What clinical analysis of antipsychotic-induced catatonia and neuroleptic malignant syndrome tells us about the links between these two syndromes: A systematic review.

OBJECTIVES: Antipsychotic-induced catatonia (AIC) and neuroleptic malignant syndrome (NMS) are life-threatening adverse reactions to antipsychotic medication. We conducted a systematic review of literature following the PRISMA statement guidelines to obtain a description of these syndromes (population, context of occurrence, antipsychotic agents implicated) and draw conclusions about their links. METHODS: We searched Medline and Web of science databases from January 1951 to May 2019 (further restricted from 2000 to 2019) using search terms including "catatonia", "neuroleptic malignant syndrome" and "antipsychotic agents" for case reports, case series and analytic studies. After screening 4082 records, 410 full-text articles (describing 555 events) were assessed for eligibility. We included events of AIC and/or NMS according to Diagnostic and Statistical Manual (DSM) criteria and extracted data about patients' characteristics, context of occurrence, antipsychotic agent(s) involved and treatment outcomes. RESULTS: We included 165 events (16 AIC, 129 NMS and 20 AIC + NMS) from 144 case reports and case series. The most reported diagnosis was schizophrenia. Comorbid pre-existing conditions such as central nervous system diseases and acute medical events were common. Most of the events (63.3 %) occurred during antipsychotic monotherapy. Second-generation antipsychotics (SGAs, 63.8 %) were overall more implicated than first-generation antipsychotics (FGAs, 36.2 %). DISCUSSION: Our findings highlight that any antipsychotic medication, even SGA monotherapy prescribed at recommended dose, is at risk for these side effects. FGAs and polypharmacy seem to represent risk factors for malignant catatonia in AIC. The clinical overlap observed between AIC and NMS events in our review suggests a clinical continuum between catatonia and NMS.

Comparative Effects of 30 Antipsychotics on Risk of Catatonia: An Analysis of the WHO Pharmacovigilance Database.

Objective: Catatonia is a life-threatening psychomotor syndrome that occurs in approximately 10% of patients with acute psychiatric illnesses. Although some case reports have argued that first generation antipsychotics (FGAs) are more likely to induce catatonia than second generation antipsychotics (SGAs), no large observational study has confirmed this hypothesis. We investigated whether FGAs were associated with an increased risk of reporting catatonia when compared with SGAs.Methods: A pharmacovigilance study was performed within VigiBase to compare the cases of catatonia syndromes reported in patients exposed to FGAs with those reported in patients exposed to SGAs. This approach is similar in concept to case-control study, but adapted to a pharmacovigilance database, and allows the estimation of reporting odds ratios (RORs) with 95% confidence intervals.Results: We identified 60,443 adverse effects reported in patients who received FGAs and 253,067 adverse effects reported in patients treated with SGAs. Compared with SGAs, the use of FGAs was associated with an increased risk of reporting catatonia syndromes (ROR = 2.2; 95% CI, 2.0-2.3). Consistent results were observed when the analysis was restricted to reports generated from physicians, reports from the US, and reports with the highest completeness score. The highest RORs were found for molindone (6.0; 95% CI, 3.1-10.4) and haloperidol (3.8; 95% CI, 3.5-4.0).Conclusions: In this large pharmacovigilance study of patients exposed to antipsychotics, the use of FGAs was associated with an increased risk of reporting catatonia syndromes compared to the use of SGAs. This increased risk is consistent with the pharmacodynamic hypothesis of antipsychotic-induced catatonia. Our results warrant replication in population-based studies.

Case Report: A Case of Valproic Acid-Induced Hyperammonemic Encephalopathy Associated With the Initiation of Lithium: A Re-duplicable Finding.

