Efficacy of Lurasidone in First-Episode Psychosis: Patient Phenotypes, Dosage, and Recommendations from an Expert Panel

Abstract

Introduction

For patients with psychosis, early, intensive therapeutic intervention is thought to improve long-term outcomes. Furthermore, patients with a first-episode psychosis (FEP) who experience a good early response to antipsychotic medication show a clinical and functional benefit over the longer term if they continue low-dose antipsychotic treatment. Lurasidone is an atypical antipsychotic agent which is approved in Europe for the treatment of schizophrenia in adults and adolescents (13–17 years). The efficacy and tolerability of lurasidone have been demonstrated in both antipsychotic-naïve and previously treated patients.

Areas Covered

This paper provides a review and commentary regarding the use of lurasidone in patients with FEP. Case studies based on the authors’ clinical experiences with lurasidone in real-world practice are provided.

Expert Opinion

In our experience, lurasidone has shown efficacy in FEP in different patient profiles, including those with psychoses associated with substance use disorders. Lurasidone provides clinically relevant benefits, especially in patients with affective symptomatology, and has a good tolerability profile.

Key Summary Points

Lurasidone is an effective antipsychotic treatment for patients experiencing their first psychotic episode.

Lurasidone is effective in various patient populations, including those with psychoses associated with substance use disorders.

Lurasidone provides clinically relevant benefits, especially in patients with affective symptoms.

Lurasidone is well tolerated in both antipsychotic-naïve and previously treated patients.

Introduction

Psychotic disorders encompass a wide range of conditions characterized by thought, sensoperceptive, cognitive, and affective symptoms [1–3]. They are relatively common, with up to 3% of the general population experiencing a first-episode psychosis (FEP) within their lifetime [4], and are associated with a high societal burden [1, 5].

The onset of psychotic disorders typically occurs in adolescence or early adulthood [6], although they can appear throughout life; around 50% of FEPs are associated with the use of cannabis or other substances [7, 8]. Young patients receiving antipsychotic medication may be more sensitive to treatment side effects than adult patients, or may be more likely to discontinue their medication if they experience sexual dysfunction, excessive sedation, or weight gain, potentially compromising both their recovery and their long-term prognosis [9, 10].

Lurasidone is an atypical antipsychotic agent which is approved by the European Medicines Agency for the treatment of schizophrenia in adults and adolescents aged 13 years and over [11], and by the Food and Drug Administration for the treatment of schizophrenia and depressive episodes associated with bipolar I disorder [12]. Interest in lurasidone as a treatment for FEP is based on its unique pharmacological profile and potential clinical advantages in FEP. Its high affinity for 5-HT7 and 5-HT1A receptors contributes to antidepressant and cognitive-enhancing effects, which are particularly relevant for patients with FEP who often experience depressive symptoms and cognitive deficits [13–15].

In this review, we assess the evidence for the use of lurasidone in FEP. A panel of experts was convened to assess real-world practice with lurasidone, to describe clinical cases, and to propose best practices in the treatment of patients with FEP.

Heterogeneity and Clinical Evolution of Psychotic Disorders

Patients with FEP may exhibit positive symptoms (e.g., delusions and hallucinations), disorganization (related to thoughts and behavior), and/or negative symptoms (e.g., anhedonia, apathy, and alogia) [1–3]. Outcome studies have reported that over 50% of people with FEP have a good long-term outcome [16, 17], although this rate may drop depending on the criteria used to define functional recovery [18]. In addition to the clinical heterogeneity of FEPs [1], there is an underlying biological heterogeneity which, if better understood, could help to inform the most appropriate therapy. In recent studies, the relationship between brain morphology and pathology (i.e., diagnosis, disease stage or symptoms) has been assessed, leading to the identification of neuromorphological subgroups which could potentially be used to stratify patients [11] or to predict differential clinical trajectories [19]. The heterogeneity inherent to this pathology underscores the need for real-world data and expert recommendations to guide clinicians in effective FEP management.

Considerations for FEP Management

Due to the clinical heterogeneity of psychotic disorders, an individualized assessment is required before establishing the appropriate treatment. The severity of positive and negative symptoms should be assessed alongside the characteristics of disease presentation, such as the type of onset, suicidal ideation, neurocognition, social functioning, concomitant psychiatric conditions, comorbidities, lack of efficacy, poor adherence to previous treatments, and other social factors [20].

