Download as presented by Emiliano Valles, MD

BIPOLAR DISORDERS
IN PRIMARY CARE
Kimothi Cain, MD, MPH
UNM Department of Psychiatry
as presented by Emiliano Valles, MD
Objectives
1. Discuss and promote the role of the primary care physician
in bipolar disorders
2. Criteria for bipolar illnesses
3. Review treatment strategies for bipolar disorders with a
focus on the primary care setting
BIPOLAR DISORDERS IN PRIMARY CARE
• Need for treatment at the primary care level
• Common disorder with prevalence of 3.4 – 9%
1
• Half of all mentally ill patients are treated at the primary
care level 2
• Shortage of psychiatrists:
• Long waiting periods for an initial consultation
• Community mental health centers are disappearing
NICE Clinical practice recommendations*
Assessment in primary care 2
4.4.2.1.
Primary care clinicians should ask about hypomanic symptoms when assessing a patient with depression and
overactive, disinhibited behavior.
4.4.2.3.
PCPs should urgently refer patients with mania or severe depression who are a danger to themselves or other
people, to [emergency services].
4.4.2.4.
When a patient with existing bipolar disorder registers with a practice, the [PCP] should consider referring them
for assessment by specialist mental health services and, if appropriate, development of a care plan.
4.4.2.5.
When a patient with bipolar disorder is managed solely in primary care, an urgent referral to/or consultation with
psychiatry or emergency services should be made:
•if there is an acute exacerbation, in particular the development of mania or severe depression
•if there is an increase in the degree of risk, or change in the nature of risk, to self or others.
4.4.2.6.
When a patient with bipolar disorder is managed solely in primary care, a review by psychiatry or increased
contact with primary care should be considered if:
•Significant decline in the patient’s or their condition responds poorly to treatment
•treatment adherence is a problem
*NICE: National Institute for Health and Care Excellence
ADVANTAGES OF PRIMARY CARE MGMT
• Earlier initiation of treatment
• Continuity of care
• Established therapeutic alliance
• Management of co-occurring medical diseases
BIPOLAR DISORDERS
Spectrum of disorders:
• 1. bipolar I-- requires a manic episode
• 2. bipolar II-- requires a hypomanic episode + major
depressive episode
• 3. cyclothymic disorder-- 2 years of subsyndromal mood
cycling (i.e., dysthymia and hypomania, instead).
• 4. bipolar not otherwise specified (NOS)
Making the Diagnosis
1. DSM categorical diagnosis (with screening
instruments)
2. Additional (non-DSM) features of the disorder
• Exam findings, course of illness
• Probabilistic approach (BP vs. MDD)
3. Collateral information
Screening
Mood Disorder Questionnaire (MDQ)
• 13 questions based off of DSM criteria
• Fairly sensitive
• Takes about 5 minutes
• Screen every patient with depression
• Self report version:
http://www.dbsalliance.org/pdfs/MDQ.pdf
Diagnosing Mania
Mania: 3
• Criteria A: One week of elevated, expansive, irritable
mood AND increased energy ...
• Plus 3 of the following from B Criteria:
• Distractibility
• Indiscretion or Irresponsibility
• Grandiosity
• Flight of ideas
• Activity (increased goal-directed activity)
• Sleep (decreased need for sleep)
• Talkativeness pressured speech) 4
Diagnosing Hypomania
Hypomania: 3
• Same criteria as mania ...but does NOT cause significant
functional impairment
• Shorter time requirement (4 days)
• Absence of psychosis
Frequency of Symptoms in BPAD I 4
0
Mixed
12%
(Hypo)mania
20%
Depression
68%
Depression
(Hypo)mania)
Mixed
The Complex Bipolar Patient
• Mixed episodes 3
• Both manic and depressive symptoms
•  comorbid substance use disorders
•  risk of suicide and psychosis
• Rapid cycling 3
• 4 or more cycles/year with > 8 weeks of well periods
• Occurs in Bipolar I and II
Challenges in Diagnosis
• Diagnosis is challenging with high rates of
misdiagnosis
7 of 10 pts initially misdiagnosed 5
1 in 3 wait ten years before correct diagnosis
5,6
• (Dx is longitudinal, however, majority of the misdiagnosis attributable
