Rehospitalization is common in psychosis, often due to poor adherence to antipsychotic treatments. Long-acting injectable antipsychotics (LAIs), particularly paliperidone palmitate 6-month (PP6M), have shown promise in improving adherence and reducing relapses compared to monthly or quarterly formulations . Rapid initiation of PP6M during hospitalization may further optimize post-discharge outcomes and enhance the therapeutic adherence, minimizing the risk of a new outbreak, reducing the impact of rehospitalization and improving patients’ quality of life.

To evaluate clinical outcomes and treatment adherence in schizophrenia and other psychotic disorders after rapid PP6M initiation during psychiatric hospitalization.

A retrospective analysis of 24 hospitalized patients diagnosded with schizophrenia and other psychotic disorders treated with PP6M within 7–10 days was conducted. Treatment adherence, follow-up attendance, and adverse effects were evaluated using McNemar’s test for statistical analysis.

Patients had a mean age of 36.8 years (SD=10.85), 64% were male, with an average of 2 prior hospitalizations (SD=3.16) in the past two years. Previously, 57% were on monthly LAIs. Post-discharge, 83% attended follow-ups. Antipsychotic monotherapy increased by 27% (p = .10) to 59%, while attendance at over 80% of appointments improved by 47% (p ≤ .001). Akathisia was reported in 25% of patients.

PP6M significantly improves adherence by simplifying treatment regimens. Increased follow-up attendance (47%) and greater use of monotherapy reflect better patient outcomes. These findings align with prior evidence on the efficacy of LAIs in preventing relapses. Rapid initiation of PP6M can reduce rehospitalizations and optimize hospital resources. The low incidence of akathisia (25%) supports its safety and tolerability for long-term use.

None Declared

Methylphenidate (MPH), a common stimulant medication for attention-deficit hyperactivity disorder (ADHD), has been shown to enhance both fine and gross motor skills in individuals with ADHD.

This study aims to assess the acute effects of a single dose of MPH on agility and balance motor tests, as well as physiological parameters such as heart rate (HR) and blood pressure (BP) at rest and after motor tests, in young healthy participants diagnosed with ADHD.

A randomized crossover design was employed to evaluate agility and balance motor performance with and without MPH treatment. The study included 35 physical education students (mean age 25.3±3.6 years) diagnosed with ADHD, 65.7% of whom were male. Each participant used their prescribed MPH medication. Motor tests included a zigzag agility test, with and without leading a ball, and a balance test. Physiological measurements, including HR, BP, and core temperature, were recorded at rest and after the motor tests. Subjective sense of effort was evaluated using the RPE scale.

The agility test without a ball showed a small but significant improvement following MPH treatment (without MPH 7.4±0.8, with MPH 7.4±0.8, p= 0.25) . No significant differences were found in the balance test or the agility drill with a ball, regardless of MPH treatment. Systolic blood pressure (SBP) at rest was significantly higher after MPH administration (without MPH 126.7±10.8, with MPH 131.9±12.7, p=.023). There were no significant differences in diastolic blood pressure (DBP), HR, or core temperature at rest or after the motor tests.

A single dose of MPH improved performance in the agility test without a ball but did not enhance balance or agility with a ball. These findings suggest that while MPH may enhance certain motor functions, its effects are selective and not universally beneficial across all motor tasks.

None Declared

It is necessary to know how the pharmacokinetics of psychotropic drugs changes in the body of patients during their long-term use.

To study the pharmacokinetic parameters of the anticonvulsant galodif in experimental rats at different times of drug administration.

Galodif (meta-chlorobenzhydryl urea, 100 mg/kg) was administered in rats (in suspension, intragastrically) for: 1, 5 and 15 days. Galodif was determined in the microsomal fraction of rat liver. Pharmacokinetic parameters were calculated by a model-independent method of statistical moments. The statistical significance of differences was assessed using the Kolmogorov-Smirnov λ-test at p<0.05.

A single administration of galodif to rats is accompanied by a slowdown in its elimination from the body: the values of T1/2 (18.82±6.25h), MRT (22.41±7.07h), MET (10.64±2.84h), AUC (15.01±4.86 mcg/ml) increase, indicating the retention of galodif in the body tissues. A 5-fold administration of galodif stimulates the elimination of the drug: T1/2 (2.22±0.52*h), AUC (3.68±0.79*mcg/ml), MRT (2.95±0.73*h), MET (3.00±0.65*h) decrease. The pharmacokinetic parameters of the drug indicate a pronounced tissue availability of galodif molecules. With a 15-fold administration of galodif, the elimination of the drug from the body slows down somewhat, remaining accelerated relative to a single administration: T1/2 (10.79±2.90*h), MRT (3.97±1.03*h), MET (12.05±4.10*h), AUC (19.28±7.13*mcg/ml). The revealed changes in kinetic parameters during long-term administration of galodif to rats stimulate the elimination of the drug by inducing the microsomal liver oxidative system.

The choice of a drug that combines anticonvulsant and detoxifying properties is of great importance in long-term therapy of paroxysmal disorders, epilepsy and alcoholism.

None Declared

Extrapyramidal side effects due to antipsychotics is very common but antidepressants being the causative factor is very less studied. Among antidepressants escitalopram is the most commonly reported. SSRI’s most commonly cause extrapyramidal side effects than other antidepressants. The major theories are changes in chemical, anatomical and physiological perspectives of neurological system. Reported cases shed light that akathisia occurs most commonly followed by dystonia, parkinsonism and tardive dyskinesia states in antidepressant induced extrapyramidal side effects. Desvenlafaxine (o desmethyl venlafaxine) inhibits reuptake of dopamine, serotonin and norepinephrine. EPS occurs due to inhibitory effect of serotonin on dopaminergic pathway in striatum. Females suffer from it more commonly than men. Increasing age in women,CYP2D6 inhibition by concomittently used drugs can increase the risk. SNRI’s less frequently cause EPS than SSRI’s.Although desvenlafaxine is very well tolerated this rare side effect increases noncompliance and chances of suicide. Drug induced parkinsonism also predicts future chances of parkinsonism. Usage of desvenlafaxine sometimes present to the emergency department as dystonia causing panic among care givers of the patients.

