Objective/Introduction: We sought to characterize the impact of the 90-item Symptom Checklist (SCL-90) subscales for paranoid ideation (PI) and psychoticism (P) in patients with major depressive disorder (MDD), on acute anti-depressant response and on relapse prevention.

Methods: Subjects with Structured Clinical Interview for DSM Disorders-diagnosed non-psychotic MDD were recruited into a clinical trial of open-label fluoxetine 10–60 mg/day for 12 weeks, followed by double-blind randomization of responders (n=262) to fluoxetine continuation or placebo for 12 months. PI and P were assessed with the patient-rated SCL-90. The association of these symptoms with response to treatment was assessed by logistic regression.

Results: We found significant decreases in PI and P during acute treatment phase for fluoxetine responders and nonresponders, although only 10.3% and 7.5% of patients experienced a ≥50% reduction in PI and P scores, respectively. Neither PI nor P scores significantly predicted time to relapse. P scores predicted a lower response rate to treatment with fluoxetine.

Discussion: The results of the present study suggest that there is a significant relationship between the presence of psychoticism in patients with nonpsychotic MDD, and the likelihood of overall depressive symptom improvement following a trial of monotherapy with fluoxetine.

Conclusion: An increased burden of psychoticism in depressed subjects may confer poorer response to fluoxetine, but not increased risk of relapse among fluoxetine responders.

Binge-eating disorder (BED) is associated with obesity (BMI ≥30) in approximately 40-45% of patients. Dasotraline is a long-acting dopamine/norepinephrine reuptake inhibitor with a PK profile characterized by slow absorption and an elimination half-life of 47-77 hours, permitting once-daily dosing. In a recent placebo-controlled, flexible-dose study, dasotraline demonstrated significant efficacy in patients with BED. We now report an analysis from this study of the effect of dasotraline on body weight.

Patients with moderate-to-severe BED, based on DSM-5 criteria, were randomized to 12 weeks of double-blind flexible-dose treatment with dasotraline (4-8 mg/d) vs. placebo. The primary efficacy outcome was number of binge-eating days/week. Mean change in body weight at Week 12 (assessed as a safety outcome) was analyzed by baseline body mass index (BMI, kg/m2) category. Inferential statistics were not performed.

The safety population consisted of 317 patients (female, 84%; mean age, 38.2 years; mean weight, 97.3 kg). At baseline, the proportions of patients in each BMI category were as follows: normal (<25 kg/m2: 5.7%), overweight (25 to <30 kg/m2: 18.3%), obesity class I (30 to <35 kg/m2: 24.9%), class II (35 to <40 kg/m2: 29.3%), and class III (≥40 kg/m2: 21.8%). For the overall patient sample, treatment with dasotraline significantly reduced the number of binge-eating days per week vs. placebo (-3.74 vs. -2.75; P<0.0001; effect size = 0.74). Mean changes at Week 12 in weight (kg) for completers treated with dasotraline vs. placebo, by baseline BMI category, were as follows: normal weight (-4.6 vs. -0.2), overweight (-5.8 vs. +1.3), and combined obesity classes I-III (-6.2 vs. +0.3). Among obese patients (Class I-III, combined) treated with dasotraline, weight reduction (≥5%) was observed in 45.3% of patients (vs. 4.1% on placebo); and weight reduction ≥10% in approximately 13.7% of patients (vs. none on placebo). Weight-related adverse events, for dasotraline vs. placebo, consisted of decreased appetite (19.7% vs. 6.9%), decreased weight (12.1% vs. 0%), and increased weight (0.6% vs. 1.3%).

Among patients completing 12 weeks of treatment with dasotraline, weight reduction ≥5% was observed in 45% of obese patients with a BMI ≥30. The most frequent weight-related adverse event was decreased appetite, reported in approximately one in five patients treated with dasotraline.

Clinicaltrials.gov number: NCT02564588

Supported by funding from Sunovion Pharmaceuticals Inc.

Schizophrenia is a debilitating mental illness that affects patient’s function and quality of life. Estimates indicate a lifetime prevalence of 0.48%, causing up to 13.4 million years of life burdened by disability. 30% of these patients are deemed as having treatment-resident schizophrenia (TRS), a subset of which do not respond to clozapine, the medication designated for TRS. Those that do not respond to clozapine are deemed to have clozapine-resistant schizophrenia (CRS), requiring further augmentation or multiple antipsychotics.

