Editorial
Three confounded high-risk groups for suicide in adolescents and young adults
- Mayank Gupta, Nihit Gupta, Dhanvendran Ramar
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- Published online by Cambridge University Press:
- 13 December 2021, pp. 115-117
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Suicide rates among adolescents and young adults have been increasing in the last decade. The current knowledge of the warning signs, risk factors, and the use of screening tools has many gaps. There are many views from within, critics, survivors, and advocacy groups to focus more on the contextual understanding of symptomatology. In clinical practice, many of these high-risk groups fail to raise the red flags due to the complex and ambiguous nature of presentations. Therefore, these groups need greater attention, and given their counter-initiative nature, they challenge the current approaches to address suicidality in adolescents and young adults.
Letter to the Editor
Potential role of vitamin D3 in preventing neurocognitive complications in COVID-19 survivors
- Sujita Kumar Kar, Sarvodaya Tripathy
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- Published online by Cambridge University Press:
- 20 December 2021, pp. 118-119
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Review
Psychopathy in women: insights from neuroscience and ways forward for research
- John Tully, Annalena Frey, Maria Fotiadou, Nathan J. Kolla, Hedwig Eisenbarth
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- Published online by Cambridge University Press:
- 15 December 2021, pp. 120-132
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Psychopathy is a severe form of personality disturbance, resulting in a detrimental impact on individuals, healthcare systems, and society as a whole. Until relatively recently, most research in psychopathy has focused on male samples, not least because of its link with criminal behavior and the large proportion of violent crime committed by men. However, psychopathy in women also leads to considerable problems at an individual and societal level, including substance misuse, poor treatment outcomes, and contribution to ever-increasing numbers of female prisoners. Despite this, due to relative neglect, most research into adult female psychopathy is underpowered and outdated. We argue that the field needs revitalizing, with a focus on the developmental nature of the condition and neurocognitive research. Recent work international consortia into conduct disorder in female youth—a precursor of psychopathy in female adults—gives cause for optimism. Here, we outline key strategies for enriching research in this important field with contemporary approaches to other psychiatric conditions.
Treatment strategies for clozapine-induced nocturnal enuresis and urinary incontinence: a systematic review
- Timothy Tanzer, Nicola Warren, Laura McMahon, Michael Barras, Steve Kisely, Emily Brooks, Emily Wong, Dan Siskind
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- Published online by Cambridge University Press:
- 28 January 2022, pp. 133-144
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Background
Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers.
MethodsWe systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.
ResultsWe identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence.
ConclusionsFollowing assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.
Early optimized pharmacological treatment in patients with depression and chronic pain
- Oloruntoba J. Oluboka, Martin A. Katzman, Jeffrey Habert, Atul Khullar, Margaret A. Oakander, Diane McIntosh, Roger S. McIntyre, Claudio N. Soares, Raymond W. Lam, Larry J. Klassen, Robert Tanguay
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- Published online by Cambridge University Press:
- 23 February 2022, pp. 145-156
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Major depressive disorder (MDD) is the leading cause of disability worldwide. Patients with MDD have high rates of comorbidity with mental and physical conditions, one of which is chronic pain. Chronic pain conditions themselves are also associated with significant disability, and the large number of patients with MDD who have chronic pain drives high levels of disability and compounds healthcare burden. The management of depression in patients who also have chronic pain can be particularly challenging due to underlying mechanisms that are common to both conditions, and because many patients with these conditions are already taking multiple medications. For these reasons, healthcare providers may be reluctant to treat such patients. The Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines provide evidence-based recommendations for the management of MDD and comorbid psychiatric and medical conditions such as anxiety, substance use disorder, and cardiovascular disease; however, comorbid chronic pain is not addressed. In this article, we provide an overview of the pathophysiological and clinical overlap between depression and chronic pain and review evidence-based pharmacological recommendations in current treatment guidelines for MDD and for chronic pain. Based on clinical experience with MDD patients with comorbid pain, we recommend rapidly and aggressively treating depression according to CANMAT treatment guidelines, using antidepressant medications with analgesic properties, while addressing pain with first-line pharmacotherapy as treatment for depression is optimized. We review options for treating pain symptoms that remain after response to antidepressant treatment is achieved.
Original Research
Obsessive–compulsive disorder and the associated risk of autoimmune skin diseases: a nationwide population-based cohort study
- Yu-Ju Chou, Ying-Hsuan Tai, Ying-Xiu Dai, Din-Dar Lee, Yun-Ting Chang, Tzeng-Ji Chen, Mu-Hong Chen
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- Published online by Cambridge University Press:
- 11 February 2022, pp. 157-163
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Background
The concurrent incidence of autoimmune comorbidities in obsessive–compulsive disorder (OCD) is known. However, the association between OCD and related autoimmune skin diseases (ASDs) has not been well studied.