FEPs should be treated as soon as the disease is diagnosed, as there is an association between the duration of untreated psychosis and poor clinical outcomes [21, 22]. Patients with an FEP who experience a good early response to antipsychotic medication show a clinical and functional benefit over the longer term if they continue low-dose antipsychotic treatment [23]. Thus, early, intensive, comprehensive, and sustained therapeutic interventions from the early phases of the illness may improve long-term outcomes.

In many cases, FEPs occur during adolescence, and there is evidence of differences in cortical gray matter deficits between adolescent-onset and adult-onset schizophrenia which may be related to the developmental stages of the brain when an FEP occurs [24]. It is therefore important to understand the efficacy and safety of antipsychotic medications in both the adolescent and adult populations.

Antipsychotic drugs are associated with a diverse range of adverse effects, including agranulocytosis, akathisia, constipation, dystonia, hyperprolactinemia, myocarditis, sedation, sexual side effects, tardive dyskinesia, and weight gain [25]. These are specific to each antipsychotic medication and may impact on treatment adherence and efficacy [26]. In adolescents, specific antipsychotics have been shown to be associated with a higher incidence of weight gain, sedation, and hyperprolactinemia [27]. Management strategies to reduce adverse effects may include lowering the dose, adjusting the dosing schedule, switching to a different antipsychotic treatment, or using concomitant medications to address the adverse effects [25].

Lurasidone in the Treatment of FEP

Lurasidone received marketing approval for the treatment of schizophrenia in Europe in 2014 [11], and is currently the only antipsychotic licensed for use in adolescents aged 13 and over. Its complex pharmacology includes antagonist activity at dopaminergic D2 receptors and 5-hydroxytryptamine receptors (5-HT2A and 5-HT7) and partial agonism at the 5HT-1A receptor, which together may contribute to its beneficial effects in FEP [13]. Notably, lurasidone does not bind to histaminergic or muscarinic receptors, which may account for a lower incidence of weight gain compared with other antipsychotics [27, 28].

Efficacy of Lurasidone in Patients with Psychotic Disorders

Patients with schizophrenia exhibit symptoms across multiple domains, including perception, cognition, mood, and behavior. Lurasidone has demonstrated efficacy across the spectrum of schizophrenia symptoms, including positive symptoms, disorganized thought, hostility/excitement, and depression/anxiety [29].

Efficacy in Reducing Positive Symptoms

The efficacy of lurasidone (37–148 mg/day) in reducing positive symptoms has been demonstrated following acute and long-term treatment of adults with schizophrenia across a number of clinical studies [30–36]. Two network meta-analyses have shown similar efficacy between lurasidone and other atypical antipsychotics in this regard [37, 38]. The efficacy of lurasidone at 37–74 mg/day has also been demonstrated in adolescent patients with schizophrenia in a 6-week, double-blind, placebo-controlled trial [39]. In a post hoc analysis, the efficacy of lurasidone in reducing Positive and Negative Symptom Scale (PANSS) scores in adolescent patients with schizophrenia was found to be greater in treatment-naïve patients than in previously treated patients, suggesting the effectiveness of lurasidone in FEP [40]. In Table 1, we present the case of a 15-year-old male with psychotic symptoms who showed complete remission and unremarkable side effects following treatment with lurasidone 37 mg/day (Table 1, Case 1).

Table 1.

Patient case studies highlighting lurasidone treatment for first-episode psychosis

Case no.	Treating physician	Patient	Symptoms	Initial treatments	Lurasidone maximum dose (mg/day)	Follow up
1	Dr Arango	15-year-old male	Isolation, depressive mood, agitation, self-harm, delusion, hallucinations	Treatment-naïve	37	Discharged from hospital after 3 weeks; referred to outpatient clinic (once monthly); back at school with no residual positive symptoms and no side effects from lurasidone
2	Dra Pinto	17-year-old female	Autolytic ideation, depressed mood with delusional ideas of persecution and insomnia with frequent awakenings	Previously treated with aripiprazole, risperidone, and olanzapine, with low response	55.5	Attenuation of delusional symptoms and improvement in mood; disappearance of autolytic ideas
3	Dra Pinto	30-year-old male	Delusions, hallucinations, hypotimia, anxiety, cannabis use disorder	Risperidone, aripiprazole, cariprazine, and clonazepam	111	Good control of psychotic and anxiety symptoms; abstinence to cannabis
4	Dr Martin	71-year-old male	Delusions, hallucinations, psychotic behavior	Risperidone 12 mg/day, clonazepam 4 mg/day, and lormetazepam 2 mg/day Discharged after 2 weeks but presented in outpatient clinic with psychomotor retardation, functional deterioration, and signs of parkinsonism	148	After 2 weeks of lurasidone, extrapyramidal symptoms, functionality, and psychotic symptoms improved
5	Dra Marsá	35-year-old female	Delusions, hallucinations, disorganized thought	Paliperidone i.m. due to lack of adherence to oral medication; amenorrhea, galactorrhea and sexual dysfunction appeared	92.5 mg	Decrease in hyperprolactinemia symptoms, improved galactorrhea, and recovery of menstrual cycle; improvement in psychotic symptoms (hallucinations, delusions) and in patient's quality of life

