Antipsychotic Drugs: A Concise Review of History, Classification, Indications, Mechanism, Efficacy, Side Effects, Dosing, and Clinical Application.

The introduction of the first antipsychotic drug, chlorpromazine, was a milestone for psychiatry. The authors review the history, classification, indications, mechanism, efficacy, side effects, dosing, drug initiation, switching, and other practical issues and questions related to antipsychotics. Classifications such as first-generation/typical versus second-generation/atypical antipsychotics are neither valid nor useful; these agents should be described according to the Neuroscience-based Nomenclature (NbN). Antipsychotic drugs are not specific for treating schizophrenia. They reduce psychosis regardless of the underlying diagnosis, and they go beyond nonspecific sedation. All currently available antipsychotic drugs are dopamine blockers or dopamine partial agonists. In schizophrenia, effect sizes for relapse prevention are larger than for acute treatment. A major unresolved problem is the implausible increase in placebo response in antipsychotic drug trials over the decades. Differences in side effects, which can be objectively measured, such as weight gain, are less equivocal than differences in rating-scale-measured (subjective) efficacy. The criteria for choosing among antipsychotics are mainly pragmatic and include factors such as available formulations, metabolism, half-life, efficacy, and side effects in previous illness episodes. Plasma levels help to detect nonadherence, and once-daily dosing at night (which is possible with many antipsychotics) and long-acting injectable formulations are useful when adherence is a problem. Dose-response curves for both acute treatment and relapse prevention follow a hyperbolic pattern, with maximally efficacious average dosages for schizophrenia of around 5 mg/day risperidone equivalents. Computer apps facilitating the choice between drugs are available. Future drug development should include pharmacogenetics and focus on drugs for specific aspects of psychosis.

Beneficial adjunctive effects of the 5HT3 receptor antagonist ondansetron on symptoms, function and cognition in early phase schizophrenia in a double-blind, 2 × 2 factorial design, randomised controlled comparison with simvastatin.

BACKGROUND: Variable benefits have been reported from the adjunctive use of simvastatin and the 5HT3 receptor antagonist, ondansetron, in patients with schizophrenia. We investigated their independent efficacy and possible synergy to improve negative symptoms of schizophrenia within a single trial. METHODS: A 6-month, randomised, double-blind, placebo-controlled trial with a 4-arm, 2 × 2 factorial design, in three centres in Pakistan. In total, 303 people with stable treated schizophrenia aged 18-65 were randomly allocated to add-on ondansetron, simvastatin, both or neither. The primary outcome was a Positive and Negative Syndrome Scale (PANSS) negative score at 3 and 6 months. RESULTS: Mixed model analysis and analysis of covariance revealed no main effects of simvastatin or ondansetron but a significant negative interaction between them (p = 0.03); when given alone, both drugs significantly reduced negative symptoms compared to placebo but they were ineffective in combination. Individual treatment effects versus placebo were -1.9 points (95%CIs -3.23, -0.49; p = 0.01) for simvastatin and -1.6 points for ondansetron (95%CIs -3.00, -0.14; p = 0.03). Combined treatment significantly increased depression and side effects. In those with less than the median 5 years of treatment, ondansetron improved all PANSS subscales, global functioning measures and verbal learning and fluency, whereas simvastatin did not. CONCLUSION: Small improvement in negative symptoms on simvastatin and ondansetron individually are not synergistic in combination in treating negative symptoms of schizophrenia. Ondansetron showed broad efficacy in patients on stable antipsychotic treatment within 5 years of illness. The findings suggest that ondansetron should be evaluated in patients at risk of psychosis or early in treatment.

Psychopharmacotherapy of Pica-How Much Do We Know?

There is little evidence for psychopharmacotherapy in pica. A few studies reported some benefit from the use of SSRIs, atypical antipsychotics and methylphenidate. That said, evidence to deploy these agents remains, at large, flimsy. Here, despite scarcity, we review available literature and draw some generalities that can inform decision-making on clinical grounds.

Metabolic Syndrome among Patients Taking Atypical Antipsychotics: A Comparative Cross-Sectional Study at Erada and Mental Health Complex in Taif, Saudi Arabia.

