Depressive illness in Parkinson's disease--indication of a more advanced and widespread neurodegenerative process?

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.

Male depression and suicide.

Based on the experiences of the Gotland Study that education of general practitioners about depressive illness resulted in a statistically significant reduction in the number of female suicides, leaving the rate of male suicides almost unaffected, we propose the concept of a male depressive syndrome. This syndrome comprises a low stress tolerance, an acting-out behavior, a low impulse control, substance abuse and a hereditary loading of depressive illness, alcoholism and suicide. This notion is supported by data from The Amish study as well as the concept of van Praag of a stress-precipitated, cortisol-induced, serotonin-related and anxiety-driven depressive illness most often seen in males. In order to identify depressed males, the Gotland Male Depression Scale has been developed. Some preliminary data using the scale in a group of alcohol-dependant patients are presented.

Enantioselective analysis of citalopram and metabolites in adolescents.

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.

Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients.

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.

Light treatment of seasonal affective disorder in combination with citalopram or placebo with 1-year follow-up.

This placebo-controlled, double-blind, 1-year pilot study aimed at investigating possible clinical advantages of combining initial light therapy with the selective serotonin reuptake inhibitor (SSRI) citalopram as well as the effects of continuous long-term administration of this drug in patients with seasonal affective disorder (SAD). Eight physically healthy women who met the DSM-III-R criteria for SAD were included in the study. Four women were randomized to the citalopram group receiving 40 mg citalopram daily from the first of 10 light treatment days and throughout the 1-year study. The remaining four women were allocated to the placebo group using the same double-blind repeated measures design. The clinical outcome was measured by using three versions of the Comprehensive Psychopathological Rating Scale (CPRS) and Visual Analog Scales (VAS), respectively. Taking the initial rating scores into account in covariance analyses, no statistically significant group difference was found during the light treatment period. However, during the follow-up period the full version of the CPRS and the self-rating version of CPRS and the VAS-scales for global condition and depressed mood were statistically significantly lower in the citalopram group compared with the placebo group. Thus, in this small but carefully observed sample of SAD-patients combining initial light therapy and long-term citalopram treatment was clinically more effective over time than the placebo combination. Our findings support the notion that light therapy with concomitant and continued SSRI (citalopram) treatment is a useful strategy to achieve beneficial long-term effects in patients with the SAD syndrome.

[Male depression--stress reaction combined with serotonin deficiency?]. / Manlig depression--stressreaktion kombinerad med serotoninsvaghet?

An educational programme on depressive disorders, given to general practitioners on the Swedish island of Gotland, resulted in a statistically significant reduction of the suicide rate among women, though that among men was virtually unaffected. Further analysis showed the profile of depression among men to differ from that among women, the male pattern typically being more characterised by irritability, aggressiveness, acting out, antisocial behaviour and alcohol abuse, and reduced impulse control and stress tolerance. Predisposition to affective disorders, suicide and alcoholism seems to be genetically determined. The syndrome, which is not easily recognised and is seldom properly treated or prevented, seems to be related to central serotonin deficiency and hypercortisolaemia.

Amitriptyline and clomipramine increase the concentration of administered L-tryptophan in the rat brain.

The tricyclic antidepressant amitriptyline has been shown to reduce concentrations of large neutral amino acids (LNAA) in rat plasma. Compounds with that property might interact with such amino acids used as therapeutic agents with a central site of action by causing a change in the relationship between the administered LNAA and its endogenous LNAA competitors for carrier-mediated transport through the blood-brain barrier into the brain. This study was performed to investigate if the antidepressant agents amitriptyline and clomipramine could, by such a mechanism, increase brain concentrations of administered tryptophan. Intraperitoneal administration of L-tryptophan alone (100 mg kg-1) resulted in an increase in the concentration of tryptophan in the rat brain from 14 +/- 0.7 to 100 +/- 4.3 nmol g-1 compared with rats given saline only. When rats were given tryptophan with amitriptyline (25 mg kg-1, i.p.) or clomipramine (25 mg kg-1, i.p.) brain concentrations of tryptophan were increased even further, to 150 +/- 4.5 and 157 +/- 10.2 nmol g-1, respectively. Administration of L-tryptophan alone resulted in an increase in the rat plasma tryptophan ratio [(concentration of tryptophan)/(total concentration of LNAAs)] from 0.14 +/- 0.003 to 0.42 +/- 0.011 compared with rats given saline only. When rats were given tryptophan with amitriptyline or clomipramine the plasma tryptophan ratios were increased even further to 0.52 +/- 0.017 and 0.54 +/- 0.025, respectively. All these effects were statistically significant (P < 0.001). These findings support the hypothesis that tricyclic antidepressants could interact with administered tryptophan by changing the relationship in plasma between tryptophan and its endogenous LNAA competitors for transport into the brain, resulting in higher concentrations of tryptophan in the brain. It is possible that this could be the mechanism of the previously reported finding that clomipramine and tryptophan potentiate each other in the treatment of depression.