Efficacy in Reducing Depressive Symptoms

Lurasidone has also demonstrated efficacy in reducing depressive symptoms in patients with schizophrenia [15, 41]. Depression is common in FEP and has been shown to predict a lower likelihood of psychosis remission during a 10-week follow-up [42]. In addition, suicide risk is higher in FEP compared with other periods of pyschosis, and depressive symptoms appear to be one of the most important drivers for the increased suicide risk in this population [43].

A recently published case study has reported clinical and functional improvement 3 months after the initiation of lurasidone in a 19-year-old man with FEP and predominant depressive symptoms [44]. Treatment with lurasidone led to disappearance of the depressive symptoms and a dramatic reduction in psychotic symptoms, with good tolerance to treatment. In Table 1, we illustrate the case of a 17-year-old female with autolytic ideation and low response to previous antipsychotics who showed a reduction in depressive symptoms with lurasidone 55.5 mg/day (Table 1, Case 2). This case suggests that lurasidone is a promising treatment in patients with FEP and depressive symptomatology, in line with recent studies [15, 41, 45].

Efficacy in FEP Associated with Substance Use

Substance use is strongly associated with the development of psychotic disorders [46], leading to psychoses characterized by increased alterations in consciousness, dissociative states, frequent hallucinations, and often aggressive or disruptive behavior [47]. With its broad pharmacological profile, lurasidone has the potential to interact with multiple pathways linked to psychotic symptoms in these patients. In a real-world study of patients with concurrent schizophrenia spectrum disorder and alcohol/substance use disorder (SUD), lurasidone provided a beneficial decrease in psychopathological burden, positive symptoms, and substance craving in participants using cannabis, alcohol, cocaine, or LSD [48]. Similarly, Ricci et al. have published a case series highlighting the utility of lurasidone in patients with substance-induced FEP [47]. Four patients, aged 20–25 years and presenting with cannabis-induced psychosis and increasing symptoms, were treated with lurasidone (74–148 mg/day). Despite heterogeneity in the clinical manifestation of cannabis-induced FEP among the patients, they all showed improvement in the clinical nature of their psychosis, with improvements in positive and negative symptoms and in global functioning over time. In addition, no significant side effects were reported with lurasidone [47]. In Table 1, we present the case of a 30-year-old male with cannabis use disorder, which highlights the efficacy of lurasidone in providing good control of psychotic, affective symptomatology, and abstinence to substance use (Table 1, Case 3).

Lurasidone Safety Profile

Acute and long-term treatment of patients with lurasidone is well tolerated across clinical studies [30–36]. Known adverse effects associated with lurasidone include somnolence and akathisia [49, 50], both of which are manageable. Initial sedation observed with lurasidone may be beneficial in patients with acute symptoms. In common with several other antipsychotic agents, lurasidone has been associated with hyperprolactinemia [50], which can lead to sexual side effects. However, increases in prolactin levels with lurasidone are minimal compared with risperidone and paliperidone [50], and prolactin levels are reduced on switching from risperidone to lurasidone [51]. Lurasidone is associated with a reduced risk of weight gain compared with other atypical antipsychotic medications in both adult and adolescent patients [38, 52, 53]. A network meta-analysis of randomized controlled trials showed less weight gain with lurasidone compared with other atypical antipsychotic monotherapies in adolescent patients with schizophrenia [38]. Similarly, a real-world, retrospective analysis of 15,323 adults with schizophrenia indicated a lower risk of clinically relevant weight gain with lurasidone compared with other commonly used antipsychotics [52]. The low risk of weight gain seen with lurasidone probably reflects its lack of binding to histaminergic and muscarinic receptors [11]. Lurasidone’s manageable safety profile is highlighted by high treatment retention rates. It is associated with better adherence rates and a lower risk of all-cause discontinuation compared with other atypical antipsychotic treatments [38, 54]. In an Italian real-world study, persistence with lurasidone was high, with 78% of patients with schizophrenia still on lurasidone after 6 months of treatment [55]. Importantly, lurasidone has demonstrated long-term safety in adolescents with schizophrenia, who will likely require treatment over the long term [56]. Finally, tolerability of lurasidone is demonstrated in all of the patient cases highlighted in Table 1, with cases 2 and 3 demonstrating how lurasidone can reverse weight gain caused by previous antipsychotic medications.

