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DMH Prep > Bipolar and Related > Flashcards

Bipolar and Related Flashcards

1
Q

Define a Manic Episode

A

(A) A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary).
DIG FAST

D - distractibility
I - increased goal directed activity
G - grandiosity increased
F - flight of ideas
A - activities increase that have a high potential for painful consequences
S - sleep deficit
T - talkative

(B) the symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

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2
Q

Define and compare and contrast a Manic vs Hypomanic Episode

A

Hypomanic episode - meets criterion A and B of a manic episode but the duration for a manic episode is at least 1 week duration whereas the duration of a hypomanic episode is at least 4 consecutive days.

MANIA
- at least 1 week in duration
- psychotic features
- hospitalization
- marked impairment in social or occupational functioning

HYPOMANIA
- at least 4 consecutive days
- no psychotic features
- no hospitalization
- no marked impairment in social or occupational functioning

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3
Q
  1. Define Bipolar Type 1 Disorder
  2. What is the mean age of onset of first manic/hypomanic or major depressive episode.
  3. Risk factors for BPMD 1
A
  1. Disorder in which at least one manic episode has occurred, or if manic symptoms have led to hospitalization, or if psychotic symptoms are present. The manic episode may have been preceded by and may be followed by hypomanic or major depressive episodes.
    Not better explained by a schizophrenic or schizoaffective disorder.
  2. 18 years
  3. More common in high income as compared to low income countries, strongest risk factor is a positive family history (10x increased risk). Lifetime suicide risk is 15x that of the general population.
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4
Q
  1. Define Bipolar Type 2
  2. What is the mean age of onset?
  3. What is the major risk factor?
  4. Describe the biological treatment options for BPMD 2
  5. Describe the psychosocial interventions for BPMD 2
A
  1. Disorder in which at least 1 major depressive episode and 1 hypomanic episode have occurred. No manic episode. Symptoms causing clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  2. mid-20s - slightly later than BPMD 1 and earlier than MDD
  3. Genetic - greater genetic risk exists for bipolar type 2 than for bipolar type 1 or MDD. Lifetime attempted suicide risk is similar as for that of bipolar type 1 but the lethality of the attempts may be higher for bipolar type 2.
  4. lithium, anticonvulsants, antipsychotics - never monotherapy of antidepressants
  5. Support, therapy, stable routine with eating, sleeping and exercise.
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5
Q

List the Diagnostic Criteria for Cyclothymia

A

(A) For at least 2 years (at least 1 year in children and adolescents) there have been numerous periods with hypomanic symptoms that do not meet the criteria for a hypomanic episode and numerous periods with depressive symptoms that do not meet criteria for a major depressive episode.
(B) During the above 2-year period (1 year in children and adolescents), the hypomanic and depressive periods have been preset for at least half the time and the individual has not been without symptoms for more than 2 months at a time.

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6
Q

Treatment Options for Bipolar Disorders

A
  1. Mood stabilizers
  2. Anticonvulsants
  3. Second generation antipsychotics
  4. Somatic Therapies - ECT, light therapy, TMS, VNS
  5. Non-pharmacologic therapies - CBT and other psychotherapies.
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7
Q

What is a mood stabilizer?

A

A drug that treats both acute manic and depressive episodes, and prevents recurrence of both mood states, particularly in bipolar patients.

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8
Q

Indications for Mood Stabilizers

A
  • schizoaffective disoders
  • BPMD and mood disorders secondary to GMCs
  • seizures and epilepsy
  • chronic and neuropathic pain - particularly carbamazepine
  • migraines - valproate
  • lithium and lamotrigine are effective in augmentation agents for antidepressants in patients with MDD
  • mood instability (BPD), reduce suicidality, impulsivity and aggression in patients with PDs, head injuries and other disorders.
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9
Q

In the treatment of BPMD
1. Which agents are more effective in acute mania and prevent further mania?
2. Which agents are effective in treating and preventing bipolar depression?
3. Which are first line agents for mania?
4. Which are first line agents for depressive phase?

A
  1. lithium, valproate, carbamazepine
  2. lithium and lamotrigine
  3. lithium and valproate
  4. lithium and lamotrigine.
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10
Q

Which are the most teratogenic groups of psychotropics?

A

Mood stabilizers - therefore use of antipsychotics are advised in treating bipolar in pregnancy and breastfeeding. Lithium can cross into the breastmilk in large quantities.

