Pimavanserin: First Global Approval.

Pimavanserin (Nuplazid™) is a selective and potent serotonin 2A (5-HT2A) receptor inverse agonist and antagonist developed by ACADIA Pharmaceuticals that has been approved in the US as a treatment for patients with hallucinations and delusions associated with Parkinson's disease psychosis. Up to 60 % of patients with Parkinson's disease may develop Parkinson's disease psychosis, which is associated with increased morbidity and mortality and has few treatment options. This article summarizes the milestones in the development of pimavanserin leading to this first approval for the treatment of hallucinations and delusions in patients with Parkinson's disease psychosis.

Improvement in delusions and hallucinations in patients with dementia with Lewy bodies upon administration of yokukansan, a traditional Japanese medicine.

BACKGROUND: This multicentre open-label trial examined the efficacy and safety of the traditional Japanese medicine, or Kampo medicine, yokukansan (YKS), for behavioural and psychological symptoms of dementia (BPSD) in patients with dementia with Lewy bodies. METHODS: Sixty-three dementia with Lewy bodies patients with probable BPSD (M:W, 30:33; mean age, 78.2±5.8 years) were enrolled and treated with YKS for 4 weeks. RESULTS: Significant improvements in Neuropsychiatric Inventory scores (mean decrease, 12.5 points; P<0.001) and Zarit Burden Interview-Japanese edition tests (mean decrease, 3.6 points; P=0.024) were observed. In patients who consented to an assessment after 2 weeks of treatment, a time-dependent significant improvement was observed in the Neuropsychiatric Inventory score (n=23; mean decrease, 14.4; P<0.001), each subscale, including delusions and hallucinations, the Zarit Burden Interview-Japanese edition (n=22; mean decrease, 8.2; P<0.01) and the behavioural pathology in Alzheimer's disease insomnia subscale. The Mini-Mental State Examination and the Disability Assessment for Dementia (DAD) showed no significant change. Adverse events were observed in 11 (18%) patients. Three patients (5%) discontinued YKS due to adverse reactions, namely, spasticity and exacerbation of BPSD, edema, and nausea. Hypokalaemia (<3.5 mEq/L) was present in four patients (6%) at the study endpoint. Worsening of extrapyramidal symptoms was not observed. CONCLUSION: YKS improved BPSD in dementia with Lewy bodies patients and caregiver burden scores without deterioration in cognitive function. YKS is useful for the treatment of delusions and hallucinations in BPSD.

Schizophrenia-like psychotic episode precipitated by cobalamin deficiency.

Although cobalamin deficiency is widely known and usually presents with hematologic and neuropsychiatric manifestations, the psychiatric symptoms are not usually the predominant manifestation. We describe a young single male vegetarian who developed a cobalamin-induced psychotic episode without preceding neurologic manifestations and without any hematologic symptoms. He recovered after a short course of antipsychotics and oral cobalamin supplementation and remained asymptomatic and functionally independent at 1 year of follow-up.

Different responses to rivastigmine in subcortical vascular dementia and multi-infarct dementia.

Vascular dementia (VaD) is associated with a large amount of heterogeneity, as it groups together a broad category of patients in whom various manifestations of cognitive decline are attributed to cerebrovascular or cardiovascular disease. Thus, a study was designed to determine the effects of rivastigmine on cognitive function, global daily living performance, and behavioral disorders in VaD patients versus an active control (nimodipine), stratifying patients according to the type of VaD, subcortical vascular dementia (sVAD), and multi-infarct dementia (MID). The trial was a prospective study. This study shows that long-term treatment with rivastigmine, at dosages approved for therapeutic use in Alzheimer's disease, produces significant improvement in all behavioral symptoms in 2 forms of VaD, MID and sVaD, except delusions. It also suggests that rivastigmine may enable a reduction in concomitant neuroleptics and benzodiazepines in VaD, especially in MID. The results are discussed with an overview of the literature.

[Therapeutic drug monitoring: A pharmacotherapeutic tool in psychiatry]. / Arzneimittelspiegel als pharmakotherapeutisches Werkzeug bei der Behandlung mit Psychopharmaka.

Therapeutic drug monitoring (TDM) is used increasingly for managing psychiatric outpatients, where the preanalytic error risk is high. Blood samples must be collected under steady-state conditions immediately before ingestion of the morning dose or before the next injection. In order to interpret the plasma levels accurately, age, gender, ethnicity, compliance, drug dosage, renal and hepatic function and comedication incl. smoking habits and diet (esp. caffeine intake and consumption of grapefruit juice) have to be taken into account. If in doubt, aberrant plasma levels should be confirmed by a second control under optimized conditions. Pharmacogenetic testing enables the identification of abnormal metabolizers. TDM and pharmacogenetic tests are useful tools to improve pharmacotherapy by preventing dose-dependent adverse drug events, optimizing dosage during long-term treatment and identifying ultrarapid metabolizers and malcompliance.

Occurrence of delusions during repetitive transcranial magnetic stimulation (rTMS) in major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been suggested as a potentially useful treatment for major depression. Nonpsychotic depressed patients appear to have a better outcome than those with psychotic symptoms. METHODS: We report findings in a patient suffering from recurrent, nonpsychotic major depression (DSM-IV) who had 13 daily sessions of rTMS monotherapy within a 3 week period. RESULTS: During rTMS treatment, the patient developed recurrent severe delusions, which he had never experienced before. Psychotic symptoms remitted quickly with neuroleptic medication. CONCLUSIONS: In light of preclinical findings showing increased dopaminergic activity after rTMS treatment, occurrence of psychotic symptoms should be considered a potential side effect of rTMS treatment.

[Confusion and delusions occurring during interferon-alpha treatment]. / Syndrome confuso-délirant sous IFN alpha.

A number of side effects occurring during IFN therapy have been described. Psychiatric side effects include cognitive, behavioural and affective changes, confusion and, less commonly, psychotic symptoms. We report the case of a 52-year-old patient who had been treated for almost three years with IFN alpha for a chronic myelogenous leukemia and who presented an acute confusional episode with delusions, following the reintroduction of IFN alpha after a therapy suspension of 2 weeks. Clinical improvement occurred quite rapidly after cessation of the IFN treatment; this evolution and the normality of the biological tests, EEG and cerebral imagery suggest a causal relationship between this treatment and the psychiatric symptoms.

Exorcism-resistant ghost possession treated with clopenthixol.

BACKGROUND: An Indian man now in Britain explained his criminal behaviour as episodic ghost possession. Traditional exorcisms failed to help. METHOD: A 'Western' diagnosis of dissociative state or paranoid schizophrenia was made. Treatment commenced using trifluoperazine and clopenthixol. RESULTS: The patient underwent remission during neuroleptic treatment, despite previous evidence of genuine possession. CONCLUSIONS: Many cultures give rise to apparently genuine cases of ghost possession. Neuroleptics may relieve symptoms of exorcism-resistant possession.