate mood episode with remission of symptoms, also protects from severe depression

Onset: within 3-5 days to stabilize mood (therefore short-term BZD required before mood stabilizers’ onset of effectiveness)

Mood stabilizers:

(Mania)

  • Lithium
  • Antipsychotics
  • Valproate
  • Carbamazepine

(Bipolar depression)

  • Lithium
  • Antipsychotics
  • Lamotrigine

Choice of mood stabilizer based on:

  • Response
  • Tolerability
  • Serum drug levels (TDM)
  • Avoidance of DDIs
  • Type and trend of mood episodes
  • Suicide risk
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19
Q

[Pharmacological treatment of bipolar disorder]

Which antipsychotics may be used in mania?

A

All antipsychotics can be used for mania

SGA: Olanzapine, Quetiapine, Risperidone, Aripiprazole

(Ran Out Away Quiet)

FGA: Haloperidol

If pt gets well on SGA for acute phase mania, may continue that drug for maintenance, consider using LAI (R 2w) (A 1m)

For long-term maintenance treatment, only OAQ are licensed, the other SGAs and Haloperidol are off-label use in mania

FYI: antipsychotics may relieve agitation within an hour if used alone or with BZD for rapid tranquilization

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20
Q

[Pharmacological treatment of bipolar disorder]

Which is first line in mania?

  • Lithium
  • Antipsychotics
  • Valproate
  • Carbamazepine
A

Lithium is the 1st line for maintenance and relapse/suicide prevention

But if ineffective/poorly tolerated (due to lithium toxicities), Olanzapine/Quetiapine can be considered

Valproate is least preferred

Carbamazepine is last line

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21
Q

[Pharmacological treatment of bipolar disorder]

What combinations may be used in mania?

A

If monotherapy ineffective, consider:

  • Lithium and/or Valproate +/- Antipsychotics
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22
Q

[Pharmacological treatment of bipolar disorder]

Which antipsychotics can be used in bipolar depression?

A
  • Quetiapine
  • Olanzapine + Fluoxetine (Symbyax capsule)
  • Others (FYI): Lurasidone, Cariprazine

*Olanzapine alone has limited antidepressant properties
*Quetiapine may be sedating + orthostatic hypotension
*Recall Symbyax is also used in treatment-resistant depression

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23
Q

[Pharmacological treatment of bipolar disorder]

Which is first line in bipolar depression?

  • Lithium
  • Antipsychotics
  • Lamotrigine
A

Lithium is 1st line for maintenance and relapse/suicide prevention

Lamotrigine has NO anti-manic properties

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24
Q

[Pharmacological treatment of bipolar disorder]

What combination can be used in bipolar depression?

A

Any combination:

  • Lithium
  • Olanzapine + Fluoxetine
  • Quetiapine
  • Lamotrigine
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25
Q

[Pharmacological treatment of bipolar disorder]

Maintenance therapy choice

A
  • Lithium
  • Antipsychotic for long-term maintenance: Olanzapine, Quetiapine, Aripiprazole are licensed; risperidone, haloperidol and others are off-label
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26
Q

[Lithium]

MOA

A
  • Normalizes/inhibits second messenger systems, reduce protein kinase C
  • decreases 5HT reuptake
  • decreases dopamine release
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27
Q

[Lithium]

TDM

A
  • Steady state: in 5 days
  • Acute mania: 0.8 - 1.0 mEq/L
  • Maintenance: 0.6-1.0mEq/L

Narrow therapeutic index

  • Sampling time: take samples 12h after the previous dose; 5-7 days after initiation/dose changes/interacting drug
  • Monitor serum lithium q3-6m in stable patients

*NOTE: aim lower therapeutic range for the elderly since they are more susceptible to side effects

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28
Q

[Lithium]

Side effects

A

Side effects are dose-dependent

Common SEs at >0.8mEq/L:

- Fine to coarse tremors
- Polyuria
- Hypothyroidism
- Cardiac effects (ECG changes)
- Nausea
- Weight gain
- Fatigue
- Cognitive impairment
- Diabetes insipidus

Mild (1.5-2.0 mEq/L)

  • GI SEs: nausea, vomiting, loose stools
  • CNS SEs: lethargy, confusion, coarse hand tremors, drowsiness, light-headedness

Moderate (2.0-2.5 mEq/L)

