Maria has been feeling depressed for at least two and a half years. About three years ago, her husband of 20 years left her for another woman. Devastated, she became despondent and tearful almost daily.

Eventually, her depression got worse associated with inability to function. Her appetite, energy, concentration, and sleep became impaired. She also felt hopeless and suicidal. Her psychiatrist put her on a starting dose of antidepressant. She responded initially but after a few days, she felt just like before taking the medication.

For the past two years, Maria has tried four types of antidepressants. She has taken the usual adult doses of these drugs. Although she somewhat improves, she has virtually remained the same depressed and disabled.

Maria seems to be taking the medications regularly. But why is she not responding to her antidepressants?

Maria is just one of the many depressed individuals who don't feel normal despite treatment. Depression is a treatable disease but how come some people don't do well on medications?

There are many reasons why depressed patients like Maria don't improve on antidepressants.

First, is the diagnosis correct?

Depression can be caused by many clinical entities. Sometimes, knowing the right diagnosis is a challenge. Medical disorders, medications such as beta-blockers and benzodiazepines (e.g. clonazepam), and various psychiatric disorders can cause depression and they all require different treatment. If your doctor fails to identify and treat the true cause of your depression, you will remain depressed despite the use of antidepressant.

Second, are there co-morbid disorders?

Depression can exist along with other psychiatric disorders such as anxiety disorder, alcohol or drug problems, personality disorder, dementia, and psychosis. Depression will persist if these co-morbid disorders are not treated. For instance, depressive disorder with psychosis cannot be adequately treated just with antidepressant alone. You need an antipsychotic drug added to an antidepressant to treat the illness.

Third, is there an ongoing neurological or medical disorder that precipitates, aggravates, or complicates depression?

Hypothyroidism, hyperthyroidism, vitamin B-12 deficiency, pancreatic cancer, brain tumor, Parkinson's disease, and stroke can all cause depression. If any of these disorders are present, antidepressants are less likely to help. The goal in these situations is to treat the underlying medical condition. A 65 year-old lady came to see me complaining of severe depression. On evaluation, she disclosed that she had been on three types of antidepressants for the past four years with minimal response. I checked her recent laboratory results which showed an abnormal thyroid! No wonder, she was not responding to the medication.

Fourth, are there ongoing psychosocial issues?

Financial problems, family conflict, work-related stress can all precipitate and complicate depression. Despite adequate medication treatment, some individuals will remain depressed especially if such problems are not addressed by the therapist or psychiatrist. Is there any way you can reduce the stressors? Please do so the earliest you can.

The treatment of depression is frequently straightforward. Occasionally however, various factors complicate it. For antidepressant to be effective, a psychiatrist should ensure that the diagnosis is correct, that co-morbid psychiatric disorders and medical problems are treated, and that psychosocial issues are adequately addressed.

Maria s doctor should explore further the real problem and provide the most appropriate intervention.

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