Management of Cholinergic Rebound After Abrupt Withdrawal of Clozapine: A Case Report and Systematic Literature Review.

BACKGROUND: Cholinergic discontinuation symptoms, also known as "cholinergic rebound," from abrupt clozapine discontinuation are characterized by a range of somatic and psychiatric symptoms. OBJECTIVE: The objective of this study was to describe the clinical features and management options for clozapine withdrawal-associated cholinergic rebound syndrome (henceforth referred to as CWCRS) and present an illustrative case report. METHODS: Based on a literature search of the databases PubMed, OVID Medline, and Embase as well as reviewing reference lists of relevant past reviews, we carried out a systematic review of case reports on the management of CWCRS from 1946 to 2023. RESULTS: We identified 10 previously published articles on the clinical management of CWCRS, with a total of 18 patients (6 female, 12 male) with an average age of 43 years (standard deviation 14). Half of the patients had a history of tardive dyskinesia. The mean dose of clozapine before discontinuation was 351 mg/day, with duration of clozapine treatment ranging from 3 weeks to 9 years. Clozapine was the most effective treatment, followed by benztropine. CONCLUSIONS: Given the small number of cases and the nonexperimental nature of the available studies, this review could not provide reliable data to guide management of CWCRS. The findings, however, suggest that clozapine may be more effective than other commonly used treatment options. With the high rates of discontinuation among patients on clozapine, there is a pressing need for further research into the epidemiology, natural history, and management of clozapine withdrawal syndromes.

Alprazolam: Good for Some, Not Good for All!

BACKGROUND: Although alprazolam is approved only for use in panic disorder and generalized anxiety disorder, it is used for numerous other conditions, not only by psychiatrists but also by medical professionals in general. This commentary critically analyzes the use of alprazolam. METHODS: A narrative review approach was adopted, using relevant articles and textbooks, to compile pertinent literature for the aforementioned topic. RESULTS: Among all its adverse reactions, the most bothersome concern about the use of alprazolam is its potential for abuse and dependence. This can be attributed to certain unique pharmacokinetic and pharmacodynamic properties of this benzodiazepine. Also, the withdrawal triggered by use of alprazolam is challenging to treat. Alternate pharmacological and non-pharmacological strategies for use in anxiety and insomnia are available, which might be safer than alprazolam. Also, policy changes can serve as an answer to curb alprazolam abuse to some extent. Alprazolam might still be a good choice for individuals who do not have a history of abuse of other substances, with adequate psychoeducation and close monitoring of their usage pattern. CONCLUSION: There is a need to reconsider the need for long-term use of benzodiazepines in general, and alprazolam in particular. However, they still might be an appropriate choice in individuals where abuse and dependence are less likely.

Anabolic androgenic steroids, antisocial personality traits, aggression and violence.

BACKGROUND: Anabolic androgenic steroid (AAS) use is associated with a wide range of adverse physical, psychological and social effects. While some experience few side effects, others might experience severe consequences. Aggression and violence are among the often-cited side effects associated with high-dose AAS use; however, most of the knowledge is generated from subgroups, such as prison populations. A likely hypothesis is that AAS use is associated with aggression and violence, but that these associations are complex and may be mediated by several factors, such as substance use, AAS dependence and personality traits. METHODS: In the present study, we tested this hypothesis by examining the relations between long-term AAS use and AAS dependence, aggression, interpersonal violence and potential mediating factors in a sample of male AAS exposed and non-exposed weightlifting controls (WLC), using self-report questionnaires. Based upon AAS dependence criteria, a sample of male AAS users and WLC (N = 139) were stratified into three groups: WLC (n = 66), AAS dependents (n = 41) and AAS non-dependents (n = 32). RESULTS: The results demonstrate that AAS dependents reported significantly higher levels of aggression compared to WLC and AAS non-dependents. While interpersonal violence was reported in all three groups, the highest percentage was found in the AAS dependent group. CONCLUSION: In summary, our study confirms a link between AAS use, aggression and violence in a weightlifting population. However, the association is foremost seen in AAS dependent users and it seems that antisocial personality traits are an important mediator.