Introduction: Hyperammonemic encephalopathy (HAE) is a serious adverse effect of valproate semisodium, which is facilitated by the potential for drug interaction. However, despite frequent co-prescription of valproate semisodium and lithium, the role of this combination in the occurrence of HAE has not been defined in the literature. This case report concerns the occurrence of HAE concomitant with the initiation of lithium in a 29-year-old patient who had been placed on valproate semisodium for a schizoaffective disorder. Case Report: Due to a relapse while on a combined antipsychotic and mood-stabilizing therapy (paliperidone palmitate and valproate semisodium), a cross-taper from valproate semisodium to lithium was proposed. The initiation of lithium was accompanied by an acute confusional syndrome, an elevated serum valproate level and hyperammonemia suggestive of drug-induced HAE. The discontinuation of lithium and reduction of valproate semisodium led to neurological improvement, until a recrudescence of psychiatric symptoms justified a rechallenge of the combination within the framework of a new cross-taper. As soon as Lithium was re-initiated, an increase in the serum valproate level and hyperammonemia were again noted. Discussion: The mechanisms of valproate-related HAE involve various metabolic pathways. In this case, exploration of the iatrogenic hypothesis focused on the imputability of concomitant cannabis use and co-prescriptions of benzodiazepines, antipsychotics, and in all likelihood, mood stabilizers. Conclusion: Therefore, this case study suggests that Lithium plays a role in serum valproate level elevation, and supports the hypothesis of an association between an elevated serum valproate level, hyperammonemia and reversible encephalopathy. A more in-depth pharmacokinetic exploration would provide a better understanding of the mechanisms of these interactions and support for the benefit-risk balance associated with this frequent co-prescription.

Intrusive experiences in posttraumatic stress disorder: Treatment response induces changes in the directed functional connectivity of the anterior insula.

BACKGROUND: One of the core features of posttraumatic stress disorder (PTSD) is re-experiencing trauma. The anterior insula (AI) has been proposed to play a crucial role in these intrusive experiences. However, the dynamic function of the AI in re-experiencing trauma and its putative modulation by effective therapy need to be specified. METHODS: Thirty PTSD patients were enrolled and exposed to traumatic memory reactivation therapy. Resting-state functional magnetic resonance imaging (fMRI) scans were acquired before and after treatment. To explore AI-directed influences over the rest of the brain, we referred to a mixed model using pre-/posttreatment Granger causality analysis seeded on the AI as a within-subject factor and treatment response as a between-subject factor. To further identify correlates of re-experiencing trauma, we investigated how intrusive severity affected (i) causality maps and (ii) the spatial stability of other intrinsic brain networks. RESULTS: We observed changes in AI-directed functional connectivity patterns in PTSD patients. Many within- and between-network causal paths were found to be less influenced by the AI after effective therapy. Insular influences were found to be positively correlated with re-experiencing symptoms, while they were linked with a stronger default mode network (DMN) and more unstable central executive network (CEN) connectivity. CONCLUSION: We showed that directed changes in AI signaling to the DMN and CEN at rest may underlie the degree of re-experiencing symptoms in PTSD. A positive response to treatment further induced changes in network-to-network anticorrelated patterns. Such findings may guide targeted neuromodulation strategies in PTSD patients not suitably improved by conventional treatment.

Case Report: Use of Subcutaneous Midazolam During an Episode of Catatonia.

Midazolam is a benzodiazepine (BZD) mainly used in anesthetic induction due to its pharmacokinetic features. Its place in the therapeutic management of catatonia remains to be determined. Here we present the case of a 65-year-old man who presented with a first episode of catatonia with opposition to any form of oral treatment, where a single dose of 1 mg of subcutaneous (SC) Midazolam permitted clinical improvement allowing oral treatment to be given. The patient's history notably included a renal transplant linked to Polycystic Kidney Disease (PKD) and no history of psychiatric illness nor of any use of psychotropic drugs. As the patient refused to drink or eat and ceased answering basic questions, a psychiatric assessment was required. A diagnosis of Catatonic disorder due to a general medical condition [DSM 5-293.89/ ICD10 [F06.1]] was made. A Bush-Francis Catatonia Rating Scale (BFCRS) analysis returned a score of 15 out of 62, with stupor, mutism, negativism, staring, withdrawal, rigidity, and stereotypy. As the negativism prevented the patient from taking any form of oral treatment, after a brief discussion with the unit's physician, it was decided to administer 1 mg of SC Midazolam. One hour later, the patient was more responsive and compliant, and agreed to drink, eat, and take medication. Thus, the catatonic signs of mutism, negativism, staring, and withdrawal were resolved, but waxy flexibility and catalepsy appeared, leading to a new BFCRS score of 10 out of 62. Oral treatment with 2.5 mg Lorazepam, 4 times a day, was then initiated. Midazolam could be a safer choice compared with the other options available, such as other SC BZD, considering the complex safety profile of this patient with renal insufficiency. This situation represents the first report of using SC Midazolam as an injectable treatment for catatonia. More studies are needed to assess the clinical pertinence of SC Midazolam in the treatment of catatonia.

