Research into early interventions following a first episode of psychosis (FEP) has enabled a focused approach on prognostic-modifying factors. Among these, poor medication adherence contributes to relapse, as well as cognitive and functional deterioration. Several studies report discontinuation rates of oral antipsychotics (OAPs) after FEP at 70%, regardless of the prescribed OAP. The early introduction of long-acting injectable antipsychotics (LAIAs) could present an alternative.

This study aims to review the efficacy of LAIAs in the early stages of psychosis and compare the most relevant international guidelines on this topic.

Methodology: A non-systematic literature review using the keywords “long-acting injectable” and “first episode psychosis,” limited to articles published in English and Portuguese in the last 10 years from the PubMed®/MEDLINE® database, and clinical practice guidelines on psychosis, schizophrenia, and FEP from NICE, APA, and RANZCP.

Despite frequent selection biases (such as reserving LAIAs for patients with worse prognostic factors), significant benefits of LAIAs over OAPs in preventing hospitalization and relapse during the early phases of psychosis are consistently reported. LAIAs reduce non-adherence due to forgetfulness or reduced insight, while their different pharmacokinetics minimize withdrawal symptoms, drug interactions, and fluctuations in plasma concentration, enhancing tolerability. No second-generation LAIA was found to be clearly superior in terms of efficacy. Various guidelines recommend offering this treatment option early, favoring an informed and collaborative decision-making process. However, despite documented benefits in robust studies, they do not consider LAIAs as a first-line treatment.

Discussion/Conclusions: Significant variations in the proportion of patients on LAIAs across countries suggest that factors other than efficacy may influence its use. Greater understanding of these factors could help identify potential barriers to optimal implementation. New evidence may prompt a review of the guidelines.

None Declared

Clozapine is widely regarded as a safe and highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM). Nevertheless, the absolute rate difference is not well-established due to the absence of analytic cohort studies. The clinical significance of such a potential risk remains unclear.

We aim to estimate the rate ratio and rate difference of HM associated with clozapine use.

We extracted data from a territory-wide public healthcare database from January 2001 to August 2022 in Hong Kong to conduct a retrospective cohort study of anonymized patients aged 18+ with a diagnosis of schizophrenia who used clozapine or olanzapine (drug comparator with highly similar chemical structure and pharmacological mechanisms) for 90+ days, with at least two prior other antipsychotic use records within both groups. Weighted by inverse probability of treatment based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) of HM between clozapine and olanzapine users. The absolute rate difference was also estimated.

In total, 9,965 patients were included, with 834 clozapine users. Both groups were followed up for an average of more than seven years. Clozapine users had a significant IRR of 2.22 (95% CI [1.52, 3.34]; p<0.001) for HM compared to olanzapine users. Absolute rate difference was estimated to be 57.40 (95% CI [33.24, 81.55]) per 100,000 person-years. Findings were consistent across sub-groups by age and sex in terms of effect size, although the IRR was non-significant for those aged 65 or older. Sensitivity analyses all supported the robustness of the results and showed good specificity to HM but no other cancers.

Absolute rate difference in HM incidence associated with clozapine is small despite a twofold elevated rate. Given the rarity of HM and existing blood monitoring requirements, more restrictive indication for clozapine or special warnings may not be necessary.

None Declared

Acute generalised exanthematous pustulosis (AGEP) is a rare but severe cutaneous reaction often triggered by medications like antibiotics, calcium channel blockers, and antipsychotics. It is characterised by the rapid onset of non-follicular sterile pustules, fever, and leukocytosis with neutrophilia and eosinophilia. The European SCAR study reports an incidence of 1–5 cases per million annually, with a mortality rate of up to 5% in severe cases (Szatkowski et al. JCM 2022; 11:397). While AGEP is well-documented with various drugs, AGEP induced by low-dose olanzapine is particularly noteworthy due to its rarity and the lack of substantial evidence in existing literature.

The aim of this report is to highlight the potential for AGEP to develop even at low doses of olanzapine and to review similar cases from the literature.

We present the case of a 19-year-old male treated with low-dose olanzapine (2.5 mg) for severe insomnia who developed AGEP. A literature review was conducted to identify other instances of AGEP related to olanzapine. The review utilised PubMed and Google Scholar databases, focussing on cases with detailed patient information including age, gender, dosage, and time to symptom onset (Table 1).

A 19-year-old male with a one-year history of severe sleep deprivation, reporting only one hour of sleep per day in the past week, was prescribed olanzapine 2.5 mg after failed attempts with melatonin, hydroxyzine, and mirtazapine. Two days later, he developed a pruritic rash on the neck, spreading to the trunk and limbs, along with a fever of 38.5°C. Blood tests revealed leukocytosis (12,000/μL), neutrophilia, and eosinophilia but normal liver and kidney function. Dermatological evaluation confirmed AGEP. Olanzapine was discontinued, and cetirizine, an H1 antagonist, was administered. Symptoms improved within 24 hours, and the rash resolved within a week.

