Antipsychotics (APs) have been increasingly prescribed for psychiatric disorders from schizophrenia to disruptive behavioral conditions. These drugs have been associated with considerable side effects, such as weight gain, and increasing evidence has also indicated that its use impacts gut microbiota (GM), although this connection is still little understood. To assess APs effects on the GM of patients starting or ongoing treatment, a systematic review was carried out in PubMed and Scopus databases. Twelve articles were considered eligible for the review, which investigated the effects of risperidone (5 studies), quetiapine (3), amilsupride (1), olanzapine (1), and unspecified atypical drugs (2). Eleven reported changes in GM in response to APs, and associations between the abundance of bacterial groups and different metabolic parameters were described by most of them. However, the studies were noticeably heterogeneous considering design, methods, and results. In this way, the effects of APs on GM composition and diversity were inconclusive. Despite the uncertain interactions, a more comprehensive understanding on how microbiota is affected by APs may help to optimize treatment, potentially minimizing side effects and improving adherence to treatment.

Background: As many as 60% of pediatric patients taking second-generation antipsychotics (SGA) experience weight gain (antipsychotic-induced weight gain). However, the subgroup that experienced substantial weight increase was poorly understood. This study aimed to identify the development and predictors of clinically significant weight gain (CSWG) among pediatric SGA recipients. Methods: A retrospective analysis of the 2016 to 2021 IQVIA Ambulatory EMR-US database was conducted. The study cohort comprised SGA-naive patients ages 5 to 19, continuously prescribed SGA for ≥90 days. CSWG was defined as a weight gain in BMI z-score >0.5. The development of CSWG was described using the group-based trajectory model approach, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the CSWG trajectories. Results: Of the 16,262 SGA recipients who met the inclusion criteria, 4 distinctive CSWG trajectories were identified: (1) Rapid (14.6%), (2) Gradual (12.6%), (3) Transit (7%), and (4) no CSWG (65.8%). Factors associated with a higher likelihood of having rapid or gradual CSWG versus nonsignificant weight gain were being younger (OR [95% CI] = 12-17 vs. 5-11, Rapid, 0.727 [0.655-0.806]; Gradual, 0.776 [0.668-0.903]), male (Rapid, 1.131 [1.021-1.253]), non-Hispanic White (Black vs. White: Rapid, 0.833 [0.709-0.98]), with lower baseline BMI z-score (Rapid, 0.376 [0.361-0.392]; Gradual, 0.449 [0.424-0.476]), and receiving olanzapine as the initial SGA (Rapid, 1.38 [1.093-1.74]). The Area under the Receiver operating characteristic (ROC) Curve for the comparison of rapid and gradual CSWG with no CSWG trajectory were 0.83 and 0.80, respectively. Conclusions: SGA recipients experienced four distinctive CSWG trajectories (Rapid, Gradual, Transient, and No CSWG). The risk of CSWG could be predicted using patient characteristics at the SGA initiation. This insight highlights the importance of personalized monitoring and timely intervention strategies for at-risk individuals who experienced persistent CSWG in real practice.

Background Major depressive disorder (MDD) has many facets including mixed or atypical depression that requires personalized care to improve treatment-related outcomes. Second-generation antipsychotics (SGAs) offer complementary mechanisms for clinical roles in difficult-to-treat depression and treatment-resistant depression cases. Aim/objective To further delineate a consensus on the clinical positioning of SGAs for MDD, mixed, or atypical depression, a Knowledge Attitude Perception (KAP)-mediated Delphi Statement was planned. Material/methods A literature review for the definition, diagnosis, and management of MDD, mixed, and atypical depression as treatment-resistant depression (TRD) or difficult-to-treat depression (DTD) was conducted by a steering committee of academic and clinical experts (n=6) while developing a validated KAP questionnaire. Scientific statements as clinical recommendations were evolved using the Delphi methodology before building a clinical expert consensus with an online survey (n=24). Results Twenty-four psychiatrists highlighted DTD to offer a multidimensional approach to assess treatment strategies involving selective serotonin reuptake inhibitors (SSRIs) or SGAs, while ensuring symptom, functional, and quality of life (QoL) domain improvement for improved outcomes and remission rates. MDD cases with anxiety, anhedonia, comorbidities, and risk traits require personalized care with early induction of SGAs for severe cases or symptom persisters with functional impairment. Early augmentation with SGAs including aripiprazole or cariprazine can provide a favorable risk-benefit profile for clinical cases of MDD with or without the antecedent of mixed depression or personality disorder.  Conclusion The literature review and KAP responses emphasize the importance of early identification for personalized care strategies with SGAs for DTD. Large-scale real-world evidence needs to evolve with due recognition of different phenotypes as TRD or DTD with partial or functional impairment to understand the impact of appropriate treatment pathways with SGAs.