ObjectiveThis study aimed to investigate the association between OCD and the risk of ASDs.
MethodsTo assess the risk of developing ASDs, we recruited 44 324 patients with OCD and 177 296 matched controls from the National Health Insurance Research Database in Taiwan. A Cox regression model was used for the analyses.
ResultsAfter adjusting for confounders, an increased risk of ASDs among the patients with OCD (adjusted hazard ratio [aHR]: 6.36; 95% confidence interval [CI]: 5.43-7.45) was found when compared to the controls. Statistically significant associations were found between OCD and seven individual ASDs, including psoriasis (aHR: 12.52; 95% CI: 8.78-17.85), lichen planus (aHR: 27.22; 95% CI: 13.09-56.60), alopecia areata (aHR: 13.69; 95% CI: 9.38-19.98), autoimmune bullous diseases (aHR: 4.30; 95% CI: 2.03-9.11), hidradenitis suppurativa (aHR: 29.95; 95% CI: 3.35-267.62), vitiligo (aHR: 9.35; 95% CI: 5.35-16.32), and lupus erythematosus (aHR: 2.10; 95% CI: 1.52-2.91).
ConclusionsPatients with OCD had an increased risk of developing ASDs compared to matched controls. Further studies are required to clarify the underlying mechanisms.
The role of psychological distress in the relationship between lifestyle and compulsivity: An analysis of independent, bi-national samples
- Mary-Ellen E. Brierley, Lucy Albertella, Kristian Rotaru, Louise Destree, Emma M. Thompson, Chang Liu, Erynn Christensen, Amelia Lowe, Rebecca A. Segrave, Karyn E. Richardson, Edouard Kayayan, Samuel R. Chamberlain, Jon E. Grant, Rico S. C. Lee, Sam Hughes, Murat Yücel, Leonardo F. Fontenelle
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- Published online by Cambridge University Press:
- 13 December 2021, pp. 164-173
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Background
Poor mental health is a state of psychological distress that is influenced by lifestyle factors such as sleep, diet, and physical activity. Compulsivity is a transdiagnostic phenotype cutting across a range of mental illnesses including obsessive–compulsive disorder, substance-related and addictive disorders, and is also influenced by lifestyle. Yet, how lifestyle relates to compulsivity is presently unknown, but important to understand to gain insights into individual differences in mental health. We assessed (a) the relationships between compulsivity and diet quality, sleep quality, and physical activity, and (b) whether psychological distress statistically contributes to these relationships.
MethodsWe collected harmonized data on compulsivity, psychological distress, and lifestyle from two independent samples (Australian n = 880 and US n = 829). We used mediation analyses to investigate bidirectional relationships between compulsivity and lifestyle factors, and the role of psychological distress.
ResultsHigher compulsivity was significantly related to poorer diet and sleep. Psychological distress statistically mediated the relationship between poorer sleep quality and higher compulsivity, and partially statistically mediated the relationship between poorer diet and higher compulsivity.
ConclusionsLifestyle interventions in compulsivity may target psychological distress in the first instance, followed by sleep and diet quality. As psychological distress links aspects of lifestyle and compulsivity, focusing on mitigating and managing distress may offer a useful therapeutic approach to improve physical and mental health. Future research may focus on the specific sleep and diet patterns which may alter compulsivity over time to inform lifestyle targets for prevention and treatment of functionally impairing compulsive behaviors.
Genome-wide DNA methylation profiling in nonagenarians suggests an effect of PM20D1 in late onset Alzheimer’s disease
- Carolina Coto-Vílchez, José J. Martínez-Magaña, Lara Mora-Villalobos, Daniel Valerio, Alma D. Genis-Mendoza, Jeremy M. Silverman, Humberto Nicolini, Henriette Raventós, Gabriela Chavarria-Soley
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- 16 December 2021, pp. 174-182
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Background
The aim of this study is to identify differentially methylated regions (DMRs) in the genomes of a sample of cognitively healthy individuals and a sample of individuals with LOAD, all of them nonagenarians from Costa Rica.
MethodsIn this study, we compared whole blood DNA methylation profiles of 32 individuals: 21 cognitively healthy and 11 with LOAD, using the Infinium MethylationEPIC BeadChip. First, we calculated the epigenetic age of the participants based on Horvath’s epigenetic clock. DMRcate and Bumphunter were used to identify DMRs. After in silico and knowledge-based filtering of the DMRs, we performed a methylation quantitative loci (mQTL) analysis (rs708727 and rs960603).
