Bipolar Disorders in Primary Care
The vital role of primary care physicians in managing bipolar disorders. Learn about diagnostic criteria, treatment strategies, and the need for early intervention. Discover clinical practice recommendations and advantages of primary care management for individuals with bipolar disorders.
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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 co- occurring 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) MDEs similar in character Seasonal pattern less likely No bipolar history Index mood episode can be postpartum Family history of bipolar disorder
DDx Secondary mania8 Substance induced Intoxication or use: alcohol, LSD, amphetamines/sympathomimetics, benzodiazepines, corticosteroids, isoniazid, levodopa, thyroxine, zidovudine Withdrawal: alcohol, benzodiazepines, -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 Intoxication or use: opiates, benzodiazepines, anticonvulsants, alcohol, reserpine Withdrawal: cocaine, amphetamines/sympathomimetics Secondary depression8 Substance induced 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, Beh et'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 na ve 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. 12 All cause mortality, die 8-9 years earlier. 13
Medical burden BPAD patients with high medical burden have: Greater number of lifetime mood episodes 12 A higher number of prescribed psychotropics 13 Longer duration of untreated illness 14 Longer psychiatric IP stays 15
First-Line Agents for Acute Manic or Mixed Episodes a Class Agent Target Dose Notable Adverse Effects Notes Lithium b Sufficient for blood level of 0.6 1.2 mEq/L, usual dose 900 1,800 mg Titrate rapidly to a blood level of 85 125 g/mL; up to 60 mg/kg Sedation, dry mouth, polyuria; more rarely kidney or thyroid failure Sedation, nausea, weight gain; may cause menstrual irregularities; rare pancreatitis or liver failure May be slower to control mania than other options Mood stabilizers Divalproex 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 Second-generation antipsychotics 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 EPS, sedation or agitation Weight gain; lipid and glucose derangements Taken with meals to improve absorption; contraindicated if history of prolonged QTc interval or in combination with QTc-prolonging medications Ziprasidone 40 80 bid a Based on Suppes, et al. 16 b Not 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 Agent Target Dose Notable Adverse Effects Sedation, weight gain, less commonly EPS Sedation, weight gain, less commonly EPS Stevens-Johnson syndrome, especially with enzyme-inhibiting medications (eg, divalproex) Sedation, dry mouth, polyuria; more rarely kidney or thyroid failure Sedation, nausea, weight gain; may cause menstrual irregularities; rare pancreatitis or liver failure Those of constituent agents Notes Quetiapine 300 600 mg/d Titrate immediate- release form over 6 days First-line treatments Olanzapine/fluoxetine combination Lamotrigine Olanzapine 6 12 mg/fluoxetine 25 50 mg 200 mg/d Titrate to target dosage based on schedule May be used as monotherapy for BPAD II Lithium Sufficient for blood level of 0.6 1.2 mEq/L; usual dose 900 1,800 mg Titrate rapidly to a blood level of 85 125 g /mL; up to 60 mg/kg Second-line treatments Divalproex 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 Combinations: SSRI or bupropion with SGA, lithium, or divalproex Antidepressants should be used only with an effective antimanic agent when treating bipolar depression a Based on Suppes, et al. 16
G.H. Vzquez et al. / Journal of Affective Disorders 183 (2015) 258262
Long-term monitoring parameters for BPAD a Patient Is Maintained On: Check Monitor For: Serum level: once therapeutic level is achieved, every 3 6 mo Subtherapeutic or toxic level Lithium 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 Divalproex 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 Carbamazepine 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 Monitor for rash Stevens-Johnson Syndrome Monitor for rash Stevens-Johnson Syndrome Lamotrigine Weight monthly for 3 mo and then every 3 mo Weight gain Second-generation antipsychotics 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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