to lack of understanding about the disorder.) 7
Misdiagnosis Rates
• MDD (60% )
• Anxiety Disorders (26%)
• Schizophrenia (18%)
• Personality disorder (BPD, ASP) (17%)
• Substance use disorders (14%)
6,7
Also: Anxiety disorders, PDs, and SUDs frequently cooccurring with BPAD
Diagnosis: MDD VS. BPAD
BPAD
MDD
• Early onset depression < 25 years
• Later onset depression > 25 years
• Multiple depressive episodes (> 5)
• Fewer episodes
• 90% have recurrent MDEs
• 50% have recurrent MDEs
• MDEs vary in character (e.g. some
episodes melancholic, some atypical)
• Seasonality (depressed late fall/
winter; manic spring)
• Index mood episode can be
postpartum
• Family history of bipolar disorder
• MDEs similar in character
• Seasonal pattern less likely
• No bipolar history
DDx
Secondary mania
8
Secondary depression
8
Substance induced
Intoxication or use: alcohol, LSD,
amphetamines/sympathomimetics, benzodiazepines,
corticosteroids, isoniazid, levodopa, thyroxine,
zidovudine
Withdrawal: alcohol, benzodiazepines, β-blockers
Metabolic
Hemodialysis, postoperative state, thyrotoxicosis,
B12 deficiency, Cushing's syndrome
Infectious
Influenza, encephalitis, HIV, neurosyphilis
Neurologic
Neoplasm, complex partial seizure, Wilson's disease,
Huntington's disease, multiple sclerosis, stroke
Substance induced
Intoxication or use: opiates, benzodiazepines,
anticonvulsants, alcohol, reserpine
Withdrawal: cocaine,
amphetamines/sympathomimetics
Metabolic
Uremia, niacin deficiency (pellagra), B12 deficiency,
anemia, hypothyroidism, Cushing's syndrome,
Addison's disease, sleep apnea, heavy metal toxicity,
paraneoplastic syndromes
Infectious
Lyme disease, neurosyphilis, HIV, Behçet's syndrome,
meningitis
Neurologic/
cerebrovascular
Ischemia, stroke (especially left-sided), neoplasm,
complex partial seizures, postictal state, normal
pressure hydrocephalus, Parkinson's disease
Medical Comorbidities
• Pts with BPAD -- significantly higher rates of metabolic
syndrome than the general population…37% according to a
meta-analysis of 7000 pts. 9
• Multifactorial cause:
• Some attributable to certain SGAs, but CV risk factors present before
the widespread use of SGAs and in treatment naïve pts.10, 11
• Lifestyle: overeating, smoking, ETOH, inactivity
• Possible genetic vulnerability independent of environmental/behavioral
factors. 10
• BP -- patients have 1.5 - 2.5x higher CVD mortality risk.
• All cause mortality, die 8-9 years earlier.
13
12
Medical burden
BPAD patients with high medical burden have:
 Greater number of lifetime mood episodes
12
 A higher number of prescribed psychotropics
 Longer duration of untreated illness
 Longer psychiatric IP stays
15
14
13
First-Line Agents for Acute Manic or Mixed Episodes a
Class
Agent
Target Dose
Notable Adverse Effects
Notes
Mood stabilizers
Lithium b
Sufficient for blood level of
0.6–1.2 mEq/L, usual dose
900–1,800 mg
Sedation, dry mouth, polyuria;
more rarely kidney or thyroid
failure
May be slower to control
mania than other options
Divalproex
Titrate rapidly to a blood level
of 85–125 μg/mL; up to 60
mg/kg
Sedation, nausea, weight
gain; may cause menstrual
irregularities; rare pancreatitis
or liver failure
Very high risk of neural tube
defects with fetal exposure;
caution in women of
childbearing age
Aripiprazole
15–30 mg/d
Akathisia and other EPS,
sedation
Among the least likely
second-generation
antipsychotics to cause
weight gain
Olanzapine c
15–20 mg/d
Sedation, weight gain, less
commonly EPS
Weight gain; lipid and glucose
derangements may be
particularly severe
Quetiapine b
400–800 mg/d
Sedation, weight gain, less
commonly EPS
Titrate immediate-release
form over 6 days. Weight
gain; lipid and glucose
derangements
Risperidone
3–6 mg/d
EPS, sedation,
hyperprolactinemia
Weight gain; lipid and glucose
derangements
Ziprasidone
40–80 bid
EPS, sedation or agitation
Taken with meals to improve
absorption; contraindicated if
history of prolonged QTc
interval or in combination with
QTc-prolonging medications
Second-generation
antipsychotics
a Based
b Not
on Suppes, et al. 16
recommended as first-line for mixed episodes.
