Central nervous system (CNS)-active polypharmacy is frequent and potentially harmful in older patients. Data on its burden outside the USA and European countries remain limited.

To estimate the period prevalence of and factors associated with out-of-hospital CNS-active polypharmacy in older adults.

We used data from a cohort of out-patients aged ≥60 years affiliated to the Hospital Italiano de Buenos Aires’ health maintenance organisation on 1 January 2021. A CNS-active polypharmacy event was defined as the concurrent exposure to ≥3 CNS-active medications (i.e. antidepressants, anti-epileptics, antipsychotics, benzodiazepines, Z-drugs and opioids) through filled out-of-hospital prescriptions. We calculated the period prevalence of CNS-active polypharmacy for 2021. We identified factors associated with CNS-active polypharmacy using a multivariable logistic regression model to estimate odds ratios and 95% confidence intervals (CI).

We included 63 857 patients. Pre-existing mental health diagnoses included anxiety (21%), depressive (14%) and sleep (11%) disorders. CNS-active polypharmacy occurred in 4535 patients, for a period prevalence of 7.1% (95% CI: 6.9–7.3%). The combination of an antidepressant, an antipsychotic and a benzodiazepine accounted for 21% of the CNS-active polypharmacy events. Frontotemporal dementia (odds ratio: 14.67; 95% CI: 4.47–48.20), schizophrenia (odds ratio: 7.93; 95% CI: 4.64–13.56), bipolar disorder (odds ratio: 7.20; 95% CI: 5.45–9.50) and depressive disorder (odds ratio: 3.50; 95% CI: 3.26–3.75) were associated with CNS-active polypharmacy.

One in 14 adults aged 60 years and older presented out-of-hospital CNS-active polypharmacy. Future studies should evaluate measures to reduce CNS-active medication use in this population.

We need to better understand the risk factors and predictors of medication-related weight gain to improve metabolic health of individuals with schizophrenia. This study explores how trajectories of antipsychotic medication (AP) use impact body weight early in the course of schizophrenia.

We recruited 92 participants with first-episode psychosis (FEP, n = 92) during their first psychiatric hospitalization. We prospectively collected weight, body mass index (BMI), metabolic markers, and exact daily medication exposure during 6-week hospitalization. We quantified the trajectory of AP medication changes and AP polypharmacy using a novel approach based on meta-analytical ranking of medications and tested it as a predictor of weight gain together with traditional risk factors.

Most people started treatment with risperidone (n = 57), followed by olanzapine (n = 29). Then, 48% of individuals remained on their first prescribed medication, while 33% of people remained on monotherapy. Almost half of the individuals (39/92) experienced escalation of medications, mostly switch to AP polypharmacy (90%). Only baseline BMI was a predictor of BMI change. Individuals in the top tercile of weight gain, compared to those in the bottom tercile, showed lower follow-up symptoms, a trend for longer prehospitalization antipsychotic treatment, and greater exposure to metabolically problematic medications.

Early in the course of illness, during inpatient treatment, baseline BMI is the strongest and earliest predictor of weight gain on APs and is a better predictor than type of medication, polypharmacy, or medication switches. Baseline BMI predicted weight change over a period of weeks, when other traditional predictors demonstrated a much smaller effect.

Patients prescribed clozapine are increasingly living into old age. However, there is a lack of studies to guide prescribing in this age group. We sought to identify all clozapine patients in Hertfordshire Partnership NHS Foundation Trust over a 5-year period and review side-effect burden and co-prescribing in all patients aged over 65 years.

We identified 69 patients. The majority (61%) were stable in terms of mental state; 94% of cases had experienced a side-effect within the past year, with constipation occurring most commonly (65% of cases).

Our findings reveal a significant side-effect burden, particularly in relation to constipation. Clozapine-induced gastrointestinal hypomotility (CIGH) can be fatal; however, increasing age has not been a recognised risk factor for constipation in clozapine patients to date. This raises questions about increasing risk to physical health as patients age and adds to concerns about the lack of monitoring for CIGH.

In England in 2021, an estimated 274 000 people were homeless on a given night. It has long been recognised that physical and mental health of people who are homeless is poorer than for people who are housed. There are few peer-reviewed studies to inform health and social care for depression or anxiety among homeless adults in this setting.

To measure the symptoms of depression and anxiety among adults who are homeless and who have difficulty accessing healthcare, and to describe distribution of symptoms across sociodemographic, social vulnerability and health-related characteristics.