Table 1: Summary of Olanzapine-Induced AGEP Cases

This case underscores the need to recognize rare hypersensitivity reactions like AGEP, even at low doses of olanzapine. Early detection and discontinuation of the drug are essential to avoid complications. Literature shows AGEP can occur across various dosages, with symptom onset typically within days. Clinicians should be cautious when prescribing olanzapine, regardless of dose, and closely monitor patients for signs of AGEP to prevent severe outcomes.

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Liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, is an interesting candidate for improving metabolic syndrome and cognition in psychiatric disorders.

We investigated the effects of liraglutide on a depression-like phenotype in mice exposed to chronic unpredictable stress (CUS).

Learning and memory were also assessed using the Morris water maze (MWM) test. Liraglutide (0.3 mg/kg/day for 21 days) was administered to mice with or without exposure to CUS. After 21 days of CUS, the forced swim test (FST) was performed to assess its antidepressant effect. To evaluate cognitive function, liraglutide was administered to mice under stress-free conditions for 21 days, and then the MWM test was performed on 6 consecutive days.

Chronic liraglutide treatment reduced FST immobility in mice with and without CUS. In the probe trial of the Morris water maze test, the search error rate was reduced and the time spent and path length in the target quadrant and the number of platform crossings were increased.

Additional animal model experiments and molecular level studies are needed to support the results obtained in this study. Liraglutide appears to exert antidepressant effects and could improve cognitive function. Based on these results, GLP-1 agonists could have potential as novel antidepressants. It may also help with metabolic syndrome, cognitive dysfunction, and depressive symptoms.

None Declared

Chlorpromazine is historically the first antipsychotic drug. It has played a decisive role in the development of neuropsychopharmacology. However, it can induce adverse effects, sometimes fatal.

To study the relationship between acute cytolytic hepatitis and treatment with chlorpromazine.

We report the case of a patient treated for schizophrenia who developed an acute cytolytic hepatitis after taking chlorpromazine.

We report the case of a 22-year-old woman with no significant medical history, has been diagnosed with schizophrenia who was admitted to our department for physical hetero-aggressiveness.

The clinical examination and laboratory tests performed on admission were normal. The patient was treated with 15 mg of haloperidol and 30 mg of diazepam and 50 mg of chlorpromazine.

On the twelfth day, the patient developed a fever of 38.4°C and abdominal pain. Laboratory tests revealed predominant hepatic cytolysis with elevated ALAT (ASAT: 372 IU/L; ALAT: 463 IU/L), with hepatic cholestasis (PAL: 156 IU/L; GGT: 238 IU/L). Total bilirubin and prothrombin levels were normal with no evidence of jaundice or pruritus

The ALAT/PAL ratio was 8.8 > 5, indicating cytolytic hepatitis. The rest of the clinical and biological examination was completely normal.

Drug-induced hepatitis was suspected and the three drugs were stopped after consultation with the regional pharmacovigilance center in Sfax. The biological control showed a decrease in transaminases (ALAT=5.4*N, ASAT=1.3*N) 3 days after stopping the treatment. Viral serology (hepatitis A,B and C) was negative and liver ultrasound showed hepatomegaly suggestive of drug-induced hepatitis.

Haloperidol-induced cytolysis was initially suspected, and the prescription of chlorpromazine was authorized. Due to the patient’s instability, she was treated with chlorpromazine at a dose of 25 mg*3/d. Twenty-four hours after administration of this neuroleptic, the patient presented a worsening of hepatic status: ALAT=20*N, ASAT=14.4*N, PAL=2.6*N, GGT=19*N. The ALAT/PAL ratio was 7.6, indicating cytolytic impairment requiring immediate discontinuation of chlorpromazine.

The pharmacovigilance investigation blamed chlorpromazine and contraindicated its use. The evolution was characterized by an improvement of the hepatic balance three days after discontinuation of chlorpromazine.

Normalization of transaminases was achieved within 3 weeks. GGT and PAL were normalized after 2 months of discontinuation.

Chlorpromazine was classified as probable (C2S3I3B3(R+)). The score was calculated according to the French Bégaud method.

Edema is not a common side effect of typical antipsychotics. However, it is crucial to emphasize that this effect can occur. Clinicians are advised to watch for edema in all patients taking antipsychotics.

None Declared

Haloperidol (Haldol®) is first-generation antipsychotic that still have a place in the treatment of schizophrenia. However, this molecule is associated with numerous side effects, particularly extrapyramidal symptoms. Edema has been rarely described with haloperidol, and may have an immunoallergic or pharmacodynamic mechanism.

Our aim is to study a rare case of facial and limb edema attributed to haloperidol.

We report the case of a 22-year-old female patient with schizophrenia who developed facial and limb edema after taking haloperidol.

We report the case of a 22-year-old woman. She was admitted to our psychiatric department “A” as an involuntary inpatient after she threatened to stab her father. She was diagnosed with schizophrenia. The patient has no past medical history. The somatic examination and the admission report were correct.

Given the need for a slow-release neuroleptic, the patient was treated with haloperidol in gradually increasing doses up to 30 mg per day.

