Practical guidance for dosing and switching paliperidone palmitate treatment in patients with schizophrenia.

OBJECTIVE: This article overviews the recommended dosing strategies for the treatment of schizophrenia patients using the recently FDA-approved once-monthly long-acting injectable atypical antipsychotic, paliperidone palmitate. METHODS: Using pharmacokinetic (PK), efficacy and safety data from clinical trials and a comprehensive population PK simulation model, dosing recommendations for paliperidone palmitate have been generated. RESULTS: The recommended initiation regimen is 150 mg eq. paliperidone palmitate (234 mg) on Day 1 followed by 100 mg eq. paliperidone palmitate (156 mg) on Day 8, each administered into the deltoid muscle, using a 1-inch 23 gauge (G) needle in those <90 kg and a 1.5-inch 22 G needle in those > or =90 kg. No oral supplementation is required. Monthly maintenance doses of paliperidone palmitate range from 25-150 mg eq. (39-234 mg; recommended dose of 75 mg eq. [117 mg]) injected into the deltoid (using weight-adjusted needle) or gluteal (using 1.5 inch 22 G needle) muscle. The Day 8 dose may be administered +/-2 days and monthly doses +/-7 days, without a clinically significant impact on plasma concentrations. In patients with mild renal impairment (creatinine clearance [CrCL]: 50-80 mL/min), dosage should be adjusted. No dose adjustment is required in patients with mild or moderate hepatic impairment; no data currently exist regarding severe hepatic impairment. Elderly patients with normal renal function should receive the same dosage as younger adult patients with normal renal function. In the event of an age-related decline in CrCL, dosage should be adjusted accordingly. Paliperidone palmitate treatment can be initiated the day after discontinuing previous oral antipsychotic treatment. Paliperidone palmitate should be initiated at the next scheduled injection, and monthly thereafter, in patients switching from other long-acting injectable antipsychotics, including long-acting risperidone. CONCLUSIONS: These data provide practical guidance to clinicians on how to use paliperidone palmitate in adult patients with schizophrenia.

Genetic association studies of schizophrenia using the 8p21-22 genes: prepronociceptin (PNOC), neuronal nicotinic cholinergic receptor alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1).

Schizophrenia is a common, genetically heterogeneous disorder with a lifetime prevalence of approximately 1% in the general population. Linkage studies of affected families have now strongly implicated a susceptibility locus on chromosome 8p21-22. Tests of allelic association with markers on 8p21-22 should be able to localise any quantitative trait nucleotides (QTN's) or susceptibility mutations to within a few hundred kilobases. Three brain expressed candidate susceptibility genes, prepronociceptin (PNOC), neuronal cholinergic receptor, nicotinic, alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1) have been mapped to chromosome 8p21-22. A case-control, allelic association study was performed using a novel highly polymorphic dinucleotide repeat, D8S2611 near the PNOC gene, two previously characterised dinucleotide repeats, D8S131 and D8S131P at the CHRNA2 locus and an RFLP at the 3'UTR of the arylamine N-acetyltransferase 1 (NAT1) gene. No differences were found in allele frequencies between the patient and control groups. DNA variations or mutations at or near the three genes under study are unlikely to increase susceptibility to schizophrenia in our population sample.

An analysis of reported deaths following electroconvulsive therapy in Texas, 1993-1998.

Since 1993, Texas law has required that all deaths that occur within 14 days of electroconvulsive therapy (ECT) be reported to the Texas Department of Mental Health and Mental Retardation. This study attempted to differentiate deaths that may have been due to ECT or the associated anesthesia from those due to other causes. Among more than 8,000 patients who received 49,048 ECT treatments between 1993 and 1998, a total of 30 deaths were reported to the mental health department between 1993 and 1998. Only one death, which occurred on the same day as the ECT, could be specifically linked to the associated anesthesia. An additional four deaths could plausibly have been associated with the anesthesia, for which the calculated mortality rate is between two and ten per 100,000, but probably not with the stimulus of the ECT or seizure. The mortality rate associated with ECT (less than two per 100,000 treatments) in Texas is extremely low.

Treatment of major depression complicated by bilateral foot drop and double incontinence with ECT.

