Bipolar Disorder Flashcards
What 5 types of medications/intervetions are used to treat an acute depressive episode in patients with bipolar disorder?
- “Antidepressants”
- Lithium
- Anticonvulsants
- Second generation antipsychotics
- ECT
What specific antidepressants are used to treat an acute depressive episode in patients with bipolar disorder? (1)
Fluoxetine (Prozac) + Olanzapine (Zyprexa) = combination drug called Symbyax
What specific anticonvulsants are used to treat an acute depressive episode in patients with bipolar disorder? (3)
- Lamotrigine (Lamictal)
- Lamotrigine (Lamictal) + Lithium
- Valproate (Depakote)
What specific second-generation antipsychotics are used to treat an acute depressive episode in patients with bipolar disorder? (4)
- Quetiapine (Seroquel)
- Lurasidone (Latuda)
- Cariprazine (Vraylar)
- Olanzapine (Zyprexa)
Are other antidepressants beyond the Symbyax combination medication used in treatment of acute bipolar disorder?
Antidepressants have a limited role as an adjunct treatment of acute bipolar depression. Use of antidepressants for acute and maintenance treatment of bipolar depression is controversial because of concerns the medications are not effective and may harm patients by causing switches from depression to mania as well as rapid cycling.
Discuss the evidence regarding the possible role of antidepressants in switching in patients with bipolar disorder.
Switching often occurs in bipolar disorder in the absence of antidepressant treatment. The natural switch rate is 41% (depression to mania, no antidepressants). Evidence is not completely clear that antidepressants as a class increase switching during acute or maintenance treatment.
- Increased rapid cycling when TCAs were introduced
- Mania rates over 2 years were highest with imipramine (vs. placebo vs. lithium)
- Antidepressants induce reversible rapid cycling in double-blind placebo-controlled studies
Randomized trials indicate that switching during the treatment of bipolar depression occurs more often with ___ or ___ compared with bupropion (Wellbutrin), SSRIs, or placebo, which have a switch rate of 3-5%.
TCAs (10-11% switch rate)
Venlafaxine (Effexor) - 12-15%
What are the most commonly prescribed medications for bipolar depression?
Antidepressants
Bupropion seems to have the least risk of switching
What historical information about patients may help determine if an antidepressant could be used for treating bipolar depression?
- History of responding favorably in the past
2. Has never taken antidepressants
What historical information about patients may help determine if an antidepressant should be avoided for treating bipolar depression?
- Previously experienced poor outcomes (switching, rapid cycling, suicidal ideation and behavior)
- Concurrent manic symptoms
- SUD
- Early age of onset for bipolar disorder
- Recent history (past 2-3 months) of mania or hypomania
Are there any predictors of a better response to antidepressants in bipolar depression?
Depressed patients with comorbid anxiety are less likely to respond to treatment than patients without anxiety.
Which anti-manic drugs should be used with an antidepressant so as to prevent switching?
- Lithium
- Valproate (Depakote)
- Carbamazpeine (Tegretol)
- Second generation antipsychotics - Olanzapine (Zyprexa), Quetiapine (Seroquel), Lurasidone (Latuda)
Switching to mania occurs less often when the aforementioned anti-manic drugs are used with an antidepressant. While it is unclear how long after remission of depression that antidepressants should be continued, in general, they are continued for ___ after remission, unless the patient has a history of what 4 things?
2-4 months
- Antideprssant associated switching to hypomania/mania
- Increases in mood cycle frequency
- History of frequent and/or severe manic episodes
- Concurrent course of rapid cycling
True or false - avoiding antidepressant monotherapy is consistent with practice guidelines.
True
Are antidepressants used in maintenance treatment of bipolar depression?
No - this does not appear to reduce the risk of depressive episodes
In treating a manic or hypomanic episode of bipolar disorder, what is the goal?
The goal is remission such that at most only 1-2 symptoms of mild intensity persist. Resolution of psychosis is required.
Patients with ___ symptoms of mania are at increased risk of relapse.
Subsyndromal
What is the difference between a severe acute manic episode and a moderate acute manic episode?
While there is no established criteria for what is a severe acute manic episode, a manic episode is considered severe if there is dangerousness (SI or behavior; HI or behavior; aggressive behavior; poor judgment that places the patient or others at imminent risk of being harmed) or psychotic features (hallucinations or delusions)
What drug classes are commonly used in the treatment of acute mania or hypomania?
