Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group.

OBJECTIVE: To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed inpatients and outpatients. METHOD: Patients with a major depressive episode (DSM-III-R), a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression (HAM-D), and > or=2 on HAM-D Item 1 (depressed mood) were randomly assigned to a 6-week treatment with either mirtazapine (N=66, 15-60 mg/day) or fluoxetine (N=67, 20-40 mg/day). The upper limit of the mirtazapine dose range was above the dose range approved in the United States (15-45 mg/day). Efficacy was evaluated by the HAM-D, Clinical Global Impressions, the Visual Analogue Mood Rating Scale (VAMRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method. RESULTS: Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group. The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period, reaching statistical significance at days 21 and 28. At assessments from day 21 and onward, the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points, the magnitude of difference usually seen between an efficacious antidepressant drug and placebo. Mean dosages at weeks 1-4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine; the respective dosages at weeks 5-6 were 56.3 mg and 35.8 mg. Similar numbers of patients dropped out due to adverse events; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group. CONCLUSION: We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy.

Clinical Features and Drug Treatment of Psychodermatological Disorders.

The skin is intricately involved with emotional and behavioural problems, both in a causative and a reactive way. This can lead to the development of psychodermatological disorders. In addition to its primary role of tactile receptivity, the skin reacts directly to emotional stimuli. The high visibility of dermatoses makes the skin a direct target for behavioural problems. Furthermore, self-destructive tendencies (such as dermatitis artefacta) and hypochondriacal features are often expressed through dermatological symptoms.In view of the clinical interface between dermatology and psychiatry, a combination of pharmacological and non pharmacological (psychotherapeutic and behavioural) therapies is recommended for the treatment of psychodermatological disorders. Psychotropic drug treatments that may be useful include benzodiazepines, antidepressants and antipsychotics.

Efficacy and tolerability of reboxetine compared with imipramine in a double-blind study in patients suffering from major depressive offsodes.

A 6-week, randomised, double-blind, multicentre study in 256 patients with a DSM-III-R diagnosis of major depression was carried out to compare the selective noradrenaline reuptake inhibitor (NARI), reboxetine, with the reference standard tricyclic antidepressant, imipramine. The efficacy of reboxetine, as measured by the extent of improvement of Hamilton Depression Rating Scale. Montgomery and Asberg Depression Rating Scale and the Clinical Global Impression Scale, was similar to that of imipramine. The improvement was observed in the overall population and in severely depressed and melancholic patients. Reboxetine tolerability compared favourably with that of imipramine. Frequency of discontinuation due to adverse events was lower in the reboxetine-treated group (10.0%) than in the imipramine-treated group (14.3%), and the cumulative risk of development (Kaplan-Meier analysis) of dry mouth, hypotension and/or related symptoms and tremor was significantly higher on imipramine than on reboxetine.

Integration of medical and psychiatric management in self-mutilation.

The traditional management of factitious patients with self-inflicted injuries consists of medical/surgical treatment of the physical lesions, followed by psychiatric referral. The former is assigned to the dermatologist, the surgeon, or the primary care physician. More often than not, the subsequent psychiatric referral for treatment of the psychiatric disorder underlying and actually causing the self-mutilation fails because of self-mutilators' notorious resistance to psychiatric help. The integration of a psychiatric strategy into the medical management is more effective than a sequential division of medical/surgical and psychiatric treatment. This integrated treatment strategy is based on three key issues: education of the medical team in understanding the self-mutilation as a morbid form of help-seeking behavior, the judicious use of confrontation as a therapeutic tool, and the combination of psychotropic drug treatment with psychotherapeutic techniques.

Training future dermatologists in psychodermatology.

The contents and design of a psychodermatology training programs (PTP) preparing future dermatologists to cope with the psychosomatic features of their practice are discussed. This program focuses on the psychosocial factors that may provoke, precipitate, and aggravate dermatoses. It singles out the secondary illness reaction which is the result of the particular somatopsychic consequences of the visibility of dermatoses, its repercussion on the patient's body image, and on his or her social and sexual life. The benefits and the risks of a grounding in psychodermatology as well as the dermatologist's specific resistance are pointed out.

Consultation-Liaison psychiatric service delivery: results from a European study.