This report describes a 56-year-old man with severe depression who developed bilateral foot drop, dual incontinence, and swallowing difficulties, which required several physical investigations and consultations before an excellent response to electroconvulsive therapy occurred with reversal of all symptoms.

A survey of psychiatrists' attitudes toward electroconvulsive therapy.

Sixty-seven psychiatrists who were employed in state hospitals in Texas were surveyed about their attitudes toward use of electroconvulsive therapy (ECT) and the laws and regulations associated with its use. The majority of respondents agreed with accepted professional guidelines on ECT usage and had a positive attitude toward ECT treatment. However, the number of referrals for ECT by these psychiatrists was low, perhaps due to the view that Texas laws and policies about ECT are restrictive and limiting to patient care. The majority of respondents indicated that more professional education about laws and policies related to ECT is needed.

Treatment of an unusual case of masochism.

Masochistic sexual activity is potentially dangerous, rarely reported voluntarily, and hard to treat. This article describes a masochist patient who received sexual gratification from being burnt or crushed. Antiandrogen medication, serotonin uptake inhibitor, and psychodynamic psychotherapy along with sexual education and social-skills training and aversive behavior therapy were all tried over a period of 9 months. The response was measured by effects of treatments on the frequency of erotic fantasies and masturbation. Antiandrogens and aversive behavior therapies may be the most effective treatments for such cases, at least in the short term, although the underlying social deficits and the need to reshape the sexual behavior ought to be addressed in the long term.

Autoenucleation--a culture-specific phenomenon: a case series and review.

Cases of autoenucleation may provide a good example of the pathoplastic effects of culture. To further characterize this phenomenon, the author reviewed the medical literature and conducted a retrospective search of the local psychiatric hospital records. Medline search did not show a single case of autoenucleation in the non-European Christian culture. Descriptive accounts of the identified seven patients show they were all psychotic at the time of the act, and five had a history of prior drug abuse. Most were religiously preoccupied before the act and displayed prominent affective symptoms, and they all interpreted the Biblical text literally. The association of sight and the concept of sin is discussed in a wider cultural context, and it is proposed that autoenucleation may be unique to the Christian West.

Prolactogenic effects of risperidone in male patients--a preliminary study.

This preliminary study describes a case of a male patient who developed gynaecomastia and sexual difficulties whilst taking risperidone for chronic paranoid schizophrenia. Laboratory tests showed raised prolactin levels and depressed testosterone levels which were reversed on cessation of medication. A small study was subsequently conducted on male psychotic patients to compare the prolactogenic effects of risperidone (n=14) with traditional antipsychotic medication (n=15). The results showed a greater but non-significant prolactogenic effect of risperidone.

Monozygotic twins, folie à deux and heritability: a case report and critical review.

A case report of shared delusional disorder, with a primary diagnosis of delusional disorder, is described in identical twins of proven zygosity. A review of literature shows that the primary diagnosis in identical twin pairs, suffering from folie à deux, is delusional disorder. This is in contrast to the reported excess of schizophrenia, as a primary diagnosis, in non-twin cases of folie à deux. Moreover, schizophrenia is poorly related to delusional disorders on the basis of demographic and familial studies. In the light of this paradox, nosological status of this disorder and the sociogenic and genetic factors are critically discussed.

Delusional disorder in a boy with phenylketonuria and amine metabolites in the cerebrospinal fluid after treatment with neuroleptics.

A case report of a 16-year-old boy with the classical form of phenylketonuria (PKU) and suffering from a delusional disorder is presented. He did not respond to a traditional antipsychotic medication but improved on an atypical antipsychotic, risperidone. The cerebrospinal fluid metabolites of the biogenic amines were measured and are also reported in the context of a recent interest in the ratios of these amine metabolites in schizophrenia. It is proposed that such dually diagnosed patients with PKU may provide a model in which to test the prevalent biogenic amine theories in psychiatric disorders.

Delusional pregnancy with polydipsia: a case report.

We report a case of delusional pregnancy with polydipsia in a female patient with paranoid schizophrenia. The contribution of psychological and physiological factors in the development of the delusion of pregnancy and polydipsia and the possible interactions between the two phenomena are discussed.