Melancholic depression

Mirtazapine is primarily metabolized by CYP450 2D6, 1A2, and 3A4. Mirtazapine is at least as effective as the tricyciic antidepressants and trazodone in a wide range of patient subgroups, including in- and outpatients with moderate to severe depression. It also appears to be at least as effective as the serotonin and norepinephrine reuptake inhibitor venlafaxine in the treatment of severely depressed melancholic patients. 

Endogenous depression. A serious melancholic state unrelated to the Individual s exteinal environment. 

Wong ML, Kling MA, Munson PJ, Listwak S, Licinio J, Prolo P et al. Pronounced and sustained central hypernor-adrenergic function in major depression with melancholic features relation to hy-percortisolism and corticotropin-releasing hormone. Proc Natl Acad Sci USA 2000 97 325-330. 

The authors wanted to select indicators that specifically tap melancholic depression. To evaluate this construct, a principal components analysis of the joint pool of K-SADS and BDI items was performed. Two independent statistical tests suggested a two-component solution, but the resulting components appeared to reflect method factors, rather than substantive factors. Specifically, all of the BDI items loaded on the first component (except for three items that did not load on either component) and nearly all of the K-SADS items loaded on the second component. In fact, the first component correlated. 98 with the BDI and the second component correlated. 93 with the K-SADS. Ambrosini et al., however, concluded that the first component reflected depression severity and the second component reflected melancholic depression. This interpretation was somewhat at odds with the data. Specifically, the second component included some K-SADS items that did not tap symptoms of melancholia (e.g., irritability and anger) and did not include some BDI items that measure symptoms of melancholia (e.g., loss of appetite). 

Insomnia Due to Another Psychiatric Illness. Insomnia is often a symptom of mood and anxiety disorders. Depression is classically associated with early-morning awakening of the melancholic type, whereas so-called atypical depression leads to hypersomnia. Anxiety commonly leads to problems falling asleep. These patterns are not invariable. One should therefore always perform a thorough assessment for anxiety or depression in patients complaining of insomnia. 

TCAs in more serious forms of depression such as melancholic or psychotic depression. Some studies have suggested that the SSRls do not work as well as the TCAs in melancholic depression (Roose et al. 1994]. Likewise, one study has suggested that venlafaxine, a drug with a mechanism of action similar to that of the TCAs, was superior to fluoxetine in the treatment of inpatients with melancholic depression (Clerc et al. 1994]. Still, other metaanalyses have failed to find a difference in the efficacy of SSRls versus TCAs in serious forms of depression [Nierenberg 1994]. Nonetheless, given that most studies have employed TCAs, and some debate exists about the utility of SSRls in severe subtypes, it may be prudent to start with a TCA in most patients until the debate is further resolved. For patients who present a significant suicide risk or who have not been able to tolerate TCAs, the SSRls in combination with a standard antipsychotic appears an effective option. 

Although some data suggest that TCAs are superior for treating melancholic depression, most clinicians choose newer agents because of improved tolerability and safety. 

TCAs derive their name from their chemical structure aU tricyclics have a three-ring nucleus. Currently, most clinicians are moving away from using TCAs as first-line drugs relative to the newer antidepressants, they tend to have more side effects, to require gradual titration to achieve an adequate antidepressant dose, and to be lethal in overdose. Some data suggest that TCAs may be more effective than SSRIs in the treatment of major depression with melancholic features (Danish University Antidepressant Group 1990 Perry 1996) however, many skilled clinicians and researchers continue to prefer the newer antidepressants, even for patients with melancholia, for the aforementioned reasons. Newer medications that affect both norepinephrine and serotonin (e.g., venlafaxine and mirtazapine) also may have superior efficacy in severely iU depressed patients or when remission is defined as the outcome (Thase et al. 2001). 

Perry PJ Pharmacotherapy for major depression with melancholic features relative efficacy of tricyclic versus selective serotonin reuptake inhibitor antidepressants. J Affect Disord 39 1—6, 1996... 

The severity of the disorder appears to contribute to the neuropsychological deficits this relationship is most clearly recognized in the so-called melancholic subtype of depression. Another relevant factor is age cognitive deficits are generally more severe and more widespread in old than in younger depressed patients (Butters et al., 2000). 

The 17-item HDRS is the most commonly used scale in antidepressant clinical trials. This version of the HDRS is heavily weighted toward melancholic symptoms. There are also 21-item, 24-item, and 28-item versions with the additional items assessing nonmelancholic symptoms. The Montgomery-Asberg Depression Scale (MADRS) is another instrument that is frequently used in antidepressant clinical trials. 

