mdl-100907 and Hallucinations

We discuss features of Parkinson's disease psychosis (PDP) including symptomology and pathophysiology. Treatment options, including non-pharmacologic strategies, dose reduction of offending agents, and the addition of non-dopaminergic antipsychotics, are addressed. The efficacy of second-generation antipsychotics and novel agents is examined.. Pimavanserin, a 5-HT

Topics: Antipsychotic Agents; Delusions; Hallucinations; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Serotonin 5-HT2 Receptor Antagonists; Urea

Sleep paralysis is a state of involuntary immobility occurring at sleep onset or offset, often accompanied by uncanny "ghost-like" hallucinations and extreme fear reactions. I provide here a neuropharmacological account for these hallucinatory experiences by evoking the role of the serotonin 2A receptor (5-HT

Topics: Animals; Dopamine; Hallucinations; Hallucinogens; Humans; Lysergic Acid Diethylamide; Neuropharmacology; Piperidines; Psilocybin; Receptor, Serotonin, 5-HT2A; Serotonin; Serotonin 5-HT2 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Sleep; Sleep Paralysis; Urea

Hallucinations are complex misperceptions, that principally occur in schizophrenia or after intoxication induced by three main classes of drugs: psychostimulants, psychedelics, and dissociative anesthetics. There are at least three different pharmacological ways to induce hallucinations: (1) activation of dopamine D2 receptors (D2Rs) with psychostimulants, (2) activation of serotonin 5HT2A receptors (HT2ARs) with psychedelics, and (3) blockage of glutamate NMDA receptors (NMDARs) with dissociative anesthetics. In schizophrenia, the relative importance of NMDAR and D2R in the occurrence of hallucinations is still debated. Slight clinical differences are observed for each etiology. Thus, we investigated whether the concept of hallucination is homogenous, both clinically and neurobiologically. A narrative review of the literature is proposed to synthesize how the main contributors in the field have approached and tried to solve these outstanding questions. While some authors prefer one explanatory mechanism, others have proposed more integrated theories based on the different pharmacological psychosis models. In this review, such theories are discussed and faced with the clinical data. In addition, the nosological aspects of hallucinations and psychosis are addressed. We suggest that if there may be common neurobiological pathways between the different pharmacological systems that are responsible for the hallucinations, there may also be unique properties of each system, which explains the clinical differences observed.

Topics: Hallucinations; Hallucinogens; Humans; Psychotropic Drugs; Receptors, Dopamine D2; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Serotonin 5-HT2 Receptor Antagonists

Clozapine was the widely accepted gold standard treatment for treatment resistant psychotic symptoms. Clozapine has efficacy of about 50% and some responding patients have to discontinue it due to serious adverse effects. The search for novel agents to use for clozapine-non-responders continues. One such possible agent is the non-dopaminergic antipsychotic pimavanserin, an inverse agonist of serotonin 5-HT2A receptors which was recently approved for the hallucinations and delusions of Parkinson's Disease Psychosis. We report here the successful results of using pimavanserin in patients with refractory hallucinations and delusions who failed to respond to clozapine. We also report similar results in refractory psychosis patients who did not receive clozapine.. We present ten cases of patients with schizophrenia and schizoaffective disorder with refractory hallucinations and delusions who received a trial of pimavanserin when clozapine or multiple antipsychotics failed. Six of ten patients had not responded to a clozapine trial. The subjects' ages ranged between 21 and 77 years and were followed up for several months.. All 10 patients with refractory hallucinations and delusions showed marked response to pimavanserin 34 mg/day within 4-8 weeks, with continuation of the response for several months of follow-up. Improvements in negative symptoms and social functioning were also observed in several patients.. This series of 10 cases of patients with refractory psychosis who responded to pimavanserin is an important new finding that has never been reported before. Controlled studies comparing clozapine and pimavanserin in refractory schizophrenia are warranted to confirm these clinical observations.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Delusions; Drug Resistance; Female; Hallucinations; Humans; Male; Middle Aged; Piperidines; Psychotic Disorders; Retrospective Studies; Schizophrenia; Serotonin 5-HT2 Receptor Antagonists; Urea; Young Adult

To document the effects of combining loxapine with aripiprazole for refractory hallucinations in 2 patients with chronic schizophrenia.. Two patients with schizophrenia and auditory hallucinations that were unresponsive to what was considered adequate treatment with multiple typical and atypical antipsychotic medications given over several years were prescribed a combination of aripiprazole 20-30 mg and high-dose loxapine (100-300 mg/day). Both patients had refused clozapine and depot antipsychotics. Aripiprazole/loxapine therapy resolved hallucinations in both patients, and discontinuation of either medication resulted in a return of persecutory voices. Breakthrough hallucinations in both individuals responded to increasing the loxapine dosage. Adverse effects included hypersalivation and tremor, which were treated with benztropine and propranolol. The patients also reported mild sedation, which resolved after several weeks of treatment. Both patients continued to do well during 2 years after starting this combination of medications.. Recent research has indicated serotonergic and dopaminergic abnormalities in the superior temporal gyrus of patients with a history of chronic auditory hallucinations. Both loxapine and aripiprazole have effects on dopaminergic and postsynaptic serotonergic (5-HT₂A) receptor systems, which could account for synergistic effects in treating refractory hallucinations. The combination appears safe, even when loxapine is given in high dosages. Patients should be monitored for the development of parkinsonian tremors.. The combination of aripiprazole and high-dose loxapine should be considered in patients with schizophrenia who develop treatment-refractory hallucinations, particularly those who are unwilling to accept treatment with either depot antipsychotics or clozapine.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dose-Response Relationship, Drug; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Hallucinations; Humans; Loxapine; Male; Middle Aged; Piperazines; Quinolones; Schizophrenia; Serotonin 5-HT2 Receptor Antagonists; Treatment Outcome

The superior temporal gyrus (STG) is strongly implicated in the pathophysiology of schizophrenia, particularly with regards to auditory hallucinations. In this study, using in situ quantitative autoradiography in postmortem tissue, we investigated the binding of the [3H]ketanserin to 5-HT(2A) receptors and [3H]mesulergine to 5-HT(2C) receptors in the left STG of 8 male schizophrenic patients compared to 8 control subjects. A strong [3H]ketanserin binding was observed in the STG, however there was a very weak [3H]mesulergine binding in the STG. A significant decrease in binding of [(3)H]ketanserin was clearly observed in schizophrenia patients in comparison with control subjects. There were no significant correlations between 5-HT(2A) binding density and age, postmortem intervals, or brain pH. These results suggest that the alterations of the 5-HT(2A) receptors contribute to the pathophysiology of the STG in schizophrenia. Furthermore, there is a clear tendency for a positive correlation between 5-HT(2A) and muscarinic M1 receptor bindings, and for negative correlations between 5-HT(2A) and GABA(A) receptor bindings and between muscarinic M1 and GABA(A) receptor bindings. This provides a possible mechanism of auditory hallucinations through interactions between 5-HT(2A), acetylcholine muscarinic and GABA transmissions in the STG in schizophrenia.

Topics: Adolescent; Adult; Aged; Hallucinations; Humans; Male; Middle Aged; Protein Binding; Receptor, Serotonin, 5-HT2A; Schizophrenia; Serotonin 5-HT2 Receptor Antagonists; Temporal Lobe