Prospective longitudinal associations between household smoke exposure in early childhood and antisocial behavior at age 12.

Young children exert little control over household tobacco smoke exposure, which is considered a developmental neurotoxicant. Using the Quebec Longitudinal Study birth cohort, we examine prospective associations between early childhood smoke exposure and later antisocial behavior. Parents of 1035 children reported on the presence of household smokers at seven follow-ups from ages 1.5 to 7.5. At age 12, children self-reported on five aspects of early antisocial dispositions. After adjusting for confounders, every standard deviation increase in household smoke exposure was prospectively associated with a 19% standard deviation unit increase in conduct problems (ß=0.07; 95% confidence interval [CI] from 0.04 to 0.09), a 11% standard deviation unit increase in proactive aggression (ß=0.04; 95% CI from 0.01 to 0.07), a 13% standard deviation unit increase in reactive aggression (ß=0.07; 95% CI from 0.03 to 0.12), a 14% standard deviation unit increase in school indiscipline (ß=0.13; 95% CI from 0.05 to 0.20), and a 10% standard deviation unit increase in dropout risk (ß=0.07; 95% CI from 0.01 to 0.12). These long-term findings warrant fostering parental awareness of developmental risks by policy-makers/health practitioners. School curricula can equally integrate these ideas into their curriculum.

[Conditions associated with impaired social skills in a convenience sample of crack users]. / Condições associadas a prejuízo de desempenho em habilidades sociais em uma amostra de conveniência de usuários de crack.

The article analyzes conditions associated with low scores on the Social Skills Inventory (SSI) among crack users in Greater Metropolitan Porto Alegre, Rio Grande do Sul State, Brazil, based on a cross-sectional study in a convenience sample of 519 individuals interviewed in 2011. Low SSI scores occurred in 52.8% of the sample, and there were no differences according to currently active use of crack (yes/no) or current addiction treatment. Higher likelihood of low SSI was associated with crack users in pre-contemplation or contemplation in University of Rhode Island Change Assessment - URICA (p = 0.031), high Beck Depression Inventory - BDI scores (p = 0.037), mourning a deceased child (p = 0.001), and having committed armed robbery to obtain crack (p = 0/020). Lower likelihood of low SSI was associated with 9 or more years of schooling (p = 0.001), high social support (p < 0.001), high resilience (p < 0.001), having lost contact with parents (p = 0.032), history of hospitalization due to crack (p = 0.009), and history of sex to obtain crack (p = 0.009). The findings are clinically useful and highlight the issue's importance.

Condições associadas a prejuízo de desempenho em habilidades sociais em uma amostra de conveniência de usuários de crack / Conditions associated with impaired social skills in a convenience sample of crack users / Condiciones asociadas a prejuicios sobre el desempeño en habilidades sociales dentro de una muestra de conveniencia con consumidores de crack

O artigo apresenta condições associadas a escores deficitários noInventário de Habilidades Sociais (IHS) entre usuários decrack da Região Metropolitana de Porto Alegre, Rio Grande do Sul, Brasil. Estudo transversal, com amostragem de conveniência de 519 indivíduos, entrevistados em 2011. Escore deficitário no IHS ocorreu para 52,8% da amostra e não houve diferenças quanto a estar ou não em uso ativo decrack, ou quanto a estar ou não em atendimento. Apresentaram probabilidade aumentada de déficit no IHS os usuários decrack em pré-contemplação ou contemplação noUniversity of Rhode Island Change Assessment - URICA (p = 0,031), com escores elevados no Inventário de Depressão de Beck- BDI (p = 0,037) os que viveram luto de filho (p = 0,001) e os que já assaltaram para obter o crack (p = 0,020). Com probabilidade diminuída estavam os que tinham escolaridade de 9 anos ou mais (p = 0,001), apoio social elevado (p < 0,001), resiliência elevada (p < 0,001), com histórico de ter perdido o contato com seus pais (p = 0,032), já tendo sido hospitalizado em função da droga (p = 0,009) e que relataram já ter mantido atividade sexual para obter a pedra (p = 0,009). Os achados têm utilidade clínica e mostram a importância do tema.

