Clinical assessments of sleep and subjective state upon waking were performed in normal controls and patients with generalised anxiety disorder, panic disorder, obsessive-compulsive disorder, primary dysthymia and major depression. Subjects were selected according to DSM-III-R criteria. As compared to normal controls, patients with generalised anxiety, dysthymia and major depression exhibit pervasive and intense complaints of insomnia, and no clear distinctions can be drawn among these groups. Patients with panic disorder do not differ from normal controls, whereas obsessive compulsive patients present limited sleep symptoms. These findings suggest that subjective sleep variables are relevant for the diagnostic discrimination of panic and obsessive-compulsive disorders.

A naturalistic study was conducted in general practice in Portugal on the efficacy and tolerance of low doses of amisulpride in the treatment of dysthymia. A total of 109 patients received low doses (50 – 100 mg) of amisulpride for four weeks. A global evaluation showed good or very good efficacy and tolerance in more than 80% of the patients. The social disability observed at baseline was significantly improved after the four-week treatment period. Few adverse events were observed and only four patients dropped out due to side effects. Our results suggest that low doses of amisulpride might be a safe and effective treatment for dysthymia in clinical practice.

Depressive conditions such as treatment-resistant depression, persistent depression and chronic mild depression have recently been the subject of much interest in Japan. The term “atypical depression” is not in common use, however depressive states falling outside the “typical” categories of the major depressive disorders (MDD) can be discussed in terms of symptomatology, etiology, and response to treatment. The term “neurasthenia” which refers to a hypochondriacal disorder with or without physical illness, as well as to a subtype of neurosis (ICD-9, 300.5), is no longer extensively used. “Dysthymia” is classically employed to signify either a dysphoric state accompanied by mild depression and irritability, as defined by the German school, or a mild depressive personality disorder; it is currently used as an alternative to “neurotic depression” (ICD-9 300.4), or “dysthymic disorder” (DSM III-R). Recurrent brief depression is not yet a prevalent concept in Japan. Despite the observation of depression with hyperphagia and/or hypersomnia, these phenomena have not received a specific designation. Therapeutic approaches to depression include both non-drug modalities (psychotherapy, environmental modification, etc) and the standard drug regimens (antidepressants, anxiolytics, etc); clinical trials are currently underway with selective serotonin reuptake inhibitors which we expect to be effective in treatment-resistant depression. Plant-based traditional remedies are still widely employed in Japan, and several of these are described. Finally, we discuss the Morita therapy, a specifically Japanese modality for treatment of mild depression with obsessive-compulsive symptoms based upon the Zen philosophy. This approach involves an initial period of absolute bed-rest, followed by gradual resumption of work and social activities with support and counseling.

The presence of affective symptoms in panic disorder has often been reported. Data from The Cross-National Collaborative Panic Study (second phase) were analysed to address the role of dysthymia in panic disorder with respect to previous illness, current psychopathology and the outcome during an 8-week study of alprazolam and imipramine. A group of dysthymic patients without current or past major depressive episode was studied. The prevalences of dysthymia varied markedly across participating sites: 2–13%. Only a few clinical characteristics of dysthymic panic disorder patients were found. They had suffered from panic disorder for a few years more than patients without affective disorder and they were slightly older. The outcome after the 8-week drug trial was not significantly different from that of patients without affective disorder. Hence, dysthymia was not suggested to be of major clinical relevance for the phenomenology of panic disorder or for the outcome of drug treatment.

Platelet serotonin-binding (Bmax), using tritiated-seroionin as the ligand, was determined in 75 patients suffering from major depression with melancholia and in 26 patients diagnosed from dysthymic disorder. Twenty-five normal subjects were used as a control group. The melancholic group had significantly lower Bmax values (mean: 6.7 ± 6.1 pmol/108 platelets) than either dysthymic (9.3 ± 3.9 pmol/108 platelets) or control (9.2 ± 4.8 pmol/108 platelets) groups, while there were no significant differences between the two latter groups. There was also a significant difference on postdexamethasone Cortisol between melancholic (6.3 ± 7.1 μg/dL) and dysthymic (1.4 ± 1.4 μg/dL) groups, with a higher rate of nonsuppressors in melancholic groups. Although both tests were abnormal in the melancholic group, no relationship was found between platelet serotonin-binding and the dexaniethasone suppression test.