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11
Q

What is the role of blood levels in the use of mood stabilizers?

A
  • compliance check
  • toxicity check
  • therapeutic dose range
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12
Q

What are the two preparations of Lithium

A

Lithium carbonate tablet
Lithium citrate liquid

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13
Q

How is Lithium metabolized

A

Lithium is not metabolized and is excreted directly from the kidneys

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14
Q

What is the weight recommendation when dosing Lithium

A

20mg/kg

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15
Q

How would you initiate Lithium and make dose alterations

A

Start at a dose of 250mg mornings and adjust every 5 days based on the Lithium levels

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16
Q

What are the clinical indications for Lithium?

A

Manic episode, bipolar depression, augmentation of antidepressants, aggression and self mutilation, reduces suicidality by 80%, lithium alone is more effective than valproate alone

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17
Q

What is the prophylactic plasma level of Lithium?

A

0.4mmol/L

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18
Q

What is the therapeutic range of serum Lithium?

A

0,6 - 0,75 mmol/L

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19
Q

What is the maintenance plasma level for Lithium?

A

0,6 - 1,2 mmol/L

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20
Q

What is a toxic Lithium level?

A

0,8mmol/L associated with high risk of renal toxicity

and levels greater than 1.5mmol/L associated with lithium toxicity

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21
Q

How should Lithium levels be monitored?

A

Blood levels need to checked when starting or changing a dose and every 3-4 days while titrating. Blood should be drawn 12 hours after the last dose.

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22
Q

What is the pre-treatment work-up before initiating Lithium and why?

A
  1. FBC
  2. Renal function - renally excreted
  3. Thyroid function - associated with hypothyroidism
  4. Cardiac function ECG - check for signs of IHD and cardiac risk factors
  5. Weight - can cause weight gain
  6. Pregnostic - potent teratogen. Needs reliable contraceptive.
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23
Q

Advice to those starting Lithium

A
  • stay well hydrated
  • have a high salt diet
  • disclose any medications that they may be taking such as ACE inhibitors, diuretics and NSAIDs.
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24
Q

Describe stable Lithium therapy monitoring

A

Every 6 months - plasma lithium levels, eGRF and thyroid function
More frequent monitoring might be required in those who are on interacting drugs, elderly or have CKD
Weight and BMI should also be checked at follow-up

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25
Q

Adverse effects of Lithium

A
  • dose and plasma level related
  • metallic taste in the mouth
  • ankle oedema
  • weight gain
  • cognitive dulling/greying
  • lack of spontaneity
  • fatigue
  • slowed reaction time
  • tremor
  • rare are seizures, myasthenia-gravis like syndrome, neuropathy and Parkinson’s features.
  • psoriasis and acne can be made worse by lithium therapy
  • increased risk of hypothyroidism
  • mild gastrointestinal upset, N and V and diarrhoea
  • ECG changes, arrythmias (abnormal heart rhythms), conduction defects, heart block, cardiac failure, syncope
  • polyuria - more frequent with the twice daily dosing
  • polydipsia
  • nephrogenic diabetes insipidus
  • levels of greater than 0.8mmol/L is associated with higher risk of renal toxicity and levels greater than 1.5mmol/L is associated with lithium toxicity
  • teratogenic - causes Ebsteins Anomaly
26
Q

Approach to Lithium and Pregnancy/Lactation

A
  • do a risk benefit analysis
  • avoid use if possible
  • strictly not for use during breastfeeding
  • if it has to be used during pregnancy, ensure god fetal heart monitoring, use the lowest possible dose, treat in conjunction with an obstetrician
  • consider the use of antipsychotics rather in pregnancy

First trimester exposure - cardiac abnormality called Ebstein’s anomaly of the tricuspid valve - floppy heart valve.

2nd and 3rd trimester exposure
- neonatal goiter and thyroid abnormalities
- heart abnormalities
- floppy infant syndrome
- preterm labour

27
Q

How does one discontinue Lithium

A

Reduce slowly over at least 1 month but preferable over 3 months

28
Q

How does lithium interact with:
1. ACE inhibitors
2. Thiazide diuretics
3. NSAIDS
4. Carbamazepine

A
  1. cause dehydration and increased sodium loss from the kidneys which can cause an increase in plasma lithium levels which can cause lithium toxicity
  2. same thing
  3. decrease the production of renal prostaglandins which causes a reduction in renal blood flow which causes in increase in sodium reabsorption which causes increased plasma sodium and therefore increased lithium levels
    4._____________
29
Q

What is the mechanism of actions of Epilim, preparations and dosage?

