Atypical depression

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Atypical depression

A woman in her 30s comes to a clinic and says that for several months she has been feeling sad and hopeless and too anxious to concentrate on her work. She is afraid she may lose her job and occasionally has thoughts of suicide. She has gained 15 pounds and feels tired all the time. She has trouble falling asleep and then sleeps through her alarm. Often she finds herself bursting into tears, with her heart pounding. The symptoms began after the breakup of a romance. Her self-esteem has always been low, she says, and she has had previous episodes of depression, usually brought on by a disappointment in love. At times she has taken diet pills and been a heavy drinker, but now she is avoiding drugs and alcohol. She does not improve when given the tricyclic antidepressant imipramine, but most of her symptoms go away in a few weeks when she is switched to phenelzine, a monoamine oxidase inhibitor (MAOI).

Although most people would not find anything unusual or remarkable about this condition, it has been called “atypical depression.” Why?

The term came into use in the late 1950s when psychiatrists noticed that for some depressed patients, tricyclic antidepressants were not effective but MAOIs (at that time the only alternative) were. These patients seem to have certain other characteristics in common. They complained of many physical symptoms, one of which, often, was a feeling of heaviness in the arms and legs. They had a tendency to oversleep and overeat. They felt worse in the evening. They were not sad all the time but able to cheer up at least momentarily in response to sympathy, compliments, or a visit from a child. They were highly sensitive to what they regarded as rejection by lovers and others. Many had phobias, panic attacks, or severe premenstrual symptoms. This picture is atypical because most depressed patients are more constantly sad, wake up early rather than oversleep, feel worse in the morning rather than the evening, and eat less rather than more than average.

Despite its special features, atypical depression has never made the cut as a distinct psychiatric disorder because it has not proved to serve the purposes of a medical diagnosis. To be useful, a diagnosis must be reliable and valid. It is reliable if informed observers more or less agree on the set of symptoms it describes, and which patients have those symptoms. It is valid if it suggests clues to genetic background, biological, psychological, or social causes, progress and outcome, and potential treatments.

The diagnosis of atypical depression has not turned out to be either reliable or valid. Experts cannot agree fully on the symptoms or find clues that clearly define a cause or treatment. The response to MAOIs suggests a distinct biology, because these drugs — isocarboxazid (Marplan), phenylzine (Nardil), and tranylcypromine (Parnate) — have a unique mechanism of action: They inhibit the activity of an enzyme that breaks down the neurotransmitters norepinephrine and serotonin. But when the selective serotonin reuptake inhibitors were introduced, they proved to be as effective as MAOIs in most cases. Some studies now suggest that an individual’s depressive symptoms are often not consistent but change from one episode to the next. A patient might have atypical symptoms in one episode and completely different ones in the next episode — the same illness taking different forms at different times.

Still, mental health professionals have not abandoned the notion of atypical depression entirely. In the fourth revised edition of the diagnostic manual of the American Psychiatric Association, an episode of bipolar disorder, major depression, or dysthymia (chronic mild to moderate depression) can be described as having atypical features: “mood reactivity” (the capacity to cheer up momentarily) plus at least two of the following: increased appetite or weight gain; excessive sleep (day or night); “leaden paralysis” (that sensation of heaviness in the limbs); and a pattern of extreme sensitivity to personal rejection, even when not depressed.

About 20% of depressive episodes are thought to have these features. They are two to three times more common in women than in men (depression itself is twice as common). Depression with atypical features begins at an earlier age, tends to last longer, and is more likely to occur in people with bipolar (manic-depressive) disorder and seasonal mood disorder (winter depression).

The official description is not the only one in circulation. Some believe that the true atypical features are early onset (before age 20), chronic nature, and failure to respond to tricyclic antidepressants, without reference to oversleeping or overeating.

Atypical depression could be a window into connections between depression and other disorders. One approach to a biological distinction between atypical and typical depression goes by way of the hypothalamic-pituitary-adrenal (HPA) axis, which governs responses to stress. The hypothalamus, at the base of the brain, sends corticotropin releasing factor (CRF) to the pituitary gland, directing it to secrete adrenocorticotropic hormone (ACTH). ACTH travels in the bloodstream to the adrenal glands, which release cortisol to prepare the body for emergency action.

The body is normally protected from excessive arousal by a feedback signal in which rising cortisol levels cause the hypothalamus to stop issuing CRF. In the rare condition known as Cushing’s disease, the pituitary is damaged and does not respond. It continues to release ACTH, and cortisol levels stay high despite low levels of CRF. Low CRF is also associated with chronic fatigue syndrome, winter depression, and postpartum depression — all of which, like Cushing’s disease, often produce atypical depressive symptoms, especially overeating and oversleeping. The HPA axis also malfunctions in typical cases of depression, but CRF levels are high rather than low, and the difference in symptoms may correspond.

Atypical depression is also linked to personality disorders. Personality is sometimes compared to the immune system and disorders like depression to infectious diseases. A person with an inadequate emotional immune system is more likely to develop symptoms of all kinds under stress. The longer an episode of depression lasts — and depressions with atypical features last longer — the more it begins to look like a reflection of personality. And the rejection sensitivity that is incorporated into the definition of atypical depression resembles a personality trait rather than a mood.

The tendency to anticipate failure and humiliation and give up easily when frustrated is a characteristic of avoidant personality (passive, timid, submissive, easily hurt). Borderline personalities are emotionally unstable, self-destructively impulsive, chronically bored or angry, with constantly shifting moods. Histrionic personalities are flamboyant, self-dramatizing, self-centered, and emotionally shallow. These personality descriptions have much in common with the rejection sensitivity and mood reactivity of atypical depression.

Bipolar depression, like atypical depression, is characterized by mood reactivity and often by the atypical physical symptoms of oversleeping and overeating. Especially in their less intense variants, bipolar symptoms can be difficult to distinguish from depression with atypical features. Some research suggests that a family history of bipolar disorder is more likely in depressed people with the atypical symptoms of leaden paralysis and oversleeping.

Some believe atypical depression is related to a whole group of disorders that involve emotional instability resulting from defective mood regulation. This category extends beyond mood disturbances in the narrow sense. It may include not only borderline personality and avoidant personality but panic disorder, obsessive-compulsive disorder, and bulimia. Many of these disorders are now routinely treated with antidepressants and mood stabilizers.

Today the diagnosis of depression with atypical features does not dictate any particular treatment. MAO inhibitors are rarely a first choice for depression because of their many side effects, which include drowsiness, dizziness, insomnia, and a sudden, potentially dangerous rise in blood pressure when combined with certain foods (pickles, cheese, red wine). The preferred antidepressants are selective serotonin reuptake inhibitors like fluoxetine (Prozac). When depression with atypical features turns out to be a form of bipolar disorder, lithium or anticonvulsants can be prescribed. Patients who also have panic disorder, phobias, or obsessive-compulsive rituals may need both behavioral treatment and antidepressants. And long-term psychotherapy (along with antidepressants) may be especially useful for patients with atypical depression because of their changeable moods and symptoms that resemble a personality disorder.

Last updated:	August 21, 2006