We completed structured questionnaires with 311 adults who were homeless and who had difficulty accessing healthcare in London, UK, between August and December 2021. We measured anxiety and depression symptoms using the 4-item Patient Health Questionnaire (PHQ-4) score. We compared median PHQ-4 scores across strata of the sociodemographic, social vulnerability and health-related characteristics, and tested for associations using the Kruskal–Wallis test.

The median PHQ-4 score was 8 out of 12, and 40.2% had scores suggesting high clinical need. Although PHQ-4 scores were consistently high across a range of socioeconomic, social vulnerability and health-related characteristics, they were positively associated with: young age; food insecurity; recent and historic abuse; joint, bone or muscle problems; and frequency of marijuana use. The most common (60%) barrier to accessing healthcare related to transportation.

Adults who are homeless and have difficulty accessing healthcare have high levels of depression and anxiety symptoms. Our findings support consideration of population-level, multisectoral intervention.

One-third to half of people with intellectual disabilities suffer from chronic constipation (defined as two or fewer bowel movements weekly or taking regular laxatives three or more times weekly), a cause of significant morbidity and premature mortality. Research on risk factors associated with constipation is limited.

To enumerate risk factors associated with constipation in this population.

A questionnaire was developed on possible risk factors for constipation. The questionnaire was sent to carers of people with intellectual disabilities on the case-loads of four specialist intellectual disability services in England. Data analysis focused on descriptively summarising responses and comparing those reported with and without constipation.

Of the 181 people with intellectual disabilities whose carers returned the questionnaire, 42% reported chronic constipation. Constipation was significantly associated with more severe intellectual disability, dysphagia, cerebral palsy, poor mobility, polypharmacy including antipsychotics and antiseizure medication, and the need for greater toileting support. There were no associations with age or gender.

People with intellectual disabilities may be more vulnerable to chronic constipation if they are more severely intellectually disabled. The associations of constipation with dysphagia, cerebral palsy, poor mobility and the need for greater toileting support suggests people with intellectual disabilities with significant physical disabilities are more at risk. People with the above disabilities need closer monitoring of their bowel health. Reducing medication to the minimum necessary may reduce the risk of constipation and is a modifiable risk factor that it is important to monitor. By screening patients using the constipation questionnaire, individualised bowel care plans could be implemented.

The frequent prescribing of psychotropics and high prevalence of polypharmacy among older adults with intellectual disabilities require close monitoring.

To describe change in prevalence, predictors and health outcomes of psychotropic use during the four waves (2009/2010, 2013/2014, 2016/2017, 2019/2020) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA).

Eligible participants were adults (≥40 years) with intellectual disabilities who participated in all four waves of IDS-TILDA and who reported medication use for the entire period. Differences between groups were tested using Cochran's Q test for binary variables and the McNemar–Bowker test for variables with more than two categories. Generalised estimating equation models were used to assess associations between psychotropic use, participants’ characteristics and health outcomes.

Across waves (433 participants) there were no significant differences in prevalence of psychotropic use (61.2–64.2%) and psychotropic polypharmacy (42.7–38.3%). Antipsychotics were the most used subgroup, without significant change in prevalence between waves (47.6–44.6%). A significant decrease was observed for anxiolytics (26.8–17.6%; P < 0.001) and hypnotics/sedatives (14.1–9.0%; P < 0.05). A significant increase was recorded for antidepressants (28.6–35.8%; P < 0.001) and mood-stabilising agents (11.5–14.6%; P < 0.05). Psychotropic polypharmacy (≥2 psychotropics) was significantly associated with moderate to total dependence in performing activities of daily living over the 10-year period (OR = 1.80, 95% CI 1.21–2.69; P < 0.05).

The study indicates an increase in usage of some classes of psychotropic, a reduction in others and no change in the relatively high rate of antipsychotic use over 10 years in a cohort of older adults with intellectual disabilities and consequent risk of psychotropic polypharmacy and medication-related harm.

There is insufficient evidence to support the pharmacological treatment of borderline personality disorder. However, previous out-patient cohorts have described high rates of polypharmacy in this group. So far, there have been no national studies that have considered polypharmacy in borderline personality disorder.

To describe psychotropic polypharmacy in people with borderline personality disorder in New Zealand.

New Zealand's national databases have been used to link psychotropic medication dispensing data and diagnostic data for borderline personality disorder. Annual dispensing data for 2014 and 2019 have been compared.

Fifty percent of people with borderline personality disorder who were dispensed medications had three or more psychotropic medications in 2014. This increased to 55.9% in 2019 (P < 0.001). Those on seven or more psychotropics increased from 8.4 to 10.7% (P < 0.023). Quetiapine was the most dispensed psychotropic medication, being given to 53.8% of people dispensed medication with borderline personality disorder in 2019. Lorazepam dispensing showed the largest increase, going from 15.5 to 26.7% between 2014 and 2019 (P < 0.001).

