The Different Faces of Depression

Depression is not a one-size-fits-all condition. Mental health professionals have long recognized that patients tend to display reasonably distinct clusters of clinical symptoms, and they increasingly regard such clusters as subtypes of depression.

The boundaries between subtypes are often fuzzy, with some overlap of symptoms, and not every depression expert agrees on the classification system. But clinical research suggests that parsing depression into subtypes is useful in guiding treatment and in gauging the long-term outcome for patients.

At a symposium presented at a meeting of the American Psychiatric Association, doctors discussed five depression subtypes that together encompass the majority of depressed persons. These include:

• Atypical depression, which studies show accounts for 23% to 36% of all cases and is under-recognized.
• Anxious depression, which afflicts 40% of patients with major depressive disorder and poses many treatment challenges.
• Melancholic depression, a severe form of disorder that is most common among persons hospitalized for depression.
• Vascular depression, a newly recognized variety that reflects the existence of silent cardiovascular disease and is most common among persons over the age of 60.
• Psychotic depression, a severe form of disorder distinguished by mood-congruent delusions and accompanied by specific changes in brain tissue.

The distinctions first emerged several decades ago on the basis of variations in response to then-available treatments. But clinicians and researchers suggest that dissecting depression into subtypes may be even more valuable today. The subtypes may represent distinct biological pathways of disorder and may ultimately provide clues to the multiple ways depression can arise as well as express itself.

Atypical depression can manifest in both bipolar and unipolar depression, psychiatrist Jonathan W. Stewart. M.D., of Columbia University reported. Patients with this variety of disorder—about 10 million Americans—have what physicians label mood reactivity: they can be cheered up at least 50% in response to positive events in their life, albeit temporarily.

In contrast to patients with classical depression, those with atypical depression overeat regularly and binge often, gaining sometimes substantial amounts of weight. They also sleep a lot, and experience a leaden paralysis and overwhelming fatigue for much of the day, feeling as if they cannot even lift themselves out of a chair.

In addition to such physical manifestations, atypical depression is marked by a longstanding pattern of extreme sensitivity to perceived interpersonal rejection that affects functioning at work, in love, and with friends. With a trail of stormy relationships patients are either never married or divorced, and are unemployed or underemployed. Given their fear of rejection, many withdraw from relationships entirely and refuse to go on job interviews.

This variety of depression begins early—median age of onset is 17—and takes a chronic course. Depression afflicts many family members, and it tends to be of the same chronic type.

Perhaps the landmark feature of atypical depression is its responsiveness to one class of antidepressants, the MAO inhibitors. While they are no longer considered a first-line treatment because of their onerous side effects, they are regarded especially useful for people with atypical depression who fail to respond to other drugs. Cognitive therapy in conjunction with drug treatment is also effective and helps restore function.

A biology of atypical depression has not been delineated, as patients appear normal on most physiologic tests. But patterns of response to mixed-up images of faces suggests that parts of the brain that interpret emotion are not working normally.

Anxious depression covers the large gray area where symptoms of depression and anxiety co-exist or overlap. Patients typically have feelings of worthlessness and pessimism, excessive worrying and guilt, and are unable to enjoy things. The disorder is expressed physically in diminished appetite, poor sleep with frequent awakenings, and restlessness and psychomotor agitation.

In one study of 255 depressed outpatients that he conducted, psychiatrist Maurizio Fava, M.D., of Harvard reported at the symposium, 51% were found to have anxiety along with their depression. It's not clear whether the anxiety follows on the heels of feelings of worthlessness. But in 40% of the anxiously depressed, the anxiety disorder started first.

Among those whose anxiety takes the form of social phobia and generalized anxiety disorder, the anxiety tends to precede major depressive disorder. But in the case of panic disorder it usually follows the onset of the depressive disorder.

Patients are young—average age 20.6 versus 28.4 among those with major depression alone—significantly functionally impaired, and take more time to recover. They are less likely to respond to treatment and more likely to relapse, and experience less change in their depressive symptoms with treatment.

The disorder may have its origins early in life among children of a distinct temperament type who are frightened by novelty. Both the anxiety and depression may be the outcome of abnormaly high levels of hormones driving the body's stress response system.

Anxious depression typically poses a treatment dilemma for doctors. Many seek to use antidepressants that have sedating properties, although it's not clear that they need to, said Dr. Fava. Studies show that all of the antidepressants work equally well against this type of depression, although high doses may be needed. Still, in practice physicians tend to prescribe a combination of drugs for such patients, usually a tranquilizer along with an antidepressant.

Given their anxiety quotient, depressives of this type are unusually sensitive to bodily sensations. As a result, common drug side effects—such as gastrointestinal distress—are often cause for discontinuing treatment. Even when treatment continues, remission can be a long time coming. Cognitive therapy can be very helpful.

Melancholic depression is often a synonym for severe depression, and it is far more common among those hospitalized for depression than among those in the community. Affected persons lack pleasure in almost all activities and do not react to pleasurable stimulation. They may experience extreme slowness of movement or agitation. Their depression is regularly worse in the morning and is accompanied by lack of appetite and weight loss.

Melancholic depressives may also ruminate over the same thoughts and experiences, and feel excessive guilt. Their depression takes on a life of its own: the more episodes they have, the more autonomous such episodes seem, less likely to be set off by stressful events. And patients do not respond to psychotherapy, at least not before successful drug treatment, reported J. Craig Nelson, M.D., of Yale.

Studies he and others have conducted show that the most helpful drugs for this type of disorder are not the SSRIs but agents that block the reuptake of norepinephrine as well as of serotonin. "Some drugs," he said, referring to dual-action agents like venlafaxine and mirtazapine, "may treat more symptoms."

Psychotic depression was once another term for severe depression, but the more refined the tools scientists apply to dissect the disorder, the more distinctive this variety appears, especially biologically. Not only is this type of depression severe, life-impairing and marked by suicide attempts, it is accompanied by delusions that reflect the depressed mood and guilt patients feel.

Biological tests show the patients have a distinct abnormality in the system that controls production of stress hormones, said Linda L. Carpenter, M.D., of Brown University. Imaging studies reveal significant brain atrophy. The decrease in brain tissue likely reflects the toxic effects of excess stress hormones, namely cortisol.

Despite the proliferation of antidepressant drugs, the best treatment for psychotic depression is electroshock therapy. But drugs now in development may offer some advantage. Dr. Carpenter specifically cites agents that interfere with cortisol by blocking receptors for it.