Psychoactive Medication, Violence, and Variant Alleles for Cytochrome P450 Genes

From the start of the use of psychoactive prescription medications in the 1950s, physicians reported paradoxical adverse reactions, ranging from newly developing depressions to an increase in existing mood disorders, and extremely violent and bizarre acts of suicide and homicide. It is hypothesized that interactions between the drugs and the enzymes that are primarily responsible for their metabolism (cytochrome P450s) could cause these reactions. In this research, we evaluate statistical associations between CYP450 variant alleles, psychoactive medication, and acts of violence. Fifty-five persons who showed violent behavior or an altered emotional state were investigated for prescribed medication. Fifty-eight volunteers with no history of violence served as the controls. Genetic testing was performed on CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Statistical analysis was applied to gender, age, number of variant alleles, number and kind of medications, and potential drug–drug, drug–gene, and drug–drug–gene interactions. Four risk factors for developing an altered emotional state and/or acts of violence were identified. There is an association between prescription drugs (most notably antidepressants and other psychoactive medication), having variant alleles for CYP450 genes, and altered emotional states or acts of violence.

Medication Related Problems

When selecting and managing psychoactive medications in older people, it is equally important to focus on avoidance of toxicity as it is to focus on efficacy. Higher psychoactive medication load is associated with increased rate and risk of all cause hospitalization. The medication classes used to treat depression and related comorbidities include antidepressants, antipsychotics, stimulants, mood stabilizers, lithium, anxiolytics and sedative hypnotics. This discussion will examine considerations to help avoid medication related problems relevant to medications used to treat depression in the antidepressant pharmacological class.

Medication Related Problems

When selecting and managing psychoactive medications in older people, it is equally important to focus on avoidance of toxicity as it is to focus on efficacy. Higher psychoactive medication load is associated with increased rate and risk of all cause hospitalization. The medication classes used to treat depression and related comorbidities include antidepressants, antipsychotics, stimulants, mood stabilizers, lithium, anxiolytics and sedative hypnotics. This discussion will examine considerations to help avoid medication related problems relevant to medications used to treat depression in the antidepressant pharmacological class.

Quetiapine withdrawal: A systematic review

Objective: Withdrawal from psychoactive medication such as quetiapine is a well-documented phenomenon. Despite the extensive use of quetiapine, there have been few studies into the presence of discontinuation symptoms. We therefore performed a systematic review of published literature for evidence of quetiapine withdrawal or symptoms associated with discontinuation. Methods: We searched PubMed, Embase, CINAHL, Medline, Web of Science, PsycINFO for articles containing the terms ‘Quetiapine’ AND ‘withdraw$’ OR ‘discontinue$’. We included all study types that reported on somatic withdrawal symptoms and had no language restrictions. We excluded studies where there was withdrawal from multiple medications or any other psychoactive substance, or where the only symptoms were psychological such as rebound psychosis or craving. Results: We included 13 papers, all of which were individual case reports. The quality of the individual case reports was sub-optimal, as assessed by the CARE Case Report Guidelines. There was an association between rapid cessation of quetiapine and onset of somatic symptoms such as nausea, vomiting, agitation, restlessness, diaphoresis, irritability, anxiety, dysphoria, sleep disturbance, insomnia, tachycardia, hypertension and dizziness. Three studies also reported the onset of a withdrawal dyskinesia characterised by abnormal choreiform movements as well as confusion and speech disturbance in some cases. However, these findings were limited by the number and quality of case reports identified. Conclusion: Discontinuation symptoms are an uncommon side effect of quetiapine cessation, which may have clinical implications. Clinicians should therefore be alert to the possibility of quetiapine withdrawal in individuals who present with somatic symptoms or choreiform movements. However, large prospective studies are required to clarify this association.