There is a large burden of psychotropic polypharmacy in people with borderline personality disorder. This is concerning because of the lack of evidence regarding the efficacy of these medications in this group.

There is limited evidence on the association between cognitive function, psychotic symptoms and doses of antipsychotics in adults under compulsory psychiatric care.

We assessed (a) the degree of cognitive impairment in adults involuntarily hospitalised for compulsory psychiatric care and (b) correlation of Montreal Cognitive Assessment (MoCA) score with psychotic symptoms, polypharmacy and prescription of high-dose antipsychotics.

This was a nationwide, cross-sectional study, conducted at the only referral state hospital for compulsory psychiatric care in Cyprus (December 2016–February 2018). Τhe MoCA was applied for the assessment of cognitive functioning. The Positive and Negative Syndrome Scale (PANSS) was applied for the assessment of psychotic symptoms.

The sample comprised 187 men and 116 women. The mean MoCA score was 22.09 (reported scale range (RSR): 3–30); the mean PANSS general symptoms subscale score was 49.60 (RSR = 41–162). The participants who reported positive psychiatric history (mean 21.71, s.d. 5.37), non-adherence to pharmacotherapy (mean 21.32, s.d. 5.56) and prescription of high-dose antipsychotics (with medication prescribed as needed: mean 21.31, s.d. 5.70; without medication prescribed as needed: mean 20.71, s.d. 5.78) had lower mean MoCA scores compared with those who reported negative psychiatric history (mean 23.42, s.d. 4.51; P = 0.017), adherence to pharmacotherapy (mean 23.10, s.d. 6.61; P = 0.003) and no prescription of high-dose antipsychotics (with medication prescribed as needed: mean 22.56, s.d. 4.90; without medication prescribed as needed: mean 22.60 s.d. 4.94; P = 0.045–0.005), respectively. Mean MoCA score was mildly and inversely associated with total PANSS score (r = −0.15, P = 0.03), PANSS general (r = −0.18, P = 0.002) and PANSS negative (r = −0.16, P = 0.005) symptoms subscales, respectively.

Our findings support the evaluation of cognitive functioning in adults under compulsory psychiatric care via the MoCA tool, with focus on those prescribed high-dose antipsychotics, with positive mental health history and non-adherence to pharmacotherapy.

Individuals with physical comorbidities and polypharmacy may be at higher risk of depression relapse, however, they are not included in the ‘high risk of relapse’ group for whom longer antidepressant treatment durations are recommended.

In individuals with comorbid depression and type 2 diabetes (T2DM), we aimed to investigate the association and interaction between depression relapse and (a) polypharmacy, (b) previous duration of antidepressant treatment.

This was a cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) from years 2000 to 2018. We used Cox regression models with penalised B-splines to describe the association between restarting antidepressants and our two exposures.

We identified 48 001 individuals with comorbid depression and T2DM, who started and discontinued antidepressant treatment during follow-up. Within 1 year of antidepressant discontinuation, 35% of participants restarted treatment indicating depression relapse. As polypharmacy increased, the rate of restarting antidepressants increased until a maximum of 18 concurrent medications, where individuals were more than twice as likely to restart antidepressants (hazard ratio (HR) = 2.15, 95% CI 1.32–3.51). As the duration of previous antidepressant treatment increased, the rate of restarting antidepressants increased – individuals with a previous duration of ≥25 months were more than twice as likely to restart antidepressants than those who previously discontinued in <7 months (HR = 2.36, 95% CI 2.25–2.48). We found no interaction between polypharmacy and previous antidepressant duration.

Polypharmacy and longer durations of previous antidepressant treatment may be associated with depression relapse following the discontinuation of antidepressant treatment.

Clozapine is commonly associated with hematological side effects. However, little research is available on the impact of adding other psychotropic medication on inducing blood dyscrasias.

The aim of the study was to explore the impact of associating psychotropic medication to clozapine in producing hematological abnormalities.

Our study was a longitudinal, retrospective chart review of adult psychiatric patients receiving clozapine treatment at our clozapine consultation between January 2000 and September 2020.