Clozapine only has limited formulations available (oral [PO] and dissolving [ODT]) and has a substantial side effect burden. Most serious among these side effects includes agranulocytosis, which in some cases can cause severe infections such as septicemia. Regular blood draws monitoring for this are vital to prevent this dangerous consequence, but place further burden on patients, requiring weekly to monthly lab work and visits. Other common and burdensome side effects include tachycardia, hypotension, sialorrhea, weight gain, and metabolic syndrome, to name a few. However, treatment for TRS is still needed, and further alternatives must be explored.

Among studies done on clozapine, few compare second-generation antipsychotics head-to-head, and those that do find similar improvement in overall symptom burden among multiple antipsychotics, especially olanzapine and paliperidone (in particular, paliperidone palmitate). Due in part to the improved receptor profile of these medications (especially 5-HT2A, 6, and 7) compared to clozapine, they can have similar or superior effect in patients with TRS without substantial patient side effect and functional burden. Paliperidone palmitate formulations are developing that can be spaced further and further apart, allowing for minimal impact on patient’s livelihood, while demonstrating similar overall effect with improved side effect profile. However, onset of action is slow, and an effective adjunct strategy may be to initially administer olanzapine for the first 6 months until peak effect is expected from paliperidone palmitate, at which point monotherapy with paliperidone is preferred.

Alternative therapies for patients with TRS may be more functional with fewer side effects, and this work indicates a particularly effective strategy may be to pursue paliperidone palmitate monotherapy long-term while utilizing the unique combination of paliperidone and olanzapine in the short-term (first 6 months) while awaiting peak efficacy.

No Funding

Adverse drug reactions (ADRs) are associated with increased morbidity, mortality, and resource utilization. Drug interactions (DDIs) are among the most common causes of ADRs, and estimates have cited that up to 22% of patients take interacting medications. DDIs are often due to the propensity for agents to induce or inhibit enzymes responsible for the metabolism of concomitantly administered drugs. However, this phenomenon is further complicated by genetic variants of such enzymes. The aim of this study is to quantify and describe potential drug-drug, drug-gene, and drug-drug-gene interactions in a community-based patient population.

A regional pharmacy with retail outlets in Arkansas provided deidentified prescription data from March 2020 for 4761 individuals. Drug-drug and drug-drug-gene interactions were assessed utilizing the logic incorporated into GenMedPro, a commercially available digital gene-drug interaction software program that incorporates variants of 9 pharmacokinetic (PK) and 2 pharmacodynamic (PD) genes to evaluate DDIs and drug-gene interactions. The data were first assessed for composite drug-drug interaction risk, and each individual was stratified to a risk category using the logic incorporated in GenMedPro. To calculate the frequency of potential drug-gene interactions, genotypes were imputed and allocated to the cohort according to each gene’s frequency in the general population. Potential genotypes were randomly allocated to the population 100 times in a Monte Carlo simulation. Potential drug-drug, gene-drug, or gene-drug-drug interaction risk was characterized as minor, moderate, or major.

Based on prescription data only, the probability of a DDI of any impact (mild, moderate, or major) was 26% [95% CI: 0.248-0.272] in the population. This probability increased to 49.6% [95% CI: 0.484-0.507] when simulated genetic polymorphisms were additionally assessed. When assessing only major impact interactions, there was a 7.8% [95% CI: 0.070-0.085] probability of drug-drug interactions and 10.1% [95% CI: 0.095-0.108] probability with the addition of genetic contributions. The probability of drug-drug-gene interactions of any impact was correlated with the number of prescribed medications, with an approximate probability of 77%, 85%, and 94% in patients prescribed 5, 6, or 7+ medications, respectively. When stratified by specific drug class, antidepressants (19.5%), antiemetics (21.4%), analgesics (16%), antipsychotics (15.6%), and antiparasitics (49.7%) had the highest probability of major drug-drug-gene interaction.

In a community-based population of outpatients, the probability of drug-drug interaction risk increases when genetic polymorphisms are attributed to the population. These data suggest that pharmacogenetic testing may be useful in predicting drug interactions, drug-gene interactions, and severity of interactions when proactively evaluating patient medication profiles.

Genomind, Inc.

This post hoc analysis investigated efficacy and tolerability of adjunctive cariprazine (CAR) in patients with major depressive disorder (MDD) using evidence-based medicine metrics of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).