ResultsOn average, the epigenetic age was 73 years in both groups, which represents a difference of over 20 years between epigenetic and chronological age in both affected and unaffected individuals. Methylation analysis revealed 11 DMRs between groups, which contain six genes and two pseudogenes. These genes are involved in cell cycle regulation, embryogenesis, synthesis of ceramides, and migration of interneurons to the cerebral cortex. One of the six genes is PM20D1, for which altered expression has been reported in LOAD. After genotyping previously reported mQTL SNPs for the gene, we found that average methylation in the PM20D1 DMR differs between genotypes for rs708727, but not for rs960603.
ConclusionsThis work supports the possible role of PM20D1 in protection against AD, by showing differential methylation in blood of affected and unaffected nonagenarians. Our results also support the influence of genetic factors on PM20D1 methylation levels.
Twenty-year trends in use of electroconvulsive therapy among homeless and domiciled veterans with mental illness
- Jack Tsai, Dorota Szymkowiak, Samuel T. Wilkinson, Paul E. Holtzheimer
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- 13 December 2021, pp. 183-189
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Background
To examine socioeconomic disparities in use of electroconvulsive therapy (ECT) among homeless or unstably housed (HUH) veterans with mental illness.
MethodsNational data from medical records in years 2000 to 2019 on 4 to 6 million veterans with mental illness, including 140 000 to 370 000 homeless veterans served annually from the U.S. Department of Veterans Affairs (VA) healthcare system, were analyzed to examine ECT utilization and changes in utilization over time.
ResultsECT utilization was higher among HUH veterans (58–104 per 1000) than domiciled veterans with mental illness (9–15 per 1000) across years with a trend toward increasing use of ECT use among HUH veterans over time. Among HUH and domiciled veterans who received ECT, veterans received an average of 5 to 9 sessions of ECT. There were great regional differences in rates of ECT utilization among HUH and domiciled veterans with the highest overall rates of ECT use at VA facilities in the Northeast and Northwest regions of the country.
DiscussionECT is commonly and safely used in HUH veterans in a comprehensive healthcare system, but geographic and local factors may impede access to ECT for veterans who may benefit from this treatment. Efforts should be made to reduce barriers to ECT in the HUH population.
Safety and efficacy of early augmentation with repetitive transcranial magnetic stimulation in the treatment of drug-free patients with obsessive–compulsive disorder
- Mohita Joshi, Sujita Kumar Kar, Pronob K. Dalal
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- 27 January 2022, pp. 190-196
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Background
Obsessive–compulsive disorder (OCD) is a chronic psychiatric disorder that results in significant disability and substantial compromise in the quality of life. Until now, the role of repetitive transcranial magnetic stimulation (rTMS) has been primarily explored in individuals with treatment-resistant OCD. In this study, we investigated the safety and efficacy of rTMS as an early augmentation strategy in drug-free patients with OCD.
MethodsThis is a randomized double-blind, placebo-controlled study that involved the administration of a total of 20 sessions of rTMS (active/sham) to drug-naïve OCD patients using a standard protocol (1-Hz; 20 trains [80 pulses/train]; 1600 pulses per session at 100% resting motor threshold) at supplementary motor area. All patients (active and sham) were started on escitalopram 10 mg/d, which was subsequently increased to 20 mg/d after 10 days.
ResultsOut of the 24 patients, 13 received active and 11 received sham rTMS. At the end of rTMS therapy, there was a substantial reduction (P = .001) in total Yale-Brown Obsessive–Compulsive Scale, obsessions (P = .030) and compulsions (P = .001) between the groups. Only few patients (N = 8) reported mild side effect with rTMS, local pain, and headache being the commonest. The study revealed large effect size (Cohen’s d = 1.6) of rTMS as an early augmentation strategy in drug-free patients of OCD.
ConclusionsrTMS is a safe and effective early augmentation strategy in the management of OCD. Larger randomized controlled trials are required to establish the therapeutic role of rTMS as early augmentation in OCD.
Pain perception and physiological correlates in body-focused repetitive behavior disorders
- Christine Lochner, Janine Roos, Martin Kidd, Gaironeesa Hendricks, Tara S. Peris, Emily J. Ricketts, Darin D. Dougherty, Douglas W. Woods, Nancy J. Keuthen, Dan J. Stein, Jon E. Grant, John Piacentini
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- 22 March 2022, pp. 197-204
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Background
Behaviors typical of body-focused repetitive behavior disorders such as trichotillomania (TTM) and skin-picking disorder (SPD) are often associated with pleasure or relief, and with little or no physical pain, suggesting aberrant pain perception. Conclusive evidence about pain perception and correlates in these conditions is, however, lacking.