The reported findings of the European Consultation-Liaison Workgroup (ECLW) Collaborative Study describe consultation-liaison service delivery by 56 services from 11 European countries aggregated on a C-L service level. During the period of 1 year (1991), the participants applied a standardized, reliability tested method of patient data collection, and data were collected describing pertinent characteristics of the hospital, the C-L service, and the participating consultants. The consultation rate of 1% (median; 1.4% mean) underscores the discrepancy between epidemiology and the services delivered. The core function of C-L services in general hospitals is a quick, comprehensive emergency psychiatric function. Reasons to see patients were the following. deliberate self-harm (17%), substance abuse (7.2%), current psychiatric symptoms (38.6%), and unexplained physical complaints (18.6%) (all means). A significant number of patients are old and seriously ill. Mood disorders and organic mental disorders are most predominant (17.7%). Somatoform and dissociative disorders together constitute 7.5%. C-L services in European countries are mainly emergency psychiatric services and perform an important bridge function between primary, general health, and mental health care.

Mirtazapine is more effective than trazodone: a double-blind controlled study in hospitalized patients with major depression.

Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were randomized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial. The dosages were 24-72 mg/day for mirtazapine and 150-450 mg/day for trazodone. The improvement on all depression rating scales used was generally greater for mirtazapine, with statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores (the Bech melancholia factor and retardation factor), the Brief Psychiatric Rating Scale total score, the General Psychiatric Impression Global Assessment Scale, the Beck score and responder rates. Mirtazapine was well tolerated, while the trazodone-treated patients experienced somnolence more frequently, particularly during the first 2 weeks of treatment. Furthermore, postural symptoms were a clinical problem in 6% of the trazodone-treated patients. In this trial, mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability.

Sleep disorders and depression: the 'chicken and egg' situation.

The question of whether sleep disorders are part of the clinical picture of depression or of its aetiology remains unanswered. Still, clinical observation in general, polysomnographic studies and the observed antidepressant effect of sleep deprivation, clearly indicate the intimate relationship between sleep disturbances and depression.

Zopiclone in the treatment of insomnia in depressed patients.

During the early treatment of a major depressive episode with amitryptiline, insomnia was treated in 81 patients in a double-blind comparative trial comparing zopiclone and flunitrazepam. The study showed no major differences in the efficacy profile and showed better tolerability for zopiclone than for flunitrazepam.

Localization of self-inflicted dermatological lesions: what do they tell the dermatologist?

The dissimulating attitude of factitious patients creates the need for objective clinical features which cannot be faked and which have a genuine value for the psychiatric diagnosis and prognosis. The psychiatric significance of the localization of self-inflicted dermatological lesions is investigated in four psychiatric areas: the type of life events preceding specific localizations, underlying psychiatric profiles that are characteristic for a given localization, differential response to treatment and psychiatric sequels.

Sulpiride in the treatment of somatoform disorders: results of a European observational study to characterize the responder profile.

An open, observational study was conducted in five European countries to obtain information concerning the profile of patients responding to sulpiride. A total of 1,356 patients were evaluable for analysis. The majority of patients (81.1%) had at least three principal somatic complaints; asthenia being the most common, followed by dizziness and headache. Most patients (76.0%) were rated as moderately to extremely ill according to the Clinical Global Impression (CGI) severity score. All patients received oral sulpiride for 3-6 weeks (mean dose, 175 mg/day). Sulpiride demonstrated good efficacy as shown by a reduction in the incidence and severity of somatic complaints, and an improvement in CGI severity score and the Hopkins Symptom Checklist--58 items. Based on a CGI rating of very much or much improved, 58.2% of patients were rated as responders. Sulpiride was well tolerated. There were no serious adverse events and only 16 patients (1.2%) were withdrawn prematurely from the study due to adverse events. There were no differences between the countries regarding the patients' profile or their response to sulpiride. Thus, the prescription profile of sulpiride appears not to be culturally dependent.

Psychodermatology: an overview.

As the skin is an organ that has a primary function in tactile receptivity and reacts directly upon emotional stimuli, dermatological practice involves a psychosomatic dimension. It is, however, the high visibility of dermatoses and their easy accessibility which make the skin a direct target for behavioural problems. Furthermore, self-destructive tendencies and hypochondriacal features often express themselves through dermatological symptoms: dermatitis artefacta and skin hypochondriasis are among the specific psychocutaneous disorders discussed here. In view of the clinical interface between dermatology and psychiatry, general guidelines are formulated and specific aspects of psychotherapy, behavioural treatment and psychotropic drug treatment are discussed.