Traumatic memory reactivation with or without propranolol for PTSD and comorbid MD symptoms: a randomised clinical trial.

Post-traumatic stress disorder (PTSD) is difficult to treat but one promising strategy is to block memory reconsolidation of the traumatic event. This study aimed to evaluate the efficacy of traumatic memory reactivation under the influence of propranolol, a noradrenergic beta-receptor blocker, in reducing PTSD symptoms as well as comorbid major depression (MD) symptoms. We conducted a double blind, placebo-controlled, randomised clinical trial in 66 adults diagnosed with longstanding PTSD. Propranolol or a placebo was administered 90 min before a brief memory reactivation session, once a week for 6 consecutive weeks. Measures included the SCID PTSD module, the PTSD Check List (PCL-S) and the Beck Depression Inventory-II (BDI-II). PTSD symptoms decreased both in the pre-reactivation propranolol group (39.28%) and the pre-reactivation placebo group (34.48 %). During the 6 treatment sessions, PCL-S and BDI-II scores decreased to similar extent in both groups and there were no treatment differences. During the 3-month follow-up period, there were no treatment effects for the mean PCL-S and BDI-II scores. However, in patients with severe PTSD symptoms (PCL-S ≥ 65) before treatment, PCL-S and BDI-II scores continued to decline 3 months after the end of treatment in the propranolol group while they increased in the placebo group. Repeated traumatic memory reactivation seemed to be effective for PTSD and comorbid MD symptoms. However, the efficacy of propranolol was not greater than that of placebo 1 week post treatment. Furthermore, in this traumatic memory reactivation, PTSD symptom severity at baseline might have influenced the post-treatment effect of propranolol.

Memory impairment following intentional self-poisoning with benzodiazepines: Should we pay more attention to attention?

STUDY HYPOTHESIS: In cases where patients attempt suicide through intentional self-poisoning, they often ingest drugs such as benzodiazepines that alter the central nervous system and memory. This is problematic, given that experts recommend the recovery of a patient's cognitive capacity before any psychiatric assessment is conducted. A previous pilot study by our group showed that cognitive tests focusing on attention are the most valuable when it comes to determining whether sufficient cognitive recovery has occurred to ensure that patients will remember the assessment after intentional self-poisoning with benzodiazepines. The main aim of our study was to determine cognitive predictors of the recall of the psychiatric assessment after a suicide attempt. The second aim was to determine the threshold for episodic memory. METHODS: We recruited 97 patients admitted for intentional self-poisoning. At the time of the psychiatric assessments, we quantified plasma benzodiazepine levels and performed a cognitive assessment. We then used a linear regression model to identify the associations in a control and a benzodiazepine group between cognitive functions and episodic memory scores obtained 24 hours after psychiatric assessment. RESULTS: Our model accounted for 28% and 37%, respectively, of the variance in memory in the control and benzodiazepine groups. The most significant correlations were found for the Wechsler Adult Intelligence Scale coding test in both groups. In the control group, tests such as visual and verbal memory were also associated with recall. CONCLUSIONS: Benzodiazepines particularly affect memory by impairing what is remembered of attentional tests. These are, however, the most suitable cognitive tests for predicting recall of the memory assessment.

Traumatic Hystero-Neurasthenia in Professor Charcot's Leçons du Mardi.