- Lithium
- Anticonvulsants
- Antipsychotics
- Benzodiazpines
How are benzodiazepines used in the treatment of acute mania or hypomania?
Primarily as adjunctive treatments for insomnia, agitation, or anxiety
What is the general approach to treatment of a severe manic episode?
Combination therapy:
- Lithium + antipsychotic
- Valproate (Depakote) + antipsychotic
What is the general approach to treatment of a mild/moderate manic episode or hypomanic episode?
Monotherapy:
- Lithium
- Anticonvulsants
- Antipsychotics
How long does a medication regimen need to be given to tell if it is working for treatment of a manic or hypomanic episode?
While there is no formally established timeline, you generally need to allow for 2 weeks. Most research studies and randomized trials last 3 weeks and the superior efficacy of the medication compared with placebo generally begins to be seen within the first week
What are predictors of a good response to medication in the treatment of bipolar disorder?
Clinical features that consistently predict a good response have not been identified.
Some studies show mixed features predict a poorer response, but other studies did not replicate this finding.
If a medication works for a patient but the patient stops the medication and has a relapse, is the medication less likely to be effective?
The few studies that have looked at this question suggest this is not the case.
For bipolar patients who relapse often, what is the treatment recommendation?
Medication combinations for both acute and maintenance treatment
What is the first line medication treatment recommendation for a severe manic episode?
Lithium + antipsychotic
Valproate + antipsychotic
(Better than Lithium or valproate monotherapy, time to response is shorter)
List 5 antipsychotics recommended in the treatment of a severe manic episode.
Aripiprazole (Abilify) Haloperidol (Haldol) or other FGAs Olanzapine (Zyprexa) Quetiapine (Seroquel) Risperidone (Risperdal)
Which antipsychotic is not recommended in treating a severe manic episode?
Ziprasidone (Geodon)
List 6 anticonvulsants NOT recommended for treating mania.
Carbamazepine (Tegretol) Lamotrigine (Lamictal) Gabapenin (Neurontin) Topiramate (Topamax) Tiagabine (Gabatril) Oxcarbamazepine (Trileptal)
How is Lithium or Valproate (Depakote) + which antipsychotic to be used chosen?
No head-to-head trials have compared antipsychotics in combination with lithium or valproate. Thus, the choice between lithium and valproate, and the choice of which antipsychotic is based on other factors, including - past response to medications, side effect profiles, comorbid medical conditions, potential for drug-drug interactions, drug preparation, patient preference, cost
Lithium often used for classic manic euphoria and Depakote for mixed features (dysphoric/irritable); also Depakote is often used for patients with comorbid substance use
What is done for treatment resistant patients with severe manic episodes?
A severe manic episode that does not respond to one medication combination should then be treated with a second medication combination. Generally, Lithium is switched to Valproate, or vice versa.
For patients who do not respond to either, it is suggested to do a trial of a third medication combination but with a different antipsychotic. The choice between Lithium and Valproate is based on clinical judgment of the efficacy and tolerability of the prior two trials.
Define treatment refractory patients with severe manic episodes.
Patients who do not respond to 4-6 medication combinations
What is done for treatment refractory patients with severe manic episodes?
ECT
Lithium or Valproate + Clozapine (Clozaril)
What is the first line medication treatment recommendation for hypomania and mild to moderate manic episodes?
Monotherapy
Reasonable choices include:
Aripirazole (Abilify), Asenapine (Saphris), Cariprazine (Vraylar), Haloperidol (Haldol) Olanzapine (Zyprexa), Paliperidone (Invega), Quetiapine (Seroquel), Risperidone (Risperdal), Ziprasidone (Geodon)
Carbamazepine (Tegretol), Lithium, Valproate (Depakote)
Based on studies that looked at overall efficacy and frequency of treatment discontinuation for any reason, it is reasonable to first start monotherapy treatment with ___ or ___ when treating a hypomanic or mild to moderate mania.