To determine desvenlafaxine’s role in causing extraPyramidal side effects

We report here 8 cases of desvenlafaxine induced extrapyramidal side effects. All follow up cases of depression coming for follow up to dept of psychiatry IMS & Hospital who were on desvenlafaxine was analysed.the patients developong extrapyramidal side effects were detected and detailed evaluation and appropriate management was done for those specific cases..all these cases were collected over a period of last 4 years.

In our case series we bring into light rare occurences of extrapyramidal side effects due desvenlafaxine. 5 out of 8 cases were females.most of the symptoms of developed within 5 days of starting the medicine.4 of these cases resulted in secondary parkinsonism, 3 of them resulted in akathisia and one resulted in acute dystonia post adminstration of desvelafaxine. The average dose of desvenlafaxine in all the cases were within 50-100mg. When after extrapyramidal side effects desvenlafaxine was withdrawn replacement with mirtzapine, escitalopram, sertraline or duloxetine was used instead of it resulting in good symptom reduction of primary illness.

Extrapyramidal symptoms with desvenlafaxine is extremely rare. In our case series we highlighted the importance of a keen eye to check for Extrapyramidal side-effects even with the administration of Antidepressants. Future reasearch is needed to find predictors and exact mechanism of action for the same.

None Declared

In 1975 Clozapine was retired after 16 cases of severe neutropenia, with a mortality of 50%. It wasn´t until 5 years later when its effectiveness in treatment resistant schizorenia, with a mandatory hematological follow up.

In studies available we find that clozapine treatment is related to neutropenia and not leukopenia. In the case we present below neutrophils are within range, but it´s lymphocytes that are affected.

We hope that our expirience, and review can help other professionals in the future who find themselves in this situation.

We used the Pubmed and Uptodate databases.

We present the following clinical case.

Male, 36 years old, with a diagnosis of Schizophrenia. Several admissions to the Acute Unit over the years, requiring treatment with ECT. Maintenance treatment with Olanzapine, with which he maintained some delirious ideation and tendency to isolation. He was admitted again in 2023 due to a destabilization of his pathology, presenting delusions of harm, persecution, self-referentiality, auditory hallucinations, imperative phonemes, etc. with important affective and behavioral repercussions. Several pharmacological treatments were tried (Olanzapine, risperidone, aripiprazole), finally the patient showed some improvement with Lurasidone although his functionality was still impaired.

It was decided to start treatment with Clozapine, to minimize the psychotic symptoms, after a hemogram study, which was normal.

During the weekly follow-up of the treatment, a decrease in lymphocytes was observed, with normal neutrophils. The treatment was proving to be ineffective, so it was decided to continue in this line.

Seven months after starting the treatment, the patient suffered a catarrhal process, and once resolved, we observed in addition of the lymphopenia, anaemia and grade 2 neutropenia in the hemogram. Succeeding a consult with hematology specialist we decided to stop the treatment.

The week following the suspension of the treatment, the hemogram normalizes, but the psychotic symptomatology worsens (inability to relate to others, thought blocks, etc.). Taking into account that the blood alterations occured after a cold, and the mental deterioration that the patient presented, it is agreed with the family and the patient to restart the treatment. Wich resulted in improvement of the psychotic symptoms but a new leukopenia due to a slight lymphopenia is observed again.

The average time described for the resolution of severe neutropenia is 12 days. In our case, the hemogram started to improve by the fifth day following the suspensión of the treatment. As it is an infrequent side effect, we do not have studies on the effects of lymphopenia secondary to Clozapine.

We decided to mantein the Clozapine treatment due to the great improvement of the patients quality of life.

Currently he is taking Clozapine 75mg a day and remains stable.

None Declared

Antipsychotics’ adverse effects in combination with patients’ anosognosia, which is frequent among individuals with schizophrenia, lead to high rates of medication nonadherence. However, long-acting injectable (LAI) antipsychotics represent a veritable ally to the eyes of patients suffering from schizophrenia. Instead of the daily pill-taking required with oral antipsychotics, LAI antipsychotics are administered by injection at two- to four-week intervals, permitting patients to feel more independent, self-secure and free.

To explore the sociodemographic profile of patients receiving LAIs and to highlight the positive and the negative impact this treatment had on their health.

The study sample consisted of 44 patients followed-up in the Depot Outpatient Department of Papageorgiou General Hospital in Greece. The research was conducted between 2023 and March 2024. The sample was divided into subgroups according to gender, diagnoses - according to the International Classification of Diseases (ICD-10)-, and type of long-acting antipsychotic treatment. A bivariate analysis was performed to examine relationships between variables, such as: (a.) age; (b.) family status (c.) BMI; (d.) number of lifetime hospitalizations; (e.) lifetime suicide attempts.

63.6% of patients were men, 36.4% were females.

90.9% were diagnosed with Schizophrenia (F20).

31% were between 31 - 40 years old, while 26.2% were between 51 - 60 years old.

61.4% were unmarried, while 13.6% were married and 13.6% were divorced.

81.8% were unemployed/receiving welfare benefits.

68.2% lived with a relative.

56.8% claimed not suffering from physical diseases. However, when physical disorders were reported, they mainly included dyslipidaemia, diabetes and hypertension.

Based on their BMI, 37.2% were in the 2nd degree of obesity, 25.6% were in the 1st degree of obesity and 30.2% had normal weight.

