Perphenazine decanoate

Table of contents

• What is perphenazine decanoate?
• How does perphenazine decanoate work?
• Which conditions is it used or studied for?
• How is perphenazine decanoate given?
• What do the clinical trials show?
• What side effects are known?

What is perphenazine decanoate?

Perphenazine decanoate is a long-acting injectable (depot) antipsychotic medicine that belongs to the phenothiazine family and has a piperazine ethanol side chain.^[3] It is the decanoate ester form of perphenazine, a conventional (typical) antipsychotic. Perphenazine itself is available as oral tablets containing 2 mg, 4 mg, 8 mg, and 16 mg.^[2] The US Food and Drug Administration (FDA) labelling for perphenazine states that it is not approved for the treatment of patients with dementia-related psychosis.^[2] In the EU Clinical Trials Information System, the substance is investigated as one of several antipsychotic options in a Phase 3 trial for schizophrenia spectrum disorders.^[1]

How does perphenazine decanoate work?

Perphenazine decanoate is a depot antipsychotic. The term "depot" means that the medicine is given as an injection that releases the active substance slowly over time, allowing for long-term maintenance treatment.^[3] Perphenazine belongs to the phenothiazine family of antipsychotics, which act on the brain to reduce symptoms of psychosis such as hallucinations and delusions.^[2] The specific molecular target is not described in the provided sources.

Which conditions is it used or studied for?

• Schizophrenia — a long-term mental health condition that can cause hallucinations, delusions, and disordered thinking. The authorised Phase 3 trial includes people with schizophrenia.^[1]
• Schizoaffective disorder — a condition with symptoms of both schizophrenia and mood disorders such as depression or mania. This condition is included in the same trial.^[1]
• Schizophreniform disorder — a condition with symptoms similar to schizophrenia but lasting a shorter time. This condition is also included in the trial.^[1]

How is perphenazine decanoate given?

Perphenazine decanoate is given as a depot injection, which is a long-acting injectable form.^[3] In the clinical trial, perphenazine is listed as an oral medication at a dose of 24 mg, not as the decanoate injection.^[1] The oral form of perphenazine is available as film-coated tablets in strengths of 2 mg, 4 mg, 8 mg, and 16 mg.^[2]

What do the clinical trials show?

One authorised Phase 3 trial (NCT05958875) is investigating an early-intensified pharmacological treatment strategy for schizophrenia, schizoaffective disorder, and schizophreniform disorder.^[1] The trial plans to enrol 418 participants who have had a first-time treatment failure on their first-line antipsychotic treatment.^[1] Perphenazine is one of 23 antipsychotic drugs listed as possible treatments in the intensified treatment arm.^[1]

The primary outcome measure is the mean change from baseline in symptom severity as measured by the Positive and Negative Syndrome Scale (PANSS) total score at six weeks. The PANSS is a standard scale used to measure the severity of schizophrenia symptoms.^[1] The trial compares the early-intensified pharmacological treatment to treatment as usual, both for the group as a whole and for the subgroup of participants who had a first-time treatment failure on their first-line treatment.^[1]

The trial is currently authorised, which means it has received regulatory approval to proceed.^[1] Participants are randomised, meaning they are assigned by chance to either the intensified treatment arm or the treatment-as-usual arm.^[1]

What side effects are known?

The FDA labelling for perphenazine includes a boxed warning about an increased risk of death in elderly patients with dementia-related psychosis treated with antipsychotic drugs. In seventeen placebo-controlled trials, the risk of death in drug-treated patients was between 1.6 and 1.7 times the risk in placebo-treated patients. Over a typical 10-week controlled trial, the rate of death was about 4.5% in drug-treated patients compared to about 2.6% in the placebo group.^[2] Most of the deaths appeared to be either cardiovascular (such as heart failure or sudden death) or infectious (such as pneumonia) in nature.^[2] The labelling states that perphenazine is not approved for the treatment of patients with dementia-related psychosis.^[2]