The need to reduce disability worldwide

- The science of well-being: an integrated approach to mental health and its disorders

Despite modern advances in psychiatry, mental disorders remain the leading causes of disability throughout the world (8). Major depression alone results in the average loss worldwide of more than 6 years of healthy life. Combining major depression with alcohol use, drug use, and other mental disorders brings the total burden from mental disorders to over 20 years of the lives of every person age 5 and older. Mental disorders are a staggering burden for societies around the world regardless of the ethnic and economic diversity of countries.

The treatment of mental disorders has been improved with the introduction of many medications and psychotherapy techniques that show acute benefits in randomized controlled trials. Nevertheless, available treatments are unfortunately associated with frequent dropout, relapse, and recurrence of illness. For example, in the treatment of major depression, the acute response to antidepressants or cognitive behavioral therapy is only moderate. Substantial improvement occurs in about 50% to 65% of patients receiving active treatment, compared to 30% to 45% in control subjects (9). Relapse is rapid in subjects who drop out or prematurely discontinue treatment, because the interventions are directed at symptoms and do not correct the underlying causes of the disorder. Most patients with major depression who do improve acutely have recurrences within the next three years despite use of medications and cognitive behavioral therapy (10). The outcomes are likewise inadequate from available treatments for other disorders, such as schizophrenia, bipolar disorder, anxiety disorders, alcohol and drug dependence. The available medications for drug and alcohol dependence have weak acute effects and high rates of relapse and recurrence, even when clinical subtypes are distinguished (11,12). Likewise, 74% of patients with schizophrenia discontinued the antipsychotic they were prescribed before 18 months in a recent trial comparing available secondgeneration (atypical) antipsychotics to the first-generation (typical) drug perphenazine (13). All available drugs were discontinued with nearly equal frequency because of high rates of non-response, intolerable side effects, and nonadherence. The inadequacy of available treatments for most patients with mental disorders results in persistent residual symptoms of disease and distress, as well as low levels of life satisfaction and well-being.