Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.
Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomiting and as an appetite stimulant. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.
Amisulpride, sold under the brand names Solian and Barhemsys, is a medication used in the treatment of schizophrenia, acute psychotic episodes, depression, and nausea and vomiting. It is specifically used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; at low doses by mouth to treat depression; and at higher doses by mouth to treat psychosis.
Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder.
The management of schizophrenia usually involves many aspects including psychological, pharmacological, social, educational, and employment-related interventions directed to recovery, and reducing the impact of schizophrenia on quality of life, social functioning, and longevity.
Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis. Unlike other antipsychotics, pimavanserin is not a dopamine receptor antagonist, but rather is a selective inverse agonist of the serotonin 5-HT2A receptor.
Pomaglumetad (LY-404,039) is an amino acid analog drug that acts as a highly selective agonist for the metabotropic glutamate receptor group II subtypes mGluR2 and mGluR3. Pharmacological research has focused on its potential antipsychotic and anxiolytic effects. Pomaglumetad is intended as a treatment for schizophrenia and other psychotic and anxiety disorders by modulating glutamatergic activity and reducing presynaptic release of glutamate at synapses in limbic and forebrain areas relevant to these disorders. Human studies investigating therapeutic use of pomaglumetad have focused on the prodrug LY-2140023, a methionine amide of pomaglumetad (also called pomaglumetad methionil) since pomaglumetad exhibits low oral absorption and bioavailability in humans.
Ecopipam is a dopamine antagonist which is under development for the treatment of Lesch-Nyhan syndrome, Tourette syndrome, speech disorders, and restless legs syndrome. It is taken by mouth.
Cariprazine, sold under the brand name Vraylar among others, is an atypical antipsychotic developed by Gedeon Richter, which is used in the treatment of schizophrenia, bipolar mania, bipolar depression, and major depressive disorder. It acts primarily as a D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors, with high selectivity for the D3 receptor. It is taken by mouth.
Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic medication used for the treatment of major depressive disorder, schizophrenia, and agitation associated with dementia due to Alzheimer's disease.
Samidorphan is an opioid antagonist that in the form of olanzapine/samidorphan is used in the treatment of schizophrenia and bipolar disorder. Samidorphan reduces the weight gain associated with olanzapine. Samidorphan is taken by mouth.
Bitopertin is a glycine reuptake inhibitor which was under development by Roche as an adjunct to antipsychotics for the treatment of persistent negative symptoms or suboptimally controlled positive symptoms associated with schizophrenia. Research into this indication has been largely halted as a result of disappointing trial results. As of 2024, it is under development for the management of erythropoietic protoporphyria.
Basimglurant (INN) is a negative allosteric modulator of the mGlu5 receptor which is under development by Roche and Chugai Pharmaceutical for the treatment of treatment-resistant depression and fragile X syndrome. As of November 2016, it has undergone phase II clinical trials for both of these indications.
Lumateperone, sold under the brand name Caplyta, is an atypical antipsychotic medication of the butyrophenone class. It is approved for the treatment of schizophrenia as well as bipolar depression, as either monotherapy or adjunctive therapy. It is developed by Intra-Cellular Therapies, licensed from Bristol-Myers Squibb. Lumateperone was approved for medical use in the United States in December 2019 with an initial indication for schizophrenia, and became available in February 2020. It has since demonstrated efficacy in bipolar depression and received FDA approval in December 2021 for depressive episodes associated with both bipolar I and II disorders.
Brilaroxazine, also known as oxaripiprazole, is an investigational atypical antipsychotic which is under development by Reviva Pharmaceuticals for the treatment of neuropsychiatric and inflammatory disorders. It has currently completed the first of two phase III clinical trials for schizophrenia. Reviva Pharmaceuticals also intends to investigate brilaroxazine for the treatment of bipolar disorder, major depressive disorder, attention deficit hyperactivity disorder (ADHD), irritability in autism, tics, psychosis/agitation associated with Alzheimer's disease, Parkinson's disease psychosis, as well as the inflammatory disorders pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), and psoriasis. The FDA granted brilaroxazine orphan drug designation for the treatment of PAH and IPF.
Evenamide is a selective voltage-gated sodium channel blocker, including subtypes Nav1.3, Nav1.7, and Nav1.8, which is described as an antipsychotic and is under development by Newron Pharmaceuticals as an add-on therapy for the treatment of schizophrenia. The drug has shown efficacy in animal models of psychosis, mania, depression, and aggression. It has completed phase I clinical trials, and phase II clinical trials will be commenced in the third quarter of 2015.
Roluperidone (former developmental code names MIN-101, CYR-101, MT-210) is a 5-HT2A and σ2 receptor antagonist under development by Minerva Neurosciences for the treatment of schizophrenia. One of its metabolites also has some affinity for the H1 receptor. Pre-clinical findings provide evidence of the effect of roluperidone on brain-derived neurotrophic factor ("BDNF"), which has been associated with neurogenesis, neuroplasticity, neuroprotection, synapse regulation, learning and memory.
Ulotaront is an investigational antipsychotic that is undergoing clinical trials for the treatment of schizophrenia and Parkinson's disease psychosis. The medication was discovered in collaboration between PsychoGenics Inc. and Sunovion Pharmaceuticals using PsychoGenics' behavior and AI-based phenotypic drug discovery platform, SmartCube. Ulotaront is in Phase III of clinical development.
Xanomeline/trospium chloride, sold under the brand name Cobenfy, is a fixed-dose combination medication used for the treatment of schizophrenia. It contains xanomeline, a muscarinic agonist; and trospium chloride, a muscarinic antagonist. Xanomeline is a functionally preferring muscarinic M4 and M1 receptor agonist. Trospium chloride is a non-selective muscarinic antagonist.
