Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages.

A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC–MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups.

A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL.

The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Patients with remitted psychosis wish to reduce antipsychotic doses yet facing increased risks of relapse. Examining dose-tapering processes may provide insights to re-evaluate the risk-to-benefit balance. We aimed to depict and subgroup tapering trajectories, and explore factors associated with different dose-reduction patterns.

A 2-year open-label randomized prospective comparative trial from August 2017 to September 2022 in Taiwan. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomizing a proportion to conduct guided dose reduction. We depicted the trajectories of individual patients and named subgroups based on dose-tapering patterns. Predictors of baseline characteristics for designated subgroups were examined by logistic regression analysis; changes in outcomes were compared by paired t-test.

Fifty-one patients undergoing guided dose reduction, 18 (35.3%) reduced 4 steps consecutively (sequential reducers, SR), 14 (27.5%) reduced 1 to 3 steps (modest reducers, MR), 3 (5.9%) re-escalated to previous level (alert reducers, AR), 7 (13.7%) returned to baseline level (baseline returners, BR), 6 (11.7%) relapsed (failed reducers, FR) and 3 (5.9%) withdrew without relapse (early exits, EE). Patients with a history of relapse assumed a conservative dose-tapering pace; only the SR subgroup exhibited significant improvements in functioning and quality of life while failing to identify variables for predicting who would become SR or FR.

Guided dose reduction comprises dynamic processes with differences between individual trajectories. The proposed naming of dose-tapering patterns/subgroups provides a framework depicting patients undergoing dose-tapering. Longer-term observation and more flexible tapering approaches are anticipated to reveal favorable outcomes.

Patients with remitted psychosis face a dilemma between the wish to discontinue antipsychotics and the risk of relapse. We test if an operationalized guided-dose-reduction algorithm can help reach a lower effective dose without increased risks of relapse.

A 2-year open-label randomized prospective comparative cohort trial from Aug 2017 to Sep 2022. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomized 2:1 into guided dose reduction group (GDR) v. maintenance treatment group (MT1), together with a group of naturalistic maintenance controls (MT2). We observed if the relapse rates would be different between 3 groups, to what extent the dose could be reduced, and if GDR patients could have improved functioning and quality of life.

A total of 96 patients, comprised 51, 24, and 21 patients in GDR, MT1, and MT2 groups, respectively. During follow-up, 14 patients (14.6%) relapsed, including 6, 4, and 4 from GDR, MT1, and MT2, statistically no difference between groups. In total, 74.5% of GDR patients could stay well under a lower dose, including 18 patients (35.3%) conducting 4 consecutive dose-tapering and staying well after reducing 58.5% of their baseline dose. The GDR group exhibited improved clinical outcomes and endorsed better quality of life.

GDR is a feasible approach as the majority of patients had a chance to taper antipsychotics to certain extents. Still, 25.5% of GDR patients could not successfully decrease any dose, including 11.8% experienced relapse, a risk comparable to their maintenance counterparts.

There was no previous meta-analysis investigating the efficacy/tolerability of psychostimulants for symptoms of attention-deficit hyperactivity disorder (ADHD) in preschool children.

Databases including PubMed, the Cochrane Library, EMBASE, ScienceDirect, and ClinicalTrials.gov were searched from inception to March 2022 for randomized controlled trials (RCTs) on therapeutic efficacy of psychostimulants against ADHD symptoms in preschool children (age ≤6 years) compared with placebos. Primary outcomes were (a) changes in ADHD symptoms evaluated by validated rating scales from parents’/teacher’s observation, or (b) post-intervention improvements in neuropsychological performance. Secondary outcomes were risks of adverse events.