47.7% were on olanzapine, 22.7% were on paliperidone and 11.4% were on haloperidol or aripiprazole.

The average value of years on LAI treatment was 3.5 years, with a minimum of 1 month and a maximum of 12 years.

Prior LAI treatment, the average value of hospitalizations was 3.5, with a minimum of 1 hospitalization and a maximum of 21 hospitalizations. After receiving treatment, 95.5% of patients were never hospitalized.

Prior LAI treatment, 88.6% of patients had no history of suicide attempts, while 11.4% had one or two suicide attempts. After receiving treatment, no participant had any suicide attempt.

Long-acting injectable antipsychotics help patients to live their lives outside of a psychiatric ward, by drastically diminishing the number of hospitalizations as well as the number of suicide attempts. But when it comes to their physical health, patients face many adverse effects, such as obesity. Clinicians must stay vigilant to ensure the quality of physical health of their patients.

None Declared

Aripiprazole monthly (Ar1M) has been the first long-acting injectable (LAI) partial agonist antipsychotic. The benefits of long-acting injectables in terms of relapse reduction are well known.

The aim of this study is to assess the level of acceptance and the doubts presented by patients before switching to 2-monthly Aripiprazole (Ar2M).

25 patients diagnosed with schizophrenia and related disorders in symptomatic remission were asked consecutively whether they would switch to the new bimonthly formulation of aripiprazole and the doubts expressed were collected.

The sample is composed of 25 patients (12 women and 13 men). The mean age is 52.64 years. All are being treated with Ar1M with a mean dose of 408 mg/monthly. Most of the patients present a diagnosis of affective psychosis (N=12 (42%)), 36% a non-affective psychosis (N=9) and 16% a delusional disorder (N=4). Presenting an average of 3.8 previous admissions.

Acceptance was mostly positive, with an initial acceptance rate of 76 % (N=19). Twelve percent (N=3) did not initially want the treatment. Another 12% had doubts and preferred to postpone the decision. 20% of the patients had doubts, related to possible appearance of side effects. 75% of the patients who do not want the treatment have doubts, as do the patients who prefer to wait. Of the patients who initially accepted the treatment, only 1 expressed doubts about it.

The level of acceptance of Ar2M is very high, exceeding 75%. Of the doubts expressed about the possible change, the appearance of side effects is a matter of concern. Given the high level of acceptance, the treatment proposal is important given the wide-ranging benefits it can bring to patients. The clarification of doubts and the successive proposals of the treatment can contribute to a greater acceptance.

None Declared

Clozapine and olanzapine are among the most effective antipsychotic drugs. However, their use is associated with the development of metabolic syndrome and lipid profile disorders. It is therefore interesting whether they can affect the level of oxidative stress associated with the Fenton reaction, which is a source of harmful hydroxyl radicals in the blood that damage DNA.

The aim of our study was to test the in vitro antioxidant properties of two known neuroleptics – clozapine and olanzapine, which are commonly used in the treatment of schizophrenia and bipolar disorder.

The study was based on the ability of the hydroxyl radical to split deoxyribose into malondialdehyde (MDA). In the experimental system, the Fenton reaction was used as a source of the hydroxyl radical, in which the divalent iron cation reacts with hydrogen peroxide to form a highly toxic hydroxyl radical. For this purpose, deoxyribose was incubated under appropriate conditions with FeSO4 (0.5 mM), EDTA (1 mM), H2O2 (14 mM) and cloazpine or olanzapine at concentrations of 1, 5, 20 or 50 μmol/l. These concentrations corresponded to the concentration of drugs in the cerebrospinal fluid. A clean system (containing no drugs) was used as a positive control. Then, thiobarbituric acid (TBA) was added to the reaction mixtures in the presence of trichloroacetic acid.

Both olanzapine and clozapine inhibited the formation of malondialdehyde (MDA) from deoxyribose under the influence of the Fenton reaction. At concentrations of 1 and 5 μmol/l, both neuroleptics did not inhibit the reaction. At concentrations of 20 μmol/l, olanzapine inhibited the reaction by 15%, and clozapine by 20%. At concentrations of 50 μmol/l, olanzapine inhibited the reaction by 30%, and clozapine by 37%. The difference between the two neuroleptics was not statistically significant.

1. 1. At concentrations of 1 and 5 umol/l, both neuroleptics did not inhibit the studied reaction.

2. 2. At concentrations of 20 and 50 umol/l, both neuroleptics inhibited the reaction.

3. 3. The difference in the degree of inhibition of the reaction between clozapine and olanzapine was not statistically significant.

The similar results of inhibition of the reaction by both neuroleptics probably result from a similar chemical structure. The fact that clozapine and olanzapine inhibit the Fenton reaction may have a beneficial effect in protecting tissues from oxidative damage.

None Declared

Benzodiazepines and zolpidem are commonly prescribed as long-term treatments for anxiety and insomnia, although recommendations generally do not support their extended use. These medications are often prescribed for longer durations than necessary, at inappropriate doses, and with potential drug-drug interactions. In this context, rational prescribing strategies are essential. One potential strategy is the integration of a clinical pharmacist into the inpatient team for daily interdisciplinary ward rounds. However, this approach remains under-researched in the context of inpatients with mental disorders.

This study aimed to evaluate the impact of a clinical pharmacist on medication-related problems (DRPs) focused on benzodiazepine and zolpidem use during daily ward rounds within an interdisciplinary team in a Slovenian psychiatric hospital.

A retrospective observational pre-post study was conducted at Ormož Psychiatric Hospital in Slovenia, including patients treated between 2019 and 2020. During this study, clinical pharmacists provided recommendations focused on benzodiazepines and zolpidem. The primary outcomes assessed were the difference in the total number of DRPs observed at the time of hospital discharge compared to admission. The secondary outcomes evaluated adherence to existing treatment guidelines.