Associated factors of REM sleep without atonia in younger (≤ 50 years) hospitalized psychiatric patients

Background Isolated REM sleep without atonia (RSWA) as a main polysomnograhic feature of REM sleep behaviour disorder (RBD) is thought to be a prodromal or subclinical state of the disease. RSWA/RBD occurence in psychiatric population is much more frequent than in general population but its associated factors are still not known. Methods We invited 88 psychiatry in-patients to undervent video-polysomnography. The visual scoring was focused on RSWA in submentales and flexores digitales superficiales muscles. This parametr was subsequently correlated mainly with age/gender, their medication and mental status. Results The RWSA was mostly still in normal range despite the fact, that selected psychiatry patients (≤ 50 years) were taking several classes of psychoactive medication. 3,6% had convincingly RBD, although 35.7% reported rare lifetime occurence of dream-enacting behaviour and 62.8% sporadic nightmares. We found correlation between RSWA and SNRI medication class (p = 0.015), specifically venlafaxine (p = 0.029) as well as quetiapine (p = 0.030). Another significant associated factors were current anxiety (p < 0.001) and depressive symptoms (p = 0.05), but we found no relation between RSWA and given diagnosis. Conlucions Isolated RSWA in younger psychiatry patients might be a result of multiple factors, including medication and current mental status but these factors are in most cases not sufficient to manifest RBD.

Patterns of Psychoactive Medication Use in Community-Dwelling Older Adults in the US in 2016: A Descriptive Cross-Sectional Study

Objectives: We aim to quantify any use and long-term use patterns of psychoactive medications and explore differences in use by sociodemographic factors in older adults (60–85 years) using the 2016 Medical Expenditure Panel Survey. Methods: Prevalence estimates of any use and long-term use were calculated. Chi-square and crude odds ratios were calculated to estimate differences in any use and long-term use of psychoactive medication by sociodemographic characteristics of respondents. Results: Thirty percent of older adults in the US reported any use of psychoactive medications. Long-term use was significantly higher in women (28.3% [95% confidence interval: 26.5, 30.2]), white (27.8 [26.1, 29.7]), presently unmarried (27.5 [25.4, 29.7]), and low-income (30.3 [27.7, 32.9]) subgroups than in men (20.5 [18.4, 22.5]), Black (14.7 [12.3, 17.1]), presently married (22.8 [20.7, 24.9]), and high-income (21.1 [19.1, 23.1]) subgroups, respectively. Discussion: Despite continued risks associated with use, long-term use of psychoactive medications is prevalent in the older adult population in the US. Given the increased complexity of pharmacotherapy regimens in this population, enhanced efforts at improving use of psychoactive medications should be intensified.

Estimated Frequency of Psychodermatologic Conditions in Alberta, Canada

Background Psychodermatologic disorders are difficult to identify and treat. Knowledge about the prevalence of these conditions in dermatological practice in Canada is scarce. This hampers our ability to address potential gaps and establish optimal care pathways. Objectives To provide an estimate of the frequencies of psychodermatologic conditions in dermatological practice in Alberta, Canada. Methods Two administrative provincial databases were used to estimate the prevalence of potential psychodermatological conditions in Alberta from 2014 to 2018. Province-wide dermatology claims data were examined to extract relevant International Classification of Disease codes as available. Claims were linked with pharmacy dispensation data to identify patients who received at least 1 psychoactive medication within 90 days of the dermatology claim. Results Of 243 963 patients identified, 28.6% had received at least 1 psychotropic medication (mean age: 47.9 years; 67.5% female). Rates of concurrent psychotropic medications were highest for pruritus and related conditions (46.7%), followed by urticaria (44.5%) and hyperhidrosis (32.8%). Among patients with psychotropic medications, rates of antidepressants were highest (56.3%), followed by anxiolytics (37.1%). Across billing codes, besides hyperhidrosis (71.2%), diseases of hair (61.4%) and psoriasis (59.1%) had the highest rates of antidepressant dispensations. Patients with atopic dermatitis had the highest rates for anxiolytic prescriptions (54.3%). Conclusion In a 5-year window, more than a quarter of the identified dermatology patients in Alberta received at least 1 psychotropic medication, pointing to high rates of potential psychodermatologic conditions and/or concurrent mental health issues in dermatology. Diagnostic and care pathways should include a multidisciplinary approach to better identify and treat these conditions.