Long-Term Treatment in Young Patients

Lurasidone has demonstrated sustained efficacy and safety in long-term treatment settings [37, 52], which is particularly evident in young populations [57]. Correll et al. have shown that lurasidone effectively manages symptoms in adolescents with schizophrenia over the long term, emphasizing its potential for early intervention [58], while its minimal side effects suggest that it is a practical option for maintenance treatment [56]. A recent pooled analysis of two 12-month extension studies further supports these findings, highlighting lurasidone’s balance of efficacy and tolerability in adolescents and young adults with schizophrenia, and its potential for sustained use across diverse psychiatric conditions [59].

Dosage

Clinicians should ensure that an adequate dosage of lurasidone is administered to patients to maximize clinical benefit [20]. The recommended starting dose of lurasidone is 37 mg once daily and the maximum daily dose is 74 mg in adolescents and 148 mg in adults [11]. In our experience, lurasidone is frequently administered below the recommended dose, possibly due to a lack of awareness of appropriate dosing schedules or overcautiousness when using a lesser-known drug. In either case, the effectiveness of lurasidone may be compromised. A randomized, controlled trial in patients hospitalized with acute schizophrenia found that increasing the lurasidone dose from 80 to 160 mg/day provided significantly greater improvement in schizophrenia symptoms in early non-responders compared with continuing the initial dose [60]. Similarly, in a pooled analysis of short-term placebo-controlled studies in patients with schizophrenia, the maximum daily dose of lurasidone was the most efficacious across all five domains of PANSS [29]. Notably, a post hoc analysis of pooled data from five short-term, randomized, controlled trials found that the benefit of higher doses of lurasidone is more apparent in patients with more severe agitation based on PANSS-Excited Component (PANSS-EC) scores [61]. In this study, lurasidone significantly reduced agitation from Days 3/4 to Week 6 in patients with an acute exacerbation of schizophrenia and high levels of agitation (often associated with substance use-related psychotic behavior [47]), and lurasidone 120–160 mg/day was particularly effective in patients with more severe agitation at baseline [61].

In Table 1, we highlight the case of a 71-year-old male with severe deterioration and a history of side effects with prior antipsychotic medication (Table 1, Case 4). In this patient, lurasidone at its maximum dose (148 mg/day) was effective in controlling agitation and aiding functional recovery.

Comparison with Other Antipsychotic Agents for FEP

Compared with other antipsychotics, lurasidone demonstrates similar efficacy in reducing psychotic symptoms while offering distinct advantages, such as minimal metabolic side effects, including lower risks of weight gain and dyslipidemia [62]. Additionally, it is less likely to cause extrapyramidal symptoms and has shown promising outcomes in improving both negative and depressive symptoms [33]. In comparison with other second-generation antipsychotics, lurasidone has shown similar effectiveness, with the exception of clozapine [50, 63]. Compared with brexpiprazole and cariprazine, lurasidone has shown similar efficacy and safety outcomes, with the 160-mg dose showing superiority for changes in PANSS and Clinical Global Impression-Severity scores [63]. Lurasidone has a favorable side-effect profile, with significantly less weight gain and metabolic disturbances compared with olanzapine, quetiapine, and risperidone [38]. Hyperprolactinemia, which is a concern with many antipsychotics, occurs at a lower frequency with lurasidone compared with risperidone and paliperidone [38]. However, akathisia has been reported in approximately 12.7% of patients treated with lurasidone, which is higher than with some other second-generation antipsychotics [e.g., asenapine (6.8%)], although lower than with cariprazine (17.2%) [64]. Akathisia with lurasidone is generally mild and manageable [32]; strategies to manage akathisia include dose reduction, slower titration, or the addition of beta-blockers or benzodiazepines as needed [20]. Overall, the characteristics of lurasidone help to position it as a potentially valuable treatment option for patients with FEP, and in particular those requiring long-term management.