  • GI SEs: severe nausea, vomiting, diarrhea
  • CNS SEs: slurred speech, worsening confusion, ataxia, blurred vision, profound lethargy, tinnitus, apathy

Severe (>3.0 mEq/L)

  • GI SEs: severe nausea, vomiting, diarrhea
  • CNS SEs: seriously impaired consciousness, increase deep tendon reflexes, stupor, coma, seizures, death

Note that toxicity may increase from mild to severe within hours bc fluid and electrolyte loss cause further increase in lithium concentration)

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29
Q

[Lithium]

Counseling points

A
  • Stomach upset/nausea - take with food
  • Increased thirst and urination - sip enough water ~2L, but not excessively
  • Tremors, nausea - inform Dr if worsens
  • Weight gain - healthy diet, exercise
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30
Q

[Lithium]

  • Drug interactions
A

Lithium toxicity (elevated lithium levels) with: STAND

  • Sodium depletion
  • Thiazide diuretics
  • ACEi/ARBs
  • NSAIDs
  • Dehydration
  • also: Fluoxetine

Others:

  • Neurotoxicity when combined with lithium: carbamazepine, diltiazem, losartan, methyldopa, metronidazole, phenytoin, verapamil
  • Enhance renal elimination of lithium: caffeine, theophylline
31
Q

[Lithium]

Explain the mechanism of how sodium depletion causes lithium toxicity

Sodium depletion can be due to: diuretics use, salt restriction, excess water intake

A

Sodium and Lithium are small monovalent cations

In hyponatremia, kidney reabsorbs sodium and inevitably reabsorbs lithium back as well, thereby causing elevated lithium levels and thus lithium toxicity

32
Q

[Lithium]

  • Use in liver and renal impairment
A

lithium is NOT cleared by the liver, 100% cleared by kidneys

Therefore,

  • Lithium can be used in liver impairment
  • Caution for use in kidney impairment (half-life of lithium increases in elderly and renal impairment, may cause toxicity)

Note: lithium has no CYP interactions

33
Q

[Lithium]

What labs/monitoring are required and why?

A

Physical exam (baseline):

  • ECG, pregnancy test, urine toxicology

ECG (annually)

  • For lithium if >40y or cardiac disease; as lithium may cause ECG changes

FBC (baseline, 6-12m)

Renal panel and electrolytes + calcium (baseline, q3m for 1st 6m, then q6-12m)

  • Monitor low Na+ (risk of lithium toxicity due to sodium depletion)
  • Monitor Ca2+ levels
  • Renal impairment

TFT (baseline, q3m for 1st 6m, then q6-12m)

  • Lithium may cause hypothyroidism

Metabolic - FBG, lipids, BMI (baseline, q3m for 1st 6m, then q6-12m)

  • Lithium may cause weight gain, diabetes insipidus

TDM

34
Q

[Lithium]

Use of lithium in pregnancy

A

Lithium is teratogenic - ebstein anomaly, fetal thyroid goiter

If pregnant patient is already on maintenance lithium:

  • If risk of relapse is high, consider switching to SGA or lower dose of lithium (~0.3mmol/L) to keep recurrence risk low

Because lithium withdrawal causes relapse!

35
Q

[Lithium]

Administration, bioavailability

A

Delayed absorption: 60-90%

Food may slow down absorption

36
Q

[Sodium Valproate]

MOA

A

Increase GABA levels
Decrease dopamine turnover
May decrease protein kinase C
Normalize Na+ and Ca+ channels
Antikindling properties

37
Q

[Sodium Valproate]

Loading dose of sodium valproate may be given, but often not done in clinical practice because…?

A

Benzodiazepine started while waiting for valproate onset

38
Q

[Sodium Valproate]

TDM

A
  • Steady-state: 3-5 days
  • Target: 50-125mcg/mL
  • Sampling time: trough sample needed, at least 2-3 days after initiation/changes in dose

TDM required (not routinely required for valproate unless evidence of poor adherence/effectiveness, or toxicity)

39
Q

[Sodium Valproate]

SEs

A
  • Hepatotoxicity in children
  • Rash, SJS/TEN
  • Alopecia

High dose:

  • GI: nausea - take after food
  • Decrease platelets (thrombocytopenia)
  • Pancreatitis (abdominal pain)
  • Dizziness, somnolence - take at bedtime
  • Hyperammonemia
  • Ataxia, tremor - if worsen, consult Dr
  • Weight gain - healthy diet and lifestyle
40
Q

[Sodium Valproate]

Metabolism

A

Metabolized by the liver => inactive metabolites

  • Substrate of CYP2C19
  • Inhibitor of CYP2C9, 2D6, 3A4, 3A3

Half-life longer in liver impairment

41
Q

[Sodium Valproate]

Drug interactions

A

Risk of SJS with Lamotrigine

  • Valproate decreases the clearance of Lamotrigine (incr Lamotrigine concentration)
42
Q

[Sodium Valproate]

What labs/monitoring are required and why?