Our sample consisted of 15 women (23.5%) and 49 men (76.5%), mean age was 41.34 ±9.32 years. Polypharmacy was found in 70.3% of the cases. Association of clozapine to other psychotropic agents was found in 67.2% of the cases. Most prescribed add-on medication was valproic acid in 27 cases, benzodiazepines in 21 cases, promethazine and hydroxyzine in 16 cases, lithium in 8 cases and haloperidol in 6 cases. We found blood dyscrasias in 21 patients (32.8%). Hematological abnormalities were as follow: 2 cases of agranulocytosis, 8 cases of neutropenia, 13 cases of thrombocytopenia, 5 cases of leukocytosis, 5 cases of eosinophilia and 3 cases of anemia. In our sample we did not find a significant association between psychotropic polypharmacy and blood dyscrasias.

Many psychiatric patients on clozapine require polypharmacy to better stabilize their condition. Such co prescriptions may carry the risk of inducing more side effects especially blood dyscrasias. In our study, we did not find a significant association between psychotropic medication added to clozapine and hematological abnormalities. But further research is warranted to better explore this association.

No significant relationships.

Polypharmacy can be the cause of deliberate discontinuation of medication and consequent relapse of schizophrenia.

To establish the one-year rate of relapse in the patients with schizophrenia with regard to monotherapy or polypharmacy.

The sample of all hospitalized patients with schizophrenia in a five-year period was analyzed. Descriptive statistics were used.

Total of 87 participants (57 women), the median age was 43 years. Antipsychotic monotherapy was used in 31 (35.6%) of the participants. In one year period, 32 (36.8%) of all participants had a relapse. Prior to relapse, significantly more participants were treated with polypharmacy (p<0,05).

Antipsychotic polypharmacy is related to a higher rate of relapse in patients with schizophrenia.

No significant relationships.

Iatrogenic factors, such as polypharmacy and prescription cascade, are some of the main causes of delirium in the elderly. We present a case of delirium of months of evolution that improved after applying a pharmacological de-prescription strategy.

To report a case and review the available literature on the concepts of prescription cascade and de-prescription in delirium in the elderly.

A 92-year-old woman with a history of cerebrovascular accidents and no psychiatric history or dementia was admitted to a psychogeriatric clinic due to disorientation, delusions of harm and gait apraxia. Several months earlier she had required admission to the general hospital for agitation. In view of the suspicion of delirium, an exhaustive examination and complementary tests were performed, including a neuropsychological assessment and a brain scan (Image 1).

The patient had previously received multiple high-dose psychotropic drugs (Gabapentin, trazodone, Zolpidem, Quetiapine), which had reduced the agitation but had not resolved the problem. Organic causes were treated in a multidisciplinary team (pressure ulcers), together with a gradual tapering of medication. Although underlying vascular dementia was diagnosed, the patient’s gait and cognitive status improved, with a significant impact on her autonomy and quality of life.

Despite an extensive literature on the subject, delirium in the elderly remains an under-diagnosed medical condition, especially the hypoactive subtype, just as cascade prescribing remains common. It is important to raise awareness among specialists in training to prevent and diagnose it.

No significant relationships.

Research on the effectiveness of pharmacotherapies for schizophrenia and comorbid substance use disorder (SUD) is very sparse, and non-existent on the prevention of the development of SUDs in patients with schizophrenia.

To compare the real-world effectiveness of antipsychotics in schizophrenia in decreasing risk of developing an initial SUD, and psychiatric hospital admission and SUD-related hospital admission among patients with an SUD.

Two independent national cohorts including all persons diagnosed with schizophrenia (N = 45 476) were followed up for 22 (Finland: 1996–2017) and 11 (Sweden: 2006–2016) years. Risk of developing an SUD was calculated with between-individual models, and risks of psychiatric and SUD-related hospital admission were calculated with within-individual models, using Cox regression and adjusted hazard ratios (aHRs) for using versus not using certain antipsychotics.

For patients with schizophrenia without an SUD, clozapine use (Finland: aHR 0.20, 95% CI 0.16–0.24, P < 0.001; Sweden: aHR 0.35, 95% CI 0.24–0.50, P < 0.001) was associated with lowest risk of developing an initial SUD in both countries. Antipsychotic polytherapy was associated with second lowest risk (aHR 0.54, 95% CI 0.44–0.66) in Sweden, and third lowest risk (aHR 0.47, 95% CI 0.42–0.53) in Finland. Risk of relapse (psychiatric hospital admission and SUD-related hospital admission) were lowest for clozapine, antipsychotic polytherapy and long-acting injectables in both countries. Results were consistent across both countries.

Clozapine and antipsychotic polytherapy are most strongly associated with reduced risk of developing SUDs among patients with schizophrenia, and with lower relapse rates among patients with both diagnoses.