The article analyzes conditions associated with low scores on the Social Skills Inventory (SSI) among crack users in Greater Metropolitan Porto Alegre, Rio Grande do Sul State, Brazil, based on a cross-sectional study in a convenience sample of 519 individuals interviewed in 2011. Low SSI scores occurred in 52.8% of the sample, and there were no differences according to currently active use of crack (yes/no) or current addiction treatment. Higher likelihood of low SSI was associated with crack users in pre-contemplation or contemplation in University of Rhode Island Change Assessment - URICA (p = 0.031), high Beck Depression Inventory - BDI scores (p = 0.037), mourning a deceased child (p = 0.001), and having committed armed robbery to obtain crack (p = 0/020). Lower likelihood of low SSI was associated with 9 or more years of schooling (p = 0.001), high social support (p < 0.001), high resilience (p < 0.001), having lost contact with parents (p = 0.032), history of hospitalization due to crack (p = 0.009), and history of sex to obtain crack (p = 0.009). The findings are clinically useful and highlight the issue's importance.

El artículo presenta las condiciones asociadas a marcadores deficitarios en elInventario de Habilidades Sociales (IHS) entre usuarios decrack de la Región Metropolitana de Porto Alegre, Río Grande do Sul, Brasil. Se trata de un estudio transversal, con una muestra de conveniencia de 519 individuos, entrevistados en 2011. El marcador deficitario en el IHS se produjo en un 52,8% de la muestra y no hubo diferencias en cuanto a estar o no consumiendo activamente crack, o en cuanto a estar no bajo supervisión médica. Tuvieron una probabilidad mayor de déficit en el IHS los consumidores de crack pre-contemplados o contemplados en elUniversity of Rhode Island Change Assessment - URICA (p = 0,031), con marcadores elevados en Beck Depression Inventory - BDI (p = 0,037), quienes vivieron luto por un hijo (p = 0,001) y los que ya robaron para obtener crack (p = 0,020). Con probabilidad disminuida estaban quienes tenían una escolaridad de 9 años o más (p = 0,001), apoyo social elevado (p < 0,001), resiliencia elevada (p < 0,001), con historial de haber perdido el contacto con sus padres (p = 0,032), ya habiendo sido hospitalizado por crack (p = 0,009) y que ya informaron haber mantenido relaciones sexuales para obtener crack (p = 0,009). Los hallazgos tienen utilidad clínica y muestran la importancia del tema.

Anti-Social Behaviors Associated with Anabolic-Androgenic Steroid Use among Male Adolescents.

Anabolic-androgenic steroids (AAS) have been linked to a range of problematic behaviors, but AAS use is still sometimes portrayed as more benign than other forms of classical drug abuse. To address this issue, we compared the prevalence of anti-social behaviors among adolescent AAS users, non-AAS illicit drug users, and drug non-users. We examined 3 waves (2004, 2008, and 2012) of self-reported cross-sectional data from a secondary school survey conducted in Stockholm, Sweden (total n = 19,773; response percentage, 79.6%). Across all survey years, the risk ratios for virtually all measured anti-social behaviors were significantly higher among AAS users compared to non-AAS illicit drug users and to drug non-users.

The impact of toxins on the developing brain.

The impact of toxins on the developing brain is usually subtle for an individual child, but the damage can be substantial at the population level. Numerous challenges must be addressed to definitively test the impact of toxins on brain development in children: We must quantify exposure using a biologic marker or pollutant; account for an ever-expanding set of potential confounders; identify critical windows of vulnerability; and repeatedly examine the association of biologic markers of toxins with intellectual abilities, behaviors, and brain function in distinct cohorts. Despite these challenges, numerous toxins have been implicated in the development of intellectual deficits and mental disorders in children. Yet, too little has been done to protect children from these ubiquitous but insidious toxins. The objective of this review is to provide an overview on the population impact of toxins on the developing brain and describe implications for public health.

