Depression subtypes, treatment

The initial choice of therapy is also dictated by the severity of the depression (e.g., the severity of depressive symptoms impedes an adequate trial of psychotherapy), subtype of depression (e.g., presence of psychosis, seasonal depression, or treatment-resistant depressions) presence of comorbid disorders, prior treatment history, child and parent motivation toward treatment, and the clinician s motivation and expertise in implementing any specific intervention. 

Major depression represents a syndrome of different etiologies. Thus, various depressive subtypes may respond differently to different treatments. Unfortunately, to date, no litmus test for matching the depressive subtype to the appropriate treatment has been identified. Therefore, what we now call stage I TRD may often be more accurately construed as treatment mismatching. 

Anton RF Jr, Burch EA Jr Response of psychotic depression subtypes to pharmacotherapy. J Affect Disord 28 125-131, 1993 Anton SF, Robinson DS, Roberts DL, et al Long-term treatment of depression with nefazadone. Psychopharmacol Bull 30 165-169, 1994 Aoba A, Kakita Y, Yamaguchi N, et al Absence of age effect on plasma halopeiidol neuroleptic levels in psychiatric patients. J Gerontol 40 303-308, 1985 Appel SC Treatment of Alzheimer disease, in Chnical Imphcations of Neurotrophic Factors. Edited by Appel SC. Philadelphia, PA, Dppincot-Raven, 1997, pp 156-175... 

Aronson TA, Shukla S, Hoff A, et al. Proposed delusional depression subtypes preliminary evidence from a retrospective study of phenomenology and treatment course. J Affect Disord 1988 14 69-74. 

A therapeutic alternative for treatment of anxiety and depression is the use of 5-HT1A agonists. Azapirones comprise the major class of 5-HT1A agonists of which buspirone (Buspar [4]) is the only FDA-approved 5-HT1A selective agonist (relative to the other 13 serotonin receptor subtypes) for anxiety currently on the US market (Scheme 19.1). Buspirone has shown efficacy in randomized controlled trials of GAD for which it was approved [5-7]. Unlike benzodiazepines, buspirone is not addictive... 

Future directions for research on hypericum may continue the work done in clinical efficacy. More specifically, studies may be of interest that examine its effects in treatment of more severe depression and different subtypes of depression. The comparative efficacy of different hypericum preparations could be further investigated, and optimum dosages need to be established (Linde et al. 1996). Further work is needed to compare hypericum s efficacy and side effects with those of the SSRIs or atypical antidepressants, because published studies to date have only compared it with tricyclics. 

The term "bipolar disorder" originally referred to manic-depressive illnesses characterized by both manic and depressive episodes. In recent years, the concept of bipolar disorder has been broadened to include subtypes with similar clinical courses, phenomenology, family histories and treatment responses. These subtypes are thought to form a continuum of disorders that, while differing in severity, are related. Readers are referred to the Diagnostic and Statisticial Manual of Mental Disorders of the American Psychiatric Association (DSM-IV) for details of this classification. 

It is likely that TCA drugs produce their therapeutic benefits by acting at both serotonin and norepinephrine synapses. The literature also supports the notion of an interdependence of these two monoamine systems in the treatment of depression. The time-dependent changes in the flow of synaptic information through individual receptor subtypes within the norepinephrine and serotonin synapses following chronic TCA administration are summarized in Figure 33.3. 

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. 

Charney DS, Nelson JC Delusional and nondelusional unipolar depression further evidence for distinct subtypes. Am J Psychiatry 138 328-333, 1981 Charney DS, Menekes DB, Heninger GR Receptor sensitivity and the mechanism of action of antidepressant treatment. Arch Gen Psychiatry 38 1160-1180, 1981 Charney DS, Price LH, Heninger GR Desipramine-yohimbine combination treatment for refractory depression. Arch Gen Psychiatry 43 1155-1161, 1986 Charney DS, Goodman WK, Price LH, et al Serotonin function in OGD a comparison of the effects of tryptophan and mGPP in patients and healthy subjects. Arch Gen Psychiatry 45 177-185, 1988... 

Prusoff, B.A., Weissman, M.M., Klerman, G.L., Rounsaville, B.J. Research diagnostic criteria subtypes of depression their role as predictors of differential response to psychotherapy and drug treatment. Arch. Gen. Psychiatry 37, 796-801, 1980. 

Clarify atypical or specific subtypes of presentations that may not benefit from standard treatments (e.g., atypical or psychotic depressive disorders). 

Failure to identify the specific subtype may delay the most effective treatment, particularly with psychotic depression. 

The search for any biological markers of depression, let alone those that might be predictive of antidepressant treatment responsiveness has been disappointing. It is currently not possible to predict which patient will respond to antidepressants in general or to any specific antidepressant drug. However, it is well established that no matter what the subtype, some patients with any known form of unipolar depression will respond to antidepressants, including those individuals with melancholia as well as those with dysthymia. 

Meanwhile, benzodiazepines became second-line treatments or augmentation treatments for these anxiety disorder subtypes in the 1990s. While buspirone continues to be recognized as a first-line general anxiolytic, it has not developed a convincing efficacy profile for anxiety disorder subtypes or for the treatment of major depressive disorder. 

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