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Depression is a disorder with heterogenic etiology and variable clinical features. Response to the treatment is defined as a 50% reduction in admission symptoms. Recent studies with large numbers of patients have revealed that acute phase treatment should last for 6 weeks, including at least 4 weeks with effective dosages. Approximately 60% of patients have a response to the first antidepressant treatment. The remainder, 40% of patients, either has a partial response or they are non-responders (Fava 1996).
At the end of 6 weeks with optimum treatment dosing, if symptoms have not reduced by 20-25%, patients are described as non-responders and drug treatment should be switched to another type of antidepressant medication. Patients, who do not respond to trials of adequate dosages and periods of two or more different classes of antidepressant treatments, are considered as treatment-resistant depression (TRD). If there is a partial response to antidepressant treatment, waiting for couple of weeks is the rational approach. The patients who have high depression scores at the initial evaluation have relatively higher degrees of partial or non-response to antidepressant medications. These cases are more likely to have comorbid axis 1 and axis 3 physical disorders. An 8-12 week period of effective antidepressant treatment should be applied in these cases. Thase and Rush, proposed 5-stage-model for the description of TRD (1997). Later in the STAR D study, Rush et al. developed sequences of treatment alternatives for relieving depression (Rush et al. 2003).
On the other hand, increasing drug dosages results in more side effects and adverse reactions. Some patients may be low metabolizers and higher doses may result in significant side effects. Also fast metabolizer patients may respond to higher doses of medications. Efficacy of atypical antipsychotics, stimulants, pindolol, lithium, and lamotrigine have been tested for augmentation in ongoing treatment for TRD in clinical trials (Caravalho et al 2009). In severe cases with no response or partial response to treatment, inpatient treatment should be considered.
Non-responders or partial responders can be treated with electro convulsive therapy with anesthesia or non-responders can be treated with rTMS (Paul et al 2006). Selected non-responsive cases may be treated with more invasive techniques such as deep brain stimulation or vagus nerve stimulation. Biological predictors should be identified to irecognize patients who will not respond to two adequate trials of different antidepressant.
In addition, psychotherapeutic interventions during the treatment period, such as observing and revealing automatic thoughts, assumptions, and basic beliefs and depressive schemas, should be evaluated and behavioral and cognitive interventions can be applied. Activity scheduling and participating in regular exercise might also be helpful to some degree.