Nonresponse to treatment of bipolar depression in adults and young people
If the patient has an inadequate response to pharmacotherapy for bipolar depression within 4 to 6 weeks, address any factors in Key questions to assess nonresponse to pharmacotherapy for bipolar depression that could account for the response.
Consider the following questions if a patient does not respond to pharmacological treatment of bipolar depression or has a relapse.
- Is the diagnosis correct?
- Have possible medical causes (eg use of steroids) of symptoms been identified and treated?
- Have alcohol or other substance use problems been addressed?
- Has the patient been treated with adequate doses for an adequate duration?
- Is an interacting drug reducing the response [NB1]?
- Is the patient adherent to therapy [NB2]?
- Have they been taking their drugs regularly? Count the patient’s pills and consider checking the drug blood concentration [NB3] [NB4].
- Is the patient experiencing an adverse effect?
- Have psychosocial factors that could negatively impact adherence been addressed?
NB1: Many drugs are metabolised by cytochrome P450 enzymes. Information on drug interactions mediated through these enzymes can be found at the University of Indiana School of Medicine’s drug interaction website.
NB2: Risk factors for nonadherence include persistent adverse effects, impaired insight, disorganised thinking, cognitive impairment, lack of community support, psychosocial stressors, inadequate community treatment and lack of patient or caregiver education.
NB3: A list of Australian laboratory test databases is available at the Australasian Association for Clinical Biochemistry and Laboratory Medicine (AACB) ‘Testing for health’ website.
NB4: 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.
If alternative reasons for nonresponse have been discounted, seek psychiatrist advice. Options to modify treatment include:
- augment pharmacotherapy with psychological treatment—psychotherapies such as cognitive behavioural therapy and psychoeducation techniques are effective in bipolar depression
- if using monotherapy:
- switch to a different drug for monotherapy
- switch to combination therapy with an antidepressant and another drug
- psychiatrists may add a drug recommended for prophylaxis of bipolar disorder
- if using selective serotonin reuptake inhibitor (SSRI)–based combination therapy:
- switch to a different SSRI (see the drug regimens here)
- combine the SSRI with a different drug; options include lithium, lurasidone, olanzapine, quetiapine or sodium valproate (see the drug regimens here)1
- psychiatrists may switch to a different class of antidepressant. Options include a serotonin noradrenaline reuptake inhibitor (SNRI), a tricyclic antidepressant (TCA) or a monoamine oxidase inhibitor (MAOI)
- psychiatrists may consider electroconvulsive therapy (ECT)—ECT is particularly effective if the patient has psychotic depression, depressive stupor or displays significant psychomotor retardation or agitation.