Introduction: Second-Generation Antipsychotics (SGAs) are widely used for treating psychiatric disorders due to their favorable side effect profile compared to First-Generation Antipsychotics (FGAs). However, SGAs are associated with significant metabolic side effects. This study aims to explore the sociodemographic and health differences between individuals using SGAs and those not using them. Methods: A comparative cross-sectional study was conducted with 148 participants, including 102 SGA users and 46 non-users. Data were collected from patients and medical records, encompassing sociodemographic factors and health variables including diabetes mellitus, hypertension, cardiovascular disease, hyperlipidemia, waist circumference, fasting blood glucose, cholesterol, triglycerides, HDL, LDL, and BMI. Statistical analyses included chi-square and Fisher's exact tests to compare the two groups. Results: SGA users had higher rates of overweight and obesity compared to non-users (p = 0.000), with 30.4% overweight and 29.4% obese among SGA users versus 21.7% overweight and 4.3% obese among non-users. A higher prevalence of cardiovascular disease was observed in SGA users (11.8% vs. 2.2%, p = 0.076). Although not statistically significant, trends indicated higher rates of diabetes mellitus and hyperlipidemia in non-users (30.4% vs. 18.6%, p = 0.110 and 7% vs. 0%, p = 0.083, respectively). Conclusion: This study highlights significant differences in BMI and cardiovascular disease prevalence between SGA users and non-users, reinforcing the need for comprehensive metabolic monitoring in patients treated with SGAs. The findings underscore the importance of considering sociodemographic factors in managing the health risks associated with SGA use. Further research with larger sample sizes and longitudinal designs is warranted to better understand these associations and develop targeted interventions.

Sublingual Atropine Administration for Clozapine-Induced Sialorrhea in Bipolar Disorder: A Case Report Highlighting its Efficacy, Safety Concerns and Challenges.

We discuss a case with off-label sublingual administration of atropine for clozapine-induced sialorrhea (CIS) after failure of two commonly used agents to manage CIS. Atropine had a demonstrable efficacy, as measured by means of sialometry conducted before and after its administration. The salivary rate, initially measured at 0.60 g/min one hour before atropine administration, reduced to 0.23 g/min two hours after administration. Sublingual administration of atropine was found to be an efficacious option for this patient, but safety issues particularly tachycardia and pragmatics such as risk of inadvertent overdose led to its discontinuation after the initial dose. Developing micro-dosing devices for sublingual atropine could enhance administration precision, reduce side effects, and provide a cost-effective solution. The case report also underscores the need to employ sialometry for the objective assessment of treatment outcomes in future research trials for hypersalivation.

Preferences for attributes of oral antipsychotic treatments: results from a discrete-choice experiment in respondents with schizophrenia or bipolar I disorder.

BACKGROUND: Antipsychotic medications are effective treatments for schizophrenia (SZ) and bipolar I disorder (BD-I), but when presented with different treatment options, there are tradeoffs that individuals make between clinical improvement and adverse effects. As new options become available, understanding the attributes of antipsychotic medications that are valued and the tradeoffs that individuals consider when choosing among them is important. METHODS: A discrete-choice experiment (DCE) was administered online to elicit preferences across 5 attributes of oral antipsychotics: treatment efficacy (i.e., improvement in symptom severity), weight gain over 6 months, sexual dysfunction, sedation, and akathisia. Eligible respondents were aged 18-64 years with a self-reported clinician diagnosis of SZ or BD-I. RESULTS: In total, 144 respondents with SZ and 152 with BD-I completed the DCE. Of those with SZ, 50% identified themselves as female and 69.4% as White, with a mean (SD) age of 41.0 (10.1) years. Of those with BD-I, most identified themselves as female (69.7%) and as White (77.6%), with a mean (SD) age of 40.0 (10.7) years. In both cohorts, respondents preferred oral antipsychotics with better efficacy, less weight gain, no sexual dysfunction or akathisia, and lower risk of sedation. Treatment efficacy was the most important attribute, with a conditional relative importance (CRI) of 31.4% for respondents with SZ and 31.0% for those with BD-I. Weight gain (CRI = 21.3% and 23.1%, respectively) and sexual dysfunction (CRI = 23.4% and 19.2%, respectively) were adverse effects in this study that respondents most wanted to avoid. Respondents with SZ were willing to accept 9.8 lb of weight gain or > 25% risk of sedation for symptom improvement; those with BD-I were willing to accept 8.5 lb of weight gain or a > 25% risk of sedation. CONCLUSIONS: In this DCE, treatment efficacy was the most important attribute of oral antipsychotic medications among respondents with SZ and BD-I. Weight gain and sexual dysfunction were the adverse effects respondents most wanted to avoid; however, both cohorts were willing to accept some weight gain or sedation to obtain better efficacy. These results highlight features that patients value in antipsychotic medications and how they balance benefits and risks when choosing among treatments.

