Approach to treating bipolar depression

See Principles of managing bipolar depression in adults and young people for advice on the setting in which initial treatment should be delivered, the requirement for psychiatrist oversight and an overview of management.

Consider whether this is the first presentation of bipolar depression or if the patient is currently receiving treatment for bipolar depression and is relapsing or not responding. For patients currently receiving treatment and not responding, see Nonresponse to treatment for bipolar depression.

Although bipolar depression can be more difficult to treat than unipolar depression, most patients eventually respond to treatment. Because there is a limited evidence base to inform treatment choices, there are divergent international views on the optimal treatment of bipolar depression, in particular the role of antidepressants. Subsequently, recommendations for bipolar depression in international guidelines vary considerably. In general, treatment options for the acute treatment of bipolar depression are either monotherapy or combination therapy. Often monotherapy alone is ineffective or only partially effective for bipolar depression, so many patients require combination therapy. There have been no controlled head-to-head studies comparing the efficacy or tolerability of monotherapy to combination therapy.

The drugs recommended for monotherapy for bipolar depression are cariprazine, lamotrigine, lithium, lurasidone, olanzapine and quetiapine—these drugs have been demonstrated in controlled trials to be effective for bipolar depression without leading to switches into mania or rapid cycling. Do not use antidepressant monotherapy for bipolar depression because this can induce mania or rapid cycling.

Note: Do not use antidepressant monotherapy for bipolar depression.

Often monotherapy alone is ineffective or only partially effective for bipolar depression, so many patients require combination therapy. Combination therapy for bipolar depression involves combining an antidepressant with one of the following drugs to prevent manic switch: cariprazineRANZCP 2020 guidelines, lithium, lurasidone, olanzapine, quetiapine or sodium valproate. If the patient has a history of rapid cycling, mixed features, antidepressant-induced mood elevation or ongoing active substance use, combination therapy with an antidepressant should be used cautiously and guided by a psychiatrist because of the risk of inducing manic episodes or rapid cycling.

The decision to use monotherapy or combination therapy, and the choice of regimen, is influenced by the patient’s current treatment and past response to and tolerance of pharmacotherapy for bipolar depression. Consider the drug’s propensity to cause adverse effects, in particular the adverse effects of antipsychotics. Consult a drug information source for advice on contraindications, precautions, adverse effects, dosage adjustments, clinical monitoring requirements before and during therapy, and therapeutic drug monitoring12. Drug therapy is usually prolonged (up to 12 months for an acute episode or longer if the patient requires prophylaxis of bipolar disorder), so consider tolerability carefully. Monitor patients for adverse effects of drug treatment. If adverse effects are suspected, lower the dose or switch to another drug with a lower propensity for adverse effects.

For drug regimens, see here for monotherapy and here for combination therapy.

See also additional considerations:

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