Abstract
Schizophrenia remains one of the most severe medical diseases. Current dopamine modulating first-generation and second-generation antipsychotics target mainly positive symptoms, but not/inadequately negative and cognitive symptoms. Additional challenges include non-adherence and adverse effects, especially cardiometabolic dysregulation. This review evaluates new/emerging pharmacological treatments for schizophrenia. Therapies targeting total symptoms include cannabidiol, D3 antagonist/5-HT1A partial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated receptor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2 antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal® and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved by U.S. Food and Drug Administration, and positive results were announced for Risperidone ISM®, each achieving therapeutic levels within 24 hours, without need for initial oral cotreatment/loading injection-strategies. Paliperidone palmitate 6-monthly intramuscularly injectable and Risperidone subcutaneously injectable TV46000 are currently under investigation. Finally, the samidorphan+olanzapine combination targets reduced weight gain liability, while maintaining olanzapine's efficacy. Most of these trial programs are still ongoing or have yielded mixed or even negative results. Thus, additional mechanisms of action and agents require study to improve schizophrenia outcomes for total/positive symptoms with reduced adverse effects, but also cognitive symptoms, negative symptoms, and treatment resistance, the areas of greatest need in schizophrenia currently.
Highlights
IntroductionSchizophrenia is a still all-too-often chronic and debilitating psychiatric disorder that is characterized by a combination of positive and negative symptoms, cognitive dysfunction, affective and motor disturbances that often result in functional impairment and poor quality of life.1,2Current treatment guidelines suggest long-term treatment with antipsychotic medications in conjunction with psychological interventions, for people with first episode psychosis, an acute exacerbation or recurrence of psychosis. Despite pharmacologic advances in recent years, an effective treatment of schizophrenia remains an issue, as knowledge about the pathophysiology of this complex disorder is lacking. The most challenging components of treatment effectiveness are adherence and efficacy for negative and cognitive as well as residual positive symptoms and adverse effects.1Dopamine modulating antipsychotics remain the primary and only currently approved treatment for schizophrenia, and over the past years many differentA
Successful phase-III and/or phase-II trial programs have included (i) new formulations of aripiprazole lauroxil long-acting injectable antipsychotics (LAIs) and risperidone LAI that have been able to avoid the need for oral cotreatment, as well as, in the case of the two risperidone LAI formulations, loading/booster
Injections in the initial phases of LAI treatment,100,111,114 leading to FDA approval of Aripiprazole Lauroxil NanoCrystal® Dispersion (ALNCD; Aristada Initio) and once-monthly subcutaneously injected PerserisTM Risperidone (RBP-7000); (ii) the treatment of acutely exacerbated schizophrenia with lumateperone, a novel antipsychotic modulating dopamine, serotonin and, via D1 agonism, glutamatergic transmission50 that is currently being evaluated by the FDA for approval for acutely exacerbated schizophrenia, and (iii) the combination of samidorphan plus olanzapine in one pill for the reduction of body weight gain with ALKS3831 at 3 and 6 months,123,125,126 while maintaining olanzapine’s efficacy
Summary
Schizophrenia is a still all-too-often chronic and debilitating psychiatric disorder that is characterized by a combination of positive and negative symptoms, cognitive dysfunction, affective and motor disturbances that often result in functional impairment and poor quality of life.1,2Current treatment guidelines suggest long-term treatment with antipsychotic medications in conjunction with psychological interventions, for people with first episode psychosis, an acute exacerbation or recurrence of psychosis. Despite pharmacologic advances in recent years, an effective treatment of schizophrenia remains an issue, as knowledge about the pathophysiology of this complex disorder is lacking. The most challenging components of treatment effectiveness are adherence and efficacy for negative and cognitive as well as residual positive symptoms and adverse effects.1Dopamine modulating antipsychotics remain the primary and only currently approved treatment for schizophrenia, and over the past years many differentA. Schizophrenia is a still all-too-often chronic and debilitating psychiatric disorder that is characterized by a combination of positive and negative symptoms, cognitive dysfunction, affective and motor disturbances that often result in functional impairment and poor quality of life.. Current treatment guidelines suggest long-term treatment with antipsychotic medications in conjunction with psychological interventions, for people with first episode psychosis, an acute exacerbation or recurrence of psychosis.. Despite pharmacologic advances in recent years, an effective treatment of schizophrenia remains an issue, as knowledge about the pathophysiology of this complex disorder is lacking.. The most challenging components of treatment effectiveness are adherence and efficacy for negative and cognitive as well as residual positive symptoms and adverse effects.. Dopamine modulating antipsychotics remain the primary and only currently approved treatment for schizophrenia, and over the past years many different
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
