Lithium, sodium valproate or carbamazepine for acute mania in adults and young people

See Overview of pharmacotherapy for acute mania in adults and young people for the role of lithium, sodium valproate and carbamazepine in the maintenance treatment of mania and use in specific populations (eg young people, females of childbearing potential, pregnant people, males of reproductive potential).

Lithium is the most effective drug for preventing relapse of mania. Sodium valproate and carbamazepine are not as effective as lithium as maintenance treatments—carbamazepine has less data than sodium valproate and is associated with significant adverse effects.

Consult a drug information source for advice on contraindications, precautions, adverse effects, dosage adjustments, clinical monitoring requirements before and during therapy, and therapeutic drug monitoring¹ ².

For maintenance treatment of mania, use one of the following drugs, concurrently with an antipsychotic for acute mania. Use:

1 lithium carbonate immediate-release 500 to 1000 mg orally, daily, in 2 or 3 divided doses or as a single dose at night—divided doses may improve tolerability whereas once-daily dosing may improve adherence. After 5 to 7 days of treatment, determine lithium blood concentration. Target a concentration of 0.8 to 1.2 mmol/L, depending on clinical response and tolerability; adjust daily dose in increments of 250 to 500 mg. A daily dose of 1000 to 2500 mg is usually required, except in people 60 years or older, who require a third to half of this dose because of poorer tolerability. After acute mania has resolved, target a concentration of 0.6 to 0.8 mmol/L. Continue for at least 6 to 12 months to prevent relapse, then assess if prophylaxis is required¹ ² ³ ⁴ bipolar disorder, acute mania lithium lithium lithium

OR

1 lithium carbonate modified-release 450 to 900 mg orally, daily, in 2 divided doses or as a single dose at night—divided doses may improve tolerability whereas once-daily dosing may improve adherence. After 5 to 7 days of treatment, determine lithium blood concentration. Target a concentration of 0.8 to 1.2 mmol/L, depending on clinical response and tolerability; adjust daily dose in increments of 225 to 450 mg. A daily dose of 900 to 2250 mg is usually required, except in people 60 years or older, who require a third to half of this dose because of poorer tolerability. After acute mania has resolved, target a concentration of 0.6 to 0.8 mmol/L. Continue for at least 6 to 12 months to prevent relapse, then assess if prophylaxis is required¹ ² ³ ⁴lithium lithium lithium

OR

2 sodium valproate 200 to 400 mg orally, twice daily. Increase the daily dose by 200 to 500 mg every 2 to 3 days. After 3 days of treatment, determine sodium valproate blood concentration. Target a concentration between 660 and 875 micromol/L (94 and 125 mg/L), depending on clinical response and tolerability. A daily dose of 1000 to 2000 mg is usually required; maximum daily dose 3000 mg. Continue for at least 6 to 12 months to prevent relapse, then assess if prophylaxis is required¹ ² bipolar disorder, acute mania sodium valproate sodium valproate sodium valproate

OR

2 sodium valproate (loading dose regimen for inpatient treatment) 20 mg/kg orally, daily. After 3 days of treatment, determine sodium valproate blood concentration. Target a concentration between 660 and 875 micromol/L (94 and 125 mg/L), depending on clinical response and tolerability. A daily dose of 1000 to 2000 mg is usually required; maximum daily dose 3000 mg. Continue for at least 6 to 12 months to prevent relapse, then assess if prophylaxis is required¹ ² sodium valproate sodium valproate sodium valproate

OR

3 carbamazepine immediate-release 100 to 200 mg orally, twice daily. Increase the daily dose by 100 to 200 mg every 2 to 3 days. After 5 to 7 days of treatment at a daily dose of 400 mg or more, determine carbamazepine blood concentration. Titrate to response and tolerability, within the range of 20 to 50 micromol/L (5 to 12 mg/L). Maximum daily dose 1600 mg. Continue for at least 6 to 12 months to prevent relapse, then assess if prophylaxis is required¹ ² bipolar disorder, acute mania carbamazepine carbamazepine carbamazepine

If there is no response to treatment within a few weeks, see Nonresponse to treatment for acute mania.

If there is an acceptable response, continue treatment for at least 6 to 12 months to prevent relapse, then assess if prophylaxis of bipolar disorder is required.

¹ A list of Australian laboratory test databases is available at the Australasian Association for Clinical Biochemistry and Laboratory Medicine (AACB) ‘Testing for health’ website.Return

² For information on therapeutic reference ranges of psychotropics, see Hiemke C, Bergemann N, Clement HW, Conca A, Deckert J, Domschke K, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry 2018;51(1-02):9-62. [URL]Return

³ Measure lithium blood concentration 8 to 12 hours after the last dose.Return

⁴ Seek advice from a renal physician if the patient has kidney impairment; dose reduction and more frequent measurement of lithium concentrations are required.Return