Antipsychotic Medications: Enhancing Use to Improve Outcomes

Hiroyoshi Takeuchi; Stefan Leucht; John M. Kane; Ofer Agid; Gary Remington

Disclosures

Schizophr Bull. 2021;47(5):1201-1204. 

In This Article

Antipsychotic Dosing

Antipsychotics are routinely prescribed once daily or in divided dosing if their plasma half-lives are ≥24 hours or <24 hours, respectively; however, neuroimaging work examining the relationship between dopamine D2 occupancy and response has challenged this notion.[24] More recently, a systematic review summarized studies evaluating the time course of dopamine D2 receptor occupancy and antipsychotic blood concentrations, concluding that peripheral antipsychotic pharmacokinetics do not mirror what is observed centrally.[25] More specifically, there was a slower reduction in central dopamine D2 occupancy compared to that observed in antipsychotic blood concentrations, regardless of antipsychotic type. In line with this observation, there are a number of randomized controlled trials (RCTs) comparing efficacy and tolerability between the 2 dosing regimens specific to risperidone (half-life: 23 h),[26–28] olanzapine (half-life: 30–60 h),[26] quetiapine (half-life: 7 h),[29] asenapine (half-life: 24 h),[30] and perphenazine (half-life: 8–12 h),[31] although there has been only a single small study for quetiapine and asenapine. A recent meta-analysis combining these studies concluded that once daily antipsychotic administration is not inferior to divided dosing in terms of efficacy, while clinical superiority is observed for at least some side effects, eg, sleepiness.[32] In terms of clozapine (half-life: 12–16 hours), a cross-sectional study involving 2 large academic settings indicated once daily administration in approximately 75% of patients, with no significant difference in positive symptom remission or risk of seizures versus divided dosing.[33] It warrants comment, though, that peak and trough plasma clozapine concentration is higher and lower, respectively, in once daily dosing compared to divided dosing,[34] and plasma clozapine concentration is associated with abnormal electroencephalograms.[35] Taken together, evidence indicates that all currently approved antipsychotics, regardless of plasma half-life, can be prescribed once daily, preferably at bedtime given sedative effects, a strategy that may be advantageous in terms of side effects as well as medication adherence, which, in turn, can translate to improved outcomes.

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