CYP2D6 gene test in psychiatric patients and healthy volunteers.

BACKGROUND: Antipsychotic drug therapy meets difficulties in predicting response in psychiatric patients. The medical treatment of these patients may be improved significantly by systematic phamacogenetic diagnosis identifying the drug metabolic capacities of each patient. Genetic polymorphisms in the coding sequence for the drug metabolizing cytochrome P450 enzyme CYP2D6 represent a pharmacogenetic target. METHODS: A cohort (n = 225) representing psychiatric patients seen during an 18-month trial period was included in the project after the subjects accepted a blood sample being taken to analyse their CYP2D6 allelic composition. To investigate any putative difference in allele frequencies among the psychiatric patients compared to earlier publications on allele frequencies in Caucasian populations, another cohort (n = 122) of local healthy volunteers was likewise included. RESULTS: Allelic frequencies in the psychiatric patients and healthy volunteers were indistinguishable. Alleles *1 and *2 encoding for normal enzyme activity and alleles *3, *4, *5, *6, *13/*16 representing non-active forms were found as well as alleles *9, *10, *41 encoding for enzymes with decreased activity. Furthermore, examples of the previously described duplications of *1 and *2, which result in enhanced enzyme activity, were also identified. CONCLUSION: A systematic CYP2D6 gene test of hospitalized psychiatric patients revealed the identification of pharmacogenetically relevant alleles affecting capacity to metabolize antipsychotics. The frequencies of phenotypes in affected patients were 8.4 % intermediate metabolizers (IMs), 8.4 % poor metabolizers (PMs) and 3.1 % ultrafast metabolizers (UMs), whereas 52.4 % were extensive metabolizers (EMs) and 27.6 % heterozygous EMs.

Paroxetine and imipramine treatment of depressive patients in a controlled multicentre study with plasma amino acid measurements.

In a 12-week double-blind study with 36 patients with major depressive episode (DSM-III), paroxetine (Seroxat, Aropax) showed significantly quicker onset of efficacy on the Melancholia Scale, and better tolerance than imipramine. Plasma concentration analyses showed no clear concentration-efficacy correlation in either treatment group. During long-term treatment paroxetine seemed to be superior to imipramine in preventing relapse; both treatments were well tolerated. A significant correlation between baseline plasma tryptophan: large neutral amino acids ratio and final Hamilton Rating Scale for Depression (HRSD) score and a trend towards an inverse correlation between this ratio and percentage reduction in HRSD score were seen in the paroxetine group but not in the imipramine group. In line with previous studies, these results support the hypothesis that paroxetine is an effective and well tolerated antidepressant.

[The reliability of the Danish translation of the Gottfires-Bråne-Steen scale]. / Reliabiliteten af dansk oversaettelse af Gottfries-Bråne-Steen skalaen.

The Gottfries-Bråne-Steen scale (GBS) is assessed for use in evaluating functional deficiencies in demented persons. The scale is translated into different languages, and reliability studies have been published from Sweden and Norway. This investigation is a reliability study of the Danish version. Fourty-nine patients were rated by several independent raters from the staff at the same time. Preceding this, all raters had been video-trained in the use of the scale. The results show that the scale has sufficient and satisfactory inter-rater reliability. It is concluded that the Danish version of the GBS-scale is also a useful tool for evaluating dementia processes and therapeutic measures.

[Functional levels in nursing homes residents assessed by the Gottfries-Bråne-Steen scale]. / Funktionsniveau hos plejehjemsbeboere vurderet ved Gottfries-Bråne-Steen skalaen.

Thirty-three inhabitants in a nursing home were evaluated by the Gottfries-Bråne-Steen scale. The evaluation showed that more than one third of the residents had marked dementia, especially with intellectual symptoms. The residents showed a high degree of motoric problems. It is concluded that dementia is a common cause for placement in a nursing home, although it seldom is recorded in detail as such before admission.

[Placing of patients with dementia in nursing homes as evaluated by the Gottfries-Bråne-Steen scale]. / Demente patienters placering i plejeinstitution, vurderet ved Gottfries-Bråne-Steen skalaen.

Sixteen gerontopsychiatric inpatients were compared with 33 residents in a somatic nursing home by Gottfries-Bråne-Steen scale. Both groups showed symptoms of mental deterioration of intellectual and also emotional character. The gerontopsychiatric inpatients showed significantly more emotional deterioration than the others. It was concluded, that especially the emotional defect in combination with intellectual deterioration is the cause of the placement in a psychiatric ward.

Zuclopenthixol and perphenazine in patients with acute psychotic states. A double-blind multicentre study.

Fifty-four patients with acute psychotic states were included in a double-blind multicentre study of zuclopenthixol and perphenazine given orally. Fourteen patients had not received test preparations for a minimum of 3 weeks as stated in the protocol, and were excluded. The remaining 40 patients received the test preparations for 3 to 12 weeks, with an average of 49 days for patients receiving zuclopenthixol and 45 days for patients receiving perphenazine. Clinical evaluations were done at baseline and at weeks 1, 2, 4, 6, 8, and 12 including the CGI, a CPRS subscale for schizophrenia, and the UKU Side Effects Rating Scale. The patients received on average 37 mg zuclopenthixol or 30 mg perphenazine daily. Statistically, significant reductions on the CGI, severity of illness, and on the CPRS (total score) were found for both drugs when comparing baseline with later scores. No significant differences between the drugs were found. It was also impossible to demonstrate a difference in clinical profile between the two drugs on the basis of the single items on the CPRS. Although small differences between the two drugs were found, as regards number and type of side effects, it is concluded that the pattern of side effects was almost identical in the two treatment groups.

Increase in weight after treatment with depot neuroleptics.

A trial has been performed investigating changes in weight in 99 female patients who have been treated with clopenthixol decanoate or perpehnazine enanthate after prior treatment with different oral neuroleptics. We found a significantly higher mean weight after the oral treatment period and a slight, but not statistically significant, further weight increase after the following depot period. In addition the rate of increase in weight was significantly lower during the depot treatment period. These increases might be due to achievement of a steady-state in weight during the first treatment period with oral intake. We found no difference between clopenthixol decanoate and perphenazine enanthate as regards change in weight or rate of change in weight.