Data sources were five completed Phase II/III, 6-8 week, randomized, double-blind, placebo-controlled studies. Efficacy outcomes included acute response (≥50% decrease from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS] total score). Tolerability outcomes included commonly occurring adverse events (AEs) and rates of discontinuation because of an AE, with data pooled across all studies for the CAR 1-2 mg/day plus 1.5 mg/day dose groups, 2-4.5 mg/day plus 3 mg/day dose groups, and for all groups where CAR dose was ≥1 mg/day. NNT and NNH were calculated for adjunctive CAR vs. adjunctive placebo.

MADRS response rates at Week 8 for CAR 2-4.5 mg/day vs. placebo were 134/271 (49.4%) vs. 101/264 (38.3%), resulting in a NNT of 9 (95% CI 6-36). In study NCT03738215, MADRS response rates at Week 6 for CAR 1.5 mg/day vs. placebo were 110/250 (44.0%) vs. 87/249 (34.9%), resulting in a NNT of 11 (95% CI 6-193). For the pooled CAR ≥1 mg/day group, MADRS response rates at Week 6 were 765/1887 (40.5%) for CAR vs. 354/1101 (32.2%) for placebo, resulting in a NNT of 12 (95% CI 9-21). For the pooled CAR ≥1 mg/day group, rates of akathisia vs. placebo were 209/1893 (11.0%) vs. 25/1108 (2.3%) for placebo, resulting in a NNH of 12 (95% CI 10-14). This appears dose related as the NNH for akathisia vs. placebo was 24 (95% CI 17-43) for the 1-2 mg/day plus 1.5 mg/day dose groups, and 9 (95% CI 7-11) for the 2-4.5 mg/day plus 3 mg/day dose groups. For the pooled CAR ≥1 mg/day group, rates of discontinuation because of an AE vs. placebo were 122/1893 (6.4%) vs. 26/1108 (2.3%) for placebo, resulting in a NNH of 25 (95% CI 19-38). This appears dose related as the NNH for discontinuation because of an AE vs. placebo was 94 (ns) for the 1-2 mg/day plus 1.5 mg/day dose groups, and 17 (95% CI 13-28) for the 2-4.5 mg/day plus 3 mg/day dose groups. For the pooled CAR ≥1 mg/d group, rates of weight gain ≥7% from baseline vs. placebo were 35/1893 (1.8%) vs. 12/1108 (1.1%) for placebo, resulting in a NNH of 131 (ns). LHH comparing MADRS response vs. discontinuation because of an AE is >1, and >>1 for the lower dose range. Indirect comparisons of the above results with that of the effect sizes seen in positive studies of other adjunctive antipsychotic treatments vs. adjunctive placebo in MDD demonstrate similar values for NNT for response, and when the lower dose range of CAR is used, a more favorable NNH regarding discontinuation because of an AE.

The benefit-risk profile of CAR is favorable for adjunctive treatment of MDD.

AbbVie

Four medications are FDA approved for bipolar depression: lurasidone (LUR), cariprazine (CAR), quetiapine IR & XR (QUE), and olanzapine-fluoxetine combination (OFC). Indirect comparisons for efficacy using Number Needed to Treat (NNT) and for tolerability using Number Needed to Harm (NNH) can be useful clinical benchmarks to aid treatment decisions. Benefit and risk may also be examined using the Likelihood to be Helped or Harmed (LHH). In this post-hoc analysis, we examined the benefit-risk ratio of the four treatments using LHH.

Individual and pooled monotherapy data from short-term clinical registration trials of patients with bipolar depression were assessed for LUR, CAR, pooled QUE (300 and 600 mg), and pooled OFC (considered as monotherapy for this study at fixed doses of 6/25, 6/50, 12/50 mg) data. NNT estimates were calculated using the proportions of MADRS responders (defined as ≥ 50% improvement at study endpoint) and MADRS remitters (defined as a score of ≤ 10 [for LUR and CAR] and ≤ 12 [for QUE and OFC]) at study endpoint. NNH data were calculated for the proportions of patients who discontinued due to an adverse event (AE) and for individual AEs commonly associated with each treatment. LHH was calculated as the ratio of NNH/NNT to determine the benefit-risk ratio.