MethodsA multisite international study examined pain perception and its physiological correlates in adults with TTM (n = 31), SPD (n = 24), and healthy controls (HCs; n = 26). The cold pressor test was administered, and measurements of pain perception and cardiovascular parameters were taken every 15 seconds. Pain perception, latency to pain tolerance, cardiovascular parameters and associations with illness severity, and comorbid depression, as well as interaction effects (group × time interval), were investigated across groups.
ResultsThere were no group differences in pain ratings over time (P = .8) or latency to pain tolerance (P = .8). Illness severity was not associated with pain ratings (all P > .05). In terms of diastolic blood pressure (DBP), the main effect of group was statistically significant (P = .01), with post hoc analyses indicating higher mean DBP in TTM (95% confidence intervals [CI], 84.0-93.5) compared to SPD (95% CI, 73.5-84.2; P = .01), and HCs (95% CI, 75.6-86.0; P = .03). Pain perception did not differ between those with and those without depression (TTM: P = .2, SPD: P = .4).
ConclusionThe study findings were mostly negative suggesting that general pain perception aberration is not involved in TTM and SPD. Other underlying drivers of hair-pulling and skin-picking behavior (eg, abnormal reward processing) should be investigated.
Sex differences in patients with Tourette syndrome
- José Fidel Baizabal-Carvallo, Joseph Jankovic
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- 16 February 2022, pp. 205-211
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Background
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and phonic tics. It is at least three times more common in males compared with females; however, the clinical phenomenology between sexes has not been fully examined. We aimed to contrast the clinical features between males and females with TS and chronic tic disorder.
MethodsWe studied 201 consecutive patients fulfilling the diagnostic criteria for TS, persistent (or chronic) motor and vocal tic disorder and provisional tic disorder that were considered within the TS spectrum disorder. We performed blinded evaluations of video-recordings and retrospectively reviewed the clinical charts of all patients.
ResultsAge ranges between 4 and 65 years. Males represented 77.6% of patients in the cohort. Overall, no differences were observed in the frequency, distribution and complexity of tics between sexes, except for a higher frequency of attention-deficit/hyperactivity disorder (ADHD) (P = .003) among males. Patients younger than 18-years old, in addition to a higher frequency of ADHD (P = .026), males had a statistically higher frequency of complex motor tics (P = .049) and earlier age at onset (P = .072) than females in the multivariate regression analysis. However, these differences were lost in patients older than 18 years, due to increased complexity of tics in females with aging.
ConclusionsA sexual dimorphism was observed between patients with TS mainly before age of 18 years, suggesting an earlier onset of some types of tics and ADHD in males compared to females.
Abstracts
Aripiprazole: Examining the Clinical Implications of D2 Affinity
- Adiba Anam, Sean Lynch, Nafiz Mosharraf, Chloe Soukas, Dmitriy Gekhman
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- 14 April 2023, p. 213
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Background
Aripiprazole has high binding affinity for the dopamine D2 receptor, which is thought to be responsible for the antipsychotic effect, though aripiprazole is not the most potent of the second-generation antipsychotics. Theoretically, aripiprazole could displace or outcompete more potent antipsychotics, prompting decreased antipsychotic effect. We describe a case of aripiprazole potentially worsening psychiatric symptoms by blocking paliperidone.
CaseMs. A is a 43-year-old woman with schizophrenia, multiple inpatient hospitalizations, and a history of court-ordered treatment. She historically has had good response to oral and long-acting formulations of risperidone and paliperidone. Ms. A requested a medication change and was transitioned to aripiprazole lauroxil injection with plan for bimonthly administration. Approximately 1 month after receiving her aripiprazole lauroxil injection, Ms. A presented to our CPEP due to symptoms of psychosis and was admitted to our inpatient unit. She was restarted on oral paliperidone, titrated up to her previously effective dose, and was transitioned to paliperidone palmitate LAI. In contrast to prior admissions, she did not respond well to paliperidone and displayed continued and worsened psychosis.
DiscussionPrior studies have examined how adding aripiprazole to another, more potent D2 antagonist can cause a relapse in psychotic symptoms; however, few studies have investigated the inverse relationship or mechanism. Those that have proposed mechanisms typically refer to aripiprazole’s partial agonist activity as the causative factor, rather than an impediment to antipsychotic binding which we have described. Prescribers should be aware of this potential interaction and carefully consider initiating long-acting injectable forms of aripiprazole to avoid this phenomenon.
