Drug-induced delusion: A comprehensive overview of the WHO pharmacovigilance database.

INTRODUCTION: A number of prescribed medicines have been reported in cases of drug-induced delusion, such as dopaminergic agents or psychostimulants. But to this day, most studies are based on a limited number of cases and focus on a few drug classes, so a clear overview of this topic remains difficult. To address this issue, we provide in this article a comprehensive analysis of drug-induced delusion, based on the World Health Organization (WHO) pharmacovigilance database. METHODS: We performed a disproportionality analysis of this database using the information component (IC). The IC compares observed and expected values to find associations between drugs and delusion, using disproportionate Bayesian reporting. An IC0.25 (lower end of the IC 95% credibility interval) > 0 is considered statistically significant. RESULTS: Here we present an analysis of 4559 suspected drug-induced delusion reports in the WHO pharmacovigilance database. These results identified 66 molecules statistically associated with delusion and an extensive analysis of confounding factors and coprescriptions was performed, using full database as background with an IC0.25 > 0. The main drug classes involved were antidepressants, antiepileptics, dopaminergic agents, opioids, antiinfective agents, benzodiazepines, anti-dementia drugs and psychostimulants. CONCLUSION: These results will help clinicians identify potential suspected drugs associated with delusion and decide which drug to discontinue and eventually lead to a re-evaluation of drug labels for some molecules.

Acute Onset Psychosis With Mystical Delusions in a Young Male Patient Following Discontinuation of Corticosteroid Therapy: A Case Report.

Corticosteroid-based drugs are widely used in the general population to treat several acute and chronic inflammatory conditions. However, the therapeutic efficacy of these drugs is often accompanied by severe psychiatric adverse effects through a yet unknown mechanism. To further complicate this situation, therapeutic strategies to counteract psychotic symptoms associated with these agents have yet to be devised. We report a case of a young white male Jehovah's Witness admitted to the psychiatry ward of the Maggiore della Carità Hospital, Novara, Italy. At admission, the patient presented with psychomotor agitation, auditory hallucinations, and thought disturbances, resulting in the working diagnosis of a manic episode with psychotic features. During the 16 days of his hospital admission, the patient was treated with antipsychotic medications (aripiprazole and haloperidol) and with benzodiazepines (lorazepam), and he achieved a complete remission of all psychotic symptoms. While his psychiatric history was negative, his medical records revealed a recent discharge from the infectious disease ward with a diagnosis of infectious mononucleosis treated with intravenous betamethasone. Thus, at discharge, a diagnosis of steroid-induced psychosis was made. In conclusion, our findings are suggestive of a potential role played by corticosteroids in the development of psychotic symptoms, for which routine screening protocols and therapeutic guidelines are still lacking.

Patricide and overkill: a review of the literature and case report of a murder with Capgras delusion.

Despite being an infrequent crime, parental homicide has been associated with schizophrenia spectrum disorders in adult perpetrators and a history of child abuse and family violence in adolescent perpetrators. Among severe psychiatric disorders there is initial evidence that delusional misidentification might also play a role in parricide. Parricides are often committed with undue violence and may result in overkill. The authors present the case of an adult male affected by schizoaffective disorder and Capgras syndrome who committed patricide. Forensic pathologists classify such cases as overkill by multiple fatal means comprising stabbing, blunt trauma and choking. Accurate crime scene investigations coupled with psychiatric examinations of perpetrator allow reconstruction of the murder stages. This overkill case is discussed in the context of a broad review of the literature.

[Psychosis Associated with Herbal Products: Iatrogenic Delusional Disorder]. / Psicose Associada a Produtos de Ervanária: Perturbação Delirante Orgânica de Carácter Iatrogénico.

Metabolic, toxic or structural brain changes may present as psychotic symptoms. Organic delusional disorders are characterized by the presence of delusional ideas with evidence of brain dysfunction. Iatrogenesis may be a cause of this dysfunction. We present a case of neuropsychiatric symptoms, including delusional disorder, secondary to the use of herbal products. The patient's perception regarding the safety of natural products might result in an omission to report their use during clinical history taking, and thus its use should be actively questioned.