The study involved 20 participants with a mean age of 57.2 years (SD = 17.1). A total of 23 recommendations related to DRPs associated with benzodiazepine and zolpidem use were performed (1.15 per patient). Of these, 19 DRPs (82.6%) were identified as potential issues, while 4 DRPs (17.4%) were already expressed. Most DRPs concerning benzodiazepines and zolpidem were classified as unnecessary treatment, with 18 recommendations (78.3%). The remaining five recommendations (21.7%) addressed treatment effectiveness. The most common recommendation was the discontinuation of benzodiazepine and zolpidem therapy, suggested in 12 cases (56.5%), followed by adjustments to the treatment regimen, predominantly dose reductions, in 9 cases (39.1%). In only one case (4.3%) was the recommendation to initiate benzodiazepine treatment. Initially, the acceptance rate of recommendations was 100.0% (N = 23) at the time of discharge, but this decreased to 82.6% (N = 19) three months after discharge. Adherence to treatment guidelines improved (p < 0.05).

The results indicate that this approach led to fewer DRPs, improved adherence to treatment guidelines, and a high acceptance rate. This is the first retrospective pre-post study in the European Union to include this collaboration in daily rounds at psychiatric hospitals, focusing on these medications. However, the study has notable limitations (non-randomized design and small sample size), which should be addressed in future research.

M. Stuhec Grant / Research support from: Matej acknowledges the financial support from the Slovenian Research and Innovation Agency (research core funding No. J3-50127)., A. Gazdag: None Declared, Z. Cuk: None Declared, R. Oravecz: None Declared, B. Batinić: None Declared

Generalized anxiety disorder (GAD) is a chronic and disabling disorder with an estimated lifetime prevalence of up to 7.8% in the US. MM120 (lysergide D-tartrate), a tartrate salt of D-lysergic acid diethylamide (LSD), is currently under development as a potential treatment for GAD. The mechanism of action (MOA) by which MM120 may elicit profound lasting psychological changes is not fully understood. Studies suggest that it has significant effects on functional brain activity across several networks, likely a result of serotonergic agonism mediated by 5HT2A activity and subsequent changes in neural network connectivity.

A series of Good Laboratory Practice (GLP) compliant studies were conducted to evaluate abuse potential of MM120.

In vitro assessments of MM120, and its main metabolite 2-oxo-3-hydroxy LSD, receptor binding activity were performed using Eurofins CEREP BioPrint. To examine single dosing effects, MM120 was administered by oral gavage to male Sprague Dawley rats (n=6/group) at doses of 0 (vehicle only), 0.5, 2.0, and 6.0 mg/kg. A Modified Irwin test evaluated shorter acting drug effects at 15, 60, 120, and 240 minutes post-dosing compared to pre-dose baseline, with long-term, single dose neurological effects studied in a functional observation battery (FOB) on the day of dosing and 24 hours post dose. To compare potential chronic MM120 effects, male and female Sprague Dawley rats were dosed daily for four weeks via oral gavage at 0 (vehicle only), 0.5, 2.0, and 6.0 mg/kg (n=10-15/sex/group) followed by a 4-week recovery phase. FOB was performed pre-dose, dosing day 27, and day 25 of recovery phase. Additional assessments included toxicological and toxicokinetic evaluations.

Receptor binding assay confirmed MM120’s MOA is mediated by the serotonin system and hallucinogenic effects are driven by agonism at 5-HT2A and 5-HT2C receptors. MM120 demonstrated agonist activity at 5-HT1A, 5-HT1B, 5-HT1D, 5-HT5A, 5-HT6, and 5HT7 receptors and only nanomolar affinity at D2 dopaminergic receptors. Single dose MM120 at 0.5 mg/kg, had no effects on behavioral or physiological states. Following 6 mg/kg MM120, vocalization was recorded in 1/6 rats 2-4 h post dose, and incidences of mild piloerection were recorded in 3/6 rats from 4 to 24 h post dose. In the chronic study, there were no MM120-related changes in basic or fine movements, total ambulation, total rears, or total distance traveled.

Binding studies suggest no indication for elements of abuse for MM120 even with binding at serotonergic and, to a smaller degree, dopaminergic receptors. in vivo studies with MM120 evaluated supratherapeutic doses and demonstrated no evidence of physical dependence or withdrawal after sustained, daily administration for four weeks.

J. Tripp Employee of: Mind Medicine, Inc., G. Smagin Employee of: Mind Medicine, Inc.

Treatment resistant schizophrenia (TRS), according to HOWES et al. 2017, is defined as a patient’s condition in which, despite two or more treatment cycles with adequate dosage and duration of antipsychotic treatment, the patient’s condition does not improve to the extent expected with positive or negative or cognitive symptoms persisting. The heterogeneity of patients with resistant psychosis is high, and some may show the resistance in the course of the disease after years. However, several patients show resilience from the first psychotic episode.

Treatment resistant psychosis is probably a distinct subtype of schizophrenia, with a different etiopathogenetic mechanism. Clozapine is currently considered the drug of choice with proven efficacy, whereas atypical antipsychotic drugs are inferior in efficacy in the treatment of resistant psychosis.

The mechanism of action of the drug is unknown and there is a potential for serious side effects to occur, which necessitates the adoption of a specific protocol for clozapine administration and patient monitoring in regular psychiatric clinical practice.

The Adult Psychiatric Clinic of Sismanoglio General Hospital in Athens, Greece, in its effort to create a systematic and integrated treatment and monitoring of patients who take clozapine, has created, in collaboration with the cardiology and hematology department of Sismanoglio Hospital a special unit for paients with treament resistant scizophrenia.