FundingNo Funding
Analyzing Demographic Variabilities Associated With Age of Diagnosis of Schizophrenia Among Patients in Controlled Clinical Trials
- Vijay Singh, Mahmoud Alnsour, Nikhil Gopal, Amber Shin, Shreedhar Kulkarni, Aghaegbulam Uga
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- Published online by Cambridge University Press:
- 14 April 2023, pp. 213-214
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Background
Prior literature and epidemiological data suggests that the age of diagnosis of schizophrenia (AOD) follows a bimodal and trimodal distribution for males and females, respectively. The studies used to generate these findings were often small and relied on self-reported patient data from a single geographic region in addition to other methodological limitations. We replicated these studies using a modern big data approach by combining raw data from large randomized controlled clinical trials.
MethodsPatient-level data from 15 similarly designed, randomized, double-blind, placebo-controlled, crossover studies with patients using paliperidone extended-release tablets, paliperidone palmitate 1-month, and paliperidone palmitate 3-month, were obtained through the Yale Open Data Access Initiative (YODA). Descriptive statistics and histograms were calculated for continuous variables. A multivariable linear regression was performed with AOD as the outcome variable. Race and sex were used as predictor variables.
ResultsOur final analysis included 7881 patients consisting of male (n=4962) and female (n=2919) patients among different racial demographics. Race was consolidated into the following groups: Asian (n=949), Black (n=1692), Hispanic (n=3), Southeast Asian (n=17), White (n=4769), and other (n=343) based on patient self-identification on the YODA datasets. A chi-square test revealed that there is a statistically significant association between patient sex and AOD (x2=295.61, df=68, p < 0.0001). By proxy, this likely means that sex affects age of onset (AOS) as well. Our linear regression output with sex as a predictor of AOD revealed that only the male variable was found to have a statistically significant relationship (p<0.0001) with AOD and resulted in a lower AOD. Histograms generated with the frequency of occurrences against AOD for both male and female patients appeared to be unimodally distributed and skewed right. However, the AOD for female and male patients were found to be 28.79 and 25.44 years old, respectively. This demonstrates that while both male and female AOD are distributed unimodally, there are slight differences in their distributions.
ConclusionOur analysis differs from previous studies and finds that AOD for male and female patients are seen in a unimodal distribution as compared to previous literature that shows a bimodal and trimodal distribution. Our findings not only call for a re-evaluation of previous epidemiological understandings of AOD but may support future efforts in understanding the origins and typical clinical presentations of patients with newly developed symptomatology of schizophrenia as well as support clinicians’ perspectives as part of clarifying differential diagnoses. Further studies can also continue to evaluate possible correlations among different races.
FundingNo Funding
Thanatotic Infestation: Ekbom’s Syndrome as an Exordium to Cotard’s Delusion
- Ahmed A. Chaudhry, Jack W. Hirsch
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- 14 April 2023, p. 214
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Introduction
Ekbom’s delusion as a prelude to Cotard’s syndrome, has not heretofore been described.
MethodsCase study: A 45-year-old woman with a past diagnosis of bipolar disorder with psychotic features was admitted, having been up all night conversing with spirits, proclaiming that she had made a deal with Satan. Convinced that her grandmother was possessed by the devil, she smashed her grandmother’s head with a two-by-four. Results: Mental Status Examination: self conversing with her eyes darting around the room. Poor hygiene. Behavior: guarded and withdrawn. Oriented x2. Speech: hyperverbal. Insight and judgment: poor. Mood: hostile, aggressive, and angry. Thought process disorganized, incongruent, and tangentiality. She was convinced she was infested with little black bugs crawling around her insides which had been placed there by the devil. After two days of olanzapine she reported the bugs were no longer present, but rather that she herself was dead and that her organs were decomposing, which persisted through the remainder of the hospitalization.
DiscussionNeuroimaging abnormalities in Ekbom’s syndrome involve the striatum, basal ganglia (putamen and caudate nucleus), insular and cingulate cortices, cortex (prefrontal, right parietal, and temporal lobes), right lingual and orbitofrontal gyri, and thalamus. In Cotard’s syndrome, abnormalities have been identified in the striatum, frontal and temporal lobes, and right-sided and bilateral hemispheres. An overlap between the delusions exists in the striatum, inferior parietal, and temporal lobes. A single lesion in the nondominant inferior parietal lobe may cause both syndromes, due to its substantial interconnection with the temporo-limbic areas. Since the parietal lobe is also involved in somatosensory processing, peradventure distorted sensory perception with associated sensation of formication may have been the nidus for the delusional infestation as well as a nidus for the perception of thanatos habitus. Such misperception may have then been amplified into a delusion because of a hyperconnection between the parietal lobe and the limbic system. This may represent a variant of the two-factor hypothesis of delusions whereby a distorted sensory perception is then misrepresented in a delusion. Dysfunction of the right hemisphere, which normally acts to censor the left, allows the delusion to manifest. A single lesion of the inferior parietal lobule may be sufficient for both sensory distortions and loss of inhibition of delusional interpretation of distorted sensation by the frontal lobe, yclept the sensorialist hypothesis.
