Suicide Risk and Melancholic Features of Major Depressive Disorder: A Diagnostic Imperative Robert I. Simon, M.D.* Suicide risk is increased in patients with Major Depressive Disorder with Melancholic Features compared to patients with Major Depressive Disorder. Gruneberg et al (1) compared suicide attempts associated with melancholic versus non-melancholic major depression in 377 patients who were consecutively enrolled in the depression protocols of two university hospitals. One hundred fifty-one participants (40%) met DSM-IV criteria for melancholia. They found that melancholic patients had more serious suicide attempts and increased probability and lethality of future attempts. Patients without melancholia usually did not require psychiatric hospitalization as frequently as melancholic patients. McGrath et al (2), using a STAR*D protocol, found that 23.5% of outpatients met the DSM-IV criteria for melancholic symptom features. These patients were significantly more likely than study participants without melancholic features to have made prior suicide attempts and were judged to be a suicide risk at the time of study entry. The finding that approximately a quarter of patients with major depression met DSM-IV specifier criteria for Melancholic Features is
consistent with other studies (3). Study participants who met criteria for melancholic features demonstrated higher depression severity scores, greater Axis I comorbidity (mainly anxiety and substance use disorders), and a lower likelihood of remission rate with treatment by an SSRI. Melancholia Leventhal et al (4) found that melancholic depression is qualitatively different in symptomatology than non-melancholic depression. The distinction is supported by biological ( endogenous ) factors, personality traits, unresponsiveness to treatment and increased risk of suicide. Khan et al. found that socio-demographic and other external factors usually are not as prominent as occurs with non-melancholic depressed patients (3). They conclude that genetic or biological factors play an important role in the development of melancholic symptoms. The DSM-IV-TR (5) specifier criteria for Melancholic Features, condensed below, include: A. Either of the following: Loss of interest or pleasure in all, or almost all, activities Lack of reactivity to pleasurable stimuli 2
B. Three (or more) of the following: Distinct quality of mood (e.g., different from bereavement sadness) Depression worse in the morning Early morning awakening (at least 2 hours before usual awakening) Marked psychomotor retardation or agitation Significant anorexia or weight loss Excessive or inappropriate guilt DSM-IV-TR lists a number of clinical and biological markers associated with melancholic depression. These include: Psychomotor changes nearly always present (observable) Less likely to have a premorbid personality disorder Less likely to have a clear precipitant Less likely to respond to a trial of placebo medication More frequent as inpatients than outpatients Less likely to occur in milder compared with more severe Major Depressive Episodes 3
More likely to occur in patients with psychotic features More frequently associated with laboratory findings: Dexamethasone nonsuppression Elevated cortisol concentrations in plasma, urine and saliva Alteration of sleep EEG profiles Abnormal asymmetry on dichotic listening tasks Suicide Risk Next to eating disorders, major depression is the psychiatric disorder most frequently associated with suicide (6). As noted above, Melancholic Features substantially increase suicide risk (1). Melancholia bristles with suicide risk factors, in addition to the increased severity of depression. Concurrent psychosis, comorbidity and the lower likelihood of remission add increased suicide risk. McGrath et al (2) found that melancholic features were associated with significantly reduced remission following treatment with Selective Serotonin Reuptake Inhibitors (SSRIs). 4
The diagnosis of Melancholic Features can be missed for a variety of reasons. A lack of diagnostic rigor may not distinguish between melancholic and non-melancholic depression. Moreover, the increased risk of suicide associated with Melancholic Features may not be considered. Clinical settings can also influence diagnosis. Shortened inpatient length of stay may not allow time for correct diagnosis, especially when clinicians treat patients for brief periods of time. In Partial Hospitalization Programs (PHPs), allied mental health professionals may not place sufficient emphasis on diagnosis, focusing more on patients psychological dynamics and interpersonal relationships. Melancholic patients are less frequently treated in outpatient settings. Thus, clinicians may have less experience in the diagnosis of this condition. Split treatment where the psychiatrist sees patients infrequently for 10 or 15 minutes for medication management may not allow for a sufficient time to make the correct diagnosis, even after an initial 45 minute or hour evaluation. Moreover, the diagnosis of Melancholic Features may only become apparent over time. Close collaboration and communication between psychiatrist and therapist can facilitate accurate diagnosis (7). All patients diagnosed with major depression should be carefully assessed for Melancholic Features. 5