Sintomas psicóticos podem constituir a forma de apresentação de alterações estruturais, metabólicas ou tóxicas. As perturbações delirantes orgânicas são caraterizadas pela presença de ideias delirantes com evidência de disfunção cerebral. A iatrogenia pode ser uma causa desta disfunção. Apresentamos um caso de sintomas neuropsiquiátricos, incluindo perturbação delirante, secundária ao uso de produtos de ervanária. A noção de inocuidade associada a estes produtos origina que o consumo dos mesmos não seja referido espontaneamente pelo doente na recolha da história clínica, pelo que a sua utilização deve ser ativamente questionada.

The effects of Cannabis on hallucinations in Parkinson's disease patients.

Cannabis use is on the rise both as medical treatment and recreational use. There is evidence that cannabis can cause hallucinations and psychosis especially with heavy and prolonged use. Parkinson's disease (PD) carries an increased risk for development of hallucinations and psychosis. It is possible that cannabis may exacerbate this risk and result in earlier and greater amounts of hallucinations and psychosis in this vulnerable population. A literature review was performed to determine the answer to that question. Two articles were found which listed the incidence of hallucinations and delusions during the use of cannabis in PD patients. 21.3% or 10 out of 47 patients reported development of hallucinations while treated with cannabis and 2.8% developed delusions. While these numbers are within the range of prevalence of hallucinations and psychosis in PD, the number of studies and patients evaluated are too small to make any definite conclusions pointing to the need for more research in this area.

Zolpidem stimulant effect: Induced mania case report and systematic review of cases.

INTRODUCTION: Zolpidem is the most widely prescribed hypnotic agent worldwide. This easy-access drug seems to have a high addictive potential among specific populations and is now listed by the World Health Organization (WHO) as being as dangerous as benzodiazepines for dependence and abuse. Many side effects have been reported, but drug-induced mania is still extremely rare. We conducted a systematic review to study the zolpidem-induced stimulation, euphoric or manic effects. METHODS: MEDLINE, PsycINFO, Science Direct, and Google Scholar were searched for articles in English, French, German, Italian and Spanish published up to the 15th October 2018. RESULTS: Eighteen relevant cases were identified, highlighting the need for more reports; therefore, one case that occurred in our department was included. The mean usual dose was 363.31 mg (± 292.2), the minimum dose was 10 mg, the maximum dose was 2000 mg, and the mean intake duration was 35.20 months (±48.0). We found that 89.4% of cases were euphoric and 15.7% had drug-induced mania with delusions. A total of 15.7% of cases took zolpidem for relaxant and stimulant effects, 47% of cases suffered various depression or anxiety disorders, of which 62.5% used zolpidem to cope with depression or an anxiety disorder. A total of 26.3% of cases had concomitant drug dependence or abuse. Seventy-five percent of cases suffering from depression consumed zolpidem for more than 1 year, with significantly more increased daily doses than in non-depressed cases (p < .5). CONCLUSIONS: The latest FDA recommendations for lowering zolpidem doses should be adopted by all countries. Zolpidem prescriptions should be contraindicated for populations with identified risk factors.

Psychotic Decompensation During Nalmefene Treatment in a Patient With Schizoaffective Disorder: A Case Report.

Objective: Nalmefene is a kappa-opioid receptor agonist/antagonist which is currently prescribed to reduce heavy drinking days. Adverse events (AEs) have previously been described in trials, but these trials excluded patients with psychiatric comorbidities. This is important as psychiatric disorders are frequently associated with alcohol use disorders; therefore, the specific AEs in this population should be investigated. Methods: Here, we describe the case of a patient with diagnosed alcohol use disorder and schizoaffective disorder who received treatment with nalmefene. Results: The patient showed decompensation of psychotic symptoms after two doses of medication, consisting of auditory hallucinations, delusions, and ideas of persecution. The symptoms improved two days after treatment discontinuation. Conclusions: This case indicates that the AEs of nalmefene should be specifically investigated in patients with psychiatric disorders.

