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Mania - Initiating Pharmacotherapy and Providing Management

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Text below adapted from The patient who has mania in Psychiatry in primary care by Roger S McIntyre,  (CAMH, 2019).

Adjunctive treatment generally is recommended for patients who do not sufficiently respond to antimanic monotherapy after one to two weeks. If the patient stabilizes on combination therapy (e.g., divalproex and an atypical antipsychotic) and tolerates the treatment, the combination regimen should continue for one to two years. If tolerability concerns (e.g., weight gain, menstrual irregularities) make a patient hesitant to accept either treatment, consider engaging a psychiatric consultation as treatment moves into the continuation/maintenance phase.

Most primary care practitioners initiate treatment for bipolar disorder while the patient is actively depressed. The evidence presented in Table 2 is  an important guide to selecting and sequencing treatment. Antidepressant monotherapy is generally discouraged because it can destabilize bipolar disorder. First-line medications for bipolar depression are lithium, lamotrigine or an atypical antipsychotic, such as quetiapine. Adding an antidepressant to these first-line medications is suggested for severe depression.

Related

  • Psychiatry in Primary Care: A Concise Canadian Pocket Guide 2019

    Read More

  • Bipolar Disorder: Health Information for your Patient

    Read More

  • Bipolar Disorder: An Information Guide

    Read More

Table 2 Recommended medications and dosing for bipolar disorder

Antiepileptic

Medication Dosing Laboratory Measures

Common Side-effectsa / Other Notes



Divalproex



Initiation: 500–1000 mg

qhs; dosing based on 12 hrs trough plasma level (350–700 mmol/L) 



Pre-treatment: CBC, electrolytes, TSH, liver function. Ensure contraceptive use (teratology risk); menstrual history required (associated with polycystic ovarian syndrome); repeat blood work including VPA level q6 months

if stable 



Sedation, somnolence, weight gain, menstrual irregularities, alopecia, tremor



Lithium



Initiation: 600–900 mg qhs; dosing based on 12 hrs trough plasma levels (0.8–1.2 meq/L,

acute mania; 0.6–0.8 meq/L, maintenance/ depression



Pre-treatment: CBC; electrolytes (including Ca++), TSH, BUN, creatinine (EKG > age 40 or heart disease/ risk factors) 

Maintenance: lithium level – CBC; electrolytes (including Ca++), TSH, BUN, creatinine. Q6 months if stable; more often if symptomatic



Sedation, cognitive dulling, weight gain, dermatological reactions

(acne, eczema), polyurea, polydipsia, tremor



Carbamazepine



Initiation: 600–900 mg;

titrate as tolerated, 600–1200 mg



Pre-treatment: same as divalproex; not associated with polycystic ovary syndrome/td>



Sedation, somnolence, slurred speech, confusion, tremor



Oxcarbazepine



Initiation: 150–300 mg;

maintenance: 300–1500 mg



Same as carbamazepine



Same as carbamazepine



Novel Antipsychotic

   

Laboratory Measures



Common Side-effectsa / Other Notes



Olanzapine



Initiation: 10–15 mg;

maintenance: 5–20 mg. Higher dosing in mania



Pre-treatment: weight, BMI, fasting blood glucose, lipid fractionation, LFT, CBC, electrolytes. Repeat q6 months. Repeat metabolic parameters more often in patients gaining weight



Extrapyramidal symptoms, weight gain, dysglycemia, metabolic syndrome, sedation, somnolence, transient LFT elevation



Cariprazin



For mania, start at 1.5 mg on day 1; 3 mg on day 2; titrate 3 mg for mania mixed; for bipolar depression, start at 1.5 mg. efficacious dose 1.5–3 mg



EPS gastro- intestinal (e.g., nausea)



Risperidone



Initiation: 1–2 mg, with target of

3–6 mg per day



Same as olanzapine



Same as olanzapine. LFT elevation

not typically seen; prolactin elevation/prolactin- related side- effects



Quetiapine



Initiation: 300–600 mg

for acute mania; 150–300 mg for acute depression

Maintenance: usually 150–450 mg.  Titrate as tolerated (achieve recommended dose in 1–2 weeks)

Quetiapine XR: initiate 200 mg; increase to 300–600 mg in 2 days



Same as olanzapine



Same as olanzapine. LFT elevation not typically seen



Ziprasidone



Initiation: 60–120 mg;

maintenance: 60–160 mg.

Titrate as tolerated



Same as olanzapine, EKG


 



EPS, tremor, agitation, greater propensity to prolong QT interval, akathisia, restlessness, minimal weight gain or metabolic disruption



Asenapine



Initiation: 10 mg. Flexibly dose 10–20 mg



BMI, weight, circumference, metabolics, CBC



Oral hypoaesthesia, taste disturbance, EPS, minimal weight gain or metabolic disruption

Do not eat or drink for at least 10 minutes after administration



Lurasidone



Dosing as monotherapy or combination with lithium/divalproex



Same as asenapine



EPS, somnolence, metabolically neutral, low weight- gain liability

Only drug approved as monotherapy and adjunctive

therapy for bipolar depression

Must take with food, minimum 350 calories



Aripiprazole



Initiation: 2.5–20 mg for acute; maintenance: 2.5–30 mg. Titrate as tolerated



Same as olanzapine



Same as ziprasidone



Novel Antidepressant


Medication



Dosing



Laboratory Measures



Common Side-effectsa / Other Notes



SSRI, SNRI, NaSSA



See Table 1



Mobilization of hypo/mania and rapid cycling


(a) No bipolar disorder treatment is established as safe in pregnancy. Each drug has terato-genetic effects. Neural tube defects are associated with divalproex and carbamazepine. Oral cleft defect may be associated with lamotrigine. Contraception is recommended for women on any bipolar disorder treatment.

Consider electroconvulsive therapy for patients who do not respond adequately to pharmacotherapy while they are depressed, who present with severe symptomatology (e.g., psychotic symptoms) or who experience functional impairments..

A first-line mood stabilizer is often used to treat depressive symptoms in patients ambiguously presenting with major depression or bipolar II disorder. Opportunistic screening for clinical presentations that suggest hypomania is warranted during long-term treatment. With the exception  of lamotrigine, pharmacological treatments for bipolar disorder are more effective at forestalling or reducing the risk of recurring hypomania/mania than depression. This explains why pernicious subsyndromal (dysthymic/ dysphoric) symptoms are a common clinical presentation even when patients adhere to treatment.

Figure 1 Treatment algorithm for acute mania
Treatment Algorithm for Acute Mania
Please note: this treatment algorithm was developed for psychiatrists treating bipolar mania, and its later steps are beyond the clinical practice of most primary care practitioners.

 

Treatment Algorithm for Acute Mania

In Mania

  • The Primary Care Practitioner Role
  • Screening & Assessment
  • Diagnosis
  • Treatment
    • Pharmacotherapy
      • Initiating Pharmacotherapy and Providing Management
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Pharmacotherapy
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