New classification of depressive subtypes of depression proposed

May 3 2010

Lichtenberg and Belmaker propose a new classification of depressive subtypes of depression in the current issue of Psychotherapy and Psychosomatics. They argue that a simple diagnosis is no longer sufficient to guide treatment.

Recent years have witnessed a growing awareness of problems that call for a reassessment of how best to classify depression. It is unlikely that a syndrome as polymorphic and widely diagnosed as major depressive disorder (MDD) will reflect a single process. Attempts to delineate different forms of depression by statistically analyzing the symptomatology of large samples of patients without taking into consideration life events or childhood history have been unsuccessful. It may be necessary to consider childhood trauma, marital and employment stress, and medical health in diagnosing subtypes of depression. Epidemiologic data on the effects of childhood trauma, unemployment and divorce on depression incidence are strong. DSM-IV does make one allowance for circumstances by including a bereavement exclusion. However, it seems that bereavement is not different from other losses and stresses that are associated with depression.

In clinical practice, depression is often resistant to standard antidepressant medication, and a large percentage of patients respond just as well to placebo. The DSM broad diagnosis of MDD does not encourage a search for subtypes of depression that may require specific treatment. Most studies are commercially sponsored multicenter projects, and lump many possible subgroups under the rubric of MDD.

In fact, most clinicians subtype depression as a matter of course when describing patients to colleagues. It may be that the era of large commercial studies of antidepressants using MDD as a diagnosis is over. It may be possible to kick start the system by subtyping depression to encourage a period of small investigator-initiated studies of potential new treatments by subtype. In this paper, the Authors propose an intuition-based proposal for heuristically classifying depressions which, of course, is not  an evidence-based replacement of the present DSM-IV MDD. These subtypes are the following:

Type A: Depression with Anxiety, characterized by an enduring tendency to experience anxiety and depression, and to show poor resilience under stress.

Type B: Acute Depression. This subtype has episodes that are relatively discreet and develop with no apparent precipitating stress, or the stress may be disproportionate to the intensity and duration of the depression. The severity of the depression can deteriorate into intense psychological pain and psychomotor retardation or agitation. Several authors have suggested that this subtype of depression should be termed 'melancholia'.

Type C: Adult Depression after Childhood Trauma. This form of depression may be unique. Individuals suffering early trauma or loss may develop lasting neurobiological changes, which render them vulnerable to stress throughout their life. In particular, sensitization of the hypothalamic-pituitary-adrenal (HPA) axis may remain throughout life.

Type D: Depressive Reaction to Separation Stress. This can be precipitated by acute psychosocial trauma such as bereavement, divorce, job loss or forced emigration, and may sometimes be more severe than other forms of depression. For months, and sometimes years afterwards, some may experience sadness, apathy, insomnia and pessimism.

Type E: Postpartum Depression. This has a typical peak onset in the first 3 months following delivery. There are vast reductions in estradiol and progesterone levels postpartum, but their exact relevance to the development of depression remains unproven. Psychosocial factors, such as an unsupportive partner or an unwanted pregnancy, have also repeatedly been found to be relevant to the development of postpartum depression.

Type F: Late-Life Depression. This occurs in elderly people with no prior personal or family history of depression, but often with risk factors for cardiovascular disease, such as hypertension, diabetes mellitus, smoking or hypercholesterolemia. The patient describes a gradual loss of energy and interest, and a diminishing ability to cope. Cognitive testing may show impairment.

Type G: Psychotic Depression. This form features delusions and severe disturbances in work and social function. Hyperactivity of the HPA axis as measured by dexamethasone nonsuppression is present in at least half of the patients. Antipsychotic medication in addition to antidepressants is indicated.

Type H: Atypical Depression. This subtype characterizes patients who show hypersomnia and hyperphagia instead of the insomnia and weight loss typical of acute depression. They have more anxiety, including panic disorder and social phobia, and they are more likely to be a suicide risk and to abuse drugs.

Type I: Bipolar Depression. This occurs in patients with previous episodes of mania and should also be considered in depressed patients with a strong family history of bipolar disorder.

Type J: Depression Secondary to Substance Abuse or to a Medical Condition. This subtype, which is recognized by DSM-IV, is a diverse group of disorders that can be difficult to treat. It is a striking biological fact that substances and medical conditions as diverse as therapeutic corticosteroids, illicit cocaine use or pancreatic carcinoma can cause depression.

Perhaps it is time for a paradigm shift. The subtypes discussed above can be operationalized, and new treatment trials powered for the smaller populations available for each subtype. The large pool of world depression investigators occupied with multicenter clinical trials of diminishing returns might be encouraged to initiate smaller trials in some of the specific subtypes. There is no guarantee of success in such a paradigm shift, but it is time for a change.

Subtyping of depression could lead to identification of subtypes that are more responsive to current pharmacological treatment, and aid in separating out the large burden of worldwide depression for which current antidepressants are not a highly effective treatment. This could help resolve the controversy over the appropriateness of current antidepressant education campaigns in the developing world.