The NNT estimates for response vs. placebo were: 5 for both LUR 20–60 mg and 80–120 mg; 10 for both CAR 1.5 mg and 3.0 mg; 6 for QUE; and 4 for OFC. The NNTs for remission vs placebo were: 7 for LUR 20–60 mg and 9 for LUR 80–120 mg; 10 for CAR 1.5 mg and 13 for CAR 3.0 mg; 6 for QUE; and 5 for OFC. The NNH estimates for discontinuations due to AEs were: 642 for LUR 20–60 mg and −151 for LUR 80–120 mg; 298 for CAR 1.5 mg and 31 for CAR 3.0 mg; 10 for QUE; and −37 for OFC. NNH values that were negative were assigned a value of 1000 to permit LHH to be calculated. The LHHs for response vs discontinuation due to an AE were: 128.4 for LUR 20–60 mg and 200 for LUR 80–120 mg; 29.8 for CAR 1.5 mg and 3.1 for CAR 3.0 mg; 1.7 for QUE; and 250 for OFC. The LHHs for response vs akathisia were: 3.6 for LUR 20–60 mg and 2.4 for LUR 80–120 mg; 3.6 for CAR 1.5 mg and 1.3 for CAR 3.0 mg; 34 for QUE; and not available (NA) for OFC. The LHHs for response vs EPS were: 8 for LUR 20–60 mg and 3.2 for LUR 80–120 mg; 5 for CAR 1.5 mg and 2.5 for CAR 3.0 mg; NA for QUE; and NA for OFC. The LHH for response vs weight gain was 5.8 for LUR 20–60 mg and 1110 for LUR 80–120 mg; 5 for both doses of CAR; 2.7 for QUE; and 1.5 for OFC.

LHH can illustrate the trade-offs regarding potential benefits versus potential harms. Across a variety of measures, the lower-dose groups for both LUR and CAR generally evidenced a better benefit-risk profile than the higher-dose groups. While quetiapine and OFC demonstrated robust efficacy, their reduced tolerability resulted in a more marginal benefit-risk ratio for some of the outcomes.

Sunovion Pharmaceuticals Inc.

There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD).

In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10–20 mg daily for 8 weeks. Responders continued escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2)—measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response.

Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.

Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.

Dopaminergic mechanisms are involved in addiction but few effective drugs have been developed to treat it. Recent research has highlighted dopamine D2 receptor partial agonists, like aripiprazole, as a potential treatment for different types of substance dependence. In this study we investigate the use of both oral or long-acting injectable (LAI) aripiprazole in the treatment of dual disorders, specifically focusing on patients with psychotic disorder and comorbid substance use disorder.

Retrospective mirror-image study was conducted at an adult psychiatry inpatient unit from a tertiary care center (Ramon y Cajal University Hospital, Madrid, Spain). Patients included were those with a comorbid psychotic disorder and substance-related disorders (excluding tobacco and caffeine), according to DSM-5 criteria, who started aripiprazole in 2017. The number of psychiatric acute inpatient admissions and psychiatric emergency room visits, six months before and after aripiprazole initiation, were obtained from patients’ records. Sociodemographic factors, average length of stay, antipsychotic polypharmacy, type of substance and change on clinical global impression (GCI) scale during hospitalization were also obtained. Data was analyzed using the IBM SPSS, v21. The Wilcoxon signed-rank test was used in the analysis.

11 patients were included; 7 (63.6%) were males, the mean age was 40.37 (SD:13.23) years and the average length of stay was 11.27 (SD:7.53) days. LAI aripiprazole was prescribed in 7 (63.6%) patients (all of them receiving 400mg monthly) and oral aripiprazole was prescribed in 4 (36.4%) patients (mean daily dose= 16.25mg; SD:10.30). Antipsychotic polypharmacy was observed in 6 (54.5%) patients: 4 with quetiapine (mean daily dose=75mg; SD:61.23), 1 with clotiapine 20mg daily and 1 olanzapine 15mg daily. There were 6 (54.5%) polysubstance users and the substances used were cannabis (63.7%), alcohol (36.4%), stimulants (27.3%), opioids (9.1%), hallucinogens (9.1%) and sedative-hypnotics (9.1%).

The mean of inpatient admissions before and after aripiprazole initiation was 1.00 (SD:1.00) and 0.18 (SD:0.60) (p=0.047). The mean of emergency room visits before and after aripiprazole initiation was 1.64 (SD:1.85) and 0.36 (SD:0.67) (p=0.026). With respect to CGI scale, the severity of illness score was 5.09 (SD:0.94) and the global improvement score was 2.00 (SD:0.63) (p=0.004).

These results suggest that aripiprazole could be an effective treatment in psychotic patients with comorbid substance use disorders. However, the results should be taken with caution due to some limitations in our study: a small sample, the short period of time studied, the retrospective design and the inherent biases associated with this type of research. Preliminary investigations on the topic and the results of our study allow clinicians to be optimistic about the use of D2 receptor partial agonist in the treatment of dual disorders.