Clinical characteristics of a total cohort of female and male applicants for sex reassignment: a descriptive study.

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.

Factors predictive of regret in sex reassignment.

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.

Prevention of depression and suicide by education and medication: impact on male suicidality. An update from the Gotland study.

Depression is an endemic disease with high morbidity, and a high mortality in depression-related suicide. Suicidal tendencies, especially among males, are increasing today in East European countries. General practitioners are considered to have a very important role in the prevention and treatment of depression. Matters of depression are more openly discussed in society. Patients showing up in primary care are nowadays less reluctant to see depression as a causative factor behind their symptoms. Taboos concerning the stigma of depression and suicidality are weaker. In spite of this, important problems still exist regarding poor diagnostic and treatment routines in primary care and the inability of depressive and suicidal men to seek for help or to be recognized. In the years 1983-1984, the Swedish Committee for Prevention and Treatment of Depression (PTD) offered an educational programme to all general practitioners (GPs) on the Swedish island of Gotland. During the 1980s this education was shown to lead to a significant decrease in inpatient care, morbidity, suicide, mortality and costs of depressive illness on the island. The use of anxiolytic and sedative medication decreased and that of antidepressant medication increased. This all showed that an educational programme in primary care on depression and suicide was effective. However, the effects faded and, unexpectedly, the number of male suicides was almost unaffected by the educational programme and by the GPs' ability to diagnose and treat depression. Repeated educational activities during the 1990s again led to a decrease in suicides, mainly in females. Also, the increase in antidepressant prescriptions following GP education in the 1990s was mostly in the treatment of female patients. One of the reasons was that few suicidal males are known to the medical services although many of these people are known to the police and social welfare services. The reasons why depressed and suicidal men do not show up in the medical services are discussed, and found to lie in the differences between the male and the female depressive syndrome, leading to difficulties in reaching, diagnosing and treating these patients. Strategies for finding and treating suicidal depressives are discussed. One conclusion is that males are as often depressed as females, but in different ways, and that one of the reasons behind the dramatic over-representation of males amongst suicide victims may be found in the low rate of diagnosis and treatment of the male depressive syndrome, (hit J Psych Clin Pract 1997; 1: 39-46).

Prevalence, incidence and sex ratio of transsexualism.

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.

Incidence and sex ratio of transsexualism in Sweden.

The incidence and sex ratio of transsexualism in Sweden were calculated during the period between 1 July 1972 and 30 June 1992 using a case register kept on file at the Swedish Bureau of Social Welfare. Only cases of primary/genuine transsexualism were considered. The study is unique in that it has been performed in exactly the same way as a previous study by one of the authors (JW) in the 1960s and early 1970s. The data can therefore be reliably compared. The results show that the incidence figures remain constant over time and that the incidence of primary/genuine transsexualism is equally common in men and women. A larger group consisting of all those individuals who had applied for sex reassignment revealed a preponderance of men. Analysis showed that this large group included not only primary/genuine transsexuals but also effeminate homosexuals, transvestites and diagnostically uncertain cases. The importance of describing the exact methods used when calculating epidemiological data is highlighted.

Cost-effectiveness of clozapine treatment in therapy-refractory schizophrenia.

The costs and effects of clozapine treatment of refractory schizophrenic patients have been discussed recently. This study shows that 18 months of clozapine treatment results in an improvement of symptoms and social functioning in approximately 70% of treatment-refractory schizophrenic patients, compared with treatment with conventional neuroleptics during a similar period of time. Treatment with clozapine reduces the cost of inpatient care but places increased demands on active rehabilitation resources in outpatient care. This leads to increased total costs in a short-term perspective, but clozapine treatment is cost-saving for annual maintenance therapy. These costs must be weighed against the positive effects on psychotic symptoms and social functioning.