OBJECTIVE:The aims were to study if the type and complexity of Parkinsonian symptoms, as well as treatment, could be related to the occurrence and severity of later depressive symptoms. Furthermore, the aim was to study if there is a different depressive symptomatology in Parkinson's disease (PD) patients compared with depressive illness in an age-matched group of patients with major depression but without Parkinson's disease.METHODS:Eleven PD-patients with major depression (MD) were compared to 14 PD-patients without depression and to 12 MD patients without PD.RESULTS:PD patients who later developed a depressive illness were younger at the debut of PD than patients without depression (P < 0.05). At inclusion the depressed PD patients were more disabled than PD patients without depression with higher level in the H&Y scale (P<0.05), and they had more involuntary movements according to Unified Parkinson's Disease Rating Scale (UPDRS IV) (P < 0.01). A family history of depression was found in one third of the depressed non-parkinsonian patients but in none of the PD groups. Sleep disturbances were significantly more common among depressed PD patients than in PD patients without depression but even more common in depressed patients without PD.CONCLUSIONS:Depressed PD patients had a longer duration of PD and more severe motor symptoms than PD patients without depression, although tremor as an initial symptom seemed to be more common in PD without a later depression. It cannot be excluded that depression in PD reflects a more advanced and widespread neurodegeneration, including serotonergic as well as dopaminergic neurons. Sleep disturbances is common and could be overlooked as an expression of depression.

To study how implementation of a naturalistic trial design for mirtazapine treatment in major depressive disorder for six (up to 12) months could be used and evaluated by means of clinical efficacy and safety.

The prescribing of selective serotonin reuptake inhibitors for adolescents is extensive despite the fact that there are few pharmacokinetic (PK), efficacy, safety, or tolerability studies on this group. This study reports the PK findings from two trials in adolescents treated with citalopram (CIT) in naturalistic clinical settings: one retrospective and one prospective. The aim of our study was to describe serum concentrations of CIT, desmethylcitalopram (DCIT), and didesmethylcitalopram (DDCIT) (trough values in steady state) in adolescents in relation to daily dose and clinical information obtained from therapeutic drug monitoring request forms. Altogether, 44 patients younger than 21 years were scrutinized using this combined open-label approach. The main findings were that (1) there was a pronounced interindividual variability of serum CIT, DCIT, and DDCIT concentrations in all doses prescribed, in agreement with previous studies on adults; on correcting for dose, the coefficient of variance was about 50% for CIT, DCIT, and DDCIT; (2) the transformation of CIT to DCIT and of DCIT to DDCIT was similar within the dose range 20 to 60 mg/day; (3) there was a difference between the sexes on comparing the dose-corrected concentrations of CIT and DCIT, with girls presenting significantly higher values than boys; and (4) there was a strong dose-serum concentration relationship in three identified subgroups of adolescents: (a) nonsmokers (CIT, r(2) = 0.71; DCIT, r(2) = 0.81), (b) girls not taking oral contraceptives (CIT, r(2) = 0.75; DCIT, r(2) = 0.71,), and (c) girls in the last 14 days of the menstrual cycle (CIT, r(2) = 0.68; DCIT, r(2) = 0.64). In summary, the present study tentatively supports influences of sex, oral contraceptives, and smoking habits on the disposition of CIT in younger patients. Hence, future studies on CIT should assess these parameters.

Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(−)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(−)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.

OBJECTIVE:This study was initiated in order to describe and evaluate the effects of a therapeutic drug monitoring (TDM) routine of selective serotonin reuptake inhibitors (SSRIs) on treatment strategies and drug costs in depressed elderly patients.METHOD:Blood samples were drawn from elderly depressed patients and analysed for steady-state trough serum concentrations of citalopram (n = 48), paroxetine (n = 48) or sertraline (n = 39). A global efficacy evaluation was made at baseline and after 6-9 months. Antidepressant drug costs before and after TDM were estimated.RESULTS:Eight samples were excluded due to technical problems or noncompliance. In 65 of the 127 (51.2%) remaining cases, the treatment strategy was changed according to the TDM outcome, in most a reduction of the prescribed dose. Bioanalytical TDM costs included the antidepressant drug costs after TDM were reduced by 10.2%.CONCLUSION:The results support the utility of TDM in the search for the individual minimum effective SSRI dose in the elderly.