Adolescent inhalant use and executive cognitive functioning.

BACKGROUND: This study investigates the association between inhalant use and executive cognitive functioning (ECF) and processing speed (PS) in 754 adjudicated poly-substance users on a series of neuropsychological tests. Poly-substance users who used inhalants (PSI = 262) and poly-substance users who did not use inhalants (PSO = 492) neuropsychological tests scores were compared. Hispanic Americans comprised 72% of the participants; European Americans, African Americans and Asian Americans comprised 28% of the participants. METHODS: Standardized neuropsychological tests were used to assess ECF and PS. Psychosocial and substance abuse standardized surveys were used to assess drug use severity and psychosocial problems associated with substance use. RESULTS: Multiple Analysis of Covariance shows that PSI users who used inhalants performed worse on ECF and PS measures in comparison to non-inhalant poly-substance users (PSO). PSI users were younger, used more drugs and had more psychiatric admissions than PSO users. CONCLUSION: PSI users initiate substances at a younger age and experienced more ECF and PS deficits, and behavioural problems in comparison to PSO users. The results of this study suggest that PS has direct effect on ECF and psychosocial outcomes in PSI users.

Alcohol-related aggression and antisocial behaviour in sportspeople/athletes.

OBJECTIVES: There is no empirical research on alcohol-related aggression and antisocial behaviour in non-US collegiate athletes. The present study addressed this gap by examining these behaviours in Australian university sportspeople. DESIGN: Cross-sectional. METHODS: University sportspeople and non-sportspeople completed questionnaires on alcohol consumption, aggressive and antisocial behaviours (e.g., abused, hit or assaulted someone, made unwanted sexual advance, damaged property) when intoxicated. Participants also reported whether they had been the victim of similar aggressive or antisocial behaviours. Demographic data and known confounders were collected. RESULTS: Hierarchical logistic regression models accounting for confounders and alcohol consumption scores found that university sportspeople were significantly more likely than non-sportspeople to have displayed aggressive behaviour (i.e., insulted or assaulted someone; OR 1.65, 95% CI: 1.19, 2.28, p=.003), and damaged property (OR 1.98, 95% CI: 1.38, 2.84, p<.0005) in the past year when intoxicated. Sportspeople were no more likely to have received aggression, had property damaged due to others intoxication (OR 1.21, 95% CI: .90, 1.62, p=.20; and OR 1.10, 95% CI: .79, 1.53, p=.57, respectively), or to have made unwanted sexual advances (OR 1.10, 95% CI: .65, 1.83, p=.74). Sportspeople were less likely to have reported being sexually assaulted when intoxicated (OR .44, 95% CI: .23, .83, p<.01). CONCLUSIONS: Consistent with work from the US alcohol-related aggressive and antisocial behaviours were greater in male Australian university sportspeople/athletes than in their female and non-sporting counterparts. There is a need for research explicating the interaction between alcohol, contextual and cultural aspects of sport, and sport participants.

The significance of anabolic androgenic steroids in a Swedish prison population.

Use of anabolic androgenic steroids (AAS) has been associated with adverse psychiatric effect, violent behavior, and criminality. The aim of this study was to further investigate the motives for and consequences of AAS use, with focus on violent and antisocial behavior. Fifty-nine prisoners were interviewed on their use of AAS, and their history was mapped with Addiction Severity Index interviews. Of these prisoners, 56% admitted previous use of AAS, of whom 24% declared to have committed violent crimes in connection with use of AAS. However, the only significant difference between users and nonusers with regard to criminal history when measured with the Addiction Severity Index was that the AAS users more often stated that they had been prosecuted for crimes labeled as "other crimes," which did not include violent crimes. The reported side effects of AAS corresponded well to those previously reported. These results indicate that use of AAS is common among Swedish prisoners and that the motives and consequences of such use are similar to what has been observed in other AAS-using populations. Furthermore, this study supports earlier notions that misuse of AAS might cause violent behavior, but only in certain individuals and mainly in combination with other substances.

