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Autism Spectrum Disorders (ASDs) are a group of severe developmental and neuropsychiatric disorders usually apparent by the age of three. Autism, referred to as autism spectrum disorder in the 11th revision of the International Classification of Diseases (ICD-11), is a neurodevelopmental condition characterised by persistent deficits in social interaction and social communication, as well as a range of restricted, repetitive behaviours (World Health Organization 2018). The onset of autism is in the developmental period (0–18 years of age), though for some autistic persons the symptoms may manifest later in life, at a time of increased social demands (World Health Organization 2018). In addition to the aforementioned core autistic features, many autistic people have associated symptoms, including hypo- or hypersensitivities to sensory stimuli, difficulties describing their emotional state (alexithymia), and problems with gross motor co-ordination The chapter will discuss the interface between autism spectrum disorder and intellectual disability and the potential management of the disorder. It will also cover the gender variations in presentation.
There is an increasing trend of the prescribing of psychotropic medications for children. This chapter explores the various issues associated with medicating children with people with intellectual disability.
Aggression is often defined with reference to the intended consequences of an act exhibited by a person, or as any behaviour exhibited by a person where they intentionally acted to cause harm to another. Behaviours which cause harm but without associated intent tend not to be defined as aggression. Some people with intellectual disability may engage in behaviours with intent to cause harm to another, while for others, especially those with severe to profound intellectual disability, an absence of intent may exist. Aggressive behaviour exhibited by people with intellectual disability can take the form of verbal threats, physical aggression directed towards others including punching, kicking, slapping and biting, amongst other behaviours, as well as property damage and destruction. Aggressive behaviour can cause serious harm to others which may be life-threatening and result in social exclusion and a reduced quality of life. This chapter provides an overview of severe aggression and self-injurious behaviour relevant to people with disorders of intellectual development, and focuses on the evidence base for the various challenging behaviours and whether there is benefit from medication or alternative approaches.
Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages.
Methods
A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC–MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups.
Results
A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL.
Conclusions
The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.
Edited by
Nevena V. Radonjić, State University of New York Upstate Medical University,Thomas L. Schwartz, State University of New York Upstate Medical University,Stephen M. Stahl, University of California, San Diego
The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis.
Aims
To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole.
Method
Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method.
Results
A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml).
Conclusions
The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.
Resting cerebral blood flow (rCBF) in striatum and thalamus is increased in medicated patients with psychosis, but whether this is caused by treatment or illness pathology is unclear. Specifically, effects of partial dopamine agonism, sex, and clinical correlates on rCBF are sparsely investigated. We therefore assessed rCBF in antipsychotic-naïve psychosis patients before and after aripiprazole monotherapy and related findings to sex and symptom improvement.
Methods
We assessed rCBF with the pseudo-Continuous Arterial Spin Labeling (PCASL) sequence in 49 first-episode patients (22.6 ± 5.2 years, 58% females) and 50 healthy controls (HCs) (22.3 ± 4.4 years, 63% females) at baseline and in 29 patients and 49 HCs after six weeks. RCBF in striatum and thalamus was estimated with a region-of-interest (ROI) approach. Psychopathology was assessed with the positive and negative syndrome scale.
Results
Baseline rCBF in striatum and thalamus was not altered in the combined patient group compared with HCs, but female patients had lower striatal rCBF compared with male patients (p = 0.009). Treatment with a partial dopamine agonist increased rCBF significantly in striatum (p = 0.006) in the whole patient group, but not significantly in thalamus. Baseline rCBF in nucleus accumbens was negatively associated with improvement in positive symptoms (p = 0.046), but baseline perfusion in whole striatum and thalamus was not related to treatment outcome.
Conclusions
The findings suggest that striatal perfusion is increased by partial dopamine agonism and decreased in female patients prior to first treatment. This underlines the importance of treatment effects and sex differences when investigating the neurobiology of psychosis.
To investigate the relationship between lean muscle mass and treatment response in treatment-resistant late-life depression (TR-LLD). We hypothesized that lower lean muscle mass would be associated with older age, higher physical comorbidities, higher depressive symptom severity, and poorer treatment response.
Design:
Secondary analysis of a randomized, placebo-controlled trial.
Setting:
Three academic hospitals in the United States and Canada.
Participants:
Adults aged 60+ years with major depressive disorder who did not remit following open treatment with venlafaxine extended-release (XR) (n = 178).
Measurements:
We estimated lean muscle mass using dual-energy X-ray absorptiometry (DEXA) scans prior to and following randomized treatment with aripiprazole or placebo added to venlafaxine XR. Multivariate regressions estimated influence of demographic and clinical factors on baseline lean muscle mass, and whether baseline lean muscle mass was associated with treatment response, adjusted for treatment arm.
