DOES HALF-LIFE MATTER AFTER ANTIPSYCHOTIC DISCONTINUATION?

A relapse comparison in schizophrenia with 3 different formulations of paliperidone.

Preventing or delaying relapse is a major goal in the treatment of schizophrenia. Relapse is at best disruptive; at worst it can be lethal.1

Relapse has a multitude of negative consequences to a person’s physiological, psychological and social well-being.2,4

Continuous exposure to antipsychotic medication is key to effective long-term treatment of schizophrenia because it provides sustained symptom control and optimizes clinical and psychosocial outcomes.5-8 However, patients with schizophrenia often have difficulty consistent medication adherence and relapse is often inevitable.9-12

It is of primary importance to mitigate this problem where possible, and antipsychotic formulations with longer half-lives may potentially delay relapse by providing continuous exposure well beyond the point of medication discontinuation.13-19

While the premise that relapse may be delayed longer after discontinuing a long-acting injectable formulation than after discontinuing its oral formulation seems intuitive, few studies has examined, the relationship between the half-lives of antipsychotic formulations and time to relapse following discontinuation.

The results of the analysis demonstrated that 50% of patients who withdrew treatment from oral paliperidone, PP1M (once monthly paliperidone palmitate), or PP3M (once every 3 months paliperidone palmitate) remained relapse free for  approximately 2 months, 6 months and 13 months respectively20.

Of the three formulations evaluated, PP3M conferred the most enduring relapse prevention and may represent a buffer against medication interruptions, proving clinicians and caregivers with an extended opportunity to ensure follow-up and treatment continuity.20

 

"Antipsychotic formulations with longer half-lives may potentially delay relapse by providing continuous exposure well beyond the point of medication discontinuation"

 

 

However, a recent publication by Weiden et al20, presents a post-hoc analysis of data from three similarly designed clinical  trials21,22,23 comparing time to relapse in patients receiving once daily oral formulation of paliperidone, PP1M and PP3M. These formulations contain the same active substance but deviate in their administration intervals and half-lives.1,16,20,24

The results of the analysis demonstrated that 50% of patients who withdrew treatment from oral paliperidone, PP1M, or PP3M remained relapse free for  approximately 2 months, 6 months and 13 months respectively20. Of the three formulations evaluated, PP3M conferred the most enduring relapse prevention and may represent a buffer against medication interruptions, proving clinicians and caregivers with an extended opportunity to ensure follow-up and treatment continuity.20

 

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