ConclusionIn those with monothematic delusions, the search for transient fluctuation in delusional states may be revealing.
FundingNo Funding
Psychomotor Side Effects of Carbamazepine in an Elderly Patient With Bipolar Disorder and Cognitive Impairment
- Alejandro Compaired, Javier Torres
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- 14 April 2023, pp. 214-215
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Introduction
The management of elderly bipolar patients can become very complex due to higher prevalence of medical comorbidities and sensitivity to treatment-related adverse effects. One of the antiepileptic drugs used for their treatment, carbamazepine, has had a number of cognitive and psychomotor effects linked to it: deterioration in measures of information processing speed, and attention and faster motor skills after discontinuation, among others. The literature concerning them is quite sparse.
MethodologyWe report the case of a 75-year-old woman with bipolar disorder and unspecified cognitive impairment who was brought to the emergency department by her family due to global functional decline dating 3 weeks back.
ResultsThe patient had been diagnosed and in treatment with bipolar disorder for 40 years. About 2 months before the current episode, because of the presence of tremor and family reports of marked functional decline (from being independent for daily life activities to being bound to a wheelchair and with worsening cognitive symptoms), the psychiatrist opted for a gradual switch from valproate to carbamazepine. During our interview, her husband pointed to the complete dose of 100 mg of carbamazepine 3 weeks ago as the onset of her current symptoms. The patient demonstrated clear psychomotor inhibition, with an absence of spontaneous movement and sporadic, almost monosyllabic, responses to only the simplest questions. Although aware that she was in a hospital, she could not recall its name and was completely disoriented in regards to time. Barely capable of emoting with her facial muscles, she denied feeling depressed and only acknowledged a stomachache. After spending the night in observation, and the suspension of carbamazepine, the patient experienced an improvement of her cognitive functions: although still not fully oriented in space and time, she could now speak in sentences and answer most of our questions. Even though she still maintained not being depressed, when pressed about any weird sensations she admitted to the feeling of being dead inside. The decision was made to transfer her to the psychogeriatric hospitalization unit.
DiscussionThe initial assessment of the patient was complicated due to a variety of factors. Beyond the physical comorbidities, the psychomotor inhibition impeded a thorough examination of her emotional state. Only the suppression of her evening dose of carbamazepine allowed for the diagnosis of Cotard-like major depressive symptoms. Even though the cognitive impairment was apparent before, the state of the patient was markedly improved with just the removal of carbamazepine and was confirmed by her family to be a lot closer to her base state of more than a month ago.
ConclusionThe use of anticonvulsant therapy in elderly bipolar patients with cognitive impairment can have important side effects. Further evidence of the prevalence and specific nature and frequency of its side effects is needed.
FundingNo Funding
Pure Verbal Autopalinacousis
- Alisa Trinh, Alan Hirsch
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- Published online by Cambridge University Press:
- 14 April 2023, p. 215
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Introduction
Palinacousis, the phenomenon in which sounds are internally perseverated or repeated has not heretofore been reported occurring exclusively to an individual’s own voice.
MethodsA 52-year-old woman started to experience auditory hallucinations of her voice at 3 years old when she began talking out loud. The auditory hallucinations of her own voice, yclept autopalinacousis, consisting of one to three words, were affectively neutral, rarely disruptive, and unchanged by psychiatric medications. During these palinacoustic phenomena, she would hear the last few words she had spoken out loud repeat inside her head in both ears. When the autopalinacousis occurred, the words were repeated just once. Sound quality was an exact replication of how it was originally spoken. She only experienced the palinacousis to her own voice and never to any other sounds. For the palinacousis to occur, she had to verbally state the words loud enough for her to hear. If she spoke out loud but could not hear her own voice, via occlusion of her external auditory canal or presence of loud noise, the internal auditory repetition would not occur. However, after the auditory stimulus was sensed, nothing could reduce the palinacousis. The palinacousis could occur if she read out loud, but not if she read silently. The frequency of the autopalinacousis ranged from a few times a week to several times a day and was associated with reduced sleep, but unaffected by mood, psychiatric medications, or headaches. Five months prior to her psychiatric hospitalization, she began to experience paranoid delusions, decreased sleep, increased activity, rapid speech, and auditory hallucinations of one male and two female voices. In contrast to autopalinacousis, these auditory hallucinations consisted of full phrases or sentences, were affectively charged, intrusive, and diminished by psychiatric medications. No palinacousis occurred with the hallucinated voices.