Six weeks after starting treatment, the patient developed progressive edema of the face, eyelids and all 4 limbs, with a marked increase in weight and body mass index from 31 to 36.6.

The patient was examined by internists. An etiologic investigation of this edema was initiated, excluding renal origin (strictly normal renal work-up and negative proteinuria), cardiac origin (in view of a negative pro-brain natriuretic peptide, D-dimer and troponins and a normal cardiac echography), hepatic (in the presence of a strictly normal work-up including: protidemia, albuminemia, transaminases, PAL, GGT, bilirubin and prothrombin levels) and endocrine (a normal thyroid work-up) origin.

The edema progressively worsened on haloperidol over a period of 10 days. A drug-induced origin was suspected. We contacted the regional pharmacovigilance center in Sfax, which incriminated haloperidol and recommended its immediate discontinuation.

After discontinuing the drug, the edema regressed progressively until it disappeared completely after 15 days, confirming that haloperidol was the drug responsible and contraindicating its further use.

The responsibility of haloperidol in the genesis of the edema was retained with a plausible score (C2S2I2B3). The scores were calculated according to the French Bégaud method.

Edema is not a common side effect of typical antipsychotics, especially haloperidol. However, it is important to emphasize that this effect, although rare, can occur. Clinicians are advised to be aware of edema in all patients taking first or second antipsychotics.

None Declared

Neuroleptic Malignant Syndrome (NMS) is a rare, idiosyncratic, and potentially lethal reaction to psychopharmacological treatment. Several heat-related disorders are influenced by psychopharmacological use, making differential diagnosis challenging. As there are no specific clinical or laboratory findings for NMS, excluding other causes of hyperthermia is essential for accurate diagnosis.

To describe a case of severe NMS and review the key elements of differential diagnosis and treatment options.

A case report and a non-systematic review of the literature.

A 54-year-old male was admitted to the hospital after being found unconscious on the street during a hot August day, with apparent cranioencephalic trauma and a core temperature of 41°C. The patient had a known history of chronic schizophrenia, managed with risperidone (6 mg/day) and quetiapine (800 mg/day), with no recent medication changes. Initial examination in the Emergency Department revealed tachycardia, tachypnea, normotension, diaphoresis and confusion. Laboratory results showed mild leukocytosis with neutrophilia, hyperkalemia, hypernatremia, and elevated acute phase reactants, including a creatine kinase (CK) level exceeding 3000 IU/L. Lactic acidosis and impaired renal function (creatinine 1.9 mg/dL) were also noted. Infectious causes were ruled out, and neuroimaging did not reveal any acute findings to account for the symptoms. Due to persistent decreased consciousness, the patient required intubation and supportive care in the Intensive Care Unit (ICU).

The patient exhibited persistent hyperthermia that was unresponsive to antipyretics and physical cooling measures. Upon suspicion of NMS, antipsychotic medications were discontinued, and treatment with a dopamine agonist and dantrolene was initiated. Muscle rigidity, which developed later, further supported the NMS diagnosis. Electroencephalography (EEG) findings were consistent with NMS. Given the patient’s slow recovery, electroconvulsive therapy (ECT) was started but discontinued after two sessions due to ICU-related infectious complications.

After 19 days of hospitalization and treatment, the patient showed significant clinical improvement, allowing for extubation and discontinuation of intensive care interventions.

This case emphasizes the importance of early recognition and treatment of Neuroleptic Malignant Syndrome to avoid complications and mortality. Differentiating NMS from classical heat stroke can be challenging, with muscle rigidity serving as a critical diagnostic feature.

None Declared

Antipsychotic drugs are known as the major cause of non-neoplastic hyperprolactinemia.

This study aimed to investigate the levels of serum prolactin elevation depending on the use of antipsychotic drugs in patients through the Clinical Data Warehouse.(CDW)

We conducted a cohort search in the CDW application with the following condition. The subjects who aged more than 18 years old and visited from March 1, 2017, to May 31, 2022 at the Department of St. Vincent’s Hospital, The Catholic University of Korea. The subjects were diagnosed according to ICD-10 for schizophrenia, schizotypal and delusional disorders, manic episodes, and bipolar affective disorders. And the subjects who was taking one of risperidone, blonanserin, amisulpride, and olanzapine. The subjects also conducted serum prolactin level tests. After that, we reviewed the medical data.

Among the 117 subjects included in the analysis, the mean serum prolactin level was 64.654.6ng/ml. Serum prolactin levels were significantly higher in subjects taking risperidone or amisulpride compared to blonanserin and olanzapine. The female subjects who took blonanserin, olanzapine, and risperidone had significantly higher prolactin levels, but there was no difference in serum prolactin levels between the sex in the subjects who took amisulpride.

This study suggests the need for regular monitoring of serum prolactin levels in patients who are taking antipsychotics, especially in female patients. And we showed that there is a possibility to conduct more effective and simpler big data research using the CDW. Further studies on the subjects with controlled confounding variables and larger sample groups are needed.

