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

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

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

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

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

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.

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

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

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

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

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

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

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

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

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

Stuttering is a disruption in speech fluency, characterised by repetition of sounds, syllables, or words, consonant prolongations, and blockages. It can be classified as developmental or acquired, the latter being psychogenic or neurogenic. Neurogenic stuttering is often associated with brain injuries, stroke, neurodegenerative conditions, or side effects of certain medications. Drug-induced stuttering (DIS) is a recognised but rare side effect of psychotropic medications, particularly antipsychotics. Although uncommon, DIS significantly impacts quality of life, especially in males aged 20 to 40. Clinicians may mistakenly attribute the onset of stuttering to the progression of psychiatric or neurological conditions, overlooking the potential role of medication. The exact mechanism of DIS remains unclear, but it is likely related to disruptions in neurotransmitter systems.

This review aims to explore the pathophysiology and neurochemical pathways involved in antipsychotic-induced stuttering (AIS) through a literature review.

A non-systematic literature review was conducted using PubMed with the keywords “psychopharmacology”, “stuttering”, and “fluency disorder”.

Clozapine emerges as the primary drug implicated in DIS, though cases involving olanzapine, risperidone and aripiprazole have also been reported. The pathogenesis of AIS likely involves neurotransmitter system disruptions, particularly dopamine, glutamate and serotonin, within circuits such as the cortico-basal ganglia-thalamocortical loop and white matter fiber tracts. Dopamine dysregulation appears to play a central role, as antipsychotics that block dopamine receptors may impair motor control in speech-related pathways, and additionally in the prefrontal cortex and nigrostriatal pathway. This disruption alters the balance between different brain regions, leading to deficits in motor control over the muscles involved in verbal articulation, which subsequently manifest as stuttering. Furthermore, cognitive and sensory disorders may also contribute to DIS pathogenesis.

Interestingly, stuttering improvement has been noted in some individuals with the same medications that induce it in others, reflecting the variability of dopamine’s role in different brain processes.

DIS, particularly from antipsychotic medications, is a rare but significant clinical issue that may be overlooked. It can cause substantial social impairment, especially in psychiatric patients, who are vulnerable to stigma. Careful monitoring of medication side effects, particularly in those with no prior stuttering history, is essential to provide the best possible care. Drug withdrawal or dose adjustment is often an effective intervention for managing DIS.

None Declared

Clozapine, the first atypical antipsychotic agent, serves as the gold standard treatment for treatment-resistant schizophrenia (TRS), being the most effective choice. Despite the fact that early commencement of clozapine is related to a higher response rate of patients, many psychiatrists remain reluctant towards its initiation. Identifying sociodemographic and clinical features correlating to clozapine response could facilitate the prompt clozapine initiation and ameliorate clinical outcomes.

Our department presents the preliminary results of a prospective cohort study on patients diagnosed with TRS, as defined by the Treatment Response and Resistance in Psychosis (TRRIP) Working Group criteria, before clozapine initiation prospectively for 6 months. The study aims to evaluate the potential association of several sociodemographic and clinical factors with clozapine response.

The patients included in our study were required to have a history of treatment-resistant schizophrenia, as specified by the TRRIP criteria and no history of treatment with clozapine. The TRS patients were submitted to clinical assessments in baseline and 6 months after clozapine initiation included the following: the Positive and Negative Syndrome Scale (PANSS), the Perrsonal and Social Performance Scale (PSP), past medical history, sociodemographic data, blood tests, and monitoring of clozapine blood levels.

30 patients have been screened until now, of which, 26 met the inclusion criteria. 4 patients withdrew from the study before the 6-month follow-up, 4 patients discontinued clozapine due to serious adverse events. 18 patients successfully completed the follow-up. 50% of the TRS patients showed significant clinical response to clozapine, as described by >20% increase in PANSS score. Clozapine responders also showed a significant increase in functionality, as assessed by the elevation of the PSP score (p <0,001), as expected. However, neither PSP score nor PANSS positive, negative or total score at baseline were predictive of clozapine response. Regarding the patients’ sociodemographic data, no statistically significant differences were identified between clozapine responders and non-responders.This study is also in accordance with the existing literature suggesting a significant delay in clozapine prescription by physicians. In our study, 80% of patients were prescribed more than three different antipsychotics before clozapine was initiated.

Clozapine is an effective treatment for TRS, as supported by the preliminary results of our study. 50% of the TRS patients showed significant clinical response to clozapine, as shown by reduction in PANSS score, and increase in PSP score, as a measure of functionality. However, larger clinical samples are needed to showcase further, more delicate differences among the two groups, to highlight potential predictive factors of clozapine response.

None Declared

Major Depressive Disorder (MDD) is a chronic, recurrent illness characterized by various combinations of signs and symptoms, severity levels, and loss of functions. Among the available pharmacological treatments for MDD, Vortioxetine, a serotonin transporter inhibitor (SERT), has been widely used for its multimodal action on serotonin neurotransmission, which produces important changes also on glutamate, GABA, norepinephrine, acetylcholine, and dopamine.

The aim of this systematic review and meta-analysis is to evaluate the acute efficacy of Vortioxetine across multiple dosing to evaluate if there is a dose response effect and as well is there a dose response issue with respect to side effects.

According to PRISMA guidelines we systematically searched 3 major electronic databases (PubMed/MEDLINE, PsycINFO, and Cochrane Central Register of Controlled Trials) for Randomized Controlled Trial (RCT) studies published between January 2013 and April 2024. The RCTs evaluate the efficacy of Vortioxetine on acute depression, compared with placebo or other antidepressants, through improvements in depressive symptoms based on MADRS or HAM-D scores. Twenty-four studies were included in the analysis.