The unit called “CLOZAPINE UNIT” will ensure the regular and continuous monitoring of patients receiving clozapine during and after their hospitalization in the psychiatric clinic.

None Declared

Tardive dyskinesia is a movement disorder mostly associated with long-term antipsychotic use. Patients may present with a wide variety of clinical features such as stereotypic movements, dystonia, etc. There are many treatment approaches but the level of evidence is low. (Vasan et al. StatPearls Pub 2024)

To draw attention to the clinical presentation of tardive dyskinesia and its treatment.

A detailed case report is documented.

A 43-year-old woman, married, housewife, diagnosed with psychotic disorder. Last year, she admitted to our outpatient clinic for the first time. She was receiving Amisulpride 400 mg/g, Zuclopentixol deconoate 200 mg/month, Biperiden 4 mg/g, Propranolol 80 mg/g on admission. Her complaints were slowed movements and difficulty in doing housework. On examination, mouth puckering and periodic head movement were noticeable. She complained of contractions in her legs and numbness in her tongue. Her speech and walking were slow. In cerebellar tests she was clumsy. She stated that her complaints increased sometimes, the contraction in her neck and legs never stopped, but the mouth puckering movement ceased at night. Her AIMS scale point was 11.

It was learned that about 4 years ago she had started to complain of feeling that she was being spied on and hearing bad things. She had been hospitalized and diagnosed with psychotic disorder. Paliperidone and aripiprazole long-acting injections, olanzapine, quetiapine treatments had been tried during hospitalization and outpatient follow-up. She had been continuously switched to another treatment because of her suspicion. Lastly zuclopentixol deconoate had been started and combined with amisulpride. She stated all her complaints of movement appeared shortly after first hospitalization. Biperiden and propranolol were added to treatment, but her complaints didn’t improve.

During our follow-up she was consulted to neurology. Her current picture was evaluated as tardive dyskinesia. Her treatments were gradually stopped. Clonazepam was started and gradually increased to 2 mg/g and combined with vitamin E and its dosage was increased to 1200 mg/g. After discontinuation of antipsychotics during close follow-ups she had no psychotic complaints. Within 5 months, mouth puckering movement, stereotypic left-turning movement in the neck, numbness in the tongue and contraction in the leg completely resolved. Her speech and walking improved. Last AIMS scale point was 3.

Tardive dyskinesia is an iatrogenic movement disorder. Many methods have been proposed for treatment but no definite treatment is known. It’s thought that vitamin E may be beneficial with its antioxidant effect and clonazepam may be effective above 2 mg. The case is important in terms of demonstrating the efficacy of the combination of vitamin E and clonazepam. (Cornett et al. Ochsner journal (2017):162-174.)

None Declared

The dopaminergic hypothesis of schizophrenia has been constantly revised and virtually all the antipsychotics currently available for the treatment of schizophrenia are based on this pathogenetic hypothesis. However, the involvement of cholinergic, glutamate, gamma-amino-butyric acid, serotonin, neurotrophins, and pro-inflammatory cytokines in the onset of psychotic disorders is attracting more and more interest. This interest is fueled by the high rates of treatment resistance in schizophrenia, which reaches 15-40% (Wong et al Transl Psychiatry 2024;50 14) and requires second-line treatment, frequently associated with significant adverse events. Finding new pharmacological agents that can be used either as monotherapy or as add-ons to the ongoing treatment in patients with schizophrenia is essential for improving the chances of functional recovery.

To review the evidence supporting the modulation of cholinergic neurotransmission as a potential pharmacological target for treating schizophrenia.

Two clinical studies repositories (US National Library of Medicine- clinicaltrials.gov and WHO International Clinical Trials Registry Platform-https://www.who.int/clinical-trials-registry-platform) and the PubMed database were explored using “choline*” and “schizophrenia” or “psychotic disorders” or “schizophrenia spectrum disorders” for studies and reviews focused on cholinergic agents targeting symptoms of schizophrenia.

Positive allosteric modulation of the α7 nicotine receptors and M1/M4 muscarinic receptor agonism are the two pharmacodynamic mechanisms explored for cholinergic-based antipsychotics. Other possible mechanisms of interest are positive allosteric modulation of the M5 muscarinic receptors, selective M4 positive allosteric modulation, and cholinesterase inhibition. Out of these preclinically explored options, only xanomeline, an M1/M4 muscarinic receptor agonist, has reached phase III of clinical research with significant antipsychotic effects. The currently explored formula is an association of a fixed dose of xanomeline (selective M1/M4 cholinergic agonist) and trospium (a cholinergic antagonist), the last agent being included to decrease the risks of peripheric cholinergic adverse events. Studies investigating cholinesterase inhibitors have not been associated with favorable results, and the tolerability was low. Positive allosteric modulators of the α7 nicotine receptors are investigated in preclinical studies, but in phase 1b such an agent, i.e., AVL-3288, failed to show efficacy versus placebo.

The association of xanomeline, an M1/M4 receptor agonist, and trospium, a peripheric cholinergic antagonist, led to favorable results in phase III trials. Other molecules with cholinergic mechanisms are also explored in schizophrenia, but the results are not yet clinically significant.

None Declared

Major depressive disorder (MDD) is associated with high rates of incomplete response during treatment, with only one-third of the patients reaching remission after the first trial of antidepressants, according to the STAR*D trial. Based on the results of the same study, only 67% of the patients with MDD obtained remission after four trials of antidepressants, including a monoamine oxidase inhibitor, i.e., tranylcypromine, and various augmenting strategies. However, in STAR*D, no atypical antipsychotics (AAPs) were used, which is an important shortcoming of this trial. Exploring the efficacy of AAPs as add-on agents to antidepressants in the case of MDD with partial responsiveness may improve the prognosis of patients who did not remit during either antidepressant monotherapy or antidepressant therapy augmented with other psychotropic agents.