None Declared

Clozapine has the strongest evidence for efficacy for schizophrenia that has proved refractory to adequate trials of standard antipsychotic medication. Its use is limited to these cases due to the uncommon but severe adverse effect agranulocytosis or severe neutropenia, defined as a neutrophil count under 500/microL. It is seen in 0,4 % of clozapine patients and it usually occurs in the first three months. Risk is managed with close blood count (BC) monitoring protocol.

This work aims to improve the understanding and management of this condition.

With this purpose, we present a clinical report and rewiew its management in literature.

We present the case of a 60-year-old man with the diagnosis of resistant schizophrenia who is hospitalized in the acute Psychiatry Unit due to decompensation, where clozapine is initiated with gradual dose augmentation and weekly BC. After improvement of psychotic symptoms, the patient is transferred to a subacute care facility. Two months later, BC revealed mild neutropenia (1000/microL; defined as 1000-1500/microL) becoming severe (100/microL) on the next test one week later. Clozapine is then interrupted and replaced with olanzapine. Neutrophils descend to zero within one day and three days later, with all granulocytes in low levels, the patient presents fever and diarrhea, being finally hospitalized in Internal Medicine. Empirical intravenous antibiotic therapy is prescribed as well as filgastrim, a granulocite-colony stimulating factor (G-CSF). Antibiotic is adjusted after Enterococo Faecalis is isolated in blood cultives. Despite eleven days without clozapine and eight days with G-CSF, agranulocytosis persisted. Taking in consideration the severity of the case and the non existence of acute psychotic symptoms, olanzapine is interrupted and benzodiacepine medication is increased, with BC normalization within three days and remission of digestive symptoms and fever. G-CSF is interrupted and the patient is re-transferred to the subacute unit, with initiation of aripiprazol in the following days.

Upon the appereance of mild neutropenia, closer blood monitorization is recommended (three times a week); with interruption of clozapine and daily monitoring in case of moderate or severe neutropenia. In relation to when to reintroduce antipsychotic treatment, clinical guidelines are cautious, emphasizing the need of close hematological monitoring and careful evaluation of risks and benefits. However, most recommend waiting for complete neutrophil recovery, taking into account the severity of the psychotic symptoms. Olanzapine, with similar mechanism of action but much lower risk, is usually the election.

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Although clozapine-induced agranulocytosis is rare, its complexity and severity requires a fine review of its management, considering that this probably has an impact on the patient’s clinical evolution.

None Declared

A frequent developmental condition of inattention that may or may not be accompanied by hyperactivity is known as Attention Deficit Hyperactivity Disorder.1One’s inability to focus, excessive activity, and behavior that is inappropriate for their age, all of these traits are indicative of ADHD.2The data for Atomoxetine indicates that it is safe and effective in treating ADHD in children and teenagers3. For kids and teenagers with disruptive behaviors, ADHD, and developmental disorders, Risperidone may be a safe, effective medication. Numerous investigations have demonstrated the high effectiveness of risperidone4

To study the Efficacy of Atomoxetine alone vs. Atomoxtine with Antipsychotic (Risperidone) on ADHD children.

This follow-up study was carried out from January to June 2024 on 54 ADHD children (6–18 years old) who were receiving treatment at the psychiatry clinic at Al Hussian University Hospital in Cairo, Egypt. This study was authorized by the Al-Azhar Faculty of Medicine’s Ethical Committee. Following an explanation of the purpose of the study and the acquisition of verbal agreement, all children underwent semi-structured clinical interviews and were excluded from other psychiatric & medical conditions.

Based on the DSM IV criteria, ADHD has been diagnosed in all of the study children. Conner’s 2 test for ADHD, or SCID, was used for every child in the study. Implementing medicinal treatment for every child and monitoring their progress, who were divided into two groups. The first group, which consisted of 27 children diagnosed as ADHD children, received only Atomoxetine, independent of the kind of ADHD. In contrast, 27 recently diagnosed children with ADHD, irrespective of their kind of ADHD, received a combination of Atomoxetine and antipsychotic(Risperidone) medication in the second group.

SPSS 20.0 was employed. The qualitative data were expressed in terms of percentages and figures, and the significance of the outcomes was assessed at the 5% level.

When Atomoxetine was administered to 27 children, it demonstrated a moderate level of efficacy to 12 from 27 patients (44.4%) for all children with ADHD, regardless of type, but it significantly improved the inattention type of ADHD in 4 from 4 patients (100%).Given to 27 children, the combination of Atomoxetine and Risperidone demonstrated greater effect on 24 from 27 patients with (88.9%) for all ADHD children, and it showed a discernible improvement on 9 out of 9 with (100%) for ADHD hyperactivity type.

All types of ADHD are responsive to Atomoxetine or Atomoxetine / Antipsychotic (Risperidone) combination, But Atomoxetine effect is more on Attention deficit variant than other variants, while Antipsychotic (Risperidone) is more effective on hyperactivity and aggression.