A

Physical exam (baseline):

  • ECG, pregnancy test, urine toxicology

FBC (baseline, 1st month, q6m, then anually)

  • Thrombocytopenia (dcr platelets)

LFTs (baseline, 1st month, q6m, then anually)

  • Hepatotoxicity in children

Metabolic - FBG, lipids, BMI (baseline, 6-12m)

  • Sodium Valproate may cause weight gain

TDM

43
Q

[Sodium Valproate]

Use in pregnancy

A
  • Contraindicated in pregnant women for bipolar disorder
  • CI in women of childbearing potential, unless conditions of pregnancy prevention program fulfilled

If a pregnant woman is already on VPA,

  • consider switching to SGA such as Olanzapine (watch for gestational diabetes)
44
Q

[Carbamazepine]

MOA

A

Increase glutamate transport
Block voltage-sensitive Na+ channels

(SODIUM CHANNEL ONLY)

45
Q

[Carbamazepine]

TDM

A
  • Target >7mg/L for bipolar (VS 4-12mg/L for epilepsy)
  • Sampling: trough
  • Steady-state: 2-4 weeks (due to autoinduction), look out for toxicity in first 4 weeks
  • After initial 4 weeks, steady-state achieved after 3-5 days

Monitor

  • q6m for 1st year, then annually
46
Q

[Carbamazepine]

SEs

A
  • GI: constipation - sip water
  • Dry mouth - sip water
  • CNS: somnolence - take at bedtime; dizzy - rise up slowly
  • Hyponatremia (worse with Oxcarbazepine) => worsen seizure
  • Blood dyscrasias (esp aplastic anemia) (agranulocytosis with Clozapine)
  • Rash, SJS/TEN - see Dr immediately
  • Fever/sore throat - see Dr immediately
47
Q

[Carbamazepine]

PK - metabolism

A

Hepatic metabolism

  • active metabolite: 10,11-epoxide
  • autoinduction (3A4, 2C9)
  • inducer of CYP1A2, 2C9, 3A4
  • substrate of CYP2C8, 3A4
48
Q

[Carbamazepine]

Drug interactions

A

Agranulocytosis with Clozapine

CYP interactions (inducer)

49
Q

[Carbamazepine]

What labs/monitoring are required and why?

A

HLA-B*1502 allele

Physical exam (baseline):

  • ECG, pregnancy test, urine toxicology

FBC (baseline, 6-12m)

  • agranulocytosis

LFTs (baseline, 6-12m)

Electrolytes and renal panel

  • Hyponatremia - repeat 2w after initiation, q1m for first 3m

TDM

50
Q

[Lamotrigine]

MOA

A

Blocks voltage-sensitive Na+ and Ca+ channels

51
Q

[Lamotrigine]

TDM

A

NIL

52
Q

[Lamotrigine]

SEs

A
  • Rash, SJS/TEN (esp in initial 8w, slow titration, incr dose 2 weekly intervals) - see doctor immediately
  • GI: nausea - take with food
53
Q

[Lamotrigine]

Lamotrigine may be preferred because:

A
  • less sedation
  • less weight gain
  • safer choice in pregnancy
54
Q

[Lamotrigine]

Interactions

A

SJS risk with Valproate

  • Valproate increases concentration and half-life of Lamotrigine
  • Max 100mg Lamotrigine (dose 50-200mg/day) if combined with VPA
55
Q

[Lamotrigine]

Metabolism

A

Hepatic metabolism

  • half life longer in hepatic impairment
56
Q

[Lamotrigine]

What labs/monitoring are required and why?