ResultsAbnormalities: Mental Status Examination: Speech: pressured. Oriented x2. Memory: ability to remember 5 digits forwards and 2 digits backwards. She is not able to spell with word “world.” Calculation ability: poor. MRI of brain with and without contrast: normal.
DiscussionIn cases where patients with psychotic illness experience palinacousis, the palinacousis always appear after the psychotic illness has already manifested, anywhere from less than a year to 15 years later. Our patient’s palinacousis presented almost 5 decades before the onset of her auditory hallucinations and paranoid delusions. Furthermore, her palinacousis only occurred to her own spoken voice and never to any other voices. In those who present with auditory hallucinations, query as to the presence and characteristics of palinacousis is warranted.
FundingNo Funding
STARS Adjunct Trial: Evidence for the Effectiveness of a Digital Therapeutic as Adjunct to Treatment With Medication in Pediatric ADHD
- Amanda Maple, Lisa Palko, Elena Cañadas, Anil Jina
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- Published online by Cambridge University Press:
- 14 April 2023, pp. 215-216
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Background
Treatment of attention deficit hyperactivity disorder (ADHD) includes pharmacological and non-pharmacological interventions, both of which have demonstrated short-term efficacy. While efficacious, there are limitations to both modalities of treatment. Due partly to these limitations, there has been considerable interest in additional approaches to augmenting ADHD management. Digital therapeutics may offer improved access, minimal side effects, and low potential for abuse, while providing targeted treatment options for improving cognitive functions such as attention. AKL-T01 (EndeavorRx®) is the first and only FDA-cleared nonpharmacological prescription digital therapeutic delivered through a video game interface for the treatment of ADHD.
ObjectiveThe objective is to summarize the data from a clinical trial in support of FDA clearance using AKL-T01 adjunctively in children currently taking stimulant medication for ADHD.
MethodsThe STARS-Adjunct Trial was a multicenter, 12-week, open-label study of AKL-T01 in 206 children aged 8 to 14 years with a confirmed diagnosis of primarily inattentive or combined-type ADHD. The study included two cohorts: (1) subjects currently treated with ADHD medication (n=130) and (2) subjects not on any ADHD medication (n=76). Subjects had an ADHD Impairment Rating Scale (IRS) score ≥3 at baseline, and both cohorts used AKL-T01 for approximately 25 minutes per day, 5 days per week, over two 4-week treatment periods separated by a 4-week treatment pause.
ResultsAKL-T01 significantly improved (lowered) ADHD-related impairment as measured with the IRS (clinician rated) after the first 4-week treatment in both cohorts (P< 0.001). Results show that effects persist during a 4-week treatment pause and further improve with a second 4-week treatment period. A majority of parents and children indicated a perceived improvement in ability to pay attention after the trial. Most common device-related adverse events were decreased frustration tolerance, headache, and irritability which ranged from mild to moderate. No serious adverse events were reported.
ConclusionsThis study adds to and extends the clinical evidence base for AKL-T01, a video game-based treatment for improving attentional functioning in 8–12-year-old children with ADHD. Continued evaluation of the effects of AKL-T01 on other important aspects of functioning, like academic and social functioning, health utilization, and health outcomes, would continue to add to the evidence base that the effects observed in this and previous studies have substantial clinical and functional impact.
FundingAkili Interactive
Impact of Cariprazine on Weight and Blood Pressure in Bipolar I Depression: A Real-World Study Using Electronic Medical Records
- Christoph U. Correll, François Laliberté, Guillaume Germain, Sean D. MacKnight, Huy-Binh Nguyen, Mousam Parikh, Sally W. Wade, Andrew J. Cutler
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- Published online by Cambridge University Press:
- 14 April 2023, p. 216
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Introduction
Patients with a severe mental illness such as bipolar I disorder (BP-I) have a higher prevalence of obesity and related metabolic comorbidities than the general population. This study evaluated the impact of cariprazine on weight and blood pressure in patients with BP-I depression using electronic medical records (EMRs) from a nationally representative database.