None Declared

Therapeutic window in psychopharmacology is the range of drug concentrations that achieve desired effects safely, with treatment failure more likely when levels fall outside this optimal range. The role of dopamine receptor partial agonists (DRPA) in the treatment of depression is a case in point.

We discussed the unique mechanisms, and effective antidepressant doses of DRPAs within their therapeutic windows.

PubMed search was conducted, focusing on randomized controlled trials, open-label studies, and reviews evaluating aripiprazole, brexpiprazole, and cariprazine as augmentation therapies for major depressive disorder in adults.

Clinical trials have investigated aripiprazole, brexpiprazole, and cariprazine as adjuncts to antidepressants, and the effective antidepressant dose is generally lower than the minimal antipsychotic dose. Specifically, the antidepressant doses are 2 – 10 mg for aripiprazole (antipsychotic dose 10 – 30 mg), 2 – 3 mg for brexpiprazole (antipsychotic dose 4 mg), and 1.5 – 3 mg for cariprazine (antipsychotic dose 1.5 – 4.5 mg). This is because at subantipsychotic doses partial agonists increase the dopamine signal, but at antipsychotic doses they reduce the dopamine signal to the level of the intrinsic activity of the drug (generally 25 – 40% of the maximal dopamine signal) which is generally inadequate for an antidepressant response.

DRPAs can increase or reduce the dopamine signal depending on receptor occupancy. At higher receptor occupancy they reduce the dopamine signal, while at lower receptor occupancy (when unoccupied receptors can interact with endogenous dopamine) their intrinsic activity can increase the dopamine signal. Understanding the drug-receptor relationship is crucial, as the assumption that higher doses are always more effective is incorrect.

None Declared

In 2015, the United States Food and Drug Administration (FDA) approved Brexpiprazole as an adjuvant treatment for adults with major depressive disorder and as a treatment for adults with schizophrenia. Although studies suggest that Brexpiprazole is an effective adjunctive treatment for major depressive disorder in Europe, the European Medicines Agency (EMA) approved Brexpiprazole only for the treatment of schizophrenia in adult patients.

To observe the safety, tolerability, and efficacy of brexpiprazole in patients with bipolar depression.

We followed, during 2 months, six patients diagnosed with bipolar disorder who met DSM-5 criteria for a major depressive episode. Four of them were women, two men. All were being treated with mood stabilizing drugs (2 with valproic acid and 4 with lithium). The average age was 43 years.

Visits were conducted every 15 days. At each visit, we evaluated depressive symptom improvement, any adverse effects, and the emergence of manic or hypomanic symptoms.

All patients were informed of the off-label use of this drug and gave their consent.

Five out of six patients continued treatment throughout the study; only one patient discontinued due to adverse effects (amenorrhea). All patients who maintained treatment demonstrated a subjective improvement in depressive symptoms, as observed by both, clinicians and the patients themselves. No patients presented with manic or hypomanic symptoms suggestive of a shift to a manic pole.

Although off-label, brexpiprazole may be beneficial for certain patients with depressive symptoms and a diagnosis of bipolar disorder. It displayed a good tolerability profile, with no observed shifts to mania in our small sample.

None Declared

The administration of high-dose sertraline for the treatment of obsessive-compulsive disorder has been investigated as a potentially more efficacious strategy in cases of treatment resistance, compared to standard dosing regimen. Studies have also evaluated the safety and tolerability of doses as high as 650 mg/day (Levy et al. Compr Psychiatry 2024; 133:152486).

To highlight the importance of understanding the potential use of high-dose sertraline for the treatment of treatment-resistant obsessive-compulsive disorder.

Case report and literature review

This is a 50-year-old woman referred from the emergency department, where she presented with thoughts of death and was diagnosed with ‘Depressive Disorder. Impulsion Phobia without warning signs’ and treated with Sertraline 100 mg. During the first consultation, the patient reported the following symptoms:

• - Marked emotional overwhelm and hypervigilance.

• - Intrusive thoughts related to her father, generating significant guilt.

• - Thoughts in which she feels the desire to harm herself.

• - Compulsive need to check everything she writes, regardless of the context, to confirm she has not written anything bad about herself or her family.

• - Compulsive need to review past actions to ensure she did not say anything inappropriate (despite not having spoken).

• - Compulsive need to revisit conversations to ensure she had not said anything inappropriate, which eventually led her to stop speaking altogether.

• - Mixed insomnia due to anticipatory anxiety about the thoughts she might have during the night.

During this initial visit, a diagnosis of Obsessive-Compulsive Disorder with mixed obsessive thoughts and acts (ICD-10; F42.2) was made. The Y-BOCS was administered, with the patient scoring 19 for obsessions and 12 for compulsions (total score: 31, indicating severe OCD). The dose of sertraline was increased to 300 mg, and aripiprazole was added. However, aripiprazole had to be discontinued after 15 days due to poor tolerance, and risperidone was introduced, which also had to be discontinued after 15 days due to poor tolerance.

