benztropine and Psychomotor-Agitation

Blockade of dopamine D2 receptors remains a common feature of all antipsychotics. It has been hypothesized that the extrastriatal (cortical, thalamic) dopamine D2 receptors may be more critical to antipsychotic response than the striatal dopamine D2 receptors. This is the first double-blind controlled study to examine the relationship between striatal and extrastriatal D2 occupancy and clinical effects. Fourteen patients with recent onset psychosis were assigned to low or high doses of risperidone (1 mg vs 4 mg/day) or olanzapine (2.5 mg vs 15 mg/day) in order to achieve a broad range of D2 occupancy levels across subjects. Clinical response, side effects, striatal ([11C]-raclopride-positron emission tomography (PET)), and extrastriatal ([11C]-FLB 457-PET) D2 receptors were evaluated after treatment. The measured D2 occupancies ranged from 50 to 92% in striatal and 4 to 95% in the different extrastriatal (frontal, temporal, thalamic) regions. Striatal and extrastriatal occupancies were correlated with dose, drug plasma levels, and with each other. Striatal D2 occupancy predicted response in positive psychotic symptoms (r=0.62, p=0.01), but not for negative symptoms (r=0.2, p=0.5). Extrastriatal D2 occupancy did not predict response in positive or negative symptoms. The two subjects who experienced motor side effects had the highest striatal occupancies in the cohort. Striatal D2 blockade predicted antipsychotic response better than frontal, temporal, and thalamic occupancy. These results, when combined with the preclinical data implicating the mesolimbic striatum in antipsychotic response, suggest that dopamine D2 blockade within specific regions of the striatum may be most critical for ameliorating psychosis in schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Benztropine; Dopamine Antagonists; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Muscarinic Antagonists; Neostriatum; Positron-Emission Tomography; Prolactin; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Pyrrolidines; Raclopride; Receptors, Dopamine D2; Salicylamides; Schizophrenia; Schizophrenic Psychology

A patient with tardive neuroleptic-induced akathisia was investigated with multiple pharmacological challenges. It was noted that the patient responded positively to benztropine, bromocriptine, and propranolol, and negatively to physostigmine, and showed little or no response to discontinuation of neuroleptics and challenges with metoclopramide, metoprolol, atenolol, and clonidine. The implications of this pharmacological characterization for the understanding of the pathophysiology of tardive akathisia in relation to acute akathisia and tardive dyskinesia are discussed.

Topics: Administration, Oral; Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Arousal; Atenolol; Benztropine; Brain; Bromocriptine; Chronic Disease; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Humans; Infusions, Intravenous; Male; Metoclopramide; Metoprolol; Physostigmine; Propranolol; Psychomotor Agitation; Schizophrenia, Paranoid

Twelve DSM-IIIR diagnosed schizophrenics, with neuroleptic-induced akathisia (NIA), were treated with either propranolol or matched placebo for two days, followed by a treatment crossover phase for five more days. Raters and patients were "blind" to treatment. This study shows that 120 mg of propranolol a day is more effective than placebo in reducing akathisia, and that propranolol's antiakathisic effect may require several days of treatment.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Benztropine; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Neurologic Examination; Propranolol; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology

Akathisia tends to develop as an early complication of antipsychotic treatment in a dose-dependent manner. Although withdrawal akathisia has been reported after the discontinuation or dose reduction of typical antipsychotic drugs, akathisia following atypical antipsychotic drug withdrawal remains a rare phenomenon.. A 24-year-old woman with an acute psychotic episode was admitted and initially treated with aripiprazole. The aripiprazole dose was titrated up to 30 mg/day over 9 days and maintained for the next 3 days; however, her psychotic symptoms persisted without change. She was switched to amisulpride, with the dose increased over 2 weeks to 1000 mg/day. Subsequently, although the patient's psychotic episode subsided, her serum prolactin levels increased markedly. After discharge, the amisulpride dose was increased to 1200 mg/day owing to auditory hallucinations and was maintained with quetiapine (100-200 mg/day) and benztropine (1 mg/day) for 13 weeks. Given the potential for hyperprolactinemia as a side effect, the amisulpride dose was reduced to 800 mg/day concurrently with the discontinuation of benztropine; however, these changes resulted in severe restlessness without other extrapyramidal symptoms. The withdrawal akathisia disappeared over 2 weeks after switching to aripiprazole (10 mg/day) with propranolol (40 mg/day) and the patient's prolactin levels had normalized after 6 months of aripiprazole monotherapy.. The present case highlights the potential for the development of withdrawal akathisia when the dose of amisulpride is tapered abruptly. Thus, a slow tapering and careful monitoring are recommended when switching from amisulpride to other antipsychotic drugs. Furthermore, this case suggests that changing the regimen to aripiprazole with propranolol may be a potential option for amisulpride withdrawal akathisia superimposed on pre-existing hyperprolactinemia.

