Monitoring and titrating antipsychotic therapy for a first episode of psychosis

Monitoring antipsychotic therapy involves assessment of treatment response and monitoring for adverse effects. If daytime sedation is an issue with daily doses, give the dose at night. See Antipsychotic adverse effects for advice on monitoring for, preventing and addressing adverse effects.

Positive symptoms should start to improve within 1 week of starting an antipsychotic; it may take several weeks and achievement of target dose before symptoms adequately respond. Negative symptoms, however, may not respond to antipsychotic therapy—see Managing negative symptoms in psychoses including schizophrenia for targeted treatment.

The frequency of dose increases depends on the patient’s severity of symptoms and degree of distress, the setting in which treatment is delivered, and the pharmacokinetics of the drug. A slower dose increase may be required for some people (eg younger people, older adults), particularly those who are antipsychotic naive, to reduce the likelihood of antipsychotic adverse effects.

If there is an inadequate response at the target dose, address any factors in Key questions to assess nonresponse to an antipsychotic that could account for the response—if poor adherence is likely, consider starting a long-acting injectable formulation. If the inadequate response is not explained by these factors, increase to the maximum antipsychotic dose. If there is still minimal response after 4 weeks of treatment at the maximum dose, or no response after 2 weeks, and alternative reasons for treatment failure have been excluded, switch to an oral antipsychotic with a different dopaminergic receptor occupancy profile (for which adverse effect profile is a surrogate).
Figure 1. Key questions to assess nonresponse to an antipsychotic

Consider the following questions if a patient does not respond to an antipsychotic or has a relapse.

  • Is the diagnosis correct?
  • Have possible medical causes of their symptoms been identified and treated?
  • Have alcohol or other substance use problems been addressed?
  • Has the patient been treated with an adequate dose of the antipsychotic for an adequate duration?
  • Is an interacting drug reducing the response? [NB1]
  • Is the patient adherent to therapy [NB2]?
    • Have they been taking their antipsychotic regularly? Count the patient’s pills and consider checking the antipsychotic blood concentration [NB3] [NB4].
    • Is the patient experiencing an adverse effect?
    • Have psychosocial factors that could negatively impact adherence been addressed?
Note:

NB1: Many antipsychotics 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, negative symptoms, 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].

Sequential trials of monotherapy may be required until the best balance of effectiveness and adverse effects is achieved. If symptoms of psychosis do not substantially settle after monotherapy with 2 different antipsychotics, see Treatment-resistant schizophrenia.