After four months of follow-up and monotherapy with sertraline, the patient presented with almost complete resolution of symptoms, a stable mood, calm demeanor, and regained control over her thoughts, along with the disappearance of the compulsive checking behavior. A Y-BOCS was administered again, with a score of 8 for obsessions and 5 for compulsions (mild severity).

The use of high-dose sertraline (250-400 mg/day) may be an effective alternative for maintaining monotherapy in patients with treatment-resistant obsessive-compulsive disorder. However, it is important to consider that previous studies have shown a better response but not a higher overall response rate (Ninan et al. J Clin Psychiatry 2006; 67:15-22).

None Declared

Current evidence on psychological adverse effects (AEs) of antipsychotic medication after remission of First Episode Psychosis (FEP), and the impact of these AEs on daily life, is limited.

To investigate serial cross-sectional associations between antipsychotic medication regimen and psychological AEs after remission of FEP.

This Ecological Momentary Assessment (EMA) study investigates baseline data of 56 participants from the HAMLETT trial (Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment). Momentary mental states indicative of blunted affect intensity and variability, reduced initiative of social contact, avolition and tiredness were assessed 10x/day for eight consecutive days. Based on neurobiological mechanisms likely mediating these psychological AEs, antipsychotic medications were grouped based on their Dopamine-2 (D2) and Histamine-1 (H1) receptor profile. Multilevel mixed-effects regression models were employed overall and separately for mornings, daytimes and evenings, to investigate serial cross-sectional associations between medication type or dosage and concurrent psychological AEs. All models were adjusted for fixed effects of age, gender, tobacco and cannabis use in the past month and symptom severity during FEP (based on the Comprehensive Assessment of Symptoms and History, CASH).

In total, 85 out of 453 HAMLETT-participants took part in the EMA add-on study. At baseline, 56 (66%) of those participants completed >26 EMA questionnaires and were currently taking antipsychotic medication, yielding a total of 3,005 questionnaires for our analyses. The distribution of antipsychotic medication regimens was relatively equally spread (25% high affinity D2 antagonists, 48% low affinity D2 antagonists, 27% partial D2 agonists). Higher dosage (Beta (B) = -1.11 [95% Confidence Interval (CI): -1.97; -0.24]) and use of high affinity D2 antagonists, as compared with partial D2 agonists (B = 12.98 [95%CI: 2.43; 23.53]) and low affinity D2 antagonists (B = 10.04 [95% CI: 0.59; 19.49]), were associated with decreased positive affect (PA) (see Figure 1). Higher dosage was also associated with small increases in PA variability (B = 0.23 [95% CI: 0.04; 0.42]. The remaining psychological AEs were not associated with dosage or D2 profile, neither was H1 profile associated with these AEs. Results were relatively consistent across daytimes, though effect sizes were greatest in the evenings.

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After remission of FEP, higher dosage of antipsychotic medication and use of high affinity D2 antagonists, as compared with partial D2 agonists and low affinity D2 antagonists, can be associated with decreased, though not invariable, positive affect as estimated using EMA.

None Declared

The treatment strategies for antipsychotics induced hyperprolactinemia apart from switching to prolactine-sparing antipsychotics, reducing the doses of antipsychotics and adding dopamine agonists such is bromocriptine, include add-on therapy with third generation antipsychotics (aripiprazole, cariprazine)

During the previous years, some studies with adjunctive aripiprazole therapy have been conducted, however the research with cariprazine in this purpose are absent.

The main goal of this research is to analyse both short-term and long-term changes in the level of prolactine after adding cariprazine in the long acting risperidone treatment of patients with psychotic disorders.

Six inpatients threated during the first three months of 2024, that were consecutive diagnosed with hyperprolactinemia induced by long acting risperidone Depo therapy, were included for the participation in this research. For all study participants, the long acting antipsychotics therapy was previously used for more than 3 months and in all of them other possible causes of hyperprolactinemia were excluded by neuroimaging procedures and examinations of consultant endocrinologist. After starting adjunctive therapy with cariprazine in the dose range between 1.5 and 3mg daily, for at least three weeks, while risperidone therapy remained at the same dose, prolactine levels were firstly re-examined. The second control of prolactine levels were done after 6 months.

All patients were diagnosed with ICD 10 categories of psychotic disorders, 2 of them (33.3%) with F20 category (Schizophrenia), 3 of them (50%) with F 29 category (nonspecific psychosis) and 1 of them (16,6%) with F23 category (acute psychosis). On average age of the patients were 37,6 years, 3 of them had male and 3 female sex. Prolactine base values (T0) were between 612 mlU/L and 4051,53 mlU/L (on average 2150,7 mlU/L). After introducing cariprazine adjunctive therapy for at least three weeks, the levels of prolactine (T1) substantially declined in five out of six patients (83,3%). This second values of prolactine were in the range between 306 mlU/L and 2014,4 mlU/L which represents 22,9% to 67% reduction of their initial level (on average 47,34%). In only one study case, the prolactine level has raised from 667,73 to 765,88 (14,7%). The third value of prolactine (T2) were re-examined after the 6 months of introducing the cariprazine treatment and values of prolactine remained at low levels.