Combined NMDA Inhibitor Use in a Patient With Multisubstance-induced Psychotic Disorder.

: Novel psychoactive substance use is a major social concern. Their use may elicit or uncover unpredictably as yet undescribed clinical pictures. We aimed to illustrate a multisubstance use case indistinguishable from paranoid schizophrenia, so to alert clinicians on possibly misdiagnosing substance-induced psychotic disorders. CASE REPORT: We describe a case of a 32-year-old man who started at 18 years with cannabinoids and ketamine, and is currently using N-methyl-D-aspartate (NMDA) antagonists. At age 23, he developed social withdrawal after being assaulted by a stranger, but did not consult psychiatrists until age 26; during this period, he was using internet-purchased methoxetamine and ketamine, and was persecutory, irritable, suspicious, and insomniac and discontinued all received medical prescriptions. He added dextromethorphan to his list of used substances. At age 31, while using phencyclidine, and, for the first time, methoxphenidine, he developed a religious delusion, involving God calling him to reach Him, and the near-death experiences ensured by NMDA antagonists backed his purpose. He received Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnosis of multisubstance-induced psychotic disorder and was hospitalized 8 times, 6 of which after visiting the emergency room due to the development of extreme anguish, verbal and physical aggression, and paranoia. He reportedly used methoxphenidine, methoxyphencyclidine, ethylnorketamine, norketamine, and deschlorketamine, to achieve near-death experiences, and eventually to reach God in heavens. CONCLUSIONS: This case points to the need for better control of drugs sold on the internet. It also illustrates that people using NMDA antagonists may present clinical pictures indistinguishable from those of major psychoses and are likely to be misdiagnosed.

Toxicokinetics of the Synthetic Cathinone α-Pyrrolidinohexanophenone.

Synthetic cathinones inhibit monoamine transporters, such as serotonin, norepinephrine, and dopamine transporters, and act on the central nervous system via increasing synaptic concentrations of monoamines. These compounds, which are highly addictive and potentially poisonous, are new psychoactive substances. In this study, we investigated the toxicokinetics of the synthetic cathinone, α-pyrrolidinohexanophenone (α-PHP), and assessed the relationship between the toxicokinetics and the long-term clinical symptoms induced by α-PHP in a male patient. The patient (39 years old) suddenly started uttering inarticulate words and demonstrating incomprehensible behavior in his house, and was brought to the emergency department of Iwate Medical University hospital. He presented with psychotic symptoms, such as hallucinations and delusion; however, his vital signs were normal. The hallucinations and delusion improved by the third day of hospitalization. Toxicological analysis was performed using liquid chromatography-tandem mass spectrometry with QuEChERS extraction. α-PHP was detected in his serum at a concentration of 175 ng/mL on his arrival at the hospital. His serum concentrations of α-PHP were serially determined and their natural logarithms were plotted against time after arrival. Although serum concentrations at early time points were lacking, the obtained curve was consistent with a two-compartment model and indicated a serum elimination half-life of 37 h. The long-lasting psychotic symptoms induced by synthetic cathinones appear to be correlated with their toxicokinetic characteristics, such as their long half-lives. Finally, interpreting the toxicokinetics of synthetic cathinones may provide useful information for the toxicological assessment of new psychoactive substances for forensic and clinical purposes.

Rare presentation of intrathecal morphine withdrawal psychosis.