MethodsAnalyses were based on data from EMRs in the Symphony Health’s Integrated Dataverse® from March 2015 to October 2018. Patients ≥18 years of age with ≥2 cariprazine fills (first dispensing=index date) and clinical activity for ≥12 months pre-index (baseline) and ≥1 month post-index were included. Patients also had a diagnosis of BP-I depression at their most recent episode prior to cariprazine initiation. The on-treatment period spanned from the index date to the earliest of cariprazine discontinuation, a switch to another atypical or long-acting injectable antipsychotic, end of clinical activity, or end of data. Metabolic outcomes of interest were weight and blood pressure (systolic and diastolic). For each outcome, patients were required to have ≥1 measurement in both the baseline and on-treatment periods. Linear trajectories during those periods were estimated using mixed-effects models; 95% confidence intervals (CIs) were calculated using non-parametric bootstrap procedures.
ResultsIn total, 1702 patients who met study eligibility criteria had ≥1 weight measurement recorded in the baseline and on-treatment periods; of these patients, 178 had bipolar I depression as their most recent episode. Patients gained an average of 2.43 kg/year during the baseline period and 0.60 (95% CI: -1.97, 3.70) kg/year during the on-treatment period. Analyses of blood pressure change (n=179) showed that cariprazine had neutral effects over the on-treatment period. Patients’ systolic blood pressure increased at 1.12 mmHg/year during baseline and decreased at -0.63 (95% CI: -3.59, 2.25) mmHg/year during the on-treatment period. For diastolic blood pressure, increases of 0.25 mmHg/year during baseline and 0.44 (95% CI: -1.65, 2.16) mmHg/year during the on-treatment period were observed.
ConclusionsAlthough patient weight was increasing prior to cariprazine initiation, a neutral weight trajectory was seen with long-term cariprazine treatment among those with a most recent BP-I depression episode. Cariprazine also had minimal impact on systolic or diastolic blood pressure. Overall, these findings are consistent with prior short- and long-term studies showing that cariprazine has a neutral weight and metabolic profile.
FundingAbbVie
Treatment Success and Psychiatric Stability in Adults With Tardive Dyskinesia: Post Hoc Analyses of Two Long-Term Valbenazine Studies
- Andrew J. Cutler, Rakesh Jain, Alon Bloom, Scott Siegert, Leslie Lundt
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- Published online by Cambridge University Press:
- 14 April 2023, pp. 216-217
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Introduction
Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with exposure to antipsychotics and other dopamine receptor blocking agents. Effective and comprehensive treatment of TD requires reducing patients’ abnormal involuntary movements without disrupting their psychiatric stability. This can be especially challenging when patients have complex psychiatric conditions (e.g., >1 psychiatric diagnosis) and are taking multiple medications. Valbenazine, a highly potent and selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved for the once-daily treatment of TD. This post hoc analysis of two long-term studies (KINECT 3, KINECT 4) was conducted to evaluate changes in psychiatric status and clinician- and patient-reported treatment success in study participants who received valbenazine (40 or 80 mg) for 48 weeks.
MethodsData from KINECT 3 and KINECT 4 were pooled and analyzed in participants categorized by their primary psychiatric diagnosis: schizophrenia/schizoaffective disorder (“SCHZ”) or mood disorder (“MD”). Concomitant medications needed for managing these and other psychiatric or medical conditions were allowed. Treatment success was defined as achieving a rating of “much improved” or “very much improved” at Week 48, as assessed using the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) and Patient Global Impression of Change (PGIC). Psychiatric stability was monitored using the following scales: Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) in the SCHZ subgroup; Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) in the MD subgroup. Suicidal ideation/behavior was monitored using the Columbia-Suicide Severity Rating Scale.
ResultsMore than 75% of study participants in the SCHZ subgroup achieved treatment success with valbenazine, based on clinician assessment (CGI-TD, 79.7%) and patient self-report (PGIC, 78.0%). Mean changes from baseline to Week 48 for PANSS scores (positive symptoms [-0.7], negative symptoms [‑0.6], general psychopathology [-1.9], total [-3.2]) and CDSS total score (-0.5) indicated maintenance of psychiatric stability in the SCHZ subgroup. Similar treatment success rates were found in the MD subgroup for both CGI-TD (77.6%) and PGIC (84.5%), with mean changes from baseline in YMRS total score (-1.0) and MADRS total score (+0.3) indicating psychiatric stability was maintained. No emergence of suicidal ideation/behavior was observed during the studies.
ConclusionsPooled analyses from two 48-week studies indicate that long-term treatment of TD with once-daily valbenazine resulted in substantial clinician- and patient-reported global improvements in TD, while psychiatric stability was maintained regardless of primary psychiatric condition.
FundingNeurocrine Biosciences, Inc.