The diagnosis of Melancholic Features can also be overlooked because of symptom overlap between Melancholic and Non-Melancholic core depression. Melancholia, as a specifier, does not have the diagnostic clarity of a stand-alone psychiatric disorder. In addition, the A criteria of Melancholic Features (loss of pleasure in all, or almost all, activities, and lack of reactivity to usually pleasurable stimuli) are dimensional expressions of severe depression, while the B criteria are categorical. The core feature of melancholia is the severity of depression, a dimensional criterion that can be difficult to assess diagnostically. Treatment and Management The elevated suicide risk associated with melancholic patients requires accurate diagnosis, systematic suicide risk assessment and evidence-based treatments. Melancholic patients respond more favorably to tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), than SSRIs. (8) (9). In addition, electroconvulsive therapy (ECT) is also indicated for the melancholic patient, especially if the patient is acutely suicidal and unresponsive to pharmacotherapy (10) (11). Some melancholic patients are responsive only to ECT. If a patient diagnosed with Major Depressive Disorder is not improving despite aggressive treatment, the diagnosis should be revisited to rule in or out 6
Melancholic Features. With delay in treatment, the depression can become entrenched, resulting in the patient experiencing hopelessness, demoralization and increased suicide risk. Delay may also adversely affect the patient s employment status and personal relationships. Conclusion All patients with the diagnosis of Major Depressive Disorder should be assessed for Melancholic Features. Melancholic patients usually experience greater severity of depression than non-melancholic patients. In addition, psychosis, comorbidity (frequently anxiety and substance abuse), poor response to SSRIs and increased suicide risk are associated with melancholia. Systematic suicide risk assessment coupled with aggressive treatment with TCAs, MAOIs or ECT are indicated for the suicidal, melancholic patient. 7
References 1. Grunebaum MF, Hanga CG, Oquendo MA, et al: Melancholia and the probability and lethality of suicide attempts. British Journal of Psychiatry 184:534-535, 2004 2. McGrath PJ, Khan AY, Trivedi MH, et al: Response to selective serotonin reuptake inhibitors (citalopram) in major depressive disorder with melancholic features: a STAR*D report. Journal of Clinical Psychiatry 69:1847-1855, 2008 3. Khan A, Carrithers J, Preskorn SH, et al: Clinical and demographic factors associated with DSM-IV melancholic depression. Annals of Clinical Psychiatry 18:91-98, 2006 8
4. Leventhal AM, Rehm LP: The empirical status of melancholia: implications for psychology. Clinical Psychology Review 25:5-44, 2005 5. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. Text Revision (DSM-IV-TR) American Psychiatric Association, Washington, DC, 2000, pp 419-420 6. Harris CE, Barraclough B: Suicide as an outcome for mental disorders. British Journal of Psychiatry 170:205-228, 1997 7. Simon RI: Assessing and Managing Suicide Risk: Guidelines for Clinically Based Risk Management. American Psychiatric Publishing. Arlington, VA, 2004 8. Peselow ED, Sanfilipo MP, Difiglia C, et al: Metabolic/endogenous psychiatry. American Journal of Psychiatry 149:1324-1334, 1992 9. Angst J, Scheidegger P, Stahl M: Efficacy of moclobemide in different patient groups: results of new subscales of the Hamilton Depression Rating Scale. Clinical Neuropsychopharmacology 1993; 26 (suppl 2) S55-S62 10. Kim HF, Marangell LB, Yudofsky SC: Psychopharmacological Treatment and Electroconclusive Therapy in Simon RI, Hales RE: Textbook of Suicide 9
Assessment and Management. American psychiatric Publishing, Arlington, VA, 2006, pp 199-220 11. Practice Guidelines for the Treatment of Psychiatric Disorders. Compendium 2006. American Psychiatric Association, Arlington, VA 2006, p 800 10