The main conclusion of this pilot study can be that cariprazine adjunctive therapy is valuable pharmacological intervention for the treatment of risperidone induced hyperprolactinemia and that these effects sustain over the 6 months period. However, the number of participants in this research is rather small, and for that reason, further investigation at the bigger number of participants are necessary for definite conclusions.

J. Dedovic Grant / Research support from: In the past I have received several honoraria for lectures organised by Richter Gedeon. However this research has not been paid by any commercial organisation., A. Tomcuk: None Declared, A. Macic Grant / Research support from: In the past I have received several honoraria for lectures organised by Richter Gedeon. However this research has not been paid by any commercial organisation., V. Roganovic: None Declared, S. Dedovic: None Declared

Duration of untreated psychosis (DUP) is defined as the time from manifestation of the first psychotic symptom to initiation of adequate antipsychotic drug treatment. It is associated with poorer response rates to antipsychotic medications and impaired cognition, which traslates in worse positive and negative symtomps. Various hypotheses for how untreated psychosis could impact brain function have been proposed. Dopaminergic hyperactivity leading to a progressive reduction in regional brain volumes and oxidative injury due to persistent catecholaminergic activity and prolonged activation of the hypothalamic–pituitary–adrenal axis provide possible explanations for how chronic psychosis could be neurotoxic. In addition, glutamate-mediated excitotoxicity may also contribute to these effects through neuronal overstimulation that leads to an excessive influx of calcium and subsequent excitotoxicity and, ultimately, cell death via apoptosis.

To analyze the advantages of long-acting injectable therapy in the treatment of psychotic disorders in patients with prolongued duration of untreated psychosis with a case communication.

We present a 61 year old female patient, native of a rural area of Peru who moved to Spain and started treatment in our outpatient department. She does not provide any medical report. The family reports that she began to present symptoms from her first pregnancy, and has had to be admitted to hospital several times for suicide attempts. She had never taken any antipsychotic drug. During the last 30 years she developed symptoms consisting of erotomaniac and paranoid delusional ideation, cenesthetic and auditory hallucinations, soliloquy, self care deficit and disorganised speech and behaviour. She presented periods of maniac mood. As a result, she ended up isolated, taken care by his father and highly dependent on instrumental activities of daily living.

Treatment with Risperidone was started, although the patient presented poor adherence to it. She was finally admitted to hospital for a month and we introduced once-monthly Risperidone and Valproate with significant clinical improvement.

Long acting injectables are a good therapeutic option in patients with psychotic disorders, even with prolongued duration of untreated psychosis.

None Declared

Perampanel is a selective antagonist of the AMPA receptor for glutamate, primarily approved for the treatment of certain types of epilepsy. With the evolving understanding of psychiatric disorders’ neurobiology, it’s hypothesized that targeting the glutamatergic system could offer substantial therapeutic benefits (Perversi F, Costa C, Labate A, Lattanzi S, Liguori C, Maschio M, et al. The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy. Front Neurol [Internet]. 2023 [cited 2024 Sep 2] ;14:1182304).

The purpose of this study is to evaluate the effectiveness of perampanel in managing psychiatric symptoms such as sleep disturbances, depression, anxiety, and irritability.

A comprehensive review of scientific studies was carried out, centering on clinical trials and observational research that explored the application of perampanel in individuals exhibiting psychiatric symptoms. The review included articles published between 2013 and 2024, utilizing databases like PubMed, Scopus, and PsycINFO for sourcing. The inclusion criteria covered studies that assessed the impact of perampanel on psychiatric conditions, detailing both the clinical results and any side effects.

Findings indicate that perampanel may have beneficial effects in reducing symptoms of insomnia (Abenza-Abildúa MJ, Suárez-Gisbert E, Thuissard-Vasallo IJ, Andreu-Vazquez C. Perampanel in chronic insomnia. Clin Neurol Neurosurg. 2020 May 1;192), depression and anxiety (Scorrano G, Lattanzi S, Salpietro V, Giannini C, Chiarelli F, Matricardi S. The Cognitive and Behavioural Effects of Perampanel in Children with Neurodevelopmental Disorders: A Systematic Review. J Clin Med [Internet]. 2024 Jan 10 [cited 2024 Sep 3];13(2)) in certain patient groups. However, significant adverse effects were also reported, including behavioural changes and increased aggression in some cases, necessitating careful monitoring during treatment.

Numerous antiepileptic medications have been effectively utilized in treating psychiatric conditions. Perampanel, in particular, has demonstrated effectiveness in managing nocturnal seizures, preserving sleep architecture, and treating restless legs syndrome. A study conducted in Spain revealed that combining perampanel with either an antidepressant or an anxiolytic significantly enhances sleep quality after three months in patients without epilepsy (Abenza-Abildúa MJ, Suárez-Gisbert E, Thuissard-Vasallo IJ, Andreu-Vazquez C. Perampanel in chronic insomnia. Clin Neurol Neurosurg. 2020 May 1;192).