Aripiprazole/Sertraline Combination: Clinical and Cost-Effectiveness in Comparison With Quetiapine for the Treatment of Bipolar Depression (ASCEnD Trial)-Protocol for a Nested Qualitative Study.

INTRODUCTION: Bipolar disorder is a recurrent mental health disorder with a prevalence rate of 1.4%. On average, there can be a delay of 9.5 years from the initial presentation of symptoms to a confirmed diagnosis. Individuals living with bipolar disorder have a reduced life expectancy. There is limited evidence regarding the effectiveness of antidepressants in treating bipolar disorder. The ASCEnD clinical trial will test the clinical and cost-effectiveness of the aripiprazole/sertraline combination in comparison with quetiapine for the treatment of bipolar depression (individuals who suffer from depressive episodes in bipolar disorder) and will include a nested qualitative study. METHODS: The qualitative study will use semi-structured interviews to explore pilot trial participants' and clinicians' perspectives on recruitment procedures, the acceptability of the intervention, the management of bipolar disorder and attitudes to medication combinations. CONCLUSION: Findings will inform recruitment strategies and optimise training for the participating sites in the ASCEnD full trial. They will also help to illuminate the lived experience of people with bipolar disorder and the clinicians who work with people with bipolar disorder. The discussion will explore perspectives on the delay in diagnosis, having a diagnosis, the impact of living with bipolar disorder and attitudes to treatment, including drug combinations. PATIENT OR PUBLIC CONTRIBUTION: A Lived Experience Advisory Panel (LEAP) has been convened with the support of the McPin Foundation, which will contribute to the ASCEnD trial and its nested qualitative study to provide input on the design and delivery of the trial and qualitative study, analysis of qualitative data and dissemination of findings.

Challenging pharmacotherapy management of a psychotic disorder due to a delicate pharmacogenetic profile and drug-drug interactions: a case report and literature review.

This report presents challenging psychopharmacotherapy management of a psychotic disorder in a patient with a delicate pharmacogenetic profile and drug-drug interactions. A 31-year old woman diagnosed with schizophrenia in 2017 was referred by her psychiatrist to a clinical pharmacologist for interpretation of a pharmacogenetic test and advice regarding optimal psychopharmacotherapy. In spite of adherence to aripiprazole, olanzapine, risperidone, and levomepromazine, and rational anxiolytic therapy, she still experienced anxiety, anhedonia, loss of appetite, sleeping problems, and auditory hallucinations with commands to harm herself. Due to a lack of alternative therapeutic steps, low aripiprazole serum concentrations, and a lack of explanation for pharmacotherapy unresponsiveness, pharmacogenetic testing was performed. The patient was defined as CYP2D6 *1/*1, CYP1A2 *1F/*1F, CYP3A4 *1/*1B, CYP3A5 *1/*3, and having increased activity of the enzymes UGT1A4 and UGT2B7, intermediate activity of ABCB1 transporter, and low activity of COMT. Carbamazepine was discontinued, aripiprazole was increased to a maximum of 30 mg/day orally with long-acting injection (400 mg monthly), and olanzapine was increased to a daily dose of 35 mg orally. These changes led to an optimal therapeutic drug concentration and improved clinical status. At the last follow-up, the patient was without severe auditory hallucinations, became more engaged in daily life, had more interaction with others, had found a job, and even had started an emotional relationship. In psychiatry, pharmacogenetic testing is an important tool for guiding pharmacological therapy, particularly in patients with an unsatisfactory clinical response and a lack of alternative therapeutic steps for pharmacotherapy unresponsiveness.

Antipsychotic Treatment in People at Clinical High Risk for Psychosis: A Narrative Review of Suggestions for Clinical Practice.