Environmental causes of violence.

Violent and anti-social behavior is usually attributed to social factors, including poverty, poor education, and family instability. There is also evidence that many forms of violent behavior are more frequent in individuals of lower IQ. The role of exposure to environmental contaminants has received little attention as a factor predisposing to violent behavior. However a number of environmental exposures are documented to result in a common pattern of neurobehavioral effects, including lowered IQ, shortened attention span, and increased frequency of antisocial behavior. This pattern is best described for children exposed to lead early in life, but a similar pattern is seen upon exposure to polychlorinated biphenyls and methyl mercury. Although not as extensively studied, similar decrements in IQ are seen upon exposure to arsenic and secondhand smoke (SHS) exposure. Prenatal and postnatal SHS exposure is also associated with increased rates of conduct disorder and attention deficit hyperactivity. Recent evidence suggests that temporal trends in rates of violent crime in many nations are consistent with earlier preschool blood lead trends, with a lag of about 20 years. These ecologic correlations are consistent with many controlled studies suggesting that lead-exposed children suffer irreversible brain alterations that make them more likely to commit violent crimes as young adults. If this pattern is true for lead and other contaminants, the most effective way to fight crime may be to prevent exposure to these contaminants.

Surface dental enamel lead levels and antisocial behavior in Brazilian adolescents.

Lead poisoning has been reportedly linked to a high risk of learning disabilities, aggression and criminal offenses. To study the association between lead exposure and antisocial/delinquent behavior, a cross-sectional study was conducted with 173 Brazilian youths aged 14-18 and their parents (n=93), living in impoverished neighborhoods of Bauru-SP, with high criminality indices. Self-Reported Delinquency (SRD) and Child Behavior Checklist (CBCL) questionnaires were used to evaluate delinquent/antisocial behavior. Body lead burdens were evaluated in surface dental enamel acid microbiopsies. The dental enamel lead levels (DELL) were quantified by graphite furnace atomic absorption spectrometry (GFAAS) and phosphorus content was measured using inductively coupled plasma optical emission spectrometry (ICP-OES). Logistic regression was used to identify associations between DELL and each scale defined by CBCL and SRD scores. Odd ratios adjusted for familial and social covariates, considering a group of youths exposed to high lead levels (>or=75 percentile), indicated that high DELL is associated with increased risk of exceeding the clinical score for somatic complaints, social problems, rule-breaking behavior and externalizing problems (CI 95%). High DELL was not found to be associated with elevated SRD scores. In conclusion, our data support the hypothesis that high-level lead exposure can trigger antisocial behavior, which calls for public policies to prevent lead poisoning.

Parsing the associations between prenatal exposure to nicotine and offspring psychopathology in a nonreferred sample.

PURPOSE: Several studies have suggested an association between maternal smoking during pregnancy and both attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) in the offspring of women who smoke during pregnancy. However, it is unclear whether one or both of the documented links are spurious, given the considerable comorbidity between these disorders. The main aim of this study was to disentangle the association between maternal smoking during pregnancy with psychopathological outcomes, adjusting for possible confounders. METHODS: Two large, identically designed, longitudinal, case-control family studies of male and female probands with and without ADHD were combined. We used data from the nonreferred siblings of the probands from both studies (n = 536). All subjects were blindly assessed with structured diagnostic interviews. Logistic regression analysis was used to determine the adjusted effect of exposure to maternal smoking during pregnancy. RESULTS: Among all siblings, maternal smoking during pregnancy was significantly associated with ADHD, independent of CD and other covariates. In contrast, maternal smoking during pregnancy was a risk factor for CD only in siblings of control probands, after adjusting for covariates. CONCLUSIONS: These results support the hypothesis that maternal smoking during pregnancy is a risk factor for both ADHD and CD, independently of each other. However, the risk for CD appears to be conditional on family risk status.