While there are no large-scale clinical trials specifically targeting mood disorders, some ongoing research is exploring the broader psychiatric effects of Perampanel, including its impact on anxiety disorders.

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Hypericum spp., particularly Hypericum perforatum (such as St. John’s Wort), produce hypericin and hyperforin, secondary metabolites that play critical roles in the plant’s defense mechanisms. These compounds, characterized by their polycyclic and lipophilic properties, have evolved to deter herbivores and protect against pathogens. Understanding the evolutionary pressures that shaped these compounds enhances our knowledge of their biochemical roles.

This review aims to synthesize current knowledge on the evolutionary development of hypericin and hyperforin within the Hypericum genus, focusing on how these metabolites evolved to fulfill defensive ecological functions.

A comprehensive literature review was conducted, examining phylogenomic studies, structural analyses, and biochemical research related to the biosynthesis of hypericin and hyperforin. We reviewed relevant phylogenetic data to understand the diversification of these compounds across Hypericum spp.

The literature supports that hypericin and hyperforin evolved in response to selective pressures during the Cretaceous-Paleogene boundary, with their complex polycyclic aromatic structures optimized for defense. These structures, which include conjugated π-systems, are central to the compounds’ ability to deter herbivores and resist pathogens, reflecting an evolutionary adaptation that is conserved across the genus.

The evolution of hypericin and hyperforin within Hypericum spp. is a prime example of how secondary metabolites serve dual purposes in nature and human use. The phylogenetic and biochemical insights reviewed highlight the importance of these compounds as both ecological defenses and pharmacologically active agents.

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The use of antidepressants is becoming more prevalent among athletes due to the growing awareness of mental health issues in sports. However, the impact of these medications, especially selective serotonin reuptake inhibitors (SSRIs), on physical performance remains uncertain. Studies on psychotropic drugs’ effects on athletic capabilities raises concerns about their use in sports, particularly under anti-doping regulations.

This review aims to assess the impact of antidepressants on physical exercise performance and muscle metabolism, in order to clarify how they influence physical capabilities.

A literature search was conducted on PubMed in September 2024 using search terms such as “sports” AND “antidepressants,” “physical activity” AND “antidepressants,” “exercise” AND “selective serotonin reuptake inhibitors,” among others. Only systematic reviews and meta-analyses were included, without restrictions on language or year. Three articles met the scope of this work.

The effects of antidepressants on athletes are inconsistent, with some studies indicating no significant change in performance, while others report reduced endurance. Paroxetine and fluoxetine, commonly prescribed SSRIs, may impair endurance due to increased serotonin levels, which can exacerbate fatigue, known as central fatigue hypothesis. It is also emphasized that SSRIs may reduce athletic performance, especially under thermal stress, by affecting thermoregulation, alongside its interference in serotonin pathways. Potential metabolic impact of these drugs was found, as chronic exposure to SSRIs showed modulation of glucose uptake, mitochondrial respiration, and muscle mass. Furthermore, SSRIs also induced changes in electrical muscle activity.

The evidence on the effects of antidepressants, particularly SSRIs, on physical performance and muscle function remains inconclusive. Athletes and healthcare providers must weigh these risks carefully, considering both the clinical and ethical implications of psychotropic drug use in competitive sports. Therefore, future research should focus on more consistent study protocols and explore the long-term metabolic consequences of SSRIs in physically active populations.

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Doctors Without Borders works in humanitarian settings. In these settings, we have observed a notable movement away from first generation medications such as haloperidol towards second-generation antipsychotics, where these medications are available. We began to question whether the evidence clearly justified this and decided to contribute to the evidence.

To assess the clinical benefits and harms of haloperidol compared to olanzapine for people with schizophrenia and schizophreniaspectrum disorders.

Searched the Cochrane Schizophrenia study-based register of trials, screened the references of all included studies. We contacted relevant authors of trials for additional information where clarification was required or where data were incomplete. The register was last searched on 14 January 2023.

We didn’t find a statistically significant difference between haloperidol and olanzapine in global state (RR 0.84, 95% CI 0.69 to 1.02), nor in relapse (RR 1.42, 95% CI 1.00 to 2.02). Haloperidol resulted in an increase of extrapyramidal side effects compared to olanzapine (RR 3.38, 95% CI 2.28 to 5.02). For weight gain, there may be a large reduction in the risk with haloperidol compared to olanzapine (RR 0.47, 95% CI 0.35 to 0.61). Haloperidol may result in an increase of leaving the study early compared to olanzapine (RR 1.99, 95% CI 1.60 to 2.47).

Overall, the certainty of the evidence was low to very low for the main outcomes in this review, making it difficult to draw reliable conclusions. There is no clear difference between haloperidol and olanzapine in terms of global state and relapse. Different side effect profiles were noted. These findings should contribute to continue using haloperidol and olanzapine.

Many studies did not use equivalent doses of the two medications when they were compared. Most studies used comparatively higher doses of haloperidol compared to olanzapine.

None Declared