At the end of the 19th century, several authors became interested in the physical and psychological symptoms resulting from traumatic life events. Oppenheim presented 42 detailed clinical observations. He suggested the term "traumatic neurosis." Charcot, who was interested in male hysteria, published over 20 cases of traumatic hysteria between 1878 and 1893. The symptoms were considered to have a dynamic or functional origin. The role of horror and terror during the trauma was emphasized. However, Charcot opposed the idea of traumatic neuroses as specific syndromes as he considered them to be only an etiological form of hystero-neurasthenia. In The Tuesday Lessons (Les Leçons du Mardi), he presents several observations. They are surprising when compared with the current criteria for posttraumatic stress disorder (PTSD). Although he had rejected this new entity, a hundred years before the appearance of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, Charcot described most of the symptoms mentioned for a diagnosis of PTSD such as intrusion (reliving the trauma, nightmares, and severe emotional distress), avoidance, negative changes in thinking and mood (negative thoughts, lack of interest, etc.), arousal, and reactivity (trouble sleeping, trouble concentrating, being easily startled or frightened, irritability, etc.).

[Emergency departments and psychiatry]. / Urgences et psychiatrie.

Psychiatric care is becoming an increasingly important part of general emergency departments. Historically incorporated into the psychiatric hospital, emergency mental health care has since been moved to the general hospital. This move was intended to boost the accessibility and deinstitutionalisation of psychiatry. The end of the "asylum" opened up new dialogue with the somatic care network.

Iodine-123 fluoropropyl-carbomethoxy-3-ß-(4-iodophenyltropane) single-photon emission computed tomography findings before and after electroconvulsive therapy in major depressive disorder with Parkinsonism.

BACKGROUND: To date, only a few cases of improvement of Parkinsonism in depressed patients treated with electroconvulsive therapy (ECT) have been reported. However, no functional imaging data are available to support this finding. OBJECTIVE: To describe the first observation of increase in dopamine transporter uptake after ECT. METHODS: Iodine-123 fluoropropyl-carbomethoxy-3-ß-(4-iodophenyltropane) single-photon emission computed tomographic imaging was conducted in a 77-year-old depressed patient displaying symptoms of Parkinson disease (PD) before and after a series of 12 bilateral ECTs. RESULTS: The patient displayed improvement in PD symptoms and increase in dopamine transporter uptake after ECT. CONCLUSIONS: Our observation suggests that the PD symptoms and decrease in striatal uptake appearing in the context of a depressive episode might warrant further attention, as they might be reversible.

Increased overlap between the brain areas involved in self-other distinction in schizophrenia.

Self-awareness impairments are frequently mentioned as being responsible for the positive symptoms of schizophrenia spectrum disorders. However, the neural correlates of self-other distinction in this pathology are still poorly understood. In the present study, we developed an fMRI procedure in order to examine self-other distinction during speech exchange situations. Fifteen subjects with schizophrenia were compared to 15 matched controls. The results revealed an increased overlap between the self and non-self cortical maps in schizophrenia, in the medial frontal and medial parietal cortices, as well as in the right middle temporal cortex and the right inferior parietal lobule. Moreover, these neural structures showed less BOLD amplitude differences between the self and non-self conditions in the patients. These activation patterns were judged to be independent of mirror-like properties, familiarity or body-ownership processing. Significantly, the increase in the right IPL signal was found to correlate positively with the severity of first-rank symptoms, and thus could be considered a "state-marker" of schizophrenia, whereas temporal and medial parieto-frontal differences appear to be "trait-markers" of the disease. Such an increased overlap between self and non-self cortical maps might be considered a neuro-physiological signature of the well established self-awareness impairment in people suffering from schizophrenia.

Course of posttraumatic stress symptoms over the 5 years following an industrial disaster: a structural equation modeling study.

The present study examined individual latent changes in posttraumatic stress disorder (PTSD) symptoms over a 60-month period after an industrial disaster. Participants were recruited from survivors of a factory explosion. Participants were assessed retrospectively for peritraumatic reactions and acute stress symptoms. Posttraumatic stress disorder symptoms were then assessed at 6, 15, and 60 months. Using structural equation modeling, the authors tested 3 hypotheses of individual latent change: stability of PTSD symptoms between 6, 15, and 60 months; change between 6 and 15 months; and change between 15 and 60 months. Only one model provided a good fit suggesting that PTSD symptoms evolved between 6 and 15 months after trauma exposure and remained stable at the individual level thereafter.