Nonresponse to treatment of acute mania in adults and young people
If the patient has an inadequate response to pharmacotherapy for acute mania within a few weeks, address any factors in Key questions to assess nonresponse to pharmacotherapy for acute mania that could account for the response.
Consider the following questions if a patient does not respond to pharmacological treatment of acute mania or has a relapse.
- Is the diagnosis correct?
- Have possible medical causes of symptoms been identified and treated (eg have antidepressants, steroids or stimulants been stopped)?
- 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 treatment failure have been discounted, other treatment strategies that a psychiatrist may use include:
- switching to a different drug (eg switching to a different antipsychotic; switching from lithium to sodium valproate or carbamazepine)
- continuing combination therapy with an antipsychotic plus lithium, sodium valproate or carbamazepine beyond resolution of acute mania
- combining 2 of the 3 drugs used for maintenance therapy (lithium, sodium valproate or carbamazepine)
- electroconvulsive therapy (ECT)—evidence supports the use of ECT for acute mania as an adjunct to pharmacotherapy; it may be effective even if the patient has not responded to multiple drugs.