Data on dysthymia and personality presented here are derived from the Zurich cohort study, which followed 591 subjects from the ages of 20 to 35. From childhood on, dysthymics experienced themselves as far more anxious and less self-confident than did major depressives or controls. They manifested more behavioural problems and high neuroticism and introversion scores. Dysthymics scored low in terms of quality of life, self-esteem and mastery, whereas they scored high in avoiding/denying behaviours. The hypothesis is advanced that behavioural problems, anxiety, high levels of neuroticism and personality disorders constitute risk factors for chronic depression. Evidence is presented of the existence of bipolar dysthymia.

Dysthymia is the last diagnostic label introduced after a series of precursors to describe a disorder whose nosological status has long been dubious. The results of published epidemiological, as well as clinical studies about its presentation, course and outcome partly support the validity of this construct — although their interpretation is limited by methodological difficulties: same prevalence in many locations in the world, always lower than that of major depression, somewhat specific clinical pattern, course and outcome.

As part of the WHO-PPGHC study aimed to better understand the form, frequency and burden of psychiatric conditions in primary care throughout the world, the clinical characteristics of dysthymic patients consulting in primary care were examined. A total of 25,916 general health care attenders at 15 sites in 14 countries were screened using the 12-item General Health Questionaire (GHQ-12). Of those screened, 5,438 were assessed in detail using a Primary Health Care version of the Composite International Diagnostic Interview (CIDI-PHC) in conjunction with among others the Brief Disability Questionnaire (BDQ) and the 28-item General Health Questionnaire (GHQ-28). General practitioners (GPs) gave their opinion on the existence of a psychological problem and indicated what therapeutic intervention was proposed to patients they recognised as psychological cases. The estimated current prevalence of dysthymia as defined by the ICD-10 was 2.1%. The social disability was found to be substantial in patients with dysthymia (52.2% of patients moderately or severely disabled) similar to that observed in patients with Depressive Episode (DE) (57.4%). When both conditions were present, the level of disability was even higher (63.6%). The symptoms presented by dysthymic patients without DE were mostly those specific for the diagnosis of dysthymia (ie, tearful, hopeless, inability to cope, pessimism) while these symptoms were less frequent when dysthymia was complicated by a DE. On the contrary, fatigue and loss of interest were more rarely observed in “pure” dysthymics. In spite of a lower symptomatic severity about half of the patients with dysthymia were recognised as cases by their GPs, a proportion similar to those with DE. However, dysthymics without DE were not, in contrast to patients with DE or with dysthymia and DE, more treated with drugs than non-depressed patients.

If some recent studies seem to reveal a more specific familial relationship for dysthymia in addition to a previously known familial relationship to mood disorders, and if results concerning the relationship between dysthymia and depressive personality as well as the search for possible biological and psychological correlates support the nosological validity of dysthymia, comorbidity studies raise difficult questions. Both comorbidity studies with Axis I and Axis II disorders challenge the validity of dysthymia, but as well they question the categorical model presently in use more than the validity of a definite category.

However, there are now enough data confirming some of the hypotheses implied by the nosological construct of dysthymia inside this model for this category not to be discarded. For instance, dysthymia is definitely not a personality disorder, and appears also distinct from major depression. The problem of the complex nature of the relationship between dysthymia and major depression still remains unsolved.

In Germany a major distinction is made between endogenous and neurotic depression. While traditionally neurotic depression was seen as being amenable only to psychotherapy, there is an increasing tendency to treat neurotic patients presenting the full depressive syndrome with antidepressant drugs. Those psychiatrists who are aware of the concept of atypical depression in the stricter sense (anxiety-depression, depression with reversed somatic symptoms, etc) tend to treat these patients with monoamine oxidase inhibitors. The diagnosis of “dysthymia”, Possibly equivalent to “neurotic depression”, has not yet come into common usage. While the term “neurasthenia” is traditional, general Practitioners prefer other designations; treatment involves supportive psychotherapy, benzodiazepines and sedative antidepressants. Mixed anxiety-depression is treated with anxiolytic antidepressants, sedatives or, for the milder cases, with low-dose neuroleptics. This indication for neuroleptics is controversial, and a treatment protocol has been codified for use by the general practitioners so as to avoid the potential major adverse reactions seen with the class. The new concept of recurrent brief depression is confined to academic milieu, where treatment is the same as for unipolar depression.