To assess the available data on the efficacy and tolerability of atypical antipsychotic augmentation in patients with MDD who obtained only partial response to antidepressants.

This review included three databases (Google Scholar, PubMed, and EMBASE) that were searched from their inception until June 2024 for papers published in English corresponding to the keywords “major depressive disorder,” and “partial response” and “atypical antipsychotics”. Both primary and secondary reports were included.

Systematic reviews dedicated to this topic reported significantly superior responses to placebo for ziprasidone, risperidone, aripiprazole, brexpiprazole, cariprazine, and quetiapine when added to antidepressants. The tolerability of these augmenting agents was low, with high rates of early treatment discontinuation reported. Only risperidone was reported in a systematic review as similar to placebo in terms of tolerability for this population. Network meta-analyses showed positive results for quetiapine, olanzapine, aripiprazole and brexpiprazole in terms of efficacy, but in terms of acceptability, no difference between these four antipsychotics and between each of them and placebo were found; tolerability was low for all antipsychotics vs. placebo, but the certainty of most evidence was evaluated as low and very low. Aripiprazole, quetiapine, olanzapine, brexpiprazole and cariprazine are approved by the FDA for the adjunctive treatment of MDD that does not respond to antidepressant monotherapy.

AAPs are an efficient option for augmenting antidepressants when MDD is only partially responsive to antidepressants, but careful monitoring of this strategy’s tolerability is needed, and high rates of treatment discontinuation are reported.

None Declared

Dysphagia is a rare but significant side effect of antipsychotic medications, often associated with extrapyramidal symptoms. These adverse effects become particularly relevant when dosages are increased, as seen with various antipsychotics. This report describes a case involving a 57-year-old male with a long-standing diagnosis of schizophrenia who developed dysphagia following an increase in amisulpride dosage. The patient was admitted to the psychiatric unit due to psychotic decompensation after interrupting his treatment regimen of aripiprazole 30 mg/day and amisulpride 200 mg/day for two weeks. His psychotic relapse was also precipitated by the hospitalization of his critically ill mother. Following his admission, his previous treatment was reintroduced, and the amisulpride dose was increased to 600 mg/day, with diazepam 15 mg/day added. Subsequently, he developed bradykinesia, tremor, rigidity, and oral dysphagia, necessitating a liquid diet. Despite the introduction of biperiden 4 mg/day, symptoms persisted. Comprehensive physical and neurological examinations, blood tests, and a cranial computed tomography (CT) scan were performed, revealing no abnormalities other than the parkinsonian-like symptoms. An otolaryngological assessment indicated that the dysphagia was likely of neurological origin and probably related to the use of antipsychotic medications.

To present a case of dysphagia and parkinsonian symptoms triggered by an increase in amisulpride dosage in a patient with schizophrenia, highlighting the importance of careful monitoring during dose adjustments.

This is a case report describing a single patient. The methodology involves a detailed examination of this unique case, including clinical evaluation, diagnostic testing, treatment modifications, and outcomes.

Due to the persistence of symptoms and their temporal association with the increase in amisulpride dosage, amisulpride was discontinued and switched to olanzapine 10 mg/day. Gradual improvement in both parkinsonian symptoms and dysphagia was noted over the subsequent days. Dysphagia resolved within one week, and by the time of follow-up, the patient had resumed a normal diet and experienced significant improvement in motor symptoms.

This case highlights the potential for amisulpride to induce extrapyramidal symptoms, including dysphagia, particularly when doses are increased. The temporal relationship between the amisulpride dose increase and the onset of symptoms, along with the resolution of symptoms after discontinuation, supports this association. Clinicians should be vigilant in monitoring for such side effects, especially in patients requiring dose adjustments of antipsychotic medications.

None Declared

The continuous exploration of new treatments in the field of psychopharmacology has brought a new light on psychedelics, raising the provocative question of how these drugs of abuse (DOA) may become useful in clinical practice. Psychedelics are included in the category of “psychoplastogens”, substances that are known for their effects of enhancing neuroplasticity in the nervous central system via the modulation of Brain-derived Neurotrophic Factor (BDNF) signaling. However, psychedelics were originally known as DOA; therefore, ascribing them to therapeutic use for patients with psychiatric disorders may seem largely counterintuitive.

To review the current data on the benefits and risks of psychoplastogens in patients with psychiatric disorders.

A literature review was conducted in four electronic databases (PubMed, EMBASE, Cochrane, and Clarivate/Web of Science) and the US National Library of Medicine database for clinical trials (www.clinicaltrials.gov) to find clinical and preclinical sources published between January 2000 and September 2024. The keywords used were “psychoplastogens,” “neuroplastogens,” “neuroplasticity,” “psychoactive drugs,” “drugs in the pipeline,” and all the main psychiatric diagnosis categories. Both primary and secondary reports were allowed, but only those published in English were selected.

Ketamine and each of its stereoisomers, as well as psilocybin, are the most extensively explored drugs in this class, but also MDMA, DMT, psilocin (ELE-101), CYB003 (a psilocybin analog), and lisuride have received increased attention in the last decade. Such agents are investigated for indications such as treatment-resistant major depression, posttraumatic stress disorder, binge eating disorder, and substance use disorders. One important direction of research is the evaluation of psilocybin in patients with cancer-related depression and/or anxiety. Hallucinations and altered states of consciousness that may receive mystical interpretations are typical for high doses of psychedelics, raising questions about the use of these drugs in clinical populations with already severe mood, thought and perceptual disturbances. Safety and tolerability aspects are extremely important in deciding when, to whom, and how much psychoplastogens may be recommended for different psychiatric disorders. Creating psychoplastogens with less or no psychotomimetic activity is expected to increase the interest of clinicians in the use of such agents for patients with psychiatric disorders, especially in treatment-resistant cases.

