Suicidality from SSRIs

A review of the database of the Food and Drug Administration showed 77 suicides among 48 277 patients who had participated in placebo-controlled trials of antidepressants (22). The rate of suicide with SSRIs (0.59% Cl = 0.31, 0.87) was similar to that of other antidepressants (0.76% Cl = 0.49, 1.03) and placebo (0.45% Cl = 0.01, 0.89). While these data are reassuring, patients considered clinically at high risk of suicide were excluded from the trials and the patients received a greater degree of supervision than would occur in routine practice. 

Paroxetine increases the risk of birth defects in women taking the drug during their first trimester of pregnancy. Evidence from case studies, epidemiological studies, experimental research, and theory supports the view that SSRIs increase suicide risk for some patients. 

In addition to a different side-effect profile, SSRIs differ from TCAs by virtue of their wider safety margin, because they do not cause life-threatening toxic effects (e.g., patients having survived acute ingestion of amounts equal to 10 times the daily dose) (434). For this reason, many clinicians prefer these drugs in patients who may be a significant suicide risk. 

Gunnell, D., Saperia, J., Ashby, D. 2005, Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults meta-analysis of dmg company data from placebo controlled, randomised controlled trials submitted to the MHRA s safety review, Br.Med.f, vol. 330, no. 7488, p. 385. 

In general, the pattern of adverse reactions is similar among all the SSRIs and some of the other new antidepressants that block the reuptake of serotonin, especially venlafaxine. As a result, the FDA has required class label warnings for them in regard to suicidality and to the array of stimulant adverse reactions, from agitation and hostility to mania. 

By contrast, 60% continued to believe that some medications were more likely to improve suicidality, with the vast majority citing the SSRIs as most helpful in relieving suicidality in children and youth. This flew in the face of evidence from controlled clinical trials and observations by the FDA indicating that antidepressants are no better than placebos in treating childhood depression. 

Over the last decade there has been a debate as to whether SSRIs might increase the risk of suicide in certain individuals. Some patients can respond to SSRIs by becoming agitated and restless and developing symptoms that resemble akathisia. Case reports have suggested that adverse effects of this type could underlie an increased risk of self-harm and aggression. However, results from the placebo-controlled randomized trials carried out for regulatory purposes have not supported the proposal that SSRIs increase the risk of suicide of suicidal behavior. 

Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) have been associated with increasing suicidal ideation in some populations of patients. Recent studies have led the British Department of Health to warn physicians against using paroxetine off label. Fluoxetine was specifically exempted from this recommendation. Long-term studies of patients with depression who were treated with fluoxetine have shown it to be fairly well tolerated. Primary adverse effects include nausea (23%), headache (21%), and insomnia (20%). 

There has been recent concern from unpublished data in industry-sponsored trials of SSRIs in child and adolescent depression suggesting that these drugs may lead to an increased rate of suicidal ideation. This prompted a review of their use by the UK Committee on Safety of Medicines (CSM) in 2003, which raled that for major depressive disorder (MDD) in children and adolescents under the age of 18 ... 

Limited effectiveness and toxicity are the major reasons for switching a patient from one antidepressant drug to another. SSRIs are sometimes superior to tiicychcs in their clinical efficacy, and in this case amitriptyline had not proved effective after a reasonable trial (8 weeks). At that time, the depressive symptoms in this patient included feelings of worthlessness and possibly suicidal ideation. Tricyclic overdose is especially dangerous in depressed patients, who often use medications close at hand in attempting suicide. Ingestion of just a 2-week supply of amitriptyline can cause severe hypotension, cardiac arrhythmias, seizures, coma, and death ( one-prescription lethal ). 

Clinical trials have concluded that 2 or 3 of every 100 children and teenagers treated with antidepressants might be at higher risk of suicidal behavior. Data regarding suicidal behavior varies among the antidepressants, whioh leads to the conolusion that no antidepressant is free from risk at this time. Most of the suicides have occurred with the SSRIs, especially paroxetine (Paxil)... 

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