Meta-analysis of nine eligible trials including 544 preschool children (mean age=4.86 years, female=11.98%, median treatment duration=4.33 weeks) supported the efficacy of psychostimulants against global symptoms from observations of parents (Hedges’ g=0.6152, p<0.0001) and teachers (Hedges’ g=0.6563, p=0.0039). Efficacy of psychostimulants was also noted against symptoms of inattention and hyperactivity/impulsivity, especially the latter (i.e., main symptoms in preschool children). Moreover, male gender, older age, and longer treatment duration were associated with better efficacy. Regarding adverse events, only the risk of poor appetite was higher in the psychostimulant group (odds ratio [OR]=2.39). However, the qualities of evidence were low to very low, indicating potential discrepancy between the true and estimated effect.

Our results showed that psychostimulants might be beneficial for preschool children with ADHD, especially hyperactivity/impulsivity from teachers’ observation, with tolerable side effects. Nevertheless, the true magnitude of the effect needs to be confirmed with more research due to low to very low certainty of the evidence.

A proportion of patients with bipolar disorder (BD) manifests with only unipolar mania (UM). This study examined relevant clinical features and psychosocial characteristics in UM compared with depressive-manic (D-M) subgroups. Moreover, comorbidity patterns of physical conditions and psychiatric disorders were evaluated between the UM and D-M groups.

This clinical retrospective study (N = 1015) analyzed cases with an average of 10 years of illness duration and a nationwide population-based cohort (N = 8343) followed up for 10 years in the Taiwanese population. UM was defined as patients who did not experience depressive episodes and were not prescribed adequate antidepressant treatment during the disease course of BD. Logistic regression models adjusted for relevant covariates were used to evaluate the characteristics and lifetime comorbidities in the two groups.

The proportion of UM ranged from 12.91% to 14.87% in the two datasets. Compared with the D-M group, the UM group had more psychotic symptoms, fewer suicidal behaviors, a higher proportion of morningness chronotype, better sleep quality, higher extraversion, lower neuroticism, and less harm avoidance personality traits. Substantially different lifetime comorbidity patterns were observed between the two groups.

Patients with UM exhibited distinct clinical and psychosocial features compared with patients with the D-M subtype. In particular, a higher risk of comorbid cardiovascular diseases and anxiety disorders is apparent in patients with D-M. Further studies are warranted to investigate the underlying mechanisms for diverse presentations in subgroups of BDs.

The Brain Health Test-7 (BHT-7) is a revised tool from the original BHT, containing more tests about frontal lobe function. It was developed with theaim of identifying patients with mild cognitive impairment (MCI) and early dementia.

Here we report the validity of the BHT-7 versus the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in differentpsychiatry or neurology clinics.

Patients with memory complaints were recruited in this study from the outpatient clinic of psychiatry or neurology in 3 different kinds of hospitals. Allpatients underwent the evaluation of the BHT-7, MMSE, MoCA, and clinical dementia rating (CDR). The clinical diagnosis (normal, MCI, dementia) was made by consensus meeting, taking into account all available data.

Demographic data and the scores of the MMSE, MoCA, and BHT-7 between groups were compared. Logistic regression was adopted for analysis of optimal cutoff values, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), receiver operating characteristic (ROC) curve,and the area under the ROC curve (AUC).

We enrolled a total of 1090 subjects (normal 402, MCI 317, dementia 371); of them, 705 (64.7%) were female. There was a statistically significant differencein age, years of education, and 3 cognitive test scores among the 3 groups.

Compared with the MMSE and MoCA, the BHT-7 performed slightly betterthan MMSE and MoCA in differentiating MCI or dementia from the normalcontrols (Table 1). For BHT- 7, the cutoff point was 17 between normal andMCI, and 14 between normal and dementia. These cutoff points for BHT-7were consistent through 3 different clinical settings, but inconsistent for MMSE and MoCA. The testing time for the BHT-7 was about 5-7 minutes, shorter than that of the MMSE and MoCA.

Compared with MMSE and MoCA, the BHT-7 showed slightly better performance in differentiating normal from MCI or dementia subjects. The testing time for the BHT-7 was shorter, and its cutoff points were consistent through different outpatient clinic settings. The results support that BHT-7 is auseful cognitive screening tool for MCI or early dementia in various hospital settings.

Table 1

Comparisons of the performance of BHT-7, MMSE, MoCA