Somatic symptom disorder (SSD) involves physical symptoms like palpitations, pain, weakness, dizziness, and pseudo-neurological symptoms. These symptoms are accompanied by excessive thoughts, emotions, and behaviors related to the symptom, causing significant distress and impairment lasting at least six months. They may not be explained by any underlying medical conditions. SSD can be resistant to standard treatment modalities like Cognitive Behavioral Therapy (CBT), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs). Antipsychotics, in particular second generations, have also been used to treat SSD but not as frequently. This case report shows the improvement in symptomatology of SSD after low-dose quetiapine was used for its management. This case is a 41-year-old Hispanic male with a diagnosis of SSD who presented to the outpatient clinic for severe somatic symptoms. The use of low-dose second-generation antipsychotic (SGA), in particular quetiapine, to successfully improve symptoms and patient functionality after just four weeks on quetiapine as the patient and wife both reported significant normalization of intrusive thoughts and health-related behaviors. To the best of our knowledge, this is the first case demonstrating symptom improvement in SSD following the addition of low-dose quetiapine to SNRI treatment.

Conduct disorder (CD) is characterized by repetitive and persistent antisocial behaviors, being among the most frequently reported reasons of referral in youth. CD is a highly heterogeneous disorder, with possible specifiers defined according to age at onset, Limited Prosocial Emotions (LPE) otherwise known as Callous-Unemotional (CU) traits, Emotional Dysregulation (ED), and patterns of comorbidity, each with its own specific developmental trajectories.
The authors review the evidence from published literature on the clinical presentations, diagnostic procedures, psychotherapeutic and psychoeducational approaches, and pharmacological interventions from RCT and naturalistic studies in youth. Evidence from studies including youths with LPE/CU traits, ED and aggression are also reviewed, as response moderators.
Due to its clinical heterogeneity, relevant subtypes of CD should be carefully characterized to gain reliable information on prognosis and treatments. Thus, disentangling this broad category in subtypes is crucial as a first step in diagnosis. Psychosocial interventions are the first option, possibly improving LPE/CU traits and ED, especially if implemented early during development. Instead, limited information, based on low-quality studies, supports pharmacological options. Second-generation antipsychotics, mood stabilizers, and stimulants are first-line medications, according to different target symptoms, such as aggression and emotional reactivity. Developmental pathways including ADHD suggest a specific role of psychostimulants.

Our case report highlights the importance of understanding various mechanisms of an atrioventricular block (AVB) and recognizing potential iatrogenic culprits. Despite the prevalent use of second-generation antipsychotics and the growing popularity of long-acting formulations, it is not routinely recognized as a cause for AVB. Second-generation antipsychotics such as risperidone have a dose-dependent pro-arrhythmic effect and are known to cause first-degree AVB. Our case presents an opportunity to recognize an unappreciated cause for AVB and switch to safer alternatives. In the era of long-acting injectables, it is important to monitor for these effects prior to escalating doses and risking high-degree AVB.

A 29-year-old male presented to the emergency department with complaints of shortness of breath and numbness in bilateral upper and lower extremities that started a few hours prior to arrival. On physical examination, the patient was afebrile, disoriented, tachypneic, tachycardic, and hypertensive with generalized muscle rigidity. Further investigation revealed that the patient had recently been prescribed ciprofloxacin and restarted on quetiapine. The initial differential diagnosis was acute dystonia, and subsequently, the patient was placed on fluids, lorazepam, diazepam, and later benztropine. The patient\'s symptoms began to resolve, and psychiatry was consulted. Given the patient\'s autonomic instability, altered mental status, muscle rigidity, and leukocytosis, psychiatric consultation revealed an atypical case of neuroleptic malignant syndrome (NMS). It was postulated that the patient\'s NMS was caused by a drug-drug interaction (DDI) between ciprofloxacin, a moderate cytochrome P450 (CYP) 3A4 inhibitor, and quetiapine, which is primarily metabolized by CYP3A4. The patient was then taken off quetiapine, admitted overnight, and discharged the next morning with complete resolution of his symptoms along with a prescription for diazepam. This case highlights the variable presentation of NMS and the need for clinicians to consider DDI when managing psychiatric patients.

