Choice of drug for prophylaxis of bipolar disorder in adults and young people

If there was a sufficient response to the drug used for acute therapy, use the same drug for prophylaxis; the effective dose or target blood concentration may be lower than when the drug was used for acute treatment. If a patient is stabilised on and adherent to an oral antipsychotic, to minimise the risk of adverse effects, slowly reduce to the lowest effective dose; see Approach to reducing antipsychotic dose for a chronic severe psychiatric disorder for approach. Also offer the option of switching to a long-acting injectable formulation, but do not insist upon switching if the patient is tolerating their oral antipsychotic.

Drugs used for prophylaxis of bipolar disorder and their efficacy in preventing manic and depressive episodes outlines the drugs used for prophylaxis of bipolar disorder and their efficacy in preventing manic and depressive episodes. If the patient has bipolar I disorder (ie at least one prior episode of mania) they will require a drug effective in preventing future episodes of mania. While monotherapy is preferred, sometimes more than one drug is required to achieve optimal response.

The choice of drug may also be influenced by the propensity of the preferred treatment to cause adverse effects. Drug therapy is usually prolonged, so consider tolerability carefully.

Antipsychotic choice, in particular, needs to balance efficacy and tolerability (consider both short- and long-term adverse effects). If prophylaxis with an antipsychotic is being considered, discuss antipsychotic choice with the patient and, if they consent, their significant others, family or carers using the discussion points here.

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. Monitor patients for adverse effects of drug treatment.

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 antipsychotic adverse effects).

See also the additional considerations:

Table 1. Drugs used for prophylaxis of bipolar disorder and their efficacy in preventing manic and depressive episodes
[NB1] [NB2] [NB3]
Drug	Comments
First-line therapy
lithium [NB4]	usually considered first line because it has the most substantive body of evidence supporting its efficacy in preventing manic episodes evidence of efficacy in preventing depression is less robust reduces suicidal behaviour and death from suicide
Second-line therapy
aripiprazole	more effective at preventing manic, rather than depressive, episodes consider antipsychotic adverse effects
asenapine	more effective at preventing manic, rather than depressive, episodes consider antipsychotic adverse effects
lamotrigine	most effective drug for preventing episodes of bipolar depression either ineffective or weakly effective in preventing mania
paliperidone	more effective at preventing manic, rather than depressive, episodes consider antipsychotic adverse effects
quetiapine	effective in preventing manic and depressive episodes consider antipsychotic adverse effects
risperidone long-acting intramuscular injection [NB5]	more effective at preventing manic, rather than depressive, episodes consider antipsychotic adverse effects
sodium valproate	efficacy in preventing manic or depressive episodes observed in a randomised open-label trial but not in a double-blind randomised controlled trial [NB6] consider in patients that have predominantly manic episodes because of its modest efficacy in treating acute mania
ziprasidone	more effective at preventing manic, rather than depressive, episodes consider antipsychotic adverse effects
Third-line therapy
carbamazepine	limited evidence of efficacy for prophylaxis only use if other drugs are not suitable
olanzapine	effective in preventing manic and depressive episodes consider antipsychotic adverse effects—significant cardiometabolic adverse effects when used long term
Note: NB1: The information in this table is based on a combination of trial data and expert opinion; it is intended as a guide only and clinicians should apply clinical judgement. NB2: The propensity of the drug to cause adverse effects should also be considered. NB3: For dose recommendations, see Drug regimens for prophylaxis of bipolar disorder in adults and young people. NB4: Although lithium is first line, other drugs may be preferred for a patient based on their preference or considerations such as previous response (or nonresponse), tolerability, predominant polarity or safety in specific populations. If there was a sufficient response to the drug used for maintenance therapy, use the same drug for prophylaxis. NB5: For dose recommendations, see Long-acting injectable antipsychotics for maintenance therapy after acute mania. NB6: Balance investigators collaborators, Geddes JR, Goodwin GM, Rendell J, Azorin JM, Cipriani A, et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. Lancet 2010;375(9712):385-95. [URL] Bowden CL, Calabrese JR, McElroy SL, Gyulai L, Wassef A, Petty F, et al. A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group. Arch Gen Psychiatry 2000;57(5):481-9. [URL]

For drug regimens for prophylaxis of bipolar disorder see here.

Discuss the duration of prophylaxis with the patient and, if they consent, their significant others, family or carers. Long-term pharmacotherapy can be associated with significant harms (eg cardiometabolic and other serious adverse effects of antipsychotics). Assess the harm–benefit ratio of these drugs, with consideration that recurrence can also be associated with significant harm. Prophylaxis may be time-limited (3 to 5 years) or indefinite, depending on history of recurrences, response to treatment, patient age and treatment tolerability. If the decision is made to stop prophylaxis, ensure the patient understands the associated risks and provide further psychoeducation. Ensure withdrawal of the drug is gradual and carefully monitored because there is an increased risk of suicide if patients withdraw treatment rapidly. If stopping an antipsychotic, see Stopping an antipsychotic.

If a patient experiences a relapse while on maintenance therapy, see Nonresponse to prophylaxis of bipolar disorder.

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