Contemporary data relating to antipsychotic prescribing in UK primary care for patients diagnosed with severe mental illness (SMI) are lacking.

To describe contemporary patterns of antipsychotic prescribing in UK primary care for patients diagnosed with SMI.

Cohort study of patients with an SMI diagnosis (i.e. schizophrenia, bipolar disorder, other non-organic psychoses) first recorded in primary care between 2000 and 2017 derived from Clinical Practice Research Datalink. Patients were considered exposed to antipsychotics if prescribed at least one antipsychotic in primary care between 2000 and 2019. We compared characteristics of patients prescribed and not prescribed antipsychotics; calculated annual prevalence rates for antipsychotic prescribing; and computed average daily antipsychotic doses stratified by patient characteristics.

Of 309 378 patients first diagnosed with an SMI in primary care between 2000 and 2017, 212,618 (68.7%) were prescribed an antipsychotic between 2000 and 2019. Antipsychotic prescribing prevalence was 426 (95% CI, 420–433) per 1000 patients in the year 2000, reaching a peak of 550 (547–553) in 2016, decreasing to 470 (468–473) in 2019. The proportion prescribed antipsychotics was higher among patients diagnosed with schizophrenia (81.0%) than with bipolar disorder (64.6%) and other non-organic psychoses (65.7%). Olanzapine, quetiapine, risperidone and aripiprazole accounted for 78.8% of all antipsychotic prescriptions. Higher mean olanzapine equivalent total daily doses were prescribed to patients with the following characteristics: schizophrenia diagnosis, ethnic minority status, male gender, younger age and greater relative deprivation.

Antipsychotic prescribing is dominated by olanzapine, quetiapine, risperidone and aripiprazole. We identified potential disparities in both the receipt and prescribed doses of antipsychotics across subgroups. To inform efforts to optimise prescribing and ensure equity of care, further research is needed to understand why certain groups are prescribed higher doses and are more likely to be treated with long-acting injectable antipsychotics compared with others.

Short-term exposure to antipsychotics has proven to be beneficial. However, naturalistic studies are lacking regarding the long-term use of antipsychotics. This study aimed to investigate changes in use of antipsychotics over 20 years after a first-episode schizophrenia.

This study is part of the Danish OPUS trial (1998–2000), including 496 participants with first-episode schizophrenia. Participants were reassessed four times over 20 years. The main outcomes were days on medication, redeemed prescriptions of clozapine, psychiatric hospitalizations, and employment.

At the 20-year follow-up, an attrition of 71% was detected. In total, 143 out of 496 participated, with 36% (n = 51) in remission-of-psychotic-symptoms-off-medication. The lowest number of days on medication (mean [s.d.], 339 [538] days) was observed in this group over 20 years. Register data on redeemed antipsychotics were available for all trial participants (n = 416). Individuals in treatment with antipsychotics (n = 120) at the 20-year follow-up had spent significantly more days in treatment (5405 [1857] v. 1434 [1819] mean days, p = 0.00) and more had ever redeemed a prescription of clozapine (25% v. 7.8%, p = 0.00) than individuals who had discontinued antipsychotics (n = 296). Further, discontinuers had significantly higher employment at the 20-year follow-up (28.4% v. 12.5%, p = 0.00).

In a cohort of individuals with first-episode schizophrenia, 36% were in remission-of-psychotic-symptoms-off-medication. However, high attrition was detected, potentially affecting study results by inflating results from individuals with favorable outcomes. From register data, free from attrition, approximately 30% were in treatment with antipsychotics, and 70% had discontinued antipsychotics. Individuals in treatment had the least favorable outcomes, implying greater illness severity.

Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians’ treatment choices for post-traumatic stress disorder (PTSD).

The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148).

About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct “profiles” of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines.

Clinicians’ decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

Apathy is a primary lack of motivation that is frequently reported in Parkinson’s disease (PD) and often misdiagnosed as depression. In PD, apathy worsens over time with motor symptom progression. Evidence over the past 15 years has documented that use of selective serotonin reuptake inhibitors (SSRIs) is associated with increased apathy in patients with depression, including individuals with PD. In PD, this appears to be related to downregulation of dopaminergic systems by serotonin. Despite increasing evidence, SSRIs continue to be heavily prescribed in individuals with PD— potentially worsening apathy and decreasing quality of life for these individuals. This study is an update, re-examining the relationship between apathy and the use of SSRIs and other antidepressants in a large cohort of individuals with PD.