UNASSIGNED: Antisocial personality disorder (AsPD) is a pervasive pattern of violation of others\' rights, related to the concept of psychopathy. AsPD is stable over time from adolescence, with evidence of conduct disorder (CD) before 15 years. DSM-5 included a specifier \'with limited prosocial emotions\' (LPE), which characterizes adolescents with higher developmental vulnerability to develop AsPD. Despite being relatively frequent with considerable societal impact, AsPD is a difficult-to-treat condition with high comorbidity rates and poor evidence for effective pharmacological interventions.
UNASSIGNED: We conducted a narrative review and searched PubMed up to September 2022. We included RCTs and naturalistic studies evaluating pharmacological interventions on AsPD in adults, including those with comorbid substance use disorder or psychopathic traits. Evidence in youths with CD, callous-unemotional (CU) traits and aggression were also reviewed, exploring the role of CU traits as moderators of response.
UNASSIGNED: Psychosocial interventions are the first option, with possible improvement of CU traits, beyond behavioral and affective symptoms, particularly if implemented early during development. Limited information, based on low-quality studies, supports the pharmacological options. Second-generation antipsychotics, lithium, anti-epileptic drugs, and stimulants are first-line medications, according to different target symptoms. Developmental pathways including ADHD suggest a specific role of psychostimulants.

BACKGROUND: Weight gain is a frequent side effect of treatment with SGAs (second-generation antipsychotics) and a leading cause for nonadherence. Several candidate genes have been identified that could influence the amount of AIWG (antipsychotic-induced weight gain). The polymorphism rs17782313 near the MC4R (human melanocortin 4 receptor gene) was strongly associated with obesity in a large scale GWAS (genome wide association study), yet previous studies investigating its impact on AIWG did not lead to a definite conclusion regarding its effect. In particular, they were all relatively short and had a naturalistic design.
OBJECTIVE: We therefore examined the influence of the rs17782313 polymorphism on SGA-related weight gain.
METHODS: Participants of a multicenter randomized, controlled, double-blind study comparing two treatment strategies in individuals with schizophrenia or schizoaffective disorder were genotyped using a rapid-cycle polymerase chain reaction. Up to 252 individuals completed the first 2 weeks (phase I), 212 the entire 8 weeks (hence \'completers\'). Patients received either amisulpride or olanzapine or both consecutively. Thirty-seven had their first episode. Weight gain occurring in different genotypes was statistically compared and confounding factors were adjusted by stepwise multiple linear regression. A correction for multiple testing was included.
RESULTS: Within 212 \'completers\', carriers of the C allele had a higher absolute weight gain than those homozygous for the T allele (2.6 kg vs. 1.2 kg), though this observation was not significant (P = 0.063). In the amisulpride subpopulation, this association appeared stronger and reached significance (2.5 kg vs. 0.7 kg, P = 0.043), though failed to remain significant after correction for multiple testing. A stepwise multiple linear regression showed a significant association in both the whole study population (P < 0.001) and the amisulpride subpopulation (P < 0.001).
CONCLUSIONS: Our results indicate that the rs17782313 polymorphism might influence antipsychotic-induced weight gain and therefore confirm some of the earlier conclusions.

34-year-old African American male with a diagnosis of schizophrenia was placed on aripiprazole and risperidone for psychosis and mood stabilization. Two days after medication initiation, the patient\'s mentation was altered and he appeared confused with an elevated creatine kinase (CK) at 7101. Medications were held and CK normalized with IV fluids. Quetiapine was initiated after medical stabilization along with lithium and paliperidone palmitate injections. After the second dose of paliperidone palmitate, the patient\'s mentation was altered, and repeat CK was 4272. The patient received 4 liters of IV fluid and his mental status returned to baseline. There were two case studies noted that had marked increases in serum CK with risperidone use. The first was in an adolescent who was titrated to a dose of risperidone 3mg/ day but the only abnormality was an increase in his CK levels. The next case report was in a 40-year-old female who was on risperidone 2.5mg /day for one year. She had an intention tremor, minor muscle weakness of the lower extremities with a blood pressure of 140/100 and a pulse of 100. She manifested more clinical signs of possible Neuroleptic Malignant Syndrome (NMS). This case highlights the importance of laboratory investigations when there is a high suspicion of possible NMS. It also highlights that some cases of NMS may only present as altered mental status and increased CK in which quick treatment may lead to the prevention of full-blown clinical manifestations of NMS which could be life-threatening.