Results:
Low lean muscle mass was present in 22 (12.4%) participants. Older age and female sex, but not depressive symptom severity, were independently associated with lower lean muscle mass at baseline. Marital status, baseline depressive symptom severity, and treatment group were associated with improvement of depressive symptoms in the randomized treatment phase. Baseline lean muscle mass was not associated with improvement, regardless of treatment group.
Conclusion:
As expected, older age and female sex were associated with lower lean muscle mass in TR-LLD. However, contrary to prior results in LLD, lean muscle mass was not associated with depression severity or outcome. This suggests that aripiprazole augmentation may be useful for TR-LLD, even in the presence of anomalous body composition.
Amenorrhea secondary to hyperprolactinemia is one of the frequent adverse effects associated with the use of atypical antipyschotics. It is often neglected but can interrupt the compliance of treatment. Several studies indicate that olanzapine does not significantly affect serum prolactin levels in the long term, although contrary has been observed in few case reports.
Objectives
To report a case of olanzapine-induced amenorrhea due to hyperprolactinemia.
Methods
A 27-year-old woman with history of stillbirth 5 months prior, presented to OPD with hallucinatory behaviour and socio-occupational dysfunction for 5 months. She was on tianeptine 12.5 mg, escitalopram 10 mg and alprazolam 0.5 mg at presentation and was having regular menses. On assessment, she was diagnosed with unspecified psychosis. Her ongoing medications were stopped and she was started on Olanzapine (optimized to 20 mg/day) after which she reported significant improvement however developed amenorrhea within next 2 months hence advised to consult Obgyn. Urine pregnancy test came out negative and prolactin level was found to be 64.2 ng/ml. Other investigations including MRI were within normal limit. Olanzapine was cross tapered with Aripiprazole (maintained at 10 mg/day). Clonazepam was advised SOS for anxiety.
Results
After 1 month of aripiprazole treatment, monthly menses resumed and prolactin level returned to normal range. No biological dysfunction or other side effects were reported by the patient.
Conclusions
Olanzapine-induced amennorhea secondary to hyperprolactinemia, is a rare but possible event. We report a case in which olanzapine induced amenorrhea normalized after switching to aripiprazole. Baseline prolactin level should be obtained as they help in the management of patients with neuroleptic-induced hyperprolactinemia.
Nowadays, relapses are typical in patients with schizophrenia and may have serious implications due to most of them are caused by a lack of adherence to treatment.Therefore, numerous long-acting injectable antipsychotics (LAI) have been developed as aripiprazole depot who need a proper oral supplementation. Since November 2020, FDA approved a new treatment indication with a double injection start and a single dose of 20mg of oral aripiprazole, with the aim of avoiding oral supplementation during the next 14 days.
Objectives
The purpose of our study is to expose our experience with the new double injection start with aripiprazole LAI, regarding the rehospitalization rate.
Methods
A prospective study (n=17 patients) has been developed between November 2020 and October 2021 with the purpose of studying the rehospitalization and antipsychotic adherence after the new guideline of aripiprazole
Results
After an 11-month-follow-up, it is noticed a 65% non-rehospitalization rate and a 76% proper treatment persistence rate. The 94% did not present any kind of side effects, only one patient had a case report of bullous pemphigoid. Regarding the concomitant use of other antipsychotics, 82% of the patients remained in monotherapia. The average stay time was shortened (11 days) regarding the standard dose (14 days).
Conclusions
The new LAI regimen is well tolerated in our patients obtaining a high treatment persistence after several months of hospital discharge. It was already possible to shorten the time of rehospitalization, not having to add oral aripiprazole for 14 days. Most patients were discharged are on antipsychotic monotherapy and have not been rehospitalized in the short term.
Aripiprazole long-acting treatments can significantly control symptom, improve adherence and reduce the risk of relapse compared to oral drugs. An alternative start-up guideline has recently been approved in several countries that simplifies its administration.
Objectives
To present a case report of a patient with schizophrenia treated with alternative starting regimen of aripiprazole long-acting treatment.
Methods
Presentation of a clinical case supported by a non-systematic review of literature.
Results
We present the case of a 22-year-old patient diagnosed with schizophrenia, whose symptoms started after the birth of her son, 2 years ago. She has presented a poor clinical evolution, requiring several admissions to our inpatient service after discontinuation of her medication. The patient has taken different antipsychotics, including olanzapine and paliperidone long-acting treatment, which were suspended due to side effects (weight gain and increased prolactin levels). A switch to oral aripiprazole 20mg was made, which showed good response and tolerance. Given the persistence of irregular intake, it was decided to switch to aripiprazole long-acting treatment, applying an alternative initial regime consisting of two doses of aripiprazole long-acting treatments 400mg and one oral aripiprazole 20mg. The patient has since had no delusions or hallucinations and is living independently at home.