Participants included a convenience sample of 387 nondemented individuals with idiopathic PD who were in their mid-60's (mean age=64.9+8.72 years), well-educated (mean=14.95+2.78 years), predominantly male (72.4%), non-Hispanic white (94.5%), and in mid-stage of disease severity (on medication Unified Parkinson Disease Rating Scale motor score=25.3+10.1). All scored above clinical cutoff for dementia on a cognitive screener (Dementia Rating Scale-2 (DRS) > 125). Medications, cognitive, mood, and clinical data were extracted from chart review. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped into SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs) and other. Analyses included bootstrapped Pearson’s correlations, Pearson’s chi-square, and linear regressions

Among 387 individuals with PD, 41.3% (N=160) were taking antidepressant medications. Of these 160, 61.3% were on SSRIs, 24.4% on SNRIs, and the remainder on other antidepressants. Approximately 36.9% of the 387 PD patients exceeded recommended clinical cutoffs for apathy (AS >14) and 23.5% for depression (BDI-II >14) (Starkstein et al., 1992; Beck et al., 1996). Individuals taking SSRIs (N=98, x2=5.14, p=0.023) or SNRIs (N=39; x2=5.43, p=0.020) were more likely to be clinically apathetic than those taking other depression medications (N=23; x2=1.28, p=0.26). Results of a multiple regression with age, education, disease duration, motor severity, DRS-2, BDI-II, and all psychotropic medications (anti-depressants, anti-anxiety, anti-psychotics) as independent variables explained 42.8% of the variance in total apathy scores (F[17,285]=12.550, p<0.001). SSRIs were the only medication to significantly predict greater AS scores (ß=0.110, p=0.020) in this model. Less education (ß=-0.119, p=0.017) worse cognition (ß=-0.128, p=0.009), and greater depressive symptoms (ß=0.561, p<0.001) were also significant predictors of apathy.

These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy as a potential adverse effect when determining which anti-depressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative anti-depressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study. Longitudinal studies are also needed to elucidate the relationship of apathy and anti-depressant use over time, specifically to determine potential causality of this observed association. Funding: T32-NS082168

Determining neurobiological mechanisms underlying risk-taking behavior is paramount toward developing targeted therapeutics for psychiatric conditions with such behavioral deficits. Therapies are urgently needed given risk-taking is strongly linked to suicidal behavior. Risk-taking is often assessed in tasks of varied rewards and losses, complicating the interpretation of chasing rewards vs. avoiding punishments. A novel task in rats was designed which utilizes varying rewards only, so as to determine mechanisms contributing to ‘chasing’ higher rewards. This task was used to determine that the high reward (risk) preference of male rats was increased by pramipexole treatment [a dopamine D2 receptor-(D2R) family agonist] and decreased by optogenetic inhibition of D2R expressing neurons. The impact of D2R antagonists and sex-dependent differences were not examined however and remains unclear. Here, we trained female and male rats in the task to determine sex-differences in risk preference at baseline and in response to pharmacological challenges of pramipexole, the D2R antagonist sulpiride, and the dopamine transporter inhibitor GBR-12909.

In operant boxes animals could choose from one of two nose-pokes, one that delivered a 50 μl strawberry milkshake reward (safe-option), and the other a 10 μl reward with 75% probability and 170 μl reward with 25% probability (risky-option). Once trained to a stable baseline of risk preference, rats were treated with pramipexole (0.15- or 0.3-mg/kg; Experiment 1) or sulpiride (30-mg/kg; Experiment 2) for 3 days, each separated by a saline washout. Animals were once again trained to a stable baseline, then injected with GBR-12909 (5- or 16-mg/kg; Experiment 3).

Baseline: females were less risk-adverse/more risk-prone than males. Experiment 1: there was a main effect of drug on percent risk choice (%RC) change from baseline [F(1,18)=10.5, p<0.01], with pramipexole increasing %RC. When analyzed across each testing day, a main effect of session [F(6,108)=3.6, p<0.005] was observed, as was a session*sex*drug interaction [F(6,108)=2.2, p<0.05]. Post hoc analyses revealed females differed from males in the timing of their response to pramipexole based on dose. Experiment 2: there was a main effect of drug on %RC change from baseline [F(1,6)=20, p<0.01], with sulpiride decreasing %RC. There was also evidence for a drug*sex interaction [F(1,6)=3.6, p=0.11], with more pronounced attenuation by sulpiride in females. A similar pattern was observed when analyzed across testing days. Experiment 3: there was a main effect of drug on %RC change from baseline [F(2,26)=4.0, p<0.05], with the high dose of GBR-12909 (16-mg/kg) increasing %RC compared to VEH (p<0.05) and low dose (5-mg/kg).