PURPOSE: The "early intervention" paradigm in psychiatry holds significant promise for preventing psychosis. Recent evidence showed that individuals at clinical high risk for psychosis (CHR-P) with antipsychotic (AP) prescription at baseline have higher psychosis transition rates compared with those without AP, although the underlying cause remains unclear. In this article, we reviewed international guidelines on early intervention in CHR-P people, paying specific attention to clinical recommendations on AP treatment. Then, we comment on these suggestions in the light of recent empirical evidence examining AP prescription in CHR-P populations within "real-world" clinical settings. METHODS: This search was conducted on PubMed/MEDLINE, PsycINFO, EMBASE, and Google, looking for both "Guidelines AND CHR-P OR UHR OR Early Psychosis." RESULTS: International guidelines generally recommend not using AP as first-line treatment, but only when psychosocial interventions have failed. CHR-P people with AP drug showed high prevalence rates and had more severe clinical picture at entry. Is this a "warning signal" for potentially higher psychosis transition risk? Is it a direct AP iatrogenic effect? Is it possible to detect specific CHR-P subgroup that may benefit from AP? These are the questions that this article seeks to explore. CONCLUSIONS: The current framework for identifying CHR-P subjects has defined psychometric criteria mainly based on positive symptoms. In our opinion, this is reductive, especially for evaluating therapeutic outcomes and prognosis. A more comprehensive assessment considering quality of life, psychiatric comorbidity, persistent negative symptoms, subjective experience of CHR-P psychopathology, and social/personal recovery is thus needed.

Quetiapine-induced urinary retention.

A 22-year-old woman, known to have a BMI of 12 kg/m2 and a personality disorder, developed urinary retention on a normal dose of quetiapine. She had earlier tolerated a dose of 800 mg quetiapine without complications. The daily dose was 600 mg in combination with oxazepam and zolpidem. Reduction had no effect. The patient intervened with intermittent urinary catheterization the next 19 months. Normal urinary function returned three days after the last dose of quetiapine 25 mg. This case report shows that patients with a low BMI may be more receptive of the anticholinergic effects of quetiapine.

Disability and Adverse Effects of Oral Versus Long-Acting Injectable Antipsychotics in Schizophrenia-Spectrum and Bipolar Disorder: A Comparison Based on Data-Driven Taxonomy.

BACKGROUND: Patients undergoing antipsychotic treatment for psychiatric disorders may experience challenges in functioning, either stemming from the severity of the illness or from the tolerability issues of prescribed medications. OBJECTIVES: The aims of this cross-sectional study are to investigate the impact of adverse effects of antipsychotic drugs on patients' daily life functioning, comparing oral and long-acting injectable (LAI) antipsychotics, and further dividing antipsychotics by receptor-binding profiles based on recently defined data-driven taxonomy. METHODS: This study involved patients with schizophrenia and bipolar spectrum disorders taking oral or LAI antipsychotics. Disability and functioning levels were assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and the adverse effects of medications were evaluated using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and its subscales. RESULTS: The total sample consisted of 126 participants with a diagnosis of schizophrenia-spectrum or bipolar disorder, and included 54 males and 72 females ranging from 18 to 78 years of age (mean 45.1, standard deviation 14); 78 patients were taking oral antipsychotics and 48 were taking LAI antipsychotics, with subcategories of muscarinic (31), adrenergic/low dopamine (25), serotonergic/dopaminergic (23), dopaminergic (1), LAI muscarinic (15), LAI adrenergic (6), and LAI serotonergic/dopaminergic (25). The UKU total score for adverse effects showed significant correlations with WHODAS total score (ρ = 0.475; p < 0.001). Compared with oral antipsychotics, LAIs showed significantly lower scores in psychological (p = 0.014), autonomic (p = 0.008), other (p = 0.004), and sexual adverse effects (p = 0.008), as well as the UKU total score (p = 0.002). The Kruskal-Wallis test showed a significant difference in adverse effects between LAI and oral muscarinic subgroups, with LAIs having lower scores compared with antipsychotics binding to muscarinic receptors (p = 0.043). CONCLUSION: These findings indicate clinically relevant differences in adverse effects among formulations, warranting further investigation for future observational studies.

Association of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine versus patients treated with olanzapine, risperidone, or quetiapine: A systematic review and meta-analysis.

