Antipsychotics for acute mania in adults and young people

See Overview of pharmacotherapy for acute mania in adults and young people for the role of antipsychotics in the treatment of mania, as well as advice on assessing efficacy and tolerability and use in specific populations (eg pregnant people, young people).

For patients with sufficient insight and awareness, discuss the following with them and, if they consent, their family, carers or significant others:

  • the purpose of antipsychotic therapy and its place in multimodal treatment
  • which antipsychotic adverse effects are acceptable to the patient and how these effects are monitored, prevented and addressed
  • the importance of treatment adherence; poor adherence is a cause of relapse.
Note: Antipsychotic choice must balance efficacy and tolerability.
Antipsychotic choice must balance efficacy and tolerability (consider both short- and long-term adverse effects). For drugs with similar efficacy, choice should be guided by the adverse effect profile and whether these are acceptable to the patient. If a long-acting injectable antipsychotic is preferred for maintenance therapy, consider using the oral form of a long-acting injectable antipsychotic for acute mania (see Long-acting injectable antipsychotics for maintenance therapy after acute mania). Also consider the cost and accessibility of drugs to patients (see also Off-label prescribing for psychiatric disorders).

Of the antipsychotics listed below, olanzapine, risperidone and haloperidol are the most effective antipsychotics for initial treatment of acute maniaCipriani 2011. Metabolic disturbance is associated with antipsychotic treatment, particularly olanzapinePillinger 2020. Young people in particular are at risk of antipsychotic adverse effects including extrapyramidal adverse effects, effects due to elevated blood prolactin concentration, and weight gain. The use of haloperidol is limited by its association with extrapyramidal adverse effects.

Establish baseline values of parameters that can be affected by antipsychotic therapy—see Baseline parameters potentially affected by antipsychotic therapy. Dosage should be guided by response to therapy and tolerability (regularly monitor for adverse effects). Slower dose escalation may be required for people who are antipsychotic naive, to reduce the likelihood of antipsychotic adverse effects.

If adverse effects are suspected, lower the dose or switch to another drug with a lower propensity for adverse effects—see Switching antipsychotics.

For initial treatment of acute mania, use one of the following antipsychotics, concurrently with lithium, sodium valproate or carbamazepine. Use:

1olanzapine 10 to 15 mg orally, daily; titrate to response and tolerability. Maximum daily dose of 30 mg. Stop olanzapine once acute symptoms have remitted (see Stopping an antipsychotic) and continue with lithium, sodium valproate or carbamazepine monotherapy1 olanzapine olanzapine olanzapine

OR

1risperidone 2 mg orally, daily; titrate to response and tolerability in increments of 1 mg daily every few days. Maximum daily dose of 6 mg. Stop risperidone once acute symptoms have remitted (see Stopping an antipsychotic) and continue with lithium, sodium valproate or carbamazepine monotherapy risperidone risperidone risperidone

OR

2aripiprazole 10 to 15 mg orally, daily; titrate to response and tolerability. Maximum daily dose of 30 mg. Stop aripiprazole once acute symptoms have remitted (see Stopping an antipsychotic) and continue with lithium, sodium valproate or carbamazepine monotherapy aripiprazole aripiprazole aripiprazole

OR

2asenapine 5 to 10 mg sublingually, twice daily; titrate to response and tolerability. Maximum daily dose of 20 mg in 2 divided doses. Stop asenapine once acute symptoms have remitted (see Stopping an antipsychotic) and continue with lithium, sodium valproate or carbamazepine monotherapy2 asenapine asenapine asenapine

OR

2cariprazine 1.5 mg orally, daily; increase to 3 mg daily on the second day; titrate to response and tolerability. Maximum daily dose of 6 mg. Stop cariprazine once acute symptoms have remitted (see Stopping an antipsychotic) and continue with lithium, sodium valproate or carbamazepine monotherapyPericlou 2020Durgam 2015Sachs 2015Calabrese 2015 cariprazine cariprazine cariprazine

OR

2paliperidone modified-release 3 to 6 mg orally, daily3; titrate to response and tolerability. Maximum daily dose of 12 mg. Stop paliperidone once acute symptoms have remitted (see Stopping an antipsychotic) and continue with lithium, sodium valproate or carbamazepine monotherapy paliperidone paliperidone paliperidone

OR

2quetiapine immediate-release 150 mg orally, twice daily on the first day; increase to 300 mg twice daily on the second day; titrate to response and tolerability. Maximum daily dose of 800 mg. Stop quetiapine once acute symptoms have remitted (see Stopping an antipsychotic) and continue with lithium, sodium valproate or carbamazepine monotherapy quetiapine quetiapine quetiapine

OR

2quetiapine modified-release 300 mg orally, daily on the first day; increase to 600 mg once daily on the second day; titrate to response and tolerability. Maximum daily dose of 800 mg. Stop quetiapine once acute symptoms have remitted (see Stopping an antipsychotic) and continue with lithium, sodium valproate or carbamazepine monotherapy quetiapine quetiapine quetiapine

OR

2ziprasidone 40 mg orally, twice daily; titrate to response and tolerability. Maximum of 80 mg twice daily. Stop ziprasidone once acute symptoms have remitted (see Stopping an antipsychotic) and continue with lithium, sodium valproate or carbamazepine monotherapy ziprasidone ziprasidone ziprasidone

OR

3haloperidol 2 mg orally, daily as a single dose or in 2 divided doses; titrate to response and tolerability. Maximum daily dose of 10 mg. Stop haloperidol once acute symptoms have remitted (see Stopping an antipsychotic) and continue with lithium, sodium valproate or carbamazepine monotherapy. haloperidol haloperidol haloperidol

If daytime sedation is an issue with once-daily doses, give the dose at night.

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

If there is an acceptable response, antipsychotic therapy is continued and is usually stopped once acute mania symptoms have remitted and the patient is euthymic (ie has a stable mental state that is neither manic nor depressed)—see Pharmacological treatment of acute mania in bipolar disorder in adults and young people. Refer to the psychiatrist’s treatment plan for duration of antipsychotic treatment and approach to stopping the antipsychotic.

Continue with lithium, sodium valproate or carbamazepine as monotherapy for at least 6 to 12 months to prevent relapse, then assess if prophylaxis of bipolar disorder is required.

1 The maximum daily dose of oral olanzapine in accepted usage for short-term treatment of acute mania is greater than the maximum suggested in the Australian approved product information. If treatment with an antipsychotic is needed for maintenance therapy, use a maximum dose of 20 mg.Return
2 Asenapine wafers should not be swallowed—efficacy relies upon sublingual absorption.Return
3 Starting paliperidone at 3 mg may improve tolerability.Return