Open trials with tricyclics, classical monoamine oxidase inhibitors (MAOIs) or lithium in dysthymia yielded a response rate in 45% of subjects. A long-term treatment of dysthymia with 276 patients treated during 4 years with either moclobemide, tranylcypromine or a combination of amitryptiline plus chlordiazepoxide is described. After discontinuation there was a relapse rate of 89.1%. The controlled studies with tricyclics, MAOIs, reversible inhibitors of monoamine oxidase (RIMAs), specific serotonin reuptake inhibitor (SSRIs) or benzamides showed that drugs well-tolerated work better in dysthymia, due to the fact that the treatment must be long-term. Sertraline was studied vs placebo or imipramine in primary dysthymia. Moclobemide, imipramine and placebo were also studied in 315 patients. Mean doses were 650 mg/d of moclobemide and 203.2 mg/d of imipramine. Moclobemide and sertraline were both efficacious and well tolerated. In a long term treatment the clinician should assess the risk-benefit ratio. Dysthymic patients are very sensitive to unwanted effects and compliance is a serious issue.

We assessed whether cytokine production–interleukin (IL)-1β, IL-6 and tumour necrosis factor-α (TNFα)–is affected in depressed patients, dysthymia (Dt) and major depression (MD), and its association with various parameters of severity and clinical course. We found a possible different pattern of interleukin production between Dt and MD.

Dysthymia clinical trials raise several methodological issues. The validity of the concept remains a matter of concern, as does the need for specific instruments, the difficulties in assessment of change and long-term assessments. Diagnostic criteria for inclusion should be used in a polydiagnostic approach. This paper summarises the main assessment tools and diagnostic criteria used in clinical trials on dysthymia. Severity criterion for inclusion could be a Hamilton Depression Rating Scale score (HAMD-17) between 13 and 17. The main response criteria should be a decrease of at least 50% of the total score on this scale and a final score under a predetermined limit. However, other response criteria may be useful: depression self-ratings, global assessments, general psychopathology assessments, personality and defense mechanisms, quality of life, psychosocial and functional impairment, diagnostic criteria (presence or absence) and side-effect assessment.

The understanding and classification of persistently depressed mood has undergone many changes since the term ‘dysthymia’ was first used nearly 150 years ago. Originally it was applied to both melancholia and mania; later it was applied to depressive personality. The Diagnostic and Statistical Manual (DSM)-III in 1980 and in subsequent updates classified dysthymia as a mood disorder, characterized by a frequently insidious onset and a course that is chronic and unremitting. The assessment of clinical response in the pharmacologic treatment of dysthymia has been more difficult than that for major depression. The Hamilton Rating Scale for Depression, among others, is oriented towards episodic rather than chronic states of depression. A new rating scale, the Cornell Dysthymia Rating Scale, has been developed to better assess milder symptomatology in chronically depressed patients. Early studies suggest its utility, but further validation of the scale is needed in patients with dysthymia and without major depression.

In an attempt to better delineate demographic and clinical characteristics of mild chronic depressions, 46 outpatients fulfilling DSM III-R criteria for dysthymia were compared with patients suffering from a chronic major depressive episode. The profile obtained from our dysthymic sample matches with those reported by other authors. The comparison between “minor” and major chronic depression was also carried out by subdividing these latter into unipolar - recurrent and single episode - and bipolar depression. Dysthymics showed a bipolar family history closer to that of bipolar chronic major depressives which was significantly higher than that recorded in the other sub-categories.

More than half of all patients consulting at public health facilities in Cali, Colombia have been shown to present mental disorders, the majority of which were non-psychotic; there is a high female preponderance amongst the affective disorders. As in other developing countries, in Colombia depressive disorders tend to present as somatic complaints, rather than as mood disturbances. The nomenclature used to describe these disorders is poorly codified, with most patients classed as “neurotic” or “depressed”; the diagnosis of “dysthymia” is very seldom encountered. Mental disorders are frequently misdiagnosed in primary care settings; when identified, treatment of depression by GPs generally involves TCAs or MAOIs, sometimes in conjunction with anxiolytics or neuroleptics. Only very severe cases are referred to psychiatrists, and many patients purchase drugs upon the recommendation of a pharmacist. Diagnostic trends and treatment results of a comparative study of amisulpride and viloxazine carried out in 80 patients assessed by DSM III-R criteria are reported.

The results of early therapeutic trials (1960s and 70s) in mild chronic depression (neurotic patients) are difficult to extrapolate to dysthymia. Most studies conducted in the early 1980s showed reference drugs (TCAs and MAOIs) to be poorly effective in chronic mild depression usually defined with RDC. The most recent trials using DSM-III-R criteria for dysthymic recruitment showed TCAs, new MAOIs (RIMA) and SSRI to be effective. AU these compounds have a rather similar pharmacological mechanism of action. It is therefore of both practical and theoretical interest that amisulpride, a benzamide derivative blocking D2 and D3 pre-synaptic receptors, has been found effective in the treatment of dysthymia in different placebo and reference controlled trials. This result is in line with the pharmacological data on animal ‘anhedonic models’.