The purpose of the study was to investigate whether a patient's adaptive occupational functioning is related to diagnoses of schizophrenia or mood disorders. The Occupational Case Analysis Interview and Rating Scale (OCAIRS) was used to examine the patient's adaptation in everyday occupation. Three groups of patients were studied: patients with schizophrenia (n = 18), major depression (n = 20), and bipolar disorders (n = 22). The adaptive occupational functioning of patients with schizophrenia and those with bipolar disorders was significantly reduced, to the same levels as that of patients with major depression. Thus, a patient's adaptive occupational functioning seems to be related to the studied psychiatric diagnoses. This observation may be used as a first step when screening patients for occupational therapy.

A Swedish version of the Occupational Case Analysis Interview and Rating Scale (OCAIRS-S) has been tested earlier for interrater reliability. The present study, using the second version of OCAIRS-S and including a sample of 145 patients, showed interrater correlations between .88 and .96 (Intraclass Correlation Coefficient). The results indicate that OCAIRS-S predicts which patients should be included in and excluded from occupational therapy and identifies patients who should be observed more before making such decisions. The study indicates a need for further investigations regarding which components in OCAIRS-S influence the occupational therapist in judging the patient's need for occupational therapy.

The objective of this study was to evaluate the features and calculate the frequency of sex‐reassigned subjects who had applied for reversal to their biological sex, and to compare these with non‐regretful subjects. An inception cohort was retrospectively identified consisting of all subjects with gender identity disorder who were approved for sex reassignment in Sweden during the period 1972‐1992. The period of time that elapsed between the application and this evaluation ranged from 4 to 24 years. The total cohort consisted of 218 subjects. The results showed that 3.8% of the patients who were sex reassigned during 1972‐1992 regretted the measures taken. The cohort was subdivided according to the presence or absence of regret of sex reassignment, and the two groups were compared. The results of logistic regression analysis indicated that two factors predicted regret of sex reassignment, namely lack of support from the patient's family, and the patient belonging to the non‐core group of transsexuals. In conclusion, the results show that the outcome of sex reassignment has improved over the years. However, the identified risk factors indicate the need for substantial efforts to support the families and close friends of candidates for sex reassignment.

The objective of this study was to compare the features of female‐to‐male transsexuals (F‐M) with those of male‐to‐female transsexuals (M‐F) in the cohort of all applicants for sex reassignment over a 20–year period. In an observational, cross‐sectional design the cohort was retrospectively identified, consisting of all 233 subjects who applied for sex reassignment in Sweden during the period 1972–1992. The cohort was subdivided into the groups M‐F (n=134) and F‐M (n=99), and the two groups were compared. M‐F were older when applying for sex reassignment surgery than F‐M, and more often had a history of marriage and children than their F‐M counterparts. M‐F also had more heterosexual experience. F‐M, on the other hand, more frequently exhibited cross‐gender behaviour in childhood than did M‐F transsexuals. The present and previous studies strongly support the view that transsexualism manifests itself differently in males and females. Various models for understanding these differences are discussed.

Blood alcohol concentration data that were previously obtained from 34 healthy Japanese subjects with limited sampling times were reanalyzed. Characteristics of the data were that the concentrations were obtained from only the early part of the time-concentration curve.To explore significant covariates for the population pharmacokinetic analysis of alcohol by incorporating external data using a Bayesian method, and to estimate effects of the covariates.The data were analyzed using a Markov chain Monte Carlo Bayesian estimation with NONMEM 7.3 (ICON Clinical Research LLC, North Wales, Pennsylvania). Informative priors were obtained from the external study.A 1-compartment model with Michaelis-Menten elimination was used. The typical value for the apparent volume of distribution was 49.3 L at the age of 29.4 years. Volume of distribution was estimated to be 20.4 L smaller in subjects with the ALDH2*1/*2 genotype than in subjects with the ALDH2*1/*1 genotype.A population pharmacokinetic model for alcohol was updated. A Bayesian approach allowed interpretation of significant covariate relationships, even if the current dataset is not informative about all parameters. This is the first study reporting an estimate of the effect of the ALDH2 genotype in a PPK model.