Risperidone; Olanzapine
Other factors in addition to the efficacy and frequency of treatment discontinuation for any reason that may be considered and lead to a recommended medication include…
Patient's past response to medications Past response of patient family members with bipolar disorder to medications Specific symptoms Adverse drug effects Comorbid medical ilnlnesses Concurrent medications (risk of drug-drug interactions) Cost Maintenance therapy consideratoins
Since all patients with bipolar disorder should receive maintenance therapy, long-term implications of treatment from maintenance therapy also needs to be considered. Discuss the considerations of lithium vs. haloperidol.
Lithium - widely studied, efficacious, may reduce risk of suicide attempts
Haloperidol - generally not used for maintenance treatment due to risk of movement disorders and increased risk of bipolar depression
What is done for treatment resistant patients with hypomania or mild to mdoerate mania?
If the patient’s manic episode does not respond to the monotherapy trial within 2 weeks of reaching the target dose or if the patient does not tolerate the medication, then the medication should be tapered and discontinued. A second monotherapy medication trial should be started in conjunction with the tapering and discontinuation of the first medication.
If a patient has not responded to 3-5 monotherapy trials, the next step would be a trial of Lithium + antipsychotic or Valproate + antispsychotic
What is the first line maintenance treatment of bipolar disorder?
Usually the same medication regimen that successfully treated the acute hypomanic or manic episode
What is the second line maintenance treatment of bipolar disorder if the patient is not tolerating the first line? Comment on risk of relapse and efficacy for each medication.
- Lithium - most widely studied, reduces risk of relapse by ~30%, reduces risk of suicide
- Valproate - third line for female patients of childbearing age due to teratogenicity concerns, reduces risk of relapse by ~30%
- Quetiapine - effective in preventing depression recurrences
- Lamotrigine - reduces risk of relapse by ~16% vs. placebo (note - good for maintenance, not good for acute mania)
What is the third line maintenance treatment of bipolar disorder? Comment on each medication.
- Olanzapine (Zyprexa) - efficacy is comparable to second-line medications, but tolerability is poorer due to weight gain and increased risk of causing DM
- Aripiprazole (Abilify) or Risperidone (Risperidal) - available in oral or LAI form; evidence for preventing recurrent mood episodes is less extensive and less consistent compared to second line medications
What other medications can be used for maintenance treatment of bipolar disorder? Which one of these is not recommended for treatment of acute mania?
While supporting evidence is less compelling compared with second or third line medications, other options include:
- Asenapine (Saphris)
- Carbamazepine (Tegretol)
- Oxcarbazepine (Trileptal) - not recommended for treatment of acute mania
- Paliperidone (Invega)
What is the treatment for patients who relapse often?
Medication combinations for acute and maintenance treatment of these relapses
- Lithium or valproate + an antipsychotic (may be quetiapine, risperidone, ziprasidone, olanzapine, aripiprazole)
- ECT
When should ECT be considered in patients with bipolar disorder?
Patients who responded to ECT for acute mood episodes or who failed many (5+) other maintenance medication regimens
What medications are to be avoided in maintenance treatment of bipolar disorder?
Antidepressants (concerns for destabilization)
Benzodiazepines (may be associated with increased risk of recurrence)
How long do patients with bipolar disorder need maintenance treatment?
Patients may require maintenance for many years, some for their entire lives. The more severe course of illness, the longer the maintenance treatment.
What factors should be considered when determining the length of maintenance treatment?
Number of years patient has had bipolar disorder
Lifetime number of mood episodes and hospitalizations; length of time to stabilize the patient; how many years since last mood episode
Lifetime number of suicide attempts
List 6 challenges of treating bipolar disorder.
- Complex clinical picture (often comorbidities)
- Need for phase relevant treatment strategy
- Lack of treatment adherence
- Chronic episode course
- Disability
- Mortality risk (suicide, accidents, medical illness)
DSM-5 Diagnostic Criteria for Bipolar I Disorder?
A/B - criteria currently or previously met for a manic or mixed episode
C - sufficiently severe to cause marked impairment in functioning or to necessitate hospitalization, or if there are psychotic features
D - not due to physiological effects of a substance or medical condition
Not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified/unspecified schizophrenia spectrum/psychotic disorders
True or false - a depressive episode is required for the diagnosis of bipolar disorder.
False - A depressive episode is NOT required for the diagnosis of bipolar disorder.
DSM-5 Diagnostic Criteria of a manic episode?
