Depression, suicidality and antidepressants: A coincidence?

Byline: Vithyalakshmi. Selvaraj, Snehamala. Veeravalli, Sriram. Ramaswamy, Richard. Balon, Vikram. Yeragani Major depressive disorder is currently one of the leading causes of disability world-wide and projected by the World Health Organization (WHO) to become the second leading cause of disability after heart disease by the year 2020. Suicidal ideation and behavior are the most serious and common psychiatric emergencies among the depressed population. In 2004, suicide was the eleventh leading cause of death in the U.S.[sup] [1] The overall rate was 10.9 suicide deaths per 100,000 people. An estimated 8 to 25 attempted suicides occur per every suicide death. It is reassuring that depressed patients usually respond to treatment with antidepressants. In fact, population-based studies examining rates of antidepressant use and suicide over time, have generally found lower rates of suicide with increasing rates of antidepressant use. [sup] [2],[3],[4],[5],[6],[7],[8] However, in 2003, publication of data linking antidepressant use to suicide and suicidal behavior in children and teenagers sparked off worldwide public health concern. This prompted the US Food and Drug Administration (FDA) to mandate manufacturers of all antidepressants (including tricyclic antidepressants [TCAs] and monoamine oxidase inhibitors) to include a warning stating that antidepressants may increase the risk of suicidal ideation and behavior in children, adolescents and young adults less than 25 years old. The 'black box' warning, although meant to safeguard public health has had serious spillover effects on pharmacotherapy of depression. There have been recent reports of a rise in suicide rates among the youth and a decline in depression care among the older adults. We critically evaluate this association in order to provide more clarity while assessing the benefits of antidepressant use versus any risk of self-harm associated with them. Impact of Depression Depression is a pathological and pervasive state of mood. The lifetime risk of developing major depressive disorder is 16.2% in the United States. Recurrence is the rule, and about one-third of patients go on to develop chronic depression. Depression increases mortality because it worsens many medical conditions such as cardiovascular disease and diabetes and increases the risk of suicide. Depressed patients are high utilizers of healthcare services and typically perform poorly in the workplace. The mean age of onset, from a number of studies, is in the late 20s. Although twice as many females as males report or receive treatment for clinical depression, this gap has significantly narrowed in the recent past. Also, this difference disappears after the age of 50-55, when most females are post-menopausal. Suicidal ideation and attempts are common in depressed patients. Each year, about 30,000 people in the United States and one million worldwide die by suicide. Approximately 650,000 people in the United States receive emergency treatment each year after attempting suicide. Antidepressants Benefits and Risks Mono amine oxidase inhibitors (MAOI) and tricyclic antidepressants (TCA) were the mainstays of treatment for depression until the introduction of Serotonin Reuptake Inhibitors (SSRIs) in the late 1980's. Currently, SSRIs are the most commonly prescribed antidepressants. The therapeutic effects of antidepressants are believed to be related to their ability to facilitate serotonin, norepinephrine and/or dopamine neurotransmission. Despite the early increase in concentration of monoamine neurotransmitters at receptor sites, clinical antidepressant benefits are not evident until several weeks. One explanation for this therapeutic lag is the theory that "down-regulation" of neurotransmitter receptors is a consequence of excess signaling, a process that takes several weeks and ultimately responsible for the alleviation of depressive symptoms. Overall, antidepressants are very effective in treating depression and its associated complications. …