Together these data indicate a sex-specific modulation of baseline risk preferences as measured explicitly via reward seeking behaviors. Additionally, female rats may be more sensitive to D2R manipulations on such risky decision-making behavior, highlighting the necessity of tracking sex-based differences in such tasks. Ongoing studies will determine whether D2R activity reveal a similar sex-specific change during such reward-seeking risk-preference. Furthermore, ongoing studies will determine the link of such behavior to effortful decision making and more traditional measures of risk-taking behavior, such as the Iowa Gambling Task used both in rodents and humans.

Although some animal research suggests possible sex differences in response to THC exposure (e.g., Cooper & Craft, 2018), there are limited human studies. One study found that among individuals rarely using cannabis, when given similar amounts of oral and vaporized THC females report greater subjective intoxication compared to males (Sholler et al., 2020). However, in a study of daily users, females reported indistinguishable levels of intoxication compared to males after smoking similar amounts (Cooper & Haney, 2014), while males and females using 1–4x/week showed similar levels of intoxication, despite females having lower blood THC and metabolite concentrations (Matheson et al., 2020). It is important to elucidate sex differences in biological indicators of cannabis intoxication given potential driving/workplace implications as states increasingly legalize use. The current study examined if when closely matching males and females on cannabis use variables there are predictable sex differences in residual whole blood THC and metabolite concentrations, and THC/metabolites, subjective appraisals of intoxication, and driving performance following acute cannabis consumption.

The current study was part of a randomized clinical trial (Marcotte et al., 2022). Participants smoked ad libitum THC cigarettes and then completed driving simulations, blood draws, and subjective measures of intoxication. The main outcomes were the change in Composite Drive Score (CDS; global measure of driving performance) from baseline, whole blood THC, 11-OH-THC, and THC-COOH levels (ng/mL), and subjective ratings of how “high” participants felt (0 = not at all, 100 = extremely). For this analysis of participants receiving active THC, males were matched to females on 1) estimated THC exposure (g) in the last 6 months (24M, 24F) or 2) whole blood THC concentrations immediately post-smoking (23M, 23F).

When matched on THC exposure in the past 6 months (overall mean of 46 grams; p = .99), there were no sex differences in any cannabinoid/metabolite concentrations at baseline (all p > .83) or after cannabis administration (all p > .72). Nor were there differences in the change in CDS from pre-to-post-smoking (p = .26) or subjective “highness” ratings (p = .53). When matched on whole blood THC concentrations immediately after smoking (mean of 34 ng/mL for both sexes, p = .99), no differences were found in CDS change from pre-to-post smoking (p = .81), THC metabolite concentrations (all p > .25), or subjective “highness” ratings (p = .56). For both analyses, males and females did not differ in BMI (both p > .7).

When male/female cannabis users are well-matched on use history, we find no significant differences in cannabinoid concentrations following a mean of 5 days of abstinence, suggesting that there are no clear biological differences in carryover residual effects. We also find no significant sex differences following ad libitum smoking in driving performance, subjective ratings of “highness,” nor whole blood THC and metabolite concentrations, indicating that there are no biological differences in acute response to THC. This improves upon previous research by closely matching participants over a wider range of use intensity variables, although the small sample size precludes definitive conclusions.

The aim of this systematic review is to examine the cognitive impact of psychotropic medications including benzodiazepines, antidepressants, mood stabilizers, antipsychotics, or a combination of these drugs on older adults.

Systematic review.

We searched Medline, PsycINFO, and Embase through the Ovid platform, CINAHL through EBSCO, and Web of Science.

Randomized control trials (RCTs) and cohort studies that used a validated scale to measure cognition with a follow-up period of at least six months were included.

The primary outcome of interest was cognitive change associated with psychotropic medication use.

A total of 7551 articles were identified from the primary electronic literature search across the five databases after eliminating duplicates. Based on full-text analysis, 27 articles (two RCTs, 25 cohorts) met the inclusion criteria. Of these, nine each examined the impact of benzodiazepines and antidepressants, five examined psychotropic combinations, three on antipsychotic drugs, and one on the effects of mood stabilizers.

This is the first systematic review to examine the cognitive impact of multiple psychotropic drug classes in older adults over an extended follow-up period (six months or more) using robust sample sizes, drug-free control groups, and validated cognitive instruments. We found evidence to indicate cognitive decline with the cumulative use of benzodiazepines and the use of antidepressants, especially those with anticholinergic properties among older adults without cognitive impairment at baseline. Further, the use of antipsychotics and psychotropic combinations is also associated with cognitive decline in older adults.