- Abnormal mood that is persistently elevated (classic - euphoric), expansive (unceasing interest in just about anything), or irritable
- 3+ symptoms (or 4+ if mood is irritable)
- For 1 week (meet criteria in less time if patient is hospitalized)
DSM-5 Diagnostic Criteria - symptoms of a manic episode?
Distractibility
Insomnia (decreased need for sleep)
Grandiosity (increased self-esteem)
Flight of ideas (or racing thoughts)
Activities/Agitation (increased goal-directed activity or psychomotor agitation)
Speech (pressured or increased quantity)
Thoughtlessness (poor judgment, pleasure seeking)
DSM-5 Diagnostic Criteria of a hypomanic episode?
Same as mania - 3+ symptoms for 4+ days, not as severe as mania (not severe enough to cause marked impairment in functioning or to necessitate hospitalization), but change is notable by others who know the patient
Mania is to ___ as Hypomania is to ___.
Major Depression; Depressive Episode
DSM-5 Diagnostic Criteria of Bipolar II Disorder?
-Current or history of major depressive episode + current or history of hypomanic episode + no history of manic or mixed episode
DSM-5 Diagnostic Criteria of Cyclothymia?
2+ years of mood symptoms (hypomanic and depressive) that do not meet criteria for a major depressive episode
- Have not been without the symptoms for more than 2 months at a time
- No mania, major depressive, or mixed episodes
DSM-5 Diagnostic Criteria of a Mixed Episode?
- Person simultaneously meets manic criteria with some MDD symptoms OR MDD with some manic symptoms
- For at least 1 week (the same week)
- Any part of the Bipolar spectrum can have mixed features
Define rapid cycling.
At least 4 episodes/year of MDD, mania, or hypomania
Rapid cycling is more common in which gender?
F>M
What medical abnormality may be seen in rapid cycling?
Thyroid abnormality
What % of patients with Bipolar I have rapid cycling?
5-15%`
List 9 clinical clues of manic behavior.
- High number of marriages
- Wearing clothes/jewelry of bright colors in outlandish combinations
- Disrobing in public places
- Sudden trips, vacations, cross country travel
- Many career changes
- Business successes and failures
- Idea preoccupation n(religious, financial, sexual, persecutory)
- Pathologic gambling
- Drastic changes in lifestyle, religious beliefs over a lifetime
DDx for Bipolar Disorder?
- Bipolar I (manic +/- MDD episodes)
- Bipolar II (hypoman8ic + MDD episodes)
- Cyclothymia (hypomania + dysthymia, NO mania or MDD)
- Bipolar NOS (doesn’t fit anything else)
- General Medical Condition
- Substance-Induced
- ADHD
- Borderline Personality Disorder
- Psychotic Disorder (schizoaffective disorder, schizophrenia, delusional disorder)
When would Bipolar Disorder NOS be considered?
- Rapid switches mania to depression, but does not meet the time criteria
- Recurrent hypomania, but no MDD
- Hypomania + depression symptoms very far apart (does not meet cyclothymia time criteria)
- Etiology unclear (primary vs. medical vs. substance)
What must be ruled out to diagnose bipolar disorder?
General Medical Condition
Substance-Induced
Psychotic Disorder
69% of people with Bipolar Disorder are diagnosed incorrectly initially - what is the most common misdiagnosis?
MDD
What is the diagnostic lag for Bipolar Disorder?
3-10 years (35% lag of >10 years)
General Medical Conditions that can present like Bipolar Disorder?
- Neurological (epilepsy, HIV, neurosyphilis, Huntington’s disease, migraines, MS, brain tumor, TBI - R-hemisphere lesion, Wilson’s disease)
- Endocrine (Cushing’s, Addison’s, postpartum, hyper/hypothyroid)
- Other - AIDS, SLE, uremia, vitamin deficiencies (B12, C, folate, niacin, thiamine)
Substances that can induced bipolar disorder?
Antidepressants Amphetamines/stimulants Baclofen Bromocriptine Captopril Cocaine Corticosteroids Cyclosporine Disulfiram Hallucinogens Hydralazine Interferon Isoniazid Levodopa Opiates
Which antidepressant has the highest risk of inducing bipolar disorder?
TCAs
Compare ADHD and Bipolar Disorder
ADHD - inattention, hyperactivity, impulsivity
Bipolar - distractibility, increased goal directed activity/psychomotor agitation, dangerous pleasurable activities (impulsivity)
Compare Borderline Personality Disorder and Bipolar Disorder.
