Challenge to Treatment of Depression: Time of Onset to Clinical Response

Posted in: Clinical Trials

Depression is a form of mood disorder.  The key behavioral feature expressed by  people who suffer from depression is a pervasive feeling of being unusually sad or down in the dumps for an extended period of time.  This in turn commonly results in a loss of interest or pleasure in nearly all activities. Additional features that are commonly seen in people suffering from depression include changes in appetite, weight, energy, sleep, difficulties in thinking and concentrating and difficulties in making decisions.  Recurrent thoughts of death or suicidal ideation, plans or attempts are not uncommon, and are serious enough to demand immediate attention.

Fortunately, there are many medications currently available to aid in the treatment of depression.  The most common medications used nowadays to treat depression belong to a class of drugs known as selective serotonergic reuptake inhibitors or SSRIs for short.  An important issue associated with the onset of treatment is how long it takes for the patient to realize the onset of a noticeable clinical benefit.  At issue is the fact that while the pharmacological actions of antidepressants on their targets within the central nervous system occur almost immediately, the clinical benefit appears to lag by as much as two to four weeks.  The reason for this continues to remain elusive and an area of intense research.

This lag in the apparent onset of an appreciable clinical response has potentially troubling and even serious implications for the treatment of patients who suffer from depression.  If patients do not realize some recognizable relief quickly, they might get discouraged and stop taking their antidepressant medication.  Of greater concern would be for those patients with suicidal thoughts or plans.  A lack of a quick response could have serious consequences.

It is important, therefore, for people to fully understand that it will take time for any benefit from the antidepressant medication they have been prescribed to be realized.  However, the notion that it will likely take two to four weeks to realize any sign of a clinical benefit might not necessarily be the case.   For example, in a literature review and meta-analyses (a survey and combined reanalysis of many previously published reports) conducted by Taylor et al (Archives of Gen. Psychiatry, 63(11) :  1217-23, 2006,) it was reported that “one third of the total (clinical) effect of selective serotonin re-uptake inhibitors (SSRIs) after six weeks of treatment was seen in the first week” following initiation of treatment. Additional meta analyses suggest that if a clinical response is not seen within the first two to three weeks following initiation of treatment, the likelihood of seeing a favorable outcome is very low (Strassen et al, Eur. Psychiatry, 12:  166-76, 1997; Szegedi et. al., J. Clin. Psychiatry, 69:  946-58, 2009; Katz et. al., J. Clin. Psychopharm.,37:  193-218, 2011).

Hopefully, the above will help people initiating treatment with an antidepressant to better appreciate what to expect, and to query their behavioral medicine professional about how best to proceed with treatment in the event a clinical response is not experienced within an acceptable period of time.  It is also important to keep in mind that, while a person might not respond favorably to one medication, there may be another that will provide the benefit the individual is looking for.

Another avenue to consider is participation in a clinical research trial targeting depression.  There are currently a number of such clinical research trials being conducted at reputable medical institutions throughout the United States.  Good resources to find where such studies are being conducted include and  Once on these websites, you can search for ongoing clinical trials being conducted in your locale.  If, for example, you live within the New York City Metropolitan Area, you could refine your search to a keyword term such as Depression Research Studies NYC.  You can even refine you search to a specific borough of city, such as Brooklyn, by typing in the keyword string Depression Research Studies Brooklyn.

Whichever approach you take, it is important to take that first step to seek out the help you need.  Depression is a treatable disorder.  If you have not already done so, talk to your primary care physician or seek out a therapist or behavioral medicine profession to discuss how best to treat your symptoms.

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