Treatment Switching

Treatment switching to lurasidone is an option in patients who experience a lack of efficacy or intolerable adverse effects with other antipsychotic treatments. For example, patients switched from olanzapine to lurasidone have shown significant reductions in body weight and improvements in metabolic parameters after 6 months of treatment [65]. Similarly, after switching from risperidone to lurasidone, patients with schizophrenia have shown reductions in weight, metabolic parameters, and prolactin levels, while maintaining improvements in PANSS total score [51, 66]. The elderly patient highlighted above (Table 1, Case 4) switched to lurasidone due to parkinsonism exhibited with risperidone-based antipsychotic treatment. After 2 weeks of treatment with 148 mg/day lurasidone, he showed an improvement in extrapyramidal effects, functionality, and psychotic symptoms. We also highlight the case of a 35-year-old female who experienced amenorrhea, galactorrhea, and sexual dysfunction associated with hyperprolactinemia while receiving paliperidone for psychotic symptoms (Table 1, Case 5). Following a switch to lurasidone, this patient’s hyperprolactinemia and psychotic symptoms both improved. While data to support switching of different antipsychotic medications are sparse, switching to lurasidone is supported by several studies, as highlighted by a recent systematic review [67].

Contraindications

Both lurasidone and its active metabolite are primarily metabolized by CYP3A4. Lurasidone is contraindicated with strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, cobicistat, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole). Coadministration of lurasidone with medicinal products that moderately inhibit CYP3A4 (e.g., diltiazem, erythromycin, fluconazole verapamil) may increase exposure to lurasidone. Lurasidone is also contraindicated with strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampicin, and St John’s wort [Hypericum perforatum]). Coadministration of lurasidone with mild (e.g. armodafinil, amprenavir, aprepitant, prednisone, rufinamide) or moderate (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) inducers of CYP3A4 would be expected to reduce exposure to lurasidone [11].

Limitations

To date, the information available on lurasidone in the context of FEP is limited to clinical case reports [47]. The case studies included in this review are intended to complement the existing body of literature in the broader schizophrenia population and to provide real-world insights into the use of lurasidone in this specific population. However, we acknowledge that case studies are anecdotal and are presented here as part of a broader effort to address the significant gaps in evidence for lurasidone in FEP. In support of this approach, a systematic review has suggested that the effects of antipsychotics in various patient subgroups are generally similar to those observed in the broader population of patients with schizophrenia [68]. Some conclusions in this review are based on retrospective or post hoc analyses, which are inherently subject to selection bias and limited by the lack of control over confounding variables. Unlike prospective, randomized controlled trials, these study designs cannot establish causality and may reflect pre-existing patient characteristics or treatment conditions rather than the true effects of the intervention. Additionally, the absence of randomization and potential for incomplete data further restrict the generalizability of these findings. There is therefore a need for prospective, controlled studies to validate these observations and to provide a more robust evidence base for the use of lurasidone in FEP.

Conclusions

Lurasidone is a new antipsychotic drug which has demonstrated efficacy and tolerability in both the acute phase of schizophrenia and as maintenance treatment to reduce the risk of relapse. As the duration of untreated psychosis is associated with poor clinical outcomes, FEPs should be treated as soon as the disease is diagnosed [21, 22]. Based on its favorable efficacy and safety profile, including minimal metabolic side effects, and its approval for use in adolescents aged 13 years and over, lurasidone represents a valuable treatment option for patients with FEP, particularly in populations where tolerability and long-term safety are critical considerations. There is a broad experience with lurasidone in clinical practice, both as a first-line treatment and after switching from other antipsychotic drugs. Real-world case studies presented here suggest that lurasidone has utility in a range of FEP scenarios, including treatment-naïve patients, patients with agitation and/or aggressiveness, those requiring a switch from other antipsychotic medications on account of low efficacy or poor tolerability, and patients with substance-induced psychosis. Lurasidone may be particularly beneficial in FEP with prominent affective symptoms.

Due to the high variability of conditions and symptoms encompassed in psychosis, there is no homogeneity in the way patients are treated with lurasidone. Selecting the correct dose of lurasidone is key to maximizing efficacy, but, in real-world settings, the dosage of lurasidone is suboptimal in many cases of FEP. According to the European label [11], lurasidone is effective in a dose range of 37–148 mg/day, but the maximum daily dose of lurasidone has been shown to be the most effective across all five domains of PANSS [29]. In clinical practice, the maximum doses are reached within 1–5 days of treatment, depending on tolerability [20].