Conclusions
The administration of a simplified initial regime with aripiprazole long-acting treatments could improve therapeutic adherence while maintaining the same effectiveness and similar side effects.
Hyperprolactinemia is a common unwanted antipsychotic-induced adverse effect, particularly in female patients, and can induce poor adherence to treatment. Aripiprazole is an antipsychotic with partial agonist activity over the dopamine D2 receptors which can be effective in reducing hyperprolactinemia in patients treated with antipsychotics.
Objectives
We investigate the efficacy of adjunctive treatment with aripiprazole for olanzapine-induced hyperprolactinemia and related hormonal side effects (amenorrhea, oligomenorrhea) in female patients with schizophrenia.
Methods
Eight female patients (22 to 40 years old) participated in this study with a diagnosis of schizophrenia and hyperprolactinemia-related hormonal side effects (amenorrhea, oligomenorrhea). Patients were treated with aripiprazole 10 mg/day added to a fixed olanzapine dose of 20 mg/day. Serum prolactin levels were measured at baseline and after 2, 4, 6, and 8 weeks. Symptoms and side effects were assessed using the Brief Psychiatric Rating Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale.
Results
Adjunctive treatment with aripiprazole resulted in significantly lower prolactin levels beginning at week 2. 87.5 % of patients at week 8 had prolactin levels normalize. Among 8 patients with menstrual disturbances, 75% of patients regained menstruation during the study. No significant changes were observed regarding psychopathology and adverse effect ratings.
Conclusions
Adjunctive aripiprazole treatment is effective for resolving olanzapine-induced hyperprolactinemia and reinstatement of menstruation in female patients, provides significant improvement and it appears to be safe with a lower risk of metabolic syndrome, without increased risk of adverse effects.
Obsessive compulsive disorder (OCD) is a pathology represented by thoughts, images, impulses or feelings that generate great anxiety and discomfort, as well as the development of compulsive acts and rituals that cause great dysfunction.
The comorbidity of different psychiatric disorders with OCD is known, such as impulse control disorder and tic disorder.
Objectives
The objective of this study is to describe the clinical characteristics, comorbidities and the treatment used in a patient with an OCD diagnosis and motor tics.
Methods
Description of a clinical case of motor tics associated with OCD in an adult patient.
Results
A 29-year-old man begins mental health follow-up for presenting, as a result of a choking episode, obsessive thoughts with significant emotional and behavioral repercussions, to the point of restricting his diet and losing several kilos of weight. He also manifested checks and rituals in order to avoid possible choking.Treatment with sertraline and clonazepam was started, without evidence of improvement in symptoms. Months later, bucolingual and guttural tics, difficult to control by the patient and which caused bite lesions in the mouth and tongue, were added to the described clinic. Oral aripiprazole was associated to the treatment and then prolonged- release intramuscular administration was used, achieving improvement in obsessive symptoms and motor tics.
Conclusions
The usefulness of adjuvant treatment with atypical antipsychotics has been demonstrated in adults with OCD who present an insufficient response to an SSRI. Injectable prolonged-release antipsychotics can help improve long-term prognosis by ensuring adherence.
We present the case of a 21 year-old male, with history of a psychotic episode, currently with monthly follow-up in an outpatient facility, with a favorable clinical evolution after one year of intensive follow-up. In the context of abandonment of his medication and a problematic family situation, the patient starts to show suspicious, with insomnia and a progressive social isolation. Despite an attempt of ambulatory treatment with oral aripiprazole, showing good tolerance, the patient refuses such treatment, showing active clinical psychotic with great distress and behavioral repercussion, finally requiring hospital admission.
Objectives
To perform a literature review about the treatment initiation with two vials of aripiprazole long-acting injection.
Methods
Literature review of scientific articles using Pubmed as search engine. We considered articles published both in English and Spanish.
Results
During hospital stay, treatment with 2 intramuscular injections of 400mg of aripiprazole is started, combined with a single dose of oral aripiprazole 20mg on day 1, assuring correct dosing, with good tolerance and favoring therapeutic adherence. Progressively, the patient starts to feel calmer, adequate, collaborative and emotionally stable, recuperating chronobiological rhythms, with remission of the hallucinations and appearing more distant from delusions.
Conclusions
According to the currently available studies, the use of this posology could avoid the potential impact that lack of adherence to oral treatment could have in the therapeutic outcome, assuring a correct dosing and favoring adherence from day 1. Furthermore, this would help simplify the medication regiment for patients, physicians and caregivers.
Tourette syndrome (TS) as well as its most common comorbidities are associated with a higher propensity for risky behaviour in everyday life. However, it is unclear whether this increased risk propensity in real-life contexts translates into a generally increased attitude towards risk. We aimed to assess decision-making under risk and ambiguity based on prospect theory by considering the effects of comorbidities and medication.