INTRODUCTION: Many articles suggest that clozapine was strongly associated with a higher incidence of new-onset diabetes mellitus, and the issue has remained unsettled. Many articles have compared clozapine with FGAs, but few have compared clozapine with SGAs. We aimed to compare the risk of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine and other SGAs. METHODS: We conducted a comprehensive search of databases from their inception up until August 26, 2023. The specific databases include PubMed, Embase and others. We included non-randomized controlled trials involving the use of SGAs such as clozapine, olanzapine, risperidone, quetiapine, amisulpride, and zotepine, with a focus on new-onset diabetes mellitus as an outcome. We utilized odds ratio with 95 % credible intervals (95 % CI) as our effect size measures. The study protocol is registered with PROSPERO, number CRD42024511280. RESULTS: We included 7 studies with sufficient data to include in the meta-analysis. A total of eight studies with 641,48 participants met the eligibility criteria. The OR of the incidence rates of new-onset diabetes between clozapine and olanzapine was 0.95 (95 % CI:[0.82-1.09]), between clozapine and risperidone was 1.25 (95 % CI: [1.09-1.44]), between clozapine and quetiapine was 1.44 (95 % CI: [0.92-2.25]). CONCLUSION: In patients with schizophrenia, clozapine has been found to have a higher rate of new-onset diabetes mellitus compared to risperidone. However, there was no significant difference in incidence rate between clozapine versus olanzapine and quetiapine. These findings can assist clinicians in balancing the risks and benefits of those drugs.

Evaluation of Clinical Correlation between Insulin Resistance and Antipsychotic Drug Therapy in Patients with Schizophrenia.

BACKGROUND: Treatment with different antipsychotics can lead to various metabolic side effects in patients with psychosis, impacting long-term prognosis. This study aimed to compare the changes and clinical efficacy of insulin resistance in patients treated with olanzapine and ziprasidone. METHOD: A retrospective analysis was conducted on the clinical data of 80 patients with schizophrenia. The patients were divided into olanzapine treatment group and ziprasidone treatment group. Parameters including body weight, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin resistance index, and Positive and Negative Syndrome Scale (PANSS) scores were recorded and compared before and after treatment. RESULTS: BMI, FPG, FPI, homeostatic model assessment of insulin resistance (HOMA-IR), CHO, TG and LDL in both groups were significantly higher than before treatment (p < 0.05). These parameters were significantly higher in the olanzapine group than in the ziprasidone group (p < 0.05). The level of HDL in both groups was significantly decreased after treatment, and the level of HDL in the olanzapine group was significantly lower than that in the ziprasidone group after treatment (p < 0.05). After treatment, the total score and score of PANSS in both groups were significantly lower than before treatment (p < 0.05). After treatment, there was no significant difference in total score and PANSS score between both groups (p > 0.05). The incidence of insulin resistance (IR) was significantly higher in the olanzapine group compared to the ziprasidone group (χ2 = 4.021, p < 0.05). In the IR group, BMI, FPG, FPI, TG, and LDL levels were higher than in the non-IR group (p < 0.05). Multivariate analysis indicated that BMI, FPG, FPI, TG, and LDL were independent risk factors for IR (odd ratio (OR) >1, p < 0.05). CONCLUSIONS: Treatment with olanzapine and ziprasidone improves clinical symptoms in patients with schizophrenia, but increases the risk of insulin resistance. The metabolic side effects of olanzapine are more pronounced.

Plasma Clozapine and N -Desmethylclozapine (Norclozapine) Concentrations and the Clozapine/Norclozapine Ratio : Effect of Dose, Sex, and Cigarette Smoking.