Landén M, Wålinder J, Lundström B. Prevalence, incidence and sex ratio of transsexualism.Scand 1996: 93: 221–223. © Munksgaard 1996.Frequency figures for transsexualism, concerning incidence, prevalence and sex ratio calculated in the 1960s and 1970s, were compared with recent reports. The incidence figures remained constant over time, whereas the prevalence figures tended to increase during the review period. The incidence was found to be of the same magnitude in men and women, while the corresponding ratio for prevalence figures was 3:1. It is suggested that men seeking sex reassignment represent a more heterogeneous group than women, and that the reported male predominance to date is due to a lack of categorical studies of primary/ genuine transsexualism. It would appear that genuine transsexualism is, on the whole, insensitive to societal changes. The fundamental disturbance underlying this psychosexual identity disorder is suggested to be neurobiological in origin.

Electroconvulsive therapy (ECT) was given to 16 non-depressed, non-demented patients with advanced Parkinson's disease (PD). In all the patients an antiparkinsonian effect was seen, lasting for 18 months in one patient, 3-5 months in seven patients, and a few days to four weeks in eight patients. After ECT the levels of homovanillic acid and neuropeptide Y in cerebrospinal fluid (CSF) were significantly increased. The eight patients with long lasting motor improvement after ECT had significantly lower CSF-3-methoxy-4-hydroxyphenylglycol compared to the group with short lasting improvement. Five patients developed transitory mental confusion after ECT. In these patients, and in no others, a high albumin-ratio was found already before ECT was given - an indication of blood CSF barrier damage. Our results suggest that ECT is valuable in patients with drug refractory PD or PD with intolerance to antiparkinsonian drugs.

An international clinical trial programme was undertaken to evaluate the clinical safety and tolerability of remoxipride during a 12 month long-term study and to evaluate safety, tolerability and efficacy of remoxipride for up to 6 months in a double-blind comparison with haloperidol. A total of 145 patients were treated with remoxipride for at least 12 months. In the double-blind evaluation 106 patients on remoxipride and 50 on haloperidol were included. The doses of remoxipride ranged between 90-600 mg daily and of haloperidol between 5-45 mg daily. The therapeutic efficacy of remoxipride obtained in short-term studies was maintained during long-term treatment in most patients and was similar to that of haloperidol. Remoxipride had a clear cut advantage concerning extrapyramidal symptoms and anticholinergic drugs were needed less frequently with remoxipride than with haloperidol. The tolerability and safety showed no clinically significant differences compared to the data from short-term studies. This indicates that remoxipride can be used safely and with maintained efficacy for long-term treatment.

ABSTRACT— Since the first publications on a sex reassignment operation in Denmark in the early fifties, the European environment in which sex reassignment surgery (SRS) takes place has changed drastically. However the possibilities differ considerably between one country and another. To get a picture of the European situation a questionnaire was sent out to gender clinics and private practitioners treating transsexuals in 15 European countries. Questions were asked about evaluation of candidates for a treatment program, details of such programs, the legal and financial situation in the different countries and attitudes and place of psychotherapy in the SRS procedure. By and large there seems to be fairly good consensus within those European SRS treatment programs we had the opportunity to evaluate.

In a previous double‐blind, 3‐week study we compared the effect of clomipramine + placebo with clomipramine + tryptophan in 24 patients with endogenous depression. The patients in the latter group showed a significantly more rapid improvement than those in the former group, especially with regard to the depression‐anxiety cluster of symptoms.These results prompted us to perform a similar study in which zimelidine, a more specific inhibitor of 5‐HT reuptake, was used instead of clomipramine. In other respects the design was practically identical to that used in the previous study.Unexpectedly, tryptophan in combination with zimelidine, was not superior to placebo + zimelidine with respect to antidepressant activity. In comparison with the previous study, the antidepressant action of zimelidine showed no statistically significant difference from clomipramine. However, the patients tended to show a more prompt response after zimelidine + placebo than after clomipramine + placebo. The changes in CSF amine metabolites were likewise different in the two studies. In the two studies taken together 12 out of 49 patients showed prompt improvement within one week. This raises the question whether the therapeutic response to antidepressant drugs necessarily involves a delay as is generally assumed. Side effects were remarkably few and mild in the second study.