Methods
Fifty-four individuals with TS and 32 healthy controls performed risk and ambiguity decision-making tasks under both gains and losses conditions. Behavioural and computational parameters were evaluated using (i) univariate analysis to determine parameters difference taking independently; (ii) supervised multivariate analysis to evaluate whether our parameters could jointly account for between-group differences (iii) unsupervised multivariate analysis to explore the potential presence of sub-groups.
Results
Except for general ‘noisier’ (less consistent) decisions in TS, we showed no specific risk-taking behaviour in TS or any relation with tics severity or antipsychotic medication. However, the presence of comorbidities was associated with distortion of decision-making. Specifically, TS with obsessive–compulsive disorder comorbidity was associated with a higher risk-taking profile to increase gain and a higher risk-averse profile to decrease loss. TS with attention-deficit hyperactivity disorder comorbidity was associated with risk-seeking in the ambiguity context to reduce a potential loss.
Conclusions
Impaired valuation of risk and ambiguity was not related to TS per se. Our findings are important for clinical practice: the involvement of individuals with TS in real-life risky situations may actually rather result from other factors such as psychiatric comorbidities.
Aripiprazole, brexpiprazole and cariprazine are partial dopamine (and serotonin) agonists developed as novel antipsychotics. This article discusses their pharmacology, evidence on their licensed and off-licence uses (including psychosis, mania, bipolar depression, Tourette syndrome and autism spectrum disorder) and side-effects. In schizophrenia, they have a low risk of Parkinsonism or hyperprolactinaemia, cause modest increases in body weight and are of moderate efficacy.
This article discusses dopamine partial agonism, which is the main mechanism of action of the psychiatric drugs aripiprazole, brexpiprazole and cariprazine. It outlines the principles of receptor theory and the structure of dopamine receptors; characterises agonists, antagonists and partial agonists; and summarises the dopamine hypothesis of psychosis and the role of dopamine and serotonin in depression.
Problems in sexual function associated with psychotropic drugs in adolescents with psychotic disorders are common in clinical practice. However, they are usually not taken into account in follow-up and are rarely reported by patients.
Objectives
1. To analyze if there is sexual dysfunction in adolencents with antipsychotic treatment. 2. To assess the degree of sexual dysfunction.
Methods
Descriptive study in psychiatric outpatient clinics involving 14 men (aged 16 to 19) with antipsychotic treatment. Record prospectively through interviews between 2 and 4 months from the start of treatment. Sexual function was evaluated with the questionnaire SALSEX Informed consent.
Results
Initially, no sexual dysfunction scores are obtained. At 4 months, records of sexual dysfunction were observed in 67% of the patients with less impact in those with aripiprazole as antipsychotic treatment, with a moderate intensity (mean score 8.2; SD 4.7). 33% of cases report the problem spontaneously. Breaking down the reasons for sexual dysfunction: 50% decrease in libido, 20% delay in ejaculation and 7% impotence. The global tolerance to sexual dysfunction was poor, 45% with ideas to abandon treatment.
Conclusions
In our experience, sexual dysfunction is one of the main causes that make young patients abandon treatment and even follow-up. For what we consider, it is very relevant to systematically evaluate and be able to quantify this vital aspect of our patients, which on many occasions is not addressed in the consultation. Likewise, it will be necessary in future studies to describe in detail the psychotropic drugs associated with sexual dysfunction for better management and dose adjustment.
As disorders of thought, delusions are modified by patients’ background, and so their content varies widely according to location and throughout the ages. The COVID-19 pandemic has shown its global impact on society and mental health of the population, thus becoming a new delusional topic.
Objectives
We report a case where the COVID-19 pandemic has been integrated into a patient’s delusion in an attempt to raise professional awareness for this new psychotic presentation.
Methods
Review of clinical notes and literature review.
Results
A 38-year-old female patient with no prior psychiatric history presented with psychotic symptoms characterized by self-referential ideas, feelings of guilt and delusions of ruin, with a sudden onset of less than 24 hours prior to observation. The patient claimed that she was the coronavirus and, as such, she was a common topic of conversation in both television and social media, and the reported deaths caused by COVID-19 were her own doing. As a result of this, the patient was asking doctors to kill her in order to save everyone else affected by the virus. After evaluation, a diagnosis of Acute and Transient Psychotic Disorder was considered. The patient was initially treated with paliperidone, but due to hyperprolactinemia and menstrual changes this was switched to aripiprazole. Symptoms remitted fully after 21 days of treatment, and six months later no recurrences have been described.
Conclusions
This case illustrates the potential of the coronavirus pandemic outbreak as a new delusional topic. Possible side effects of treatment are also discussed.