In general, Vortioxetine significantly improved depression severity, anxiety symptoms, cognitive function, with high response and remission rates. It was also well tolerated with a relatively low occurrence of severe or serious treatment emergent adverse events (TEAEs), with nausea as the most frequent adverse event, and/or discontinuation due to intolerability. Observing the results of the meta-analysis, the effect was significant for both Vortioxetine 10 and 20 mg with a greater effect-size for vortioxetine 20 mg. These different results could explain a better clinical efficacy of Vortioxetine 20 mg than Vortioxetine 10 mg for acute symptoms of depression.

In conclusion, the results of the present study underlined the efficacy and safety of Vortioxetine and pointed out that the optimal dosage of Vortioxetine for the treatment of acute symptoms of depression varies between 10 and 20 mg with 20 mg for a better management of acute depression. When choosing initial therapy for MDD in clinical practice, it is important to consider not only drug efficacy but also patient preferences such as AEs and possible adherence. Thus, Vortioxetine should be consider efficacious as a first, and second line therapy.

None Declared

Xerostomia, or dry mouth caused by reduced salivary flow, is a frequently reported adverse effect of various psychiatric medications, particularly tricyclic antidepressants (TCAs), antipsychotics, SSRIs, SNRIs, and anticholinergics. This condition can lead to severe oral health problems causing many patients to discontinue their medication. Anticholinergics and psychotropic medications cause xerostomia by blocking acetylcholine from binding to muscarinic receptors in the salivary glands. Determining rates of xerostomia among psychotropic medications could be useful for those who are at higher risk of xerostomia.

To investigate the prevalence and clinical impact of xerostomia caused by psychiatric medications and to identify effective management strategies.

A narrative literature review of clinical trials, observational studies, and case reports was performed to gather data on the prevalence, severity, and management of xerostomia in patients on psychiatric medications. The review included TCAs (amitriptyline, nortriptyline), antipsychotics (clozapine, olanzapine, chlorpromazine), SSRIs (paroxetine, fluoxetine, sertraline, citalopram), SNRIs (venlafaxine, duloxetine), and anticholinergics (benztropine, trihexyphenidyl). Patient-reported outcomes and interventions were analyzed.

Table 1: Prevalence of Xerostomia by Medication

*Anticholinergics include benztropine and trihexyphenidyl, commonly used to manage extrapyramidal symptoms.

The prevalence of xerostomia was highest with amitriptyline (30-50%), followed by paroxetine (20-40%) and clozapine (10-30%). Anticholinergics contributed to xerostomia in 20-65% of cases. Amitriptyline and anticholinergics often caused moderate to severe cases of xerostomia. Management strategies included the use of saliva substitutes and pilocarpine for TCAs and anticholinergics, dose reduction and increased hydration for antipsychotics, and sugar-free chewing gum for SSRIs. Other medications not listed that are notable for significantly inducing xerostomia among their medication class include citalopram for SSRIs, venlafaxine for SNRIs, and chlorpromazine for antipsychotics.

TCAs and anticholinergics pose the highest risk for the side effect of xerostomia among psychiatric medications. Effective management requires a multifaceted approach, including pharmacologic and non-pharmacologic interventions. Future research should aim to explore alternative medications with lower xerostomia risk.

None Declared

Hypericum perforatum, commonly known as St. John’s Wort, is a widely used herbal remedy for mild to moderate depression. It significantly affects drug metabolism by inducing the Cytochrome P450 enzyme system, particularly the CYP3A4 enzyme. This interaction can alter the metabolism of various medications, including oral contraceptives, cancer drugs, HIV antiretrovirals, and antidepressants. St. John’s Wort increases levels of serotonin, dopamine, and norepinephrine via reuptake inhibition, similar to the action of selective serotonin reuptake inhibitors (SSRIs). However, combining St. John’s Wort with SSRIs can dangerously elevate serotonin levels, potentially leading to serotonin syndrome, a serious and potentially life-threatening condition. This review explores the interactions between St. John’s Wort and SSRIs, focusing on metabolic effects and the risk of serotonin syndrome.

To determine the impact St. John’s Wort has on the metabolism of anti-depressants and to discover the differences in severity of serotonin syndrome between various SSRI’s.

A comprehensive literature review was conducted using PubMed, Google Scholar, and Medline. The review focused on documented drug-drug interactions between St. John’s Wort and SSRIs, particularly their effects on the CYP enzyme system and the incidence of serotonin syndrome in patients taking both therapies.

The review identified that St. John’s Wort affects the metabolism of several antidepressants, primarily through the CYP3A4, CYP2C9, and CYP2C19 enzymes. SSRIs such as citalopram, escitalopram, and sertraline, metabolized by CYP2C19, are more likely to interact with St. John’s Wort than those metabolized by CYP2D6, such as paroxetine, fluoxetine, and fluvoxamine. The most significant adverse effect observed was serotonin syndrome, with case studies highlighting sertraline and paroxetine as the most commonly involved SSRIs. Dosages of SSRIs ranged from 20 mg to 75 mg, with St. John’s Wort dosages typically between 600 mg to 900 mg per day. All reported cases of serotonin syndrome involved both sertraline and paroxetine, suggesting that these SSRIs may have a higher risk when combined with St. John’s Wort, though a larger sample size is needed for statistical validation.

The literature underscores the critical need to screen for patient’s who may have added St.John’s Wort into their treatment regimen, especially when taking SSRIs. St. John’s Wort can significantly alter the metabolism of SSRIs and increase the risk of serotonin syndrome. While interactions with sertraline and paroxetine are well-documented, further research is necessary to determine the risk profile of other SSRIs in combination with St. John’s Wort.

None Declared