Service users taking long-acting injectable antipsychotics (LIAs) may experience recurrence of symptoms as they approach trough levels within a steady-state cycle. Limited research exists around symptom variation between peak-to-trough plasma concentrations of LIA inter-dose intervals. Different LIAs have variable rates of change in dopamine receptor occupancy during this peak-to-trough variation due to differing elimination half-lifes. It is unclear what rate of change in D2 blockade is tolerated by patients at present, which this trial aims to determine through observing symptom severity differences during peak-to-trough variation.

A real-world observational longitudinal cohort study is proposed. Inclusion criteria would be working-age adults (18–65 years) who have received five consecutive and timely LIA administrations of a consistent drug and dose. The study would exclude anyone with significant hepatic or renal impairment, anyone on concurrent oral antipsychotic medication or anyone deemed not to yet be within steady-state plasma levels of their LIA medication.

Serum assays for drug level will be obtained at both peak and trough concentrations during an LIA cycle. Expected timings for peak levels will be determined by derived tmax values from existing pharmacokinetic literature for individual drugs. Trough levels will be taken within 24 hours of the next LIA administration being due. Plasma drug concentrations will then be used to calculate expected striatal D2 blockade using EC50 values and maximal occupancy for individual drugs derived from existing PET scan data.

Symptom severity will be assessed by completing Positive and Negative Symptom Scores (PANSS) questionnaires with service users at the time of both peak and trough plasma concentrations of LIA. The difference in these scores will then be plotted alongside the difference in expected D2 blockade derived from plasma drug concentrations.

We hypothesize that the rate of D2 occupancy change would correlate with symptom severity differences in an exponential manner, in that drugs with shorter elimination half-life would have greater difference in symptom severity between peak and trough. We expect that service users would be able to tolerate such change to a degree without significant emergence of symptoms; the trial aims to determine the threshold for what most service users can tolerate, which may then assist in guiding how to effectively reduce and discontinue medications.

This outlines a research protocol to monitor response to pharmacokinetic variation within inter-dose intervals of LIA medication, which may ultimately aid service users in reducing and discontinuing antipsychotics.