Although expected to be a paradigm-shifter in psychiatry, the exploration of psychoplastogens should consider not only the potential benefits, which require further and extensive studies, but also their adverse events. For this purpose, long-term studies are needed with both efficacy and tolerability outcomes carefully monitored.

None Declared

Aripiprazole once monthly 400mg (AOM400) is a long-acting injectable (LAI) available with a two-injection start initiation regimen (AOM400-TIS) for the maintenance treatment of adult patients with schizophrenia stabilised with oral aripiprazole.

This survey sought to explore the perspectives and experiences of HCPs using AOM400-TIS across Europe.

HCPs who had prescribed and/or administered the AOM400-TIS regimen to ≥3 patients with schizophrenia were invited to participate in an online survey. The survey was launched in two waves across the target countries (wave 1: Italy, Germany, United Kingdom (UK); wave 2: Denmark, Italy, Sweden). The survey aimed to understand HCPs’ perspectives and attitudes towards prescribing and/or administering AOM400-TIS according to the European label in clinical practice, including reasons for its use, potential benefits, and common barriers and/or concerns. Analysis was descriptive; data was collected between February 1–March 21, 2024 (wave 1) and September 16-October 28 (wave 2).

216 HCPs completed the survey (wave 1: 31 from Italy, 31 Germany, 32 UK; wave 2: 28 from Denmark, 64 Italy and 30 Sweden) including psychiatrists (67%) and psychiatric nurses (27%). HCPs estimated 30.0% (median; IQR: 20.0–50.0) of patients in their caseload were diagnosed with schizophrenia, and of these, 50.0% were treated with LAIs (median; IQR: 25.0–65.0). 46% of HCPs were primarily responsible for prescribing AOM400-TIS, 26% for administering it, and 28% were responsible for both. HCPs estimated that 42% of patients typically spent 14–28 days on oral aripiprazole prior to AOM400-TIS, with HCPs rating the severity of symptoms of patients initiated with AOM400-TIS as mild (18% of HCPs), moderate (65% of HCPs) and/or severe (53% of HCPs). The most common reasons for initiating AOM400-TIS after transitioning from oral aripiprazole were poor adherence (88%) and relapse(s) (52%), and the most reported goals for prescribing AOM400-TIS were to improve adherence (69%) and prevent relapses (64%). Common barriers to the use of AOM400-TIS were patient reluctance to receive two injections (55%), concerns about tolerability (34%) and safety of administering a high dose in a single day (35%). Prior treatment adherence (56%) and efficacy (46%) were the most cited factors influencing prescribing of AOM400-TIS. Overall, HCPs “agreed”, or “strongly agreed”, that AOM400-TIS was easy to administer (84%) and that it had a similar safety/tolerability profile to the single injection start regimen (60%), while the majority were satisfied with patient outcomes with AOM400-TIS (85%).

Overall, HCPs with experience of using AOM400-TIS reported that it is easy to administer, well tolerated, and improves treatment outcomes, while barriers to its use include patient reluctance and perceived safety concerns.

M. Yildirim Employee of: Murat Yildirim is a full time employee of H.Lundbeck A/S, Valby, Copenhagen., C. Beckham Employee of: Clodagh Beckham is a full-time employee of Otsuka Pharmaceutical Europe Ltd., Berkshire, UK., A. Fagiolini Grant / Research support from: Angelini, Boehringer Ingelheim, Lundbeck, Janssen, Otsuka, Pfizer, Recordati, Viatris, Consultant of: Angelini, Boehringer Ingelheim, Idorsia, Italfarmaco, Lundbeck, Janssen, Medicamenta, Mylan, Otsuka, Pfizer, Recordati, Rovi, Sunovion, Teva, Viatris, K. Leopold Grant / Research support from: Janssen, Otsuka, Consultant of: Boehringer Ingelheim, Lundbeck, Janssen, Otsuka Recordati, ROVI, Speakers bureau of: Boehringer Ingelheim, Lundbeck, Janssen, Otsuka Recordati, ROVI, W. Cottam Employee of: Will Cottam is a full-time employee of OPEN Health (London)., J. Hickey Employee of: Joe Hickey is a full-time employee of OPEN Health (London)., O. Rogerson Employee of: Olivia Rogerson is a full-time employee of OPEN Health (London)., S. Pappa Grant / Research support from: Recordati, Janssen, Consultant of: Lundbeck, Janssen, Otsuka, Recordati, Rovi, Gedeon Richter, Sunovion, Speakers bureau of: Lundbeck, Janssen, Otsuka, Recordati, Rovi, Gedeon Richter, Sunovion.

Suicidal ideations are severe and serious symptoms in the clinical presentation of schizophrenia, as well as adverse reactions such as oculogyric crises. In certain situations, they may be associated with specific pharmacogenetic factors, such as gene variations for the serotonin transporter (SERT) and the CYP2D6 enzyme.

A 37-year-old patient with treatment-resistant schizophrenia, characterized by frequent suicidal ideations, is regularly treated with clozapine (100 mg/day). Additionally, during disease exacerbations, the patient is given haloperidol (10 mg/day) as supplemental therapy, resulting in the development of oculogyric crises.

Due to the lack of therapeutic response and a predisposition to side effects, a pharmacogenetic analysis revealed CYP2D6 genotype *4/*9 and 5-HTTLPR genotype SA/SA. This indicates CYP2D6 intermediate enzyme activity and SERT low activity. Due to these findings, haloperidol was discontinued, and paliperidone palmitate was introduced at a dose of 75 mg monthly, after which the oculogyric crises no longer occurred. The pharmacogenetic results showed reduced SERT activity, which may be associated with the decreased therapeutic response to clozapine and the persistence of suicidal ideations.