A
  1. inhibit the catabolism of GABA, acts on the sodium channels and neuropeptides
  2. Valproic acid, sodium valproate, semi-sodium valproate
  3. 250mg to 2000mg BD (20mg/kg/day) sometimes up to 30mg/kg/day
30
Q

Indications for Epilim

A
  • acute mania and hypomania
  • acute bipolar depression
  • may accelerate the response to antipsychotics in psychotic disorders
  • reductions of depression
  • epilepsy
  • migraines
31
Q

Pre-treatment work-up for Epilim

A

Baseline FBC
LFTs and weight
BMI
Should be repeated every 6 months

32
Q

Monitoring and stopping Epilim

A

FBCs and LFTs and weight if clinically indicated
Reduce slowly over at least 1 month

33
Q

What are the advantages of Epilim over Lithium?

A

Has a wider therapeutic margin and therefore safer in overdose and less likely to become toxic
Lack of the renal toxicity effects and therefore safer in those patients at risk for renal dysfunction such as HPT, DM and prone to dehydration

34
Q

What are the disadvantaged of Epilim as compared to Lithium?

A

Can cause potentially fatal but rare liver and pancreatic effects
Broken down by the liver via the P450 enzymes - has some interactions with other drugs being broken down by this system.
Most teratogenic

35
Q

Common on the side effects of Epilim

A
  • most of the adverse effects of Epilim are dose related and increase in frequency and severity with a plasma level of greater the 100mg/L
  • Metabolized by the liver but eliminated by the kidneys partly in the form of ketone bodies and can therefore give a false positive urine ketone test
  • Causes bone marrow suppression - can cause a leucopenia, anemia or thrombocytopenia. Can cause a pancytopenia.
  • Hepatotoxicity - can cause severe liver dysfunction and the LFTs can be raised more than 3-4x the normal. This can be fatal in young patients especially and requires stopping the drug immediately.
  • Can cause PCOS - enlarged ovaries that contain many small cysts. Causes infertility, irregular or absent menses, excessive hair growth on the face and body, male-pattern baldness, associated with HPT, DM, weight gain and high cholesterol.

Common effects:
- GI irritation, nausea, sedation, tremor, weight gain, hair loss

36
Q

Comment on the use of Epilim in women of child bearing age.

A
  • contraindicated and other mood stabilizers should be used
  • should not be initiated without specialist advice
  • those who do require it and are trying to conceive should receive prophylactic folate
  • women with mania likely to be sexually disinhibited and therefore long-acting and reliable contraceptives must be used.
  • causes neural tube defects and can also cause ID
  • do a risk benefit analysis on every patient

1st trimester - neural tube defects and spina bifida
If it has to be used, use with folate and treat with obs, sonar and amniocentesis
2nd and 3rd trimester - minor facial and fingernail abnormalities
Lactation - use with caution, safer than Lithium

37
Q

Comment on the interaction of Epilim with other drugs.

A
  • highly protein bound and can be displaced by other protein-bound drugs such as aspirin leading to toxicity. Aspirin also inhibits the metabolism of valproate, a dose of at least 300mg of aspirin is required
  • less strongly bound drugs such as warfarin can be displaced by valproate leading to higher free levels and toxicity of Warfarin
  • hepatically metabolized and therefore drugs than inhibit the CYP enzymes can increase valproate levels - erythromycin, fluoxetine and cimetidine
38
Q

What is the mechanism of action of Carbamazepine (Tegratol)?

A

Blocks voltage-dependent sodium channels thus inhibiting repetitive neuronal firing. It reduces glutamate release and decreases the turnover of dopamine and noradrenaline. Carbamazepine has a similar molecular structure to TCAs.

39
Q

What are the available formulations of Carbamazepine?

A

liquid, chewable, immediate release and controlled release tablets

40
Q

What are the indications of Carbamazepine?

A

Mania (but not as a first line)
Prophylaxis of bipolar disorder - third line after antipsychotics and valproate
Bipolar depression
Unipolar depression
Aggression
Alcohol withdrawal
Those who do not respond to Lithium

41
Q

What are the adverse effects of Carbamazepine?

A

dizziness
diplopia
ataxia
nausea
headaches
hyponatremia
sexual dysfunctions
rash
agranulocytosis
aplastic anaemia

42
Q

What are the pre-treatment tests for initiation of carbamazepine?