BACKGROUND: Smoking enhances plasma clozapine clearance, but the magnitude of the effect across the dose and age ranges is unclear. METHODS: We audited clozapine dose and predose plasma clozapine and N -desmethylclozapine (norclozapine) concentrations by sex and smoking habit in samples submitted for clozapine TDM, 1996-2017. RESULTS: There were 105,316/60,792 and 34,288/31,309 samples from male/female smokers/nonsmokers, respectively. There were distinct dose-median plasma concentration trajectories for male/female smokers/nonsmokers across the range <50 to >850 mg d -1 . For both sexes, the percentage difference in median plasma clozapine in nonsmokers versus smokers averaged 50% but was greatest for men (76%) and women (59%) in the 151 to 250 mg d -1 dose band. In men, the percentage difference declined steadily to 34% at doses of ≥850 mg d -1 . In women, the difference after falling initially remained relatively constant at 40% to 54%. The pattern in median plasma clozapine/norclozapine ratio by plasma clozapine concentration and dose groups was independent of sex and smoking habit, but increased with plasma clozapine concentration (higher ratio at higher concentrations) and also changed with dose. Median plasma clozapine concentration and median clozapine dose by sex and smoking habit were similar up to age 60 years. Proportional weight gain was similar over time in smokers and nonsmokers of either sex. IMPLICATIONS: These data explain the variations in the effect size of starting or stopping smoking on plasma clozapine concentration at constant dose reported in different studies. Changes in smoking habit in patients prescribed clozapine require prompt dose adjustment.

An Updated Safety Review of the Relationship Between Atypical Antipsychotic Drugs, the QTc Interval and Torsades de Pointe As: Implications for Clinical Use.

INTRODUCTION: The rising prevalence of psychiatric disorders has resulted in a significant increase in the use of antipsychotic medications. These agents may prolong the corrected QT interval (QTc), running the risk of precipitating ventricular arrhythmias, notably Torsades de Pointes (TdP). Current recommendations vary regarding the optimal approach to safe prescribing practices and QTc surveillance for antipsychotics. This review summarizes the current literature addressing these clinical concerns. AREAS COVERED: The physiologic basis of the QTc interval, mechanisms underlying its susceptibility to pharmacological influence, specific risks associated with atypical antipsychotic agents, and recommendations for safe prescription practices. We performed a literature review using Pubmed and Embase databases, searching for 'antipsychotics' and 'torsades de pointes.' EXPERT OPINION: Finding a safe and universally accepted protocol for prescribing antipsychotics remains a persistent challenge in medicine. Predictive models that integrate clinical history with demographic and ECG characteristics can help estimate an individual's susceptibility to therapy-associated risks, including QTc prolongation. Agents such as ziprasidone and iloperidone are significantly more likely to prolong the QTc interval compared to others such as brexpiprazole, cariprazine, olanzapine, and clozapine. A personalized approach using low-risk medications when clinically feasible, and at the lowest efficacious dose, offers a promising path toward safer antipsychotic prescribing.

Antipsychotic medications are used to treat conditions such as schizophrenia and bipolar disorder; however, they can also affect cardiac electrical conduction. This effect on cardiac function increases the risk of a dangerous heart rhythm, which can potentially be fatal. Patients and doctors need to be aware of and monitor for these potential heart-related side effects, although antipsychotics can be very helpful for mental health conditions.

Efficacy and acceptability of long-acting antipsychotics in acutely ill individuals with schizophrenia-spectrum disorders: A systematic review and network meta-analysis.

To assess the effect of Long-acting injectable (LAI) antipsychotics in acutely ill patients, we systematically searched major databases for randomized controlled trials (RCTs) comparing LAIs with other LAIs, oral antipsychotics, or placebo in acutely symptomatic adults with schizophrenia-spectrum disorders. Data were analyzed with a random-effects network meta-analysis. Co-primary outcomes were efficacy (mean change in psychopathology rating scales) and acceptability (all-cause discontinuations) at study endpoint. Of 25 RCTs, 19 studies tested second-generation LAIs (SGA-LAIs) and six first-generation LAIs (FGA-LAIs). Due to a disconnected network, FGA-LAIs were analyzed separately, with poor data quality. The SGA-LAIs network included 8,418 individuals (males=63%, mean age=39.3 years). All SGA-LAIs outperformed placebo in reducing acute symptoms at study endpoint (median follow-up=13 weeks). They were more acceptable than placebo with the only exception of olanzapine, for which no differences with placebo emerged. Additionally, we distinguished between different LAI formulations of the same antipsychotic to explore potential pharmacokinetic differences. Most formulations outperformed placebo in the very short-term (2 weeks or less), regardless of the need for initial oral supplementation. SGA-LAIs are evidence-based treatments in acutely ill individuals with schizophrenia-spectrum disorders. Findings support the use of SGA-LAIs to manage psychopathology and improve adherence right from the acute phases of illness.