Topics: Adult; Amisulpride; Antipsychotic Agents; Aripiprazole; Benztropine; Female; Humans; Hyperprolactinemia; Prolactin; Propranolol; Psychomotor Agitation; Psychotic Disorders; Young Adult

Diphenylpyraline hydrochloride (DPP) is an internationally available antihistamine that produces therapeutic antiallergic effects by binding to histamine H₁ receptors. The complete neuropharmacological and behavioral profile of DPP, however, remains uncharacterized. Here we describe studies that suggest DPP may fit the profile of a potential agonist replacement medication for cocaine addiction. Aside from producing the desired histamine reducing effects, many antihistamines can also elicit psychomotor activation and reward, both of which are associated with increased dopamine concentrations in the nucleus accumbens (NAc). The primary aim of this study was to investigate the potential ability of DPP to inhibit the dopamine transporter, thereby leading to elevated dopamine concentrations in the NAc in a manner similar to cocaine and other psychostimulants. The psychomotor activating and rewarding effects of DPP were also investigated. For comparative purposes cocaine, a known dopamine transporter inhibitor, psychostimulant and drug of abuse, was used as a positive control. As predicted, both cocaine (15 mg/kg) and an equimolar dose of DPP (14 mg/kg) significantly inhibited dopamine uptake in the NAc in vivo and produced locomotor activation, although the time-course of pharmacological effects of the two drugs was different. In comparison to cocaine, DPP showed a prolonged effect on dopamine uptake and locomotion. Furthermore, cocaine, but not DPP, produced significant conditioned place preference, a measure of drug reward. The finding that DPP functions as a potent dopamine uptake inhibitor without producing significant rewarding effects suggests that DPP merits further study as a potential candidate as an agonist pharmacotherapy for cocaine addiction.

Topics: Animals; Behavior, Animal; Benztropine; Central Nervous System Stimulants; Cocaine; Cocaine-Related Disorders; Dopamine Uptake Inhibitors; Exploratory Behavior; Histamine H1 Antagonists; Illicit Drugs; Kinetics; Male; Mice; Mice, Inbred C57BL; Motor Activity; Nucleus Accumbens; Piperidines; Psychomotor Agitation; Reward; Spatial Behavior

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benztropine; Humans; Male; Middle Aged; Parasympatholytics; Pilot Projects; Psychomotor Agitation; Schizophrenia; Tryptophan

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Benztropine; Humans; Propranolol; Psychomotor Agitation; Tropanes

Three cases of akathisia are described in which the manifestations of motor restlessness were subtle enough to be easily missed, but in which the resultant propensities to behavioral "action" nonetheless contributed to significant difficulties for the patients. Appropriate medication adjustments, including adequate treatment with antiparkinsonian agents or suitable lowering of neuroleptic dosage, were beneficial. Subtle manifestations of akathisia of this sort may occur more frequently than is commonly recognized.

Topics: Acting Out; Adolescent; Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benztropine; Female; Humans; Male; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Akathisia, Drug-Induced; Amoxapine; Benztropine; Depressive Disorder; Dibenzoxazepines; Dyskinesia, Drug-Induced; Humans; Male; Psychomotor Agitation

Topics: Adolescent; Akathisia, Drug-Induced; Benztropine; Diagnosis, Differential; Dyskinesia, Drug-Induced; Humans; Intellectual Disability; Male; Psychomotor Agitation; Tropanes

Topics: Adult; Aggression; Akathisia, Drug-Induced; Benztropine; Humans; Intellectual Disability; Male; Psychomotor Agitation; Thioridazine