25 Patients suffering from severe depression, for example, reach a score of at least 25 on the HAM-D17 scale26 or 30 on the MADRS.27 The subdivision according to the severity of depression is of clinical importance because for example, the NICE (National Institute for Clinical Excellence) guidelines28 recommend antidepressant

treatments in primary care in moderate and severe, but not mild, depression. For patients suffering from mild depression, NICE recommends “watchful observation” or psychological intervention as first-line treatment, and antidepressants only in the case of refractoriness.28 In moderate Inhibitors,research,lifescience,medical depression, EGFR inhibitor nonbiological treatments are also the first choice in some guidelines although, in reality, most moderately depressed patients do require additional antidepressant medication. Furthermore, there is a distinct probability of response using phytotherapcuti.es such as hypericum perforatum (St Johns wort)29-32 or benzodiazepines without Inhibitors,research,lifescience,medical antidepressants (even if this option is not Inhibitors,research,lifescience,medical recommended due to their potential for causing dependency and addiction)33 only in people with mild-to-moderate depression. Moreover, it has been suggested that drug-placebo differences after treatment with antidepressant medication are relatively small and increase as a function of baseline

severity of depression.34 However, according to other reports about the effectiveness of antidepressants, eg, duloxetine35 or fluoxetine,36 in mild-tomoderate depression,

the treatment of those subgroups of depressed patients also has been recommended.37 Nevertheless, there is some evidence that especially severe depressive Inhibitors,research,lifescience,medical syndromes show a better response to ECT, to tTCAs38 (TCA) and to dually acting Inhibitors,research,lifescience,medical substances39 such as vcnlafaxine, duloxetine, or mirtazapine. Especially in severely depressed and hospitalized patients, mixed serotonergic and noradrenergic TCAs compared favorably with selective serotonin reuptake inhibitors (SSRIs)38, 40 and the reversible monoamine oxidasc-A inhibitor (RIMA) moclobemide41 However, escitalopram has also shown good results in severe depression42 (Montgomery et al, unpublished data). Summarizing PAK6 published study results of recent years, in spite of the discouraging meta-analytic results of Kirsch et al,43 it has to be stated that there is an overall worldwide consensus that antidepressants are efficacious in the treatment of depression, regardless of the severity of the disease.41 Depression with psychotic symptoms Psychotic features of depression such as hallucinations or delusions, eg, delusional hypochondria, feelings of guilt or nihilistic thoughts, are predominantly mood-congruent, but may also be noncongruent to the depressed mood.