Depressive subtype, particularly psychotic or melancholic as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV)... 

ECT should be considered for more severe forms of depression (e.g., those associated with melancholic and psychotic features, particularly when the patient exhibits an increased risk for self-injurious behavior) or when there is a past, well-documented history of nonresponse or intolerance to pharmacological intervention. Limited data indicate that bipolar depressed patients may be at risk for a switch to mania when given a standard TCA. A mood stabilizer alone (i.e., lithium, valproate, carbamazepine, lamotrigine), or in combination with an antidepressant, may be the strategy of choice in these patients. Some elderly patients and those with acquired immunodeficiency syndrome may also benefit from low doses of a psychostimulant only (e.g., methylphenidate) (see also Chapter 14, The HIV-Infected Patient ). Fig. 7-1 summarizes the strategy for a patient whose depressive episode is insufficiently responsive to standard therapies. 

Hicks F, Robins E, Murphy G. Comparison of adinazolam, amitriptyline, and placebo in the treatment of melancholic depression. Psychiatry Res 1987 23 221-227. 

ECT is the most effective treatment for more severe depressive disorders, often characterized by melancholic and/or psychotic features. Although primarily used for an acute episode, ECT may also be a useful maintenance strategy for patients with frequent relapses despite adequate pharmacotherapy. 

In an open trial of antipsychotics for outpatients with BPD, Teicher and colleagues ( 243) noted that sustained melancholic depression developed in three patients, necessitating removal from the trial and treatment with antidepressants. In this context, Gardner and Cowdry (248) also reported that melancholia developed in three patients on CBZ, necessitating drug discontinuance and treatment for depression. Flence, clinicians should anticipate that severe depression can develop in some patients with BPD and be prepared to treat with antidepressants. 

Lipid Profile Levels in Patients with Major Depression with Melancholic... 

In clinical studies, major depressive disorder has had four specifiers, including melancholic feature, atypical feature, catatonic feature, and postpartum onset. In the future, we should investigate the distributions of the four specifiers of depression among patients with physical illness and discuss which biological markers could link the depressive disorder and the physical illness. 

Although there are papers that discuss the relationships between cholesterol, lipid profiles, and major depression [34-39], there are few data that discuss the association between lipid profiles and depressive disorders with different phenotypes. Huang and Chen investigated the correlation between serum lipid, lipoprotein concentration, and major depressive disorder in patients evaluated for general health screening [41]. They found that analysis of covariance after age adjustment revealed significant differences in patients with melancholic feature and patients with atypical feature in serum concentrations of TG and VLDL in men and HDL in women [41]. However, there are still no reports that discuss the relationships between lipid profiles and major depression with postpartum onset or catatonic feature. In the future, large sample numbers will be needed to clarify the clinical differences in this field. 

Huang TL, Chen JF. Lipid and lipoprotein levels in depressive disorders with melancholic feature or atypical feature and dysthymia. Psychiatry Clin Neurosci 2004 58 295-299. 

Gold PW, Chroussos GP (2002) Organisation of the stress system and its dysregulation in melancholic and atypical depression high vs low CRH/NE states. Mol Psychiatry 7 254-275... 

Some individual trials of antidepressants that found no overall effects, found a relatively stronger effect in some of the most severely depressed subjects in post hoc analysis (Elkin et al. 1989 Paykel et al. 1988). However post hoc analysis is where the authors look for significant results without predetermining what particular tests are of interest. This sort of analysis is commonly referred to as a fishing expedition and it is well known that it can highlight results that are positive just by chance. Another similar trial conducted in primary care found no association between melancholic depression, that is the most severe depression, and antidepressant efficacy (Malt et al. 1999). These trials were conducted exclusively with people with relatively mild depression and so could not assess the relation over the whole severity range. The meta-analyses too were based mostly on outpatient studies. On the... 

Since different pathologies may underlie the syndrome of depression, different immunological states might be involved. Indeed, different types of MD v ere observed to exhibit different immune profiles The subgroup of melancholic depressedpatients shov ed a decreased type-1 activation— as it was observed in schizophrenic patients (Muller and Schwarz, 2007)— wMe the non-melancholic depressed patients showed signs of inflammation such as increased monocyte count and increased levels of aj-macroglobulin (Rothermundt etal., 2001). 

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