Haloperidol is metabolized via CYP2D6, and its intermediate activity can lead to higher plasma concentration, resulting in extrapyramidal side effects such as oculogyric crises. Paliperidone is a metabolite of risperidone, and the activity of CYP450 enzymes has a minimal impact on its therapeutic response and potential for adverse reactions. HTTLPR regulates the transcriptional activity of the 5-HTT gene, so genotypes with low expressions, such as S’/S’ or S’/L’, may exhibit a weaker response to clozapine, which may include the persistence of suicidal ideations.

The personalized antipsychotic treatment according to an individual’s pharmacogenetic profile may prevent adverse reactions and potentially explain therapeutic resistance in such cases where clozapine is otherwise indicated. Effective modern psychopharmacological treatment requires understanding pharmacogenetic factors and their influence on therapeutic response and the development of adverse reactions.

None Declared

One of the main mechanisms of action of LSD in psychedelic-assisted psychotherapy (PAP) is the activation of 5HT2A receptors. This triggers a cascade of neurochemical processes with the release of neurotransmitters and neurohormonal substances. The release of oxytocin in this process is well documented in pre-clinical studies, with recent evidence in healthy subjects. We have no data on oxytocin reactivity during LSD treatment in patients with psychiatric problems. It would be of great scientific interest to identify treatment biomarkers in this field.

The main objective of this pilot study is to obtain preliminary data on the reactivity of salivary oxytocin during a single LSD intake as part of PAP for anxiety disorders or depression. The secondary objective is to establish preliminary correlations between variations in oxytocin levels, intensity of perceived effects, intensity of psychedelic mystical experience, and the overall clinical response to treatment (anxiety-depression symptoms).

Participants are recruited among patients with resistant anxiety-depressive disorders enrolled in the psychedelic-assisted psychotherapy (PAP) program of the Division of Addictology, Department of Psychiatry (Geneva University Hospital). Salivary oxytocin is measured at four different time-points: before LSD intake, then 60, 90 and 180 minutes after intake. Self-perceived intensity of effects is also measured at these time points and a self-report questionnaire of mystical experience (MEQ-30) is administered at the end of the LSD session. Of note, self-reported symptoms of depression (BDI-II) and anxiety (SATI-T) are measured when participants enroll the PAP program, then a few months later right before the treatment and three weeks after treatment. ClinicalTrials.gov:NCT06557239

Six participants (out of 10 planned) have completed the entire protocol. Four additional participants will receive treatment within the next two weeks. Saliva samples are stored at -20.C and will be sent for analysis once recruitment will be over (November 2024). A significant effect of time (P= 0.02) of perceived intensity effects is observed across different time-points (30, 60, 90, 180, 360 minutes after treatment), with a peak effect at 180 minutes. We also observe a significant interaction (P=0.03) between self-perceived intensity of effects and the intensity of mystical experience measured with the MEQ-30. BECK and STAI-T scores will be analysed after post-treatment assessment.

Our preliminary data show a clear effect of self-perceived treatment intensity and a relation between this effect and self-reported mystical experience. It will be of great interest to include oxytocin data in this analysis as well as the evolution of self-reported symptoms of anxiety and depression. With the successful recruitment and easy adherence to the protocol, we will certainly have all data available by the end of 2024.

None Declared

Historically, psychiatric disorders are studied according to a strictly behavioral approach taking into account the manifest symptomatology.

The present work aims to deepen the investigation of neural substrates through the use of neurophysiological recording techniques in an attempt to identify biomarkers related to these pathologies. Investigating whether neurophysiological indices are able to predict the symptomatic improvement and socio-relational functioning of the sample in a transversal manner with respect to the diagnostic category and the symptomatic severity of the psychiatric disorder. Further research is necessary.

The subjects were evaluated through the scale that measures psychopathological severity (BPRS, PANSS), global functioning (HoNOS) and cognitive (MMSE, CDT). The users were categorized based on the diagnosis and divided into the two Clusters, taking into account the number of hospitalizations of each user during the current year. The following neurophysiological parameters were detected using the Rehacor-T device: electroencephalographic (frontocentral brain oscillations), electrocardiographic (heart rate and HRV) and skin conductance (EDA). For a total procedure duration of 10 minutes (6 minutes of rest, 4 minutes in which the Stroop Test task was performed). Statistical analyses (Random Forest Clustering, Logistic Regression, ANOVA) were performed with the Jasp software (JASP 0.17.3.0).

83 users hospitalized at the Psychiatric Unit of the M. Bufalini hospital in Cesena were recruited and categorized according to the clinical diagnosis. Using a Random Forest Clustering algorithm the population was divided into two different Clusters based on the extent of improvement, assessed based on the low or high number of hospitalizations in the last year. Cluster 1 includes people with a higher number of hospitalizations, while Cluster 2 includes those with a lower number. From logistic regression analyses, a single neuropsychophysiological parameter was identified that was able to predict the classification of users within the two Clusters, namely the Beta oscillations (13-30 Hz) recorded in the fronto-central position in the resting state with eyes closed (resting state). Greater power was recorded in the group of subjects who reported a significant improvement in the symptomatic picture (Cluster 2). The variable of sex was not relevant, while the diagnosis, in Cluster 2, a greater concentration of people with depressive disorder was found.

This work highlights how the fronto-central Beta oscillations recorded in the resting state with eyes closed can be a predictive index of the improvement of the psychopathological conditions of the sample. The remaining neurophysiological indices taken into consideration (delta, theta, alpha and beta oscillations, ECG, EDA), did not show the same predictive capacity.

None Declared