A

Physical exam (baseline):

  • ECG, pregnancy test, urine toxicology

FBC (baseline only)

LFTs (baseline, 6-12m)

Electrolytes and renal panel (baseline only)

57
Q

[Antipsychotics]

  • MOA
  • SE
  • Labs, monitoring
A

MOA:

  • dopamine antagonist
  • (SGA) 5HT2A antagonist

SEs:

  • EPSE
  • Incr prolactin
  • Metabolic SE: weight gain

Labs, monitoring:

  • ECG
  • FBG
  • Lipid panel

Relatively safe in pregnancy, just watch for gestational diabetes with Olanzapine, mod - Quetiapine

58
Q

[Treatment approaches to manage POOR response]

  • Augmentation
  • Switching
A

If mania has not responded within 2-4 weeks, consider:

  • augment with second agent (partial response)
  • switch to SGA (no response or intolerable)

Carbamazepine is considered if all of the above failed

59
Q

[Treatment approaches to manage POOR response]

What non-pharmaco can be considered?

A

ECT

  • rapidly reduces manic/depressive symptoms in severe or treatment-resistant mania/depression
  • maintenance ECT can also be considered (esp an option in pregnancy)
60
Q

Define treatment-resistant bipolar disorder

A

For Bipolar Disorder, “resistance” is considered following treatment trials for at least 6 weeks in mania, 12 weeks in bipolar depression, and 12 months or more for long-term maintenance treatment

“Treatment-resistance” refers to refractoriness to multiple trials of different mood stabilisers.

Treatment resistance in Bipolar Disorder should be referred to a specialist. (i.e. Undergrad students are not expected to advise on its treatment)

61
Q

ECT

  • What drugs should be omitted prior to ECT?
A

Omit Lithium, Anticonvulsants, Benzodiazepines (at least 12h) before ECT

(Due to cognitive side effects such as delirium)

62
Q

Treatment option in bipolar disorder with rapid cycling (4 or more mood episodes per year)

A
  • Avoid antidepressants/stimulants in rapid cycling or history of antidepressant-induced mania
  • For antidepressant-induced rapid cycling, avoid and taper off antidepressants and other agents that increase NE or dopamine activity (e.g., CNS stimulants, sympathomimetic, caffeine)
  • Evaluate and treat underlying conditions (e.g., hypothyroidism, hormonal imbalance, substance abuse)
  • Optimize mood stabilizer treatment: Valproate, Lithium Lamotrigine
63
Q

[Special populations]

Pregnancy

A
  • Avoid valproate (risk of neural tube defects)
  • Avoid lithium (ebstein anomaly, fetal thyroid goiter)
  • Avoid carbamazepine (malformation risk)
  • Safer options: antipsychotics (quetiapine, olanzapine, risperidone), ECT for severe mania

Refer to specialist for pregnant pt or pt planning pregnancy

64
Q

[Special populations]

Women of childbearing age

A

For females of child-bearing potential who requires a mood stabiliser for Bipolar Disorder:

  • Avoid Valproate
  • Also avoid Carbamazepine (as this is not first-line option anyways)
  • Lithium, Lamotrigine and SGA are reasonable options for the non-pregnant patient
65
Q

[Special populations]

Breastfeeding

A

All mood stabilizers secreted in breastmilk, weigh risk vs benefits

66
Q

[Special populations]

Liver impairment

A

Lithium

  • 100% cleared renally, not affected by hepatic impairment
67
Q

[Special populations]

Renal impairment

A

Consider Valproate

  • Monitor serum levels closely
68
Q

[Special populations]

Cardiac disease

A

Consider Valproate

  • Monitor BP, HR, peripheral edema
69
Q

[Special populations]

Children, Adolescents

A

Consider Lithium, Valproate

70
Q

[Special populations]

Elderly

A

Consider Lamotrigine

All psychotropics increase risk of side effects (anticholinergic, sedation)

Avoid renally-excreted drugs (e.g., Lithium)

Avoid Carbamazepine (hyponatremia, DDIs)

71
Q

[Special populations]

Suicidal behavior

A

Optimize dose and levels of Lithium

72
Q

[Special populations]

Aggression/Violence

A

Optimize dose and levels of existing Lithium or Valproate, consider adding antipsychotic

(Combi)

73
Q

Which drug option is safest as there is less propensity for acute overdose?

A

Antipsychotics

74
Q

Evaluation of therapeutic outcomes

A

Therapeutic outcomes require regular monitoring by clinician

  • Initially 2 weekly, then monthly, then 3 monthly when stabilized

Pts and caregiver should actively monitor for:

  • Target symptoms
  • Efficacy of treatment
  • Adverse effects and drug interactions
  • Compliance

3153 IC9,10,11,12,14 Psychiatric (10 decks)

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