C Olanzapine
is not generally recommended as first-line due to metabolic adverse effects.
Abbreviation: EPS = extrapyramidal symptoms.
Medications for acute bipolar depression a
First-line treatments
Agent
Target Dose
Notable Adverse
Effects
Notes
Quetiapine
300–600 mg/d
Sedation, weight gain,
less commonly EPS
Titrate immediaterelease form over 6 days
Olanzapine/fluoxetine
combination
Olanzapine 6–12
mg/fluoxetine 25–50 mg
Sedation, weight gain,
less commonly EPS
Lamotrigine
200 mg/d
Stevens-Johnson
syndrome, especially
with enzyme-inhibiting
medications (eg,
divalproex)
Second-line treatments Lithium
a
Based on Suppes, et al. 16
Sufficient for blood level
of 0.6–1.2 mEq/L; usual
dose 900–1,800 mg
Sedation, dry mouth,
polyuria; more rarely
kidney or thyroid failure
Divalproex
Titrate rapidly to a blood
level of 85–125 μg /mL;
up to 60 mg/kg
Sedation, nausea,
weight gain; may cause
menstrual irregularities;
rare pancreatitis or liver
failure
Combinations: SSRI or
bupropion with SGA,
lithium, or divalproex
Antidepressants should
Those of constituent
be used only with an
agents
effective antimanic agent
when treating bipolar
depression
Titrate to target dosage
based on schedule
May be used as
monotherapy for BPAD II
Very high risk of neural
tube defects with fetal
exposure; caution in
women of childbearing
age
While these
combinations are a
common practice,
evidence of their efficacy
is controversial
G.H. Vázquez et al. / Journal of Affective Disorders 183 (2015) 258–262
Long-term monitoring parameters for BPAD a
Patient Is Maintained On:
Check
Monitor For:
Lithium
Serum level: once therapeutic level is achieved,
every 3–6 mo
Subtherapeutic or toxic level
EUC: every 3–6 mo
Renal insufficiency, nephrogenic diabetes insipidus
Calcium, TSH, weight: after 6 mo and then annually
Thyroid/parathyroid dysfunction
Serum level: during initial therapy and then as
clinically indicated
Subtherapeutic or toxic level
Weight, complete blood count, menstrual history,
liver function tests every 3 mo for the first year and
then annually
Weight gain, thrombocytopenia, dysmenorrhea, liver
failure
Blood pressure, fasting blood glucose, lipid profile,
bone densitometry (if risk factors)
Metabolic syndrome, anticonvulsant-related
osteopenia
Serum level: during initial therapy and then as
clinically indicated
Subtherapeutic or toxic level
Complete blood count, liver function tests, EUC
monthly for 3 mo then annually
Blood dyscrasias, liver failure, hyponatremia
Bone densitometry and evaluation of oral
contraceptive efficacy when applicable
Anticonvulsant-related osteopenia, increased
metabolism of oral contraceptives
Divalproex
Carbamazepine
Monitor for rash
Stevens-Johnson Syndrome
Lamotrigine
Monitor for rash
Stevens-Johnson Syndrome
Second-generation antipsychotics
Weight monthly for 3 mo and then every 3 mo
Weight gain
Blood pressure, fasting blood glucose, lipid profile
every 3 mo and then annually
Metabolic syndrome
Monitor for abnormal movements
Acute dystonias, drug-induced parkinsonism, tardive
dyskinesia
Electrocardiogram, prolactin as clinically indicated
QTc prolongation/dysrhythmias, hyperprolactinemia
aBased
on Ng et al.17
Abbreviations: EUC = electrolytes, urea, creatinine; TSH = thyroid-stimulating hormone.
Maintenance
• Primary goal: Maintenance of euthymia and is best achieved through the use of
long-term medication.
• Lithium as first-line treatment: Prevents both manic and depressive relapse, as
well as suicide in meta-analytic reviews of randomized controlled trials.18,19
• Divalproex has somewhat less evidence than lithium, but may also be considered
a first-line treatment. Caution with women of childbearing years: Ebstein anomaly
and PCOS. 20
• Lamotrigine: efficacy in preventing depressive relapse and may be a good option
for more depression-prone patients. 21
• SGAs: have demonstrated efficacy in preventing relapse among acute
responders. 21
• Long acting injectables: prevent relapse based on randomized trials. For many
patients, maintenance therapy will be the medication to which they responded
acutely.
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