The objective of the study is to evaluate the differences in health outcomes as well as treatment satisfaction and functionality, focusing particularly in cognitive deficits and perceived disability among stable psychotic patients with therapeutic adherence treated with oral antipsychotics (OA) vs Aripiprazole Long Acting Inyectable (A-LAI).

Naturalistic study, descriptive and transversal. Inclusion criteria: Schizophrenia; 18-65 years old; CGI≤3; treatment OA or A-LAI; no changes antipsychotic therapy in last 3months. Sociodemographic and clinical variables were recorded using self-applied scales (TSQM;EQ-5;SDI;PDQ) and heteroaplied (PSP;CGI;UKU). A mirror analysis was performed in the A-LAI group comparing number of psychiatric drugs and antipsychotic used, previous admissions and emergency care visits.

50 patients (25 OA, 25 A-LAI), 62% male, age 43,9±11,1, psychotic illness evolution 15,9±9,9. In comparison with OA, A-LAI patients present greater functionality scores (PSP) 75±11,5 vs 61,8,±10,5 (p.001) and better results in quality of life (EQ-5D), both quantitatively, 69±18,6 vs 48,3±22,1 (p.005), and qualitatively (particularly in everyday tasks, OR 0,15 (p.009), and better health during the last year OR 0,16 (p.011). Additionally A-LAI patients showed less disability compared to OA, particularly in work areas (4,7 vs 6,8,p.017), social life (4,5 vs 6,6,p.006), overall disability (13 vs 18,p.022) and perceived stress (4,2 vs 6,2,p.020). Perceived cognitive deficits were lower in the A-LAI group, particularly in attention and concentration. There were significant differences in weight gained OR 0,22 (p.082) and sexual disfunction OR 0,078 (p.000) in favor of A-LAI. Prolactin levels are higher for the OA group, 41,7±30,8 vs 8,6±11,67ng/ml (p.003). Treatment satisfaction (TSQM) was significantly higher in A-LAI patients in all 4 dimensions. The factor that most influences the improvement in the functionality is the treatment with A-LAI instead of OA (–10,9±4,1,p.0117). A-LAI patients required a lower number of psychiatric drugs than OA. In A-LAI patients group was observed a statistical significant difference in the number of hospitalizations (1,8 vs 0,08,p.002), the number of admission days to the hospital (45,4 vs 1,5,p.010) and the number of emergency care needed (3,96 vs 0,6,p.000); furthermore, the number of antipsychotics was significantly reduced (2±1,3 vs 0,2±0,4) as well as the number of overall psychotic drugs (4,5±2,1 vs 2,2±1,4).

According to the data from our study patients with schizophrenia that are treated with A-LAI show better results in quality of life, functionality, less perceived disability and cognitive deficits compare to those that received OA, as well as more levels of treatment satisfaction. Tolerance of A-LAI has been better than OA, particularly in the sexual and weight areas, being prolactin levels also lower. The change to A-LAI has allowed a reduced use of health resources.

Approved therapeutics for bipolar depression are associated with a range of undesirable side effects. Lumateperone (LUMA), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. The efficacy of LUMA in bipolar depression was previously established in two Phase 3 trials, as monotherapy (NCT03249376) and as adjunctive to lithium or valproate (NCT02600507).

A recent Phase 3 multi-center trial, Study 401 (NCT02600494) investigated the efficacy and safety of LUMA in bipolar depression and comprised a 6-week, randomized, double-blind, placebo-controlled period and a 6-month open-label extension (OLE) period. Here, we report the results of the OLE period, examining long-term safety.

Patients, aged 18–75 years, with a clinical diagnosis of bipolar I or II disorder who were experiencing a major depressive episode (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score ≥20 and a Clinical Global Impression Scale-Bipolar Version, Severity [CGI-BP-S] score ≥4) were eligible for Study 401. Patients who completed the double-blind study were eligible for direct rollover into the OLE or were re-screened if completing the double-blind period prior to the initiation of the OLE. During the OLE, LUMA 42 mg was administered once-daily in the evening for 25 weeks.

The primary objective was safety and tolerability of LUMA as measured by incidences of adverse events (AEs) and changes in laboratory parameters, cardiometabolic measurements, electrocardiogram (ECG), and vital signs. The secondary objective was improvement/maintenance of symptoms of depression as measured MADRS and CGI-BP-S Total scores.