A systematic review and meta-analysis of data from randomized controlled trials in the general population (including adults, adolescents, and children) suggests that second-generation antipsychotics differ to a greater extent in their tolerability profiles than in their antipsychotic efficacy. Thus, lurasidone, with its good tolerability profile, is well positioned among antipsychotics that minimize clinically significant side effects such as metabolic syndrome, hyperprolactinemia, or parkinsonism [68].

In conclusion, our experience indicates that lurasidone has efficacy in FEP in different patient profiles, including those with SUD, and provides clinically relevant benefits with a good tolerability profile.

Author Contributions

Miquel Bernardo designed and created the first draft of the manuscript and collated feedback from the other authors. Miquel Bernardo, Marina Díaz Marsá, Ana González-Pinto, Manuel Martín Carrasco, Víctor Pérez Sola, Pilar Alejandra Sáiz, Eduard Vieta, Marta Torrens, Celso Arango and Benedicto Crespo-Facorro provided feedback for the subsequent drafts and approved the final version of the manuscript.

Funding

This paper was funded by unrestricted support from Angelini Pharma, including the study and open-access fee. The company had no influence on article content.

Declarations

Conflict of Interest

Miquel Bernardo has received grants and/or served as a consultant, advisor or speaker for AB-Biotics, Abartis Pharma, Adamed, Angelini Pharma, Casen Recordati, Esteve, Janssen-Cilag, Menarini, Rovi and Takeda. Marina Díaz Marsá has received grants and/or served as a consultant, advisor or speaker for Alter, Angelini, Idorsia, Janssen-Cilag, Lundbeck, Novartis, Otsuka, Rovi, Takeda, the Ministry of Science (Carlos III Institute), the Basque Government, and the European Framework Program of Research. Ana González-Pinto has received grants and/or served as a consultant, advisor or speaker for Janssen-Cilag, Lundbeck, Otsuka, Alter, Angelini, Novartis, Rovi, Takeda, Servier, the Spanish Ministry of Science and Innovation (CIBERSAM), the Ministry of Science (Carlos III Institute), the Basque Government, and the European Framework Program of Research. Manuel Martín Carrasco has received grants and served as a consultant, advisor or CME speaker for Angelini, Esteve, Idorsia, Janssen-Cilag, Lundbeck, Novartis, Pfizer, Rovi, the Ministry of Science (Carlos III Institute), and the Navarra Government. Víctor Pérez Sola has received grants and/or served as a consultant, advisor or speaker for AB-Biotics, AstraZeneca, Bristol-Myers-Squibb, Johnson & Johnson, Lundbeck, Medtronic, Otsuka, and Servier. Pilar Alejandra Sáiz has received grants and/or served as a consultant, advisor or speaker for Adamed, Alter Medica, Angelini Pharma, CIBERSAM, Ethypharm Digital Therapy, European Commission, Government of the Principality of Asturias, Instituto de Salud Carlos III, Johnson & Johnson, Lundbeck, Otsuka, Pfizer, Plan Nacional Sobre Drogas and Servier. Eduard Vieta has received grants and/or served as a consultant, advisor or speaker for AB-Biotics, AbbVie, Adamed, Angelini Pharma, Biogen, Beckley-Psytech, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, GlaxoSmithKline, HMNC, Idorsia, Johnson & Johnson, Lundbeck, Luye Pharma, Medincell, Merck, Neuraxpharm, Newron, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, Teva, and Viatris. Marta Torrens has received grants and/or served as a consultant, advisor or speaker for Adamet, Angelini Pharma, Camurus, Lundbeck, Otzuka, and Servier. Celso Arango has received grants and/or served as a consultant, advisor or speaker for Acadia, Ambrosetti S.p.A, Angelini, Bristol-Myers Squibb, Comunidad de Madrid, Fundación Alicia Koplowitz, Fundación Familia Alonso, Fundación Mutua Madrileña, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Ministerio Educación, Otsuka, Rovi, Stanley Foundation, Sunovion, Teva, and Takeda. Benedicto Crespo-Facorro has received grants and/or served as a consultant, advisor or speaker for Angelini, Johnson & Johnson, Lundbeck, Otsuka, and Rovi.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.