A multi-target drug treatment in schizophrenia and schizoaffective disorder using adjunctive agents with non-D 2 mechanisms of action

Abstract

Pharmacologic actions to reduce neurotransmission through the D2 receptor have been the only proven therapeutic mechanism for schizophrenia (SZ) and schizoaffective (SA) disorder. However, in view of the multifactorial genesis and pathogenesis of these psychoses, it is unlikely that any antipsychotic drug would work equally well against all symptoms and behavioral disturbances. The absence of a single therapeutic target for SZ/SA disorder has prompted the use of polypharmacy strategies including multi-target pharmacotherapy, consisting of various add-on medications and supplements. Multi-target polypharmacy strategies include the off-label prescription of adjunctive agents such as antidepressants, mood stabilizers, and benzodiazepines already in use, and novel potential adjunctive agents (newer molecules or compounds) based on several non-dopaminergic hypotheses (serotonergic, noradrenergic, glutamatergic, gamma-aminobutyric acid related, and cholinergic neurotransmission, neuroprotective mechanisms and brain neuroplasticity). This chapter is an overview of the current state of evidence for the augmentation of antipsychotics with antidepressants, lithium, antiepileptic agents, benzodiazepines, and new molecules and compounds for the treatment of people with SZ/SA disorder with a special focus on research data published within the past 5–7 years. Using these agents for the augmentation of antipsychotics based on a multi-target drug treatment approach entails the combination of two or more drugs/agents with different mechanisms of action on the central nervous system in an attempt to enhance efficacy.