Borderline: affective instability due to marked mood reactivity, impulsivity, recurrent suicidal behavior, unstable and intense relationships
Bipolar: increased self-esteem/grandiosity, dangerous pleasurable activities, may have suicidal behavior, may have unstable and intense relationships
Work-up for mania? (History)
Detailed medical/neuro history Medicatoins Substance use (past and current) Past psychiatric history (mania, hypomania, MDD, psychosis) Family history
Work-up for mania? (Labs)
CMP (w/LFTs) UDS TSH CBC B12 RPR/VDRL HIV
Peak age of onset of bipolar disorder? Mean age of onset of bipolar disorder?
Peak: 15-19 years
Mean: 19-21 years
(If >60 years, medical illness is first consideration)
Bipolar Disorder - gender prevalence?
Bipolar I: M=F
Bipolar II: F>M
Bipolar Disorder - marital status?
Single, div`orced > married
Prevalence of Bipolar I disorder?
~1% (0.8-1.6%)
Prevalence of Bipolar II disorder?
0.5-5.5%
Prevalence of Cyclothymia?
0.4-1%
Prevalence of Bipolar Spectrum?
2.6-6.5%
Risk of Bipolar I Disorder if a first degree relative has the diagnosis?
15%
8-18x more likely to have Bipolar Disorder
2-10x more likely to have MDD
Concordance rates of Bipolar Disorder?
Di - 20%
Mono - 70%
Risk of Bipolar Disorder if family history on maternal vs. paternal side?
2x risk if + history on maternal side vs. paternal side
Maternal - 27.3% affected, Paternal - 14% affected
Bipolar disorder and schizophrenia share many genes (also depression, autism, ADHD). These genes are often involved in what process?
Calcium channel signaling
First episode of bipolar disorder - male vs. female?
Male - mania more likely
Female - depression more likely
What is the relapse risk after a first episode of bipolar disorder?
If the first episode is mania, 85-90% risk of a second episode (mania or depression).
if the first episode is depression, 50% risk of second episode (depression).
On average, a manic episode lasts ___ months, with 1 episode every ___ years. Without medication prophylaxis, the lifetime average is ___ episodes.
1.5-4 months
2 years
9-10 episodes
Discuss episode duration over time in bipolar disorder.
Increases over time
33% patients continuously ill for 2-4 years
10% continuously ill for up to 7 years
Bipolar patient suicide risk?
25-50% attempt
20% complete
When is suicide risk increased for patients with bipolar disorder?
Mixed episodes and depressive episodes
Why does the inter-episode interval between active episodes decrease over time?
Kindling theory - consequence of repeated sub-threshold stimuli that progressively lead to more episodes
Subsequent application of a single sub-threshold stimuli will evoke an episode
What is the bipolar drug of choice?
Lithium - should be used unless there is a specific reason not to or a specific reason to use another drug
Who is the ideal candidate for lithium?
Euphoric, + family history, no substance use, no rapid cycling, few episodes
What is the short-term acute response rate to Lithium?
70-80% based on double blind studies
Helps significantly in 2-4 weeks
Therapeutic trial should last at least 4-6 weeks
1/3 will be completely symptom free and most will have a great decrease in illness frequency or symptom severity
If lithium is effective for acute mania, it should be continued as maintenance treatment - how long?
At least 9-24 months
If 1 manic episode, can consider d/c
If 2 manic episodes, always maintenance treatment
Felt to decrease the number of recurrent affective episodes by at least 50% and the recurrences that do occur are less severe
Advantages to Depakote?
1/3 will be completely symptom free
Most will have a great decrease in illness frequency or symptom severity
Can rapidly load - responders show the most improvement in the first 3 days
Why are SGAs generally preferred over FGAs in treating bipolar disorder?
Decreased EPS side effects and Tardive Dyskinesia
Almost all are effective
Depression generally does not worsen (unlike FGAs)
Some are specifically approved for bipolar disorder
List 10 possible triggers for an affective switch in patients with bipolar disorder.
- Sleep loss
- Alcohol/substance use
- Rapidly stopping Lithium
- Antidepressant use or discontinuation
- Seasonality
- East-west travel
- Conflict/trauma
- Loss of support systems
- Grief
- Success
