It is a commonly held belief among mental health care providers that patients from the Western Pacific region with major depressive disorder (MDD) and anxiety disorders disproportionately present with somatic symptoms as opposed to emotional symptoms. Cultural norms, such as the stigma associated with psychiatric disorders, may lead members of this population to ignore the emotional aspects of these disorders or deny the presence of psychological symptoms. Empirical support is provided by the lower prevalence of these disorders in some Western Pacific nations in relation to the rest of the world. For example, MDD rates in India (9%), Japan (2%), China (2% to 4%), Malaysia (8%) and Australia (3%) are generally lower than rates in the United States (16%) and worldwide (10%). These discrepancies may be the result of missed diagnoses. Misdiagnosis is related to the increased somatization of MDD symptoms in these populations. As defined by the WHO, the Western Pacific region consists of 37 countries with a total population of 1.8 billion people (1.3 billion in China alone) with diverse cultural backgrounds and demographic profiles, which makes the issue of cultural effects on MDD diagnosis more complex.

Patients with MDD or anxiety disorders worldwide often present with somatic symptoms, which frequently accompany psychological symptoms. For example, in a recent report of pooled data from Canada, scores on the Somatic Symptoms Inventory, the 17-item Hamilton Rating Scale for Depression (HAM-D17), and the Hamilton Rating Scale for Anxiety (HAM-A) were used to evaluate the association between somatic symptoms and MDD. Of the 2,191 patients randomly enrolled in the study, 78% reported moderate-to-severe fatigue and weakness. Painful physical symptoms commonly occur in patients with anxiety disorders as well. In a European study, painful physical symptoms were reported by 28% of those without anxiety disorders and 45% of those with anxiety disorders.

Treatment-resistant depression (TRD) may be defined, both pragmatically and clinically, as the failure of an episode of major depression to respond fully to the adequate administration of a treatment that is known to be effective (Slide 1). It is important for the clinician, in terms of not inadvertently reinforcing stigma, to bear in mind, as the definition indicates, that it is the disease state or episode of depression that is treatment resistant, and not the patient, per se. The treatment that has failed must be a valid one and must also have been delivered effectively before one can conclude that this episode of major depression is resistant to any particular level of treatment.

When patients do not respond to an initial course of antidepressant treatment, clinicians may opt for a number of alternatives. First, re-evaluating the diagnosis to make sure that no comorbidities were missed, and that the diagnosis of major depressive disorder (MDD) is accurate, particularly with respect to recognition of clinical features that might suggest previously unrecognized bipolarity or psychotic features. Secondly, clinicians should ensure that the patient has adhered to the recommended medication. When finally reaching the point of certainty or near certainty that the patient has not benefited from a truly adequate course of treatment lasting ≥8 weeks, the next major considerations usually are to either switch antidepressants or to augment the original choice of treatments. Lastly, selection of the most appropriate “next choice” strategy should take into account the tolerability of and degree of improvement observed with the initial antidepressant medications. Many clinicians prefer to switch patients who have poorer tolerability and minimal symptom improvement and try to augment therapy when the initial antidepressant has been well tolerated and resulted in some degree of symptom improvement.

Antidepressants have been available since the 1950s, when the monoamine oxidase inhibitors were first discovered. Since then, our armamentarium of antidepressants has progressively expanded with the discovery of the tricyclic antidepressants (TCAs) in the 1960s, the selective serotonin reuptake inhibitors (SSRIs) in the 1980s, and, subsequently, the serotonin norepinephrine reuptake inhibitors (SNRIs), and other agents possessing a diverse mechanism of action including buproprion, and mirtazapine.