We report a case of a 57-year-old male patient with intrathecal morphine pump failure who presented with psychosis as part of a clinical presentation of opioid withdrawal. The patient was being treated for chronic back pain with an intrathecal morphine pump for several years. The patient spontaneously started to experience psychotic symptoms which included disorganized thinking, delusional thoughts, paranoia, auditory and visual hallucinations. Upon interrogation of intrathecal pump, it was found not to be functioning, thereby not delivering intrathecal morphine. After opioid rotation with administration of oral oxycodone, the patient's psychosis improved dramatically within a few days, clinically confirming psychosis due to morphine withdrawal. Therefore, it is important for physicians to consider opioid withdrawal in patients experiencing isolated psychosis.

Differences in the symptom profile of methamphetamine-related psychosis and primary psychotic disorders.

We examined the lifetime experience of hallucinations and delusions associated with transient methamphetamine-related psychosis (MAP), persistent MAP and primary psychosis among a cohort of dependent methamphetamine users. Participants were classified as having (a) no current psychotic symptoms, (n=110); (b) psychotic symptoms only when using methamphetamine (transient MAP, n=85); (c) psychotic symptoms both when using methamphetamine and when abstaining from methamphetamine (persistent MAP, n=37), or (d) meeting DSM-IV criteria for lifetime schizophrenia or mania (primary psychosis, n=52). Current psychotic symptoms were classified as a score of 4 or more on any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations or unusual thought content in the past month. Lifetime psychotic diagnoses and symptoms were assessed using the Composite International Diagnostic Interview. Transient MAP was associated with persecutory delusions and tactile hallucinations (compared to the no symptom group). Persistent MAP was additionally associated with delusions of reference, thought interference and complex auditory, visual, olfactory and tactile hallucinations, while primary psychosis was also associated with delusions of thought projection, erotomania and passivity. The presence of non-persecutory delusions and hallucinations across various modalities is a marker for persistent MAP or primary psychosis in people who use methamphetamine.

Methamphetamine: Effects on the brain, gut and immune system.

Methamphetamine (METH) is a powerful central nervous system stimulant which elevates mood, alertness, energy levels and concentration in the short-term. However, chronic use and/or at higher doses METH use often results in psychosis, depression, delusions and violent behavior. METH was formerly used to treat conditions such as obesity and attention deficit hyperactivity disorder, but now is primarily used recreationally. Its addictive nature has led to METH abuse becoming a global problem. At a cellular level, METH exerts a myriad of effects on the central and peripheral nervous systems, immune system and the gastrointestinal system. Here we present how these effects might be linked and their potential contribution to the pathogenesis of neuropsychiatric disorders. In the long term, this pathway could be targeted therapeutically to protect people from the ill effects of METH use. This model of METH use may also provide insight into how gut, nervous and immune systems might break down in other conditions that may also benefit from therapeutic intervention.

Delusional infestation may be caused by recreational drug usage in some patients, but they may not disclose their habit.

BACKGROUND: Patients with delusional infestation (DI) believe that their skin is infested with organisms or inanimate particles, despite objective evidence to the contrary. Previous studies indicate a higher rate of recreational drug use among patients with DI. It is known that symptoms of infestation such as formication can be secondary to use of recreational drugs and alcohol. We carried out a pilot study observing the prevalence of recreational drug use in patients with DI. AIM: To observe the prevalence of recreational drug use in patients with DI. METHODS: A retrospective review of 86 consecutive patient records was carried out over a 3-year period (1 March 2012 to 1 March 2015) to determine current or previous recreational drug use. Additionally, 24 consecutive patients with DI attending clinic between 1 December 2014 and 1 March 2015 were prospectively offered a urine test for recreational drugs. RESULTS: Of the 86 patients, 19 had recreational drug use documented in their medical notes (22.1%). Of the 24 patients offered a urine test, 18 accepted (75%); the remaining 6 patients agreed to provide a urine sample immediately after consultation, but did not do so. Of the 18 samples collected, 6 were positive (33.3% of completed tests) for recreational drugs. Cannabis was the most commonly used drug. CONCLUSIONS: This study indicates that the prevalence of recreational drug use in patients with DI is high, and that patients do not always disclose their habit. It is hoped that this pilot study will lead to further research into this finding.