The proper identification of melancholia as outlined in the position paper requires the presence of prototypic signs across all or most of the following domains:
• Disturbance in affect, usually disproportionate to any stressor and marked by unremitting apprehension, morbid thoughts, and blunted emotional response: so that clear reactivity of mood is generally inconsistent with a diagnosis of melancholia
• Psychomotor retardation that may be expressed in reduced facial and vocal reactivity, as well as by anergia or, in severe instances, torpor
• Psychomotor agitation that may manifest the painful melancholic mood by profound apprehension, anguish, bewilderment, perplexity, and motor agitation (eg, hand-wringing and pacing) or in severe instances, by pathologic guilt, importuning themes, and stereotypic movements
• Cognitive impairment with distinctly impaired concentration
• Vegetative dysfunction displayed by loss of sleep (most commonly early morning wakening), appetite, and weight, as well as diurnal variation (with mood and energy generally worse in the morning)
• Psychosis (in some patients) expressed as delusions and/or hallucinations; nihilistic convictions of hopelessness, guilt, sin, ruin, or disease are common preoccupations
Patients with melancholia are very likely to have disorders in endocrine metabolism that can be identified through laboratory tests, Fink said.
Three tests help define melancholia, Fink said: the dexamethasone(Drug information on dexamethasone) suppression test (DST), with measurement of cortisol levels; the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH); and a sleep electroencephalogram (EEG).
“The TSH response to TRH test is more often abnormal in melancholic depression than in other forms of illness, but this test is not as sensitive as the DST. The DST is a measure of the severity of melancholia. Results normalize with remission of the illness and become abnormal again with relapse. The sleep EEG is abnormal in many patients who have melancholia, but it is not an easy test, and it is best used to better define the syndrome,” Fink said.
While lacking absolute sensitivity and specificity for diagnosing melancholia, the tests could be helpful, Parker said, noting that further clarification studies are needed.
Patients with melancholic depression generally respond well to tricyclic antidepressants (TCAs) or ECT, Fink said. Remission rates for effective ECT are on the order of 80%.
“Studies of melancholic depression do not show a benefit from psychotherapy,” Fink said. “Among melancholic depressed patients treated with psychotherapy only, there is a high incidence of suicide.”
Parker reported that there is a 10% response to placebo, a 30% to 40% response to SSRIs, a 40% to 50% response to dual-action antidepressants, a higher response to TCAs, and possibly a slightly higher again response to monoamine oxidase inhibitors (MAOIs).
“Adding low-dose atypical antipsychotic drugs (or lithium(Drug information on lithium)) to the antidepressant can further advance a response in some patients, due to true augmentation effects,” he said. “Melancholia responds well to ECT, although it is rarely required. The age of the patient has a distinct effect on treatment outcome (ie, as patients become older, their response to narrow-action drugs (eg, SSRIs) diminishes.”
Parker told Psychiatric Times that at the Black Dog Institute, they are using a computer-based algorithm of 32 clinical features to identify patients with melancholia.4 “Clinically, we also weigh the presence of a family history, and episodes that are more severe and persistent than might be expected by any (if any) antecedent stressors,” he said.
Recently, Black Dog Institute began a clinical trial for melancholic depression. The 12-week trial consists of 3 separate treatments involving patients with melancholic depression in each group. The treatments are individual cognitive behavioral therapy (CBT), an SSRI, and a broad-action antidepressant drug approach. Patients in the third group will start therapy with a dual-action antidepressant. If no response occurs with the dual-action drug, a progressive broadening strategy of medication (ie, antipsychotic, TCA, MAOI) will be followed.
“Clearly, the hypothesis is that medication is superior to CBT and that broad-action approaches are superior to an SSRI,” Parker said. “The study is powered on relevant data (ie, a meta-analysis showing that TCAs are 3 times more effective than SSRIs), and we anticipate that we will need a sample size in excess of 100.”