Ingrid Castberg

Does Level of Care, Sex, Age, or Choice of Drug Influence Adherence to Treatment With Antipsychotics?

Abstract Rates of nonadherence during treatment with antipsychotics have been found to vary in a wide range from 20% to 90%. The aim of the present study was to investigate the influence of inpatient versus outpatient status on the adherence to treatment with olanzapine and clozapine. In the period from 1999 to 2007, olanzapine and clozapine were the 2 most frequently analyzed antipsychotics at the Department of Clinical Pharmacology at St. Olavs University Hospital, Trondheim, Norway, with more than 24,000 and more than 18,000 samples, respectively. In total, 111 patients on olanzapine and 95 patients on clozapine had provided samples in both the inpatient and outpatient settings and were included in the study. The primary outcome variable was the serum concentration-to-dose ratio (C/D ratio), that is, the serum drug concentration per milligram of drug given. For olanzapine, the C/D ratio in the outpatient setting was 10.7% lower than in the inpatient setting (P = 0.013). No such difference was found for clozapine. The difference in the olanzapine group was exclusively attributed to a lower outpatient ratio in females. For clozapine, no sex influence was found. No effect of age on the C/D ratios was found either for olanzapine or for clozapine. The lower C/D ratio in females using olanzapine in the outpatient setting might imply that they, in contrast to males, are less adherent to their medication when outside hospital. For clozapine, there were no indications of differences in adherence between inpatients and outpatients.

Characterisation of zuclopenthixol metabolism by in vitro and therapeutic drug monitoring studies

Davies SJC, Westin AA, Castberg I, Lewis G, Lennard MS, Taylor S, Spigset O. Characterisation of zuclopenthixol metabolism by in vitro and therapeutic drug monitoring studies.

Prescribing patterns and the use of therapeutic drug monitoring of psychotropic medication in a psychiatric high-security unit.

The aim of this study was to investigate the use of psychotropic medication and therapeutic drug monitoring in a high-security psychiatric unit and to compare the doses and serum concentrations both with the recommended intervals and with the doses and serum concentrations in a control group. One hundred thirty-two patients were admitted in the period from January 2000 to December 2005. All available samples were used when comparing serum concentrations and doses with the recommended ranges. For the comparison of doses and serum concentration-to-dose (C:D) ratios with the control group only 1 sample from each patient was used. A total of 459 analyses of 27 different drugs in samples from 8 women and 73 men were included. The median number of therapeutic drug monitoring analyses per patient was 4 (range 1-29). Thirty-seven of the 81 patients (46%) used 2 or more antipsychotics at the same time. Clozapine, lamotrigine, olanzapine, quetiapine, ziprasidone, and zuclopenthixol were often given in doses above the recommended. The serum levels were frequently above those recommended for clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zuclopenthixol. The serum levels were significantly higher in the study group than in the control group for clozapine, lamotrigine, quetiapine, and zuclopenthixol. The given dose was significantly higher in the study group than in the control group for clozapine, lamotrigine and zuclopenthixol. The C:D ratio was significantly lower in the study group than in the control group for olanzapine but higher for quetiapine. The non-evidence based practice of high-dose polypharmacy with several antipsychotics is widely used in this unit. The use of higher doses in the study group than in the control group was not due to differences in metabolism or adherence to treatment between the 2 groups. The frequent use of therapeutic drug monitoring did not seem to have a great impact on the prescribed doses.

Adverse drug reactions of antidepressants and antipsychotics: Experience, knowledge and attitudes among Norwegian psychiatrists

Efficient prevention of adverse drug reactions (ADRs) requires knowledge about their severity and pharmacological mechanisms and is dependent on reliable data on their frequencies and possible risk factors. The study was conducted to investigate the prescribers’ experience and understanding of the ADRs of psychotropic drugs, and their attitude towards reporting these. In a questionnaire, physicians treating adult psychiatric patients were asked which ADRs that they regarded bothersome for some of the most widely used antidepressants and antipsychotics. Questions about the relationship between blockade of drug receptors and ADRs, and about the physicians’ personal experience of and attitudes towards reporting of ADRs were also included. In total, 70 of 91 questionnaires (78%) were returned. The mean number of ADRs regarded bothersome ranged from 2.4 to 9.3 for the various drugs/drug classes. Qualified psychiatrists stated a significantly higher number of bothersome ADRs than did the residents. The percentage of physicians associating blockade of a receptor with a specific ADR varied from 76% (histamine receptor blockade and sedation) to 37% (α1-adrenergic blockade and tachycardia). Thirty-nine per cent of the physicians had never reported an ADR to the Norwegian Medicines Agency. The number of ADRs considered bothersome was relatively high. The pattern of these ADRs generally mirrored the typical ADR profiles of the drugs. The knowledge of the underlying mechanisms of ADRs was more or less incomplete. The reporting rate of ADRs to the national regulatory authorities was low.

Treatment With Antipsychotics in Pregnancy: Changes in Drug Disposition

Although pregnancy is known to cause changes in drug pharmacokinetics, little is known about its impact on serum levels of antipsychotics. In this study we retrospectively assessed 201 routine serum antipsychotic therapeutic drug monitoring concentration measurements obtained from a total of 110 pregnancies in 103 women, and 512 measurements from the same women before and after pregnancy. Serum concentrations in the third trimester were significantly lower than baseline for quetiapine (−76%; confidence interval (CI), −83%, −66%; P < 0.001) and aripiprazole (−52%; CI, −62%, −39%; P < 0.001), but not for olanzapine (−9%; CI, −28%, +14%; P = 0.40). For the remaining antipsychotics (perphenazine, haloperidol, ziprasidone, risperidone, and clozapine), our dataset was limited, but it indicates that concentrations may decline at least for perphenazine and possibly also for haloperidol. Even though the clinical consequence of the serum concentrations decline remains to be elucidated, our results warrant close clinical monitoring throughout pregnancy, preferentially supported by therapeutic drug monitoring.

Effects of age and gender on the serum levels of clozapine, olanzapine, risperidone, and quetiapine

To investigate serum concentrations of second‐generation antipsychotics in relation to age and gender in a population ranging from 18 to 100 years.

[Irreversible, non-selective monoamine oxidase inhibitors].

Irreversible, non-selective monoamine oxidase (MAO) inhibitors were among the first antidepressants. No drugs in this group are currently marketed in Norway, but many physicians will see patients using them, as they can be prescribed on a named patient basis after application to the Norwegian Medicines Agency. This article presents adverse effects, interactions and precautions related to the use of these drugs.