The association between DRD2/ANKK1, 5-HTTLPR gene, and specific personality trait on antisocial alcoholism among Han Chinese in Taiwan.

Cloninger suggested that type II alcoholism was associated with higher novelty seeking and less harm avoidance behaviors, which was similar to antisocial alcoholism. Most previous studies have failed to recruit subjects that have antisocial personality disorder without alcoholism due to the high coexisting likelihood of having antisocial personality disorder with alcoholism in the majority of the examined populations. Thus, recruitment of individuals with antisocial non-alcoholism (antisocial personality disorder) served as an important control group in examining Cloninger's hypothesis. Due to the documented protective effects against alcoholism of ALDH2*1/*2 or *2/*2 genotype among the Han Chinese population, we recruited antisocial non-alcoholics from the Han Chinese population in Taiwan to verify Cloninger's hypotheses. A total of 127 Han Chinese subjects were recruited who met the diagnosis of antisocial alcoholism (n = 43) or antisocial non-alcoholism (n = 84). We found that the antisocial alcoholism group scored higher on the novelty seeking behavior than did the antisocial non-alcoholism group (t = 2.61, P = 0.01), but no difference was observed on the harm avoidance dimension between these two groups (t = 0.15, P = 0.88). In the novelty seeking scores, after stratification of DRD2 TaqI A genotypes, only a significant difference in 5-HTTLPR polymorphisms between antisocial alcoholics and antisocial non-alcoholics was found, indicating an interaction between DRD2 TaqI A1+ (include A1/A1 or A1/A2) and 5-HTTLPR S/S genotype (t = 2.75, P = 0.01) However, no significant difference was found in the harm avoidance personality trait between these two groups of Han Chinese in Taiwan.

Environmental stressors and violence: lead and polychlorinated biphenyls.

Many environmental risk factors for antisocial and violent behavior have been described. In recent years, this topic has become widely researched in the fields of environmental health, psychology, sociology, and many other disciplines. The results from a myriad of studies have shown that the etiologies of violent and aggressive behavior range from definitive biological environmental stressors like lead or polychlorinated biphenyls to various socio-cultural environmental stressors, such as social, economic, and racial factors. The aim of this paper is (a) to provide an overview of the specific effects of the environmental stressors that have been associated with violent behavior, and (b) to discuss current policies and regulations implemented by the United States government for minimizing exposure to environmental toxins contributing to violence in our society.

Effects of different subanaesthetic doses of (S)-ketamine on psychopathology and binocular depth inversion in man.

The role of the N-methyl-D-aspartate (NMDA) neurotransmitter system in relation to psychoses is not completely understood, but represent a challenge in neurobiological research. The psychotic states induced by NMDA antagonists such as phencyclidine and ketamine have been described as being most similar to schizophrenia and the NMDA system has been implicated in the pathogenesis of schizophrenia. Binocular depth inversion, an illusion of visual perception, has been shown to be impaired in psychotic and psychotomimetic states in healthy and schizophrenic subjects. In this study, pictures of natural and artificial objects were presented stereoscopically to 12 healthy male volunteers and depth perception assessed using an operationalized method. The effects of the psychotomimetic S-enantiomer of the anaesthetic ketamine in two different subanaesthetic doses were compared with those of a placebo. In spite of dose dependence and grave subjective and significant objective psychopathology, no significant impairment of binocular depth perception was found with (S)-ketamine. Implications related to memory function, perceptogenesis and 'bottom-up' processing in ketamine model psychosis and schizophrenia are discussed.

Prozac and crime: who is the victim?

Prozac has been cited in more medication defense criminal cases in the United States than has any other psychotropic drug. In the majority of these cases, defendants are arguing that they are the victims of the drug. Defendants assert that they are victimized by their own involuntary intoxication or that of witnesses and crime victims who have been adversely influenced by Prozac. This article reviews 12 criminal cases in the United States in which Prozac victimization is a salient theme, and it calls for mental health professional organizations to intervene in a growing legal conundrum.