A total of 127 patients were enrolled in the OLE, with 74 (58.3%) completing the study. Treatment-emergent AEs (TEAEs) occurred in 73 patients (57.5%) with 54 (42.5%) experiencing a drug-related TEAE. TEAEs that occurred in ≥5% of patients were headache, dry mouth, dizziness, nausea, somnolence, anxiety, and irritability. Most TEAEs were mild or moderate in severity. Extrapyramidal-symptom-related TEAEs were rare. Most patients who had normal metabolic laboratory values at baseline remained normal during the treatment period. Mean changes in blood pressure, pulse rate, ECG, and body morphology were minimal. Symptoms of depression improved as measured by the mean change from baseline to Day 175 in MADRS Total score (−8.9) and CGI-BP-S Total score (−2.3).

In patients with bipolar depression, long-term LUMA treatment was generally well tolerated with low risk of extrapyramidal symptoms, weight gain, and cardiometabolic effects. These data further support the safety, tolerability, and effectiveness of LUMA in patients with bipolar depression.

Intra-Cellular Therapies, Inc.

Cotard’s syndrome is a nihilistic delusion where the individual believes they are dead, partly dead, or replaced by an animal. The delusion that their body has been replaced by a purely inanimate azooic (but physical entity), such as a robot or a droid, has not hitherto been described.

Case study: This 60-year-old, right-handed, female, with a past history of schizophrenia presented with complaints of depression, irritability, and anger. When confronted with commitment papers signed by her father, she denied their truthfulness, insisting that he had been replaced by an imposter. This belief persisted unabated, despite treatment with 20 mg of haloperidol per day. Over time, she expressed the belief that she had been replaced by another person, whom she refused to identify. The following day she refused all food and water proclaiming that she had died and been replaced by a machine revealing, “I am not her. I am a robot.” Soon thereafter she developed tremulousness, stiffness, and rigidity. After haloperidol was decreased and benztropine started, these parkinsonism symptoms subsided, but her delusions persisted.

Abnormalities in physical examination: General: decreased blink frequency. Neurologic examination: Mental status examination: bradyphrenia, hypoverbal, blunted affect. Oriented ×2. Motor examination: bradykinetic, cogwheel rigidity in both upper extremities. Gait examination: slow shuffling gait, reduced bilateral arm swing. Cerebellar examination: resting tremor in both upper extremities at 3 cycles per second. Other: EEG: focal sharp transients in the left temporal region. MRI with and without contrast: normal. Toxicological, metabolic, endocrine screening: normal.

This illustrated sequential presentations of three delusions of misidentification. Upon presentation, she exhibited Capgras syndrome, the delusional belief that a familiar person has been replaced by a double. The nidus for this may have been the discovery that her father had signed her commitment papers. This was followed by the belief she was a double of herself, which is the syndrome of Reverse Subjective Doubles. Finally, she manifested Cotard’s syndrome in a previously undescribed manner, believing she had died and become a robot. Cotard’s and Capgras syndromes are known to present sequentially rather than concurrently, whereas the patient presented concurrently with all three syndromes. Drug-induced parkinsonism may have made the patient subjectively feel stiff, which she interpreted as being rigid like a robot. She was bradykinetic, did not eat or drink, and had rigidity, suggesting that these were somatic manifestations of her underlying delusion of being a robot or alternatively, may have been the somatic nidus for the delusion. Those who present with Cotard’s syndrome warrant evaluation for underlying medical conditions, serving as a substrate for this delusion.

No funding

The psychological barrier of college students in employment is increasingly serious in contemporary society, which has a serious impact on their mental health and employment prospects. Macro-education model is an education mode that pays full attention to the development of students. By providing more diversified and comprehensive educational resources, it is expected to alleviate the psychological barriers of college students in employment.

This study selected 50 college students from a certain university as the research subjects, and collected data through questionnaire surveys and on-site observations. The main data collected is information on the degree of employment psychological barriers among college students and the effectiveness of macro education models in alleviating their employment psychological barriers. In this study, SPSS software was used to process and analyze the collected data.

The results showed that the degree of psychological barriers in employment was relatively low among the college students who accepted the macro-education model. By providing abundant employment guidance and practical opportunities, the macro education model enhances college students’ confidence and readiness for employment.

From the perspective of psychology, the macro education model has a certain easing effect on the psychological barriers of college students in employment. By providing more diversified and comprehensive educational resources, this mode of education helps college students to enhance their confidence and readiness for employment, and reduce anxiety and pressure.