Prescription Psychoactive Medication Use in Adolescent Survivors of Childhood Cancer and Association With Adult Functional Outcomes

Background This study estimates the prevalence and identifies predictors of psychoactive medication use in adolescent survivors of childhood cancer (aged 12-18 years) and its associations with functional outcomes at young adulthood (aged 18-28 years). Methods This retrospective cohort study includes 5665 adolescent survivors of childhood cancer at no less than 5 years postdiagnosis (53.8% male, median age = 15 years, interquartile range [IQR] = 13-16 years) and 921 adolescent sibling controls. Parent-reported psychoactive medication use during adolescence was collected at baseline. After a median of 8 years, functional outcomes and social attainment were self-reported during adulthood (n = 3114, median age = 22 years, IQR = 20-24 years). Multivariable log-binomial models evaluated associations among risk factors, medication use, and adult outcomes. Results Higher prevalence of psychoactive medication use was reported in survivors compared with siblings (18.3% vs 6.6%; 2-sided P &lt; .001), with trends for increasing antidepressant and stimulant use in recent treatment eras. After adjusting for cancer treatment and baseline cognitive problems, psychoactive medication use during adolescence was associated with impaired task efficiency (relative risk [RR] = 1.20, 95% confidence interval [CI] = 1.01 to 1.43) and memory (RR = 1.27, 95% CI = 1.05 to 1.52) during adulthood. Survivors who reported continued use of medications from adolescence to adulthood demonstrated poorer emotional regulation (RR = 1.68, 95% CI = 1.24 to 2.27) and organization (RR = 1.82, 95% CI = 1.28 to 2.59) compared with nonusers. Adolescent opioid use was associated with somatization symptoms (RR = 1.72, 95% CI = 1.09 to 2.73) during adulthood, after adjusting for cancer treatment and baseline behavioral problems. They were also more likely to not complete college (RR = 1.21, 95% CI = 1.04 to 1.41) or work full-time (RR = 1.60, 95% CI = 1.23 to 2.08) compared with nonusers. Conclusion Use of psychoactive medication is more prevalent among adolescent survivors compared with siblings and does not normalize adult outcomes, as evidenced by poorer functional outcomes during young adulthood.

PATTERNS OF PSYCHOACTIVE MEDICATION USE IN COMMUNITY-DWELLING OLDER ADULTS IN THE UNITED STATES IN 2015

Per the 2015 Beer’s Criteria, most psychoactive medications are identified as potentially inappropriate for use in older adults as this population is especially vulnerable to the potential adverse effects associated with psychoactive medications, including sedation, anticholinergic effects, and falls. Past studies found increasing use of psychoactive medications in community-dwelling older adults; however, patterns of use by other sociodemographic, socioeconomic, and clinical subgroups have not been explored. This is a cross-sectional analysis of 2015 Medical Expenditure Panel Survey in a sample of 6122 older adults (60-85 years). We utilized Andersen’s Behavioral Model of Health Services Utilization to guide logistic regression model development and estimated odds ratios (OR) with 95% confidence intervals (CI) to quantify the association between psychoactive use and predisposing(sex and race); enabling(marital status, education, poverty, insurance); and need-based[multi-morbidity and activities of daily living (ADL) limitations] factors. Over 30% of older adults in the U.S. reported taking a psychoactive medication in 2015. Prevalence of use was significantly higher in women (35.9%), the unmarried(34.1%), low-income(35.7%), white(34.0%), multimorbid (32.0%), and ADL limitation groups (45.9%) compared to men, married, high-income, other races, not multimorbid, and no ADL limitations groups, respectively. Female sex [OR=1.62(1.38-1.91)], low-income [OR=1.30(1.04-1.6)], multimorbidity [OR=3.2(2.6-3.9)], and ADL limitations [OR=2.2(1.7-2.8)] were identified as independent predictors of psychoactive use. There is differential use of psychoactive medications by sociodemographic, socioeconomic, and clinical factors. Given the increased complexity of pharmacotherapy regimens, especially in those with multimorbidity and ADL limitations, improved efforts aimed at prudent use of psychoactive medications should be intensified.