Management of self-mutilation. Confrontation and integration of psychotherapy and psychotropic drug treatment.

The management of diverse types of self-mutilation is discussed with a particular emphasis on the selective use of open confrontation of the dissimulating patient with the self-inflicted nature of the lesions. Integration of psychotherapy with psychotropic drug treatment in self-mutilating patients is a necessity.

Social reintegration of sexual delinquents by a combination of psychotherapy and anti-androgen treatment.

The high frequency of recidivism with convicted sexual perverts is mainly due to the compulsive character of perversion. The classical methods of treatment are seldom satisfactory: Surgery provokes ethical objections, psychopharmaca and oestrogens lead to disagreeable side effects, psychotherapy of any kind is unlikely to be efficacious because of the unfavourable atmosphere the nature of perversion causes it to take place in. However, the climate of both psychoanalytical treatment and suggestive and directive psychotherapy can be enhanced by a combination with an anti-androgen treatment, which eliminates the patient's fear of conviction by inhibiting his sexual urge. Two cases illustrate this combined method. On the basis of a positive disposition, which arises from the improved climate, sublimation of the sex drive and the achievement of a feeling of social responsibility is aimed at. The advantages of the combined therapy are then discussed in comparison with the existing treatments. It is concluded that this combined treatment, next to social guidance and an attempt at solving the fundamental problem of loneliness, can promote the social reintegration of the convicted sexual pervert.

Self-mutilation: diagnosis and practical treatment.

The management of self-inflicted lesions requires an understanding of the dynamics of the act of self-mutilation. The overview of practical techniques allows the non-psychiatrist physician to deal with self-inflicted disorders more effectively. The efficacy of behavioral and psychotherapeutic techniques is enhanced when combined with psychopharmaca.

An update of panic disorders. Somatization, biological markers and treatment outcome.

Psychiatric underdiagnosis of panic disorders is due to its particular somatization profiles. Cardial somatization is very common, but focal neurological symptoms and a pattern of gastro-intestinal complaints deserve more attention. Recent research into biological data is discussed, and the importance of psychological issues--childhood separation or sexual victimisation--and cognitive factors is stressed. Breaking up outcome data in degree of remission and relapse rate for an exact judgment of different treatment strategies is needed.

Valproate as psychotropic agent. Interactions and adverse cerebral reactions.

Recent data stress the psychotropic actions of valproate in schizo-affective disorder. Four patients are reported presenting an altered state of consciousness and prominent EEG dysfunction following combined valproate/neuroleptic drug treatment. Similar cerebral reactions have been reported in anti-epileptic poly- and monotherapy, and the pathogenetic considerations are discussed. Further investigations of the interactions of valproate with other psychotropic agents are highly mandatory.

Somatization of psychiatric illness in Mediterranean migrants in Belgium.

Mediterranean migrants with acute psychiatric problems show a predominance of dramatic somatization in their symptom patterns, when compared with Belgian patients with similar psychiatric problems and admitted after identical recruiting and referral procedures. D.S.M. III diagnoses of the Mediterranean patients, however, reveal neither a correspondingly high incidence of somatoform disorders nor histrionic personalities. Adult and adolescent Mediterranean migrants appear to convey psychological problems through contrasting forms of somatization. Adolescents somatize mainly through self-inflicted symptoms, whereas adults express somatization in a more 'natural' way--insubjective bodily sensations, psychophysiological symptoms or psychosomatic syndromes. The main reason for acute psychiatric admission among Belgian adolescents is outward aggressive behaviour. In Mediterranean adolescents in Belgium it is a combination of somatization and aggression in self-inflicted physical symptoms.

Congenital malformations caused by psychotropic drugs in pregnancy.

After a description of the harmful effects of psychotropic drugs as well as of the moments of vulnerability to any teratogenic effect, this paper reviews prospective, retrospective and epidemiological studies of the teratogenic effects of anticonvulsants (phenytoin, valproic acid, carbamazepine and barbiturates), lithium, anti-psychotics, benzodiazepines and anti-depressive agents. It is found that the results of these studies are not unequivocal. Only lithium and valproic acid are shown to be teratogenic. In cases where malformations of the fetus are observed, the treatment often consisted in a combination of various psychotropic drugs. The review is completed with data on the psychopharmacological problems during delivery and their side-effects on the newborn.