Flupentixol: A Comprehensive Monograph on its Pharmacology, Clinical Use, and Safety Profile

1.0 Executive Summary

Flupentixol is a first-generation, or typical, antipsychotic agent belonging to the thioxanthene chemical class.[1] First introduced in 1965, it occupies a distinct niche in psychopharmacology due to its dose-dependent dual functionality, serving as a maintenance treatment for schizophrenia at higher doses and as a rapid-acting antidepressant at lower doses.[1] Its primary mechanism of action involves potent, non-selective antagonism of central dopamine D1 and D2 receptors, which is the basis for its antipsychotic efficacy.[3] The drug also exhibits antagonist activity at various other neuroreceptors, including serotonin 5-HT2A, alpha-1 adrenergic, and muscarinic M1 receptors, contributing to its complex profile of therapeutic and adverse effects.[3]

Clinically, Flupentixol is most prominently used for the long-term maintenance therapy of chronic schizophrenia, specifically in patients whose primary symptoms do not include excitement, agitation, or hyperactivity.[3] Its utility in this population is significantly enhanced by the availability of a long-acting intramuscular depot formulation, flupentixol decanoate. This formulation, administered every two to four weeks, addresses the critical challenge of medication non-adherence, a common cause of relapse in this patient population.[1]

The safety profile of Flupentixol is characteristic of a typical antipsychotic and is dominated by a high propensity for dose-dependent neurological adverse effects. These include acute extrapyramidal symptoms (EPS) such as parkinsonism, akathisia, and dystonia, as well as the risk of tardive dyskinesia (TD), a potentially irreversible movement disorder, with long-term use.[1] Other significant risks include hyperprolactinemia and cardiovascular effects, notably QTc interval prolongation.[1]