A

FBC
U and E
LFT
Repeated every 6 months

43
Q

Is carbamazepine teratogenic?

A

Yes, causes neural tube defects.
Cover the patient with folate.

44
Q

What is the dosage range of Carbamazepine?

A

400mg-1200mg per day - drug levels can be done of the drug.
Therapeutic levels 4-12mg/L

45
Q

Comment on drug to drug interactions with Carbamazepine

A

Potent inducer of the hepatic cytochrome enzymes and is metabolized by CYP3A4
Carbamazepine can decrease the plasma levels of most antidepressants, antipsychotics, benzodiazepines, warfarin, estrogens and steroids which can lead to treatment failure of these drugs.

Drugs that inhibit CYP3A4 will increase carbamazepine plasma levels and may precipitate toxicity - examples are fluconazole, cimetidine, diltiazem, verapamil. erythromycin and some SSRIs

46
Q

What is the mechanism of action of Lamotrigine?

A

Largely unknown
Blocks sodium channels
Stabilizes membranes
inhibits glutamate and aspartate release
increase in the plasma serotonin concentration and inhibits serotonins reuptake.
Generally well tolerated drug

47
Q

What are the indications for Lamotrigine

A

Bipolar disorder
Effective against depressive episodes in bipolar disorder but have poor anti-manic effect

48
Q

What are the adverse effects of Lamotrigine?

A
  • dizziness, ataxia, somnolence, headache, diplopia, blurred vision, sedation
  • SJS - hectic!!
    -ranges from mild to life threatening rash
  • Can be SJS, TEN or angio-oedema
  • More likely to occur when high starting dose of lamotrigine or quick upward dose titration
  • therefore - start low and go slow
  • Valproate doubles the dose of lamotrigine which may precipitate the fatal rash, therefore must halve the dose of Lamotrigine when adding valproate.
49
Q

What is the recommended dosing of Lamotrigine?

A

Starting dose is 12.5mg PO at night
Titrate by 12.5mg every 2 weeks to avoid the rash
Maintenance dose is 100-200mg mg PO at night.

50
Q

Why is Lamotrigine a good mood stabilizing choice in BPMD II?

A

Lamotrigine has greater effectiveness in controlling the depressive phase of illness than the manic or hypomanic phases and since those with BPMD II spend about 90% of the illness in the depressive phase of illness, greater value is seen here.

51
Q

Which drug is thought to be a good mood stabilizer of choice in pregnant patients?

A

Quetiapine is a good mood stabilizer of choice as it does not cross the placental barrier and is not teratogenic

52
Q

Which fetal abnormality is most commonly associated with Lithium use in pregnancy?

A

Cardiac abnormality called Ebstein’s Anomaly

53
Q

Which of the mood stabilizers has a role in the treatment of chronic migraines?

A

Epilim

54
Q

Which two mood stabilizers are thought to be effective choices for antidepressant augmentation in the treatment of resistant unipolar depression?

A

Lithium
Lamotrigine

55
Q

What types of fetal abnormalities are associated with Lamotrigine?

A

Cleft lip and palate

56
Q

Briefly comment on the MOA of Epilim (Valproic Acid)

A

Inhibits the catabolism of GABA, acts on sodium channels and neuropeptides

57
Q

What are some advantages of Epilim over Lithium?

A
  • has a wider therapeutic margin (wider gap between the therapeutic and toxic doses) than Lithium, therefore less likelihood of toxicity with valproate and safer in overdose
  • lack of renal toxic effects and therefore safer in those with renal dysfunction
58
Q

What are some of the disadvantages of Epilim as compared with Lithium?

A
  • may cause potentially fatal but rare liver and pancreatic effects
  • broken down in the liver by the P450 enzymes and therefore will have some interactions with other drugs being broken down by this system
  • most teratogenic of all mood stabilizers
59
Q

Comment on the adverse effects of Valproate

A
  • dose related and generally seen increase in frequency and severity when the plasma level is >100mg/L
  • valproate eliminated through the kidneys partly in the form of ketone bodies and can give a false positive urine test for ketones
  • bone marrow suppression - can cause a PANCYTOPENIA
  • hepatotoxicity - liver enzymes can be raised 3-4x the regular levels which can actually be life threatening in young or at risk patients
  • PCOS - enlarged ovaries that contain many small cysts.
  • side effects - GI irritation, nausea, sedation, tremor, weight gain, hair loss
60
Q
A

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